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Sample records for mice inoculated orally

  1. Comparison of mucosal and systemic humoral immune responses and subsequent protection in mice orally inoculated with a homologous or a heterologous rotavirus.

    Science.gov (United States)

    Feng, N; Burns, J W; Bracy, L; Greenberg, H B

    1994-12-01

    Rotaviruses are the single most important cause of severe diarrhea in young children worldwide, and vaccination is probably the most effective way to control the disease. Most current live virus vaccine candidates are based on the host range-restricted attenuation of heterologous animal rotaviruses in humans. The protective efficacy of these vaccine candidates has been variable. To better understand the nature of the heterologous rotavirus-induced active immune response, we compared the differences in the mucosal and systemic immune responses generated by heterologous (nonmurine) and homologous (murine) rotaviruses as well as the ability of these infections to produce subsequent protective immunity in a mouse model. Sucking mice were orally inoculated with a heterologous simian or bovine rotavirus (strain RRV or NCDV) or a homologous murine rotavirus (wild-type or tissue culture-adapted) strain EHP at various doses. Six weeks later, mice were challenged with a virulent murine rotavirus (wild-type strain ECW) and the shedding of viral antigen in feces was quantitated. Levels of rotavirus-specific serum immunoglobulin G (IgG) and fecal IgA prior to challenge were measured and correlated with subsequent viral shedding or protection. Heterologous rotavirus-induced active protection was highly dependent on the strain and dose of the virus tested. Mice inoculated with a high dose (10(7) PFU per mouse) of RRV were completely protected, while the protection was diminished in animals inoculated with NCDV or lower doses of RRV. The ability of a heterologous rotavirus to stimulate a detectable intestinal IgA response correlated with the ability of the virus to generate protective immunity. Serum IgG titer did not correlate with protection. Homologous rotavirus infection, on the other hand, was much more efficient at inducing both mucosal and systemic immune responses as well as protection regardless of the virulence of the virus strain or the size of the immunizing dose.

  2. Coxsackie B virus infection of mice: inoculation by the oral route protects the pancreas from damage, but not from infection.

    NARCIS (Netherlands)

    Bopegamage, S.; Kovacova, J.; Vargova, A.; Motusova, J.; Petrovicova, A.; Benkovicova, M.; Gomolcak, P.; Bakkers, J.; van Kuppeveld, F.; Melchers, W.J.; Galama, J.M.

    2005-01-01

    The pathogenesis of coxsackie B virus (CVB) infections is generally studied in mice by intraperitoneal (i.p.) injection, whereas the gastrointestinal tract is the natural porte d'entree in humans. The present study was undertaken to compare systematically the influence of infection route on

  3. Changes in composition of caecal microbiota associated with increased colon inflammation in interleukin-10 gene-deficient mice inoculated with Enterococcus species.

    Science.gov (United States)

    Bassett, Shalome A; Young, Wayne; Barnett, Matthew P G; Cookson, Adrian L; McNabb, Warren C; Roy, Nicole C

    2015-03-11

    Human inflammatory bowel disease (IBD) is a chronic intestinal disease where the resident microbiota contributes to disease development, yet the specific mechanisms remain unclear. Interleukin-10 gene-deficient (Il10-/-) mice develop inflammation similar to IBD, due in part to an inappropriate response to commensal bacteria. We have previously reported changes in intestinal morphology and colonic gene expression in Il10-/- mice in response to oral bacterial inoculation. In this study, we aimed to identify specific changes in the caecal microbiota associated with colonic inflammation in these mice. The microbiota was evaluated using pyrotag sequencing, denaturing gradient gel electrophoresis (DGGE) and quantitative real-time PCR. Microbiota profiles were influenced by genotype of the mice and by bacterial inoculation, and a strong correlation was observed between the microbiota and colonic inflammation scores. Although un-inoculated Il10-/- and C57 mice had similar microbiota communities, bacterial inoculation resulted in different changes to the microbiota in Il10-/- and C57 mice. Inoculated Il10-/- mice had significantly less total bacteria than un-inoculated Il10-/- mice, with a strong negative correlation between total bacterial numbers, relative abundance of Escherichia/Shigella, microbiota diversity, and colonic inflammation score. Our results show a putative causative role for the microbiota in the development of IBD, with potentially key roles for Akkermansia, or for Bacteroides, Helicobacter, Parabacteroides, and Alistipes, depending on the composition of the bacterial inoculum. These data support the use of bacterially-inoculated Il10-/- mice as an appropriate model to investigate human IBD.

  4. Granulomatous enteritis following oral inoculation of newborn rabbits with Mycobacterium paratuberculosis of bovine origin.

    OpenAIRE

    Mokresh, A H; Butler, D G

    1990-01-01

    To assess the rabbit as a model for the study of paratuberculosis infection, two groups of newborn rabbits were orally inoculated at one to two days of age with Mycobacterium paratuberculosis (ATCC 19698 or field strain 22206) and compared to uninoculated controls. Nine of thirteen rabbits (69%) inoculated with ATCC 19698, and all three rabbits inoculated with 22206, experienced episodes of intermittent diarrhea starting four months after inoculation. Multifocal granulomas containing acid-fas...

  5. Oral lactoferrin protects against experimental candidiasis in mice.

    Science.gov (United States)

    Velliyagounder, K; Alsaedi, W; Alabdulmohsen, W; Markowitz, K; Fine, D H

    2015-01-01

    To determine the role of human lactoferrin (hLF) in protecting the oral cavities of mice against Candida albicans infection in lactoferrin knockout (LFKO(-/-)) mice was compared to wild-type (WT) mice. We also aim to determine the protective role of hLF in LFKO(-/-) mice. Antibiotic-treated immunosuppressed mice were inoculated with C. albicans (or sham infection) by oral swab and evaluated for the severity of infection after 7 days of infection. To determine the protective role of hLF, we added 0·3% solution of hLF to the drinking water given to some of the mice. CFU count, scoring of lesions and microscopic observations were carried out to determine the severity of infection. LFKO(-/-) I mice showed a 2 log (P = 0·001) higher CFUs of C. albicans in the oral cavity compared to the WT mice infected with C. albicans (WTI). LFKO(-/-) I mice given hLF had a 3 log (P = 0·001) reduction in CFUs in the oral cavity compared to untreated LFKO(-/-) I mice. The severity of infection, observed by light microscopy, revealed that the tongue of the LFKO(-/-) I mice showed more white patches compared to WTI and LFKO(-/-) I + hLF mice. Scanning electron microscopic observations revealed that more filiform papillae were destroyed in LFKO(-/-) I mice when compared to WTI or LFKO(-/-) I + hLF mice. Human LF is important in protecting mice from oral C. albicans infection. Administered hLF may be used to prevent C. albicans infection. Human LF, a multifunctional iron-binding glycoprotein can be used as a therapeutic active ingredient in oral healthcare products against C. albicans. © 2014 The Society for Applied Microbiology.

  6. Effect of inoculating C57BL/6NTac mice with different gut microbiotas on gut colonization and glucose tolerance

    DEFF Research Database (Denmark)

    Ellekilde, Merete; Viscardi, Monika; Rune, Ida

    In recent decades, the gut microbiota (GM) has been demonstrated influential in diseases of immunological and inflammatory origin such as asthma, allergy, arthritis and diabetes. This indicates a possibility to affect disease development by changing the GM composition. Previously our group has...... demonstrated a possibility to affect GM composition by inoculation in germfree mice. The aim of this study was to investigate, whether it was also possible to change the GM of conventional mice and secondly if this change would affect glucose tolerance. 64 five week old C57BL/6NTac mice (half males, half...... females) were given oral ampicillin for three weeks to eliminate their GM. At the age of eight weeks, the mice were then split in four groups receiving an oral suspension of GM from a BALB/c mouse, a DBA mouse, a B6-Lepob mouse or PBS as control. GM composition was analyzed prior to antibiotic treatment...

  7. Brucella abortus RB51 induces protection in mice orally infected with the virulent strain B. abortus 2308.

    Science.gov (United States)

    Pasquali, Paolo; Rosanna, Adone; Pistoia, Claudia; Petrucci, Paola; Ciuchini, Franco

    2003-05-01

    Brucellae are gram-negative, facultative intracellular bacteria which are one of the most common causes of abortion in animals. In addition, they are the source of a severe zoonosis. In this trial, we evaluated the effect of oral inoculation of Brucella abortus RB51 in mice against a challenge infection with B. abortus 2308. First, we showed that a gastric acid neutralization prior to the oral inoculation contributed to a more homogeneous and consistent infection with both vaccine strain B. abortus RB51 and virulent strain B. abortus 2308. Successively, we assessed the clearance and the immune response following an oral infection with B. abortus RB51. Oral inoculation gave a mild infection which was cleared 42 days after infection, and it induced a delayed humoral and cell-mediated immune response. Finally, we immunized mice by oral inoculation with B. abortus RB51, and we challenged them with the virulent strain B. abortus 2308 by an oral or intraperitoneal route 42 days after vaccination. Oral inoculation of B. abortus RB51 was able to give protection to mice infected with the virulent strain B. abortus 2308 by the oral route but not to mice infected intraperitoneally. Our results indicate that oral inoculation of mice with B. abortus RB51 is able to give a protective immunity against an oral infection with virulent strains, and this protection seems to rely on an immune response at the mucosal level.

  8. Changes in Composition of Caecal Microbiota Associated with Increased Colon Inflammation in Interleukin-10 Gene-Deficient Mice Inoculated with Enterococcus Species

    Directory of Open Access Journals (Sweden)

    Shalome A. Bassett

    2015-03-01

    Full Text Available Human inflammatory bowel disease (IBD is a chronic intestinal disease where the resident microbiota contributes to disease development, yet the specific mechanisms remain unclear. Interleukin-10 gene-deficient (Il10-/- mice develop inflammation similar to IBD, due in part to an inappropriate response to commensal bacteria. We have previously reported changes in intestinal morphology and colonic gene expression in Il10-/- mice in response to oral bacterial inoculation. In this study, we aimed to identify specific changes in the caecal microbiota associated with colonic inflammation in these mice. The microbiota was evaluated using pyrotag sequencing, denaturing gradient gel electrophoresis (DGGE and quantitative real-time PCR. Microbiota profiles were influenced by genotype of the mice and by bacterial inoculation, and a strong correlation was observed between the microbiota and colonic inflammation scores. Although un-inoculated Il10-/- and C57 mice had similar microbiota communities, bacterial inoculation resulted in different changes to the microbiota in Il10-/- and C57 mice. Inoculated Il10-/- mice had significantly less total bacteria than un-inoculated Il10-/- mice, with a strong negative correlation between total bacterial numbers, relative abundance of Escherichia/Shigella, microbiota diversity, and colonic inflammation score. Our results show a putative causative role for the microbiota in the development of IBD, with potentially key roles for Akkermansia, or for Bacteroides, Helicobacter, Parabacteroides, and Alistipes, depending on the composition of the bacterial inoculum. These data support the use of bacterially-inoculated Il10-/- mice as an appropriate model to investigate human IBD.

  9. Systemic immune response after rotavirus inoculation of neonatal mice depends on source and level of purification of the virus: implications for the use of heterologous vaccine candidates.

    Science.gov (United States)

    Reimerink, Johan H J; Boshuizen, Jos A; Einerhand, Alexandra W C; Duizer, Erwin; van Amerongen, Geert; Schmidt, Nico; Koopmans, Marion P G

    2007-02-01

    Rotavirus is an important cause of morbidity and mortality worldwide and vaccines are currently under development, with clinical trails conducted in humans worldwide. The immune responses in infant BALB/c mice were examined following oral inoculation with murine rotavirus EDIM (2 x 10(4) focus-forming units) and with three CsCl gradient-purified fractions of heterologous simian rotavirus SA11 (standardized at 2 x 10(6) CCID(50)) that differed in antigen composition: fraction 1 was enriched for double-layered rotavirus particles, fraction 2 for triple-layered particles and fraction 3 consisted mainly of cell components. Diarrhoea and high IgG responses, but marginal IgA responses, were observed after inoculation with all three SA11 fractions. Virus shedding was observed in all EDIM-inoculated mice, but in none of the SA11-inoculated mice. Rotavirus-specific IgG1 : 2a ratios were similar in mice inoculated with EDIM and SA11 fraction 1, but higher for SA11 fraction 3- and lower for SA11 fraction 2-inoculated mice. A higher IgG1 : 2a ratio indicates a more Th2-like immune response. This undesirable response is apparently mostly induced by inoculation with heterologous rotavirus in the presence of abundant cell-associated and soluble rotavirus proteins, compared with infection with a more purified preparation or with homologous virus. These data show that, following inoculation with a standardized amount of infectious virus, the composition of the fraction influences the outcome of the immune responses significantly.

  10. Toxoplasma gondii infections in red-tailed hawks inoculated orally with tissue cysts.

    Science.gov (United States)

    Lindsay, D S; Dubey, J P; Blagburn, B L

    1991-04-01

    The response to inoculation of Toxoplasma gondii tissue cysts was examined in 3 red-tailed hawks (Buteo jamaicensis). One hawk (hawk 1) was inoculated orally with 3.000 tissue cysts of the GT-1 isolate of T. gondii and 2 hawks (hawks 2 and 3) each were inoculated orally with 12,000 tissue cysts of a mixture of 8 isolates of T. gondii. None of the hawks developed clinical signs of toxoplasmosis. Serum antibodies were measured with the modified direct agglutination test using formalin-fixed tachyzoites. Hawk 1 had a titer of 1:40 prior to inoculation and did not have an increase in titer during the study. Hawks 2 and 3 had titers of 1:5 and 1:10, respectively, prior to inoculation, and both had increased titers (titers greater than or equal to 1:60) by 1 wk postinoculation and remained T. gondii antibody positive throughout the 10 wk of the study. Toxoplasma gondii was isolated from the heart and breast muscle of hawk 1. The biologic behavior of this T. gondii isolate was different from the 1 inoculated, and it probably represents a prior natural infection. Toxoplasma gondii was isolated from the brain, heart, breast muscle, and a mixture of gizzard and proventriculus from hawk 2 and from breast muscle of hawk 3. Toxoplasma gondii was not isolated from the eye, lung, liver, kidney, or spleen of any red-tailed hawk.

  11. Experimental inoculation of porcine circoviruses type 1 (PCV1) and type 2 (PCV2) in rabbits and mice.

    Science.gov (United States)

    Quintana, Josefina; Balasch, Monica; Segalés, Joaquim; Calsamiglia, Maria; Rodríguez-Arrioja, Gabriela M; Plana-Durán, Juan; Domingo, Mariano

    2002-01-01

    The objective of this work was to investigate the susceptibility of rabbits and mice experimentally inoculated with porcine circoviruses type 1 (PCV1) and type 2 (PCV2) to infection and development of disease and/or lesions. Forty six New Zealand rabbits and 50 ICR-CDI mice were both divided into two groups comprising PCVI and PCV2 inoculated animals, and a third group inoculated with non-infected cell culture medium. Rabbits were inoculated intranasally while mice were inoculated intraperitoneally. Clinical signs and body weights were recorded at the start of the experiment and at necropsy. Animals were bled, euthanised and necropsied at days 0, 3, 7, 10, 14 and 20 post-inoculation and samples were collected for histopathological, serological, in situ hybridisation and PCR analysis. No clinical signs or gross and microscopic lesions compatible with PCV2 infections such as those seen in pigs were observed. No presence of PCV2 nucleic acid was detected in rabbits and mice by in situ hybridisation. Only one mouse inoculated with PCV1 seroconverted on day 20 P1. PCV1 and PCV2 genome was detected in serum by PCR in mice inoculated with each porcine circovirus, while rabbits were negative for both viral types. These studies indicated that porcine circoviruses did not cause any disease or microscopic lesions in inoculated rabbits and mice during the experimental period. However, intraperitoneally inoculated mice might have harboured PCV2 in circulation without evidence of viral replication.

  12. Herpes simplex virus ophthalmic disease induced using two different methods of mice inoculation

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    Sílvia Regina Ferreira Gonçalves Pereira

    Full Text Available Two different procedures for inoculation of HSV on corneas of BALB/c mice were evaluated. The first was by the use of HSV suspensions directly on the corneas and the other was after corneal scarification. Animals by this later method presented greater morbidity and mortality than those of first group, suggesting that inoculation of HSV without scarification of the cornea should be the method of choice for the study of HSV ophthalmic infection. This model showed also be an efficient experimental system to testing antiviral drugs.

  13. Host selenium deficiency increases the severity of chronic inflammatory myopathy in Trypanosoma cruzi-inoculated mice.

    Science.gov (United States)

    Gomez, Ricardo M; Solana, Maria E; Levander, Orville A

    2002-06-01

    Weanling C3H/HeN mice were fed either a torula yeast-based diet deficient in selenium (Se) or the same diet supplemented with 0.2 ppm Se as sodium selenite. After 4 wk of feeding, the mice were inoculated intraperitoneally with the CA-I strain (clone K98) of Trypanosoma cruzi (TC). Before inoculation, mean serum Se levels were 430 versus 61 ng/ml in adequate and deficient mice, respectively. During the ascending phase of parasitemia, the Se-deficient mice exhibited significantly higher levels of parasites at 22-34 days postinfection (PI). However, no difference was found in the subsequent descending phase. As judged by visual examination at 2-mo-PI, some Se-deficient infected mice presented clinical signs of motor dysfunction. At 3-mo-PI, the end of the observation period, this chronic disease developed into a hind limb flaccid paralysis affecting 5 of 8 infected deficient mice. No signs of paralysis were seen in noninfected mice fed either diet or in infected mice fed the Se-adequate diet. At the histological level, both Se-adequate and Se-deficient infected mice showed mild myocarditis and moderate to severe myositis, with increasing intensity from 1- to 3-mo-PI in both groups. However, the severity of myositis was always more intense in the Se-deficient mice so that prominent areas of skeletal muscle replaced by fibrotic tissue were frequently observed. Thus, it can be concluded that Se deficiency in the murine host increases the severity of TC-induced myositis.

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

    OpenAIRE

    Barreto-de-Albuquerque, Juliana; Silva-dos-Santos, Danielle; P?rez, Ana Rosa; Berbert, Luiz Ricardo; de Santana-van-Vliet, Eliane; Farias-de-Oliveira, D?sio Aur?lio; Moreira, Otacilio C.; Roggero, Eduardo; de Carvalho-Pinto, Carla Eponina; Jurberg, Jos?; Cotta-de-Almeida, Vin?cius; Bottasso, Oscar; Savino, Wilson; de Meis, Juliana

    2015-01-01

    Oral transmission of Chagas disease has been documented in Latin American countries. Nevertheless, significant studies on the pathophysiology of this form of infection are largely lacking. The few studies investigating oral route infection disregard that inoculation in the oral cavity (Oral infection, OI) or by gavage (Gastrointestinal infection, GI) represent different infection routes, yet both show clear-cut parasitemia and heart parasitism during the acute infection. Herein, BALB/c mice w...

  15. Protective action of camel milk in mice inoculated with Salmonella enterica.

    Science.gov (United States)

    Cardoso, Roberto R De Almeida; Ponte, Marina; Leite, Vanuza

    2013-01-01

    In some countries people believe that camel milk can protect against various aggressors, whether due to infections, diabetes, or even autism. Little has been scientifically demonstrated regarding the veracity of these beliefs. To study the anti-infectious action of camel milk. Fifty mice were divided into 5 groups of 10 animals each: 3 control groups and 2 test groups. Except for one of the control groups, all groups were intraperitoneally inoculated with a strain of Salmonella enterica. The rations in the test groups were supplemented with camel milk or cow milk. A statistically significant survival was observed in the mice supplemented with camel milk. The death rate after Salmonella inoculation was only 40% in the study group, as compared to 100% in the control groups where the mice were not protected, and 80% in the group supplemented with cow milk and injected with Salmonella. Camel milk is an excellent nutrient and because of its specific properties, particularly its anti-infectious action, should be used to replace other milks.

  16. Polyomavirus-induced pilomatricomas in mice: from viral inoculation to tumour development.

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    Símula, Silvina; Ozuna, Paola Villán; Otero, Javier; Casas, José; Sanjuan, Norberto

    2012-05-01

    Polyomavirus has been used extensively to study tumour induction in mice. Although most neoplasms are well characterized, those arising from hair follicles have been referred to by different names during the last four decades. The purpose of this research was to contribute to a more accurate histological characterization of these tumours as well as to study the viral progression from the onset of infection to the development of neoplasms. Polyomavirus A2 was inoculated into newborn C3H/BiDa mice, and at different time-points (from 5 to 70 days post-inoculation) the mice were sacrificed and studied using histological, immunocytochemical, ultrastructural and virological methods. The fully developed hair follicle tumours consisted of a proliferation of matrix cells that evolved into 'shadow' cells with empty nuclei and finally into amorphous keratin; the tumours were therefore diagnosed as pilomatricomas. Viral VP-1 was observed only in fully differentiated cells and not in proliferating-cell-nuclear-antigen (PCNA)-positive cells in the same tumour. In conclusion, Polyomavirus first replicated in the skin, and then disseminated through the blood and reached the outer sheath of the hair follicles and finally infected matrix cells, leading to the development of pilomatricomas from which infectious virus was isolated. © 2011 The Authors. APMIS © 2011 APMIS.

  17. Thalidomide promotes leukocytosis in mice inoculated with 4T1 mammary carcinoma

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    Diego Carlos dos Reis

    2014-02-01

    Full Text Available The aim of this study was to evaluate the therapy effect of thalidomide in the 4T1 murine mammary carcinoma. 4T1 cell suspension was injected into the posterior left flank of all animals to obtain solid tumors. Five days after inoculation, the treatment group was orally administered 150 mg/kg of thalidomide for seven days. Tumors were measured every 48 hours until the end of treatment. Whole blood was collected for hematology analysis. Our results suggest that thalidomide therapy increase the number of circulating leukocytes in the 4T1 murine mammary carcinoma, and this response is accompanied by a decrease in tumor growth.

  18. Persistent gastric colonization with Burkholderia pseudomallei and dissemination from the gastrointestinal tract following mucosal inoculation of mice.

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    Andrew Goodyear

    Full Text Available Melioidosis is a disease of humans caused by opportunistic infection with the soil and water bacterium Burkholderia pseudomallei. Melioidosis can manifest as an acute, overwhelming infection or as a chronic, recurrent infection. At present, it is not clear where B. pseudomallei resides in the mammalian host during the chronic, recurrent phase of infection. To address this question, we developed a mouse low-dose mucosal challenge model of chronic B. pseudomallei infection and investigated sites of bacterial persistence over 60 days. Sensitive culture techniques and selective media were used to quantitate bacterial burden in major organs, including the gastrointestinal (GI tract. We found that the GI tract was the primary site of bacterial persistence during the chronic infection phase, and was the only site from which the organism could be consistently cultured during a 60-day infection period. The organism could be repeatedly recovered from all levels of the GI tract, and chronic infection was accompanied by sustained low-level fecal shedding. The stomach was identified as the primary site of GI colonization as determined by fluorescent in situ hybridization. Organisms in the stomach were associated with the gastric mucosal surface, and the propensity to colonize the gastric mucosa was observed with 4 different B. pseudomallei isolates. In contrast, B. pseudomallei organisms were present at low numbers within luminal contents in the small and large intestine and cecum relative to the stomach. Notably, inflammatory lesions were not detected in any GI tissue examined in chronically-infected mice. Only low-dose oral or intranasal inoculation led to GI colonization and development of chronic infection of the spleen and liver. Thus, we concluded that in a mouse model of melioidosis B. pseudomallei preferentially colonizes the stomach following oral inoculation, and that the chronically colonized GI tract likely serves as a reservoir for dissemination

  19. Duck Tembusu virus exhibits pathogenicity to Kunming mice by intracerebral inoculation

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    Jinfeng eTi

    2016-02-01

    Full Text Available In this study, Kunming mice were used as the animal models to study the pathogenicity of TMUV. Three groups of 3-week-old female Kunming mice (n=15 mice per group were infected with the SDSG strain of TMUV in 50μL allantoic fluid (104.8 ELD50/ 0.2ml respectively by the intracerebral (i.c., subcutaneous (s.c. and intranasal (i.n. routes. The control group (n=15 mice was inoculated with 50μL sterile phosphate-buffered saline (PBS. Clinical signs, gross and microscopic lesions, viral loads in different tissues, and serum antibody titers were examined and recorded. Kunming mice infected intracerebrally showed typical clinical symptoms, including severe hindlimb paralysis, weight loss and death. Only dead mice presented severe intestinal mucosal edema. No gross lesions were observed in mice sequentially euthanized. However, microscopic lesions in the brain, spleen, liver, kidney and lung were very typical including varying degrees of viral encephalitis, lymphocytes depletion, liver cell necrosis and nephritis, etc. Viral loads in different tissues were detected by the SYBR Green I real-time PCR assay. Viral loads in the brain, liver and spleen were first detected and maintained a longer time, which indicated that these organs may be the target organs of TMUV. The level of viral loads was consistent with the severity of clinical signs and microscopic lesions in different tissues. The neutralizing antibody began to seroconvert at 8dpi. Clinical signs, microscopic lesions, viral loads and serum neutralizing antibodies weren’t observed in other groups. In summary, TMUV can cause systemic infections and death in Kunming mice by i.c., which provides some experimental basis for further study of the significance of TMUV in public health.

  20. Welfare Assessment following Heterotopic or Orthotopic Inoculation of Bladder Cancer in C57BL/6 Mice.

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    Amy Miller

    Full Text Available Few studies have assessed whether mice used as cancer models experience pain. Despite this possibility, the usual practice is to withhold analgesics as these are generally viewed as confounding. However, pain also alters cancer progression, so preventing it might not only be beneficial to welfare but also to study validity. Establishing the extent to which different cancer models result in pain is an important first step towards their refinement. We used conditioned place preference (CPP testing and body-weight and behaviour analyses to evaluate the assumption that heterotopically implanted tumours result in less pain and fewer welfare concerns than those implanted orthotopically. C57Bl/6 mice received MB49Luc luciferase expressing bladder cancer cells or saline implanted subcutaneously or into the bladder. These tumour-bearing or control groups underwent 2 daily 45 minute conditioning trials to saline or morphine (2mg/kg and then a 15 minute drug-free preference test on day 3 of a 3 day cycle, continuing until the study ended. Tumours were imaged and behaviour data obtained following preference tests. Development of preference for the morphine-paired chamber (morphine-seeking was determined over time. Heterotopic tumour development had no effect on morphine-seeking, and although the restraint used for heterotopic inoculation caused greater initial weight losses than anaesthesia, these mice steadily gained weight and behaved comparatively normally throughout the study. Orthotopic tumour inoculation caused no initial weight losses, but over the final 7 days these mice became less active and lost more body weight than cancer-free controls. This indicated orthotopic implantation probably caused a more negative impact on welfare or conceivably pain; but only according to the current test methods. Pain could not be confirmed because morphine-seeking in the tumour-bearing groups was similar to that seen in controls. Imaging was not found to be an

  1. Antitumor activity in mice of orally administered polysaccharide from Kefir grain.

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    Shiomi, M; Sasaki, K; Murofushi, M; Aibara, K

    1982-04-01

    The antitumor activity of a water-soluble polysaccharide (KGF-C), isolated from the Kefir grain, was studied in the mice subcutaneously inoculated with Ehrlich carcinoma (EC) or Sarcoma 180 (S-180). The growth of EC and S-180 solid tumor was inhibited by 40-59% and 21-81%, respectively, by oral administration of KGF-C as compared with the unadministered mice. The tumor growth was similarly inhibited by intraperitoneal administration. The mechanism of the antitumor activity of KGF-C was considered to be host-mediated because of the lack of direct in vitro effect on tumor cells.

  2. Allergic airway inflammation by nasal inoculation of particulate matter (PM2.5 in NC/Nga mice.

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    Keiki Ogino

    Full Text Available To evaluate the effect of airborne particulate matter 2.5 (PM2.5 in winter on airway inflammation, water-soluble supernatant (Sup and water-insoluble precipitate (Pre in PM2.5 were inoculated in NC/Nga mice with high sensitivity to mite allergens. Sup with aluminum oxide was injected intraperitoneally for sensitization. Five days later, Sup, Pre or both Sup and Pre were inoculated via the nasal route five times for more sensitization and a challenge inoculation on the 11th day in NC/Nga mice. On the 12th day, mice were examined for airway hyperresponsiveness (AHR, BALF cell count and IL-1β concentration, mRNA expression of Th1 and Th2 cytokines, chemokines such as eotaxin 1 and eotaxin 2, inflammasomal complex molecules such as IL-1β, caspase 1 and the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3 in lung tissue as well as histopathology. The synergistic effect of Sup and Pre was observed in terms of increases in AHR, BALF cells, the mRNA expression of IL-13, eotaxin1 and IL-1β, and the IL-1β concentration in BALF. Intracellular deposits of insoluble particulates were observed in macrophages around inflammatory granulation of the mouse group treated with Sup and Pre. These results suggest that PM2.5 can induce airway hyperresponsiveness in mice with genetically high sensitivity to mite allergens by an inflammasome-associated mechanism and synergistic action of insoluble particulates and soluble components.

  3. Enhancing immune responses to inactivated porcine parvovirus oil emulsion vaccine by co-inoculating porcine transfer factor in mice.

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    Wang, Rui-ning; Wang, Ya-bin; Geng, Jing-wei; Guo, Dong-hui; Liu, Fang; Chen, Hong-ying; Zhang, Hong-ying; Cui, Bao-an; Wei, Zhan-yong

    2012-07-27

    Inactivated porcine parvovirus (PPV) vaccines are available commercially and widely used in the breeding herds. However, inactivated PPV vaccines have deficiencies in induction of specific cellular immune response. Transfer factor (TF) is a material that obtained from the leukocytes, and is a novel immune-stimulatory reagent that as a modulator of the immune system. In this study, the immunogenicity of PPV oil emulsion vaccine and the immuno-regulatory activities of TF were investigated. The inactivated PPV oil emulsion vaccines with or without TF were inoculated into BALB/c mice by subcutaneous injection. Then humoral and cellular immune responses were evaluated by indirect enzyme-linked immunosorbent assays (ELISA), fluorescence-activated cell sorter analyses (FACS). The results showed that the PPV specific immune responses could be evoked in mice by inoculating with PPV oil emulsion vaccine alone or by co-inoculation with TF. The cellular immune response levels in the co-inoculation groups were higher than those groups receiving the PPV oil emulsion vaccine alone, with the phenomena of higher level of IFN-γ, a little IL-6 and a trace of IL-4 in serum, and a vigorous T-cell response. However, there was no significant difference in antibody titers between TF synergy inactivated vaccine and the inactivated vaccine group (P>0.05). In conclusion, these results suggest that TF possess better cellular immune-enhancing capability and would be exploited into an effective immune-adjuvant for inactivated vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Transcervical Inoculation with Chlamydia trachomatis Induces Infertility in HLA-DR4 Transgenic and Wild-Type Mice.

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    Pal, Sukumar; Tifrea, Delia F; Zhong, Guangming; de la Maza, Luis M

    2018-01-01

    Chlamydia trachomatis is the leading cause of infection-induced infertility in women. Attempts to control this epidemic with screening programs and antibiotic therapy have failed. Currently, a vaccine to prevent C. trachomatis infections is not available. In order to develop an animal model for evaluating vaccine antigens that can be applied to humans, we used C. trachomatis serovar D (strain UW-3/Cx) to induce infertility in mice whose major histocompatibility complex class II antigen was replaced with the human leukocyte antigen DR4 (HLA-DR4). Transcervical inoculation of medroxyprogesterone-treated HLA-DR4 transgenic mice with 5 × 105C. trachomatis D inclusion forming units (IFU) induced a significant reduction in fertility, with a mean number of embryos/mouse of 4.4 ± 1.3 compared to 7.8 ± 0.5 for the uninfected control mice (P < 0.05). A similar fertility reduction was elicited in the wild-type (WT) C57BL/6 mice (4.3 ± 1.4 embryos/mouse) compared to the levels of the WT controls (9.1 ± 0.4 embryos/mouse) (P < 0.05). Following infection, WT mice mounted more robust humoral and cellular immune responses than HLA-DR4 mice. As determined by vaginal shedding, HLA-DR4 mice were more susceptible to a transcervical C. trachomatis D infection than WT mice. To assess if HLA-DR4 transgenic and WT mice could be protected by vaccination, 104 IFU of C. trachomatis D was delivered intranasally, and mice were challenged transcervically 6 weeks later with 5 × 105 IFU of C. trachomatis D. As determined by severity and length of vaginal shedding, WT C57BL/6 and HLA-DR4 mice were significantly protected by vaccination. The advantages and limitations of the HLA-DR4 transgenic mouse model for evaluating human C. trachomatis vaccine antigens are discussed. Copyright © 2017 American Society for Microbiology.

  5. Oral-tolerance induction in diet-induced obese mice.

    Science.gov (United States)

    Mito, Natsuko; Kaburagi, Tomoko; Yoshino, Haruka; Imai, Atsuko; Sato, Kazuto

    2006-08-08

    It is known that immune functions are altered in various ways by obesity. However, changes in the intestinal immune system resulting from obesity remain poorly understood. Oral tolerance is a system that suppresses antigen specific immune responses to orally administrated antigens. The intestinal immune system is intimately associated with the oral tolerance system, that acts to prevent allergic and inflammatory diseases. In this study we investigated the effect of obesity on induction of oral tolerance to ovalbumin (OVA) in an animal model of obesity. Obese mice induced by a high fat diet and control mice were allowed free access for 3 days to a 1%-ovalbumin (OVA) solution in drinking water. After continuous feeding of the antigen, all the mice were immunized by two intraperitoneal injections of OVA administered 7 days apart. In the control mice, induction of oral tolerance caused an increase in antigen specific IgG1 levels and a decrease in IgG2a levels. In contrast, the IgG1/IgG2a ratio was reversed in obese mice. OVA-specific IL-2 production was suppressed by antigen feeding in both the control and obese mice; however, suppression of OVA-specific IL-10 was observed only in the control mice. Although OVA-specific IgA and IgM were not affected by antigen feeding, the obese groups of mice had significantly lower titers of antibodies. These findings suggest that obesity may affect induction of oral tolerance following antigen feeding and that these changes may be related to the inflammatory reaction.

  6. Early systemic inflammatory response in mice after a single oral gavage with live Escherichia coli is evidenced by increased TNF-alpha and nitric oxide production.

    Science.gov (United States)

    Nemec, Ana; Jerin, Aleš; Zdovc, Irena; Budefeld, Tomaž; Verstraete, Frank J M; Eržen, Damijan; Sentjurc, Marjeta; Petelin, Milan; Hitti, Tina; Pavlica, Zlatko

    2012-06-01

    Twenty-four female BALB/c mice were orally inoculated with 10(8) CFU Escherichia coli ATCC 25922 and euthanized 2.5, 7, 13 and 25 h post-inoculation. The levels of organ nitric oxide (NO) and plasma endotoxin, TNF-alpha and nitrite/nitrate (NO(x)) were compared to those found in sham-inoculated mice, to evaluate systemic host-response to a low-level oral exposure to Gram-negative bacteria. Organ bacterial culture and immunohistochemistry for iNOS were performed on lungs, liver, kidneys and brain from all mice. Organ NO and plasma TNF-alpha levels were higher in E. coli-inoculated animals, but no differences were detected in plasma endotoxin levels, NO(x) or iNOS immunostaining for any of the animal groups. Single oral gavage with live E. coli stimulates an early systemic immune response in clinically healthy mice as evidenced by increased plasma TNF-alpha and organ NO levels, but bacteremia and endotoxemia are not related to this inflammatory response. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Kinetics of cytokine profile during intraperitoneal inoculation of Japanese encephalitis virus in BALB/c mice model.

    Science.gov (United States)

    Saxena, Vandana; Mathur, Asha; Krishnani, Narendra; Dhole, Tapan N

    2008-01-01

    Infection with Japanese encephalitis virus (JEV) is mostly asymptomatic/subclinical in 90% of the individuals. Host immune response during subclinical JEV infection is poorly understood. We assessed iNOS, IFN-gamma, TNF-alpha, IL-10 and IL-4 production in spleen, brain and sera of intraperitoneally challenged BALB/c mice by RT-PCR and ELISA along with brain histopathology at different days post inoculation (d.p.i.). In spleen of virus infected mice, expression of all cytokines including iNOS mRNA were upregulated till 5d.p.i. followed by decline. At 5d.p.i., IL-10 expression outcompeted TNF-alpha, IFN-gamma and IL-4. However, in the virus infected mice sera, IL-4 production predominated over TNF-alpha and IL-10 at 5d.p.i. Conversely, cytokines expression and iNOS mRNA remained unchanged in the brain of virus infected mice from 1 to 7d.p.i. A significant increase in the cytokine expression was observed at 11d.p.i. (P<0.05) in virus infected mice brain, with the predominance of IL-10 along with the presence of meningeal inflammation and viral RNA by histology and RT-PCR, respectively. We report a biased pattern of cytokine production in sera, brain and spleen of mice intraperitoneally challenged with JEV. IL-10 exerts neuroprotective function during JEV and regulates deleterious effects of proinflammatory cytokines; however, its mechanism needs further investigation.

  8. Oral cadmium chloride intoxication in mice

    DEFF Research Database (Denmark)

    Andersen, O; Nielsen, J B; Svendsen, P

    1988-01-01

    Diethyldithiocarbamate (DDC) is known to alleviate acute toxicity due to injection of cadmium salts. However, when cadmium chloride was administered by the oral route, DDC enhanced rather than alleviated the acute toxicity; both oral and intraperitoneal (i.p.) administration of DDC had this effect....... Thus, orally administered DDC enhanced cadmium-induced duodenal and ileal tissue damage and inhibition of peristalsis, as indicated by an increased intestinal transit time. At low cadmium doses, the whole-body retention of cadmium was increased by oral DDC administration. Intraperitoneally administered...... DDC increased cadmium-induced acute mortality and testicular necrosis, and it enhanced cadmium-induced reduction of intestinal motility and increased the whole-body retention of cadmium, indicating increased intestinal cadmium absorption. Also, DDC changed the organ distribution of absorbed cadmium...

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

    Directory of Open Access Journals (Sweden)

    Juliana Barreto-de-Albuquerque

    2015-06-01

    Full Text Available Oral transmission of Chagas disease has been documented in Latin American countries. Nevertheless, significant studies on the pathophysiology of this form of infection are largely lacking. The few studies investigating oral route infection disregard that inoculation in the oral cavity (Oral infection, OI or by gavage (Gastrointestinal infection, GI represent different infection routes, yet both show clear-cut parasitemia and heart parasitism during the acute infection. Herein, BALB/c mice were subjected to acute OI or GI infection using 5x10(4 culture-derived Trypanosoma cruzi trypomastigotes. OI mice displayed higher parasitemia and mortality rates than their GI counterparts. Heart histopathology showed larger areas of infiltration in the GI mice, whereas liver lesions were more severe in the OI animals, accompanied by higher Alanine Transaminase and Aspartate Transaminase serum contents. A differential cytokine pattern was also observed because OI mice presented higher pro-inflammatory cytokine (IFN-γ, TNF serum levels than GI animals. Real-time PCR confirmed a higher TNF, IFN-γ, as well as IL-10 expression in the cardiac tissue from the OI group compared with GI. Conversely, TGF-β and IL-17 serum levels were greater in the GI animals. Immunolabeling revealed macrophages as the main tissue source of TNF in infected mice. The high mortality rate observed in the OI mice paralleled the TNF serum rise, with its inhibition by an anti-TNF treatment. Moreover, differences in susceptibility between GI versus OI mice were more clearly related to the host response than to the effect of gastric pH on parasites, since infection in magnesium hydroxide-treated mice showed similar results. Overall, the present study provides conclusive evidence that the initial site of parasite entrance critically affects host immune response and disease outcome. In light of the occurrence of oral Chagas disease outbreaks, our results raise important implications in terms

  10. Preparation of Mosquito Salivary Gland Extract and Intradermal Inoculation of Mice.

    Science.gov (United States)

    Schmid, Michael A; Kauffman, Elizabeth; Payne, Anne; Harris, Eva; Kramer, Laura D

    2017-07-20

    Mosquito-transmitted pathogens are among the leading causes of severe disease and death in humans. Components within the saliva of mosquito vectors facilitate blood feeding, modulate host responses, and allow efficient transmission of pathogens, such as Dengue, Zika, yellow fever, West Nile, Japanese encephalitis, and chikungunya viruses, as well as Plasmodium parasites, among others. Here, we describe standardized methods to assess the impact of mosquito-derived factors on immune responses and pathogenesis in mouse models of infection. This protocol includes the generation of mosquito salivary gland extracts and intradermal inoculation of mouse ears. Ultimately, the information obtained from using these techniques can help reveal fundamental mechanisms of interaction between pathogens, mosquito vectors, and the mammalian host. In addition, this protocol can help establish improved infection challenge models for pre-clinical testing of vaccines or therapeutics that take into account the natural route of transmission via mosquitoes.

  11. Antibody-secreting cell responses and protective immunity assessed in gnotobiotic pigs inoculated orally or intramuscularly with inactivated human rotavirus.

    Science.gov (United States)

    Yuan, L; Kang, S Y; Ward, L A; To, T L; Saif, L J

    1998-01-01

    Newborn gnotobiotic pigs were inoculated twice perorally (p.o.) (group 1) or intramuscularly (i.m.) (group 2) or three times i.m. (group 3) with inactivated Wa strain human rotavirus and challenged with virulent Wa human rotavirus 20 to 24 days later. To assess correlates of protection, antibody-secreting cells (ASC) were enumerated in intestinal and systemic lymphoid tissues from pigs in each group at selected postinoculation days (PID) or postchallenge days. Few virus-specific ASC were detected in any tissues of group 1 pigs prior to challenge. By comparison, groups 2 and 3 had significantly greater numbers of virus-specific immunoglobulin M (IgM) ASC in intestinal and splenic tissues at PID 8 and significantly greater numbers of virus-specific IgG ASC and IgG memory B cells in spleen and blood at challenge. However, as for group 1, few virus-specific IgA ASC or IgA memory B cells were detected in any tissues of group 2 and 3 pigs. Neither p.o. nor i.m. inoculation conferred significant protection against virulent Wa rotavirus challenge (0 to 6% protection rate), and all groups showed significant anamnestic virus-specific IgG and IgA ASC responses. Hence, high numbers of IgG ASC or memory IgG ASC in the systemic lymphoid tissues at the time of challenge did not correlate with protection. Further, our findings suggest that inactivated Wa human rotavirus administered either p.o. or parenterally is significantly less effective in inducing intestinal IgA ASC responses and conferring protective immunity than live Wa human rotavirus inoculated orally, as reported earlier (L. Yuan, L. A. Ward, B. I. Rosen, T. L. To, and L. J. Saif, J. Virol. 70:3075-3083, 1996). Thus, more efficient mucosal delivery systems and rotavirus vaccination strategies are needed to induce intestinal IgA ASC responses, identified previously as a correlate of protective immunity to rotavirus.

  12. Oral inoculation of young dairy calves with Mycoplasma bovis results in colonization of tonsils, development of otitis media and local immunity.

    Directory of Open Access Journals (Sweden)

    Fiona Maunsell

    Full Text Available Because M. bovis otitis media is an economically important problem, there is a need to understand the pathogenesis of disease, not only to improve our understanding of the factors contributing to the development of this disease but also to inform the development of improved diagnostic tests and therapy. Oral ingestion of M. bovis-contaminated milk is linked, but not definitively proven, to development of otitis media. In the current study, we demonstrate that oral ingestion of M. bovis infected colostrum can result in an ascending infection and development of otitis media. Importantly, M. bovis was found to have a previously unrecognized tendency for colonization of the tonsils of calves, which most likely contributed to the subsequent development of otitis media. In contrast, transtracheal inoculation failed to produce clinically significant upper respiratory tract disease, although did induce lower respiratory tract disease. The upper respiratory tract was the major site of M. bovis-specific B cell and mucosal IgA responses in calves inoculated by the oral route. The oral inoculation route of infection presented here is particularly suited to the study of host-pathogen interactions during initial colonization of the tonsils, expansion of infection and dissemination to the lower respiratory tract and middle ear. In addition, it could be used to investigate potential new preventative or control strategies, especially those aimed at limiting colonization of the tonsils and/or spread to the middle ear.

  13. Oral inoculation of young dairy calves with Mycoplasma bovis results in colonization of tonsils, development of otitis media and local immunity.

    Science.gov (United States)

    Maunsell, Fiona; Brown, Mary B; Powe, Joshua; Ivey, James; Woolard, Matthew; Love, Wees; Simecka, Jerry W

    2012-01-01

    Because M. bovis otitis media is an economically important problem, there is a need to understand the pathogenesis of disease, not only to improve our understanding of the factors contributing to the development of this disease but also to inform the development of improved diagnostic tests and therapy. Oral ingestion of M. bovis-contaminated milk is linked, but not definitively proven, to development of otitis media. In the current study, we demonstrate that oral ingestion of M. bovis infected colostrum can result in an ascending infection and development of otitis media. Importantly, M. bovis was found to have a previously unrecognized tendency for colonization of the tonsils of calves, which most likely contributed to the subsequent development of otitis media. In contrast, transtracheal inoculation failed to produce clinically significant upper respiratory tract disease, although did induce lower respiratory tract disease. The upper respiratory tract was the major site of M. bovis-specific B cell and mucosal IgA responses in calves inoculated by the oral route. The oral inoculation route of infection presented here is particularly suited to the study of host-pathogen interactions during initial colonization of the tonsils, expansion of infection and dissemination to the lower respiratory tract and middle ear. In addition, it could be used to investigate potential new preventative or control strategies, especially those aimed at limiting colonization of the tonsils and/or spread to the middle ear.

  14. Effects of Dietary Glutamine Supplementation on the Body Composition and Protein Status of Early-Weaned Mice Inoculated with Mycobacterium bovis Bacillus Calmette-Guerin

    Directory of Open Access Journals (Sweden)

    Ivanir S. O. Pires

    2011-08-01

    Full Text Available Glutamine, one of the most abundant amino acids found in maternal milk, favors protein anabolism. Early-weaned babies are deprived of this source of glutamine, in a period during which endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress, mainly during infections. The objective of this study was to verify the effects of dietary glutamine supplementation on the body composition and visceral protein status of early-weaned mice inoculated with Mycobacterium bovis Bacillus Calmette-Guérin (BCG. Mice were weaned early on their 14th day of life and seperated into two groups, one of which was fed a glutamine-free diet (n = 16 and the other a glutamine-supplemented diet (40 g/kg diet (n = 16. At 21 days of age, some mice were intraperitoneally injected with BCG. Euthanasia was performed at the 28th day of age. BCG inoculation significantly reduced body weight (P < 0.001, lean mass (P = 0.002, water (P = 0.006, protein (P = 0.007 and lipid content (P = 0.001 in the carcass. Dietary glutamine supplementation resulted in a significant increase in serum IGF-1 (P = 0.019 and albumin (P = 0.025 concentration, muscle protein concentration (P = 0.035 and lipid content (P = 0.002 in the carcass. In conclusion, dietary glutamine supplementation had a positive influence on visceral protein status but did not affect body composition in early-weaned mice inoculated with BCG.

  15. Orally administered lactoferrin restores humoral immune response in immunocompromised mice.

    Science.gov (United States)

    Artym, Jolanta; Zimecki, Michal; Paprocka, Maria; Kruzel, Marian L

    2003-10-09

    Cyclophosphamide (CP) is an anti-tumor drug commonly used in the chemotherapy of human cancer and autoimmune diseases. In our previous studies, we have demonstrated that lactoferrin (LF), given orally to CP-immunosuppressed mice, could reconstitute a T cell mediated immune response by the renewal of the T cell population. The aim of this present study was to evaluate the effects of LF on humoral responses in mice treated with cyclophosphamide. We demonstrate that a single, sublethal dose of cyclophosphamide (400 mg/kg body weight) profoundly inhibited the humoral immune response of CBA mice to sheep red blood cells (SRBC), as measured by the number of antibody forming cells (AFC) in the spleen after 5 weeks following CP treatment. Administration of 0.5% bovine LF in drinking water for 5 weeks partially reconstituted the AFC number (30-40% of the control values, but 7-10x more than in CP-treated controls). Determination of T and B cell levels in the spleens by flow cytometry revealed that the content of CD3+ and CD4+ as well as Ig+ splenocytes was elevated in the immunocompromised mice treated with LF. In addition, the number of peritoneal macrophages was partially restored following LF treatment. Evaluation of the proliferative response to concanavalin A (ConA) and pokeweed mitogen (PWM) demonstrated that the diminished reactivity of splenocytes from CP-treated mice was significantly enhanced by LF. In summary, we conclude that the prolonged, oral treatment of immunocompromised mice with LF led to partial reconstitution of the humoral response, associated with elevation of T and B cell and macrophage content and the proliferative response of splenocytes to mitogens.

  16. Chemotherapy Induces Oral Mucositis in Mice Without Additional Noxious Stimuli

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    M. Bertolini

    2017-08-01

    Full Text Available Oral mucositis (OM is a serious side effect of cancer chemotherapy. The pathobiology of oral mucositis remains incompletely understood due to lack of appropriate models which recapitulate the human condition. Existing rodent models are intraperitoneal and require radiation, chemical or mechanical injury to the chemotherapy protocol to induce oral lesions. We aimed to develop an OM mouse model that is induced solely by chemotherapy and reproduces macroscopic, histopathologic and inflammatory characteristics of the human condition. Female C57BL/6 mice were given intravenous 5-Fluorouracil (5-FU injections every 48 hours, for 2 weeks. A high daily dose of intraperitoneal administration was tested for comparison. Mice were monitored daily for weight loss. Epithelial histomorphometric analyses in tongue, esophageal and intestinal tissues were conducted coupled with assessment of apoptosis, cell proliferation, neutrophilic infiltration and the integrity of adherens junctions by immunohistochemistry. Neutropenia was assessed in peripheral blood and bone marrow. Tissues were analyzed for pro-inflammatory cytokines at the protein and mRNA levels. Daily intraperitoneal administration of 5-FU led to rapid weight loss and intestinal mucositis, but no oral inflammatory changes. Intravenous administration triggered atrophy of the oral and esophageal epithelium accompanied by reduction in cell proliferation and increased apoptosis. Coincidental with these changes were up-regulation of NF-κB, TNFα, IL-1β, GM-CSF, IL-6 and KC. Despite neutropenia, increased oral neutrophilic infiltration and reduced E-cadherin was observed in oroesophageal mucosae. We developed a novel experimental tool for future mechanistic studies on the pathogenesis of chemotherapy-induced OM.

  17. Dehydroxymethylepoxyquinomicin (DHMEQ) therapy reduces tumor formation in mice inoculated with tax-deficient adult T-cell leukemia-derived cell lines.

    Science.gov (United States)

    Ohsugi, Takeo; Kumasaka, Toshio; Okada, Seiji; Ishida, Takaomi; Yamaguchi, Kazunari; Horie, Ryouichi; Watanabe, Toshiki; Umezawa, Kazuo

    2007-11-18

    Adult T-cell leukemia (ATL) is an aggressive neoplasm caused by human T-cell leukemia virus type I (HTLV-I), which induces nuclear factor-kappaB (NF-kappaB), a molecule central to the ensuing neoplasia. The NF-kappaB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) has been shown to inhibit NF-kappaB activation in Tax-expressing HTLV-I-infected cells. In this study, we used NOD/SCID beta2-microglobulin(null) mice to show that intraperitoneal inoculation with Tax-deficient ATL cell lines caused rapid death, whereas DHMEQ-treated mice survived. Furthermore, DHMEQ treatment after subcutaneous inoculation inhibited the growth of transplanted ATL cells. These results demonstrate that DHMEQ has therapeutic efficacy on ATL cells, regardless of Tax expression.

  18. Protection of oral or intestinal candidiasis in mice by oral or intragastric administration of herbal food, clove (Syzygium aromaticum).

    Science.gov (United States)

    Taguchi, Yuuki; Ishibashi, Hiroko; Takizawa, Toshio; Inoue, Shigeharu; Yamaguchi, Hideyo; Abe, Shigeru

    2005-01-01

    We examined the effect of a clove (Syzygium aromaticum) administered by two different routes on Candida albicans growth, using a murine oral candidiasis model. When the clove preparation was administered into the oral cavity of Candida-infected mice, their oral symptoms were improved and the number of viable Candida cells in the cavity was reduced. In contrast, when the clove preparation was administered intragastrically, oral symptoms were not improved, but viable cell numbers of Candida in the stomach and feces were decreased. These findings demonstrate that oral intake of an herbal food, clove, may suppress the overgrowth of C. albicans in the alimentary tract including the oral cavity.

  19. [Studies of the origin of malignant rhabdoid tumor(MRT)--experimental researches on the MRT evolving in nude mice inoculated with violently variable HeLa cells].

    Science.gov (United States)

    Zhang, D L; Huang, G S; Li, L J; He, X Y; Xia, G T; Gao, B X; Bai, X H; Liu, S G

    2000-01-01

    Under the prerequisite that the incidence of cancer or tumor in negatively-controlled nude mice inoculated subcutaneously with feline or canine kidney cell cultures purified in vitro at passage 3 or higher (the modal chromosome number of FKC on passage 3 was 38 of diploid at the rate of 80%) was 0%(0/22) and 0%(0/10) respectively, and the incidence of progressively negative growing tumor in controlled nude mice inoculated subcutaneously with repeatedly-frozen- and thawed-HeLa cell cultures of X strain was 20%(1/5), the negative growing malignant tumor (MT) was found in half of the nude mice inoculated subcutaneously with HeLa cell cultures of H strain(with modal chromosome number of 78 +/- 2 of sub-tetraploid at the rate of 40%), the progressively-growing malignant tumor was found in all the other 40 nude mice inoculated subcutaneously with HeLa cell cultures of other strains, with the incidence of MT in nude mice with KB strain (with modal chromosome number of 60 +/- 3 of hyperdiploid at the rate of 72%-76%) 10/10, the incidence of poorly-differentiated MT originated from epithelia in nude mice with X strain (with modal chromosomal number of 62 +/- 3 of hyperdiploid at the rate of 69%) 25/25, and the incidence of MRT in nude mice with in vitro cultured tumor cell NM20/X strain (with modal chromosome number of 68 +/- 3 of both hyperdiploid and subtetraploid at the rate of 52%) 5/5. After being continuously cultivated for 20 passages in vitro, HeLa cell of X strain was subcutaneously inoculated into nude mice and cultivated for 1 passage in vivo within 15 days, and then the developed growing MT was collected as HeLa cell of NM20/X strain on passage 0 and continuously cultivated for 11 passages to prepare for transplanting into nude mice again. Therefore, the highly variable strain of HeLa cells can be successfully selected by alternate cultivation in vitro and in vivo. Occasionally in another experiment, the progressively-growing MRT was found in all the 4 nude mice

  20. Long-term humoral antibody responses by various serologic tests in pigs orally inoculated with oocysts of four strains of Toxoplasma gondii

    DEFF Research Database (Denmark)

    Dubey, J.P.; Andrews, C.D.; Thulliez, P.

    1997-01-01

    Antibody titers to Toxoplasma gondii were determined in 16 pigs orally inoculated with 1000 or 10000 oocysts of one of the four strains (GT-1, ME-49, TS-2, TC-2) of T. gondii. Pigs were euthanized on postinoculation days 103-875 and their tissues were bioassayed for T. gondii. Antibody titers were...... measured in the modified agglutination test (MAT) using formalin-preserved (test A) or acetone-preserved (test B) tachyzoites, latex agglutination test (LAT), indirect hemagglutination test (IHA), enzyme-linked immunobsorbant assay (ELISA), and the Sabin-Feldman dye test (DT). Toxoplasma gondii...

  1. Growth of L. monocytogenes strain F2365 on ready-to-eat turkey meat does not enhance gastrointestinal listeriosis in intragastrically inoculated A/J mice

    Science.gov (United States)

    Peterson, Luke D.; Faith, Nancy G.; Czuprynski, Charles J.

    2015-01-01

    There have been significant outbreaks of listeriosis associated with consumption of contaminated ready-to-eat (RTE) turkey meat products. In this study, we investigated whether growth on RTE deli turkey meat sends environmental signals to listerial cells that makes them more virulent in the gastrointestinal tract of mice. L. Listeria monocytogenes strain F2365 grew from a starting inoculum of 103 CFU/mL to final numbers of 108–109 CFU/mL (within 12 days at 10 °C) when inoculated onto sliced processed, or whole muscle, turkey breast, or into emulsified whole turkey breast. We did not observe any difference in the numbers of CFU recovered from the spleens and livers of A/J mice inoculated intragastrically with L. monocytogenes grown on sliced turkey meat, in emulsified turkey meat, or in brain heart infusion broth. These results suggest that growth on RTE sliced deli turkey, or in RTE emulsified deli turkey, does not enhance the ability of L. monocytogenes F2365 to cause gastrointestinal listeriosis in intragastrically challenged A/J mice. PMID:18559288

  2. Molecular Characterization of the Onset and Progression of Colitis in Inoculated Interleukin-10 Gene-Deficient Mice: A Role for PPARα

    Directory of Open Access Journals (Sweden)

    Bianca Knoch

    2010-01-01

    Full Text Available The interleukin-10 gene-deficient (Il10-/- mouse is a model of human inflammatory bowel disease and Ppara has been identified as one of the key genes involved in regulation of colitis in the bacterially inoculated Il10-/- model. The aims were to (1 characterize colitis onset and progression using a histopathological, transcriptomic, and proteomic approach and (2 investigate links between PPARα and IL10 using gene network analysis. Bacterial inoculation resulted in severe colitis in Il10-/- mice from 10 to 12 weeks of age. Innate and adaptive immune responses showed differences in gene expression relating to colitis severity. Actin cytoskeleton dynamics, innate immunity, and apoptosis-linked gene and protein expression data suggested a delayed remodeling process in 12-week-old Il10-/- mice. Gene expression changes in 12-week-old Il10-/- mice were related to PPARα signaling likely to control colitis, but how PPARα activation might regulate intestinal IL10 production remains to be determined.

  3. Oral Treatment with the Ghrelin Receptor Agonist HM01 Attenuates Cachexia in Mice Bearing Colon-26 (C26) Tumors.

    Science.gov (United States)

    Villars, Fabienne O; Pietra, Claudio; Giuliano, Claudio; Lutz, Thomas A; Riediger, Thomas

    2017-05-05

    The gastrointestinal hormone ghrelin reduces energy expenditure and stimulates food intake. Ghrelin analogs are a possible treatment against cancer anorexia-cachexia syndrome (CACS). This study aimed to investigate whether oral treatment with the non-peptidergic ghrelin receptor agonist HM01 counteracts CACS in colon-26 (C26) tumor-bearing mice. The C26 tumor model is characterized by pronounced body weight (BW) loss and muscle wasting in the absence of severe anorexia. We analyzed the time course of BW loss, body composition, muscle mass, bone mineral density, and the cytokines interleukin-6 (IL-6) and macrophage-inhibitory cytokine-1 (MIC-1). Moreover, we measured the expression of the muscle degradation markers muscle RING-finger-protein-1 (MuRF-1) and muscle atrophy F-box (MAFbx). After tumor inoculation, MIC-1 levels increased earlier than IL-6 and both cytokines were elevated before MuRF-1/MAFbx expression increased. Oral HM01 treatment increased BW, fat mass, and neuronal hypothalamic activity in healthy mice. In tumor-bearing mice, HM01 increased food intake, BW, fat mass, muscle mass, and bone mineral density while it decreased energy expenditure. These effects appeared to be independent of IL-6, MIC-1, MuRF-1 or MAFbx, which were not affected by HM01. Therefore, HM01 counteracts cachectic body weight loss under inflammatory conditions and is a promising compound for the treatment of cancer cachexia in the absence of severe anorexia.

  4. Antibody-Secreting Cell Responses and Protective Immunity Assessed in Gnotobiotic Pigs Inoculated Orally or Intramuscularly with Inactivated Human Rotavirus†

    OpenAIRE

    Yuan, Lijuan; Kang, S.-Y.; Ward, Lucy A.; To, Thanh L.; Saif, Linda J.

    1998-01-01

    Newborn gnotobiotic pigs were inoculated twice perorally (p.o.) (group 1) or intramuscularly (i.m.) (group 2) or three times i.m. (group 3) with inactivated Wa strain human rotavirus and challenged with virulent Wa human rotavirus 20 to 24 days later. To assess correlates of protection, antibody-secreting cells (ASC) were enumerated in intestinal and systemic lymphoid tissues from pigs in each group at selected postinoculation days (PID) or postchallenge days. Few virus-specific ASC were dete...

  5. Inoculation of BALB/c mice with Lacazia loboi Inoculação de Lacazia loboi em camundongos BALB/c

    Directory of Open Access Journals (Sweden)

    Suzana MADEIRA

    2000-10-01

    Full Text Available In a previous study, the authors inoculated Swiss mice with Lacazia loboi (L. loboi and succeeded in maintaining a granulomatous infiltrate and viable fungal cells up to one year and six months after inoculation. Considering the experimental work on paracoccidioidomycosis, 0.03 ml of a fungal suspension obtained from a biopsy of a Jorge Lobo's Disease patient were inoculated into both hind foot pads of 32 six week-old BALB/c mice of both sexes. The animals were sacrificed 1, 4, 7 and 10 months post inoculation. The suspension contained 1.3 x 10(6 fungi/ml and presented 38% viability. Seven months after inoculation, most of the animals presented profuse infiltrates consisting of isolated histiocytes, foreign body and Langhans' giant cells and a large number of fungi, most of them viable. Emergence of macroscopic lesions was observed during the 8th month. Based on fungal count, viability index before and after inoculation, presence of macroscopic lesions and histopathological findings similar to the findings in humans, the authors believe that BALB/c mice may be a good experimental model to study Jorge Lobo's Disease, mainly regarding therapeutic evaluation.Em trabalho anterior, os autores inocularam camundongos Suíços com o Lacazia loboi (L. loboi conseguindo a manutenção de um infiltrado granulomatoso e células fúngicas viáveis por até um ano e 6 meses após a inoculação. Considerando-se trabalhos experimentais realizados na paracoccidioidomicose, eles inocularam 0,03 ml de suspensão fúngica, obtida de biópsia de lesão de um paciente portador da doença de Jorge Lobo, em ambos coxins plantares traseiros de 32 camundongos BALB/c, de ambos os sexos e com 6 semanas de idade. Os animais foram sacrificados com 1, 4, 7 e 10 meses pós-inoculação. A suspensão possuía 1.3x10(6 de fungos/ml e 38% de índice de viabilidade. Após 7 meses de inoculação a maioria dos animais já apresentava um infiltrado exuberante constituído por histi

  6. [Dentification ability of inbred strain mice tooth germs homologically transplanted into oral submucosa].

    Science.gov (United States)

    Li, Heng; Que, Guoying; Zhang, Lei

    2010-05-01

    To establish a suitable environment for the bioengineered teeth in vivo by observing the dentification ability of BALB/C mice tooth germs homologically implanted into the oral submucosa. The first molar tooth germs of BALB/C mice 4 days after birth were transplanted into the oral submucosa of BALB/C male mice, and then recycled for regular histological observation after 1, 2, 3, and 6 week transplantation. The tooth germs in the oral submucosa grew well with continuing developing enamelum and pulpodentinal complex, and the dentinal tubules were clear. The environment of the BALB/C male mice oral submucosa is favorable for the growth of tooth germs in inbred strain BALB/C mice, and it can provide a new environment for the development of bioengineered teeth in vivo.

  7. Mendelian analysis of a metastasis-prone substrain of BALB/c nude mice using a subcutaneously inoculated human tumour

    DEFF Research Database (Denmark)

    Schou, M; Brünner, N; Spang-Thomsen, M

    2006-01-01

    Most nude mice do not allow the formation of metastases after heterotransplantation of human malignant tumours. Here we describe a substrain of BALB/c nude mice (BALB/c/AnNCr) that reproducibly allows some human cancers to metastasize. By Mendelian analysis of hybrids between this substrain and C57......BL/6J +/+ mice we found that the ability to allow a human tumour (MDA-MB-435 BAG) to express its metastatic phenotype is determined by a recessively inheritable trait in the mouse host. We are presently working to identify the genetics responsible for development of metastases. The study also...... includes immunohistochemical and electron microscopic analysis of the test tumour, originally assumed to be a human mammary carcinoma, but shown to possess characteristics of a malignant melanoma (1). The ultimate aim of our ongoing study is to establish a substrain of nude mice that will allow metastasis...

  8. Epstein-Barr virus (HHV-4) inoculation to rabbits by intranasal and oral routes results in subacute and/or persistent infection dissimilar to human disease.

    Science.gov (United States)

    Rajčáni, Julius; Szenthe, Kalman; Durmanová, Vladimira; Tóth, Agnes; Asványi, Balazs; Pitlik, Ervin; Stipkovits, Laszlo; Szathmary, Susan

    2014-01-01

    We report the infection of New Zealand white rabbits with Epstein-Barr virus (EBV). EBV prepared in B95-8 (producer) cells was inoculated to rabbits by combined intranasal and oral routes. Blood and white blood cell (WBC) samples were taken before infection, then on days 8, 28 and 98 post-infection (p.i.). Administration of either 3 × 10(8) (group A, 11 rabbits) or 1 × 10(9) (group B, 10 rabbits) EBV DNA copies per animal induced subacute and/or persistent infection. The IgG antibodies in plasma were detected by ELISA as well as by immunoblot (IB). The IB bands showed mainly antibodies to the BZRF1/Zta transactivation polypeptide (69.2%), the p54 early protein (53.4%) and to the p23 capsid protein (35.8%). No anti-EBNA1 antibody was detected throughout. Viral DNA could be detected by PCR in WBCs and/or spleen of 7 out of 21 infected rabbits (30%), while 60-80% of them showed serologic response. The transiently present EBV DNA was accompanied by LMP1 antigen. Rabbits developed persistent EBV infection in the absence of EBNA1 antibodies and by the lack of typical infectious mononucleosis-like syndrome. The absence of EBNA1 antibody may reflect the lack of EBNA1 in B cells of EBV-inoculated rabbits. © 2014 S. Karger AG, Basel

  9. Antibody responses measured by various serologic tests in pigs orally inoculated with low numbers of Toxoplasma gondii oocysts

    DEFF Research Database (Denmark)

    Dubey, J. P.; Andrews, C.D.; Lind, Peter

    1996-01-01

    ) infective oocysts, and 6 pigs served as uninoculated controls. Blood (serum) samples were obtained at 1- to 3-week intervals until euthanasia. At necropsy, the brain, heart, and tongue of pigs were bioassayed in mice and cats for isolation of T gondii. Modified agglutination test (MAT), using whole, fixed...

  10. Orally administered indomethacin acutely reduces cellular prion protein in the small intestine and modestly increases survival of mice exposed to infectious prions.

    Science.gov (United States)

    Martin, Gary R; Sharkey, Keith A; Jirik, Frank R

    2015-05-01

    The oral uptake of infectious prions represents a common way to acquire a prion disease; thus, host factors, such as gut inflammation and intestinal "leakiness", have the potential to influence infectivity. For example, the ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) is known to induce intestinal inflammation and increase intestinal permeability. Previously, we reported that normal cellular prion protein (PrP(C)) expression was increased in experimental colitis, and since the level of PrP(C) expressed is a determinant of prion disease propagation, we hypothesized that NSAID administration prior to the oral inoculation of mice with infectious prions would increase intestinal PrP(C) expression and accelerate the onset of neurological disease. In the long-term experiments, one group of mice was gavaged with indomethacin, followed by a second gavage with brain homogenate containing mouse-adapted scrapie (ME7). Control mice received ME7 brain homogenate alone. Brain and splenic tissues were harvested at several time points for immunoblotting, including at the onset of clinical signs of disease. In a second series of experiments, mice were gavaged with indomethacin to assess the acute effects of this treatment on intestinal PrP(C) expression. Acutely, NSAID treatment reduced intestinal PrP(C) expression, and chronically, there was a modest delay in the onset of neurological disease. In contrast to our hypothesis, brief exposure to an NSAID decreased intestinal PrP(C) expression and led to a modest survival advantage following oral ingestion of infectious prions.

  11. Molecular immune responses to aerosol challenge with Francisella tularensis in mice inoculated with live vaccine candidates of varying efficacy.

    Directory of Open Access Journals (Sweden)

    Hua Shen

    2010-10-01

    Full Text Available Francisella tularensis is a facultative intracellular bacterial pathogen and the etiological agent of tularemia. The subspecies F. tularensis tularensis is especially virulent for humans when inhaled and respiratory tularemia is associated with high mortality if not promptly treated. A live vaccine strain (LVS derived from the less virulent holarctica subspecies confers incomplete protection against aerosol challenge with subsp. tularensis. Moreover, correlates of protection have not been established for LVS.In the present study we compare molecular immune responses elicited by LVS and two defined deletion mutants of clinical subsp. tularensis strain, SCHU S4, that confer enhanced protection in a mouse model. BALB/c mice were immunized intradermally then challenged with an aerosol of SCHU S4 six weeks later. Changes in the levels of a selected panel of cytokines and chemokines were examined in the lungs, spleens, and sera of vaccinated and challenged mice. Mostly, increased cytokine and chemokine levels correlated with increased bacterial burden. However, after adjusting for this variable, immunization with either of the two Schu S4 mutants resulted in higher levels of several pulmonary cytokines, versus those resulting after LVS immunization, including IL-17. Moreover, treatment of mice immunized with ΔclpB with anti-IL-17 antibodies post-challenge enhanced lung infection.This is the first report characterizing local and systemic cytokine and chemokine responses in mice immunized with vaccines with different efficacies against aerosol challenge with virulent F. tularensis subsp. tularensis. It shows that increases in the levels of most of these immunomodulators, including those known to be critical for protective immunity, do not superficially correlate with protection unless adjusted for the effects of bacterial burden. Additionally, several cytokines were selectively suppressed in the lungs of naïve mice, suggesting that one mechanism of

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

    Directory of Open Access Journals (Sweden)

    Raul Ramos Furtado Dias

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

  13. Toxoplasma gondii Oral Infection Induces Intestinal Inflammation and Retinochoroiditis in Mice Genetically Selected for Immune Oral Tolerance Resistance

    Science.gov (United States)

    Dias, Raul Ramos Furtado; de Carvalho, Eulógio Carlos Queiroz; Leite, Carla Cristina da Silva; Tedesco, Roberto Carlos; Calabrese, Katia da Silva; Silva, Antonio Carlos; DaMatta, Renato Augusto; de Fatima Sarro-Silva, Maria

    2014-01-01

    Toxoplasmosis is a worldwide disease with most of the infections originating through the oral route and generates various pathological manifestations, ranging from meningoencephalitis to retinochoroiditis and inflammatory bowel disease. Animal models for these pathologies are scarce and have limitations. We evaluated the outcome of Toxoplasma gondii oral infection with 50 or 100 cysts of the ME-49 strain in two lines of mice with extreme phenotypes of susceptibility (TS) or resistance (TR) to immune oral tolerance. Therefore, the aim of this study was to evaluate the behaviour of TS and TR mice, orally infected by T. gondii, and determine its value as a model for inflammatory diseases study. Mortality during the acute stage of the infection for TR was 50% for both dosages, while 10 and 40% of the TS died after infection with these respective dosages. In the chronic stage, the remaining TS succumbed while TR survived for 90 days. The TS displayed higher parasite load with lower intestinal inflammation and cellular proliferation, notwithstanding myocarditis, pneumonitis and meningoencephalitis. TR presented massive necrosis of villi and crypt, comparable to inflammatory bowel disease, with infiltration of lymphoid cells in the lamina propria of the intestines. Also, TR mice infected with 100 cysts presented intense cellular infiltrate within the photoreceptor layer of the eyes, changes in disposition and morphology of the retina cell layers and retinochoroiditis. During the infection, high levels of IL-6 were detected in the serum of TS mice and TR mice presented high amounts of IFN-γ and TNF-α. Both mice lineages developed different disease outcomes, but it is emphasized that TR and TS mice presented acute and chronic stages of the infection, demonstrating that the two lineages offer an attractive model for studying toxoplasmosis. PMID:25437299

  14. Oral inoculation of neonatal Suffolk sheep with the agent of classical scrapie results in PrP(Sc) accumulation in sheep with the PRNP ARQ/ARQ but not the ARQ/ARR genotype.

    Science.gov (United States)

    Greenlee, Justin J; Smith, Jodi D; Hamir, Amir N

    2016-04-01

    Scrapie is a transmissible spongiform encephalopathy that can be transmitted amongst susceptible sheep. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent. This study reports the failure to detect PrP(Sc) in nervous or lymphoid tissues of Suffolk sheep of the PRNP ARQ/ARR genotype after oral inoculation with a U.S. scrapie isolate. Lambs were inoculated within the first 24 h of birth with 1 ml of a 10% (wt./vol.) brain homogenate derived from a clinically affected ARQ/ARQ sheep. The inoculated sheep were observed daily throughout the experiment for clinical signs suggestive of scrapie until they were necropsied at 86 months post inoculation. Tissues were collected for examination by immunohistochemistry and enzyme immunoassay, but all failed to demonstrate evidence of scrapie infection. Neonatal sheep of the ARQ/ARQ genotype receiving the same inoculum developed scrapie within 24 months. Lambs of the ARQ/ARR genotype that received the same inoculum by intracranial inoculation develop scrapie with a prolonged incubation period and with abnormal prion present within the central nervous system, but not peripheral lymphoid tissues. Results of this study suggest that ARQ/ARR sheep are resistant to oral infection with the scrapie isolate used even during the neonatal period. Published by Elsevier Ltd.

  15. Suppression of human solid tumor growth in mice by intratumor and systemic inoculation of histidine-rich and pH-dependent host defense-like lytic peptides.

    Science.gov (United States)

    Makovitzki, Arik; Fink, Avner; Shai, Yechiel

    2009-04-15

    Previously, we reported that intratumor or systemic inoculation of a cationic 15-mer, innate immunity-like lytic peptide composed of d- and l-amino acids ([D]-K(6)L(9)) caused growth arrest of 22RV1 prostate carcinoma xenografts in a mouse model. However, despite its therapeutic potential, this peptide has significant systemic toxicity at concentrations slightly higher than the therapeutic one. Here, we used the acidic environment created by solid tumors as a trigger to activate anticancer lytic peptides by making them cationic only at low pH levels. We achieved this selectivity by substituting lysines (pKa, approximately 10.5) for histidines (pKa, approximately 6.1) in the parental peptide [D]-K(6)L(9). Histidine is protonated below pH 7. For that purpose, we replaced either three or all six lysines in the parental peptide with histidines to obtain the peptides [D]-K(3)H(3)L(9) and [D]-H(6)L(9). Interestingly, in vitro experiments showed pH-dependent activity only with [D]-H(6)L(9) mainly toward cancer cell lines. However, both peptides showed reduced systemic toxicity compared with the parental peptide. Intratumor and systemic inoculation of these peptides resulted in a significant decrease in the 22RV1 prostate cancer tumor volume and systemic secretion of prostate-specific antigen in a xenograft mice model. Moreover, histologic modifications revealed a significant reduction in new blood vessels selectively in tumor tissues after treatment with the peptides compared with the untreated tumors. The lytic mode of action of these new peptides, which makes it difficult for the cancer cells to develop resistance, and their selective and pH-dependent activity make them potential candidates for treatment of solid cancer tumors.

  16. Time course of fetal tissue invasion by Listeria monocytogenes following an oral inoculation in pregnant guinea pigs.

    Science.gov (United States)

    Williams, Denita; Dunn, Sherry; Richardson, Arena; Frank, Joseph F; Smith, Mary Alice

    2011-02-01

    Pregnant women are 20 times more likely to develop listeriosis than are members of the general population, and infection can result in abortion, stillbirth, or neonatal illness. The objective of this study was to orally challenge pregnant guinea pigs with Listeria monocytogenes to assess maternal and fetal tissue invasion at postinoculation days 2, 6, 9, and 21. The time course of invasion was followed by fluorescence microscopy and a traditional culture method. Guinea pigs were treated on gestation day 35 with L. monocytogenes doses ranging from 10(4) to 10(8) CFU. L. monocytogenes was isolated and viewed in maternal and fetal tissues as early as 2 days postinoculation. L. monocytogenes was isolated from placentas, fetal livers and brains, and maternal spleens at similar rates, suggesting that invasion of the spleen could be indicative of fetal invasion. When comparing fecal shedding, all animals treated with 10(4) CFU were shedding L. monocytogenes by postinoculation day 7, and all animals treated with the higher doses (10(6) or 10(8) CFU) were shedding L. monocytogenes by postinoculation day 5. These data suggest that L. monocytogenes crosses the fetoplacental barrier and invades the fetus by day 2 after maternal ingestion. When comparing the sensitivities of microscopy and culture, neither method consistently detected L. monocytogenes at a higher rate. However, detection in individual tissues differed. Microscopy was significantly more sensitive with fetal liver (P<0.001) and brain (P<0.001) at the highest dose of 10(8) CFU, but at the lowest dose of 10(4) CFU culture was significantly more sensitive with maternal spleen (P=0.04). Copyright ©, International Association for Food Protection

  17. Oral toxicity of elephant foot yam (Amorphophallus paeoniifolius tuber in mice

    Directory of Open Access Journals (Sweden)

    Yadu Nandan Dey

    2017-02-01

    Full Text Available Context: Amorphophallus paeoniifolius tuber is an important constituent of Ayurvedic system of medicine. The tuber of this plant has high medicinal value and is consumed as a food. It is associated with acridity (itchy sensation in mouth and throat upon oral consumption and presence of high oxalates raphides. Aims: To evaluate the acute and subacute oral toxicity studies of methanolic (APME and aqueous (APAE extracts of Amorphophallus paeoniifolius tuber in Swiss albino mice according to OECD guidelines. Methods: In acute oral toxicity study, the mice were orally administered a single dose of APME or APAE (2000 mg/kg and clinical signs and mortality were observed for 14 days. In subacute (repeated dose oral toxicity study, the mice were administered once daily, orally with APME or APAE (1000 mg/kg up to 28 days. The parameters assessed were behavior, clinical signs, body weight, feed and water consumption, urinary, biochemical, hematological and major organ weights and histology. Results: In acute toxicity study, there was no treatment related mortality and morbidity in any of the group. In subacute toxicity study, there were no significant changes in behavior, body weight, feed and water consumption, urinary, biochemical, hematological and organ weight and histological parameters compared to vehicle treated group. There was no treatment related mortality or morbidity. Conclusions: Administration of methanolic and aqueous extracts of Amorphophallus paeoniifolius tuber, individually in acute and 28 days repeated dose in mice, did not exhibit any toxicity or adverse effect at the doses used.

  18. Effects of oral administration of titanium dioxide fine-sized particles on plasma glucose in mice.

    Science.gov (United States)

    Gu, Ning; Hu, Hailong; Guo, Qian; Jin, Sanli; Wang, Changlin; Oh, Yuri; Feng, Yujie; Wu, Qiong

    2015-12-01

    Titanium dioxide (TiO2) is an authorized additive used as a food colorant, is composed of nano-sized particles (NP) and fine-sized particles (FP). Previous study reported that oral administration of TiO2 NPs triggers an increase in plasma glucose of mice. However, no previous studies have focused on toxic effects of TiO2 FPs on plasma glucose homeostasis following oral administration. In the current study, mice were orally administered TiO2 FPs greater than 100 nm in size (64 mg/kg body weight per day), and effects on plasma glucose levels examined. Our results showed that titanium levels was not changed in mouse blood, livers and pancreases after mice were orally administered TiO2 FPs. Biochemical analyzes showed that plasma glucose and ROS levels were not affected by TiO2 FPs. Histopathological results showed that TiO2 FPs did not induce pathology changes in organs, especially plasma glucose homeostasis regulation organs, such as pancreas and liver. Western blotting showed that oral administration of TiO2 FPs did not induce insulin resistance (IR) in mouse liver. These results showed that, TiO2 FPs cannot be absorbed via oral administration and affect plasma glucose levels in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. The effects of repeated oral gavage on the health of male CD-1 mice.

    Science.gov (United States)

    Arantes-Rodrigues, Regina; Henriques, Andreia; Pinto-Leite, Rosário; Faustino-Rocha, Ana; Pinho-Oliveira, Jacinta; Teixeira-Guedes, Catarina; Seixas, Fernanda; Gama, Adelina; Colaço, Bruno; Colaço, Aura; Oliveira, Paula A

    2012-05-01

    Oral gavage is a widely used method for administering substances to animals in pharmacological and toxicological studies. The authors evaluated whether oral gavage causes behavioral indicators of stress, increased mortality rate, alterations in food and water consumption and body weight or histological lesions in CD-1 mice. Gavage was carried out once per d for 5 d per week over 6 consecutive weeks. The mortality rate of mice in this study was 15%. Mice subjected to gavage did not undergo changes in food or water consumption during the study, and their mean body weights and relative organ weights were similar to those of mice in the control group. Serum cortisol levels at the time of euthanasia in mice in both groups were within the normal range. Histopathology showed acute esophagitis and pleurisy, indicative of perforation of the esophagus, in the two mice that died but no abnormalities in the other mice. The results suggest that animal stress and mortality related to oral gavage can be minimized when the procedure is carried out by an experienced technician.

  20. Evidence that active protection following oral immunization of mice with live rotavirus is not dependent on neutralizing antibody.

    Science.gov (United States)

    Ward, R L; McNeal, M M; Sheridan, J F

    1992-05-01

    Studies were performed to determine whether active immunity against murine rotavirus (EDIM) infection of mice correlated with titers of neutralizing antibody to the challenge virus. Neonatal mice administered either murine or heterologous rotaviruses all developed diarrhea and high titers of serum rotavirus IgG. However, only mice given EDIM, the murine EB, or simian SA11-FEM strains were protected against EDIM infection when challenged 60 days later. Other serotype 3 strains (RRV, SA11-SEM), as well as strains belonging to serotypes 5 and 6 (OSU, NCDV, WC3), were not protective. Serum neutralizing antibody titers to EDIM were almost undetectable after rotavirus infection with any strain and could not, therefore, be correlated with protection. Likewise, intestinal neutralizing antibody titers were extremely low 21 days after EDIM infection, and by 60 days after inoculation, EDIM-infected mice had no greater intestinal neutralizing antibody titers than uninoculated controls. Mice inoculated with SA11-FEM as neonates had much higher serum rotavirus IgG responses than mice inoculated as adults, and only those infected with this virus as neonates were protected. Thus, although immunity to EDIM did not correlate with the presence of neutralizing antibody to EDIM, it did correlate with the overall magnitude of the immune response after inoculation with SA11-FEM.

  1. Oral L-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice

    DEFF Research Database (Denmark)

    Clemmensen, Christoffer; Smajilovic, Sanela; Smith, Eric P

    2013-01-01

    in vivo, to augment postprandial insulin secretion and improve glucose tolerance. To test this, we administered l-arginine or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in lean and diet-induced obese mice. In both lean and obese mice oral l-arginine increased plasma GLP-1......Pharmacological and surgical interventions that increase glucagon-like peptide 1 (GLP-1) action are effective to improve glucose homeostasis in type 2 diabetes mellitus. In light of this, nutritional strategies to enhance postprandial GLP-1 secretion, particularly in the context of diet......-induced obesity, may provide an alternative therapeutic approach. Importantly, recent evidence suggests the amino acid l-arginine, a well-known insulin secretagogue, can also stimulate release of GLP-1 from isolated rat intestine. Here we tested the hypothesis that oral l-arginine acts as a GLP-1 secretagogue...

  2. [Enhancing effect of Ulex europaeus agglutinin I modified liposomes on oral insulin absorption in mice].

    Science.gov (United States)

    Zhang, Na; Ping, Qi-neng; Xu, Wen-fang

    2004-12-01

    To investigate the enhancing effect on insulin absorption through GI. tract in mice by using the Ulex europaeus agglutinin I (UEA1) modified liposomes as the carrier. UEA1 modified phosphatidylethanolamine (PE) was prepared by conjugating method of 1-ethyl-3-(3'-dimethylaminopropyl) carbodiimide (EDC), then the modified compound (PE-UEA1) was incorporated into the conventional liposomes of insulin to obtain UEA1 modified liposomes. The agglutination test was performed to examine the UEA1 biological activities after synthesis and modification. When liposomes were applied to healthy mice or diabetic mice at insulin dose of 350 u x kg(-1) orally, the hypoglycemic effect was investigated according to the blood glucose level determination. The blood glucose levels of the healthy mice reduced by UEA1 modified liposomes were (84 +/- 15)% at 4 h, (78 +/- 11)% at 8 h and (90 +/- 12)% at 12 h after oral administration. The conventional liposomes and saline showed no effect. The blood glucose levels of the diabetic mice reduced by UEA1 modified liposomes were (73 +/- 7)% at 4 h, (74 +/- 9)% at 8 h, (86 +/- 9)% at 12 h after oral administration. The UEA1 modified liposomes promote the oral absorption of insulin due to the specific-site combination on M cell membrane.

  3. Indomethacin Treatment of Mice with Premalignant Oral Lesions Sustains Cytokine Production and Slows Progression to Cancer.

    Science.gov (United States)

    Johnson, Sara D; Young, M Rita I

    2016-01-01

    Current treatment options for head and neck squamous cell carcinoma (HNSCC) patients are often ineffective due to tumor-localized and systemic immunosuppression. Using the 4-NQO mouse model of oral carcinogenesis, this study showed that premalignant oral lesion cells produce higher levels of the immune modulator, PGE2, compared to HNSCC cells. Inhibiting prostaglandin production of premalignant lesion cells with the pan-cyclooxygenase inhibitor indomethacin stimulated their induction of spleen cell cytokine production. In contrast, inhibiting HNSCC prostaglandin production did not stimulate their induction of spleen cell cytokine production. Treatment of mice bearing premalignant oral lesions with indomethacin slowed progression of premalignant oral lesions to HNSCC. Flow cytometric analysis of T cells in the regional lymph nodes of lesion-bearing mice receiving indomethacin treatment showed an increase in lymph node cellularity and in the absolute number of CD8(+) T cells expressing IFN-γ compared to levels in lesion-bearing mice receiving diluent control treatment. The cytokine-stimulatory effect of indomethacin treatment was not localized to regional lymph nodes but was also seen in the spleen of mice with premalignant oral lesions. Together, these data suggest that inhibiting prostaglandin production at the premalignant lesion stage boosts immune capability and improves clinical outcomes.

  4. Expression of prion protein in the gut of mice infected orally with the 301V murine strain of the bovine spongiform encephalopathy agent.

    Science.gov (United States)

    González, L; Terry, L; Jeffrey, M

    2005-05-01

    Transmissible spongiform encephalopathies (TSEs) are characterized by the accumulation of an abnormal, disease-associated prion protein (PrP(d)). Expression of its normal cellular counterpart (PrP(c)) by the host is a pre-requisite for the spread of infection to the central nervous system and the development of disease. Moreover, cells expressing PrP(c) at specific sites such as the gastrointestinal tract might be regarded as the initial point of PrP(c)-PrP(d) conversion after infection by the oral route. In this study, inbred mice of the I/M strain were infected orally with the 301V murine strain of the bovine spongiform encephalopathy agent. The expression of PrP(c) and the accumulation of PrP(d) in the intestine was then investigated immunohistochemically, together with the variations in immunoreactivity that resulted from different pretreatments of the tissue. After proteinase K (PK) pretreatment, abnormal PrP was still detectable only in the gut-associated lymphoid tissue (GALT) of clinically affected mice and, to a much more limited degree, in the enteric nervous system (ENS). Cellular PrP that disappeared after PK treatment was particularly conspicuous in the ENS and present to a lesser extent in the GALT of all mice examined after inoculation with 301V or with normal brain homogenates, as well as in uninoculated controls. These findings suggested that not all PrP found in infected mice was PrP(d) and that part of the PrP(d) was sensitive to PK treatment. Reactivity to PrP antibody 1A8 was consistently found in the absorptive epithelium of the intestinal villi, with or without PK pretreatment. However, epithelial immunolabelling was comparable in inoculated and uninoculated mice and was also consistently seen in PrP "knockout" mice used as controls. It is therefore concluded that immunohistochemically detectable accumulation of PrP(d) in the gut of mice is a relatively late event in the pathogenesis of experimental infection in this model and that the

  5. Evaluation of Mice Undergoing Serial Oral Gavage While Awake or Anesthetized.

    Science.gov (United States)

    Jones, Carissa P; Boyd, Kelli L; Wallace, Jeanne M

    2016-11-01

    Although oral gavage is the most straightforward approach to achieve precise enteric administration in rodents, it is associated with potential adverse consequences. Here we compare the effects of serial oral gavage in awake compared with anesthetized mice. Female C57BL/6J mice (n = 20 per group) were assigned to 1 of 3 treatment groups (control, awake gavage, or anesthetized gavage) and gavaged daily with 0.2 mL of saline (with no manipulation on weekends) for a total of 18 treatment days. Body weight and clinical appearance were monitored throughout the treatment period, after which mice were euthanized and necropsied. Endpoints evaluated included adrenal gland weight, plasma corticosterone, lymphocyte:neutrophil ratio, and esophageal histopathology. Mean body weight did not differ between groups. Compared with other groups, the awake gavage group had more mice removed (3 of 20) prior to study completion due to body weight loss greater than 10%, with corresponding gross and histopathologic lesions attributed to the gavage procedure. Mice gavaged when awake had an over 20-fold higher incidence of incomplete retention of the administered saline than did anesthetized mice. Of the mice that completed the study, esophageal inflammation was not apparent at necropsy regardless of treatment, with the exception of a single mouse in the awake gavage group. Although WBC and lymphocyte counts were lower in mice in the anesthetized gavage group compared with other groups, none of the endpoints measured to evaluate stress (adrenal gland weight, neutrophil:lymphocyte ratio, plasma corticosterone) differed. These findings support the use of brief isoflurane anesthesia when performing serial oral gavage in mice.

  6. Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration

    DEFF Research Database (Denmark)

    Bruun, Susanne W.; Josefsen, Knud; Tanassi, Julia T

    2016-01-01

    Gluten promotes type 1 diabetes in nonobese diabetic (NOD) mice and likely also in humans. In NOD mice and in non-diabetes-prone mice, it induces inflammation in the pancreatic lymph nodes, suggesting that gluten can initiate inflammation locally. Further, gliadin fragments stimulate insulin...... secretion from beta cells directly. We hypothesized that gluten fragments may cross the intestinal barrier to be distributed to organs other than the gut. If present in pancreas, gliadin could interact directly with the immune system and the beta cells to initiate diabetes development. We orally...

  7. Modulation of ovomucoid-specific oral tolerance in mice fed plant extracts containing lectins

    DEFF Research Database (Denmark)

    Kjær, Tanja; Frøkiær, Hanne

    2002-01-01

    We investigated the effect of feeding extracts of four different legumes (red kidney bean (Phaseolus vulgaris), peanut (Arachis hypogaea), soyabean (Glycine max) and pea (Pisum sativum) on the specific immune response against a food protein. Mice were fed ovomucoid and the specific immune response...... was evaluated. Ovomucoid fed alone resulted in oral tolerance induction measured as both a reduced ovomucoid-pecific spleen cell proliferation and antibody response. Feeding kidney-bean extract prevented induction of oral tolerance to ovomucoid measured as spleen cell proliferation in vitro. Pure kidney......-bean lectin also prevented oral tolerance induction, suggesting that lectin in the kidney-bean extract caused inhibition of oral tolerance. Parenteral administration (intravenous and intraperitoneal) of pure kidney-bean lectin had no significant influence on oral tolerance induction. Soyabean extract also...

  8. Evidence of Oral Translocation of Anionic G6.5 Dendrimers in Mice

    Science.gov (United States)

    Thiagarajan, Giridhar; Sadekar, Shraddha; Greish, Khaled; Ray, Abhijit; Ghandehari, Hamidreza

    2013-01-01

    Development of carrier systems to improve oral bioavailability and target drugs to specific sites continues to be an unmet need. The goal of this study was to evaluate the potential of anionic generation (G) 6.5 poly(amido amine) (PAMAM) dendrimers in oral drug delivery by assessing their in vivo oral translocation. G6.5-COOH dendrimers were characterized for their physiochemical characteristics and acute oral toxicity was assessed in CD-1 mice. The dendrimers were labeled with 125I and their stability evaluated. Oral bioavailability was assessed in the same mouse model. Investigation of the radioactivity profile in plasma, revealed presence of both large and small molecular weight compounds. Detailed area under the curve analysis suggests an effective 9.4% bioavailability of radiolabeled marker associated with G6.5-COOH. Results reported here suggest the potential of dendrimers in permeating gastrointestinal barriers in vivo. PMID:23286733

  9. Incidental Abnormalities in Oral Mucosal Carcinogenesis of v-H-ras Transgenic Mice OF v-H-ras TRANSGENIC MICE

    Directory of Open Access Journals (Sweden)

    Dewi Agustina

    2012-10-01

    Full Text Available The effect of individual oncogene on diverse cell types could be studied by using transgenic mice. The expression of transgene is mainly determined by the regulatory sequences chosen. Fifty four v-H-ras transgenic FVB/N mice and 54 parental FVB/N mice were used as the experimental and the control groups respectively. Each group was divided into nine subgroups with three different treatments i.e. 4-nitroquinoline 1-oxide (4NQO-treated, phorbol 12,13-didecanoate (PDD-treated and propane-1,2-diol (PD-treated palatal of mice for 6, 16 or 24 weeks. Other four mice of parental mice were used as the untreated group. Two weeks after the last painting, all animals were sacrificed and the intra- or extra-oral tissues were removed and fixed in 4% m/v paraformaldehyde for 24 hours. Hard tissue were then decalcified after the fixation was completed. Subsequently, standard procedure for H&E staining was performed. The results of this study showed that 47 out of 54 transgenic mice produced spontaneous odontogenic, epidermal or mesenchymal neoplasms. After 24 weeks of painting with 4NQO there was minimal evidence of palatal epithelial dysplasia in both transgenic and parental strain groups and neither the PDD nor PD groups showed evidence of dysplasia. From these results it was apparent that the effect of 4NQO and PDD was slower than reported for other strain of mice and that activated v-H-ras did not increase the rate of palatal mucosal carcinogenesis in the model used. On the other hand, incidental abnormalities were much detected especially in the experimental group.DOI: 10.14693/jdi.v16i1.11

  10. Zectran fed orally to mice...cholinesterase levels in blood determined

    Science.gov (United States)

    Jean Marie Lang; Raymond R. Miskus

    1967-01-01

    Zectran, a carbamate insecticide, is being field-tested against the spruce budworm. Taken in sufficient quantity, it can induce cholinesterase (ChE) inhibition in mammals. In laboratory experiments, Zectran was fed orally to mice. Results indicated that maximum ChE inhibition occurred 15 to 30 minutes after ingestion of Zectran, and that a ChE test is unreliable in the...

  11. ATP-ase positive cells in human oral mucosa transplanted to nude mice

    DEFF Research Database (Denmark)

    Dabelsteen, E; Kirkeby, S

    1981-01-01

    A model to study the differentiation of human oral epithelium in vivo utilizing transplantation of human tissue to nude mice has been described. Previous studies have described the epithelial cells in this model. In this study we demonstrate that 8 d after transplantation, Langerhans cells, ident...

  12. Accumulation of proteinase K-resistant prion protein (PrP) is restricted by the expression level of normal PrP in mice inoculated with a mouse-adapted strain of the Creutzfeldt-Jakob disease agent.

    OpenAIRE

    Sakaguchi, S; Katamine, S.; Shigematsu, K.; Nakatani, A; Moriuchi, R.; Nishida, N.; Kurokawa, K; Nakaoke, R; Sato, H; Jishage, K

    1995-01-01

    Creutzfeldt-Jakob disease (CJD) is a transmissible neurodegenerative disease of humans caused by an unidentified infectious agent, the prion. To determine whether there was an involvement of the host-encoded prion protein (PrPc) in CJD development and prion propagation, mice heterozygous (PrP+/-) or homozygous (PrP-/-) for a disrupted PrP gene were established and inoculated with the mouse-adapted CJD agent. In keeping with findings of previous studies using other lines of PrP-less mice inocu...

  13. Serum concentrations of buprenorphine after oral and parenteral administration in male mice

    DEFF Research Database (Denmark)

    Kalliokoski, Otto; Jacobsen, Kirsten R; Hau, Jann

    2011-01-01

    Buprenorphine is the most commonly used drug for peri-operative pain relief in laboratory rodents. The systemic concentrations of buprenorphine were measured in mice following administration intravenously (IV), subcutaneously (SC), orally by gavage and by voluntary ingestion, to determine the post......-administration serum concentration of buprenorphine. Voluntarily ingested buprenorphine resulted in long-lasting high serum concentrations, as did oral gavage administration (24h serum concentration: 110ngh/mL for both routes of administration). In contrast, buprenorphine administered parenterally remained...... of the oral boli, as well as saturation of the hepatic buprenorphine metabolising pathways. Voluntary ingestion of buprenorphine was found to constitute a practical way to provide laboratory mice with efficient pain relief....

  14. Chronic oral carbamazepine treatment elicits mood-stabilising effects in mice.

    Science.gov (United States)

    Kara, Nirit Z; Karpel, Orit; Toker, Lilach; Agam, Galila; Belmaker, Robert H; Einat, Haim

    2014-02-01

    The underlying biology of bipolar disorder and the mechanisms by which effective medications induce their therapeutic effects are not clear. Appropriate use of animal models are essential to further understand biological mechanisms of disease and treatment, and further understanding the therapeutic mechanism of mood stabilisers requires that clinically relevant administration will be effective in animal models. The clinical regimens for mood-stabilising drugs include chronic oral administration; however, much of the work with animal models includes acute administration via injection. An effective chronic and oral administration of the prototypic mood stabiliser lithium was already established and the present study was designed to do the same for the mood stabiliser carbamazepine. Mice were treated for 3 weeks with carbamazepine in food. ICR mice were treated with 0.25%, 0.5% and 0.75%, and C57bl/6 mice with 0.5% and 0.75%, carbamazepine in food (w/w, namely, 2.5, 5.0 or 7.5 g/kg food). Mice were then tested for spontaneous activity, forced swim test (FST), tail suspension test (TST) and amphetamine-induced hyperactivity. Oral carbamazepine administration resulted in dose-dependent blood levels reaching 3.65 μg/ml at the highest dose. In ICR mice, carbamazepine at the 0.5% dose had no effect on spontaneous activity, but significantly reduced immobility in the TST by 27% and amphetamine-induced hyperactivity by 28%. In C57bl/6 mice, carbamazepine at the 0.75% dose reduced immobility time in the FST by 26%. These results demonstrate a behaviourally effective oral and chronic regimen for carbamazepine with mood stabilising-like activity in a standard model for mania-like behaviour and two standard models for depression-like behaviour.

  15. Aqueous Stability and Oral Pharmacokinetics of Meloxicam and Carprofen in Male C57BL/6 Mice

    Science.gov (United States)

    Ingrao, Joelle C; Johnson, Ron; Tor, Elizabeth; Gu, Yu; Litman, Marcus; Turner, Patricia V

    2013-01-01

    We found that carprofen and meloxicam under 3 environmental conditions (ambient dark, ambient light, and 4 °C) remained stable for at least 7 d. We then evaluated the oral pharmacokinetics of meloxicam (20 mg/kg) and carprofen (10 mg/kg) in male C57BL/6 mice after oral gavage or administration in the drinking water. Mice did not drink meloxicam-medicated water but readily consumed carprofen-medicated water, consuming an average of 14.19 mL carprofen-medicated water per 100 g body weight daily; mice drank more during the dark phase than during the light phase. Plasma analyzed by HPLC (meloxicam) and tandem mass spectrometry (carprofen) revealed that the peak meloxicam and carprofen concentrations were 16.7 and 20.3 μg/mL and occurred at 4 and 2 h after oral gavage, respectively. Similar blood levels were achieved after 12 h access to the carprofen-medicated water bottle. At 24 h after oral gavage, the drugs were not detectable in plasma. Meloxicam plasma AUC, elimination half-life, apparent volume of distribution, and apparent oral clearance were 160.4 mg/L × h, 7.4 h, 0.36 L/kg, and 0.125 mL/h × kg, respectively. Carprofen plasma AUC, elimination half-life, apparent volume of distribution, and apparent oral clearance were 160.8 mg/L × h, 7.4 h, 0.42 L/kg, and 0.062 mL/h × kg, respectively. No gross or microscopic evidence of toxicity was seen in any mouse. Our findings indicate that carprofen can be administered in drinking water to mice and that medicated water bottles should be placed 12 to 24 h prior to painful procedures. PMID:24041210

  16. Aqueous stability and oral pharmacokinetics of meloxicam and carprofen in male C57BL/6 mice.

    Science.gov (United States)

    Ingrao, Joelle C; Johnson, Ron; Tor, Elizabeth; Gu, Yu; Litman, Marcus; Turner, Patricia V

    2013-09-01

    We found that carprofen and meloxicam under 3 environmental conditions (ambient dark, ambient light, and 4 °C) remained stable for at least 7 d. We then evaluated the oral pharmacokinetics of meloxicam (20 mg/kg) and carprofen (10 mg/kg) in male C57BL/6 mice after oral gavage or administration in the drinking water. Mice did not drink meloxicam-medicated water but readily consumed carprofen-medicated water, consuming an average of 14.19 mL carprofen-medicated water per 100 g body weight daily; mice drank more during the dark phase than during the light phase. Plasma analyzed by HPLC (meloxicam) and tandem mass spectrometry (carprofen) revealed that the peak meloxicam and carprofen concentrations were 16.7 and 20.3 μg/mL and occurred at 4 and 2 h after oral gavage, respectively. Similar blood levels were achieved after 12 h access to the carprofen-medicated water bottle. At 24 h after oral gavage, the drugs were not detectable in plasma. Meloxicam plasma AUC, elimination half-life, apparent volume of distribution, and apparent oral clearance were 160.4 mg/L × h, 7.4 h, 0.36 L/kg, and 0.125 mL/h × kg, respectively. Carprofen plasma AUC, elimination half-life, apparent volume of distribution, and apparent oral clearance were 160.8 mg/L × h, 7.4 h, 0.42 L/kg, and 0.062 mL/h × kg, respectively. No gross or microscopic evidence of toxicity was seen in any mouse. Our findings indicate that carprofen can be administered in drinking water to mice and that medicated water bottles should be placed 12 to 24 h prior to painful procedures.

  17. A less stressful alternative to oral gavage for pharmacological and toxicological studies in mice

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Mary K., E-mail: mwalker@salud.unm.edu [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM (United States); Boberg, Jason R.; Walsh, Mary T.; Wolf, Valerie; Trujillo, Alisha; Duke, Melissa Skelton [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM (United States); Palme, Rupert [Department of Biomedical Sciences/Biochemistry, University of Veterinary Medicine, Vienna (Austria); Felton, Linda A. [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM (United States)

    2012-04-01

    Oral gavage dosing can induce stress and potentially confound experimental measurements, particularly when blood pressure and heart rate are endpoints of interest. Thus, we developed a pill formulation that mice would voluntarily consume and tested the hypothesis that pill dosing would be significantly less stressful than oral gavage. C57Bl/6 male mice were singly housed and on four consecutive days were exposed to an individual walking into the room (week 1, control), a pill being placed into the cage (week 2), and a dose of water via oral gavage (week 3). Blood pressure and heart rate were recorded by radiotelemetry continuously for 5 h after treatment, and feces collected 6–10 h after treatment for analysis of corticosterone metabolites. Both pill and gavage dosing significantly increased mean arterial pressure (MAP) during the first hour, compared to control. However, the increase in MAP was significantly greater after gavage and remained elevated up to 5 h, while MAP returned to normal within 2 h after a pill. Neither pill nor gavage dosing significantly increased heart rate during the first hour, compared to control; however, pill dosing significantly reduced heart rate while gavage significantly increased heart rate 2–5 h post dosing. MAP and heart rate did not differ 24 h after dosing. Lastly, only gavage dosing significantly increased fecal corticosterone metabolites, indicating a systemic stress response via activation of the hypothalamic–pituitary–adrenal axis. These data demonstrated that this pill dosing method of mice is significantly less stressful than oral gavage. -- Highlights: ► Developed a novel oral dosing method using a pill that mice will readily consume. ► Assessed stress by blood pressure, heart rate, and fecal corticosterone metabolites. ► Demonstrated that pill dosing is significantly less stressful than oral gavage.

  18. Oral Glutamine Is Superior Than Oral Glucose to Promote Glycemia Recovery in Mice Submitted to Insulin-Induced Hypoglycemia

    Directory of Open Access Journals (Sweden)

    Amanda Nunes Santiago

    2013-01-01

    Full Text Available The effect of the oral administration of blood glucose precursors on glycemia recovery and liver glucose production in fasted mice subjected to insulin-induced hypoglycemia (IIH was investigated. IIH was obtained with increasing doses (from 0.5 to 2.0 U·kg−1 of intraperitoneal regular insulin where glycemia was evaluated from 0 to 300 min after insulin injection. The dose of 1.0 U·kg−1 showed the best results, that is, a clear glycemia recovery phase without convulsions or deaths. Thus, this dose was used in all experiments. Afterwards, mice submitted to IIH received orally by gavage: saline (control group, glucose (100 mg·kg−1, glycerol (100 mg·kg−1, lactate (100 mg·kg−1, alanine (100 mg·kg−1, or glutamine (100 mg·kg−1. It was observed that glutamine was more effective in promoting glycemia recovery if compared with glucose, lactate, glycerol, or alanine. In agreement with these results, the best performance in terms of liver glucose production was obtained when glutamine was used as glucose precursors. These results open perspectives for clinical studies to investigate the impact of oral administration of gluconeogenic amino acids to promote glycemia recovery during hypoglycemia.

  19. Histology and immunohistochemistry of the developing juxta-oral organ in mice.

    Science.gov (United States)

    Kobayashi, Yasunao; Nakashima, Misako; Wakakuri, Takashi; Imaki, Junko; Ito, Masataka

    2015-03-01

    The juxta-oral organ is a persistent bilateral organ in the mammalian bucca. It consists of epithelial parenchyma and surrounding mesenchymal sheath with connective tissue rich in nerve fibers and sensory receptors between them. The organ develops from the embryonic oral epithelium and is separated from the oral mucosa. The morphology of this organ is very different in mice compared to humans. Although several reports have described the histology of the juxta-oral organ in rodents, its developmental changes have rarely been reported. In the present study, histological development and ultrastructure of the juxta-oral organ, with special attention to its epithelial parenchyma and mesenchymal sheath, were investigated in mice during several developmental stages. Immunohistochemical staining for pan-cytokeratin (CK) on serial paraffin sections of the head allowed easier detection of this organ. The juxta-oral organ was innervated by the buccal nerve from an early stage of organogenesis at E13.5. The organ was located adjacent to the fascia of the masticatory muscles during all developmental stages examined. The parenchymal cells were immunohistochemically positive for p63 and CK14 in both newborn and adult mice, suggesting that these epithelial cells possess characteristics of the basal cells of the stratified epithelium. Furthermore, the parenchyma was ensheathed by layers of mesenchymal cells with perineurial characteristics as shown by immunohistochemical staining and electron microscopy. Unique sensory endings and bundles of elastic fibers were observed between the epithelial parenchyma and mesenchymal sheath. The present findings concerning the structure of mouse juxta-oral organ, especially that of epithelial parenchyma and mesenchymal sheath provide baseline knowledge for the further understanding of the unique morphological features, developmental changes and functional details of this organ. Copyright © 2014 Elsevier GmbH. All rights reserved.

  20. Antitumor activity of total flavonoids from Tetrastigma hemsleyanum Diels et Gilg is associated with the inhibition of regulatory T cells in mice

    National Research Council Canada - National Science Library

    Feng, Zhengquan; Hao, Wanrong; Lin, Xiaoyang; Fan, Daping; Zhou, Juhua

    2014-01-01

    .... Total flavonoids were isolated from Radix tetrastigmae, the root of Tetrastigma hemsleyanum Diels et Gilg, and administered to C57BL/6 mice by oral gavage after inoculation with Lewis lung carcinoma (LLC) cells...

  1. Effect of oral administration of lactobacillus acidophilus on the immune responses and survival of BALB/c mice bearing human breast cancer

    Directory of Open Access Journals (Sweden)

    Soltan Dallal MM

    2010-02-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: In according to immunomodulatory effect of probiotics and effect of these bacteria on the effectiveness of immune responses, at the present work we proposed the evaluation of oral administration of L.acidophilus on the immune statues in BALB/c mice bearing breast cancer."n"nMethods: A total of 30 In-bred BALB/c mices aged from six to eight weeks weighting 25-30g were randomly enrolled in our study, in two groups each consist of 15 mices. The L.acidophilus ATCC4356 strain used in this study was inoculated in MRS broth and cultivated for a day at 37°C under anaerobic conditions, collected by centrifugation and resuspend in Phosphate Buffer Saline (PBS. After preparation of proper amount of these suspensions it was orally administered to the mice with a gastric feeding, Control mices received an equal volume of PBS in duration of study."n"nResults: Results showed the increase in production of IFnγ (p<0.005, and decrease in production of Th2 cytokines such as IL4 (p=0.347 in the L.acidophilus administered mice in comparison to control group of mice. In addition the proliferation of immune cells in probiotic group was significantly higher than controls, and most importantly probiotic administered mice showed

  2. Immune response in mice to ingested soya protein: antibody production, oral tolerance and maternal transfer

    DEFF Research Database (Denmark)

    Christensen, Hanne Risager; Pedersen, Susanne Brix; Frøkiær, Hanne

    2004-01-01

    While allergic reactions to soya are increasingly investigated, the normal immune response to ingested soya is scarcely described. In the present study, we wanted to characterise the soya-specific immune response in healthy mice ingesting soya protein. Mice fed a soya-containing diet (F0) and mice...... protein-free feed before mating, the F1 and F2 offspring generations showed no significantly different response, indicating that soya-specific immune components were not maternally transmitted. However, the ingestion of dietary soya protein by F1 mice during late pregnancy and lactation caused a lasting...... antibody response in the offspring, bat in this case in the absence of oral tolerance. This indicates that, under certain conditions, factors involved in spontaneous antibody production can be transmitted from mother to offspring. Understanding the immune response to soya protein ingested under healthy...

  3. Oral tolerance is inefficient in neonatal mice due to a physiological vitamin A deficiency.

    Science.gov (United States)

    Turfkruyer, M; Rekima, A; Macchiaverni, P; Le Bourhis, L; Muncan, V; van den Brink, G R; Tulic, M K; Verhasselt, V

    2016-03-01

    Increased risk of allergy during early life indicates deficient immune regulation in this period of life. To date, the cause for inefficient neonatal immune regulation has never been elucidated. We aimed to define the ontogeny of oral tolerance and to identify necessary conditions specific for this stage of life. Ovalbumin (OVA) was administered orally to mice through breast milk and efficiency of systemic tolerance to OVA was assessed in adulthood using a model of allergic airway inflammation. Oral tolerance induction was fully efficient starting third week of life. Inefficiency in neonates was a consequence of abnormal antigen transfer across the gut barrier and retinaldehyde dehydrogenase expression by mesenteric lymph node CD103(+) neonatal dendritic cells, resulting in inefficient T-cell activation. Neonates' serum retinol levels were three times lower than in adult mice, and vitamin A supplementation was sufficient to rescue neonatal defects and allow tolerance induction from birth. The establishment of oral tolerance required the differentiation of Th1 lymphocytes in both vitamin A-supplemented neonates and 3-week-old unsupplemented mice. This knowledge should guide the design of interventions for allergy prevention that are adapted to the neonatal stage of life such as vitamin A supplementation.

  4. Dietary medium-chain triglycerides promote oral allergic sensitization and orally induced anaphylaxis to peanut protein in mice.

    Science.gov (United States)

    Li, Jianing; Wang, Yu; Tang, Lihua; de Villiers, Willem J S; Cohen, Donald; Woodward, Jerold; Finkelman, Fred D; Eckhardt, Erik R M

    2013-02-01

    The prevalence of peanut allergies is increasing. Peanuts and many other allergen sources contain significant amounts of triglycerides, which affect absorption of antigens but have unknown effects on sensitization and anaphylaxis. We recently reported that dietary medium-chain triglycerides (MCTs), which bypass mesenteric lymph and directly enter portal blood, reduce intestinal antigen absorption into blood compared with long-chain triglycerides (LCTs), which stimulate mesenteric lymph flow and are absorbed in chylomicrons through mesenteric lymph. We sought to test how dietary MCTs affect food allergy. C3H/HeJ mice were fed peanut butter protein in MCT, LCT (peanut oil), or LCT plus an inhibitor of chylomicron formation (Pluronic L81). Peanut-specific antibodies in plasma, responses of the mice to antigen challenges, and intestinal epithelial cytokine expression were subsequently measured. MCT suppressed antigen absorption into blood but stimulated absorption into Peyer patches. A single gavage of peanut protein with MCT, as well as prolonged feeding in MCT-based diets, caused spontaneous allergic sensitization. MCT-sensitized mice experienced IgG-dependent anaphylaxis on systemic challenge and IgE-dependent anaphylaxis on oral challenge. MCT feeding stimulated jejunal-epithelial thymic stromal lymphopoietin, Il25, and Il33 expression compared with that seen after LCT feeding and promoted T(H)2 cytokine responses in splenocytes. Moreover, oral challenges of sensitized mice with antigen in MCT significantly aggravated anaphylaxis compared with challenges with the LCT. Importantly, the effects of MCTs could be mimicked by adding Pluronic L81 to LCTs, and in vitro assays indicated that chylomicrons prevent basophil activation. Dietary MCTs promote allergic sensitization and anaphylaxis by affecting antigen absorption and availability and by stimulating T(H)2 responses. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All

  5. Oral administration of Lactobacillus brevis KB290 to mice alleviates clinical symptoms following influenza virus infection.

    Science.gov (United States)

    Waki, N; Yajima, N; Suganuma, H; Buddle, B M; Luo, D; Heiser, A; Zheng, T

    2014-01-01

    Lactobacillus brevis KB290 (KB290), isolated from a traditional Japanese pickle 'Suguki', has been reported to have immunomodulatory effects. We investigated whether oral administration of KB290 has protective effects against influenza virus (IFV) infection in mice. After 14 days of administration of lyophilized KB290 suspended in phosphate-buffered saline by oral gavage, BALB/c mice were intranasally infected with 2 × MLD50 (50% mouse lethal dose) of IFV A/PR/8/34 (H1N1). Prophylactically administered KB290 significantly alleviated the loss of body weight and the deterioration in observational physical conditions induced by the infection. In addition, 7 days after infection, the levels of IFV-specific immunoglobulin (Ig)A in bronchoalveolar lavage fluid were significantly increased in mice fed KB290 compared with controls. Moreover, there was a significant elevation of serum interferon (IFN)-α in KB290 group mice, even at three and 7 days after infection, despite the administration of KB290 being stopped before IFV infection. Our results demonstrated that oral administration of KB290 before infection could alleviate IFV-induced clinical symptoms. Alleviation of clinical symptoms by KB290 consumption may have been induced by long-lasting enhancement of IFN-α production and the augmentation of IFV-specific IgA production. This study demonstrated that oral administration of Lactobacillus brevis KB290 (KB290), a probiotic strain derived from a Japanese traditional pickle, could protect against influenza virus (IFV) infection in mice. Our results demonstrated that continual intake of KB290 for 14 days prior to IFV infection alleviated clinical symptoms such as loss of body weight and deterioration in observational physical conditions induced by the infection. The beneficial effects of KB290 consumption may have been elicited by the long-lasting enhancement of interferon-α production and the augmentation of IFV-specific immunoglobulin A production. © 2013 The

  6. Oral administration of antioxidants improves skin wound healing in diabetic mice.

    Science.gov (United States)

    Pessoa, Ana Flávia Marçal; Florim, Juliana Costa; Rodrigues, Hosana Gomes; Andrade-Oliveira, Vinicius; Teixeira, Simone A; Vitzel, Kaio Fernando; Curi, Rui; Saraiva Câmara, Niels Olsen; Muscará, Marcelo N; Lamers, Marcelo Lazzaron; Santos, Marinilce Fagundes

    2016-11-01

    Oxidative stress aggravates several long-term complications in diabetes mellitus. We evaluated the effectiveness of the oral administration of antioxidants (vitamins E and C, 40 and 100 mg/kg b.w., respectively) on skin wound healing acceleration in alloxan-induced diabetic mice. Mice were wounded 30 days after the induction of diabetes. Antioxidants were effective in preventing oxidative stress, as assessed by TBARS. The enzymes catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were increased in diabetics on the 3rd day post-wounding; catalase and glutathione peroxidase remained still augmented in diabetics after 14th day postwounding, and the treatment with vitamins restored their activities to control. After 3 days, diabetic mice showed lower infiltration of inflammatory cells (including CD11b + and Ly6G + cells) and reduced levels of KC, TNF-α, IL-1β, and IL-12 p40 when compared with control mice. The treatment restored cytokine levels. After 14 days, diabetic mice showed late wound closure, persistent inflammation and delayed reepithelialization, accompanied by an increase in MIG + /CD206 - macrophages whereas CD206 + /MIG - macrophages were decreased. Cytokines IL-12p40, TNF-α, IL-1β, and KC were increased and normal levels were restored after treatment with antioxidants. These results suggest that oxidative stress plays a major role in diabetic wound healing impairment and the oral administration of antioxidants improves healing by modulating inflammation and the antioxidant system with no effect on glycemia. © 2016 by the Wound Healing Society.

  7. Antinociceptive effects of Cremophor EL orally administered to mice

    Directory of Open Access Journals (Sweden)

    Z. Tabarelli

    2003-01-01

    Full Text Available Surfactants are frequently used to improve solubilization of lipophilic drugs. Cremophor EL (CrEL is a polyoxyethylated castor oil surfactant used to solubilize water-insoluble drugs such as anesthetic, antineoplastic, immunosuppressive and analgesic drugs, vitamins and new synthetic compounds, including potential analgesics. The antinociceptive effect of CrEL (3.2, 6.4 and 10.6 g/kg, in 10 ml/kg body weight, by gavage on the abdominal writhing response induced by intraperitoneal administration of acetic acid (0.8%, 10 ml/kg body weight and on the tail immersion test was investigated in mice. Control animals received castor oil (10 ml/kg body weight or saline (0.9% NaCl, 10 ml/kg body weight. CrEL reduced nociception in a dose-dependent manner in both tests. At 10.6 g/kg, CrEL caused antinociception similar to that induced by dipyrone (300 mg/kg, by gavage in the abdominal writhing test, and antinociception similar to that induced by morphine (20 mg/kg, by gavage in the tail immersion test. The effect of castor oil was similar to that of saline in both assays. These data indicate that the appropriate controls should be used when evaluating the effects of potential antinociceptive agents dissolved in CrEL.

  8. Oral Self-Administration Of EtOH In Transgenic Mice Lacking Beta-Endorphin

    Directory of Open Access Journals (Sweden)

    Stephani Allen

    2007-01-01

    Full Text Available EtOH modifies the production and/or release of endogenous opioid peptides, including -endorphin (Gianoulakis, 2004; Przewlocka et al., 1994; Schulz et al., 1980. Opioids subsequently influence the reinforcing properties of EtOH and the development of alcoholism (Terenius, 1996; Van Ree, 1996. In this study, beta-endorphin deficient mutant mice were used to examine the effects of a specific opioid peptide on EtOH consumption. Mice were obtained from The Jackson Laboratory, Bar Harbor, ME, USA. Male and female, adult naïve mice were single housed in Plexiglas cages with corn cob bedding and ad lib access to food (mouse chow and water. A two-bottle free choice EtOH oral self-administration paradigm was administered to homozygous mutant mice (void of all beta-endorphin, heterozygous mice (50% beta-endorphin expression, and sibling wildtype mice (C57BL/6J. Subjects received increasing concentrations of EtOH (0%, 3%, 6%, 12%, and 15% each given over an eight day span, and were evaluated for preference and consumption each day. Bottles were switched every other day to avoid the development of a side preference. Overall, females drank more than males. Homozygous mutant mice (KO showed decreased preference for EtOH at all concentrations, and self-administered significantly less than heterozygous mice (HT and wildtype mice (C57. The HTs had a tendency to drink the most followed by the C57s, and the KOs drank the least. These data support the hypothesis that beta-endorphin influences the reinforcing effects of EtOH.

  9. The Protective Effects of Oral Low-dose Quercetin on Diabetic Nephropathy in Hypercholesterolemic Mice

    Directory of Open Access Journals (Sweden)

    Isabele Beserra Santos Gomes

    2015-09-01

    Full Text Available Aims: Diabetic nephropathy (DN is one of the major causes of end-stage renal disease, and the incidence of DN is increasing worldwide. Considering our previous report indicating that chronic treatment with oral low-dose quercetin (10 mg/Kg demonstrated renoprotective, anti-oxidative and anti-apoptotic effects in the C57BL/6J model of diabetic nephropathy, we investigated whether this flavonoid could also have beneficial effects in concurrent DN and spontaneous atherosclerosis using the apolipoprotein E-deficient mouse (apoE-/-. Methods: DN was induced by streptozotocin (100 mg/kg/day, for 3 days in adult apoE-/-mice. Six weeks later, the mice were divided into the following groups: diabetic apoE-/- mice treated with quercetin (DQ, 10 mg/kg/day, 4 weeks, diabetic ApoE-/- mice treated with vehicle (DV and non-treated non-diabetic (ND mice.Results: Quercetin treatment caused a reduction in polyuria (~30%, glycemia (~25%, abolished the hypertriglyceridemia and had significant effects on renal function, including decreased proteinuria (~15% and creatininemia (~30%, which were accompanied by beneficial effects on the renal structural changes, including normalization of the index of glomerulosclerosis and kidney weight.Conclusions: Our data revealed that quercetin treatment significantly reduced DN in hypercholesterolemic mice by inducing biochemical and morphological modifications. Thus, this translational study highlights the importance of quercetin as a potential nutraceutical for the management of DN, including in diabetes associated with dyslipidemia.

  10. Oral Corticosterone Administration Reduces Insulitis but Promotes Insulin Resistance and Hyperglycemia in Male Nonobese Diabetic Mice.

    Science.gov (United States)

    Burke, Susan J; Batdorf, Heidi M; Eder, Adrianna E; Karlstad, Michael D; Burk, David H; Noland, Robert C; Floyd, Z Elizabeth; Collier, J Jason

    2017-03-01

    Steroid-induced diabetes is the most common form of drug-induced hyperglycemia. Therefore, metabolic and immunological alterations associated with chronic oral corticosterone were investigated using male nonobese diabetic mice. Three weeks after corticosterone delivery, there was reduced sensitivity to insulin action measured by insulin tolerance test. Body composition measurements revealed increased fat mass and decreased lean mass. Overt hyperglycemia (>250 mg/dL) manifested 6 weeks after the start of glucocorticoid administration, whereas 100% of the mice receiving the vehicle control remained normoglycemic. This phenotype was fully reversed during the washout phase and readily reproducible across institutions. Relative to the vehicle control group, mice receiving corticosterone had a significant enhancement in pancreatic insulin-positive area, but a marked decrease in CD3+ cell infiltration. In addition, there were striking increases in both citrate synthase gene expression and enzymatic activity in skeletal muscle of mice in the corticosterone group relative to vehicle control. Moreover, glycogen synthase expression was greatly enhanced, consistent with elevations in muscle glycogen storage in mice receiving corticosterone. Corticosterone-induced hyperglycemia, insulin resistance, and changes in muscle gene expression were all reversed by the end of the washout phase, indicating that the metabolic alterations were not permanent. Thus, male nonobese diabetic mice allow for translational studies on the metabolic and immunological consequences of glucocorticoid-associated interventions in a mouse model with genetic susceptibility to autoimmune disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Oral treatment with herbal formula B401 alleviates penile toxicity in aging mice with manganism

    Directory of Open Access Journals (Sweden)

    Hsu CH

    2015-05-01

    Full Text Available Chih-Hsiang Hsu,1 Ching-Lung Lin,1 Sheue-Er Wang,1 Shuenn-Jyi Sheu,2 Chiang-Ting Chien,1 Chung-Hsin Wu1 1Department of Life Science, National Taiwan Normal University, 2Brion Research Institute of Taiwan, Taipei, Taiwan Abstract: The present study aims to elucidate the roles of nitric oxide synthase activity, oxidative stress, inflammation, and apoptosis in penile toxicity of aging mice associated with excess manganese (Mn treatment and to investigate the effect of oral treatment with the herbal formula B401 in this respect. ICR strain mice were divided into two groups: the vehicle (sham group and the B401 (50 mg/kg group. The mice were orally treated for 5 days; then a high single dose of MnCl2 (100 mg/kg was given by intraperitoneal injection to the mice. One day after MnCl2 treatment, corpora cavernosal tissues of both Mn-treated mice and their controls were simultaneously sampled to examine their immunohistochemical staining and Western blot analysis. Nitric oxide (NO production, levels of neuronal nitric oxide synthase (nNOS and endothelial nitric oxide synthase (eNOS, expression levels of factors governing angiogenesis (vascular endothelial growth factor, oxidative stress (catalase, superoxide dismutase 2,4-hydroxynonenal, inflammation (tumor necrosis factor alpha, apoptosis (B-cell lymphoma 2 [Bcl-2], Bcl-2-associated X protein [Bax], cleaved poly(adenosine diphosphate-ribose polymerase [c-PARP], cytochrome C, caspase-12, and caspase-3 were evaluated in penile corpus cavernosum of the mice. We found that penile toxicity in the mice was enhanced under excess Mn treatment through reduction of NOS activity and increase in oxidative stress, inflammation, and apoptosis in the penile cavernous tissue. Furthermore, the penile toxicity in mice with manganism was alleviated by oral B401 treatment through enhancement of both nitric oxide synthesis and angiogenesis, with simultaneous reduction of oxidative stress, inflammation, and apoptosis in

  12. Comparison of Serum Bisphenol A Concentrations in Mice Exposed to Bisphenol A through the Diet versus Oral Bolus Exposure

    OpenAIRE

    2011-01-01

    Background: Bisphenol A (BPA) is a widely produced endocrine-disrupting chemical. Diet is a primary route of exposure, but internal exposure (serum concentrations) in animals and humans has been measured only after single oral bolus administration. Objective: We compared serum concentrations of BPA over a 24-hr period after oral bolus administration or ad libitum feeding in mice and assessed for buildup with dietary exposure. Methods: Adult female mice were administered [dimethyl-d 6]-BPA (BP...

  13. Fructose- and glucose-conditioned preferences in FVB mice: strain differences in post-oral sugar appetition

    Science.gov (United States)

    Zukerman, Steven; Ackroff, Karen

    2014-01-01

    Recent studies indicate that, unlike glucose, fructose has little or no post-oral preference conditioning actions in C57BL/6J (B6) mice. The present study determined whether this is also the case for FVB mice, which overconsume fructose relative to B6 mice. In experiment 1, FVB mice strongly preferred a noncaloric 0.1% sucralose + 0.1% saccharin (S+S) solution to 8% fructose in a 2-day choice test but switched their preference to fructose after separate experience with the two sweeteners. Other FVB mice displayed a stronger preference for 8% glucose over S+S. In a second experiment, ad libitum-fed FVB mice trained 24 h/day acquired a significant preference for a flavor (CS+) paired with intragastric (IG) self-infusions of 16% fructose over a different flavor (CS−) paired with IG water infusions. IG fructose infusions also conditioned flavor preferences in food-restricted FVB mice trained 1 h/day. IG infusions of 16% glucose conditioned stronger preferences in FVB mice trained 24- or 1 h/day. Thus, fructose has post-oral flavor conditioning effects in FVB mice, but these effects are less pronounced than those produced by glucose. Further studies of the differential post-oral conditioning effects of fructose and glucose in B6 and FVB mice should enhance our understanding of the physiological processes involved in sugar reward. PMID:25320345

  14. Oral immunization of mice with gamma-irradiated Brucella neotomae induces protection against intraperitoneal and intranasal challenge with virulent B. abortus 2308.

    Science.gov (United States)

    Dabral, Neha; Martha-Moreno-Lafont; Sriranganathan, Nammalwar; Vemulapalli, Ramesh

    2014-01-01

    Brucella spp. are Gram-negative, facultative intracellular coccobacilli that cause one of the most frequently encountered zoonosis worldwide. Humans naturally acquire infection through consumption of contaminated dairy and meat products and through direct exposure to aborted animal tissues and fluids. No vaccine against brucellosis is available for use in humans. In this study, we tested the ability of orally inoculated gamma-irradiated B. neotomae and B. abortus RB51 in a prime-boost immunization approach to induce antigen-specific humoral and cell mediated immunity and protection against challenge with virulent B. abortus 2308. Heterologous prime-boost vaccination with B. abortus RB51 and B. neotomae and homologous prime-boost vaccination of mice with B. neotomae led to the production of serum and mucosal antibodies specific to the smooth LPS. The elicited serum antibodies included the isotypes of IgM, IgG1, IgG2a, IgG2b and IgG3. All oral vaccination regimens induced antigen-specific CD4(+) and CD8(+) T cells capable of secreting IFN-γ and TNF-α. Upon intra-peritoneal challenge, mice vaccinated with B. neotomae showed the highest level of resistance against virulent B. abortus 2308 colonization in spleen and liver. Experiments with different doses of B. neotomae showed that all tested doses of 10(9), 10(10) and 10(11) CFU-equivalent conferred significant protection against the intra-peritoneal challenge. However, a dose of 10(11) CFU-equivalent of B. neotomae was required for affording protection against intranasal challenge as shown by the reduced bacterial colonization in spleens and lungs. Taken together, these results demonstrate the feasibility of using gamma-irradiated B. neotomae as an effective and safe oral vaccine to induce protection against respiratory and systemic infections with virulent Brucella.

  15. Oral immunization of mice with gamma-irradiated Brucella neotomae induces protection against intraperitoneal and intranasal challenge with virulent B. abortus 2308.

    Directory of Open Access Journals (Sweden)

    Neha Dabral

    Full Text Available Brucella spp. are Gram-negative, facultative intracellular coccobacilli that cause one of the most frequently encountered zoonosis worldwide. Humans naturally acquire infection through consumption of contaminated dairy and meat products and through direct exposure to aborted animal tissues and fluids. No vaccine against brucellosis is available for use in humans. In this study, we tested the ability of orally inoculated gamma-irradiated B. neotomae and B. abortus RB51 in a prime-boost immunization approach to induce antigen-specific humoral and cell mediated immunity and protection against challenge with virulent B. abortus 2308. Heterologous prime-boost vaccination with B. abortus RB51 and B. neotomae and homologous prime-boost vaccination of mice with B. neotomae led to the production of serum and mucosal antibodies specific to the smooth LPS. The elicited serum antibodies included the isotypes of IgM, IgG1, IgG2a, IgG2b and IgG3. All oral vaccination regimens induced antigen-specific CD4(+ and CD8(+ T cells capable of secreting IFN-γ and TNF-α. Upon intra-peritoneal challenge, mice vaccinated with B. neotomae showed the highest level of resistance against virulent B. abortus 2308 colonization in spleen and liver. Experiments with different doses of B. neotomae showed that all tested doses of 10(9, 10(10 and 10(11 CFU-equivalent conferred significant protection against the intra-peritoneal challenge. However, a dose of 10(11 CFU-equivalent of B. neotomae was required for affording protection against intranasal challenge as shown by the reduced bacterial colonization in spleens and lungs. Taken together, these results demonstrate the feasibility of using gamma-irradiated B. neotomae as an effective and safe oral vaccine to induce protection against respiratory and systemic infections with virulent Brucella.

  16. A less stressful alternative to oral gavage for pharmacological and toxicological studies in mice.

    Science.gov (United States)

    Walker, Mary K; Boberg, Jason R; Walsh, Mary T; Wolf, Valerie; Trujillo, Alisha; Duke, Melissa Skelton; Palme, Rupert; Felton, Linda A

    2012-04-01

    Oral gavage dosing can induce stress and potentially confound experimental measurements, particularly when blood pressure and heart rate are endpoints of interest. Thus, we developed a pill formulation that mice would voluntarily consume and tested the hypothesis that pill dosing would be significantly less stressful than oral gavage. C57Bl/6 male mice were singly housed and on four consecutive days were exposed to an individual walking into the room (week 1, control), a pill being placed into the cage (week 2), and a dose of water via oral gavage (week 3). Blood pressure and heart rate were recorded by radiotelemetry continuously for 5h after treatment, and feces collected 6-10h after treatment for analysis of corticosterone metabolites. Both pill and gavage dosing significantly increased mean arterial pressure (MAP) during the first hour, compared to control. However, the increase in MAP was significantly greater after gavage and remained elevated up to 5h, while MAP returned to normal within 2h after a pill. Neither pill nor gavage dosing significantly increased heart rate during the first hour, compared to control; however, pill dosing significantly reduced heart rate while gavage significantly increased heart rate 2-5h post dosing. MAP and heart rate did not differ 24h after dosing. Lastly, only gavage dosing significantly increased fecal corticosterone metabolites, indicating a systemic stress response via activation of the hypothalamic-pituitary-adrenal axis. These data demonstrated that this pill dosing method of mice is significantly less stressful than oral gavage. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Recombinant baculovirus associated with bilosomes as an oral vaccine candidate against HEV71 infection in mice.

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    Balraj Premanand

    Full Text Available BACKGROUND: Human enterovirus 71 (HEV71 is one of the major pathogen responsible for hand, foot and mouth disease (HFMD. Currently no effective vaccine or antiviral drugs are available. Like poliovirus, EV71 is transmitted mainly by the feco-oral route. To date the majority of the studied EV71 vaccine candidates are administered parenterally. Injectable vaccines induce good systemic immunity but mucosal responses are often unsatisfactory, whereas mucosal vaccines provide both systemic and mucosal immunity. Therefore, oral immunization appears to be an attractive alternative to parenteral immunization. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we studied the efficacy of an orally administered vaccine candidate developed using recombinant baculovirus displaying VP1 (Bac-VP1 in a murine model. Gastrointestinal delivery of Bac-VP1 significantly induced VP1-specific humoral (IgG and mucosal (IgA immune responses. Further, we studied the efficacy of the Bac-VP1 associated with bilosomes and observed that the Bac-VP1 associated with bilosomes elicited significantly higher immune responses compared to bilosomes non-associated with Bac-VP1. However, mice immunized subcutaneously with live Bac-VP1 had significantly enhanced VP1 specific serum IgG levels and higher neutralizing antibody titers compared with mice orally immunized with live Bac-VP1 alone or associated with bilosomes. CONCLUSION: Bilosomes have been shown to possess inherent adjuvant properties when associated with antigen. Therefore Bac-VP1 with bilosomes could be a promising oral vaccine candidate against EV71 infections. Thus, Bac-VP1 loaded bilosomes may provide a needle free, painless approach for immunization against EV71, thereby increasing patient compliance and consequently increasing vaccination coverage.

  18. Immunopotentiative effect of polysaccharide from kefir grain, KGF-C, administered orally in mice.

    Science.gov (United States)

    Murofushi, M; Mizuguchi, J; Aibara, K; Matuhasi, T

    1986-08-01

    Since a water-soluble polysaccharide (KGF-C) from the kefir grains was shown to have the property of retarding tumor growth in vivo when administered orally, the effect of KGF-C was examined on antibody responses to thymus-dependent antigen, sheep red blood cells (SRBC), and thymus-independent antigen, dinitrophenyl-Ficoll and trinitrophenyl-lipopolysaccharide. Antibody response in mice intubated with KGF-C was enhanced to low doses of SRBC, but not to optimal or high doses. The optimal dose of KGF-C required for the enhancement was 100 mg/kg body weight. The time-course studies on KGF-C administration implied that KGF-C exerted its effect on the early events of anti-SRBC response. The enhancement was not due to the alteration of kinetics of anti-SRBC responses. Furthermore, the enhancing effect on antibody responses to thymus-independent antigens, such as dinitrophenyl-Ficoll and trinitrophenyl-lipopolysaccharide, was observed neither in nu/nu nor in nu/+ mice, and the effect on delayed-type hypersensitivity response to a low dose of SRBC in normal mice was also found. These findings suggest that the oral immune enhancement by KGF-C is elucidated probably through T-cell but not through B-cell participation.

  19. Efficacy of some essential oils in mice infected with Trypanosoma cruzi

    African Journals Online (AJOL)

    Purpose: To evaluate the efficacy of orally administered Cymbopogon citratus, Zingiber officinale and Syzygium aromaticum essential oils (EOs) in mice infected with Trypanosoma cruzi. Methods: Three experiments were conducted with 48 Swiss mice each. The animals were inoculated with 2 x 106 metacyclic ...

  20. Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice.

    Science.gov (United States)

    Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

    2011-04-01

    Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13-15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug.

  1. HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression

    Directory of Open Access Journals (Sweden)

    Frincke James M

    2010-10-01

    Full Text Available Abstract Background 17α-Ethynyl-5-androsten-3β, 7β, 17β-triol (HE3286 is a synthetic derivative of an endogenous steroid androstenetriol (β-AET, a metabolite of the abundant adrenal steroid deyhdroepiandrosterone (DHEA, with broad anti-inflammatory activities. We tested the ability of this novel synthetic steroid with improved pharmacological properties to limit non-productive lung inflammation in rodents and attempted to gauge its immunological impact. Methods and Results In mice, oral treatment with HE3286 (40 mg/kg significantly (p in vivo (ovalbumin immunization. When mice treated for two weeks with HE3286 were challenged with K. pneumoniae, nearly identical survival kinetics were observed in vehicle-treated, HE3286-treated and untreated groups. Conclusions HE3286 represents a novel, first-in-class anti-inflammatory agent that may translate certain benefits of β-AET observed in rodents into treatments for chronic inflammatory pulmonary disease.

  2. Plant-made subunit vaccine against pneumonic and bubonic plague is orally immunogenic in mice.

    Science.gov (United States)

    Alvarez, M Lucrecia; Pinyerd, Heidi L; Crisantes, Jason D; Rigano, M Manuela; Pinkhasov, Julia; Walmsley, Amanda M; Mason, Hugh S; Cardineau, Guy A

    2006-03-24

    Yersinia pestis, the causative agent of plague, is an extremely virulent bacterium but there are no approved vaccines for protection against it. Our goal was to produce a vaccine that would address: ease of delivery, mucosal efficacy, safety, rapid scalability, and cost. We developed a novel production and delivery system for a plague vaccine of a Y. pestis F1-V antigen fusion protein expressed in tomato. Immunogenicity of the F1-V transgenic tomatoes was confirmed in mice that were primed subcutaneously with bacterially-produced F1-V and boosted orally with transgenic tomato fruit. Expression of the plague antigens in fruit allowed producing an oral vaccine candidate without protein purification and with minimal processing technology.

  3. Effect of Orally Administered Collagen Peptides from Bovine Bone on Skin Aging in Chronologically Aged Mice

    Directory of Open Access Journals (Sweden)

    Hongdong Song

    2017-11-01

    Full Text Available Collagen peptides (CPs have demonstrated to exert beneficial effects on skin photoaging. However, little has been done to evaluate their effects on chronologically aged skin. Here, the effects of CPs from bovine bone on skin aging were investigated in chronologically aged mice. 13-month-old female Kunming mice were administered with CPs from bovine bone (200, 400 and 800 mg/kg body weight/day or proline (400 mg/kg body weight/day for 8 weeks. Mice body weight, spleen index (SI and thymus index (TI, degree of skin laxity (DSL, skin components, skin histology and antioxidant indicators were analyzed. Ingestion of CPs or proline had no effect on mice skin moisture and hyaluronic acid content, but it significantly improved the skin laxity, repaired collagen fibers, increased collagen content and normalized the ratio of type I to type III collagen in chronologically aged skin. CPs prepared by Alcalase performed better than CPs prepared by collagenase. Furthermore, CPs intake also significantly improved the antioxidative enzyme activities in skin. These results indicate that oral administration of CPs from bovine bone or proline can improve the laxity of chronologically aged skin by changing skin collagen quantitatively and qualitatively, and highlight their potential application as functional foods to combat skin aging in chronologically aged process.

  4. Oral Administration of Thioflavin T Prevents Beta Amyloid Plaque Formation in Double Transgenic AD Mice.

    Science.gov (United States)

    Sarkar, Sumit; Raymick, James; Ray, Balmiki; Lahiri, Debomoy K; Paule, Merle G; Schmued, Larry

    2015-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the fourth leading cause of death in the United States and most common cause of adult-onset dementia. The major hallmarks of AD are the formation of senile amyloid plaques made of beta amyloid and neurofibrillary tangles (NFT) which are primarily composed of phosphorylated tau protein. Although numerous agents have been considered as providing protection against AD, identification of potential agents with neuroprotective ability is limited. Thioflavin T has been used in the past to stain amyloid beta plaques in brain. In this study, Thioflavin T (ThT) and vehicle (infant formula) were administered orally by gavage to transgenic (B6C3 APP PS1; AD-Tg) mice beginning at 4 months age and continuing until sacrifice at 9 months of age at 40 mg/kg dose. The number of amyloid plaques was reduced dramatically by ThT treatment in both male and female transgenic mice compared to those in control mice. Additionally, GFAP and Amylo-Glo labeling suggest that astrocytic hypertrophy is minimized in ThT-treated animals. Similarly, CD68 labeling, which detects activated microglia, along with Amylo-Glo labeling, suggests that microglial activation is significantly less in ThT-treated mice. Both Aβ-40 and Aβ-42 concentrations in blood rose significantly in the ThT-treated animals suggesting that ThT may inhibit the deposition, degradation, and/or clearance of Aβ plaques in brain.

  5. Stable engraftment of human microbiota into mice with a single oral gavage following antibiotic conditioning.

    Science.gov (United States)

    Staley, Christopher; Kaiser, Thomas; Beura, Lalit K; Hamilton, Matthew J; Weingarden, Alexa R; Bobr, Aleh; Kang, Johnthomas; Masopust, David; Sadowsky, Michael J; Khoruts, Alexander

    2017-08-01

    Human microbiota-associated (HMA) animal models relying on germ-free recipient mice are being used to study the relationship between intestinal microbiota and human disease. However, transfer of microbiota into germ-free animals also triggers global developmental changes in the recipient intestine, which can mask disease-specific attributes of the donor material. Therefore, a simple model of replacing microbiota into a developmentally mature intestinal environment remains highly desirable. Here we report on the development of a sequential, three-course antibiotic conditioning regimen that allows sustained engraftment of intestinal microorganisms following a single oral gavage with human donor microbiota. SourceTracker, a Bayesian, OTU-based algorithm, indicated that 59.3 ± 3.0% of the fecal bacterial communities in treated mice were attributable to the donor source. This overall degree of microbiota engraftment was similar in mice conditioned with antibiotics and germ-free mice. Limited surveys of systemic and mucosal immune sites did not show evidence of immune activation following introduction of human microbiota. The antibiotic treatment protocol described here followed by a single gavage of human microbiota may provide a useful, complimentary HMA model to that established in germ-free facilities. The model has the potential for further in-depth translational investigations of microbiota in a variety of human disease states.

  6. Efficacy of oral Bifidobacterium bifidum ATCC 29521 on microflora and antioxidant in mice.

    Science.gov (United States)

    Wang, Bao-gui; Xu, Hai-bo; Xu, Feng; Zeng, Zhe-ling; Wei, Hua

    2016-03-01

    This study aimed to examine whether Bifidobacterium bifidum ATCC 29521, a species of colonic microflora in humans, is involved in the intestinal tract of mice. This study was also conducted to determine the antioxidant activity of this species by evaluating different microbial populations and reactive oxygen species isolated from feces and intestinal contents for 28 days of oral administration. Microbial diversities were assessed through bacterial culture techniques, PCR-DGGE, and real-time PCR. This study showed that the intake of B. bifidum ATCC 29521 significantly (p Bifidobacterium bifidum ATCC 29521 may also be used as a promising material in microbiological and food applications.

  7. Mice with Deletion of Neuromedin B Receptor Exhibit Decreased Oral Glucose-Stimulated Insulin Release.

    Science.gov (United States)

    Paula, G S M; Souza, L L; Bressane, N O S; Maravalhas, R; Wilieman, M; Bento-Bernardes, T; Silva, K R; Mendonca, L S; Oliveira, K J; Pazos-Moura, C C

    2016-12-01

    Neuromedin B (NB) and gastrin-releasing peptide (GRP) are bombesin-like peptides, found in the gastrointestinal tube and pancreas, among other tissues. Consistent data proposed that GRP stimulates insulin secretion, acting directly in pancreatic cells or in the release of gastrointestinal hormones that are incretins. However, the role of NB remains unclear. We examined the glucose homeostasis in mice with deletion of NB receptor (NBR-KO). Female NBR-KO exhibited similar fasting basal glucose with lower insulinemia (48.4%) and lower homeostasis model assessment of insulin resistance index (50.5%) than wild type (WT). Additionally, they were more tolerant to oral glucose, demonstrated by a decrease in the area under the glucose curve (18%). In addition, 15 min after an oral glucose load, female and male NBR-KO showed lower insulin serum levels (45.6 and 26.8%, respectively) than WT, even though blood glucose rose to similar levels in both groups. Single injection of NB, one hour before the oral glucose administration, tended to induce higher serum insulin in WT (28.9%, p=0.3), however the same did not occur in NBR-KO. They showed no changes in fasting insulin content in pancreatic islets by immunohistochemistry, however, the fasting serum levels of glucagon-like peptide, a potent incretin, exhibited a strong trend to reduction (40%, p=0.07). Collectively, mice with deletion of NB receptor have lower insulinemia, especially in response to oral glucose, and females also exhibited a better glucose tolerance, suggesting the involvement of NB and its receptor in regulation of insulin secretion induced by incretins, and also, in insulin sensitivity. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8-dependent mechanism.

    Science.gov (United States)

    Fan, Lu; Balakrishna, Shrilatha; Jabba, Sairam V; Bonner, Pamela E; Taylor, Seth R; Picciotto, Marina R; Jordt, Sven-Eric

    2016-11-01

    Nicotine is a major oral irritant in smokeless tobacco products and has an aversive taste. Mentholated smokeless tobacco products are highly popular, suggesting that menthol increases their palatability and may facilitate initiation of product use. While menthol is known to reduce respiratory irritation by tobacco smoke irritants, it is not known whether this activity extends to oral nicotine and its aversive effects. The two-bottle choice drinking assay was used to characterise aversion and preference in C57BL/6 mice to a range of menthol concentrations (10-200 µg/mL). Then, effects of menthol on oral nicotine aversion were determined. Responses were compared with those in mice deficient in the cold/menthol receptor, TRPM8, expressed in trigeminal sensory neurons innervating the oral cavity. Mice showed aversion to menthol concentrations of 100 µg/mL and above. When presented with a highly aversive concentration of nicotine (200 µg/mL), mice preferred solutions with 50 or 100 µg/mL menthol added over nicotine alone. In contrast to wild-type mice, Trpm8-/- showed a strong aversion to mentholated (100 µg/mL) nicotine (200 µg/mL) and preferred nicotine alone. Trpm8-/- mice show aversion to lower concentrations of menthol than wild-type mice. Oral menthol can reduce the aversive effects of oral nicotine and, at higher concentrations, acts as an irritant by itself. Menthol's effects in relation to nicotine require TRPM8, the cool temperature sensing ion channel that activates analgesic and counterirritant mechanisms. These mechanisms may underlie preference for menthol-containing smokeless tobacco products and may facilitate initiation of product use. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Changes in hepatic gene expression upon oral administration of taurine-conjugated ursodeoxycholic acid in ob/ob mice.

    Directory of Open Access Journals (Sweden)

    Jae-Seong Yang

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is highly prevalent and associated with considerable morbidities. Unfortunately, there is no currently available drug established to treat NAFLD. It was recently reported that intraperitoneal administration of taurine-conjugated ursodeoxycholic acid (TUDCA improved hepatic steatosis in ob/ob mice. We hereby examined the effect of oral TUDCA treatment on hepatic steatosis and associated changes in hepatic gene expression in ob/ob mice. We administered TUDCA to ob/ob mice at a dose of 500 mg/kg twice a day by gastric gavage for 3 weeks. Body weight, glucose homeostasis, endoplasmic reticulum (ER stress, and hepatic gene expression were examined in comparison with control ob/ob mice and normal littermate C57BL/6J mice. Compared to the control ob/ob mice, TUDCA treated ob/ob mice revealed markedly reduced liver fat stained by oil red O (44.2±5.8% vs. 21.1±10.4%, P<0.05, whereas there was no difference in body weight, oral glucose tolerance, insulin sensitivity, and ER stress. Microarray analysis of hepatic gene expression demonstrated that oral TUDCA treatment mainly decreased the expression of genes involved in de novo lipogenesis among the components of lipid homeostasis. At pathway levels, oral TUDCA altered the genes regulating amino acid, carbohydrate, and drug metabolism in addition to lipid metabolism. In summary, oral TUDCA treatment decreased hepatic steatosis in ob/ob mice by cooperative regulation of multiple metabolic pathways, particularly by reducing the expression of genes known to regulate de novo lipogenesis.

  10. Oral immunization of mice with Japanese encephalitis virus envelope protein synthesized in Escherichia coli induces anti-viral antibodies.

    Science.gov (United States)

    Rauthan, Manish; Kaur, Rupinderjeet; Appaiahgari, Mohan Babu; Vrati, Sudhanshu

    2004-11-01

    In order to evaluate the possibility of developing an oral vaccine against Japanese encephalitis virus (JEV), mice were fed with recombinant JEV envelope (E) protein synthesized in Escherichia coli. The protein was administered orally to mice with or without an immunostimulatory cytosine-phosphate-guanosine (CpG) motif containing synthetic oligodeoxynucleotide (ODN) as an adjuvant. The immunized mice made high-titered anti-E and anti-JEV antibodies. Mice immunized with JEV E protein along with the ODN adjuvant produced higher antibody titers and these were predominantly IgG2a type. These antibodies, however, failed to neutralize JEV activity in vitro, and the immunization did not protect the mice against lethal JEV challenge. Splenocytes from the immunized mice secreted large amounts of interferon (IFN)-gamma and showed proliferation in the presence of JEV E protein. Our results indicate that JEV E protein delivered orally to mice together with ODN generated both humoral and cellular immune responses to JEV, and these were of the Th1 type.

  11. Oral administration of Saccharomyces cerevisiae UFMG A-905 prevents allergic asthma in mice.

    Science.gov (United States)

    Fonseca, Vanessa M B; Milani, Thamires M S; Prado, Rafael; Bonato, Vania L D; Ramos, Simone G; Martins, Flaviano S; Vianna, Elcio O; Borges, Marcos de C

    2017-07-01

    The prevalence of asthma has increased in communities that adopt a Western lifestyle and become more urbanized. Probiotics may be effective in the prevention of allergic diseases, such as asthma. The aim of the current study was to examine the effects of Saccharomyces cerevisiae UFMG A-905 in an allergic model of asthma. Balb/c mice were sensitized twice with ovalbumin (OVA) intraperitoneally, 1 week apart and challenged with OVA intranasally for 3 days. Mice were daily treated with S. cerevisiae UFMG A-905 via gavaging needle 10 days before OVA sensitization and during challenges. After challenge, in vivo lung function was measured, and bronchoalveolar lavage (BAL) and lung inflammation were assessed. Oral treatment with S. cerevisiae UFMG A-905 significantly decreased airway hyperresponsiveness, total cell number and the influx of eosinophils to the airway, inflammatory cell in the lung, mucus expression in epithelial cells and the levels of IL-4, IL-5 and IL-13. Additionally, S. cerevisiae UFMG A-905 restored the levels of IL-10 and interferon (IFN)-gamma, and increased the levels of IL-17A. Oral administration of S. cerevisiae UFMG A-905 prevented the development of major asthma-like characteristics in a mouse model. © 2017 Asian Pacific Society of Respirology.

  12. Evaluation of parasitological and immunological parameters of Leishmania chagasi infection in BALB/c mice using different doses and routes of inoculation of parasites.

    Science.gov (United States)

    Oliveira, Dulcilene M; Costa, Mariana Amália F; Chavez-Fumagalli, Miguel A; Valadares, Diogo G; Duarte, Mariana C; Costa, Lourena E; Martins, Vivian T; Gomes, Rosângela F; Melo, Maria N; Soto, Manuel; Tavares, Carlos Alberto P; Coelho, Eduardo Antonio F

    2012-03-01

    Experimental vaccines to protect against visceral leishmaniasis (VL) have been developed by using BALB/c mice infected with a large (10⁷ to 10⁸) inoculum of parasites. Remarkably, prior literature has reported that the poor protection observed is mainly due to the high susceptibility of this strain. To determine factors inherent to mice that might abrogate vaccine-induced efficacy, the present research sought to investigate the impact of the administration of different infective inoculums of Leishmania chagasi (syn. L. infantum) in BALB/c mice, evaluating subcutaneous and intravenous routes of administration as well as parasitological and immunological parameters over different periods of time. This study shows that the injection of a highly infective inoculum in mice, through both subcutaneous and intravenous routes, results in a sustained infection. The mice developed a high parasite load in the liver; however, these values diminished over time. This result did not corroborate with the parasite load in the bone marrow and brain and proved to be expressively different in the spleen and draining lymph nodes, where the values increased over time. Mice infected with a low dose of parasites (10³) showed a certain resistance against infection, based mainly on the IFN-γ and oxide nitric production. Considering all the elements, it could be concluded that the models employing high doses (10⁷) of L. chagasi in BALB/c mice can bring about an imbalance in the animals' immune response, thus allowing for the development of the disease at the expense of efficacy within the vaccine candidates.

  13. Long-term oral administration of hop flower extracts mitigates Alzheimer phenotypes in mice.

    Directory of Open Access Journals (Sweden)

    Norio Sasaoka

    Full Text Available Coincident with the expanding population of aged people, the incidence of Alzheimer disease (AD is rapidly increasing in most advanced countries. At present, no effective prophylactics are available. Among several pathological mechanisms proposed for AD, the "amyloid hypothesis" has been most widely accepted, in which accumulation or deposition of Aβ is considered to be the initial event. Thus, prevention of Aβ production would be an ideal strategy for the treatment or prevention of AD. Aβ is produced via the proteolytic cleavage of its precursor protein, APP (amyloid precursor protein, by two different enzymes, β and γ-secretases. Indeed, inhibitors against either or both enzymes have been developed and tested for clinical efficacy. Based on the "amyloid hypothesis", we developed a luciferase-based screening method to monitor γ-secretase activity, screened more than 1,600 plant extracts, most of which have long been used in Chinese medicine, and observed that Hop extracts significantly inhibit Aβ production in cultured cells. A major component of the inhibitory activity was purified, and its chemical identity was determined by NMR to be Garcinielliptone HC. In vivo, oral administration of Hop extracts to AD model mice decreased Aβ depositions in the cerebral cortex of the parietal lobe, hippocampus, and artery walls (amyloid angiopathy in the brains. In a Morris water maze test, AD model mice that had daily consumed Hop extracts in their drinking water showed significant mitigation of memory impairment at ages of 9 and 12 months. Moreover, in the open field test oral administration of Hop extracts also prevented an emotional disturbance that appeared in the AD mice at 18 months. Despite lifelong consumption of Hop extracts, no deleterious side effects were observed at any age. These results support the "amyloid hypothesis", and indicate that Hop extract is a promising candidate for an effective prophylactic for AD.

  14. Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan-Yuan; Yu, Li-Fang; Zhang, Li-Na; Qiu, Bei-Ying; Su, Ming-Bo; Wu, Fang; Chen, Da-Kai; Pang, Tao; Gu, Min; Zhang, Wei; Ma, Wei-Ping; Jiang, Hao-Wen; Li, Jing-Ya, E-mail: jyli@mail.shcnc.ac.cn; Nan, Fa-Jun, E-mail: fjnan@mail.shcnc.ac.cn; Li, Jia, E-mail: jli@mail.shcnc.ac.cn

    2013-12-01

    AMP-activated protein kinase (AMPK), which is a pivotal guardian of whole-body energy metabolism, has become an attractive therapeutic target for metabolic syndrome. Previously, using a homogeneous scintillation proximity assay, we identified the small-molecule AMPK activator C24 from an optimization based on the original allosteric activator PT1. In this paper, the AMPK activation mechanism of C24 and its potential beneficial effects on glucose and lipid metabolism on db/db mice were investigated. C24 allosterically stimulated inactive AMPK α subunit truncations and activated AMPK heterotrimers by antagonizing autoinhibition. In primary hepatocytes, C24 increased the phosphorylation of AMPK downstream target acetyl-CoA carboxylase dose-dependently without changing intracellular AMP/ATP ratio, indicating its allosteric activation in cells. Through activating AMPK, C24 decreased glucose output by down-regulating mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in primary hepatocytes. C24 also decreased the triglyceride and cholesterol contents in HepG2 cells. Due to its improved bioavailability, chronic oral treatment with multiple doses of C24 significantly reduced blood glucose and lipid levels in plasma, and improved the glucose tolerance of diabetic db/db mice. The hepatic transcriptional levels of PEPCK and G6Pase were reduced. These results demonstrate that this orally effective activator of AMPK represents a novel approach to the treatment of metabolic syndrome. - Highlights: • C24 activates AMPK through antagonizing autoinhibition within α subunit. • C24 activates AMPK in hepatocytes and decreases glucose output via AMPK. • C24 exerts beneficial effects on diabetic db/db mice. • C24 represents a novel therapeutic for treatment of metabolic syndrome.

  15. Oral methylthioadenosine administration attenuates fibrosis and chronic liver disease progression in Mdr2-/- mice.

    Directory of Open Access Journals (Sweden)

    M Ujue Latasa

    Full Text Available BACKGROUND: Inflammation and fibrogenesis are directly related to chronic liver disease progression, including hepatocellular carcinoma (HCC development. Currently there are few therapeutic options available to inhibit liver fibrosis. We have evaluated the hepatoprotective and anti-fibrotic potential of orally-administered 5'-methylthioadenosine (MTA in Mdr2(-/- mice, a clinically relevant model of sclerosing cholangitis and spontaneous biliary fibrosis, followed at later stages by HCC development. METHODOLOGY: MTA was administered daily by gavage to wild type and Mdr2(-/- mice for three weeks. MTA anti-inflammatory and anti-fibrotic effects and potential mechanisms of action were examined in the liver of Mdr2(-/- mice with ongoing fibrogenesis and in cultured liver fibrogenic cells (myofibroblasts. PRINCIPAL FINDINGS: MTA treatment reduced hepatomegaly and liver injury. α-Smooth muscle actin immunoreactivity and collagen deposition were also significantly decreased. Inflammatory infiltrate, the expression of the cytokines IL6 and Mcp-1, pro-fibrogenic factors like TGFβ2 and tenascin-C, as well as pro-fibrogenic intracellular signalling pathways were reduced by MTA in vivo. MTA inhibited the activation and proliferation of isolated myofibroblasts and down-regulated cyclin D1 gene expression at the transcriptional level. The expression of JunD, a key transcription factor in liver fibrogenesis, was also reduced by MTA in activated myofibroblasts. CONCLUSIONS/SIGNIFICANCE: Oral MTA administration was well tolerated and proved its efficacy in reducing liver inflammation and fibrosis. MTA may have multiple molecular and cellular targets. These include the inhibition of inflammatory and pro-fibrogenic cytokines, as well as the attenuation of myofibroblast activation and proliferation. Downregulation of JunD and cyclin D1 expression in myofibroblasts may be important regarding the mechanism of action of MTA. This compound could be a good candidate to

  16. Use of anesthesia dramatically alters the oral glucose tolerance and insulin secretion in C57Bl/6 mice

    DEFF Research Database (Denmark)

    Windeløv, Johanne A; Pedersen, Jens; Holst, Jens J

    2016-01-01

    Evaluation of the impact of anesthesia on oral glucose tolerance in mice. Anesthesia is often used when performing OGTT in mice to avoid the stress of gavage and blood sampling, although anesthesia may influence gastrointestinal motility, blood glucose, and plasma insulin dynamics. C57Bl/6 mice...... in the time frame -15 to +150 min. Plasma insulin concentration was measured at time 0 and 20 min. All four anesthetic regimens resulted in impaired glucose tolerance compared to saline/no anesthesia. (1) hypnorm/midazolam increased insulin concentrations and caused an altered glucose tolerance; (2) ketamine...... regimens altered the oral glucose tolerance, and we conclude that anesthesia should not be used when performing metabolic studies in mice....

  17. Effect of oral administration of Butyrivibrio fibrisolvens MDT-1 on experimental enterocolitis in mice.

    Science.gov (United States)

    Ohkawara, Sou; Furuya, Hideki; Nagashima, Kousuke; Asanuma, Narito; Hino, Tsuneo

    2006-11-01

    Butyrivibrio fibrisolvens MDT-1, a butyrate-producing strain, was evaluated for use as a probiotic to prevent enterocolitis. Oral administration of the MDT-1 strain (10(9) CFU/dose) alleviated the symptoms of colitis (including body weight loss, diarrhea, bloody stool, organic disorder, and mucosal damage) that are induced in mice drinking water that contains 3.0% dextran sulfate sodium. In addition, myeloperoxidase (MPO) activity levels in colonic tissue were reduced, suggesting that MDT-1 mitigates bowel inflammation. The addition of MDT-1 culture supernatant inhibited the growth of nine clinical isolates of Campylobacter jejuni and Campylobacter coli that could potentially cause enterocolitis. Infection of mice with C. coli 11580-3, one of the isolates inhibited by MDT-1 in vitro, resulted in diarrhea, mucosal damage, increased MPO activity levels in colonic tissue, increased numbers of C. coli in the cecum, and decreased body weight gain. However, administration of MDT-1 to mice, prior to and during C. coli infection, reduced these effects. These results suggest that Campylobacter-induced enterocolitis can be alleviated by using B. fibrisolvens as a probiotic.

  18. Evaluating the enantioselective distribution, degradation and excretion of epoxiconazole in mice following a single oral gavage.

    Science.gov (United States)

    Wang, Dezhen; Qiu, Jing; Zhu, Wentao; Zhang, Ping; Deng, Nian; Wang, Xinru; Wang, Yao; Zhou, Zhiqiang

    2015-01-01

    1. The enantiomeric enrichment or degradation of epoxiconazole has been reported in grape, soil, tubifex and mealworm beetle. But, little is known about its enantioselective behaviors in mammals. 2. To further understand differences in the distribution, degradation and excretion of epoxiconazole enantiomers in vivo, male CD-1 mice were selected as the test model to investigate the enantioselective behaviors after a single oral gavage. Mice were sacrificed after 1 h, 3 h, 7 h, 12 h, 24 h, 48 h, 72 h treatment, blood, tissues and excretions were collected for epoxiconazole analysis by LC-MS/MS. 3. On the Lux-Cellulose-1 chiral column, an enrichment of the second eluting (+)-epoxiconazole was generally observed, and feces and urine showed similar EF with major tissues. 4. To elucidate the potential role of intestinal bacterial flora in stereospecific degradation of epoxiconazole, mice fecal flora were cultured in vitro and incubated with epoxiconazole for 48 h. Results showed that (-)-epoxiconazole was preferentially degraded by intestinal bacterial. 5. These results may provide useful information for risk assessment of epoxiconazole on non-target animals.

  19. DNA damage detected by the alkaline comet assay in the liver of mice after oral administration of tetrachloroethylene

    DEFF Research Database (Denmark)

    Cederberg, H.; Henriksson, J.; Binderup, Mona-Lise

    2010-01-01

    Induction of DNA damage in the liver and kidney of male CD1 mice was studied by means of the alkaline Comet assay after oral administration of tetrachloroethylene at the doses of 1000 and 2000 mg/kg/day. A statistically significant dose-related increase in tail intensity was established in hepato......Induction of DNA damage in the liver and kidney of male CD1 mice was studied by means of the alkaline Comet assay after oral administration of tetrachloroethylene at the doses of 1000 and 2000 mg/kg/day. A statistically significant dose-related increase in tail intensity was established...

  20. Corrigendum to "Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration"

    DEFF Research Database (Denmark)

    Bruun, Susanne Wrang; Josefsen, Knud; Tanassi, Julia T.

    2017-01-01

    In the article titled “Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration” [1], there was an error in the peptide sequences in Section . Gliadin Peptides, which should be corrected as follows: The sequences H-LQLQPFPQPELPYPQPELPYPQPELPYPQPQPF-OHY......In the article titled “Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration” [1], there was an error in the peptide sequences in Section . Gliadin Peptides, which should be corrected as follows: The sequences H...

  1. Active invasion of oral and aortic tissues by Porphyromonas gingivalis in mice causally links periodontitis and atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Irina M Velsko

    Full Text Available Atherosclerotic vascular disease is a leading cause of myocardial infarction and cerebrovascular accident, and independent associations with periodontal disease (PD are reported. PD is caused by polymicrobial infections and aggressive immune responses. Genomic DNA of Porphyromonas gingivalis, the best-studied bacterial pathogen associated with severe PD, is detected within atherosclerotic plaque. We examined causal relationships between chronic P. gingivalis oral infection, PD, and atherosclerosis in hyperlipidemic ApoEnull mice. ApoEnull mice (n = 24 were orally infected with P. gingivalis for 12 and 24 weeks. PD was assessed by standard clinical measurements while the aorta was examined for atherosclerotic lesions and inflammatory markers by array. Systemic inflammatory markers serum amyloid A, nitric oxide, and oxidized low-density lipoprotein were analyzed. P. gingivalis infection elicited specific antibodies and alveolar bone loss. Fluorescent in situ hybridization detected viable P. gingivalis within oral epithelium and aorta, and genomic DNA was detected within systemic organs. Aortic plaque area was significantly increased in P. gingivalis-infected mice at 24 weeks (P<0.01. Aortic RNA and protein arrays indicated a strong Th2 response. Chronic oral infection with P. gingivalis results in a specific immune response, significant increases in oral bone resorption, aortic inflammation, viable bacteria in oral epithelium and aorta, and plaque development.

  2. Inoculating for smallpox.

    Science.gov (United States)

    Greene, Jan

    2003-04-01

    In California, one hospital decided the time was right to inoculate staff volunteers with the smallpox vaccine. Weighing the same pros and cons--civic responsibility, health risk, cost and reluctance of staff--other hospitals opted out of inoculations, at least for now. What led these organizations to such divergent decisions?

  3. RHIZOBIUM CROSS-INOCULATION

    African Journals Online (AJOL)

    1993-01-13

    Jan 13, 1993 ... Six introduced and one native nitrogen fixing tree species were grown in a potted non-sterilized Inceptisol inoculated with: species-specific rhizobia strains; Rhizobium strain TAL 1145, a Leucaena isolate;. Bradyrhizobium japonicum strain TAL 169, and without inoculation. Twelve weeks later, significant.

  4. Sex differences in shotgun proteome analyses for chronic oral intake of cadmium in mice.

    Directory of Open Access Journals (Sweden)

    Yoshiharu Yamanobe

    Full Text Available Environmental diseases related to cadmium exposure primarily develop owing to industrial wastewater pollution and/or contaminated food. In regions with high cadmium exposure in Japan, cadmium accumulation occurs primarily in the kidneys of individuals who are exposed to the metal. In contrast, in the itai-itai disease outbreak that occurred in the Jinzu River basin in Toyama Prefecture in Japan, cadmium primarily accumulated in the liver. On the other hand, high concentration of cadmium caused renal tubular disorder and osteomalacia (multiple bone fracture, probably resulting from the renal tubular dysfunction and additional pathology. In this study, we aimed to establish a mouse model of chronic cadmium intake. We administered cadmium-containing drinking water (32 mg/l to female and male mice ad libitum for 11 weeks. Metal analysis using inductively coupled plasma mass spectrometry revealed that cadmium accumulated in the kidneys (927 x 10 + 185 ng/g in females and 661 x 10 + 101 ng/g in males, liver (397 x 10 + 199 ng/g in females and 238 x 10 + 652 ng/g in males, and thyroid gland (293 + 93.7 ng/g in females and 129 + 72.7 ng/g in males of mice. Female mice showed higher cadmium accumulation in the kidney, liver, and thyroid gland than males did (p = 0.00345, p = 0.00213, and p = 0.0331, respectively. Shotgun proteome analyses after chronic oral administration of cadmium revealed that protein levels of glutathione S-transferase Mu2, Mu4, and Mu7 decreased in the liver, and those of A1 and A2 decreased in the kidneys in both female and male mice.

  5. Oral Resveratrol Prevents Osteoarthritis Progression in C57BL/6J Mice Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Hailun Gu

    2016-04-01

    Full Text Available The effects of resveratrol on osteoarthritis (OA pathogenesis have been demonstrated in vitro and in animal models employing intra-articular injections. However, the potential for oral resveratrol supplements to mediate protective effects on OA have not been examined. Therefore, the aim of the present study was to investigate the potential anti-OA effects of oral resveratrol on mice fed a high-fat diet (HFD. C57BL/6J male mice were fed either a standard diet or a HFD, and a subset of the latter also received varying doses of resveratrol. Twelve weeks later, all of the animals were sacrificed and knee joints were evaluated with histological, immunohistochemical, and TUNEL analyses. Mice that received a HFD had significantly greater body weights than the control mice and also exhibited features consistent with knee OA. The mice that received a HFD in combination with low, intermediate, or high doses of resveratrol were only slightly heavier than the control mice at the end of 12 weeks. Quantitative histological assessments indicated that resveratrol treatment partly recovered joint structure in the mice that received a HFD, while high doses of resveratrol prevented the degradation of type II collagen into C-telopeptide of type II collagen (CTX-II and retained type II collagen expression in cartilage. Furthermore, TUNEL analyses revealed a reduction in chondrocyte apoptosis in the resveratrol-treated mice compared with the HFD mice. Thus, oral resveratrol appears to exert anti-OA effects in a mouse model of HFD-induced OA, thereby highlighting the potential preventive and therapeutic value of administering resveratrol for obesity-associated OA.

  6. Chimeric plant virus particles administered nasally or orally induce systemic and mucosal immune responses in mice

    DEFF Research Database (Denmark)

    Brennan, F.R.; Bellaby, T.; Helliwell, S.M.

    1999-01-01

    The humoral immune responses to the D2 peptide of fibronectin-binding protein B (FnBP) of Staphylococcus aureus, expressed on the plant virus cowpea mosaic virus (CPMV), were evaluated after mucosal delivery to mice. Intranasal immunization of these chimeric virus particles (CVPs), either alone o...... demonstrate for the first time that recombinant plant viruses have potential as mucosal vaccines without the requirement for adjuvant and that the nasal route is most effective for the delivery of these nonreplicating particles.......The humoral immune responses to the D2 peptide of fibronectin-binding protein B (FnBP) of Staphylococcus aureus, expressed on the plant virus cowpea mosaic virus (CPMV), were evaluated after mucosal delivery to mice. Intranasal immunization of these chimeric virus particles (CVPs), either alone...... to generate antibody at distant mucosal sites. IgG2a and TgG2b were the dominant IgG subclasses in sera to both CPMV and FnBP, demonstrating a bias in the response toward the T helper 1 type. The sera completely inhibited the binding of human fibronectin to the S. aureus FnBP. Oral immunization of the CVPs...

  7. Improvement of skin condition by oral administration of collagen hydrolysates in chronologically aged mice.

    Science.gov (United States)

    Wang, Zhenbin; Wang, Qing; Wang, Lin; Xu, Weidong; He, Yuanqing; Li, Yunliang; He, Song; Ma, Haile

    2017-07-01

    Collagen hydrolysates (CHs) have been demonstrated to have positive effects on skin photoaging by topical application or oral ingestion. However, there has been little research on their influence on skin chronological aging. In this study, 9-month-old female ICR mice were given normal AIN-93M diets containing CHs (2.5, 5 and 10% w/w) from Nile tilapia scale. After 6 months, the collagen content and antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activities increased significantly (P skin did not change (P > 0.05). The color, luster and quantity of hair were obviously ameliorated. Moreover, the structure of epidermis and dermis, the density and distribution of collagen fibers and the ratio of type I to type III collagen were improved in a dose-dependent manner as shown by histochemical staining. Oral ingestion of CHs increased the collagen content and antioxidant enzyme activities and improved the appearance and structure of skin. These results suggest the potential of CHs as an anti-skin-aging ingredient in nutraceuticals or functional foods. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  8. Oral administration of submerged cultivated Grifola frondosa enhances phagocytic activity in normal mice.

    Science.gov (United States)

    Wang, Lisu; Ha, Choi-Lan; Cheng, Tso-Lin; Cheng, Su-Yun; Lian, Tzi-Wei; Wu, Ming-Jiuan

    2008-02-01

    Grifola frondosa fruiting body (Maitake) has been used as a dietary supplement due to its antitumour and immunomodulatory properties. The aim of this study was to evaluate the immunomodulatory effects of orally administered submerged cultivated G. frondosa mixture, including both mycelium and culture broth, in a healthy murine model. Composition analyses showed that submerged cultivated G. frondosa mixture contained only 32.48% carbohydrate, which was less than half of fruiting bodies. The content of adenosine, a potential immunomodulatory agent in medicinal mushrooms, was 2.8 mg g(-1). After feeding 8-week-old female BALB/cByJ mice with AIN-93G diet containing 0% (C), 1% (G1), 3% (G3) or 5% (G5) (wt/wt) G. frondosa mixture for 31 days, neither body weight nor the outward appearance of organs showed any significant difference among different diet groups. Splenocyte subpopulation, mitogen-activated cytokine release and splenic NK activity were not affected by G. frondosa administration, either. On the other hand, the phagocytic activity was enhanced in leucocytes of groups G3 and G5, without exerting detectable levels of serum proinflammatory cytokines. These results suggested that oral administration of submerged cultivated G. frondosa mixture may enhance host innate immunity against foreign pathogens without eliciting adverse inflammatory response.

  9. Immunotoxic effects of imidacloprid following 28 days of oral exposure in BALB/c mice.

    Science.gov (United States)

    Badgujar, Prarabdh C; Jain, S K; Singh, Ajit; Punia, J S; Gupta, R P; Chandratre, Gauri A

    2013-05-01

    Imidacloprid, a neonicotinoid insecticide has been in use worldwide for several years in agriculture and veterinary medicine. It is possible that residue of this compound may be recycled in the food chain and thus information regarding effects from potential exposure to it is warranted. The objective of the present study was to evaluate immunotoxic effects of imidacloprid in female BALB/c mice. Imidacloprid was administered orally daily at 10, 5, or 2.5mg/kg over 28 days. Specific parameters of humoral and cellular immune response including hemagglutinating antibody (HA) titer to sheep red blood cells (SRBC; T-dependent antigen), delayed type hypersensitivity (DTH) response to SRBC, and T-lymphocyte proliferation in response to phytohemagglutinin (PHA) were evaluated. The results showed that imidacloprid at high dose, specifically suppressed cell-mediated immune response as was evident from decreased DTH response and decreased stimulation index of T-lymphocytes to PHA. At this dose, there were also prominent histopathological alterations in spleen and liver. Histopathological analysis of footpad sections of mice revealed dose-related suppression of DTH response. Imidacloprid at low dose of 2.5mg/kg/day did not produce any significant alterations in cellular and humoral immune response and it seemed to be an appropriate dose for assessment of 'no observable adverse effects level' for immunotoxicity in BALB/c mice. The results also indicated that imidacloprid has immunosuppressive effects at doses >5mg/kg, which could potentially be attributed to direct cytotoxic effects of IMD against T cells (particularly TH cells) and that long-term exposure could be detrimental to the immune system. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Comparison of serum bisphenol A concentrations in mice exposed to bisphenol A through the diet versus oral bolus exposure.

    Science.gov (United States)

    Sieli, Paizlee T; Jašarevic, Eldin; Warzak, Denise A; Mao, Jiude; Ellersieck, Mark R; Liao, Chunyang; Kannan, Kurunthachalam; Collet, Séverine H; Toutain, Pierre-Louis; Vom Saal, Frederick S; Rosenfeld, Cheryl S

    2011-09-01

    Bisphenol A (BPA) is a widely produced endocrine-disrupting chemical. Diet is a primary route of exposure, but internal exposure (serum concentrations) in animals and humans has been measured only after single oral bolus administration. We compared serum concentrations of BPA over a 24-hr period after oral bolus administration or ad libitum feeding in mice and assessed for buildup with dietary exposure. Adult female mice were administered [dimethyl-d6]-BPA (BPA-d6) as a single oral bolus (20 mg/kg body weight) or fed a diet containing 100 mg BPA-d6/kg feed weight ad libitum for 1 week. Serum concentrations were analyzed using isotope dilution liquid chromatography coupled with electrospray tandem mass spectrometry and compared between exposure groups over the first 23 hr and after 7 days of dietary exposure. Maximum concentration (Cmax) for BPA-d6 during the first 24 hr was reached at 1 hr and 6 hr for oral bolus and diet groups, respectively. Relative BPA-d6 bioavailability (unconjugated BPA-d6) was higher in diet-exposed mice than in the bolus group despite a relative lower absorption, a phenomenon consistent with an inhibitory effect of food on first-pass hepatic metabolism. In mice with ongoing dietary exposure, unconjugated BPA-d6 was higher on day 7 than on day 1. This is the first report of serum BPA concentrations in an animal model exposed to this chemical via the diet. Although bolus administration of BPA-d6 led to peak concentrations within 1 hr, Cmax for diet-exposed mice was delayed for several hours. However, bolus administration underestimates bioavailable serum BPA concentrations in animals-and presumably humans-than would result from dietary exposure. Exposure via diet is a more natural continuous exposure route than oral bolus exposure and is thus a better predictor of BPA concentrations in chronically exposed animals and humans.

  11. Interleukin-4 production in BALB/c mice immunized with Anisakis simplex

    Directory of Open Access Journals (Sweden)

    Perteguer María Jesús

    2001-01-01

    Full Text Available We investigated the interleukin (IL-4 levels in BALB/c mice immunized with Anisakis extract in single or multiple doses and in mice orally infected with a larva. From animals immunized maximum responses were obtained with the multiple doses with an only IL-4 peak. Conversely, in the mice inoculated with a larva per os, the IL-4 levels showed two peaks of different rates.

  12. Inflammatory lesion and parasite load are inversely associated in Leishmania amazonensis infected mice genetically selected according to oral tolerance susceptibility.

    Science.gov (United States)

    Tavares, Daniel; da Conceição Ribeiro, Ricardo; Carlos da Silva, Antonio

    2006-04-01

    Two strains of mice selected according to extreme phenotypes of susceptibility and resistance to oral tolerance (TS and TR mice, respectively) were infected with 1 x 10(7) Leishmania amazonensis promastigotes and studied comparatively. TS mice developed a minor pathology while permitting parasite growth with the presence of increased IL-4, IL-10 and IFN-gamma, and lower NO and IL-2 levels and delayed-type hypersensitivity (DTH). In contrast, in TR mice, footpad swelling was increased but parasite growth was reduced. They produced lower IL-4, IL-10 and IFN-gamma but increased NO, IL-2 levels, DTH, activated spleen macrophages and periarteriolar lymphoid sheaths. The results suggest that the tolerogenic TS mouse profile, with higher IL-10 production, impaired lesion development but also avoided macrophage leishmanicidal activity, maintaining in this manner a silent parasite load. On the other hand, the TR mouse profile contributed to lesion progression with controlled parasite load. To directly address the influence of oral tolerance on infection, mice were gavaged with OVA, and 7 days afterwards were infected and challenged to bystander suppression with OVA in the same footpad. In TR mice gavaged with 25 mg OVA the inflammatory lesion was largely enhanced, while with 5 mg OVA the lesion was diminished. In TS mice the footpad swelling was always lower. However, the bystander effect did not modify the establishment of infection; and similarly to the control non-bystander mice, parasite clearance was maintained in TR and prevented in TS mice. Therefore, a better comprehension of immunoregulation of innate and adaptive immunity in the early stages of infection is necessary for the development of protocols preventing inflammation and contributing to the elimination of parasites.

  13. Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice

    Directory of Open Access Journals (Sweden)

    Olakunle James Onaolapo

    2013-01-01

    Full Text Available This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.

  14. Oral treatment with herbal formula B307 alleviates cardiac failure in aging R6/2 mice with Huntington's disease via suppressing oxidative stress, inflammation, and apoptosis.

    Science.gov (United States)

    Lin, Ching-Lung; Wang, Sheue-Er; Hsu, Chih-Hsiang; Sheu, Shuenn-Jyi; Wu, Chung-Hsin

    2015-01-01

    Cardiac failure is often observed in aging patients with Huntington's disease (HD). However, conventional pharmacological treatments for cardiac failure in HD patients have rarely been studied. Chinese herbal medicines, especially combined herbal formulas, have been widely used to treat cardiac dysfunctions over the centuries. Thus, we assess whether oral treatment with herbal formula B307 can alleviate cardiac failure in transgenic mice with HD. After oral B307 or vehicle treatment for 2 weeks, cardiac function and cardiomyocytes in 12-week-old male R6/2 HD mice and their wild-type littermate controls (WT) were examined and then compared via echocardiography, immunohistochemistry, and Western blotting. We found that cardiac performance in aging R6/2 HD mice had significantly deteriorated in comparison with their WT (Paging R6/2 HD mice were significantly lower than their WT (Paging R6/2 HD mice were significantly higher than their WT (Paging R6/2 HD mice had significantly improved under oral B307 treatment (Paging R6/2 HD mice were significantly higher under oral B307 treatment (Paging R6/2 HD mice were significantly reduced under oral B307 treatment (Paging HD R6/2 mice via suppressing cardiac oxidative stress, inflammation, and apoptosis. We suggested that the herbal formula B307 may be further developed as a potential health supplement for ameliorating cardiac failure associated with aging.

  15. Cytokine profile and natural killer cell activity in Listeria monocytogenes infected mice treated orally with Petiveria alliacea extract.

    Science.gov (United States)

    Queiroz, M L; Quadros, M R; Santos, L M

    2000-08-01

    In this work, we investigated the effects of Petiveria alliacea extract on the production of Th1-type and Th2-type cytokines and on NK cells activity in normal and Listeria monocytogenes infected mice. Our results demonstrated that in normal/non-infected mice P. alliacea administration led to increased levels of Interleukin-2 (IL-2). The infection alone enhanced INF-gamma levels and NK cell activity at 48 and 72 hours of infection. The treatment with five consecutive doses of 1000 mg/kg/day of P. alliacea extract, given previously to infection, led to further increases in IL-2 levels, in relation to normal/non-infected/P. alliacea treated controls, and in INF-gamma levels at 72 h of infection, compared to infected mice. On the other hand, the production of IL-4 and IL-10 were not altered either by the infection or by the treatment with P. alliacea extract. NK cells activity increased at 48 h and 72 h following the inoculation of the bacteria. When mice were treated with P. alliacea previously to infection, NK activity was higher than that observed at 48 h, 72 h and 120 h of infection in the infected animal. Based on these findings we suggest that P. alliacea up-regulates anti-bacterial immune response by enhancing both Th1 function and the activity of NK cells.

  16. Long-term evaluation of oral gavage with periodontopathogens or ligature induction of experimental periodontal disease in mice.

    Science.gov (United States)

    de Molon, Rafael Scaf; Mascarenhas, Vinicius Ibiapina; de Avila, Erica Dorigatti; Finoti, Livia Sertori; Toffoli, Gustavo Boze; Spolidorio, Denise Madalena Palomari; Scarel-Caminaga, Raquel Mantuaneli; Tetradis, Sotirios; Cirelli, Joni Augusto

    2016-07-01

    To evaluate in long-term periods the destruction of periodontal tissues and bacterial colonization induced by oral gavage with periodontopathogens or ligature experimental periodontal disease models. Forty-eight C57BL/6 J mice were divided into four groups: group C: negative control; group L: ligature; group G-Pg: oral gavage with Porphyromonas gingivalis; and group G-PgFn: oral gavage with Porphyromonas gingivalis associated with Fusobacterium nucleatum. Mice were infected by oral gavage five times in 2-day intervals. After 45 and 60 days, animals were sacrificed and the immune-inflammatory response in the periodontal tissue was assessed by stereometric analysis. The alveolar bone loss was evaluated by live microcomputed tomography and histometric analysis. qPCR was used to confirm the bacterial colonization in all the groups. Data were analyzed using the Kruskal-Wallis, Wilcoxon, and ANOVA tests, at 5 % of significance level. Ligature model induced inflammation and bone resorption characterized by increased number of inflammatory cells and decreased number of fibroblasts, followed by advanced alveolar bone loss at 45 and 60 days (p periodontal disease induction, independent of tissue alterations. These mice models of periodontitis validates, compliments, and enhances published PD models that utilize ligature or oral gavage and supports the importance of a successful colonization of a susceptible host, a bacterial invasion into vulnerable tissue, and host-bacterial interactions that lead to tissue destruction. The ligature model was an effective approach to induce inflammation and bone loss similar to human periodontitis, but the oral gavage models were not efficient in inducing periodontal inflammation and tissue destruction in the conditions studied. Ligature models can provide a basis for future interventional studies that contribute to the understanding of the disease pathogenesis and the complex host response to microbial challenge.

  17. Effect of oral administration of Lactobacillus reuteri in increased survival and resistance to neoplasm in mice breast cancer

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    Soltan Dallal MM

    2013-02-01

    Full Text Available Background: Several reports indicate that the probiotics can increase body resistance against malignant tumors. The aim of this study is to evaluate the effect of Lactobaci-llus reuteri Persian type culture collection (PTCC 1655 in preventing tumor growth, improving weight and survival rate in mice with breast cancer.Methods: Twenty mice, the BALB/c at six weeks age, weighing approximately 17 gram were divided into two groups. Oral administration of 500 micro liters of Lactobacillus reuteri suspension performed for the first group 14 days before tumor transplantation. The second group (control received the same volume of phosphate buffer saline (PBS. Then the mice had tumor transplantation surgery. Lactobacillus reuteri was prescribed in the first group in seven-day period and three-day interruption pattern. At the same time the second group (control received PBS. This process was continued until 45 day. The tumor growth, histology and body weight were evaluated in both group and the mortality of mice was recorded.Results: In the mice transplanted tumors that had received probiotics, tumor growth decreased in comparison with control group. In this group the body weight increased (P>0/05. In addition, the survival of these mice had significantly increased compared to control group (P=0.002. The evaluation of tumor tissue also showed increased immune system function in mice receiving the probiotic (P>0/05.Conclusion: Lactobacillus reuteri can improve immune system function and have an important role to help treatment of cancer.

  18. Acute and Chronic Effects of Oral Genistein Administration in Neonatal Mice1

    Science.gov (United States)

    Cimafranca, Melissa A.; Davila, Juanmahel; Ekman, Gail C.; Andrews, Rachel N.; Neese, Steven L.; Peretz, Jackye; Woodling, Kellie A.; Helferich, William G.; Sarkar, Jhimly; Flaws, Jodi A.; Schantz, Susan L.; Doerge, Daniel R.; Cooke, Paul S.

    2010-01-01

    Soy-based infant formulas are widely used in the United States and some other countries. These formulas contain high levels of the estrogenic isoflavone genistein, leading to concern that neonatal genistein exposure could cause acute and/or long-term adverse effects on reproductive and other organs. However, previous work to assess genistein effects in rodent models has not typically replicated the route of delivery and/or serum genistein concentrations reported for soy formula-fed human infants. Our objective was to develop a mouse model that more closely mimics the oral genistein exposure and total serum genistein concentrations observed in soy formula-fed infants. Mouse pups were dosed orally with genistein in a soy formula-corn oil emulsion from Postnatal Day (PND) 1 to PND 5, then effects on reproductive and nonreproductive organs were assessed after dosing and during subsequent development. Neonatal treatment resulted in changes both at the completion of dosing (PND 5) and in adult animals. At PND 5, neonatal genistein treatment caused increased relative uterine weight and down-regulation of progesterone receptor in uterine epithelia. Estrogenic effects of genistein were also seen in the neonatal ovary and thymus, which had an increase in the incidence of multioocyte follicles (MOFs) and a decrease in thymic weight relative to body weight, respectively. The increased incidence of MOFs persisted into adulthood for neonatally treated genistein females, and estrous cycle abnormalities were seen at 6 mo of age despite normal fertility in these mice. The immediate and long-term effects in this neonatal animal model raise concerns that high serum concentrations of genistein are estrogenic and could potentially impact the development of human infants fed soy formula. PMID:20357267

  19. Automatic agar tray inoculation device

    Science.gov (United States)

    Wilkins, J. R.; Mills, S. M.

    1972-01-01

    Automatic agar tray inoculation device is simple in design and foolproof in operation. It employs either conventional inoculating loop or cotton swab for uniform inoculation of agar media, and it allows technician to carry on with other activities while tray is being inoculated.

  20. Jorge Lobo’s disease: experimental inoculation in Swiss mice Doença de Jorge Lobo. Inoculação experimental em camundongos suiços

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    Diltor Vladimir Araújo OPROMOLLA

    1999-11-01

    Full Text Available Sixty-four isogenic Swiss mice were intradermically inoculated in both hind foot pads. The inocula, consisting of fungal suspensions from biopsies obtained from Jorge Lobo’s Disease patients, had the total number of fungi and the viability index determined using a Neubauer chamber and the fluorescein diacetate-ethidium bromide technique (FD-EB, respectively. The animals were sacrificed at times ranging from ten days to eighteen months after inoculation. The cellular infiltrate, mainly consisting of macrophages containing fungi, increased progressively up to end of the study; however, no macroscopic alterations were observed in the inoculated feet. After nine months, small numbers of Langhans’ giant cells started to appear in the infiltrate. A considerable number of fungi was observed at the end of the experimental period, but only a few were viable when stained by the FD-EB technique. This fact suggests that there is a multiplication of fungal cells, which are destroyed by the macrophages but remain in the tissue for a long time due perhaps to the difficulties in their elimination. These findings led us to conclude that in spite of the maintenance of the infection in these animals, Swiss mice cannot be considered an ideal model to study Jorge Lobo’s Disease. However, the authors call attention to the possibility of other mouse strains being more susceptible to Paracoccidioides loboi.Foram inoculados por via intradérmica, os coxins plantares traseiros de 64 camundongos Suíços, isogênicos. Os inóculos constituídos de uma suspensão fúngica, obtidos de biópsias de pacientes portadores de Doença de Jorge Lobo, foram submetidos a contagem do número total de fungos em câmara de Neubauer e a determinação da viabilidade segundo técnica do diacetato de fluoresceína-brometo de etídeo (DF-BE. Os animais foram sacrificados em períodos de tempo que variaram de 10 dias a 18 meses pós-inoculação. Um infiltrado celular constitu

  1. Inhibitory effect of orally-administered sulfated polysaccharide ascophyllan isolated from ascophyllum nodosum on the growth of sarcoma-180 solid tumor in mice.

    Science.gov (United States)

    Jiang, Zedong; Abu, Ryogo; Isaka, Shogo; Nakazono, Satoru; Ueno, Mikinori; Okimura, Takasi; Yamaguchi, Kenichi; Oda, Tatsuya

    2014-04-01

    We evaluated the antitumor activity of crude extract and ascophyllan prepared from Ascophyllum nodosum in sarcoma-180 solid tumor-bearing mice with continuous intraperitoneal (i.p.) administration at a dose of 50 mg/kg body weight/day or oral administration at a dose of 500 mg/kg body weight/day. Ascophyllan and crude extract administered via the oral route showed greater antitumor effects than via i.p. route, and the tumor sizes in mice treated with ascopyllan and crude extract were reduced by a mean of 68.7±6.8% and 42.4±24.8% by the oral route, and 41.4±16.1% and 13.6±20.6% by i.p. route compared to control mice. Splenic natural killer cell activity in the mice treated with ascophyllan and crude extract by i.p. route was significantly enhanced, while only a slight increase of this activity was observed in orally-treated mice. Furthermore, increase in spleen weight of tumor-bearing mice was slightly suppressed by oral administration of ascophyllan, whereas i.p. administration resulted in further enlargement. Analysis of serum cytokines revealed that oral treatment with ascophyllan resulted in significant increase of tumor necrosis factor-α and interleukin-12 levels. Since ascophyllan showed no direct cytotoxic effect on sarcoma-180 cells, orally-administered ascophyllan is suggested to exhibit its antitumor activity through the activation of the host immune system.

  2. High hydrostatic pressure processing of murine norovirus 1-contaminated oysters inhibits oral infection in STAT-1(-/-)-deficient female mice.

    Science.gov (United States)

    Gogal, R M; Kerr, R; Kingsley, D H; Granata, L A; LeRoith, T; Holliman, S D; Dancho, B A; Flick, G J

    2011-02-01

    We have previously demonstrated that high pressure processing (HPP) is effective in preventing in vitro replication of murine norovirus strain 1 (MNV-1), a human norovirus surrogate, in a monocyte cell line following extraction from MNV-1-contaminated oysters. In the present study, the efficacy of HPP to prevent in vivo replication within mice fed HPP-treated MNV-1-seeded oyster extracts was evaluated. Oyster homogenate extracts seeded with MNV-1 were given 5-min, 400-MPa (58,016-psi) treatments and orally gavaged into immunodeficient (STAT-1(-/-)) female mice. Mice orally gavaged with HPP-treated MNV-1 showed significant (P ≤ 0.05) weight loss leading to enhanced morbidity, whereas those given 100 and 200 PFU of HPP-treated MNV-1 were comparable to uninfected controls. MNV-1 was detected, via real-time PCR, within the liver, spleen, and brain of all mice fed non-HPP-treated homogenate but was not detected in the tissues of mice fed HPP-treated homogenates or in uninfected control mice. Hepatocellular necrosis and lymphoid depletion in the spleen were observed in non-HPP-treated MNV-1 mice only. These results clearly show that HPP prevents MNV-1 infection in vivo and validates that viral inactivation by HPP in vitro is essentially equivalent to that in vivo. Further, the data suggest that HPP may be an effective food processing intervention for norovirus-contaminated shellfish and thus may decrease risk to both immunocompromised and immunocompetent individuals who consume shellfish. Copyright ©, International Association for Food Protection

  3. Intravenous inoculation of a bat-associated rabies virus causes lethal encephalopathy in mice through invasion of the brain via neurosecretory hypothalamic fibers.

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    Mirjam A R Preuss

    2009-06-01

    Full Text Available The majority of rabies virus (RV infections are caused by bites or scratches from rabid carnivores or bats. Usually, RV utilizes the retrograde transport within the neuronal network to spread from the infection site to the central nervous system (CNS where it replicates in neuronal somata and infects other neurons via trans-synaptic spread. We speculate that in addition to the neuronal transport of the virus, hematogenous spread from the site of infection directly to the brain after accidental spill over into the vascular system might represent an alternative way for RV to invade the CNS. So far, it is unknown whether hematogenous spread has any relevance in RV pathogenesis. To determine whether certain RV variants might have the capacity to invade the CNS from the periphery via hematogenous spread, we infected mice either intramuscularly (i.m. or intravenously (i.v. with the dog-associated RV DOG4 or the silver-haired bat-associated RV SB. In addition to monitoring the progression of clinical signs of rabies we used immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR to follow the spread of the virus from the infection site to the brain. In contrast to i.m. infection where both variants caused a lethal encephalopathy, only i.v. infection with SB resulted in the development of a lethal infection. While qRT-PCR did not reveal major differences in virus loads in spinal cord or brain at different times after i.m. or i.v. infection of SB, immunohistochemical analysis showed that only i.v. administered SB directly infected the forebrain. The earliest affected regions were those hypothalamic nuclei, which are connected by neurosecretory fibers to the circumventricular organs neurohypophysis and median eminence. Our data suggest that hematogenous spread of SB can lead to a fatal encephalopathy through direct retrograde invasion of the CNS at the neurovascular interface of the hypothalamus-hypophysis system

  4. Tissue distribution and elimination of BDE 47 in mice following a single oral dose

    Energy Technology Data Exchange (ETDEWEB)

    Staskal, D. [Curriculum in Toxicology, Chapel Hill, NC (United States); Diliberto, J.; DeVito, M.; Birnbaum, L. [US EPA, ORD, NHEERL, ETD, RTP (United States)

    2004-09-15

    2,2',4,4'-Tetrabromodiphenyl ether (BDE 47) is a polybrominated diphenyl ether (PBDE) congener which is part of a class of brominated flame retardants (BFRs) commonly used in a variety of highly flammable consumer goods. Concern for the effects of PBDEs has increased significantly in recent years as their presence has been detected in environmental samples and in human tissues at steadily increasing concentrations. Despite its small contribution to the PBDE global production and usage, BDE 47 is the major congener found in environmental samples and human tissue. Limited toxicology studies suggest that BDE 47 is a developmental neurotoxicant and an endocrine disruptor however, several data gaps exist and must be investigated in order to evaluate the human health risk of BDE 47. This study investigated basic toxicokinetic properties of BDE 47 in female C57BL/6J mice. Here we report the effect of time on the absorption, distribution, and excretion following a single, oral dose of 14C-labeled BDE 47. Animals were administered 1.0mg BDE 47/kg bw, a dose chosen based on previous studies. Distribution and elimination were monitored at several time points ranging from 1 hour to 21 days following exposure. Data from these basic toxicokinetic studies will be applied to studies investigating the toxicokinetics of BDE 47 in a developmental model as well as in the development of a physiologically-based pharmacokinetic (PBPK) model.

  5. Oral administration of Lactobacillus gasseri SBT2055 is effective for preventing influenza in mice.

    Science.gov (United States)

    Nakayama, Yosuke; Moriya, Tomohiro; Sakai, Fumihiko; Ikeda, Noriko; Shiozaki, Takuya; Hosoya, Tomohiro; Nakagawa, Hisako; Miyazaki, Tadaaki

    2014-04-10

    The Lactobacillus gasseri SBT2055 (LG2055) is a probiotic lactic acid bacterium with properties such as bile tolerance and ability to improve the intestinal environment. In this study, we established that the oral administration of LG2055 exhibits efficacy to protect mice infected with the influenza virus A/PR8. The body weight losses were lower with the LG2055 administration after the PR8 virus infection. At 5 days after the infection, the virus titer was significantly decreased as was the amount of produced IL-6 in the lung tissue, the number of total cells in the bronchoalveolar lavage fluid was reduced by the LG2055 administration. The expression of the Mx1 and Oas1a genes, critical for the viral clearance in the lung tissues was increased by the pre-treatment with LG2055. These findings suggest that the LG2055 administration is effective for the protection against influenza A virus infection by the down-regulation of viral replication through the induction of antiviral genes expression.

  6. Oral Treatment with the Ghrelin Receptor Agonist HM01 Attenuates Cachexia in Mice Bearing Colon-26 (C26) Tumors

    OpenAIRE

    Villars, Fabienne O.; Pietra, Claudio; Giuliano, Claudio; Lutz, Thomas A.; Riediger, Thomas

    2017-01-01

    The gastrointestinal hormone ghrelin reduces energy expenditure and stimulates food intake. Ghrelin analogs are a possible treatment against cancer anorexia-cachexia syndrome (CACS). This study aimed to investigate whether oral treatment with the non-peptidergic ghrelin receptor agonist HM01 counteracts CACS in colon-26 (C26) tumor-bearing mice. The C26 tumor model is characterized by pronounced body weight (BW) loss and muscle wasting in the absence of severe anorexia. We analyzed the time c...

  7. Oral administration of an ethanolic extract of Hypericum gentianoides attenuates spontaneous colitis in mdr1a -/- mice

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    Kelley M. K. Haarberg

    2016-05-01

    Full Text Available Background: Nutraceuticals (i.e., complementary and alternative medicines are gaining ground as therapeutic modalities for inflammatory and autoimmune disorders, primarily due to their low toxicity and high patient compliance. Several species of Hypericum have been shown to possess immunomodulatory capabilities in many disease models. However, the therapeutic potential of the chemically unique Hypericum gentianoides (HG is largely untested. We investigated the efficacy of an orally administered ethanolic extract of HG (HGEE to prophylactically inhibit/ameliorate the spontaneous colitis that develops in mdr1a deficient (mdr1a -/- mice. Methods: Beginning at six weeks of age, vehicle (5% ethanol, HGEE (4.8 mg/day or metronidazole (0.75 mg/mL were orally administered daily to mdr1a -/- or FVB WT mice until they reached 20 weeks of age or had lost ≥ 15 % of their body weight. Macroscopic disease assessment included measurement of weight loss, colon shortening, and combined colonic/cecal macroscopic lesion scores. Colonic/cecal inflammation was also scored histologically. Inflammatory responses were assessed using myeloperoxidase (MPO assay and analysis of serum cytokines/chemokines. Results: Daily administration of HGEE significantly (p < 0.05 delayed the onset of clinical signs of disease, reduced the associated morbidity, and attenuated macroscopic and microscopic disease/inflammatory scores in mdr1a -/- mice. After 14 weeks of treatment, there were no adverse macroscopic or microscopic effects observed following the daily administration of HGEE to wild type FVB mice. Histological evaluation of colonic tissue revealed a decrease in neutrophil infiltration in HGEE treated mdr1a -/- mice, which was substantiated by a significant decrease (p ≤ 0.05 in colonic MPO activity. Compared to vehicle treated mdr1a -/- mice, levels of G-CSF, KC, and TNFα were significantly lower in the serum of mdr1a -/- mice treated with HGEE. Conclusion: Oral

  8. Oral administration of Lactobacillus plantarum CJLP133 and CJLP243 alleviates birch pollen-induced allergic rhinitis in mice.

    Science.gov (United States)

    Choi, S-P; Oh, H-N; Choi, C-Y; Ahn, H; Yun, H S; Chung, Y M; Kim, B; Lee, S J; Chun, T

    2018-03-01

    In this study, we evaluated the therapeutic efficacy of selected probiotics in a mouse model of birch pollen (BP)-induced allergic rhinitis. Oral administration of Lactobacillus plantarum CJLP133 and CJLP243 ameliorated the symptoms of BP-induced allergic rhinitis by reducing airway hyperresponsiveness, and both the histological scores and the number of infiltrated cells in the nasal cavities and lungs. Compared with those from vehicle-treated mice, bronchoalveolar lavage fluid and draining lymph node samples from CJLP133 and CJLP243-administrated mice showed diminished numbers of immune cells, increased secretion of a Th1-type cytokine (IFN-γ) and decreased production of Th2-type cytokines (IL-4, IL-5 and IL-13). Consistent with these results, levels of IL-4, IL-5, IL-13, serum IgE and BP-specific serum IgG1 were decreased, whereas secretion of IFN-γ and BP-specific serum IgG2a was augmented upon administration of CJLP133 and CJLP243 in mice. Oral administration of L. plantarum CJLP133 and CJLP243 alleviates symptoms of BP-induced allergic rhinitis in mice by recovering Th1/Th2 balance via enhancement of the Th1-type immune response. Lactobacillus plantarum CJLP133 and CJLP243 have therapeutic effects on BP-induced allergic rhinitis in an animal model. © 2017 The Society for Applied Microbiology.

  9. 1'-Acetoxychavicol acetate inhibits growth of human oral carcinoma xenograft in mice and potentiates cisplatin effect via proinflammatory microenvironment alterations.

    Science.gov (United States)

    In, Lionel L A; Arshad, Norhafiza M; Ibrahim, Halijah; Azmi, Mohamad Nurul; Awang, Khalijah; Nagoor, Noor Hasima

    2012-10-09

    Oral cancers although preventable, possess a low five-year survival rate which has remained unchanged over the past three decades. In an attempt to find a more safe, affordable and effective treatment option, we describe here the use of 1'S-1'-acetoxychavicol acetate (ACA), a component of Malaysian ginger traditionally used for various medicinal purposes. Whether ACA can inhibit the growth of oral squamous cell carcinoma (SCC) cells alone or in combination with cisplatin (CDDP), was explored both in vitro using MTT assays and in vivo using Nu/Nu mice. Occurrence of apoptosis was assessed using PARP and DNA fragmentation assays, while the mode of action were elucidated through global expression profiling followed by Western blotting and IHC assays. We found that ACA alone inhibited the growth of oral SCC cells, induced apoptosis and suppressed its migration rate, while minimally affecting HMEC normal cells. ACA further enhanced the cytotoxic effects of CDDP in a synergistic manner as suggested by combination index studies. We also found that ACA inhibited the constitutive activation of NF-κB through suppression of IKKα/β activation. Human oral tumor xenografts studies in mice revealed that ACA alone was as effective as CDDP in reducing tumor volume, and further potentiated CDDP effects when used in combination with minimal body weight loss. The effects of ACA also correlated with a down-regulation of NF-κB regulated gene (FasL and Bim), including proinflammatory (NF-κB and COX-2) and proliferative (cyclin D1) biomarkers in tumor tissue. Overall, our results suggest that ACA inhibits the growth of oral SCC and further potentiates the effect of standard CDDP treatment by modulation of proinflammatory microenvironment. The current preclinical data could form the basis for further clinical trials to improve the current standards for oral cancer care using this active component from the Malaysian ginger.

  10. Oral administration of the Aureobasidium pullulans-derived β-glucan effectively prevents the development of high fat diet-induced fatty liver in mice.

    Science.gov (United States)

    Aoki, Shiho; Iwai, Atsushi; Kawata, Koji; Muramatsu, Daisuke; Uchiyama, Hirofumi; Okabe, Mitsuyasu; Ikesue, Masahiro; Maeda, Naoyoshi; Uede, Toshimitsu

    2015-07-16

    Aureobasidium pullulans-derived β-glucan (AP-PG) consisting of a β-(1,3)-linked glucose main chain and β-(1,6)-linked glucose branches is taken as a supplement to improve health. This study demonstrates that oral administration of AP-PG is effective to prevent the development of high-fat diet (HFD)-induced fatty liver in mice. Here, C57BL/6N mice were fed with a normal diet or HFD, and AP-PG diluted in drinking water was administered orally. After 16 weeks, the serological analysis showed that HFD-induced high blood cholesterol and triglyceride levels were reduced by the oral administration of AP-PG. Further, HFD induced-fatty liver was significantly reduced by the oral administration of AP-PG. The triglyceride accumulation in the liver was also significantly reduced in mice administered AP-PG. Liver injury as indicated by an increase in serum alanine aminotransferase (ALT) in the HFD-fed mice was significantly reduced in the mice administered AP-PG orally, and the gene expression of cholesterol 7 alpha-hydroxylase (CYP7A1) which is known to be involved in cholesterol degradation in the liver was significantly increased in the AP-PG administered mice. These results suggest the possibility that the oral administration of AP-PG is effective to prevent the development of non-alcoholic fatty liver disease (NAFLD).

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

    Science.gov (United States)

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

  12. Epicutaneous immunotherapy (EPIT blocks the allergic esophago-gastro-enteropathy induced by sustained oral exposure to peanuts in sensitized mice.

    Directory of Open Access Journals (Sweden)

    Lucie Mondoulet

    Full Text Available BACKGROUND: Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT on these processes. METHODS: Mice were sensitized by gavages with whole peanut protein extract (PPE given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure. RESULTS: Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm(2 and reduced villus/crypt ratios (1.6±0.15. In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines as well as esophageal eosinophilia (50 eosinophils/mm(2, p<0.05, mRNA expression of Th2 cytokines in tissue--eotaxin (p<0.05, IL-5 (p<0.05, and IL-13 (p<0.05--GATA-3 (p<0.05, and intestinal villus sub-atrophia (2.3±0.15. EPIT also increased specific IgG2a (p<0.05 and mRNA expression of Foxp3 (p<0.05 in the esophageal mucosa. CONCLUSIONS: Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT.

  13. Effects of route of inoculation on Mycoplasma gallisepticum infection in captive house finches.

    Science.gov (United States)

    Dhondt, Keila V; Dhondt, André A; Ley, David H

    2007-12-01

    The routes by which Mycoplasma gallisepticum initiates infection during outbreaks of conjunctivitis in house finches remain uncertain. As M. gallisepticum recovered from the cloaca of chickens remains viable for up to 3 days in chicken faeces, the possibility of spread via faecal contamination has been suggested. To test the hypothesis that food or water contaminated with M. gallisepticum may initiate infection, 20 house finches were experimentally inoculated by the oral or the conjunctival route. Clinical and immunological responses were compared. All inoculated birds seroconverted, thus demonstrating infection. Only two of the birds inoculated via the oral route developed very mild unilateral conjunctivitis while all 10 of those infected by eye-drop inoculation developed severe bilateral conjunctivitis. The orally inoculated birds had reduced levels of activity for only a few days, while those infected by conjunctival inoculation had reduced activity for several weeks. M. gallisepticum DNA was detected in conjunctival swabs by polymerase chain reaction in only three orally inoculated birds but in all birds in the conjunctivally inoculated group. Antibodies developed more slowly after oral inoculation than after conjunctival inoculation. We showed that oral exposure to M. gallisepticum can initiate infection, disease, and a serological response, which suggests that food or water contaminated with secretions or excretions may be a route of transmission between house finches.

  14. Alternative method of oral administration by peanut butter pellet formulation results in target engagement of BACE1 and attenuation of gavage-induced stress responses in mice.

    Science.gov (United States)

    Gonzales, C; Zaleska, M M; Riddell, D R; Atchison, K P; Robshaw, A; Zhou, H; Sukoff Rizzo, S J

    2014-11-01

    Development of novel therapeutic agents aimed at treating neurodegenerative disorders such as Alzheimer's and Parkinson's diseases require chronic and preferentially oral dosing in appropriate preclinical rodent models. Since many of these disease models involve transgenic mice that are frequently aged and fragile, the commonly used oro-gastric gavage method of drug administration often confounds measured outcomes due to repeated stress and high attrition rates caused by esophageal complications. We employed a novel drug formulation in a peanut butter (PB) pellet readily consumed by mice and compared the stress response as measured by plasma corticosterone levels relative to oral administration via traditional gavage. Acute gavage produced significant elevations in plasma corticosterone comparable to those observed in mice subjected to stress-induced hyperthermia. In contrast, corticosterone levels following consumption of PB pellets were similar to levels in naive mice and significantly lower than in mice subjected to traditional gavage. Following sub-chronic administration, corticosterone levels remained significantly higher in mice subjected to gavage, relative to mice administered PB pellets or naive controls. Furthermore, chronic 30day dosing of a BACE inhibitor administered via PB pellets to PSAPP mice resulted in expected plasma drug exposure and Aβ40 lowering consistent with drug treatment demonstrating target engagement. Taken together, this alternative method of oral administration by drug formulated in PB pellets results in the expected pharmacokinetics and pharmacodynamics with attenuated stress levels, and is devoid of the detrimental effects of repetitive oral gavage. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. SODIUM BICARBONATE FACILITATES LOW-DOSE ORAL TOLERANCE TO PEANUT IN MICE

    Science.gov (United States)

    Rationale: Oral tolerance specifically inhibits production of allergic IgE antibody and is therefore a potential method for suppressing food allergy. We have previously demonstrated that a single oral dose of one mg is sufficient to induce oral tolerance to egg white but not pean...

  16. Orally administered heat-killed Lactobacillus gasseri TMC0356 can upregulate cell-mediated immunity in senescence-accelerated mice.

    Science.gov (United States)

    Kawase, Manabu; He, Fang; Miyazawa, Kenji; Kubota, Akira; Yoda, Kazutoyo; Hiramatsu, Masaru

    2012-01-01

    The present study was conducted to test the ability of probiotic lactobacilli to alter age-related immunosenescence in host animals. Senescence-accelerated mouse prone 1 mice were orally fed heat-killed Lactobacillus gasseri TMC0356 (TMC0356) for 4 and 8 weeks at dosages of 10 mg day(-1) after a 16-week period of prefeeding with a standard diet. After 4 and 8 weeks of TMC0356 intervention, splenic activation of natural killer (NK) cells and mRNA expression of cytokines and other immune molecules in the lungs were analysed. After 4 and 8 weeks, splenic NK cell activities were significantly higher in the TMC0356-fed mice compared with control mice (P < 0.05). After 4 weeks, mRNA expression of interleukin-2 and interferon-(α and β) receptor 1 in lung cells isolated from the TMC0356-fed mice also increased significantly compared with that in lung cells from the control mice (P < 0.05). These results suggest that lactobacilli, especially certain selected strains, might enhance cell-mediated immunity in host animals and thereby alter age-related immunosenescence. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  17. Effects of oral administration of di-(2-ethylhexyl) and diisononyl phthalates on atopic dermatitis in NC/Nga mice.

    Science.gov (United States)

    Sadakane, Kaori; Ichinose, Takamichi; Takano, Hirohisa; Yanagisawa, Rie; Koike, Eiko

    2014-02-01

    Subcutaneous injection of low dose of phthalates causes adjuvant effects on immunoglobulin production. Moreover, intraperitoneal injection of di-(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DINP) at doses lower than the no-observed-adverse-effect level (NOAEL) causes aggravation of atopic dermatitis-like skin lesions (ADSLs) in mouse models. However, the effects of oral exposure to these phthalates, including their effect on atopic dermatitis (AD) symptoms, remain unclear. To investigate the effects of oral administration of DEHP and DINP at doses lower than the NOAEL on AD in an NC/Nga mouse model. NC/Nga mice were subcutaneously injected with mite-allergen (Dermatophagoides pteronyssinus) to induce ADSLs and orally administered varying doses of DEHP (0, 8.3, 166.3 or 3325 µg/animal) or DINP (0, 6.6, 131.3 or 2625 µg/animal) once a week for four weeks. Skin disease symptomatology was subsequently evaluated and immunoglobulin production levels in serum and inflammatory cytokine levels in lesion sites were measured. Oral administration of low doses of both DEHP and DINP tended to increase infiltration of eosinophils; degranulation of mast cells and local expression of inflammatory cytokines, interleukin-13 and macrophage inflammatory protein-1 alpha in subcutaneous tissue, whereas DINP administration tended to aggravate allergen-induced ADSL production. Oral administration of both DEHP and DINP at doses lower than the NOAEL tends to increase the allergic response in animal AD models, but only DINP administration slightly aggravates allergen-induced ADSL production.

  18. Comparison of mucosal and systemic humoral immune responses and subsequent protection in mice orally inoculated with a homologous or a heterologous rotavirus.

    OpenAIRE

    Feng, N; Burns, J W; Bracy, L; Greenberg, H B

    1994-01-01

    Rotaviruses are the single most important cause of severe diarrhea in young children worldwide, and vaccination is probably the most effective way to control the disease. Most current live virus vaccine candidates are based on the host range-restricted attenuation of heterologous animal rotaviruses in humans. The protective efficacy of these vaccine candidates has been variable. To better understand the nature of the heterologous rotavirus-induced active immune response, we compared the diffe...

  19. Prolonged oral cannabinoid administration prevents neuroinflammation, lowers β-amyloid levels and improves cognitive performance in Tg APP 2576 mice

    Directory of Open Access Journals (Sweden)

    Martín-Moreno Ana María

    2012-01-01

    Full Text Available Abstract Background Alzheimer's disease (AD brain shows an ongoing inflammatory condition and non-steroidal anti-inflammatories diminish the risk of suffering the neurologic disease. Cannabinoids are neuroprotective and anti-inflammatory agents with therapeutic potential. Methods We have studied the effects of prolonged oral administration of transgenic amyloid precursor protein (APP mice with two pharmacologically different cannabinoids (WIN 55,212-2 and JWH-133, 0.2 mg/kg/day in the drinking water during 4 months on inflammatory and cognitive parameters, and on 18F-fluoro-deoxyglucose (18FDG uptake by positron emission tomography (PET. Results Novel object recognition was significantly reduced in 11 month old Tg APP mice and 4 month administration of JWH was able to normalize this cognitive deficit, although WIN was ineffective. Wild type mice cognitive performance was unaltered by cannabinoid administration. Tg APP mice showed decreased 18FDG uptake in hippocampus and cortical regions, which was counteracted by oral JWH treatment. Hippocampal GFAP immunoreactivity and cortical protein expression was unaffected by genotype or treatment. In contrast, the density of Iba1 positive microglia was increased in Tg APP mice, and normalized following JWH chronic treatment. Both cannabinoids were effective at reducing the enhancement of COX-2 protein levels and TNF-α mRNA expression found in the AD model. Increased cortical β-amyloid (Aβ levels were significantly reduced in the mouse model by both cannabinoids. Noteworthy both cannabinoids enhanced Aβ transport across choroid plexus cells in vitro. Conclusions In summary we have shown that chronically administered cannabinoid showed marked beneficial effects concomitant with inflammation reduction and increased Aβ clearance.

  20. Prolonged oral cannabinoid administration prevents neuroinflammation, lowers β-amyloid levels and improves cognitive performance in Tg APP 2576 mice.

    Science.gov (United States)

    Martín-Moreno, Ana María; Brera, Begoña; Spuch, Carlos; Carro, Eva; García-García, Luis; Delgado, Mercedes; Pozo, Miguel A; Innamorato, Nadia G; Cuadrado, Antonio; de Ceballos, María L

    2012-01-16

    Alzheimer's disease (AD) brain shows an ongoing inflammatory condition and non-steroidal anti-inflammatories diminish the risk of suffering the neurologic disease. Cannabinoids are neuroprotective and anti-inflammatory agents with therapeutic potential. We have studied the effects of prolonged oral administration of transgenic amyloid precursor protein (APP) mice with two pharmacologically different cannabinoids (WIN 55,212-2 and JWH-133, 0.2 mg/kg/day in the drinking water during 4 months) on inflammatory and cognitive parameters, and on ¹⁸F-fluoro-deoxyglucose (¹⁸FDG) uptake by positron emission tomography (PET). Novel object recognition was significantly reduced in 11 month old Tg APP mice and 4 month administration of JWH was able to normalize this cognitive deficit, although WIN was ineffective. Wild type mice cognitive performance was unaltered by cannabinoid administration. Tg APP mice showed decreased ¹⁸FDG uptake in hippocampus and cortical regions, which was counteracted by oral JWH treatment. Hippocampal GFAP immunoreactivity and cortical protein expression was unaffected by genotype or treatment. In contrast, the density of Iba1 positive microglia was increased in Tg APP mice, and normalized following JWH chronic treatment. Both cannabinoids were effective at reducing the enhancement of COX-2 protein levels and TNF-α mRNA expression found in the AD model. Increased cortical β-amyloid (Aβ) levels were significantly reduced in the mouse model by both cannabinoids. Noteworthy both cannabinoids enhanced Aβ transport across choroid plexus cells in vitro. In summary we have shown that chronically administered cannabinoid showed marked beneficial effects concomitant with inflammation reduction and increased Aβ clearance.

  1. Safety of Brucella abortus strain RB51 in deer mice.

    Science.gov (United States)

    Cook, W E; Williams, E S; Thorne, E T; Taylor, S K; Anderson, S

    2001-07-01

    Brucella abortus strain RB51 is an approved brucellosis vaccine for use in cattle that may have potential as an oral vaccine for use in elk (Cervus elaphus) and/or bison (Bison bison). This study was designed to determine effects of strain RB51 on deer mice (Peromyscus maniculatus), a nontarget species that could have access to treated baits in a field situation. In February 1994, 90 mice were orally dosed or intraperitoneally injected with 1 x 10(8) colony forming units strain RB51 and 77 controls were similarly dosed with sterile saline. At weekly intervals through early April 1994, 4 to 6 mice from each group were euthanized, gross necropsies performed, spleens and uteruses cultured, and tissues examined histologically. All orally inoculated mice cleared the infection by 6 wk post-inoculation (PI). While most of the injected mice cleared the infection by 7 wk PI, a few required 9 wk. There were minimal adverse effects attributable to strain RB51. Apparently, strain RB51 would not negatively impact P. maniculatus populations if it were used in a field situation. Also, deer mice appear to be able to clear the vaccine in 6 to 9 wk, thus the probability of these mice transmitting the vaccine to other animals is low.

  2. oral

    African Journals Online (AJOL)

    association between oral candidosis and. AIDS; the first documented patient with. AIDS had oral candidosis.3 A sub- stantial amount of data now emphasise its high prevalence in HIV-infected individuals. The manifestations of candidal infection in HIV-infected persons are restricted to superficial mucosal lesions of varying ...

  3. Technetium-99m-labeled deoxynivalenol from Fusarium mycotoxin alters organ toxicity in BALB/c mice by oral and intravenous route

    Energy Technology Data Exchange (ETDEWEB)

    Chattopadhyay, P; Pandey, A; Goyary, D; Chaurasia, A; Singh, L; Veer, V. [Division of Pharmaceutical Technology, Defence Research Laboratory, Assam (India); Department of Life Sciences, Defense Research Development and Organization, New Delhi (India)

    2012-07-01

    The toxicity of deoxynivalenol, both intravenously and orally, was investigated in male and female BALB/c mice. Technetium-99m ({sup 99m} Tc)-labeled deoxynivalenol was administered to mice by tail vein injection and orally dosed. Distribution of labeled deoxynivalenol at 26 hours was monitored by gamma scintigraphy. In the evaluated organs, the accumulation of radioactive deoxynivalenol was correlated with the amount of radioactivity. In addition, the toxicity of deoxynivalenol was measured by biochemical assays followed by histopathological findings. Kidney and hepatic marker enzymes were significantly increased in intravenously administered deoxynivalenol as compared to orally treated mice. Intravenously treated mice showed severe damage in liver and kidney when compared to those orally exposed. Biodistribution of {sup 99m}Tc-labeled deoxynivalenol differed between oral and intravenous treatment. In intravenously exposed mice, deoxynivalenol was distributed primarily in the liver and kidney whereas in oral exposure, it was found in the stomach and intestines after 26 hours. Deoxynivalenol toxicity, associated with its biodistribution and organ toxicity, was greatest where it had accumulated. The results show that the toxicity of deoxynivalenol is associated with organ accumulation. (author)

  4. Technetium-99m-labeled deoxynivalenol from Fusarium mycotoxin alters organ toxicity in BALB/c mice by oral and intravenous route

    Directory of Open Access Journals (Sweden)

    P Chattopadhyay

    2012-01-01

    Full Text Available The toxicity of deoxynivalenol, both intravenously and orally, was investigated in male and female BALB/c mice. Technetium-99m (99m Tc-labeled deoxynivalenol was administered to mice by tail vein injection and orally dosed. Distribution of labeled deoxynivalenol at 26 hours was monitored by gamma-scintigraphy. In the evaluated organs, the accumulation of radioactive deoxynivalenol was correlated with the amount of radioactivity. In addition, the toxicity of deoxynivalenol was measured by biochemical assays followed by histopathological findings. Kidney and hepatic marker enzymes were significantly increased in intravenously administered deoxynivalenol as compared to orally treated mice. Intravenously treated mice showed severe damage in liver and kidney when compared to those orally exposed. Biodistribution of 99mTc-labeled deoxynivalenol differed between oral and intravenous treatment. In intravenously exposed mice, deoxynivalenol was distributed primarily in the liver and kidney whereas in oral exposure, it was found in the stomach and intestines after 26 hours. Deoxynivalenol toxicity, associated with its biodistribution and organ toxicity, was greatest where it had accumulated. The results show that the toxicity of deoxynivalenol is associated with organ accumulation.

  5. Oral administration of an aqueous extract from the oyster mushroom Pleurotus ostreatus enhances the immunonutritional recovery of malnourished mice.

    Science.gov (United States)

    Llauradó, Gabriel; Morris, Humberto J; Lebeque, Yamila; Venet, Gleymis; Fong, Onel; Marcos, Jane; Fontaine, Roberto; Cos, Paul; Bermúdez, Rosa C

    2016-10-01

    Mushroom nutriceutical components have lately attracted interest for developing immunonutritional support. However, there is relatively little information pertaining to the use of mushroom preparations for modulating the metabolic and immunological disorders associated to malnutrition. This study was aimed to evaluate the effects of oral administration of an aqueous extract (CW-P) from Pleurotus ostreatus on the recovery of biochemical and immunological functions of malnourished mice. 8-week old female BALB/c mice were starved for 3days and then refed with commercial diet supplemented with or without CW-P (100mg/kg) for 8days. Regardless of the diet used during refeeding, animal body weights and serum protein concentrations did not differ between groups. Oral treatment with CW-P normalized haemoglobin levels, liver arginase and gut mucosal weight. CW-P increased total liver proteins and also DNA and protein contents in gut mucosa. Pleurotus extract provided benefits in terms of macrophages activation as well as in haemopoiesis, as judged by the recovery of bone marrow cells and leukocyte counts. Moreover, CW-P stimulated humoral immunity (T-dependent and T non-dependent antibodies responses) compared to non-supplemented mice. CW-P extract from the oyster mushroom can be used to develop specific food or nutritional supplement formulations with potential clinical applications in the immunotherapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Cystic echinococcosis therapy: Albendazole-loaded lipid nanocapsules enhance the oral bioavailability and efficacy in experimentally infected mice.

    Science.gov (United States)

    Pensel, Patricia E; Ullio Gamboa, Gabriela; Fabbri, Julia; Ceballos, Laura; Sanchez Bruni, Sergio; Alvarez, Luis I; Allemandi, Daniel; Benoit, Jean Pierre; Palma, Santiago D; Elissondo, María C

    2015-12-01

    Therapeutic failures attributed to medical management of cystic echinococcosis (CE) with albendazole (ABZ) have been primarily linked to the poor drug absorption rate resulting in low drug level in plasma and hydatid cysts. Lipid nanocapsules (LNCs) represent nanocarriers designed to encapsulate lipophilic drugs, such as ABZ. The goals of the current work were: (i) to characterize the plasma and cyst drug exposure after the administration of ABZ as ABZ-LNCs or ABZ suspension (ABZ-SUSP) in mice infected with Echinococcus granulosus, and ii) to compare the clinical efficacies of both ABZ formulations. Enhanced ABZ sulphoxide (ABZ-SO) concentration profiles were obtained in plasma and cysts from ABZ-LNC treated animals. ABZSO exposure (AUC0-LOQ) was significantly higher in plasma and cyst after the ABZ-LNC treatments, both orally and subcutaneously, compared to that observed after oral administration of ABZ-SUSP. Additionally, ABZSO concentrations measured in cysts from ABZ-LNC treated mice were 1.7-fold higher than those detected in plasma. This enhanced drug availability correlated with an increased efficacy against secondary CE in mice observed for the ABZ-LNCs, while ABZ-SUSP did not reach differences with the untreated control group. This new pharmacotechnically-based strategy could be a potential alternative to improve the treatment of human CE. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. [Design of SCM inoculation device].

    Science.gov (United States)

    Qian, Mingli; Xie, Haiyuan

    2014-01-01

    The first step of bacilli culture is inoculation bacteria on culture medium. Designing a device to increase efficiency of inoculation is significative. The new device is controlled by SCM. The stepper motor can drive the culture medium rotating, accelerating, decelerating, overturn and suspending. The device is high practicability and efficient, let inoculation easy for operator.

  8. Effect of Jinten Hitam Seeds Oil (Nigella sativa L. In adenocarsinoma Mammae C3H Mice In Vivo An Experimental Study on C3H Mice Inoculated With Cancerous Tissue

    Directory of Open Access Journals (Sweden)

    Agus Suprijono

    2011-12-01

    Design and Methods: In this xperimental research with pre post test randomized control group design for 21 days, 24 C3H mice with tumor were divided into 4 group. K-I serves as a control given standard diet and aquades, K-II given standard diet, aquades and first dose of Jinten Hitam oil (0.1 ml/days, K-III given standard diet, aquades and second dose of Jinten Hitam oil ( 0.2 ml/days and K-IV given standard diet, aquades and third dose of Jinten Hitam oil ( 0.3 ml/days. The volume was recorded at the day 21. Results: mean of the effect of Jinten hitam oil effect in adenocarcinoma mammae for the four group were 158.83 mm³, 259.73 mm³, 191.13 mm³, K-IV 126.27 mm³ respectively. Pair t-test and Wilcoxon test showed significant difference between First dose pre-First dose post and Second dose pre-second dose-post (p0.05. Conclusion: Jinten Hitam oil has effect on the volume of Adenocarcinoma mammae in C3H mice (Sains Medika, 3(2:129-134.

  9. Stable engraftment of human microbiota into mice with a single oral gavage following antibiotic conditioning

    National Research Council Canada - National Science Library

    Christopher Staley; Thomas Kaiser; Lalit K Beura; Matthew J Hamilton; Alexa R Weingarden; Aleh Bobr; Johnthomas Kang; David Masopust; Michael J Sadowsky; Alexander Khoruts

    2017-01-01

    .... Results Here we report on the development of a sequential, three-course antibiotic conditioning regimen that allows sustained engraftment of intestinal microorganisms following a single oral gavage...

  10. Oral administration of heat-killed Lactobacillus gasseri OLL2809 reduces cedar pollen antigen-induced peritoneal eosinophilia in Mice.

    Science.gov (United States)

    Sashihara, Toshihiro; Ikegami, Shuji; Sueki, Natsuko; Yamaji, Taketo; Kino, Kohsuke; Taketomo, Naoki; Gotoh, Minoru; Okubo, Kimihiro

    2008-12-01

    Lactobacillus gasseri OLL2809 strongly stimulates the production of interleukin (IL)-12 (p70) by innate immune cells. Thus, it is expected to ameliorate allergic diseases. We investigated whether the oral administration of heat-killed L. gasseri OLL2809 suppressed eosinophilia in cedar pollen antigen-challenged mice. BALB/c mice sensitized with Japanese cedar pollen extract were intraperitoneally challenged with the same extract. The mice were orally given heat-killed L. gasseri OLL2809 at doses of 0.5, 1, or 2mg/day throughout the experimental period (21 d). After 24 hours of the challenge, the eosinophil number and cytokine levels in the peritoneal lavage fluid and the serum antigen-specific IgG levels were determined. On administering varying amounts of heat-killed L. gasseri OLL2809, the number of eosinophils among the total number of cells was significantly reduced in all groups. In addition, the eosinophil number significantly decreased, and the eosinophil-suppression rate significantly increased by 44% in the 2-mg group. Although the serum immunoglobulin (Ig) G2a and IgG1 levels were not affected, the IgG2a/IgG1 ratio increased significantly in the 2-mg group compared with that of the control group. Furthermore, the administration of heat-killed L. gasseri OLL2809 resulted in the induction of IL-2 and reduction in granulocyte-macrophage colony-stimulating factor levels in peritoneal lavage fluid. We demonstrated that the oral administration of heat-killed L. gasseri OLL2809 suppresses eosinophilia via the modulation of Th1/Th2 balance. These observations suggested that heat-killed L. gasseri OLL2809 might potentially ameliorate the increased number of eosinophils in patients with Japanese cedar pollinosis.

  11. Oral immunization of mice with engineered Lactobacillus gasseri NM713 strain expressing Streptococcus pyogenes M6 antigen.

    Science.gov (United States)

    Mansour, Nahla M; Abdelaziz, Sahar A

    2016-08-01

    The aim of this in vivo study was to evaluate the effects of a recombinant probiotic strain, Lactobacillus gasseri NM713, which expresses the conserved region of streptococcal M6 protein (CRR6), as an oral vaccine against Streptococcus pyogenes. A dose of 10(9) cells of the recombinant strain in 150 μL PBS buffer was administered orally to a group of mice. One control group received an equivalent dose of Lb. gasseri NM613 (containing the empty plasmid without insert) or and another control group received PBS buffer. Each group contained 30 mice. The immunization protocol was followed on three consecutive days, after which two booster doses were administered at two week intervals. Fecal and serum samples were collected from the mice on Days 18, 32, 46, 58 after the first immunization and Day 0 prior to immunization. Anti-CRR6 IgA and IgG concentrations were measured by ELISA in fecal and sera samples, respectively, to assess immune responses. Vaccination with the recombinant Lb. gasseri NM713 strain induced significant protection after nasal challenge with S. pyogenes, only a small percentage of this group developing streptococcal infection (10%) or dying of it (3.3%) compared with the NM613 and PBS control groups, high percentages of which developed streptococcal infection (43.3% and 46.7%, respectively) and died of it (46.7% and 53%, respectively). These results indicate that recombinant Lb. gasseri NM713 has potential as an oral delivery vaccine against streptococcus group A. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

  12. Toxicity of 4-vinyl-1-cyclohexene diepoxide after 13 weeks of dermal or oral exposure in rats and mice

    Energy Technology Data Exchange (ETDEWEB)

    Chhabra, R.S.; Elwell, M.R.; Peters, A. (National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA))

    1990-05-01

    4-Vinyl-1-cyclohexene diepoxide (VCHD) is used as a chemical intermediate and as a reactive diluent for diepoxides and epoxy resins. Toxicology studies were conducted by administering VCHD in acetone by dermal application or in corn oil by gavage to F344/N rats and B6C3F1 mice for 13 weeks. In the 13-week dermal studies, groups of 10 rats of each sex received 0.3 ml of VCHD in acetone at concentrations ranging from 6.25 to 200 mg/ml, and mice received 0.1 ml at concentrations ranging from 6.25 to 100 mg/ml. Skin lesions were observed at the site of application at the top two dose levels for both species and sexes, and consisted of acanthosis, parakeratosis, and hyperkeratosis of the epidermis and sebaceous gland hyperplasia. In mice, follicular atrophy of the ovary, characterized by decreased numbers of primary and secondary follicles, occurred at the 50- and 100-mg dose levels. In 13-week oral studies, groups of 10 rats and mice of each sex were administered VCHD at dose levels ranging from 62.5 to 1000 mg/kg in corn oil. In rats and mice, there were body weight decreases in the groups given the two highest doses. The major target organs in rats were forestomach (hyperplasia and hyperkeratosis) and kidney (tubular cell degeneration/necrosis and regeneration). In mice the target organs included forestomach (hyperplasia and hyperkeratosis), ovary (follicular atrophy), and testis (degeneration of germinal epithelium).

  13. ORALLY LACTATE CALCIUM AND SWIMMING DECREASE OSTEOCLAST AND INCREASE OSTEOBLAST IN RADIAL PERIMENOPAUSAL MICE (MUS MUSCULUS BONE

    Directory of Open Access Journals (Sweden)

    Muliani **

    2013-04-01

    Full Text Available Calcium and moderate intensity swimming exercise can increase bone density. The aim of this research is to see the effect of orally calcium consumption and swimming activity to decrease osteoclast and increase osteoblast in radial perimenopausal mice (Mus musculus bone. Pretest and pos#est control group design was used in this research. Research subject used 15-16 aged mice (Mus musculus which divided into 4 groups (each group consisted of 13 mice, that was control, lactate calcium, swimming and lactate calcium and swimming. Treatment was given 90 days. This study showed a significant difference of the mean of the pos#est osteoblast between control and experimental groups (P<0.05. There was no significant difference between lactate calcium and swimming groups (P>0.05. Enhancement of osteoblast mean in combination group was greater than the other experimental groups. There was a significant difference of the mean of the pos#est  osteoclast between control and experimental groups (P<0.05, without significant difference between lactate calcium,   swimming groups and combination of lactate calcium and swimming group (P>0.05.  Conclusion: either lactate calcium or swimming decreases osteoclast and increases osteoblast of the mice but the osteoblast enhancement will be bigger when they are given together at once

  14. Cardiovascular health effects of oral and pulmonary exposure to multi-walled carbon nanotubes in ApoE-deficient mice

    DEFF Research Database (Denmark)

    Christophersen, Daniel V.; Jacobsen, Nicklas R.; Andersen, Maria H. G.

    2016-01-01

    Exposure to high aspect ratio nanomaterials, such as multi-walled carbon nanotubes (MWCNTs) may be associated with increased risk of atherosclerosis, pulmonary disease, and cancer. In the present study, we investigated the cardiovascular and pulmonary health effects of 10 weeks of repeated oral...... or pulmonary exposures to MWCNTs (4 or 40μg each week) in Apolipoprotein E-deficient (ApoE-/-) mice fed a Western-type diet. Intratracheal instillation of MWCNTs was associated with oxidative damage to DNA in lung tissue and elevated levels of lipid peroxidation products in plasma, whereas the exposure only...

  15. Relationship between brain accumulation of manganese and aberration of hippocampal adult neurogenesis after oral exposure to manganese chloride in mice.

    Science.gov (United States)

    Kikuchihara, Yoh; Abe, Hajime; Tanaka, Takeshi; Kato, Mizuho; Wang, Liyun; Ikarashi, Yoshiaki; Yoshida, Toshinori; Shibutani, Makoto

    2015-05-04

    We previously found persistent aberration of hippocampal adult neurogenesis, along with brain manganese (Mn) accumulation, in mouse offspring after developmental exposure to 800-ppm dietary Mn. Reduction of parvalbumin (Pvalb)(+) γ-aminobutyric acid (GABA)-ergic interneurons in the hilus of the dentate gyrus along with promoter region hypermethylation are thought to be responsible for this aberrant neurogenesis. The present study was conducted to examine the relationship between the induction of aberrant neurogenesis and brain Mn accumulation after oral Mn exposure as well as the responsible mechanism in young adult animals. We used two groups of mice with 28- or 56-day exposure periods to oral MnCl2·xH2O at 800 ppm as Mn, a dose sufficient to lead to aberrant neurogenesis after developmental exposure. A third group of mice received intravenous injections of Mn at 5-mg/kg body weight once weekly for 28 days. The 28-day oral Mn exposure did not cause aberrations in neurogenesis. In contrast, 56-day oral exposure caused aberrations in neurogenesis suggestive of reductions in type 2b and type 3 progenitor cells and immature granule cells in the dentate subgranular zone. Brain Mn accumulation in 56-day exposed cases, as well as in directly Mn-injected cases occurred in parallel with reduction of Pvalb(+) GABAergic interneurons in the dentate hilus, suggesting that this may be responsible for aberrant neurogenesis. For reduction of Pvalb(+) interneurons, suppression of brain-derived neurotrophic factor-mediated signaling of mature granule cells may occur via suppression of c-Fos-mediated neuronal plasticity due to direct Mn-toxicity rather than promoter region hypermethylation of Pvalb. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Neuroendocrine stress reactivity of male C57BL/6N mice following chronic oral corticosterone exposure during adulthood or adolescence.

    Science.gov (United States)

    Shahanoor, Ziasmin; Sultana, Razia; Baker, Madelyn R; Romeo, Russell D

    2017-12-01

    Adolescence is associated with the maturation of the hypothalamic-pituitary-adrenal (HPA) axis, the major neuroendocrine axis mediating the hormonal stress response. Adolescence is also a period in development marked by a variety of stress-related vulnerabilities, including psychological and physiological dysfunctions. Many of these vulnerabilities are accompanied by a disrupted HPA axis. In adult mice, a model of disrupted HPA function has been developed using oral chronic corticosterone administration via the drinking water, which results in various physiological and neurobehavioral abnormalities, including changes in stress reactivity and anxiety-like behaviors. In an effort to further complement and extend this model, we tested the impact of HPA disruption in adolescent mice. We also examined whether this disruption led to different outcomes depending on whether the treatment happened during adolescence or adulthood. In the current set of experiments, we exposed adult (70days of age) or adolescent (30days of age) male C57BL/6N mice to 4 weeks of either 0 or 25μg/ml oral corticosterone via their drinking water. We measured body weight during treatment and plasma corticosterone levels and activation of the paraventricular nucleus (PVN), as indexed by FOS immunohistochemistry, before and after a 30min session of restraint stress. Our data indicate that adolescent animals exposed to chronic corticosterone showed weight loss during treatment, an effect not observed in adults. Further, we found stress failed to elevate plasma corticosterone levels in treated mice, regardless of whether exposure occurred in adulthood or adolescence. Despite this reduced hormonal responsiveness, we found significant neural activation in the PVN of both adult- and adolescent-treated mice, indicating a dissociation between stress-induced peripheral and central stress responses following chronic corticosterone exposure. Moreover, stress-induced neural activation in the PVN was unaffected

  17. Rapidly acquired cytotoxicity of lymphoid cells from ice inoculated with allogeneic spleen cells.

    Science.gov (United States)

    Slavina, E G; Karmanova, N V; Leipunskaya, I L; Zinzar, S N; Reinhöfer, J; Svet-Moldavsky, G J

    1976-12-01

    Spleen cells from C57BL/6J or CBA mice inoculated iv with spleen cells from BALB/c mice produced a strong nonspecific cytotoxic effect on target cells (mouse L-cells). Lymph node cells from CBA or C57BL/6J mice inoculated sc with BALB/c spleen cells also destroyed L-cells. Lymph node cells from mice inoculated with syngeneic spleen cells were not cytotoxic. The cytotoxic effect was observed ion of allogeneic but not syngeneic spleen cells. This effect was considerably reduced or completely suppressed after partial or total removal of plastic-adherent cells.

  18. Enhancement of Oral Tolerance Induction in DO11.10 Mice by Lactobacillus gasseri OLL2809 via Increase of Effector Regulatory T Cells.

    Directory of Open Access Journals (Sweden)

    Ayako Aoki-Yoshida

    Full Text Available Food allergy is a serious problem for infants and young children. Induction of antigen-specific oral tolerance is one therapeutic strategy. Enhancement of oral tolerance induction by diet is a promising strategy to prevent food allergy in infants. Thus, in this study, we evaluate the effect of probiotic Lactobacillus gasseri OLL2809 (LG2809 on oral tolerance induction in a mouse model. The degree of oral tolerance induction was evaluated by measuring the proliferation and level of IL-2 production of splenic CD4+ T cells from DO11.10 mice fed ovalbumin (OVA alone or OVA with LG2809. Oral administration of LG2809 significantly decreased the rate of proliferation and IL-2 production by CD4+ T cells from OVA-fed mice. LG2809 increased a ratio of CD4+ T-cell population, producing high levels of IL-10 and having strong suppressive activity. Moreover, LG2809 increased a ratio of plasmacytoid dendritic cells (pDCs among the lamina propria (LP in small intestine. When used as antigen presenting cells to naïve CD4+ T cells from DO11.10 mice, LP cells from BALB/c mice fed LG2809 induced higher IL-10 production and stronger suppressive activity than those from non-treated mice. These results suggest that oral administration of LG2809 increases the population of pDCs in the LP, resulting in the enhancement of oral tolerance induction by increasing the ratio of effector regulatory T cells. LG2809 could, therefore, act as a potent immunomodulator to prevent food allergies by promoting oral tolerance.

  19. Enhancement of Oral Tolerance Induction in DO11.10 Mice by Lactobacillus gasseri OLL2809 via Increase of Effector Regulatory T Cells.

    Science.gov (United States)

    Aoki-Yoshida, Ayako; Yamada, Kiyoshi; Hachimura, Satoshi; Sashihara, Toshihiro; Ikegami, Shuji; Shimizu, Makoto; Totsuka, Mamoru

    2016-01-01

    Food allergy is a serious problem for infants and young children. Induction of antigen-specific oral tolerance is one therapeutic strategy. Enhancement of oral tolerance induction by diet is a promising strategy to prevent food allergy in infants. Thus, in this study, we evaluate the effect of probiotic Lactobacillus gasseri OLL2809 (LG2809) on oral tolerance induction in a mouse model. The degree of oral tolerance induction was evaluated by measuring the proliferation and level of IL-2 production of splenic CD4+ T cells from DO11.10 mice fed ovalbumin (OVA) alone or OVA with LG2809. Oral administration of LG2809 significantly decreased the rate of proliferation and IL-2 production by CD4+ T cells from OVA-fed mice. LG2809 increased a ratio of CD4+ T-cell population, producing high levels of IL-10 and having strong suppressive activity. Moreover, LG2809 increased a ratio of plasmacytoid dendritic cells (pDCs) among the lamina propria (LP) in small intestine. When used as antigen presenting cells to naïve CD4+ T cells from DO11.10 mice, LP cells from BALB/c mice fed LG2809 induced higher IL-10 production and stronger suppressive activity than those from non-treated mice. These results suggest that oral administration of LG2809 increases the population of pDCs in the LP, resulting in the enhancement of oral tolerance induction by increasing the ratio of effector regulatory T cells. LG2809 could, therefore, act as a potent immunomodulator to prevent food allergies by promoting oral tolerance.

  20. Effect of irradiation on the viability of Toxoplasma gondii cysts in tissues of mice and pigs

    Energy Technology Data Exchange (ETDEWEB)

    Dubey, J.P.; Brake, R.J.; Murrell, K.D.; Fayer, R.

    1986-03-01

    Muscles from tongue, heart, and limbs of 14 pigs inoculated orally with Toxoplasma gondii oocysts were irradiated with 10, 20, 25, and 30 krad of gamma (cesium-137 and cobalt-60) irradiation. Viability of T gondii cysts was assayed by feeding porcine muscles to T gondii-free cats and/or by inoculation of sediment from acid-pepsin digested porcine muscle into mice. Cats fed 500-g samples of muscles irradiated with up to 20 krad shed T gondii oocysts. Cats fed muscles irradiated with 25 or 30 krad did not shed oocysts. Mice were inoculated with 8 isolates of T gondii, and tissue cysts in their brains irradiated with up to 40 krad were infective to mice; however, there was a 10,000-fold reduction in the viability of organisms in tissue cysts irradiated with 40 krad, compared with that in nonirradiated cysts. At 50 krad of gamma irradiation, there were no detectable infective organisms in infected mouse brains.

  1. [Pharmacokinetics and relative bioavailability of THC and THC-solid dispersion orally to mice at single dose].

    Science.gov (United States)

    Liao, Li; Hua, Hua; Zhao, Jun-Ning; Luo, Heng; Yang, An-Dong

    2014-03-01

    To establish a fast sensitive, reproducible LC-MS/MS method to study pharmacokinetic properties of THC, and compare relative bioavailability of THC and its solid dispersion in mice. 200 mice were divided randomly into two groups, and administered orally with THC and THC-solid dispersion after fasting (calculate on THC:400 mg x kg(-1)), used HPLC-MS/MS method to determine the THC concentration of each period at the following times: baseline ( predose ), 15, 30, 45 min, 1, 1.5, 2, 3, 4, 6, 24 h after dosing. Calculating the pharmacokinetic parameters according to the C-t curv, and then use the Phoenix WinNonlin software for data analysis. The calibration curves were linear over the range 9.06-972 microg x L(-1) for THC (R2 = 0.999). The limit of detection (LOD) was 0.7 microg x L(-1), respectively. The average extraction recoveries for THC was above 75%, The methodology recoveries were between 79% and 108%. The intra-day and inter-day RSD were less than 13%, the stability test showed that the plasma samples was stable under different conditions (RSD THC and THC-solid dispersion orally to mice shows as fllows: T(max), were 60 and 15 min, AUC(0-t) were 44 500.43 and 57 497.81 mg x L(-1) x min, AUC(0-infinity) were 51 226.00 and 68 031.48 mg x L(-1) x min, MRT(0-infinity) were 596.915 6, 661.747 7 min, CL(z)/F were 0.007 809 and 0.005 88 L x min(-1) x kg(-1). Compared with THC, the MRT and t1/2 of the THC-solid dispersion were all slightly extended, the t(max) was significantly reduced, AUC(0-24 h), AUC(0-infinity) and C(max) were all significantly higher, the relative bioavailability of THC-solid dispersion is 1.34 times of THC. The results of the experiment shows that the precision, accuracy, recovery and applicability were found to be adequate for the pharmacokinetic studies. After oral administration to mice, the relative bioavailability of THC-solid dispersion show significant improvement compared to THC.

  2. BALB/c and SWR inbred mice differ in post-oral fructose appetition as revealed by sugar versus non-nutritive sweetener tests

    Science.gov (United States)

    Kraft, Tamar T.; Huang, Donald; Lolier, Melanie; Warshaw, Deena; LaMagna, Sam; Natanova, Elona; Sclafani, Anthony; Bodnar, Richard J.

    2017-01-01

    Recent studies indicate that C57BL/6J (B6) and FVB inbred mouse strains differ in post-oral fructose conditioning. This was demonstrated by their differential flavor conditioning response to intragastric fructose and their preference for fructose versus a non-nutritive sweetener. The present study extended this analysis to SWR and BALB/c inbred strains which are of interest because they both show robust flavor conditioning responses to fructose. In the first experiment, ad-libitum fed mice were given a series of 2-day, two-bottle preference tests between 8% fructose and a more preferred, but non-nutritive 0.1% sucralose +0.1% saccharin (S + S) solution (tests 1 & 4), and fructose or S + S versus water (tests 2 and 3). In test 1, SWR mice preferred S + S to fructose, and in tests 2 and 3, they preferred both sweeteners to water. In test 4, SWR mice switched their preference and consumed more fructose than S + S. In contrast, ad-libitum fed BALB/c mice strongly preferred S + S to fructose in both tests 1 and 4, although they preferred both sweeteners to water in tests 2 and 3. Food-restricted BALB/c mice also preferred the non-nutritive S + S to fructose in tests 1 and 4. The experience-induced fructose preference reversal observed in SWR, but not BALB/c mice indicates that fructose has a post-oral reinforcing effect in SWR mice as in FVB mice. Because B6 and FVB mice prefer glucose to fructose based on the post-oral actions of the two sugars, the second experiment compared the preferences of SWR and BALB/c mice for 8% glucose and fructose solutions. Ad-libitum fed and food-restricted SWR mice strongly preferred glucose to fructose. In contrast, ad-libitum fed BALB/c mice were indifferent to the sugars, perhaps because of their overall low intakes. Food-restricted BALB/c mice, however, strongly preferred glucose. These findings indicate that SWR and BALB/c mice differ in their preference response to the post-oral actions of fructose. PMID:26485292

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

    Directory of Open Access Journals (Sweden)

    B Fux

    2000-01-01

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

  4. Attenuation of obesity-induced inflammation in mice orally administered with salmon cartilage proteoglycan, a prophylactic agent.

    Science.gov (United States)

    Hirose, Shouhei; Asano, Krisana; Nakane, Akio

    2017-03-11

    Obesity is associated with chronic inflammation of adipose tissue and causes development of type 2 diabetes. M1 macrophage population was increased in adipose tissue of obese mouse. M1 macrophages induce insulin resistance through the secretion of proinflammatory cytokines. Our previous studies demonstrated that salmon cartilage proteoglycan (PG) suppresses excess inflammation in various mouse inflammatory diseases. In this study, we examined the effect of PG on type 2 diabetes using high-fat-diet (HFD) induced obese mouse model. Oral PG administration enhanced the population of small adipocytes (area less than 1000 μm2) without body and tissue weight gain. In addition, PG administration suppressed mRNA expression of TNF-α, IL-6 and CXCL2 in adipose tissue. The proportion of M1 macrophages was decreased by PG administration. In addition, PG administration suppressed hyperglycemia after intraperitoneal glucose injection. Fasted serum insulin level was decreased in PG-administered mice. Moreover, insulin-stimulated phosphorylation of Akt was enhanced in the liver and gastrocnemius skeletal muscle of PG-administered mice. These data suggested that PG administration improves hyperglycemia and insulin sensitivity in obese mice by modulation of M1 macrophages which secrete proinflammatory cytokines in adipose tissue and activation of Akt in liver and skeletal muscle. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Oral administration of a water extract of Phytolacca dodecandra l'herit in mice--effects on reproduction.

    Science.gov (United States)

    Mamo, E; Worku, M

    1987-02-01

    Experiments were conducted to determine whether oral administration of a water extract of P. dodecandra had significant effects on reproduction in mice. The work is based on earlier reports in this journal that butanol extracts of the berries of this plant had spermatocidal properties in vitro and blastocidal activity when injected directly into the uterus of rabbits. The extract was supplied to groups of mice in the drinking water at predetermined concentrations (range 0-250 mg per liter) and treatment intervals (continuous and monthly). An analysis of variance was performed on the results of the following variables for all the groups: mean number of females giving birth in each treatment group, mean number of days taken to give birth, mean number of young born per group, and mean number of young surviving at four days post-parturition. The results indicated that there were no significant differences (p greater than 0.05) between all the groups on all of the parameters evaluated. From the results obtained a tentative conclusion was reached that bodies of water treated with molluscicidal concentrations (approximately 50-100 mg/liter) of P. dodecandra water extract, probably do not pose a great danger to reproduction in mice within the limits of the experimental conditions described.

  6. Oral Administration of Herbal Mixture Extract Inhibits 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Soon Re Kim

    2014-01-01

    Full Text Available CP001 is four traditional herbal medicine mixtures with anti-inflammatory properties. In this study, we investigated the effect of oral administration of CP001 ethanol extract on the 2,4-dinitrochlorobenzene- (DNCB- induced AD mouse models. For that purpose, we observed the effects of oral administration of CP001 on skin inflammatory cell infiltration, skin mast cells, production of serum IgE, and expression of Th2 cytokine mRNA in the AD skin lesions of DNCB treated BALB/c mice. Histological analyses demonstrated that CP001 decreased dermis and epidermis thickening as well as dermal infiltration induced by inflammatory cells. In addition, CP001 decreased mast cell infiltration in count as well as dermal infiltration induced by inflammatory cells. In the skin lesions, mRNA expression of interleukin- (IL- 4 and IL-13 was inhibited by CP001. CP001 also reduced the production of IgE level in mouse plasma. In addition, we investigated the effect of CP001 on the inflammatory allergic reaction using human mast cells (HMC-1. In HMC-1, cytokine production and mRNA levels of IL-4, IL-13, IL-6, and IL-8 were suppressed by CP001. Taken together, our results showed that oral administration of CP001 exerts beneficial effects in AD symptoms, suggesting that CP001 might be a useful candidate for the treatment of AD.

  7. Oral administration of herbal mixture extract inhibits 2,4-dinitrochlorobenzene-induced atopic dermatitis in BALB/c mice.

    Science.gov (United States)

    Kim, Soon Re; Choi, Han-Seok; Seo, Hye Sook; Ku, Jin Mo; Hong, Se Hyang; Yoo, Hye Hyun; Shin, Yong Cheol; Ko, Seong-Gyu

    2014-01-01

    CP001 is four traditional herbal medicine mixtures with anti-inflammatory properties. In this study, we investigated the effect of oral administration of CP001 ethanol extract on the 2,4-dinitrochlorobenzene- (DNCB-) induced AD mouse models. For that purpose, we observed the effects of oral administration of CP001 on skin inflammatory cell infiltration, skin mast cells, production of serum IgE, and expression of Th2 cytokine mRNA in the AD skin lesions of DNCB treated BALB/c mice. Histological analyses demonstrated that CP001 decreased dermis and epidermis thickening as well as dermal infiltration induced by inflammatory cells. In addition, CP001 decreased mast cell infiltration in count as well as dermal infiltration induced by inflammatory cells. In the skin lesions, mRNA expression of interleukin- (IL-) 4 and IL-13 was inhibited by CP001. CP001 also reduced the production of IgE level in mouse plasma. In addition, we investigated the effect of CP001 on the inflammatory allergic reaction using human mast cells (HMC-1). In HMC-1, cytokine production and mRNA levels of IL-4, IL-13, IL-6, and IL-8 were suppressed by CP001. Taken together, our results showed that oral administration of CP001 exerts beneficial effects in AD symptoms, suggesting that CP001 might be a useful candidate for the treatment of AD.

  8. Enhanced mucosal and systemic immune response with squalane oil-containing multiple emulsions upon intranasal and oral administration in mice.

    Science.gov (United States)

    Shahiwala, Aliasgar; Amiji, Mansoor M

    2008-05-01

    The objective of this study was to develop and evaluate squalane oil-containing water-in-oil-in-water (W/O/W) multiple emulsion for mucosal administration of ovalbumin (OVA) as a model candidate vaccine in BALB/c mice. Control and optimized OVA-containing W/O/W emulsion (OVA-Emul) and chitosan-modified W/O/W emulsion (OVA-Emul-Chi) formulations were administered intranasally and orally at an OVA dose of 100 mug. The mucosal and systemic immune responses were evaluated after the first and second immunization. The OVA-Emul formulations resulted in higher immunoglobulin-G (IgG) and immunoglobulin-A (IgA) responses as compared with aqueous solution. In addition, significant IgG and IgA responses were observed after the second immunization dose using the emulsions with both routes of administration. Intranasal vaccination was more effective in generating the systemic OVA-specific IgG response than the mucosal OVA-specific IgA response. Oral immunizations, on the other hand, showed a much higher systemic IgG and mucosal IgA responses as compared with the nasally treated groups. The results of this study show that squalane oil-containing W/O/W multiple emulsion formulations can significantly enhance the local and systemic immune responses, especially after oral administration, and may be adopted as a better alternative in mucosal delivery of prophylactic and therapeutic vaccines.

  9. Avaliação em camundongo da eficácia do antiveneno administrado no local da inoculação intramuscular do veneno de Crotalus durissus terrificus Evaluation in mice, of the antivenom efficacy injected at the same place of the intramuscular inoculation of the Crotalus durissus terrificus venom

    Directory of Open Access Journals (Sweden)

    Lindioneza Adriano Ribeiro

    1993-02-01

    Full Text Available A eficácia do antiveneno crotálico por via intramuscular (im no local da inoculação, também im, do veneno de Crotalus durissus terrificus foi avaliada em camundongos. Em três experimentos inocularam-se duas DLSO do veneno por via im e administrou-se o antiveneno de três formas: metade da DE50 por via intraperitoneal (ip e metade por via im, no mesmo local, imediatamente após (1º e 30' após (2º a inoculação do veneno; quatro quintos de DE50 por via ip e um quinto por via im, no mesmo local e 30' após a inoculação do veneno (3º. O antiveneno ofereceu, por via ip, maior proteção aos camundongos (menor taxa de óbito em 48 horas do que quando foi administrado, em parte, por via im, no local da inoculação do veneno (pThe efficacy of the Crotalus durissus terrificus antivenom administration by intramuscular (im injection at the same place of the im inoculation, of the C. d. terrificus venom was evaluated in mice. In three experiments two DL50 of the venom were inoculated and the antivenom was administered in three differents ways: half of the ED50 by intraperitoneal (ip administration and half by injection, at the same place, immediatelly after the venom inoculation and thirty minutes after the im venom inoculation; four fifth of ED50 by ip administration and one fifth by injection, at the same place and thirty minutes after the venom inoculation. The antivenom that was administred by intraperitoneal route provided a higher protection to mice (a lower death rate in a 48 hours period than when it was administred in parts, by intramuscular injection, at the same place of the venom inoculation (p<0,05. Therefore, it is concluded that this should not be used in human beings bitten by snakes.

  10. Increased intake of vegetable oil rich in n-6 PUFA enhances allergic symptoms and prevents oral tolerance induction in whey-allergic mice.

    Science.gov (United States)

    van den Elsen, Lieke W J; van Esch, Betty C A M; Dingjan, Gemma M; Hofman, Gerard A; Garssen, Johan; Willemsen, Linette E M

    2015-08-28

    Increased intake of vegetable oils rich in n-6 PUFA, including soyabean oil, has been associated with an increase in allergic disease. The present study aimed to determine the effect of an increasing dose of dietary vegetable oil on allergic outcomes in mice. To study this, mice received a 7 v. 10 % soyabean oil diet before and during oral sensitisation with whey or whey hyperimmune serum transfer. Another group of mice received partial whey hydrolysate (pWH) while being fed the diets before oral sensitisation. The acute allergic skin response, serum Ig level, mouse mast cell protease-1 (mMCP-1) concentration and/or splenic T-cell percentages were determined upon whey challenge. When the diets were provided before and during oral sensitisation, the acute allergic skin response was increased in mice fed the 10 % soyabean oil diet compared with the 7 % soyabean oil diet. Whey IgE and IgG1 levels remained unaltered, whereas mMCP-1 levels increased in mice fed the 10 % soyabean oil diet. Furthermore, allergic symptoms were increased in naive mice fed the 10 % soyabean oil diet and sensitised with whey hyperimmune serum. In addition to enhancing the mast cell response, the 10 % soyabean oil diet increased the percentage of activated Th1 and Th2 cells as well as increased the ratios of Th2:regulatory T cells and Th2:Th1 when compared with the 7 % soyabean oil diet. Oral tolerance induction by pWH was abrogated in mice fed the 10 % soyabean oil diet compared with those fed the 7 % soyabean oil diet during pretreatment with pWH. In conclusion, increased intake of soyabean oil rich in n-6 PUFA suppresses tolerance induction by pWH and enhances the severity of the allergic effector response in whey-allergic mice. Dietary vegetable oils rich in n-6 PUFA may enhance the susceptibility to develop or sustain food allergy.

  11. Lactobacillus gasseri K7 modulates the blood cell transcriptome of conventional mice infected with Escherichia coli O157:H7.

    Science.gov (United States)

    Sagaya, F M; Hacin, B; Tompa, G; Ihan, A; Špela, Š; Černe, M; Hurrell, R F; Matijašić, B B; Rogelj, I; Vergères, G

    2014-05-01

    As the immune cells underlying the intestinal barrier sense luminal microbial signals, blood cell transcriptomics may identify subclinical changes triggered by gut bacteria that may otherwise not be detected. We have therefore investigated how Lactobacillus gasseri K7 and enterohemorrhagic Escherichia coli O157:H7 modulate the blood cell transcriptome of mice possessing an intact microbiota. We have analysed the transcriptome of five groups of C57BL/6J mice: (i) control, (ii) inoculated with a single dose of E. coli, (iii) inoculated during 2 weeks with Lact. gasseri, (iv) co-inoculated with E. coli and Lact. gasseri, (v) inoculated with Lact. gasseri prior to E. coli infection. The transcriptome could distinguish between the five treatment groups. Gene characteristics of bacterial infection, in particular inflammation, were upregulated in the mice inoculated with E. coli. Lact. gasseri had only mild effects on the transcriptome but modified the gene expression induced by E. coli. The transcriptome differentiates mice inoculated orally with E. coli, Lact. gasseri and combinations of these two strains. These results suggest that the blood cell transcriptome can be used as a source of biomarkers to monitor the impact of probiotics in subclinical models of infectious disease. © 2014 The Society for Applied Microbiology.

  12. Inoculation Technique for Fungus Cultures

    Science.gov (United States)

    Fusaro, Ramon M.

    1972-01-01

    A plastic straw and wood applicator stick serve as a simple, inexpensive, and disposable inoculation unit for fungal studies. The method gives a uniform and intact inoculum. The technique is especially useful because a large number of agar plates can be inoculated rapidly. Images PMID:5059618

  13. Oral tolerance is inefficient in neonatal mice due to a physiological vitamin A deficiency

    NARCIS (Netherlands)

    Turfkruyer, M.; Rekima, A.; Macchiaverni, P.; Le Bourhis, L.; Muncan, V.; van den Brink, G. R.; Tulic, M. K.; Verhasselt, V.

    2016-01-01

    Increased risk of allergy during early life indicates deficient immune regulation in this period of life. To date, the cause for inefficient neonatal immune regulation has never been elucidated. We aimed to define the ontogeny of oral tolerance and to identify necessary conditions specific for this

  14. Tissue Distribution of Tungsten in Mice Following Oral Exposure to Sodium Tungstate

    Science.gov (United States)

    2010-08-31

    barrier. Interestingly, other W toxicokinetics studies did not describe the tissue distribution in the brain tissue after oral or parenteral exposure to...parameters Setting Plasma gas Argon Plasma power 1,150 W Gas Flows Nebulizer gas flow rate 0.97 L min-1 Auxiliary gas flow 0.90 L min-1

  15. Oral exposure to acrolein exacerbates atherosclerosis in apoE-null mice.

    Science.gov (United States)

    Srivastava, Sanjay; Sithu, Srinivas D; Vladykovskaya, Elena; Haberzettl, Petra; Hoetker, David J; Siddiqui, Maqsood A; Conklin, Daniel J; D'Souza, Stanley E; Bhatnagar, Aruni

    2011-04-01

    Acrolein is a dietary aldehyde that is present in high concentrations in alcoholic beverages and foods including cheese, donuts and coffee. It is also abundant in tobacco smoke, automobile exhaust and industrial waste and is generated in vivo during inflammation and oxidative stress. The goal of this study was to examine the effects of dietary acrolein on atherosclerosis. Eight-week-old male apoE-null mice were gavage-fed acrolein (2.5mg/kg/day) for 8 weeks. Atherosclerotic lesion formation and composition and plasma lipids and platelet factor 4 (PF4) levels were measured. Effects of acrolein and PF4 on endothelial cell function was measured in vitro. Acrolein feeding increased the concentration of cholesterol in the plasma. NMR analysis of the lipoproteins showed that acrolein feeding increased the abundance of small and medium VLDL particles. Acrolein feeding also increased atherosclerotic lesion formation in the aortic valve and the aortic arch. Immunohistochemical analysis showed increased macrophage accumulation in the lesions of acrolein-fed mice. Plasma PF4 levels and accumulation of PF4 in atherosclerotic lesions was increased in the acrolein-fed mice. Incubation of endothelial cells with the plasma of acrolein-fed mice augmented transmigration of monocytic cells, which was abolished by anti-PF4 antibody treatment. Dietary exposure to acrolein exacerbates atherosclerosis in apoE-null mice. Consumption of foods and beverages rich in unsaturated aldehydes such as acrolein may be a contributing factor to the progression of atherosclerotic lesions. Published by Elsevier Ireland Ltd.

  16. Effects of orally self-administered bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) in mice.

    Science.gov (United States)

    Gannon, Brenda M; Russell, Lauren N; Modi, Meet S; Rice, Kenner C; Fantegrossi, William E

    2017-10-01

    Synthetic cathinones in bath salts products are psychostimulant drugs of abuse, and 3,4-methylenedioxypyrovalerone (MDPV) is a common constituent of these products. Oral MDPV has been show to stimulate locomotor activity but reinforcing, locomotor and appetitive stimulus effects of oral MDPV are unknown. Choice procedures evaluated preference for 0.03, 0.10, 0.30, and 1.00mg/mL MDPV solutions versus 0.10mg/mL quinine solution or water. To verify that oral MDPV produced pharmacological effects, locomotor activity was monitored during and after consumption of water, quinine, or MDPV solutions. Conditioned place preference (CPP) tested the apparent appetitive effects of a preferred concentration of oral MDPV with locomotor stimulant effects (0.30mg/mL), using water as a control, and compared with results from intraperitoneally-administered MDPV. Consumption of MDPV solutions (0.03-1.00mg/mL) was low when the alternative fluid was water, but a history of MDPV consumption increased MDPV choice. When paired with a quinine control solution, MDPV solutions (0.03-0.30mg/mL) were almost exclusively preferred, and treatment with the catecholamine synthesis inhibitor αMPT decreased MDPV choice. Consumption of MDPV concentrations (0.1-1.0mg/mL) stimulated locomotor activity. Chronic (10day) access to 0.30mg/mL MDPV resulted in escalated consumption, but locomotor effects did not systematically change across the access period. Finally, consumption of 0.30mg/mL MDPV elicited CPP with a magnitude similar to the preference observed following intraperitoneal administration of MDPV. Consistent with human abuse patterns, oral MDPV has reinforcing effects in the mouse which are most likely related to its psychostimulant-like pharmacological profile. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Oral immunization of mice against Clostridium perfringens epsilon toxin with a Lactobacillus casei vector vaccine expressing epsilon toxoid.

    Science.gov (United States)

    Alimolaei, Mojtaba; Golchin, Mehdi; Daneshvar, Hamid

    2016-06-01

    Clostridium perfringens type D infects ruminants and causes the enterotoxemia disease by ε-toxin. A mutated ε-toxin gene lacking toxicity was designed, synthesized, and cloned into the pT1NX vector and electroporated into Lactobacillus casei competent cells to yield LC-pT1NX-ε recombinant strain. BALB/c mice, immunized orally with this strain, highly induced mucosal, humoral, and cell-mediated immune responses and developed a protection against 200 MLD/ml of the activated ε-toxin. This study showed that the LC-pT1NX-ε could be a promising vaccine candidate against the enterotoxemia disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Oral administration of nano-emulsion curcumin in mice suppresses inflammatory-induced NFκB signaling and macrophage migration.

    Directory of Open Access Journals (Sweden)

    Nicholas A Young

    Full Text Available Despite the widespread use of curcumin for centuries in Eastern medicine as an anti-inflammatory agent, its molecular actions and therapeutic viability have only recently been explored. While curcumin does have potential therapeutic efficacy, both solubility and bioavailability must be improved before it can be more successfully translated to clinical care. We have previously reported a novel formulation of nano-emulsion curcumin (NEC that achieves significantly greater plasma concentrations in mice after oral administration. Here, we confirm the immunosuppressive effects of NEC in vivo and further examine its molecular mechanisms to better understand therapeutic potential. Using transgenic mice harboring an NFκB-luciferase reporter gene, we demonstrate a novel application of this in vivo inflammatory model to test the efficacy of NEC administration by bioluminescent imaging and show that LPS-induced NFκB activity was suppressed with NEC compared to an equivalent amount of curcumin in aqueous suspension. Administration of NEC by oral gavage resulted in a reduction of blood monocytes, decreased levels of both TLR4 and RAGE expression, and inhibited secretion of MCP-1. Mechanistically, curcumin blocked LPS-induced phosphorylation of the p65 subunit of NFκB and IκBα in murine macrophages. In a mouse model of peritonitis, NEC significantly reduced macrophage recruitment, but not T-cell or B-cell levels. In addition, curcumin treatment of monocyte derived cell lines and primary human macrophages in vitro significantly inhibited cell migration. These data demonstrate that curcumin can suppress inflammation by inhibiting macrophage migration via NFκB and MCP-1 inhibition and establish that NEC is an effective therapeutic formulation to increase the bioavailability of curcumin in order to facilitate this response.

  19. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans.

    Science.gov (United States)

    Trammell, Samuel A J; Schmidt, Mark S; Weidemann, Benjamin J; Redpath, Philip; Jaksch, Frank; Dellinger, Ryan W; Li, Zhonggang; Abel, E Dale; Migaud, Marie E; Brenner, Charles

    2016-10-10

    Nicotinamide riboside (NR) is in wide use as an NAD + precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD + metabolism in humans. We report that human blood NAD + can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral NR elevates mouse hepatic NAD + with distinct and superior pharmacokinetics to those of nicotinic acid and nicotinamide. We further show that single doses of 100, 300 and 1,000 mg of NR produce dose-dependent increases in the blood NAD + metabolome in the first clinical trial of NR pharmacokinetics in humans. We also report that nicotinic acid adenine dinucleotide (NAAD), which was not thought to be en route for the conversion of NR to NAD + , is formed from NR and discover that the rise in NAAD is a highly sensitive biomarker of effective NAD + repletion.

  20. Transformation of Probiotic Yeast and Their Recovery from Gastrointestinal Immune Tissues Following Oral Gavage in Mice.

    Science.gov (United States)

    Hudson, Lauren E; Stewart, Taryn P; Fasken, Milo B; Corbett, Anita H; Lamb, Tracey J

    2016-02-08

    Development of recombinant oral therapy would allow for more direct targeting of the mucosal immune system and improve the ability to combat gastrointestinal disorders. Adapting probiotic yeast in particular for this approach carries several advantages. These strains have not only the potential to synthesize a wide variety of complex heterologous proteins but are also capable of surviving and protecting those proteins during transit through the intestine. Critically, however, this approach requires expertise in many diverse laboratory techniques not typically used in tandem. Furthermore, although individual protocols for yeast transformation are well characterized for commonly used laboratory strains, emphasis is placed here on alternative approaches and the importance of optimizing transformation for less well characterized probiotic strains. Detailing these methods will help facilitate discussion as to the best approaches for testing probiotic yeast as oral drug delivery vehicles and indeed serve to advance the development of this novel strategy for gastrointestinal therapy.

  1. Oral administration of Vaccinium uliginosum L. extract alleviates DNCB-induced atopic dermatitis in NC/Nga mice.

    Science.gov (United States)

    Kim, Kang-Hyun; Choung, Se-Young

    2014-12-01

    Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease that responds to the interplay of environmental, immunological, and genetic factors. To explore the effect of Vaccinium uliginosum (VU) extract on AD, we orally administrated VU total water extract to AD-induced NC/Nga mice. VU extract reduced AD-like skin lesions, ear thickness, and the frequency of scratching episodes in a time-dependent manner. VU also suppressed the levels of IgE and histamine and the ratio of IgG1/IgG2a in the serum of AD-induced NC/Nga mice. VU administration resulted in the reduction of splenic cytokine production, epidermal thickening, and the infiltration of eosinophils, mast cells, and degranulated mast cells induced by 2,4-dinitrochlorobenzene (DNCB). In addition, VU significantly reduced the mRNA expression of chemokine ligands in dorsal skin. Total water extract and subfractions of VU inhibited interleukin (IL)-4 production in splenocytes, suggesting that VU total extract has a Th2 cytokine modulating effect. These results suggest that the VU total water extract could be a candidate therapeutic agent for the treatment of AD through an immunoregulatory effect.

  2. Influence of the dual ABCB1 and ABCG2 inhibitor tariquidar on the disposition of oral imatinib in mice

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    Sparreboom Alex

    2009-07-01

    Full Text Available Abstract Background Imatinib, a tyrosine kinase inhibitor currently approved for treatment of several malignancies, has been shown to be a substrate for multiple efflux-transporter proteins, including ABCB1 (P-glycoprotein and ABCG2 (BCRP. The effect of inhibiting these transporters on tissue exposure to imatinib remains unclear. Objective To assess the role of these transporters on drug disposition, 50 mg/kg imatinib was administered to Balb/C mice, 30 minutes after receiving tariquidar (10 mg/kg, an inhibitor of both ABCB1 and ABCG2, or vehicle, via oral gavage. Methods Quantitative determination of imatinib in mouse plasma, liver and brain was performed using a newly-developed and validated liquid-chromatography-mass spectrometric method. Results: Exposure to imatinib was 2.2-fold higher in plasma, liver and brain in mice that received tariquidar, as compared to those that received the vehicle (P = 0.001. The peak plasma concentration did not increase substantially, suggesting that tariquidar is affecting the distribution, metabolism and/or excretion of imatinib, rather than absorption. Though tariquidar increased the absolute exposure of imatinib, the brain-to-plasma ratio of imatinib was unaffected. Conclusion This study suggests that intentional inhibition of ABCB1 and ABCG2 function at the blood-brain barrier is unlikely to significantly improve clinical outcome of imatinib with currently used dosing regimens.

  3. ACUTE AND SUB-CHORONIC ORAL TOXICITY OF ASIATICOSIDE TO MICE

    OpenAIRE

    Uvarajan Sampath; Vanisree Arambakkam Janardhanam; Gopinath Gopal

    2012-01-01

    The components in Centellaasiatica (gotukala, vallarai) was reported to possess different biological activities in various in vitro and in vivo test models including gastric ulcer healing, wound healing, memory enhancing, immunomodulating effects along with cytotoxic, neuroprotective, antioxidant potential. Asiaticoside is one of the major triterpenoid saponin isolated from Centellaasiatica. Currently, there is no evidence for safety details of asiaticoside in experimental mice. The purpose o...

  4. Oral 2-oleyl glyceryl ether improves glucose tolerance in mice through the GPR119 receptor

    DEFF Research Database (Denmark)

    Hassing, H A; Engelstoft, M S; Sichlau, R M

    2016-01-01

    The intestinal G protein-coupled receptor GPR119 is a novel metabolic target involving glucagon-like peptide-1 (GLP-1)-derived insulin-regulated glucose homeostasis. Endogenous and diet-derived lipids, including N-acylethanolamines and 2-monoacylglycerols (2-MAG) activate GPR119. The purpose...... of this work is to evaluate whether 2-oleoyl glycerol (2-OG) improves glucose tolerance through GPR119, using wild type (WT) and GPR 119 knock out (KO) mice. We here show that GPR119 is essential for 2-OG-mediated release of GLP-1 and CCK from GLUTag cells, since a GPR119 specific antagonist completely...... abolished the hormone release. Similarly, in isolated primary colonic crypt cultures from WT mice, GPR119 was required for 2-OG-stimulated GLP-1 release while there was no response in crypts from KO mice. In vivo, gavage with 2-oleyl glyceryl ether ((2-OG ether), a stable 2-OG analog with a potency of 5.3 µ...

  5. Oral delivery of Acid Alpha Glucosidase epitopes expressed in plant chloroplasts suppresses antibody formation in treatment of Pompe mice

    Science.gov (United States)

    Su, Jin; Sherman, Alexandra; Doerfler, Phillip A.; Byrne, Barry J.; Herzog, Roland W.; Daniell, Henry

    2015-01-01

    Summary Deficiency of acid alpha glucosidase (GAA) causes Pompe disease in which the patients systemically accumulate lysosomal glycogen in muscles and nervous systems, often resulting in infant mortality. Although enzyme replacement therapy (ERT) is effective in treating patients with Pompe disease, formation of antibodies against rhGAA complicates treatment. In this report, we investigated induction of tolerance by oral administration of GAA expressed in chloroplasts. Because full-length GAA could not be expressed, N-terminal 410-amino acids of GAA (as determined by T-cell epitope mapping) were fused with the transmucosal carrier CTB. Tobacco transplastomic lines expressing CTB-GAA were generated through site-specific integration of transgenes into the chloroplast genome. Homoplasmic lines were confirmed by Southern blot analysis. Despite low-level expression of CTB-GAA in chloroplasts, yellow or albino phenotype of transplastomic lines was observed due to binding of GAA to a chloroplast protein that has homology to mannose-6 phosphate receptor. Oral administration of the plant-made CTB-GAA fusion protein even at 330-fold lower dose (1.5 μg) significantly suppressed immunoglobulin formation against GAA in Pompe mice injected with 500 μg rhGAA per dose, with several-fold lower titre of GAA-specific IgG1 and IgG2a. Lyophilization increased CTB-GAA concentration by 30-fold (up to 190 μg per g of freeze-dried leaf material), facilitating long-term storage at room temperature and higher dosage in future investigations. This study provides the first evidence that oral delivery of plant cells is effective in reducing antibody responses in ERT for lysosomal storage disorders facilitating further advances in clinical investigations using plant cell culture system or in vitro propagation. PMID:26053072

  6. Orally administered heat-killed Lactobacillus gasseri TMC0356 alters respiratory immune responses and intestinal microbiota of diet-induced obese mice.

    Science.gov (United States)

    Yoda, K; He, F; Miyazawa, K; Kawase, M; Kubota, A; Hiramatsu, M

    2012-07-01

      To investigate the influence of heat-killed Lactobacillus gasseri TMC0356 on changes in respiratory immune function and intestinal microbiota in a diet-induced obese mouse model.   Male C57BL/6J mice were fed a high-fat diet for 16 weeks. After 8 weeks, the high-fat-diet-induced obese mice (DIO mice) were randomly divided into two 0067roups, the DIO and DIO0356 groups. DIO0356 group mice were orally fed with heat-killed TMC0356 every day for 8 weeks, while DIO group mice were exposed to 0·85% NaCl over the same time period as controls. After intervention, the pulmonary mRNA expression of cytokines and other immune molecules in DIO0356 mice compared to those in DIO group mice was significantly increased (P < 0·05, P < 0·01). In faecal bacterial profiles, analysed using the terminal restriction fragment length polymorphism (T-RFLP) method, T-RFLP patterns in 75% of the DIO0356 group mice were apparently changed compared with those in control group mice.   These results suggest that inactive lactobacilli may stimulate the respiratory immune responses of obese host animals to enhance their natural defences against respiratory infection, partially associating with their potent impact on intestinal microbiota.   We have demonstrated that oral administration of inactive lactobacilli may protect host animals from the lung immune dysfunction caused by obesity. © 2012 The Authors. Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

  7. Inoculation in Political Campaign Communication.

    Science.gov (United States)

    Pfau, Michael; Burgoon, Michael

    1988-01-01

    Posits a strategy of resistance to the influence of attack messages in political campaigns. Finds that political campaign messages can be designed to inoculate supporters of candidates against subsequent attack messages of opposing candidates. (MS)

  8. Pathological analysis of the Candida albicans-infected tongue tissues of a murine oral candidiasis model in the early infection stage.

    Science.gov (United States)

    Okada, Masashi; Hisajima, Tatsuya; Ishibashi, Hiroko; Miyasaka, Takahiro; Abe, Shigeru; Satoh, Tazuko

    2013-04-01

    The early pathological process of Candida infection and immunological responses in tongues of the mice with experimental oral candidiasis was analysed. CD-1 mice, pretreated by prednisolone were orally inoculated with Candida albicans. Symptoms were monitored by measuring the area of white tongue coating and number of viable Candida cells in oral cavity. The histopathological analysis was carried by PAS-stain and immunofluorescent staining. IL-4, IL-12p70, IFN-γ, TNF-α in recovered from the homogenates of the tongues were measured by ELISA. The fungus invaded the tongue surface of the mice and white patches developed within 24h after inoculation. Histopathological examination indicated the presence of local acute inflammation in superficial tissues of tongues covered by mycelium of C. albicans. Pathological exacerbation was observed from 24 to 48 h after the inoculation and from then the symptoms of oral candidiasis appeared to move into the recovery phase. Inflammatory cells mainly consisting of neutrophils was accumulated and located under the lesions covered by Candida-hyphae. An increase in IL-12p70 and IFN-γ in tongue homogenates was observed at 48 h after inoculation. The worst condition in the pathological process in experimental oral candidiasis was found 48 h after C. albicans inoculation. When the surface of the Candida-inoculated tongues was covered with Candida-hyphae, a dense accumulation of neutrophils was observed under the lesions and homogenates of the tongues contained increased levels of IL-12p70 and IFN-γ. These suggested that local pathological condition of Candida-infected tongues may be affected by neutrophils accumulation and increased levels of some cytokines. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Study of the pathogenic potential of Dientamoeba fragilis in experimentally infected mice

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    Eman K. El-Gayar

    2016-06-01

    Full Text Available Dientamoebafragilis (D. fragilis is a protozoan parasite whose pathogenic potential is still disputable. The aim of this study was to illustrate the pathogenicity of D. fragilis infection and to determine the infective dose for experimental mice infection. Three groups of mice (8/each were orally inoculated with in vitro cultured D. fragilis. The infected groups (G1- G3 received 103, 105 and 4 × 106 D. fragilis/0.5 ml culture, respectively. A control group (G4 only received parasite-free culture. Two weeks post-inoculation all mice were euthanized for histopathological examination. All mice of G3 (100% and three mice of G2 (37.5% were infected, and the results were confirmed by PCR and different staining methods. On the other hand, all mice from group G1 showed a completely negative result. Histopathological examination of the colon and caecum of the highly infected group G3 showed active colitis, with infiltration of mixed inflammatory cells such as eosinophils, neutrophils and lymphocytes within the lamina propria of the intestinal wall. The parasite was not invading the colonic mucosa. This study revealed that infection with D. fragilis is dose-dependent. Moreover, a dose of 105 D. fragilis/mouse or higher is necessary to infect mice through the oral route. In addition, this route of infection, although non-invasive, can induce severe inflammatory changes to the colonic and caecal mucosa in experimentally infected mice.

  10. Effects of chronic alcohol consumption on DNA damage and immune regulation induced by the environmental pollutant dibenzo[a,l]pyrene in oral tissues of mice.

    Science.gov (United States)

    Chen, Kun-Ming; Schell, Todd D; Richie, John P; Sun, Yuan-Wan; Zhang, Shang-Min; Calcagnotto, Ana; Aliaga, Cesar; Gowda, Krishne; Amin, Shantu; El-Bayoumy, Karam

    2017-10-02

    Previously, we showed that oral application of the environmental pollutant dibenzo[a,l]pyrene (DB[a,l]P) induces oral tumors in mice. Thus, in the present investigation we examined the effect of alcohol on DB[a,l]P-induced DNA damage and immune regulation; we showed that alcohol (6.4% v/v in the diet, 35% of Calories) significantly enhanced the levels of (-)-anti-trans-DB[a,l]P-dA while decreased the levels of GSH in the mouse oral tissues. Analysis of RNA expression revealed that DB[a,l]P alone upregulates inflammatory genes while alcohol suppresses several markers of immune surveillance. Collectively, these results suggest that alcohol may enhance oral carcinogenesis induced by DB[a,l]P.

  11. Small intestinal inflammation following oral infection with Toxoplasma gondii does not occur exclusively in C57BL/6 mice: review of 70 reports from the literature

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    Maximilian Schreiner

    2009-03-01

    Full Text Available Small intestinal immunopathology following oral infection with tissue cysts of Toxoplasma gondii has been described in C57BL/6 mice. Seven days after infection, mice develop severe small intestinal necrosis and succumb to infection. The immunopathology is mediated by local overproduction of Th1-type cytokines, a so-called "cytokine storm". The immunopathogenesis of this pathology resembles that of inflammatory bowel disease in humans, i.e., Crohn's disease. In this review, we show that the development of intestinal pathology following oral ingestion of T. gondii is not limited to C57BL/6 mice, but frequently occurs in nature. Using a Pubmed search, we identified 70 publications that report the development of gastrointestinal inflammation following infection with T. gondii in 63 animal species. Of these publications, 53 reports are on accidental ingestion of T. gondii in 49 different animal species and 17 reports are on experimental infections in 19 different animal species. Thus, oral infection with T. gondii appears to cause immunopathology in a large number of animal species in addition to mice. This manuscript reviews the common features of small intestinal immunopathology in the animal kingdom and speculates on consequences of this immunopathology for humankind.

  12. Pathogenic potential of Blastocystis hominis in laboratory mice.

    Science.gov (United States)

    Elwakil, Hala S; Hewedi, Iman H

    2010-08-01

    Blastocystis hominis is a ubiquitous enteric protozoan whose pathogenic potential is still controversial. This study was carried out to clarify the pathogenecity of B. hominis infection and to study the proper number of parasites for mice infection. A total of 15 albino mice were orally inoculated with B. hominis and divided according to the inoculums, 10(2), 10(5), and 4 x 10(7) B. hominis forms/100 microl saline, into three groups consisting of five mice each, GI, GII GIII, respectively. In addition with group IV (uninfected control) consisting of five mice. All mice were sacrificed 2 weeks post-infection. The results revealed that all mice of GIII and two mice of GII got the infection while all mice of GI showed a completely negative result. Histopathological examination of large intestine on highly infected group (GIII) showed that B. hominis infiltrated the lamina propria, the submucosa, and the muscle layers in the form of collection of vacuolar forms. This was accompanied by active colitis with infiltration of mixed inflammatory cells. In conclusion, this study revealed that large number of B. hominis is essential for oral infection of mice and that vacuolar forms of B. hominis can invade the lamina propria, the submucosa, and even the muscle layers.

  13. Purification of Encephalitozoon Cultures Contaminated by Mycoplasmas by Murine Intraperitoneal Inoculation

    Science.gov (United States)

    Ridoux, Olivier; Foucault, Cédric; Drancourt, Michel

    1998-01-01

    Encephalitozoon species are strict intracellular microsporidia. Cocultures with eukaryotic cell lines can become accidently contaminated by mycoplasmas. We propose a decontamination protocol based on differential cell targeting after intraperitoneal inoculation in mice. Mycoplasma-free microsporidia were isolated from the brains and spleens of inoculated mice 24 h postinoculation by using the centrifugation shell vial system. Identification was confirmed by direct sequencing of PCR-amplified 16S rRNA. PMID:9666031

  14. Effects of oral florfenicol and azithromycin on gut microbiota and adipogenesis in mice.

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    Rui Li

    Full Text Available Certain antibiotics detected in urine are associated with childhood obesity. In the current experimental study, we investigated two representative antibiotics detected in urine, florfenicol and azithromycin, for their early effects on adipogenesis, gut microbiota, short-chain fatty acids (SCFAs, and bile acids in mice. Thirty C57BL/6 mice aged four weeks were randomly divided into three groups (florfenicol, azithromycin and control. The two experimental groups were administered florfenicol or azithromycin at 5 mg/kg/day for four weeks. Body weight was measured weekly. The composition of the gut microbiota, body fat, SCFAs, and bile acids in colon contents were measured at the end of the experiment. The composition of the gut microbiota was determined by sequencing the bacterial 16S rRNA gene. The concentration of SCFAs and bile acids was determined using gas chromatography and liquid chromatography coupled to tandem mass spectrometry, respectively. The composition of the gut microbiota indicated that the two antibiotics altered the gut microbiota composition and decreased its richness and diversity. At the phylum level, the ratio of Firmicutes/Bacteroidetes increased significantly in the antibiotic groups. At the genus level, there were declines in Christensenella, Gordonibacter and Anaerotruncus in the florfenicol group, in Lactobacillus in the azithromycin group, and in Alistipes, Desulfovibrio, Parasutterella and Rikenella in both the antibiotic groups. The decrease in Rikenella in the azithromycin group was particularly noticeable. The concentration of SCFAs and secondary bile acids decreased in the colon, but the concentration of primary bile acids increased. These findings indicated that florfenicol and azithromycin increased adipogenesis and altered gut microbiota composition, SCFA production, and bile acid metabolism, suggesting that exposure to antibiotics might be one risk factor for childhood obesity. More studies are needed to

  15. Avaliação da eficácia do antiveneno botrópico administrado no local da inoculação intramuscular do veneno de Bothrops jararaca: estudo experimental em camundongos Assessment of the efficacy of antivenom injection at the site of the intramuscular inoculation of Bothrops jararaca venom in mice

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    Carla Lilian Agostini Utescher

    1994-06-01

    Full Text Available Foi determinada, em camundongos de 18 a 20 g, a dose efetiva 50% do antiveneno botrópico, por via intraperitoneal (ip, imediatamente (DE50 Oh e 30 minutos (DE50 30' após a inoculação de 2 DL50 do veneno de B. jararaca, por via intramuscular (im. A DE50 30' foi três vezes maior do que a DE50 Oh. A eficácia do antiveneno administrado no local da inoculação do veneno foi avaliada inoculando-se duas DL50 do veneno, por via im, e administrando-se a DE50 do antiveneno imediatamente (DE50 Oh e 30 minutos após (DE50 30', de duas formas a saber: totalmente por via ip (1ª e metade por via ip e metade por via im (2ª, no mesmo local da inoculação do veneno. O antiveneno ofereceu, por via ip, maior proteção aos camundongos (menor taxa de óbito em 48 horas do que quando metade do mesmo foi administrado, por via im, no local da inoculação do veneno. Conclui-se que, neste modelo experimental, quando se inicia o tratamento tardiamente há necessidade de maior dose de antiveneno botrópico e que não há benefício em administrá-lo no local da picada.The 50% effective intraperitoneal (ip dose of Bothrops jararaca antivenom (ED50 was assessed in mice immediately (ED50 Oh and thirty minutes (ED50 30' after the intramuscular (im injection of two 50% lethal dose (LD50 of Bothrops jararaca venom. The efficacy of the antivenom injected at the venom inoculation site was assessed by the inoculation of two LD50 of the venom by im route, followed immediately (ED50 Oh and 30 minutes later (ED50 30' by administration of the ED50 of the antivenom either entirely by the ip route or 50 percent ip plus 50 percent im, at the same inoculation site. It was shown that the ED50 30' was 3 times greater, than the ED50 Oh and that the antivenom was more protective to mice (lower death rate in 48 hours when given entirely ip. It was concluded that, in this experimental model, a higher dose of bothropic antivenom is needed when the treatment is started lately, and that

  16. Proglucagon Promoter Cre-Mediated AMPK Deletion in Mice Increases Circulating GLP-1 Levels and Oral Glucose Tolerance.

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    Sophie R Sayers

    Full Text Available Enteroendocrine L-cells synthesise and release the gut hormone glucagon-like peptide-1 (GLP-1 in response to food transit. Deletion of the tumour suppressor kinase LKB1 from proglucagon-expressing cells leads to the generation of intestinal polyps but no change in circulating GLP-1 levels. Here, we explore the role of the downstream kinase AMP-activated protein kinase (AMPK in these cells.Loss of AMPK from proglucagon-expressing cells was achieved using a preproglucagon promoter-driven Cre (iGluCre to catalyse recombination of floxed alleles of AMPKα1 and α2. Oral and intraperitoneal glucose tolerance were measured using standard protocols. L-cell mass was measured by immunocytochemistry. Hormone and peptide levels were measured by electrochemical-based luminescence detection or radioimmunoassay.Recombination with iGluCre led to efficient deletion of AMPK from intestinal L- and pancreatic alpha-cells. In contrast to mice rendered null for LKB1 using the same strategy, mice deleted for AMPK displayed an increase (WT: 0.05 ± 0.01, KO: 0.09±0.02%, p<0.01 in L-cell mass and elevated plasma fasting (WT: 5.62 ± 0.800 pg/ml, KO: 14.5 ± 1.870, p<0.01 and fed (WT: 15.7 ± 1.48pg/ml, KO: 22.0 ± 6.62, p<0.01 GLP-1 levels. Oral, but not intraperitoneal, glucose tolerance was significantly improved by AMPK deletion, whilst insulin and glucagon levels were unchanged despite an increase in alpha to beta cell ratio (WT: 0.23 ± 0.02, KO: 0.33 ± 0.03, p<0.01.AMPK restricts L-cell growth and GLP-1 secretion to suppress glucose tolerance. Targeted inhibition of AMPK in L-cells may thus provide a new therapeutic strategy in some forms of type 2 diabetes.

  17. Determination of plasma and brain levels of isotretinoin in mice following single oral dose by high-performance liquid chromatography.

    Science.gov (United States)

    Yang, Yongsheng; Faustino, Patrick J; Pine, P Scott; Davis, Hirsch; Grunberg, Neil; Phillips, Jennifer; Lyon, Robbe C; Yu, Lawrence X; Ciavarella, Anthony B; Del Grosso, Alfred V; Hanig, Joseph P

    2005-02-07

    An isocratic reversed-phase high-performance liquid chromatographic method was established and validated according to FDA's Guidance for Industry, "Bioanalytical Method Validation", for the determination of isotretinoin in plasma and brain tissue from mice following single and multiple oral doses of Accutane. Plasma sample preparation included deproteination with acetonitrile-perchloric acid followed by centrifugation. Brain tissue was homogenized and extracted with acetonitrile-perchloric acid followed by centrifugation. The supernatants were analyzed by high-performance liquid chromatography (HPLC). Benz[alpha]anthrancene-7,12-dione was used as the internal standard. Chromatographic separation was achieved on a C18 column using an acetonitrile-aqueous 0.5% acetic acid (85:15, v/v) elution. The average extraction efficiency was >95% for plasma and >82% for brain. The lower limit of quantification was 30 ng/mL for plasma and was 30 ng/0.1g for brain tissue, respectively. The linear range for plasma was 30-600 ng/mL, and 15-300 ng/0.1g for brain. Maximum concentrations of isotretinoin in both plasma and brain were observed at 1h after single oral dosing (25 mg/kg). The maximum concentrations in plasma and brain were 2.36 microg/mL and 0.34 microg/g, respectively. The mean area under curve (AUC) in plasma was 6.13 microg h/mL. The mean eliminate half-life in plasma was estimated as 46 min.

  18. Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50 and No Observed Adverse Effect Level (NOAEL

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    Paula Abal

    2017-02-01

    Full Text Available Tetrodotoxin (TTX is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50 and the No Observed Adverse Effect Level (NOAEL in mice by using an accurate well-characterized TTX standard.

  19. CD-1 mice Show Individual Differences in Nicotine Preference in a Modified Two-Bottle Oral Self-Administration Model.

    Science.gov (United States)

    Cao, Junran; Gautier, Nicole M; Li, Ming D

    2012-01-01

    Although both animal and human studies reveal significant contributions of genetics to smoking addiction, many human studies were underpowered or biased by potential confounding variables, and animal genetic studies are challenged by limited genetic variations and lack of convincing phenotypes. To address these concerns, we used non-sibling outbred CD-1 mice to evaluate individual differences in nicotine preference with a modified two-bottle oral self-administration model. Animals were first given free access to two bottles, one filled with nicotine dissolved in 2% saccharin and the other with saccharin only. Under this regular two-bottle choice condition, the majority of animals avoided the nicotine solution with limited individual differences. However, when we modified the model by introducing 4 days of exposure to 5% saccharin in the drinking water, the animals significantly increased nicotine consumption in the two-bottle choice test, with about 30% animals showing a nicotine preference. Nicotine preference after 5% saccharin treatment remained elevated throughout the 28 days of the experiment. Further, we found there existed striking individual differences in nicotine consumption after exposure to 5% saccharin, with a range of 0-100% of total liquid consumption. The enhanced individual differences and the ratio of nicotine consumption were observed at different concentrations of nicotine (10-80 μg/ml) and in both adolescents and adults. Further examination on the induction mechanism showed that the long-lasting nicotine preference was not correlated with nicotine consumption before the induction, 5% saccharin consumption, or weight gain during the induction. Although liquid consumption during the 4 days of 5% saccharin exposure was decreased by about 30%, comparable liquid restriction alone for 4 days did not induce nicotine preference. Together, this study showed a strong and stable nicotine preference in CD-1 mice, which was induced by a short

  20. Oral Vaccination against Bubonic Plague Using a Live Avirulent Yersinia pseudotuberculosis Strain ▿

    Science.gov (United States)

    Blisnick, Thierry; Ave, Patrick; Huerre, Michel; Carniel, Elisabeth; Demeure, Christian E.

    2008-01-01

    We evaluated the possibility of using Yersinia pseudotuberculosis as a live vaccine against plague because it shares high genetic identity with Y. pestis while being much less virulent, genetically much more stable, and deliverable orally. A total of 41 Y. pseudotuberculosis strains were screened by PCR for the absence of the high pathogenicity island, the superantigens YPM, and the type IV pilus and the presence of the pYV virulence plasmid. One strain (IP32680) fulfilled these criteria. This strain was avirulent in mice upon intragastric or subcutaneous inoculation and persisted for 2 months in the mouse intestine without clinical signs of disease. IP32680 reached the mesenteric lymph nodes, spleen, and liver without causing major histological lesions and was cleared after 13 days. The antibodies produced in vaccinated animals recognized both Y. pseudotuberculosis and Y. pestis antigens efficiently. After a subcutaneous challenge with Y. pestis CO92, bacteria were found in low amounts in the organs and rarely in the blood of vaccinated animals. One oral IP32680 inoculation protected 75% of the mice, and two inoculations induced much higher antibody titers and protected 88% of the mice. Our results thus validate the concept that an attenuated Y. pseudotuberculosis strain can be an efficient, inexpensive, safe, and easy-to-produce live vaccine for oral immunization against bubonic plague. PMID:18505804

  1. Oral vaccination against bubonic plague using a live avirulent Yersinia pseudotuberculosis strain.

    Science.gov (United States)

    Blisnick, Thierry; Ave, Patrick; Huerre, Michel; Carniel, Elisabeth; Demeure, Christian E

    2008-08-01

    We evaluated the possibility of using Yersinia pseudotuberculosis as a live vaccine against plague because it shares high genetic identity with Y. pestis while being much less virulent, genetically much more stable, and deliverable orally. A total of 41 Y. pseudotuberculosis strains were screened by PCR for the absence of the high pathogenicity island, the superantigens YPM, and the type IV pilus and the presence of the pYV virulence plasmid. One strain (IP32680) fulfilled these criteria. This strain was avirulent in mice upon intragastric or subcutaneous inoculation and persisted for 2 months in the mouse intestine without clinical signs of disease. IP32680 reached the mesenteric lymph nodes, spleen, and liver without causing major histological lesions and was cleared after 13 days. The antibodies produced in vaccinated animals recognized both Y. pseudotuberculosis and Y. pestis antigens efficiently. After a subcutaneous challenge with Y. pestis CO92, bacteria were found in low amounts in the organs and rarely in the blood of vaccinated animals. One oral IP32680 inoculation protected 75% of the mice, and two inoculations induced much higher antibody titers and protected 88% of the mice. Our results thus validate the concept that an attenuated Y. pseudotuberculosis strain can be an efficient, inexpensive, safe, and easy-to-produce live vaccine for oral immunization against bubonic plague.

  2. Oral Delivery of a Novel Attenuated Salmonella Vaccine Expressing Influenza A Virus Proteins Protects Mice against H5N1 and H1N1 Viral Infection.

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    Zenglin Pei

    Full Text Available Attenuated strains of invasive enteric bacteria, such as Salmonella, represent promising gene delivery agents for nucleic acid-based vaccines as they can be administrated orally. In this study, we constructed a novel attenuated strain of Salmonella for the delivery and expression of the hemagglutinin (HA and neuraminidase (NA of a highly pathogenic H5N1 influenza virus. We showed that the constructed Salmonella strain exhibited efficient gene transfer activity for HA and NA expression and little cytotoxicity and pathogenicity in mice. Using BALB/c mice as the model, we evaluated the immune responses and protection induced by the constructed Salmonella-based vaccine. Our study showed that the Salmonella-based vaccine induced significant production of anti-HA serum IgG and mucosal IgA, and of anti-HA interferon-γ producing T cells in orally vaccinated mice. Furthermore, mice orally vaccinated with the Salmonella vaccine expressing viral HA and NA proteins were completely protected from lethal challenge of highly pathogenic H5N1 as well as H1N1 influenza viruses while none of the animals treated with the Salmonella vaccine carrying the empty expression vector with no viral antigen expression was protected. These results suggest that the Salmonella-based vaccine elicits strong antigen-specific humoral and cellular immune responses and provides effective immune protection against multiple strains of influenza viruses. Furthermore, our study demonstrates the feasibility of developing novel attenuated Salmonella strains as new oral vaccine vectors against influenza viruses.

  3. Short-Term Effects of Oral Administration of Pistacia Lentiscus Oil on Tissue-Specific Toxicity and Drug Metabolizing Enzymes in Mice

    OpenAIRE

    Samir Attoub; Sherif M. Karam; Abderrahim Nemmar; Kholoud Arafat; Annie John; Wafa Al-Dhaheri; Mahmood Ahmed Al Sultan; Haider Raza

    2014-01-01

    Background: Pistacia lentiscus (Anacardiaceae) is a flowering plant traditionally used in the treatment of various skin, respiratory, and gastrointestinal disorders. The aim of this study was to assess whether Pistacia lentiscus oil has any short term toxic effects in vivo and in vitro. Methods: Pistacia lentiscus oil (100µl) was administered orally into mice for 5 days. Results: Measurements of body weight did not show any weight loss. Serum concentration of LDH did not show any significant ...

  4. Efficacy of oral immunotherapy with a rice-based edible vaccine containing hypoallergenic Japanese cedar pollen allergens for treatment of established allergic conjunctivitis in mice.

    Science.gov (United States)

    Fukuda, Ken; Ishida, Waka; Harada, Yosuke; Wakasa, Yuhya; Takagi, Hidenori; Takaiwa, Fumio; Fukushima, Atsuki

    2018-01-01

    We have previously shown that prophylactic oral administration of transgenic rice seeds expressing hypoallergenic modified antigens suppressed the development of allergic conjunctivitis induced by Japanese cedar pollen. We have now investigated the efficacy of oral immunotherapy with such transgenic rice for established allergic conjunctivitis in mice. BALB/c mice were sensitized with two intraperitoneal injections of Japanese cedar pollen in alum, challenged with pollen in eyedrops, and then fed for 16 days with transgenic rice seeds expressing modified Japanese cedar pollen allergens Cry j 1 and Cry j 2 or with nontransgenic rice seeds as a control. They were then challenged twice with pollen in eyedrops, with clinical signs being evaluated at 15 min after the first challenge and the eyes, blood, spleen, and lymph nodes being isolated at 24 h after the second challenge. The number of eosinophils in the conjunctiva and the clinical score for conjunctivitis were both significantly lower in mice fed the transgenic rice than in those fed nontransgenic rice. Oral vaccination with transgenic rice seeds also resulted in a significant increase in the production of IFN-γ by splenocytes, whereas it had no effect on the number of CD4 + CD25 + Foxp3 + regulatory T cells in the spleen or submandibular or mesenteric lymph nodes. Oral administration of transgenic rice seeds expressing hypoallergenic allergens ameliorated allergic conjunctivitis in the established setting. Such a rice-based edible vaccine is potentially both safe and effective for oral immunotherapy in individuals with allergic conjunctivitis. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  5. Impact of a Single Oral Acute Dose of Aflatoxin B₁ on Liver Function/Cytokines and the Lymphoproliferative Response in C57Bl/6 Mice.

    Science.gov (United States)

    Ishikawa, Angélica Tieme; Hirooka, Elisa Yoko; Alvares E Silva, Paula Leonello; Bracarense, Ana Paula Frederico Rodrigues Loureiro; Flaiban, Karina Keller Marques da Costa; Akagi, Claudia Yuri; Kawamura, Osamu; Costa, Marcio Carvalho da; Itano, Eiko Nakagawa

    2017-11-17

    Aflatoxin B₁ (AFB₁), a mycotoxin found in food and feed, exerts harmful effects on humans and animals. The liver is the earliest target of AFB₁, and its effects have been evaluated in animal models exposed to acute or chronic doses. Considering the possibility of sporadic ingestion of AFB₁-contaminated food, this study investigated the impact of a single oral dose of AFB₁ on liver function/cytokines and the lymphoproliferative response in mice. C57BL/6 mice were treated with a single oral AFB₁ dose (44, 442 or 663 μg AFB₁/kg of body weight) on the first day. Liver function (ALT, γ-GT, and total protein), cytokines (IL-4, IFN-γ, and IL-17), histopathology, and the spleen lymphoproliferative response to mitogens were evaluated on the 5th day. Although AFB₁ did not produce any significant changes in the biochemical parameters, 663 μg AFB₁/kg-induced hepatic upregulation of IL-4 and IFN-γ, along with liver tissue injury and suppression of the lymphoproliferative response to ConA (p oral dose of AFB₁ exposure can induce liver tissue lesions, liver cytokine modulation, and immune suppression in C57BL/6 mice.

  6. Impact of a Single Oral Acute Dose of Aflatoxin B1 on Liver Function/Cytokines and the Lymphoproliferative Response in C57Bl/6 Mice

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    Angélica Tieme Ishikawa

    2017-11-01

    Full Text Available Aflatoxin B1 (AFB1, a mycotoxin found in food and feed, exerts harmful effects on humans and animals. The liver is the earliest target of AFB1, and its effects have been evaluated in animal models exposed to acute or chronic doses. Considering the possibility of sporadic ingestion of AFB1-contaminated food, this study investigated the impact of a single oral dose of AFB1 on liver function/cytokines and the lymphoproliferative response in mice. C57BL/6 mice were treated with a single oral AFB1 dose (44, 442 or 663 μg AFB1/kg of body weight on the first day. Liver function (ALT, γ-GT, and total protein, cytokines (IL-4, IFN-γ, and IL-17, histopathology, and the spleen lymphoproliferative response to mitogens were evaluated on the 5th day. Although AFB1 did not produce any significant changes in the biochemical parameters, 663 μg AFB1/kg-induced hepatic upregulation of IL-4 and IFN-γ, along with liver tissue injury and suppression of the lymphoproliferative response to ConA (p < 0.05. In conclusion, a single oral dose of AFB1 exposure can induce liver tissue lesions, liver cytokine modulation, and immune suppression in C57BL/6 mice.

  7. Biological Inoculants in Forage Conservation

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    Judit Peter Szucs

    2011-05-01

    Full Text Available 3rd generation biological inoculants –containing lactic acid bacteria and enzymes – are prefered nowadays in order to coordinate the fermentation in such a way that they increase lactic acid production by leaps and bounds at the beginning of the fermentation and improve the quality and stability of silage during the fermentation and feeding. The quality of raw material (maturity of plant, chop lenght, spreading of inoculant uniformly and the proper filling, compacting, covering and wrapping have a great influence on the effectiveness of the inoculant. The mycotoxin content of malfermented silages is an undesirable risk factor. The authors established, that the Lactobacillus buchneri and enzymes containing inoculant protected better the carotene content of low, medium- and high wilteed lucerne haylages (P<0,05 compare to untreated ones Aerobic stability experiment by Honnig 1990 method was carried out with medium wilted (36 % DM lucerne haylage which was treatedtreated before ensilage with , the dosage of 105 CFU/g Pediococcus acidilactici, 1,5x105 CFU/g Lactobacillus buchneri and cellulase and hemicellulase enzimes (20 000 CMC /g remained stabyle, unspoiled after 9 days exposure to the air, while the untreated haylages spoiled after 2;4;or 7days on aerobic condition. The different Lactobacillus plantarum strains (50.000 CFU of Lactobacillus plantarum DSM 16568 + 50.000 CFU of Lactobacillus plantarum DSM 4784/ g FM of maize applied together were able to improve the aerobic stability of silomaize silage.

  8. Oral administration of Aloe vera gel powder prevents UVB-induced decrease in skin elasticity via suppression of overexpression of MMPs in hairless mice.

    Science.gov (United States)

    Saito, Marie; Tanaka, Miyuki; Misawa, Eriko; Yao, Ruiquing; Nabeshima, Kazumi; Yamauchi, Kouji; Abe, Fumiaki; Yamamoto, Yuki; Furukawa, Fukumi

    2016-07-01

    This study reports the effects of oral Aloe vera gel powder (AVGP) containing Aloe sterols on skin elasticity and the extracellular matrix in ultraviolet B (UVB)-irradiated hairless mice. Ten-week-old hairless mice were fed diets containing 0.3% AVGP for 8 weeks and irradiated UVB for 6 weeks. Mice treated with AVGP showed significant prevention of the UVB-induced decrease in skin elasticity. To investigate the mechanism underlying this suppression of skin elasticity loss, we measured the expression of matrix metalloproteinase (MMP)-2, -9, and -13. AVGP prevented both the UVB-induced increases in MMPs expressions. Moreover, we investigated hyaluronic acid (HA) content of mice dorsal skin and gene expression of HA synthase-2 (Has2). In the results, AVGP oral administration prevented UVB-induced decreasing in skin HA content and Has2 expression and attenuates the UVB-induced decrease in serum adiponectin, which promotes Has2 expression. These results suggested that AVGP has the ability to prevent the skin photoaging.

  9. 1’-Acetoxychavicol acetate inhibits growth of human oral carcinoma xenograft in mice and potentiates cisplatin effect via proinflammatory microenvironment alterations

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    In Lionel LA

    2012-10-01

    Full Text Available Abstract Background Oral cancers although preventable, possess a low five-year survival rate which has remained unchanged over the past three decades. In an attempt to find a more safe, affordable and effective treatment option, we describe here the use of 1’S-1’-acetoxychavicol acetate (ACA, a component of Malaysian ginger traditionally used for various medicinal purposes. Methods Whether ACA can inhibit the growth of oral squamous cell carcinoma (SCC cells alone or in combination with cisplatin (CDDP, was explored both in vitro using MTT assays and in vivo using Nu/Nu mice. Occurrence of apoptosis was assessed using PARP and DNA fragmentation assays, while the mode of action were elucidated through global expression profiling followed by Western blotting and IHC assays. Results We found that ACA alone inhibited the growth of oral SCC cells, induced apoptosis and suppressed its migration rate, while minimally affecting HMEC normal cells. ACA further enhanced the cytotoxic effects of CDDP in a synergistic manner as suggested by combination index studies. We also found that ACA inhibited the constitutive activation of NF-κB through suppression of IKKα/β activation. Human oral tumor xenografts studies in mice revealed that ACA alone was as effective as CDDP in reducing tumor volume, and further potentiated CDDP effects when used in combination with minimal body weight loss. The effects of ACA also correlated with a down-regulation of NF-κB regulated gene (FasL and Bim, including proinflammatory (NF-κB and COX-2 and proliferative (cyclin D1 biomarkers in tumor tissue. Conclusion Overall, our results suggest that ACA inhibits the growth of oral SCC and further potentiates the effect of standard CDDP treatment by modulation of proinflammatory microenvironment. The current preclinical data could form the basis for further clinical trials to improve the current standards for oral cancer care using this active component from the Malaysian

  10. The control of hyperglycemia by a novel trypsin resistant oral insulin preparation in alloxan induced type I diabetic mice.

    Science.gov (United States)

    Bank, Sarbashri; Ghosh, Arjun; Bhattacharya, Suman; Maiti, Smarajit; Khan, Gausal A; Sinha, Asru K

    2016-05-26

    A trypsin resistant oral insulin preparation was made by incubating insulin for 2 h at 23 °C with previously boiled cow milk at 100 °C that was coagulated with 0.6 M acetic acid. The precipitate was resuspended in the same volume of milk. The immunoblot analysis of the suspended proteins treated with 200 ng of trypsin/ml for 3 h demonstrated that the 80.1% of the insulin in the suspension survived the proteolytic degradation compared to 0% of the hormone survived in the control. The feeding of 0.4 ml (0.08 unit of insulin) of the resuspended proteins followed by 0.2 ml of the same protein to alloxan induced diabetic mice maximally decreased the blood glucose level from 508 ± 10 mg/dl to 130 ± 10 mg/dl in 7 h with simultaneous increase of the basal plasma concentration of insulin from 3 ± 1.1 μunits/ml to 18 ± 1.5 μunits/ml. In control experiment the absence of insulin in the identical milk suspension produced no hypoglycemic effect suggesting milk was not responsible for the hypoglycemic effect of milk-insulin complex. Coming out of insulin-casein complex from the intestinal gut to the circulation was spontaneous and facilitated diffusion transportation which was found from Gibbs free energy reaction.

  11. Effects of the oral administration of viable and heat-killed Streptococcus bovis HC5 cells to pre-sensitized BALB/c mice.

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    Aline D Paiva

    Full Text Available Antimicrobial peptides have been suggested as an alternative to classical antibiotics in livestock production and bacteriocin-producing bacteria could be added to animal feeds to deliver bacteriocins in the gastrointestinal (GI tract of ruminant and monogastric animals. In this study, viable (V and heat-killed (HK Streptococcus bovis HC5 cells were orally administered to pre-sensitized mice in order to assess the effects of a bacteriocin-producing bacteria on histological parameters and the immune response of the GI tract of monogastric animals. The administration of V and HK S. bovis HC5 cells during 58 days to BALB/c mice did not affect weight gain, but an increase in gut permeability was detected in animals receiving the HK cells. Viable and heat killed cells caused similar morphological alterations in the GI tract of the animals, but the most prominent effects were detected in the small intestine. The oral administration of S. bovis HC5 also influenced cytokine production in the small intestine, and the immune-mediated activity differed between V and HK cells. The relative expression of IL-12 and INF-γ was significantly higher in the small intestine of mice treated with V cells, while an increase in IL-5, IL-13 and TNF-α expression was only detected in mice treated with HK cells. Considering that even under a condition of severe challenge (pre-sensitization followed by daily exposure to the same bacterial immunogen the general health of the animals was maintained, it appears that oral administration of S. bovis HC5 cells could be a useful route to deliver bacteriocin in the GI tract of livestock animals.

  12. Effect of codon optimization and subcellular targeting on Toxoplasma gondii antigen SAG1 expression in tobacco leaves to use in subcutaneous and oral immunization in mice.

    Science.gov (United States)

    Laguía-Becher, Melina; Martín, Valentina; Kraemer, Mauricio; Corigliano, Mariana; Yacono, María L; Goldman, Alejandra; Clemente, Marina

    2010-07-15

    Codon optimization and subcellular targeting were studied with the aim to increase the expression levels of the SAG178-322 antigen of Toxoplasma gondii in tobacco leaves. The expression of the tobacco-optimized and native versions of the SAG1 gene was explored by transient expression from the Agrobacterium tumefaciens binary expression vector, which allows targeting the recombinant protein to the endoplasmic reticulum (ER) and the apoplast. Finally, mice were subcutaneously and orally immunized with leaf extracts-SAG1 and the strategy of prime boost with rSAG1 expressed in Escherichia coli was used to optimize the oral immunization with leaf extracts-SAG1. Leaves agroinfiltrated with an unmodified SAG1 gene accumulated 5- to 10-fold more than leaves agroinfiltrated with a codon-optimized SAG1 gene. ER localization allowed the accumulation of higher levels of native SAG1. However, no significant differences were observed between the mRNA accumulations of the different versions of SAG1. Subcutaneous immunization with leaf extracts-SAG1 (SAG1) protected mice against an oral challenge with a non-lethal cyst dose, and this effect could be associated with the secretion of significant levels of IFN-gamma. The protection was increased when mice were ID boosted with rSAG1 (SAG1+boost). This group elicited a significant Th1 humoral and cellular immune response characterized by high levels of IFN-gamma. In an oral immunization assay, the SAG1+boost group showed a significantly lower brain cyst burden compared to the rest of the groups. Transient agroinfiltration was useful for the expression of all of the recombinant proteins tested. Our results support the usefulness of endoplasmic reticulum signal peptides in enhancing the production of recombinant proteins meant for use as vaccines. The results showed that this plant-produced protein has potential for use as vaccine and provides a potential means for protecting humans and animals against toxoplasmosis.

  13. Hypomethylated Fgf3 is a potential biomarker for early detection of oral cancer in mice treated with the tobacco carcinogen dibenzo[def,p]chrysene.

    Science.gov (United States)

    Sun, Yuan-Wan; Chen, Kun-Ming; Imamura Kawasawa, Yuka; Salzberg, Anna C; Cooper, Timothy K; Caruso, Carla; Aliaga, Cesar; Zhu, Junjia; Gowda, Krishne; Amin, Shantu; El-Bayoumy, Karam

    2017-01-01

    Genetic and epigenetic alterations observed at end stage OSCC formation could be considered as a consequence of cancer development and thus changes in normal or premalignant tissues which had been exposed to oral carcinogens such as Dibenzo[def,p]chrysene (DBP) may better serve as predictive biomarkers of disease development. Many types of DNA damage can induce epigenetic changes which can occur early and in the absence of evident morphological abnormalities. Therefore we used ERRBS to generate genome-scale, single-base resolution DNA methylomes from histologically normal oral tissues of mice treated with DBP under experimental conditions known to induce maximum DNA damage which is essential for the development of OSCC induced by DBP in mice. After genome-wide correction, 30 and 48 differentially methylated sites (DMS) were identified between vehicle control and DBP treated mice using 25% and 10% differences in methylation, respectively. RT-PCR was further performed to examine the expressions of nine selected genes. Among them, Fgf3, a gene frequently amplified in head and neck cancer, showed most prominent and significant gene expression change (2.4× increases), despite the hypomethylation of Fgf3 was identified at >10kb upstream of transcription start site. No difference was observed in protein expression between normal oral tissues treated with DBP or vehicle as examined by immunohistochemistry. Collectively, our results indicate that Fgf3 hypomethylation and gene overexpression, but not protein expression, occurred in the early stage of oral carcinogenesis induced by DBP. Thus, Fgf3 hypomethylation may serve as a potential biomarker for early detection of OSCC.

  14. Hypomethylated Fgf3 is a potential biomarker for early detection of oral cancer in mice treated with the tobacco carcinogen dibenzo[def,p]chrysene.

    Directory of Open Access Journals (Sweden)

    Yuan-Wan Sun

    Full Text Available Genetic and epigenetic alterations observed at end stage OSCC formation could be considered as a consequence of cancer development and thus changes in normal or premalignant tissues which had been exposed to oral carcinogens such as Dibenzo[def,p]chrysene (DBP may better serve as predictive biomarkers of disease development. Many types of DNA damage can induce epigenetic changes which can occur early and in the absence of evident morphological abnormalities. Therefore we used ERRBS to generate genome-scale, single-base resolution DNA methylomes from histologically normal oral tissues of mice treated with DBP under experimental conditions known to induce maximum DNA damage which is essential for the development of OSCC induced by DBP in mice. After genome-wide correction, 30 and 48 differentially methylated sites (DMS were identified between vehicle control and DBP treated mice using 25% and 10% differences in methylation, respectively. RT-PCR was further performed to examine the expressions of nine selected genes. Among them, Fgf3, a gene frequently amplified in head and neck cancer, showed most prominent and significant gene expression change (2.4× increases, despite the hypomethylation of Fgf3 was identified at >10kb upstream of transcription start site. No difference was observed in protein expression between normal oral tissues treated with DBP or vehicle as examined by immunohistochemistry. Collectively, our results indicate that Fgf3 hypomethylation and gene overexpression, but not protein expression, occurred in the early stage of oral carcinogenesis induced by DBP. Thus, Fgf3 hypomethylation may serve as a potential biomarker for early detection of OSCC.

  15. Activation of Cellular Immunity in Herpes Simplex Virus Type 1-Infected Mice by the Oral Administration of Aqueous Extract of Moringa oleifera Lam. Leaves.

    Science.gov (United States)

    Kurokawa, Masahiko; Wadhwani, Ashish; Kai, Hisahiro; Hidaka, Muneaki; Yoshida, Hiroki; Sugita, Chihiro; Watanabe, Wataru; Matsuno, Koji; Hagiwara, Akinori

    2016-05-01

    Moringa oleifera Lam. is used as a nutritive vegetable and spice. Its ethanol extract has been previously shown to be significantly effective in alleviating herpetic skin lesions in mice. In this study, we evaluated the alleviation by the aqueous extract (AqMOL) and assessed the mode of its anti-herpetic action in a murine cutaneous herpes simplex virus type 1 (HSV-1) infection model. AqMOL (300 mg/kg) was administered orally to HSV-1-infected mice three times daily on days 0 to 5 after infection. AqMOL significantly limited the development of herpetic skin lesions and reduced virus titers in the brain on day 4 without toxicity. Delayed-type hypersensitivity (DTH) reaction to inactivated HSV-1 antigen was significantly stronger in infected mice administered AqMOL and AqMOL augmented interferon (IFN)-γ production by HSV-1 antigen from splenocytes of HSV-1-infected mice at 4 days post-infection. AqMOL administration was effective in elevating the ratio of CD11b(+) and CD49b(+) subpopulations of splenocytes in infected mice. As DTH is a major host defense mechanism for intradermal HSV infection, augmentation of the DTH response by AqMOL may contribute to their efficacies against HSV-1 infection. These results provided an important insights into the mechanism by which AqMOL activates cellular immunity. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. The Effect of Oral Intake of Low-Temperature-Processed Whey Protein Concentrate on Colitis and Gene Expression Profiles in Mice

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    Sharmila Jayatilake

    2014-06-01

    Full Text Available Inflammatory bowel disease (IBD is an autoimmune disease of unknown etiology and can lead to inflammation and cancer. Whey proteins contain many bioactive peptides with potential health benefits against IBD. We investigated the effect of low-temperature-processed whey protein concentrate (LWPC on the suppression of IBD by using a dextran sodium sulfate (DSS-induced colitis model in BALB/c mice. Oral intake of LWPC resulted in improved recovery of body weight in mice. Histological analysis showed that the epithelium cells of LWPC-treated mice were healthier and that lymphocyte infiltration was reduced. The increase in mucin due to the LWPC also reflected reduced inflammation in the colon. Transcriptome analysis of the colon by DNA microarrays revealed marked downregulation of genes related to immune responses in LWPC-fed mice. In particular, the expression of interferon gamma receptor 2 (Ifngr2 and guanylate-binding proteins (GBPs was increased by DSS treatment and decreased in LWPC-fed mice. These findings suggest that LWPCs suppress DSS-induced inflammation in the colon by suppressing the signaling of these cytokines. Our findings suggest that LWPCs would be an effective food resource for suppressing IBD symptoms.

  17. Oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein TSP-1 expression in STZ-induced type 1 diabetic ApoE-/- mice.

    Science.gov (United States)

    Ganguly, Rituparna; Sahu, Soumyadip; Ohanyan, Vahagn; Haney, Rebecca; Chavez, Ronaldo J; Shah, Shivani; Yalamanchili, Siri; Raman, Priya

    2017-03-27

    Increasing evidence suggests thrombospondin-1 (TSP-1), a potent proatherogenic matricellular protein, as a putative link between hyperglycemia and atherosclerotic complications in diabetes. We previously reported that the micronutrient chromium picolinate (CrP), with long-standing cardiovascular benefits, inhibits TSP-1 expression in glucose-stimulated human aortic smooth muscle cells in vitro. Here, we investigated the atheroprotective action of orally administered CrP in type 1 diabetic apolipoprotein E-deficient (ApoE-/-) mice and elucidated the role of TSP-1 in this process. CrP decreased lipid burden and neointimal thickness in aortic root lesions of hyperglycemic ApoE-/- mice; also, smooth muscle cell (SMC), macrophage and leukocyte abundance was prevented coupled with reduced cell proliferation. Attenuated lesion progression was accompanied with inhibition of hyperglycemia-induced TSP-1 expression and reduced protein O-glycosylation following CrP treatment; also, PCNA and vimentin (SMC synthetic marker) expression were reduced while SM-MHC (SMC contractile marker) levels were increased. To confirm a direct role of TSP-1 in diabetic atherosclerosis, hyperglycemic TSP-1-/-/ApoE-/- double knockout mice were compared with age-matched hyperglycemic ApoE-/- littermates. Lack of TSP-1 prevented lesion formation in hyperglycemic ApoE-/- mice, mimicking the atheroprotective phenotype of CrP-treated mice. These results suggest that therapeutic TSP-1 inhibition may have important atheroprotective potential in diabetic vascular disease.

  18. Inoculation Effects of Cast Iron

    Directory of Open Access Journals (Sweden)

    E. Fraś

    2012-12-01

    Full Text Available The paper presents a solidification sequence of graphite eutectic cells of A and D types, as well as globular and cementite eutectics. The morphology of eutectic cells in cast iron, the equations for their growth and the distances between the graphite precipitations in A and D eutectic types were analyzed. It is observed a critical eutectic growth rate at which one type of eutectic transformed into another. A mathematical formula was derived that combined the maximum degree of undercooling, the cooling rate of cast iron, eutectic cell count and the eutectic growth rate. One type of eutectic structure turned smoothly into the other at a particular transition rate, transformation temperature and transformational eutectic cell count. Inoculation of cast iron increased the number of eutectic cells with flake graphite and the graphite nodule count in ductile iron, while reducing the undercooling. An increase in intensity of inoculation caused a smooth transition from a cementite eutectic structure to a mixture of cementite and D type eutectic structure, then to a mixture of D and A types of eutectics up to the presence of only the A type of eutectic structure. Moreover, the mechanism of inoculation of cast iron was studied.

  19. Active protection against rotavirus infection of mice following intraperitoneal immunization.

    Science.gov (United States)

    McNeal, M M; Sheridan, J F; Ward, R L

    1992-11-01

    Active immunity to rotavirus has been demonstrated following oral inoculation with live virus but little is known about the effects of parenteral immunization. In this study, adult mice were immunized by intraperitoneal (ip) inoculation with live rotaviruses and later orally challenged with murine rotavirus (EDIM) to measure active immunity against infection. Three doses of EDIM (8 micrograms/dose) given intraperitoneally (ip) provided full protection against EDIM infection, whether administered with or without Freund's adjuvant. Only partial protection was found when the quantity of immunogen was reduced to protection of all mice. Significant protection was also observed after inoculation with one or three doses (2 micrograms/dose) of heterologous rotaviruses. Protection provided by the heterologous strains did not correlate with neutralizing antibody to EDIM, which indicated that neutralizing antibody to the challenge virus was not required for protection. uv-Inactivated EDIM also provided significant protection against EDIM, thus demonstrating that viral replication was not required for protection. These results suggest that parenteral immunization may be an effective method to vaccinate against rotavirus disease.

  20. Indole-3-carbinol, a plant nutrient and AhR-Ligand precursor, supports oral tolerance against OVA and improves peanut allergy symptoms in mice.

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    Christiane Hammerschmidt-Kamper

    Full Text Available In general, dietary antigens are tolerated by the gut associated immune system. Impairment of this so-called oral tolerance is a serious health risk. We have previously shown that activation of the ligand-dependent transcription factor aryl hydrocarbon receptor (AhR by the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD affects both oral tolerance and food allergy. In this study, we determine whether a common plant-derived, dietary AhR-ligand modulates oral tolerance as well. We therefore fed mice with indole-3-carbinole (I3C, an AhR ligand that is abundant in cruciferous plants. We show that several I3C metabolites were detectable in the serum after feeding, including the high-affinity ligand 3,3´-diindolylmethane (DIM. I3C feeding robustly induced the AhR-target gene CYP4501A1 in the intestine; I3C feeding also induced the aldh1 gene, whose product catalyzes the formation of retinoic acid (RA, an inducer of regulatory T cells. We then measured parameters indicating oral tolerance and severity of peanut-induced food allergy. In contrast to the tolerance-breaking effect of TCDD, feeding mice with chow containing 2 g/kg I3C lowered the serum anti-ovalbumin IgG1 response in an experimental oral tolerance protocol. Moreover, I3C feeding attenuated symptoms of peanut allergy. In conclusion, the dietary compound I3C can positively influence a vital immune function of the gut.

  1. Chitosan microparticles loaded with yeast-derived PCV2 virus-like particles elicit antigen-specific cellular immune response in mice after oral administration.

    Science.gov (United States)

    Bucarey, Sergio A; Pujol, Myriam; Poblete, Joaquín; Nuñez, Ignacio; Tapia, Cecilia V; Neira-Carrillo, Andrónico; Martinez, Jonatán; Bassa, Oliver

    2014-08-20

    Porcine circovirus type 2 (PCV2)-associated diseases are a major problem for the swine industry worldwide. In addition to improved management and husbandry practices, the availability of several anti-PCV2 vaccines provides an efficient immunological option for reducing the impact of these diseases. Most anti-PCV2 vaccines are marketed as injectable formulations. Although these are effective, there are problems associated with the use of injectable products, including laborious and time-consuming procedures, the induction of inflammatory responses at the injection site, and treatment-associated stress to the animals. Oral vaccines represent an improvement in antigen delivery technology; they overcome the problems associated with injection management and facilitate antigen boosting when an animals' immunity falls outside the protective window. Chitosan microparticles were used as both a vehicle and mucosal adjuvant to deliver yeast-derived PCV2 virus-like particles (VLPs) in an attempt to develop an oral vaccine. The physical characteristics of the microparticles, including size, Zeta potential, and polydispersity, were examined along with the potential to induce PCV2-specific cellular immune responses in mice after oral delivery. Feeding mice with PCV2 VLP-loaded, positively-charged chitosan microparticles with an average size of 2.5 μm induced the proliferation of PCV2-specific splenic CD4+/CD8+ lymphocytes and the subsequent production of IFN-γ to levels comparable with those induced by an injectable commercial formulation. Chitosan microparticles appear to be a safe, simple system on which to base PCV2 oral vaccines. Oral chitosan-mediated antigen delivery is a novel strategy that efficiently induces anti-PCV2 cellular responses in a mouse model. Further studies in swine are warranted.

  2. Comparison of the safety and pharmacokinetics of ST-246® after i.v. infusion or oral administration in mice, rabbits and monkeys.

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    Yali Chen

    Full Text Available ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (i.v. formulation may be required for some hospitalized patients who are unable to take oral medication. An i.v. formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation.The pharmacokinetics of ST-246 after i.v. infusions in mice, rabbits and nonhuman primates (NHP were compared to those obtained after oral administration. Ten minute i.v. infusions of ST-246 at doses of 3, 10, 30, and 75 mg/kg in mice produced peak plasma concentrations ranging from 16.9 to 238 µg/mL. Elimination appeared predominately first-order and exposure dose-proportional up to 30 mg/kg. Short i.v. infusions (5 to 15 minutes in rabbits resulted in rapid distribution followed by slower elimination. Intravenous infusions in NHP were conducted at doses of 1 to 30 mg/kg. The length of single infusions in NHP ranged from 4 to 6 hours. The pharmacokinetics and tolerability for the two highest doses were evaluated when administered as two equivalent 4 hour infusions initiated 12 hours apart. Terminal elimination half-lives in all species for oral and i.v. infusions were similar. Dose-limiting central nervous system effects were identified in all three species and appeared related to high C(max plasma concentrations. These effects were eliminated using slower i.v. infusions.Pharmacokinetic profiles after i.v. infusion compared to those observed after oral administration demonstrated the necessity of longer i.v. infusions to (1 mimic the plasma exposure observed after oral administration and (2 avoid C(max associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and i.v. administration. The administration of ST-246

  3. Oral supplementation of Ocimum basilicum has the potential to improves the locomotory, exploratory, anxiolytic behavior and learning in adult male albino mice.

    Science.gov (United States)

    Zahra, K; Khan, M A; Iqbal, F

    2015-01-01

    The aim of this project was to determine the effect of 100 mg/ml solvent/kg body weight of Ocimum basilicum leaf extract on neuromuscular co-ordination, exploratory, locomotory and short-term memory formation in male albino mice. Five weeks old, male albino mice were used as the experimental animals in order to demonstrate the effect of O. basilicum's extract on learning and memory. Each male albino mouse was weighted and orally treated either with 100 mg/ml solvent/kg body weight of O. basilicum leaf extract or with commercially available saline solution (Otsuka, Pakistan) for 7 days. Behavioral observations were made by applying a series of neurological tests (Elevated plus maze, Light and dark box, Open field and Rota rod). Dose supplementation continued during neurological testing. It was observed that 100 mg/ml solvent/kg body weight of leaf extract improves neuromuscular co-ordination and male albino mouse performance in open field, light dark box and during novel object test when compared with control group. We concluded that 100 mg/ml solvent/kg body weight of leaf extract has the potential to improve neuromuscular co-ordination, exploratory behavior, object recognition ability and transfer latency in male albino mice and can be safely administrated orally.

  4. Cholesterol reduction and lack of genotoxic or toxic effects in mice after repeated 21-day oral intake of lemongrass (Cymbopogon citratus) essential oil.

    Science.gov (United States)

    Costa, Celso A R A; Bidinotto, Lucas T; Takahira, Regina K; Salvadori, Daisy M F; Barbisan, Luís F; Costa, Mirtes

    2011-09-01

    Cymbopogon citratus (lemongrass) is currently used in traditional folk medicine. Although this species presents widespread use, there are no scientific data on its efficacy or safety after repeated treatments. Therefore, this work investigated the toxicity and genotoxicity of this lemongrass's essential oil (EO) in male Swiss mice. The single LD(50) based on a 24h acute oral toxicity study was found to be around 3500 mg/kg. In a repeated-dose 21-day oral toxicity study, mice were randomly assigned to two control groups, saline- or Tween 80 0.01%-treated groups, or one of the three experimental groups receiving lemongrass EO (1, 10 or 100mg/kg). No significant changes in gross pathology, body weight, absolute or relative organ weights, histology (brain, heart, kidneys, liver, lungs, stomach, spleen and urinary bladder), urinalysis or clinical biochemistry were observed in EO-treated mice relative to the control groups. Additionally, blood cholesterol was reduced after EO-treatment at the highest dose tested. Similarly, data from the comet assay in peripheral blood cells showed no genotoxic effect from the EO. In conclusion, our findings verified the safety of lemongrass intake at the doses used in folk medicine and indicated the beneficial effect of reducing the blood cholesterol level. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa.

    Science.gov (United States)

    Matsumoto, Kenjiro; Horie, Syunji; Ishikawa, Hayato; Takayama, Hiromitsu; Aimi, Norio; Ponglux, Dhavadee; Watanabe, Kazuo

    2004-03-12

    Mitragynine is an indole alkaloid isolated from the Thai medicinal plant Mitragyna speciosa. We previously reported the morphine-like action of mitragynine and its related compounds in the in vitro assays. In the present study, we investigated the opioid effects of 7-hydroxymitragynine, which is isolated as its novel constituent, on contraction of isolated ileum, binding of the specific ligands to opioid receptors and nociceptive stimuli in mice. In guinea-pig ileum, 7-hydroxymitragynine inhibited electrically induced contraction through the opioid receptors. Receptor-binding assays revealed that 7-hydroxymitragynine has a higher affinity for micro-opioid receptors relative to the other opioid receptors. Administration of 7-hydroxymitragynine (2.5-10 mg/kg, s.c.) induced dose-dependent antinociceptive effects in tail-flick and hot-plate tests in mice. Its effect was more potent than that of morphine in both tests. When orally administered, 7-hydroxymitragynine (5-10 mg/kg) showed potent antinociceptive activities in tail-flick and hot-plate tests. In contrast, only weak antinociception was observed in the case of oral administration of morphine at a dose of 20 mg/kg. It was found that 7-hydroxymitragynine is a novel opioid agonist that is structurally different from the other opioid agonists, and has potent analgesic activity when orally administered.

  6. Oral infection with enteropathogenic Escherichia coli triggers immune response and intestinal histological alterations in mice selected for their minimal acute inflammatory responses.

    Science.gov (United States)

    Vulcano, Amanda Bardella; Tino-De-Franco, Milene; Amaral, José Araujo; Ribeiro, Orlando Garcia; Cabrera, Wafa Hanna Koury; Bordenalli, Marcela Aparecida; Carbonare, Cristiane Barros; Álvares, Eliana Parisi; Carbonare, Solange Barros

    2014-06-01

    Enteropathogenic Escherichia coli (EPEC), a leading cause of infant diarrhea, is an important public health problem in Brazil and other developing countries. In vitro assays of bacterial adhesion to cultured cells are important tools for studying bacterial pathogenicity but do not reproduce all the events that occur in natural infections. In this study, the effects of oral infection with EPEC on mice selected for their minimal acute inflammatory response (AIR min) were evaluated. Mice were orally infected with EPEC and variations in body weight, bacterial shedding and antibody production observed. The infected animals developed seric and secretory anti-EPEC antibodies; however, neither mortality nor diarrhea was observed. Light microscopy of their intestines demonstrated histological modifications that were not present in controls. However, electron microscopy did not show bacteria attached to the intestinal epithelia to form attaching and effacing lesions, characteristic of EPEC in humans. The bacteria were detected in Peyer's patches and intestinal contents up to 5 hr post-infection. When human anti-EPEC secretory immunoglobulin A or avian immunoglobulin Y antibodies were administered to infected animals, they developed minor histological alterations compared with non-treated animals. In summary, it was found that EPEC triggers immune responses and intestinal histological alterations but does not produce evidence of diarrheal disease in mice infected by the oral route. This study of EPEC experimental infection provides a better understanding of the effects of antibodies on bacterial infections and may provide a suitable model for the design and testing of immunobiological products for active or passive immunization. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

  7. Inoculation effects on root-colonizing arbuscular mycorrhizal fungal communities spread beyond directly inoculated plants.

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    Martina Janoušková

    Full Text Available Inoculation with arbuscular mycorrhizal fungi (AMF may improve plant performance at disturbed sites, but inoculation may also suppress root colonization by native AMF and decrease the diversity of the root-colonizing AMF community. This has been shown for the roots of directly inoculated plants, but little is known about the stability of inoculation effects, and to which degree the inoculant and the inoculation-induced changes in AMF community composition spread into newly emerging seedlings that were not in direct contact with the introduced propagules. We addressed this topic in a greenhouse experiment based on the soil and native AMF community of a post-mining site. Plants were cultivated in compartmented pots with substrate containing the native AMF community, where AMF extraradical mycelium radiating from directly inoculated plants was allowed to inoculate neighboring plants. The abundances of the inoculated isolate and of native AMF taxa were monitored in the roots of the directly inoculated plants and the neighboring plants by quantitative real-time PCR. As expected, inoculation suppressed root colonization of the directly inoculated plants by other AMF taxa of the native AMF community and also by native genotypes of the same species as used for inoculation. In the neighboring plants, high abundance of the inoculant and the suppression of native AMF were maintained. Thus, we demonstrate that inoculation effects on native AMF propagate into plants that were not in direct contact with the introduced inoculum, and are therefore likely to persist at the site of inoculation.

  8. Inoculation effects on root-colonizing arbuscular mycorrhizal fungal communities spread beyond directly inoculated plants.

    Science.gov (United States)

    Janoušková, Martina; Krak, Karol; Vosátka, Miroslav; Püschel, David; Štorchová, Helena

    2017-01-01

    Inoculation with arbuscular mycorrhizal fungi (AMF) may improve plant performance at disturbed sites, but inoculation may also suppress root colonization by native AMF and decrease the diversity of the root-colonizing AMF community. This has been shown for the roots of directly inoculated plants, but little is known about the stability of inoculation effects, and to which degree the inoculant and the inoculation-induced changes in AMF community composition spread into newly emerging seedlings that were not in direct contact with the introduced propagules. We addressed this topic in a greenhouse experiment based on the soil and native AMF community of a post-mining site. Plants were cultivated in compartmented pots with substrate containing the native AMF community, where AMF extraradical mycelium radiating from directly inoculated plants was allowed to inoculate neighboring plants. The abundances of the inoculated isolate and of native AMF taxa were monitored in the roots of the directly inoculated plants and the neighboring plants by quantitative real-time PCR. As expected, inoculation suppressed root colonization of the directly inoculated plants by other AMF taxa of the native AMF community and also by native genotypes of the same species as used for inoculation. In the neighboring plants, high abundance of the inoculant and the suppression of native AMF were maintained. Thus, we demonstrate that inoculation effects on native AMF propagate into plants that were not in direct contact with the introduced inoculum, and are therefore likely to persist at the site of inoculation.

  9. Development of oral cancer vaccine using recombinant Bifidobacterium displaying Wilms' tumor 1 protein.

    Science.gov (United States)

    Kitagawa, Koichi; Oda, Tsugumi; Saito, Hiroki; Araki, Ayame; Gonoi, Reina; Shigemura, Katsumi; Hashii, Yoshiko; Katayama, Takane; Fujisawa, Masato; Shirakawa, Toshiro

    2017-06-01

    Several types of vaccine-delivering tumor-associated antigens (TAAs) have been developed in basic and clinical research. Wilms' tumor 1 (WT1), identified as a gene responsible for pediatric renal neoplasm, is one of the most promising TAA for cancer immunotherapy. Peptide and dendritic cell-based WT1 cancer vaccines showed some therapeutic efficacy in clinical and pre-clinical studies but as yet no oral WT1 vaccine can be administrated in a simple and easy way. In the present study, we constructed a novel oral cancer vaccine using a recombinant Bifidobacterium longum displaying WT1 protein. B. longum 420 was orally administered into mice inoculated with WT1-expressing tumor cells for 4 weeks to examine anti-tumor effects. To analyze the WT1-specific cellular immune responses to oral B. longum 420, mice splenocytes were isolated and cytokine production and cytotoxic activities were determined. Oral administrations of B. longum 420 significantly inhibited WT1-expressing tumor growth and prolonged survival in mice. Immunohistochemical study and immunological assays revealed that B. longum 420 substantially induced tumor infiltration of CD4 + T and CD8 + T cells, systemic WT1-specific cytokine production, and cytotoxic activity mediated by WT1-epitope specific cytotoxic T lymphocytes, with no apparent adverse effects. Our novel oral cancer vaccine safely induced WT1-specific cellular immunity via activation of the gut mucosal immune system and achieved therapeutic efficacy with several practical advantages over existing non-oral vaccines.

  10. Identification and Pharmacokinetics of Multiple Potential Bioactive Constituents after Oral Administration of Radix Astragali on Cyclophosphamide-Induced Immunosuppression in Balb/c Mice

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    Menghua Liu

    2015-03-01

    Full Text Available Radix Astragali (RA is one of the commonly-used traditional Chinese medicines (TCMs with an immunomodulatory effect confirmed in the clinic. In order to better understand the material basis for the therapeutic effects, this study was to investigate the absorbed components and their pharmacokinetic profile after oral administration of RA on cyclophosphamide-induced immunosuppression in Balb/c mice. As a result, 51 compounds in RA extract and 31 prototype compounds with nine metabolites were detected in mice plasma by the ultra-fast liquid chromatography (UFLC-DAD-Q-TOF-MS/MS method. The pharmacokinetic parameters of five main constituents, including calycosin-7-O-glucoside, ononin, calycosin, formononetin and astragaloside IV, were obtained using HPLC-MS/MS. These results offered useful information for research on the pharmacological mechanism of RA and for its further development.

  11. Interactions of manganese with iron, zinc, and copper in neonatal C57BL/6J and parkin mice following developmental oral manganese exposure

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    Melanie L. Foster

    2017-12-01

    Full Text Available High dose manganese (Mn exposure can result in changes in tissue concentrations of other essential metals due to Mn-induced alterations in metal absorption and competition for metal transporters and regulatory proteins. We evaluated responses in mice with a Parkin gene defect (parkin mice and a wildtype strain (C57BL/6J following neonatal Mn exposure. Neonatal parkin and C57BL/6J littermates were randomly assigned to 0, 11, or 25 mg Mn/kg-day dose groups with oral exposures occurring from postnatal day (PND 1 through PND 28. We report liver, femur, olfactory bulb, striatum, and frontal cortex iron, copper, and zinc concentrations and changes in hepatic gene expression of different metal transporters in PND 29 parkin and C57BL/6J mice. A companion manuscript (Foster et al., 2017 [1] describes the primary study findings. This data provides insights into strain differences in the way Mn interacts with other trace metals in mice. Keywords: Copper, Zinc, Iron, Manganese Toxicity, Mouse

  12. Listeria monocytogenes strains encoding premature stop codons in inlA invade mice and guinea pig fetuses in orally dosed dams

    DEFF Research Database (Denmark)

    Holch, Anne; Ingmer, Hanne; Licht, Tine Rask

    2013-01-01

    Listeria monocytogenes is an important food-borne bacterial pathogen and listeriosis can result in abortions in pregnant women. The bacterium can colonize food-processing environments, where specific molecular subtypes can persist for years. The purpose of this study was to determine the virulence...... the maternofetal control was found in 6 % of fetal tissue samples. As the food-processing persistent strains carry a premature stop codon in inlA but are invasive in orally dosed pregnant mice and guinea pigs, we hypothesize that listerial crossing of the placental barrier can occur by a mechanism...

  13. Transient B-cell depletion with anti-CD20 in combination with proinsulin DNA vaccine or oral insulin: immunologic effects and efficacy in NOD mice.

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    Ghanashyam Sarikonda

    Full Text Available A recent type 1 diabetes (T1D clinical trial of rituximab (a B cell-depleting anti-CD20 antibody achieved some therapeutic benefit in preserving C-peptide for a period of approximately nine months in patients with recently diagnosed diabetes. Our previous data in the NOD mouse demonstrated that co-administration of antigen (insulin with anti-CD3 antibody (a T cell-directed immunomodulator offers better protection than either entity alone, indicating that novel combination therapies that include a T1D-related autoantigen are possible. To accelerate the identification and development of novel combination therapies that can be advanced into the clinic, we have evaluated the combination of a mouse anti-CD20 antibody with either oral insulin or a proinsulin-expressing DNA vaccine. Anti-CD20 alone, given once or on 4 consecutive days, produced transient B cell depletion but did not prevent or reverse T1D in the NOD mouse. Oral insulin alone (twice weekly for 6 weeks was also ineffective, while proinsulin DNA (weekly for up to 12 weeks showed a trend toward modest efficacy. Combination of anti-CD20 with oral insulin was ineffective in reversing diabetes in NOD mice whose glycemia was controlled with SC insulin pellets; these experiments were performed in three independent labs. Combination of anti-CD20 with proinsulin DNA was also ineffective in diabetes reversal, but did show modest efficacy in diabetes prevention (p = 0.04. In the prevention studies, anti-CD20 plus proinsulin resulted in modest increases in Tregs in pancreatic lymph nodes and elevated levels of proinsulin-specific CD4+ T-cells that produced IL-4. Thus, combination therapy with anti-CD20 and either oral insulin or proinsulin does not protect hyperglycemic NOD mice, but the combination with proinsulin offers limited efficacy in T1D prevention, potentially by augmentation of proinsulin-specific IL-4 production.

  14. Lettuce-produced hepatitis C virus E1E2 heterodimer triggers immune responses in mice and antibody production after oral vaccination.

    Science.gov (United States)

    Clarke, Jihong Liu; Paruch, Lisa; Dobrica, Mihaela-Olivia; Caras, Iuliana; Tucureanu, Catalin; Onu, Adrian; Ciulean, Sonya; Stavaru, Crina; Eerde, Andre; Wang, Yanliang; Steen, Hege; Haugslien, Sissel; Petrareanu, Catalina; Lazar, Catalin; Popescu, Costin-Ioan; Bock, Ralph; Dubuisson, Jean; Branza-Nichita, Norica

    2017-12-01

    The hepatitis C virus (HCV) is a major etiologic agent for severe liver diseases (e.g. cirrhosis, fibrosis and hepatocellular carcinoma). Approximately 140 million people have chronic HCV infections and about 500 000 die yearly from HCV-related liver pathologies. To date, there is no licensed vaccine available to prevent HCV infection and production of a HCV vaccine remains a major challenge. Here, we report the successful production of the HCV E1E2 heterodimer, an important vaccine candidate, in an edible crop (lettuce, Lactuca sativa) using Agrobacterium-mediated transient expression technology. The wild-type dimer (E1E2) and a variant without an N-glycosylation site in the E2 polypeptide (E1E2∆N6) were expressed, and appropriate N-glycosylation pattern and functionality of the E1E2 dimers were demonstrated. The humoral immune response induced by the HCV proteins was investigated in mice following oral administration of lettuce antigens with or without previous intramuscular prime with the mammalian HEK293T cell-expressed HCV dimer. Immunization by oral feeding only resulted in development of weak serum levels of anti-HCV IgM for both antigens; however, the E1E2∆N6 proteins produced higher amounts of secretory IgA, suggesting improved immunogenic properties of the N-glycosylation mutant. The mice group receiving the intramuscular injection followed by two oral boosts with the lettuce E1E2 dimer developed a systemic but also a mucosal immune response, as demonstrated by the presence of anti-HCV secretory IgA in faeces extracts. In summary, our study demonstrates the feasibility of producing complex viral antigens in lettuce, using plant transient expression technology, with great potential for future low-cost oral vaccine development. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and the Association of Applied Biologists and John Wiley & Sons Ltd.

  15. Survival and virulence of copper- and chlorine-stressed Yersinia enterocolitica in Experimentally infected mice

    Energy Technology Data Exchange (ETDEWEB)

    Singh, A.; McFeters, G.A.

    1987-08-01

    The effect of gastric pH on the viability and virulence of Yersinia enterocolitica 0:8 after exposure to sublethal concentrations of copper and chlorine was determined in mice. Viability and injury were assessed with a nonselective TLY agar and two selective media, TLYD agar and CIN agar. Both copper and chlorine caused injury which was manifested by the inability of the cells to grow on selective media. CIN agar was more restrictive to the growth of injured cells than TLYD agar. Injury of the exposed cells was further enhanced in the gastric environment of mice. Besides injury, the low gastric pH caused extensive loss of viability in copper-exposed cells. Lethality in the chlorine-exposed cells was less extensive, and a portion of the inoculum reached the small intestine 5 min postinoculation. No adverse effect on the injured cells was apparent in the small intestine, and a substantial revival of the injury occurred in 3 to 4 h after intraluminal inoculation. The virulence of chlorine-stressed Y. enterocolitica in orally inoculated mice was similar to that of the control culture, but copper-stressed cells showed reduced virulence. Virulence was partly restored by oral administration of sodium bicarbonate before the inoculation of copper-exposed cells. Neutralization of gastric acidity had no effect on the virulence of the control of chlorine-stressed cells.

  16. Myxomavirus anti-inflammatory chemokine binding protein reduces the increased plaque growth induced by chronic Porphyromonas gingivalis oral infection after balloon angioplasty aortic injury in mice.

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    Alexandra R Lucas

    Full Text Available Thrombotic occlusion of inflammatory plaque in coronary arteries causes myocardial infarction. Treatment with emergent balloon angioplasty (BA and stent implant improves survival, but restenosis (regrowth can occur. Periodontal bacteremia is closely associated with inflammation and native arterial atherosclerosis, with potential to increase restenosis. Two virus-derived anti-inflammatory proteins, M-T7 and Serp-1, reduce inflammation and plaque growth after BA and transplant in animal models through separate pathways. M-T7 is a broad spectrum C, CC and CXC chemokine-binding protein. Serp-1 is a serine protease inhibitor (serpin inhibiting thrombotic and thrombolytic pathways. Serp-1 also reduces arterial inflammation and improves survival in a mouse herpes virus (MHV68 model of lethal vasculitis. In addition, Serp-1 demonstrated safety and efficacy in patients with unstable coronary disease and stent implant, reducing markers of myocardial damage. We investigate here the effects of Porphyromonas gingivalis, a periodontal pathogen, on restenosis after BA and the effects of blocking chemokine and protease pathways with M-T7 and Serp-1. ApoE-/- mice had aortic BA and oral P. gingivalis infection. Arterial plaque growth was examined at 24 weeks with and without anti-inflammatory protein treatment. Dental plaques from mice infected with P. gingivalis tested positive for infection. Neither Serp-1 nor M-T7 treatment reduced infection, but IgG antibody levels in mice treated with Serp-1 and M-T7 were reduced. P. gingivalis significantly increased monocyte invasion and arterial plaque growth after BA (P<0.025. Monocyte invasion and plaque growth were blocked by M-T7 treatment (P<0.023, whereas Serp-1 produced only a trend toward reductions. Both proteins modified expression of TLR4 and MyD88. In conclusion, aortic plaque growth in ApoE-/- mice increased after angioplasty in mice with chronic oral P. gingivalis infection. Blockade of chemokines, but not

  17. Modulation of killer cells activities in response to inoculation of irradiated tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Amino, Kayoko (Osaka Univ., Suita (Japan). School of Dentistry)

    1991-08-01

    There are two main radiation effects in therapy of malignant tumors, one is the direct cytotoxic effect of radiotherapy and another is the immunological response in the host. To investigate the state of the immunological response after radiation, the rise and fall of killer cell and cytokine activities were studied in an experimental tumor system using BALB/c mice and syngeneic Meth-A fibrosarcoma. The mice, inoculated with X-ray treated Meth-A (Rad-Meth-A-mice), acquired antitumor immunity as demonstrated by a Meth-A challenge test. Moreover, the mice inoculated with Mitomycin C treated Meth-A (MMC-Meth-A-mice) also acquired the same immunity. The effector cells in Rad-Meth-A-mice and in MMC-Meth-A-mice were mainly cytotoxic T lymphocytes (CTL). The maximum CTL activity was noted on Days 14 and 21 after inoculation in Rad-Meth-A-mice and MMC-Meth-A-mice. The spleen lymphocytes of Rad-Meth-A-mice produced Interleukin 2 (IL-2), Lymphotoxin (LT) and Interferon (IFN). On the other hand, the spleen lymphocytes of MMC-Meth-A-mice produced IL-2 and LT, but not IFN. Moreover, the responsiveness of spleen lymphocytes to IL-2 increased in quantity. Ia antigen positive ratio of spleen macrophages that were taken from Rad-Meth-A-mice and MMC-Meth-A-mice increased. Taken together, these results suggest that Meth-A treated with either X-ray or Mitomycin C can induce a specific antitumor immunological response in mice. (author).

  18. Citric Acid and Quinine Share Perceived Chemosensory Features Making Oral Discrimination Difficult in C57BL/6J Mice

    Science.gov (United States)

    Treesukosol, Yada; Mathes, Clare M.

    2011-01-01

    Evidence in the literature shows that in rodents, some taste-responsive neurons respond to both quinine and acid stimuli. Also, under certain circumstances, rodents display some degree of difficulty in discriminating quinine and acid stimuli. Here, C57BL/6J mice were trained and tested in a 2-response operant discrimination task. Mice had severe difficulty discriminating citric acid from quinine and 6-n-propylthiouracil (PROP) with performance slightly, but significantly, above chance. In contrast, mice were able to competently discriminate sucrose from citric acid, NaCl, quinine, and PROP. In another experiment, mice that were conditioned to avoid quinine by pairings with LiCl injections subsequently suppressed licking responses to quinine and citric acid but not to NaCl or sucrose in a brief-access test, relative to NaCl-injected control animals. However, mice that were conditioned to avoid citric acid did not display cross-generalization to quinine. These mice significantly suppressed licking only to citric acid, and to a much lesser extent NaCl, compared with controls. Collectively, the findings from these experiments suggest that in mice, citric acid and quinine share chemosensory features making discrimination difficult but are not perceptually identical. PMID:21421543

  19. Antiobesity and Anti-Inflammatory Effects of Orally Administered Bonito Extracts on Mice Fed a High-Fat Diet

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    Emi Ikebe

    2017-01-01

    Full Text Available Background. The condensed fermentative extract of bonito (BoE, skipjack tuna (Katsuwonus pelamis, has claimed its health conditioning effects against lifestyle-related diseases such as hypertension and type 2 diabetes. Methods. We evaluated the antiobesity and anti-inflammatory effects of BoE on mice fed a high-fat diet (HFD. Mice (9 weeks of age were maintained for 11 weeks on HFD with or without BoE (50 mg or 500 mg/kg. Results. Compared with untreated mice, BoE50 or BoE500 mice achieved maximum weight reductions of 7.4% (males and 11.4% (females, and visceral fat in male BoE500 mice was more decreased among all mice (P = 0.00459. Furthermore, an antiobesity gene uncoupling protein-1 was significantly induced in the visceral fat tissues of male BoE500 (P = 0.0110 and female BoE50 and BoE500 mice (P = 0.0110 and P = 0.0110, resp.. Finally, we detected reduced amount of granulocyte-colony stimulating factor (P = 0.0250 in the sera of female BoE50 and interleukin- (IL- 5 (P = 0.0120, IL-6 (P = 0.0118, and IL-13 (P = 0.0243 in female BoE500 mice. Conclusion. The antiobesity and anti-inflammatory effects of BoE were demonstrated with our examination system and any toxic adverse effects were not observed in mice during the 3-month investigation.

  20. Ciguatoxins and Maitotoxins in Extracts of Sixteen Gambierdiscus Isolates and One Fukuyoa Isolate from the South Pacific and Their Toxicity to Mice by Intraperitoneal and Oral Administration

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    Rex Munday

    2017-06-01

    Full Text Available Ciguatoxins (CTXs, and possibly maitotoxins (MTXs, are responsible for Ciguatera Fish Poisoning, an important health problem for consumers of reef fish (such as inhabitants of islands in the South Pacific Ocean. The habitational range of the Gambierdiscus species is expanding, and new species are being discovered. In order to provide information on the potential health risk of the Gambierdiscus species, and one Fukuyoa species (found in the Cook Islands, the Kermadec Islands, mainland New Zealand, and New South Wales, Australia, 17 microalgae isolates were collected from these areas. Unialgal cultures were grown and extracts of the culture isolates were analysed for CTXs and MTXs by liquid chromatography tandem mass spectrometry (LC-MS/MS, and their toxicity to mice was determined by intraperitoneal and oral administration. An isolate of G. carpenteri contained neither CTXs nor MTXs, while 15 other isolates (including G. australes, G. cheloniae, G. pacificus, G. honu, and F. paulensis contained only MTX-1 and/or MTX-3. An isolate of G. polynesiensis contained both CTXs and MTX-3. All the extracts were toxic to mice by intraperitoneal injection, but those containing only MTX-1 and/or -3 were much less toxic by oral administration. The extract of G. polynesiensis was highly toxic by both routes of administration.

  1. Effect of codon optimization and subcellular targeting on Toxoplasma gondii antigen SAG1 expression in tobacco leaves to use in subcutaneous and oral immunization in mice

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    Yacono María L

    2010-07-01

    Full Text Available Abstract Background Codon optimization and subcellular targeting were studied with the aim to increase the expression levels of the SAG178-322 antigen of Toxoplasma gondii in tobacco leaves. The expression of the tobacco-optimized and native versions of the SAG1 gene was explored by transient expression from the Agrobacterium tumefaciens binary expression vector, which allows targeting the recombinant protein to the endoplasmic reticulum (ER and the apoplast. Finally, mice were subcutaneously and orally immunized with leaf extracts-SAG1 and the strategy of prime boost with rSAG1 expressed in Escherichia coli was used to optimize the oral immunization with leaf extracts-SAG1. Results Leaves agroinfiltrated with an unmodified SAG1 gene accumulated 5- to 10-fold more than leaves agroinfiltrated with a codon-optimized SAG1 gene. ER localization allowed the accumulation of higher levels of native SAG1. However, no significant differences were observed between the mRNA accumulations of the different versions of SAG1. Subcutaneous immunization with leaf extracts-SAG1 (SAG1 protected mice against an oral challenge with a non-lethal cyst dose, and this effect could be associated with the secretion of significant levels of IFN-γ. The protection was increased when mice were ID boosted with rSAG1 (SAG1+boost. This group elicited a significant Th1 humoral and cellular immune response characterized by high levels of IFN-γ. In an oral immunization assay, the SAG1+boost group showed a significantly lower brain cyst burden compared to the rest of the groups. Conclusion Transient agroinfiltration was useful for the expression of all of the recombinant proteins tested. Our results support the usefulness of endoplasmic reticulum signal peptides in enhancing the production of recombinant proteins meant for use as vaccines. The results showed that this plant-produced protein has potential for use as vaccine and provides a potential means for protecting humans and

  2. Long-term repeated daily use of intragastric gavage hinders induction of oral tolerance to ovalbumin in mice.

    Science.gov (United States)

    Kinder, Jeremy M; Then, Jenny E; Hansel, Patrick M; Molinero, Luciana L; Bruns, Heather A

    2014-10-01

    Oral tolerance is dependent on the complex architecture of the mucosal system of the gastrointestinal tract, its associated lymphoid tissue, and specialized immune cells. Changes in this architecture or the failure of any of its components may hinder the generation of oral tolerance. The larynx and esophagus are the gateway to the gastrointestinal tract, serving as the site of oral antigen introduction to the immune system and may have an important role in establishing tolerance. Intragastric gavage is a common method for precise oral dosing of rodents, particularly in studies examining oral tolerance. However, complications such as esophageal trauma can occur and induce complicating factors that affect experimental outcomes. In this study, we examined the esophageal epithelium for alterations resulting from long-term repeated daily use of intragrastric gavage and its effect on the induction of tolerance. Tolerance to ovalbumin could not be achieved after using intragastric gavage for 14 d or more consecutively to introduce ovalbumin. However, tolerance was achieved when intragastric gavage was used for shorter durations. After 14 d of gavage, disruption of the esophageal mucosal epithelium indicative of an inflammatory pathology, cellular influx into the esophageal tissue, and proinflammatory cytokines in the tissue were absent, and the CD3(+) cell population in the esophageal epithelium decreased. These findings provide initial evidence for the important roles of esophageal integrity and cellular populations in the induction of oral tolerance and suggest possible immunologic sequelae in experiments involving the use of extended, repeated gavage.

  3. Listeria monocytogenes strains encoding premature stop codons in inlA invade mice and guinea pig fetuses in orally dosed dams.

    Science.gov (United States)

    Holch, Anne; Ingmer, Hanne; Licht, Tine Rask; Gram, Lone

    2013-12-01

    Listeria monocytogenes is an important food-borne bacterial pathogen and listeriosis can result in abortions in pregnant women. The bacterium can colonize food-processing environments, where specific molecular subtypes can persist for years. The purpose of this study was to determine the virulence potential of a group of food-processing persistent L. monocytogenes strains encoding a premature stop codon in inlA (encoding internalin A) by using two orally dosed models, pregnant mice and pregnant guinea pigs. A food-processing persistent strain of L. monocytogenes invaded placentas (n = 58; 10 % positive) and fetuses (3 % positive) of pregnant mice (n = 9 animals per strain), similar to a genetically manipulated murinized strain, EGD-e InlA(m*) (n = 61; 3 and 2 %, respectively). In pregnant guinea pigs (n = 9 animals per bacterial strain), a maternofetal strain (from a human fetal clinical fatal case) was isolated from 34 % of placenta samples (n = 50), whereas both food-processing persistent strains were found in 5 % of placenta samples (n = 36 or 37). One of the food-processing persistent strains, N53-1, was found in up to 8 % of guinea pig fetal liver and brain samples, whereas the maternofetal control was found in 6 % of fetal tissue samples. As the food-processing persistent strains carry a premature stop codon in inlA but are invasive in orally dosed pregnant mice and guinea pigs, we hypothesize that listerial crossing of the placental barrier can occur by a mechanism that is independent of an interaction between E-cadherin and InlA.

  4. Oral Administration of Resveratrol Alleviates Osteoarthritis Pathology in C57BL/6J Mice Model Induced by a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Mengqi Jiang

    2017-01-01

    Full Text Available Obesity has been associated with osteoarthritis (OA due to increased mass and metabolic factors which are independent of the biomechanical contribution to joint load. Resveratrol, a natural polyphenolic compound, exerts protective effects on OA through its anti-inflammatory property. However, the mechanism of resveratrol on obesity-related OA is unclear. To investigate the effect and possible mechanism of oral resveratrol on obesity-related OA, we fed C57BL/6J mice with a high-fat diet (HFD for 16 weeks to establish obesity-related OA model; then two doses (22.5 mg/kg and 45 mg/kg of resveratrol were given by gavage for additional 12 weeks. Mice with HFD significantly increased body weights compared to the control mice, while resveratrol treatment did not cause obvious weight loss. Histological assessments showed that resveratrol at 45 mg/kg significantly improved OA symptoms. Levels of serum IL-1β and leptin were decreased by resveratrol treatment and positively correlated with Mankin scores. Moreover, resveratrol significantly inhibited the expression of TLR4 and TRAF6 in cartilage. These results suggest that HFD induced obesity can lead to the occurrence of OA, and resveratrol may alleviate OA pathology by decreasing the levels of systematic inflammation and/or inhibiting TLR4 signaling pathway in cartilage. Thus, resveratrol might be a promising therapeutic treatment for obesity-related OA.

  5. DNA damage in normal and choline deficient male B6C3F1 mice treated by oral gavage with fly ash

    Energy Technology Data Exchange (ETDEWEB)

    Andrews, P.W.; Tice, R.R.; Schmitt, M.T. [Integrated Laboratory Systems, Research Triangle Park , NC (United States); Yager, J.W. [Electric Power Research Institute, Palo Alto, CA (United States)

    1994-12-31

    This study evaluated the ability of fly ash containing 199 mg/kg total arsenic to induce DNA damage in tissues of male B6C3F1 mice maintained on a choline sufficient (CS) or a choline deficient (CD) diet. DNA damage was assessed using the Single Cell Gel (SCG) assay in cells sampled from the blood, bladder, liver, lung, and skin; and micronuclei (MN) induction in bone marrow polychromatic erythrocytes (PCE). Sodium arsenite was given by oral gavage in water once or on 4 consecutive days at doses of 12.5, 25.0, and 50.0 mg/kg. Cell samples were collected at 3, 6, 24 and 48 hrs after the single treatment and at 4 hrs after the last of 4 treatments. In addition, urine was collected at 24, 48, and 72 hours after treatment to evaluate arsenic excretion kinetics. A significant depression in DNA migration (indicative of DNA crosslinking) was detected in blood cells of both CS and CD mice, and in bladder and liver cells of CS mice. Levels of MN-PCE or %PCE were not affected by a single treatment with fly ash. These preliminary data demonstrate indicate that fly ash may exhibit in vivo genotoxicity and the ability of hepatic methylation status to modulate the pattern and magnitude of the response.

  6. Use of radioactively labelled bacteria in animal experiments. 5. Fate of radioactively labelled Pasteurella multocida germs, following oral administration to mice

    Energy Technology Data Exchange (ETDEWEB)

    Flossmann, K.D.; Mueller, G.; Heilmann, P. (Akademie der Landwirtschaftswissenschaften der DDR, Jena. Inst. fuer Bakterielle Tierseuchenforschung)

    1981-09-01

    5-/sup 3/H- or 6-/sup 14/C-orotic acid labelled Pasteurella multocida were orally administered, as live or inactivated vaccine, to mice. They were soon discharged through the digestive tract but also led to growing activity in the blood, liver, spleen, and lungs. Using germs with /sup 3/H-1-D mannose-labelled cellular surface have shown that parts of the bacterial cells were easily detached and distributed through the organism, after oral, subcutaneous as well as intratracheal application. Hence, the conclusion seems to be justified that oral administration of Pasteurella multocida cells leads to resorption of bacterial cell fragments which then will readily penetrate the circulatory system, while many of these cells will soon be eliminated from the organism, largely through the digestive tract. Such elimination was found to follow an e function, and it was observed also after intratracheal and subcutaneous application, resp. Some bacteria remained in the digestive tract over a prolonged period (14 days verified). The results are discussed with regard to their possible importance to the immunological development.

  7. A murine oral model for Mycobacterium avium subsp. paratuberculosis infection and immunomodulation with Lactobacillus casei ATCC 334

    Science.gov (United States)

    Cooney, Meagan A.; Steele, James L.; Steinberg, Howard; Talaat, Adel M.

    2014-01-01

    Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) the causative agent of Johne's disease, is one of the most serious infectious diseases in dairy cattle worldwide. Due to the chronic nature of this disease and no feasible control strategy, it is essential to have an efficient animal model which is representative of the natural route of infection as well as a viable treatment option. In this report, we evaluated the effect of different doses of M. paratuberculosis in their ability to colonize murine tissues following oral delivery and the ability of Lactobacillus casei ATCC 334, a nascent probiotic, to combat paratuberculosis. Oral inoculation of mice was able to establish paratuberculosis in a dose-dependent manner. Two consecutive doses of approximately 109 CFU per mouse resulted in a disseminated infection, whereas lower doses were not efficient to establish infection. All inoculated mice were colonized with M. paratuberculosis, maintained infection for up to 24 weeks post infection and generated immune responses that reflect M. paratuberculosis infection in cattle. Notably, oral administration of L. casei ATCC 334 did not reduce the level of M. paratuberculosis colonization in treated animals. Interestingly, cytokine responses and histology indicated a trend for the immunomodulation and reduction of pathology in animals receiving L. casei ATCC 334 treatment. Overall, a reproducible oral model of paratuberculosis in mice was established that could be used for future vaccine experiments. Although the L. casei ATCC 334 was not a promising candidate for controlling paratuberculosis, we established a protocol to screen other probiotic candidates. PMID:24551602

  8. Oral administration of heat-killed Mycobacterium manresensis delays progression towards active tuberculosis in C3HeB/FeJ mice

    Directory of Open Access Journals (Sweden)

    Paula eCardona

    2016-01-01

    Full Text Available Low-dose tolerance using heat-killed mycobacteria has been tested as a means of stopping progression towards active tuberculosis (TB lesions in a human-like murine model using C3HeB/FeJ mice. In the present study, we studied the effect of different treatment schedules with heat-killed non-tuberculous-mycobacteria (NTM species when given orally, based on the hypothesis of generating oral tolerance. This study included M. manresensis, a new species belonging to the fortuitum group, present in drinking water. Oral treatment with M. manresensis for two weeks was able to induce a PPD-specific Tregs population, which has been related to a decrease in the neutrophilic infiltration found in TB lesions. Further mechanistic analysis using PPD-stimulated splenocytes links this two-week treatment with heat-killed M. manresensis to IL-10 production and memory PPD-specific Tregs, and also to a weak PPD-specific global immune response stimulation, increasing IL-6, TNF and IFN-γ production. In lungs, this treatment decreased the bacillary load, granulomatous infiltration and pro-inflammatory cytokines (TNF, IFN-γ, IL-6 and IL-17. Oral administration of M. manresensis during standard treatment for TB also significantly reduced the relapse of active TB after ending the treatment. Overall the data suggest that the use of heat-killed M. manresensis could be a new and promising tool for avoiding active TB induction and as adjunctive to TB treatment. This supports the usefulness of generating a new kind of protection based on a complex balanced immune response focused on both destroying the bacilli and including control of an excessive inflammatory response.

  9. Oral delivery of the Sj23LHD-GST antigen by Salmonella typhimurium type III secretion system protects against Schistosoma japonicum infection in mice.

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    Guo Chen

    2011-09-01

    Full Text Available BACKGROUND: Schistosomiasis japonica is a zoonotic parasitic disease and oral vaccine delivery system would be benefit for prevention of this disease. Although attenuated salmonella has been used as an antigen expression vector for oral vaccine development, the membrane-bound vacuoles in which bacteria reside hinders the presentation of expressed heterologous antigens to the major histocompatibility complex (MHC molecules. The present work used an attenuated Salmonella typhimurium strain VNP20009 to secretory expression of Sj23LHDGST bivalent antigen from Schistosoma japonicum and tested the protective efficacy against S. japonicum infection in orally immunized mice. METHODOLOGY/PRINCIPAL FINDINGS: Promoters (nirB or pagC were used to express the antigen (Sj23LHDGST and the Salmonella type III or α-hemolysin secretion system was employed to secrete it. The immunoblotting analysis and fluorescent microscopy revealed that the antigen was effectively expressed and delivered to the cytosol of macrophages in vitro. Among recombinant vaccine strains, an engineered VNP20009 which expressed the antigen by nirB promoter and secreted it through type III secretion system (nirB-sopE(1-104-Sj23LHD-GST efficiently protected against S. japonicum infection in a mouse model. This strain elicited a predominantly IgG(2a antibody response and a markedly increase in the production of IL-12 and IFN-γ. The flow cytometric analysis demonstrated that this strain caused T cell activation as evidenced by significantly increased expression of CD44 and CD69. CONCLUSION/SIGNIFICANCE: Oral delivery of antigen by nirB-driven Salmonella typhimurium type III secretion system is a novel, safe, inexpensive, efficient and convenient approach for schistosome vaccine development.

  10. Inoculation of sugarcane with diazotrophic bacteria

    Directory of Open Access Journals (Sweden)

    Nivaldo Schultz

    2014-04-01

    Full Text Available The sugarcane industry, a strategic crop in Brazil, requires technological improvements in production efficiency to increase the crop energy balance. Among the various currently studied alternatives, inoculation with diazotrophic bacteria proved to be a technology with great potential. In this context, the efficiency of a mixture of bacterial inoculant was evaluated with regard to the agronomic performance and N nutrition of sugarcane. The experiment was carried out on an experimental field of Embrapa Agrobiologia, in Seropédica, Rio de Janeiro, using a randomized block, 2 × 3 factorial design (two varieties and three treatments with four replications, totaling 24 plots. The varieties RB867515 and RB72454 were tested in treatments consisting of: inoculation with diazotrophic bacteria, N-fertilized control with 120 kg ha-1 N and absolute control (no inoculation and no N fertilizer. The inoculum was composed of five strains of five diazotrophic species. The yield, dry matter accumulation, total N in the shoot dry matter and the contribution of N by biological fixation were evaluated, using the natural 15N abundance in non-inoculated sugarcane as reference. The bacterial inoculant increased the stalk yield of variety RB72454 similarly to fertilization with 120 kg ha-1 N in the harvests of plant-cane and first ratoon crops, however the contribution of biological N fixation was unchanged by inoculation, indicating that the benefits of the inoculant in sugarcane may have resulted from plant growth promotion.

  11. Comparison of artificial inoculation methods for studying ...

    African Journals Online (AJOL)

    Establishment of disease by artificial inoculation is essential for studies of various aspects of plant pathology. Keeping this in mind, five inoculation methods were compared namely spraying, infiltration, wounding, spore suspension drop and spore suspension drop along with agarose method. The findings of the present ...

  12. Developing microbial inoculants for native Hawaiian trees

    Science.gov (United States)

    Kim H. Wilkinson

    2002-01-01

    We use certain microbial inoculants in the nursery as a part of supporting the objectives of accelerating rehabilitation of degraded land and ecosystem function, as well as reducing costs in establishment and maintenance of forest plantings. Microbial inoculants re-create natural partnerships between plants and some of the beneficial microorganisms that support plants...

  13. Analysis of the Toxicity and Histopathology Induced by the Oral Administration of Pseudanabaena galeata and Geitlerinema splendidum (Cyanobacteria) Extracts to Mice

    Science.gov (United States)

    Rangel, Marisa; Martins, Joyce C. G.; Garcia, Angélica Nunes; Conserva, Geanne A. A.; Costa-Neves, Adriana; Sant’Anna, Célia Leite; de Carvalho, Luciana Retz

    2014-01-01

    Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs in Sao Paulo, which is the most densely populated area in Brazil. In the search for toxic strains collected from water reservoirs and maintained in the Cyanobacterial Culture Collection (CCIBt) of the Institute of Botany of Brazil, the acetic acid extracts (AE) of P. galeata CCIBt 3082 and G. splendidum CCIBt 3223 were analyzed by planar chromatography, which indicated the absence of cyanotoxins. Animal tests were then carried out, and both extracts were found to induce toxic effects in mice when administered intraperitoneally. The present study aimed to investigate whether the oral ingestion of the above mentioned cyanobacteria extracts would also induce toxic effects in mice. Necropsy and histopathological studies were conducted using tissue samples from the animals, which were euthanized one week after the administration of the extracts. The AE of P. galeata did not cause death but did induce transient symptoms, including eyebrow ptosis, straub tail, and pain. The euthanized animals presented hemorrhage in the liver, whereas the histological analysis showed disorganization of the hepatic parenchyma, necrosis, hyperemia, and proximity of the centrilobular vein in the liver. In addition, alterations in the convoluted tubules of the kidneys were observed, and the lungs were unaffected. The AE of G. splendidum caused only one death, and induced transient symptoms, such as dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic focuses, alveolar collapse, and granulomatous foci. The liver presented hemorrhagic and enlarged sinusoids, hyperemia, proximity of the

  14. Analysis of the Toxicity and Histopathology Induced by the Oral Administration of Pseudanabaena galeata and Geitlerinema splendidum (Cyanobacteria Extracts to Mice

    Directory of Open Access Journals (Sweden)

    Marisa Rangel

    2014-01-01

    Full Text Available Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs in Sao Paulo, which is the most densely populated area in Brazil. In the search for toxic strains collected from water reservoirs and maintained in the Cyanobacterial Culture Collection (CCIBt of the Institute of Botany of Brazil, the acetic acid extracts (AE of P. galeata CCIBt 3082 and G. splendidum CCIBt 3223 were analyzed by planar chromatography, which indicated the absence of cyanotoxins. Animal tests were then carried out, and both extracts were found to induce toxic effects in mice when administered intraperitoneally. The present study aimed to investigate whether the oral ingestion of the above mentioned cyanobacteria extracts would also induce toxic effects in mice. Necropsy and histopathological studies were conducted using tissue samples from the animals, which were euthanized one week after the administration of the extracts. The AE of P. galeata did not cause death but did induce transient symptoms, including eyebrow ptosis, straub tail, and pain. The euthanized animals presented hemorrhage in the liver, whereas the histological analysis showed disorganization of the hepatic parenchyma, necrosis, hyperemia, and proximity of the centrilobular vein in the liver. In addition, alterations in the convoluted tubules of the kidneys were observed, and the lungs were unaffected. The AE of G. splendidum caused only one death, and induced transient symptoms, such as dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic focuses, alveolar collapse, and granulomatous foci. The liver presented hemorrhagic and enlarged sinusoids, hyperemia

  15. Oral treatment with herbal formula B307 alleviates cardiac failure in aging R6/2 mice with Huntington’s disease via suppressing oxidative stress, inflammation, and apoptosis

    Directory of Open Access Journals (Sweden)

    Lin CL

    2015-07-01

    Full Text Available Ching-Lung Lin,1 Sheue-Er Wang,2 Chih-Hsiang Hsu,1 Shuenn-Jyi Sheu,3 Chung-Hsin Wu1 1Department of Life Science, National Taiwan Normal University, Taipei, 2Department of Pathological Inspection, Soeurs de Saint Paul de Chartres Medical Corporate Body, Taoyuan City, 3Brion Research Institute of Taiwan, New Taipei City, Taiwan Abstract: Cardiac failure is often observed in aging patients with Huntington’s disease (HD. However, conventional pharmacological treatments for cardiac failure in HD patients have rarely been studied. Chinese herbal medicines, especially combined herbal formulas, have been widely used to treat cardiac dysfunctions over the centuries. Thus, we assess whether oral treatment with herbal formula B307 can alleviate cardiac failure in transgenic mice with HD. After oral B307 or vehicle treatment for 2 weeks, cardiac function and cardiomyocytes in 12-week-old male R6/2 HD mice and their wild-type littermate controls (WT were examined and then compared via echocardiography, immunohistochemistry, and Western blotting. We found that cardiac performance in aging R6/2 HD mice had significantly deteriorated in comparison with their WT (P<0.01. Cardiac expressions of superoxide dismutase 2 (SOD2 and B-cell lymphoma 2 (Bcl-2 in aging R6/2 HD mice were significantly lower than their WT (P<0.01, but cardiac expressions of tumor necrosis factor alpha (TNF-α, neurotrophin-3 (3-NT, 4-hydroxynonenal (4-HNE, Bcl-2-associated X protein (Bax, calpain, caspase 12, caspase 9, and caspase 3 of aging R6/2 HD mice were significantly higher than their WT (P<0.05. Furthermore, we found that cardiac performance in aging R6/2 HD mice had significantly improved under oral B307 treatment (P<0.05. Cardiac expressions of SOD2 and Bcl-2 of aging R6/2 HD mice were significantly higher under oral B307 treatment (P<0.01, but cardiac expressions of TNF-α, 3-NT, 4-HNE, Bax, calpain, caspase 12, caspase 9, and caspase 3 of aging R6/2 HD mice were significantly

  16. Estrogenicity of food-associated estrogenic compounds in the fetuses of female transgenic mice upon oral and IP maternal exposure

    NARCIS (Netherlands)

    Veld, ter M.G.R.; Zawadzka, E.; Rietjens, I.M.C.M.; Murk, A.J.

    2009-01-01

    The present study investigated to what extent seven food-associated in vitro estrogenic compounds can induce estrogenic effects in the fetuses of pregnant female mice with an estrogen receptor (ER)-mediated luciferase (luc) reporter gene system. The luc-induction was determined either 8 h after

  17. Oral Administration of Heat-Killed Lactobacillus gasseri OLL2809 Reduces Cedar Pollen Antigen-Induced Peritoneal Eosinophilia in Mice

    Directory of Open Access Journals (Sweden)

    Toshihiro Sashihara

    2008-01-01

    Conclusions: We demonstrated that the oral administration of heat-killed L. gasseri OLL2809 suppresses eosinophilia via the modulation of Th1/Th2 balance. These observations suggested that heat-killed L. gasseri OLL2809 might potentially ameliorate the increased number of eosinophils in patients with Japanese cedar pollinosis.

  18. An investigation into the susceptibility of cattle to bovine leukosis virus following inoculation by various routes.

    Science.gov (United States)

    Roberts, D H; Lucas, M H; Wibberley, G; Chasey, D

    1982-03-06

    The effect of different routes of inoculation on the incubation period, as indicated by the detection of antibody and by the detection of bovine leukosis virus (BLV) in lymphocytes, were compared. None of the 12-month-old steers exposed to BLV by the oral route developed BLV infection. Intratracheal, subcutaneous and intradermal inoculations were found to be particularly effective in establishing BLV infection, which was detected three to four weeks after inoculation. In the majority of animals, serum antibody and virus were detected at the same time. One out of four in-oestrus heifers inoculated via the uterus with mixtures of BLV infected lymphocytes and semen became infected. It appears that there is an inhibitory factor in fresh semen that prevents BLV infection from becoming established. Viral antigen was detected earlier in BLV infected lymphocytes using the cocultivation method than by electron microscopy to demonstrate BLV particles in mitogen stimulated lymphocytes.

  19. Development of a Novel Embedded Relay Lens Microscopic Hyperspectral Imaging System for Cancer Diagnosis: Use of the Mice with Oral Cancer to Be the Example

    Directory of Open Access Journals (Sweden)

    Yao-Fang Hsieh

    2012-01-01

    the fluorescence of cells or tissue can provide the characteristic signature for identification of normal and abnormal. In this work, the development of the ERL-MHSI system is discussed and the capability of the system is demonstrated by diagnosing early stage oral cancer of twenty mice in vitro. The best sensitivity for identifying normal cells and squamous cell carcinoma (SCC was 100%. The best specificity for identifying normal cells and SCC was 99%. The best sensitivity for identifying normal cells and dysplasia was 99%. The best specificity for identifying normal cells and dysplasia was 97%. This work also utilizes fractal dimension to analyze the morphological information and find the significant different values between normal and SCC.

  20. Improved physiologically based pharmacokinetic model for oral exposures to chromium in mice, rats, and humans to address temporal variation and sensitive populations.

    Science.gov (United States)

    Kirman, C R; Suh, M; Proctor, D M; Hays, S M

    2017-06-15

    A physiologically based pharmacokinetic (PBPK) model for hexavalent chromium [Cr(VI)] in mice, rats, and humans developed previously (Kirman et al., 2012, 2013), was updated to reflect an improved understanding of the toxicokinetics of the gastrointestinal tract following oral exposures. Improvements were made to: (1) the reduction model, which describes the pH-dependent reduction of Cr(VI) to Cr(III) in the gastrointestinal tract under both fasted and fed states; (2) drinking water pattern simulations, to better describe dosimetry in rodents under the conditions of the NTP cancer bioassay; and (3) parameterize the model to characterize potentially sensitive human populations. Important species differences, sources of non-linear toxicokinetics, and human variation are identified and discussed within the context of human health risk assessment. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Serum pharmacokinetics of choline, trimethylamine, and trimethylamine-N-oxide after oral gavage of phosphatidylcholines with different fatty acid compositions in mice.

    Science.gov (United States)

    Gao, Xiang; Jiang, Chengzi; Xu, Jie; Yanagita, Teruyoshi; Xue, Changhu; Wang, Yuming

    2016-07-13

    Little is known about the pharmacokinetics of phosphatidylcholine (PC)-derived choline, trimethylamine (TMA), and trimethylamine-N-oxide (TMAO). We therefore aim to investigate serum choline, TMA, and TMAO pharmacokinetics following different PCs gavage and compare the difference between PC emulsions and liposomes (SOL). Serum choline, TMA, and TMAO levels were measured after orally gavaged egg yolk PC emulsion (EGE), squid PC emulsion (SQE), soybean PC emulsion (SOE), and SOL in fasted mice. Time to reach peak concentration (Tmax) and productions for TMA and TMAO were more slow and less in SQE group compared with EGE and SOE groups. Tmax for choline, TMA, and TMAO prolonged, and the productions of them were significantly declined in SOL group compared to SOE group. These findings indicated that marine source squid PC could counter-regulate the potential risks of TMAO generation, and the use of liposome as the form of PC supplementary may eliminate TMAO production.

  2. Oral Combination Vaccine, Comprising Bifidobacterium Displaying Hepatitis C Virus Nonstructural Protein 3 and Interferon-α, Induces Strong Cellular Immunity Specific to Nonstructural Protein 3 in Mice.

    Science.gov (United States)

    Kitagawa, Koichi; Omoto, Chika; Oda, Tsugumi; Araki, Ayame; Saito, Hiroki; Shigemura, Katsumi; Katayama, Takane; Hotta, Hak; Shirakawa, Toshiro

    2017-04-01

    We previously generated an oral hepatitis C virus (HCV) vaccine using Bifidobacterium displaying the HCV nonstructural protein 3 (NS3) polypeptide. NS3-specific cellular immunity is important for viral clearance and recovery from HCV infection. In this study, we enhanced the cellular immune responses induced by our oral HCV vaccine, Bifidobacterium longum 2165 (B. longum 2165), by combining interferon-α (IFN-α) as an adjuvant with the vaccine in a mouse experimental model. IFN-α is a widely used cytokine meeting the standard of care (SOC) for HCV infection and plays various immunoregulatory roles. We treated C57BL/6N mice with B. longum 2165 every other day and/or IFN-α twice a week for a month and then analyzed the immune responses using spleen cells. We determined the induction of NS3-specific cellular immunity by cytokine quantification, intracellular cytokine staining, and a cytotoxic T lymphocyte (CTL) assay targeting EL4 tumor cells expressing NS3/4A protein (EL4-NS3/4A). We also treated mice bearing EL4-NS3/4A tumor with the combination therapy in vivo. The results confirmed that the combination therapy of B. longum 2165 and IFN-α induced significantly higher IFN-γ secretion, higher population of CD4(+)T and CD8(+)T cells secreting IFN-γ, and higher CTL activity against EL4-NS3/4A cells compared with the control groups of phosphate-buffered saline, B. longum 2165 alone, and IFN-α alone (p < 0.05). We also confirmed that the combination therapy strongly enhanced tumor growth inhibitory effects in vivo with no serious adverse effects (p < 0.05). These results suggest that the combination of B. longum 2165 and IFN-α could induce a strong cellular immunity specific to NS3 protein as a combination therapy augmenting the current SOC immunotherapy against chronic HCV infection.

  3. The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery.

    Science.gov (United States)

    Ma, Yiming; Fuchs, Adrian V; Boase, Nathan R B; Rolfe, Barbara E; Coombes, Allan G A; Thurecht, Kristofer J

    2015-08-01

    Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan-hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8h to 24h post-administration compared to the free NPs, due to a NP 'guarding' effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Pharmacokinetic profile of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside in mice after oral administration of Polygonum multiflorum extract.

    Science.gov (United States)

    Lv, Guiyuan; Gu, Hui; Chen, Suhong; Lou, Zhaohuan; Shan, Letian

    2012-02-01

    Stilbene glycoside (2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside) is a main bioactive component of Polygonum multiflorum, a traditional Chinese medicine (TCM) commonly used in clinic for anti-aging treatment. Its medicinal activities, such as anti-oxidation, anti-inflammation and endothelial protection, have been extensively studied, but its pharmacokinetic property is still unclear. A pharmacokinetic study was undertaken to quantitatively determine P. multiflorum stilbene glycoside (PM-SG) in mouse plasma after oral administration of 100 mg/kg P. multiflorum extract. A sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) coupled with liquid-liquid phase extraction method was employed for this study. Pharmacokinetic parameters of PM-SG were determined in mice applying both compartmental and non-compartmental analyses. The calibration curve for PM-SG in the plasma was linear (r(2) > 0.99) over the range of 0.66 to 56.40 μg/ml, and the concentration-time curve was plotted with the maximum concentration (C(max)) and time to reach maximum concentration (T(max)) of 29.62 μg/ml and 60 min, respectively. The intra- and inter-day variations were less than 3% for relative standard deviation (RSD) and relative error (RE), with a good recovery of more than 97% (RSD <3%). All pharmacokinetic parameters estimated by compartmental and non-compartmental models reached a same conclusion that PM-SG was rapidly absorbed and widely distributed throughout the body with a great efficiency of utility, followed by quick elimination and clearance. This was the first report on determination of the pharmacokinetic profile of PM-SG in mice after oral administration. The result may provide a meaningful basis for evaluating the clinical applications of such a bioactive compound from herbal medicines.

  5. Peripherally Applied Aβ-Containing Inoculates Induce Cerebral β-Amyloidosis

    Science.gov (United States)

    Eisele, Yvonne S.; Obermüller, Ulrike; Heilbronner, Götz; Baumann, Frank; Kaeser, Stephan A.; Wolburg, Hartwig; Walker, Lary C.; Staufenbiel, Matthias; Heikenwalder, Mathias; Jucker, Mathias

    2011-01-01

    The intracerebral injection of β-amyloid-containing brain extracts can induce cerebralβ-amyloidosis and associated pathologies in susceptible hosts. We found that intraperitoneal inoculation with β-amyloid-rich extracts inducesβ-amyloidosis in the brains of β-amyloid precursor protein transgenic mice after prolonged incubation times. PMID:20966215

  6. Broadly protective immunity against divergent influenza viruses by oral co-administration of Lactococcus lactis expressing nucleoprotein adjuvanted with cholera toxin B subunit in mice.

    Science.gov (United States)

    Lei, Han; Peng, Xiaojue; Jiao, Huifeng; Zhao, Daxian; Ouyang, Jiexiu

    2015-08-05

    adjuvanted with CTB as controls. Mice that received L. lactis/pNZ8008-NP adjuvanted with CTB were completely protected from homologous H1N1 virus and showed 80% protection against heterologous H3N2 or H5N1 virus, respectively. By contrast, L. lactis/pNZ8110-pgsA-HA1 adjuvanted with CTB also conferred 100% protection against H5N1 virus infection, but indicated no cross-protection against H1N1 or H5N1 virus challenge. As controls, mice vaccinated orally with L. lactis/pNZ8008-NP alone or L. lactis/pNZ8110-pgsA-HA1 alone could not survive. This study is the first to report the construction of recombinant L. lactis/pNZ8008-NP and investigate its immunogenicity with the use of CTB. Compared with L. lactis/pNZ8110-pgsA-HA1 adjuvanted with CTB, our data support 5 × 10(11) CFU of L. lactis/pNZ8008-NP adjuvanted with 1 µg of CTB is a better combination for universal influenza vaccines development that would provide cross-protective immunity against divergent influenza A viruses.

  7. Orally Administered Baker's Yeast β-Glucan Promotes Glucose and Lipid Homeostasis in the Livers of Obesity and Diabetes Model Mice.

    Science.gov (United States)

    Cao, Yan; Sun, Ying; Zou, Siwei; Li, Mengxia; Xu, Xiaojuan

    2017-11-08

    Baker's yeast glucan (BYG) has been reported to be an anti-diabetic agent. In the work described herein, further study on the effect of orally administered BYG on glucose and lipid homeostasis in the livers of ob/ob mice was performed. It was found that BYG decreased the blood glucose and the hepatic glucose and lipid disorders. Western blotting analysis revealed that BYG up-regulated p-AKT and p-AMPK, and down-regulated p-Acc in the liver. Furthermore, RNA-Seq analysis indicated that BYG down-regulated genes responsible for gluconeogenesis (G6pase and Got1), fatty acid biosynthesis (Acly, Acc, Fas, etc.), glycerolipid synthesis (Gpam and Lipin1/2), and cholesterol synthesis (Hmgcr, Fdps, etc.). Additionally, BYG decreased glucose transporters SGLT1 and GLUT2, fat emulsification, and adipogenic genes/proteins in the intestine to decrease glucose and lipid absorption. All these findings demonstrated that BYG is beneficial for regulating glucose and lipid homeostasis in diabetic mice, and thus has potential applications in anti-diabetic foods or drugs.

  8. Oral administration of apple condensed tannins delays rheumatoid arthritis development in mice via downregulation of T helper 17 (Th17) cell responses.

    Science.gov (United States)

    Nakamura, Kosuke; Matsuoka, Hideki; Nakashima, Syohei; Kanda, Tomomasa; Nishimaki-Mogami, Tomoko; Akiyama, Hiroshi

    2015-07-01

    Apples are known to contain high concentrations of phenolic compounds such as condensed tannins. Consumption of condensed tannins has been reported to reduce the risk of many types of chronic diseases including allergies. However, their therapeutic effectiveness and potential in treating autoimmune disease remain controversial. Here, the effect of oral administration of apple condensed tannins (ACT) prepared from apples (Malus pumila cv. Fuji) on bovine type II collagen (CII)-induced arthritis in DBA1/J mice, a well-established murine model of human rheumatoid arthritis (RA), was evaluated. As compared to the control (without ACT administration) group, RA development was delayed and a significant reduction in the RA clinical score was observed in the ACT-administered group. Using cultured splenocytes isolated from CII-immunized mice, ACT-administration was shown to decrease the CII-induced increases in IL-17 expression and production in vitro. We propose that downregulation of T helper (Th) 17 cells is responsible for the ACT-induced RA suppression. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. High-yield production of recombinant virus-like particles of enterovirus 71 in Pichia pastoris and their protective efficacy against oral viral challenge in mice.

    Science.gov (United States)

    Zhang, Chao; Ku, Zhiqiang; Liu, Qingwei; Wang, Xiaoli; Chen, Tan; Ye, Xiaohua; Li, Dapeng; Jin, Xia; Huang, Zhong

    2015-05-11

    Enterovirus 71 (EV71) is one of the major causative pathogens of hand, foot and mouth disease (HFMD), which is highly prevalent in the Asia-Pacific regions. Severe HFMD cases with neurological complications and even death are often associated with EV71 infections. However, no licensed EV71 vaccine is currently available. Recombinant virus-like particles (VLPs) of EV71 have been produced and shown to be a promising vaccine candidate in preclinical studies. However, the performance of current recombinant expression systems for EV71 VLP production remains unsatisfactory with regard to VLP yield and manufacturing procedure, and thus hinders further product development. In this study, we evaluated the expression of EV71 VLPs in Pichia pastoris and determined their protective efficacy in mouse models of EV71 infections. We showed that EV71 VLPs could be produced at high levels up to 4.9% of total soluble protein in transgenic P. pastoris yeast co-expressing P1 and 3CD proteins of EV71. The resulting yeast-produced VLPs potently induced neutralizing antibodies against homologous and heterologous EV71 strains in mice. More importantly, maternal immunization with VLPs protected neonatal mice in both intraperitoneal and oral challenge experiments. Collectively, these results demonstrated the success of simple, high-yield production of EV71 VLPs in transgenic P. pastoris, thus lifting the major roadblock in commercial development of VLP-based EV71 vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Oral administration of Euglena gracilis Z and its carbohydrate storage substance provides survival protection against influenza virus infection in mice.

    Science.gov (United States)

    Nakashima, Ayaka; Suzuki, Kengo; Asayama, Yuta; Konno, Makoto; Saito, Keita; Yamazaki, Noriyuki; Takimoto, Hiroaki

    2017-12-09

    Euglena gracilis Z is a micro-algae that is used as a food or nutritional supplement. Paramylon, the carbohydrate storage substance of Euglena gracilis Z has β-1, 3-glucan structure. Euglena gracilis Z and paramylon are reported to affect the immune system. In this study, we investigated the protective effects of Euglena gracilis Z and paramylon against influenza virus infection in mice. Euglena gracilis Z and paramylon were administered to mice as a 2% dietary mixture ad libitum. At 2 weeks after initiation of dietary administration, mice were infected intranasally with influenza virus A/PR/8/34 (H1N1). Survival rate was monitored 10 days after infection. In addition, we performed virus titer and cytokine profiles in the lung. High survival rates were observed for Euglena gracilis Z and paramylon-treated groups compared to the control group. Significantly lower virus titer in the lung was observed in the Euglena gracilis Z and paramylon-treated groups compared to the control group from day 1 after infection. Higher amount of IL-1β, IL-6, IL-12 (p70), IFN-γ, and IL-10 was observed in the paramylon groups compared to the control group. Our data therefore reveals a novel immunoregulatory role of the Euglena gracilis Z and paramylon which provides protection against influenza virus infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Tumorigenicity and Validity of Fluorescence Labelled Mesenchymal and Epithelial Human Oral Cancer Cell Lines in Nude Mice

    Directory of Open Access Journals (Sweden)

    Wei Xin Cai

    2016-01-01

    Full Text Available Tumorigenicity and metastatic activity can be visually monitored in cancer cells that were labelled with stable fluorescence. The aim was to establish and validate local and distant spread of subcutaneously previously injected fluorescence transduced human tongue cancer cell lines of epithelial and mesenchymal phenotype in nude mice. A total of 32 four-week-old male athymic Balb/c nude mice were randomly allocated into 4 groups (n=8. A single dose of 0.3 mL PBS containing 1 × 107 of four different cancer cell-lines (UM1, UM1-GFP, UM2, and UM2-RFP was injected subcutaneously into the right side of their posterolateral back. Validity assessment of the labelled cancer cells’ tumorigenicity was assessed by physical examination, imaging, and histology four weeks after the injection. The tumor take rate of cancer cells was similar in animals injected with either parental or transduced cancer cells. Transduced cancer cells in mice were easily detectable in vivo and after cryosection using fluorescent imaging. UM1 cells showed increased tumor take rate and mean tumor volume, presenting with disorganized histopathological patterns. Fluorescence labelled epithelial and mesenchymal human tongue cancer cell lines do not change in tumorigenicity or cell phenotype after injection in vivo.

  12. Oral administration of a probiotic Lactobacillus modulates cytokine production and TLR expression improving the immune response against Salmonella enterica serovar Typhimurium infection in mice

    Directory of Open Access Journals (Sweden)

    Perdigón Gabriela

    2011-08-01

    Full Text Available Abstract Background Diarrheal infections caused by Salmonella, are one of the major causes of childhood morbidity and mortality in developing countries. Salmonella causes various diseases that range from mild gastroenteritis to enteric fever, depending on the serovar involved, infective dose, species, age and immune status of the host. Probiotics are proposed as an attractive alternative possibility in the prevention against this pathogen infection. Previously we demonstrated that continuous Lactobacillus casei CRL 431 administration to BALB/c mice before and after challenge with Salmonella enterica serovar Typhimurium (S. Typhimurium decreased the severity of Salmonella infection. The aim of the present work was to deep into the knowledge about how this probiotic bacterium exerts its effect, by assessing its impact on the expression and secretion of pro-inflammatory (TNFα, IFNγ and anti-inflammatory (IL-10 cytokines in the inductor and effector sites of the gut immune response, and analyzing toll-like receptor (TLR2, TLR4, TLR5 and TLR9 expressions in both healthy and infected mice. Results Probiotic administration to healthy mice increased the expression of TLR2, TLR4 and TLR9 and improved the production and secretion of TNFα, IFNγ and IL-10 in the inductor sites of the gut immune response (Peyer's patches. Post infection, the continuous probiotic administration, before and after Salmonella challenge, protected the host by modulating the inflammatory response, mainly in the immune effector site of the gut, decreasing TNFα and increasing IFNγ, IL-6 and IL-10 production in the lamina propria of the small intestine. Conclusions The oral administration of L. casei CRL 431 induces variations in the cytokine profile and in the TLRs expression previous and also after the challenge with S. Typhimurium. These changes show some of the immune mechanisms implicated in the protective effect of this probiotic strain against S. Typhimurium, providing

  13. Whole body protection to lethally irradiated mice by oral administration of semipurified fraction of Podophyllum hexandrum and post irradiation treatment of Picrorhiza kurroa.

    Science.gov (United States)

    Gupta, Manju Lata; Sankhwar, Sanghmitra; Verma, Savita; Devi, Memita; Samanta, Namita; Agrawala, Paban Kumar; Kumar, Raj; Singh, Pankaj Kumar

    2008-04-20

    to evaluate the radioprotective potential of alcoholic fraction of Podophyllum hexandrum rhizomes (REC-2001) individually as well as in combination with Picrorhiza kurroa administered orally in lethally irradiated Swiss albino mice. The study was divided into different treatment groups. Whole body survival was observed upto 30 days in all the treatment groups. Besides survival, toxicity of REC-2001 was also evaluated. All the groups were studied for spleen endogenous colony forming units (CFUs), plasma antioxidant potential and hematological variables, using standard techniques. Animals in radiation alone group died with in 12 days of exposure. Single dose of REC-2001 which did not bring any toxic manifestation/mortality (MTD) was found to be 155 mg/kg b.w. On administration of 250 mg/kg b.w. (single dose) 50% of the animals died (LD50), while a dose of 350 mg/kg b.w. of REC-2001 brought 100% death. Oral administration of single dose of REC-2001 (25 mg /kg b.w. -1h) prior to irradiation (10 Gy) was observed rendering up to 48% protection. Survival enhanced to the level of 55% when the animals had pre- treatment of REC-2001 (25 mg /kg b.w. -1h) followed by irradiation (10 Gy) and post treatment with a single dose of Picrorhiza kurroa rhizome extract (pkre, 8 mg/kg b.w.+1h). Radiation induced plasma antioxidant status was significantly (P < 0.02) countered by REC-2001 administration. Post treatment of pkre elevated CFU counts (P < 0.05). Total leukocytes count and hemoglobin content in REC-2001 pretreated and pkre post treated group approached normal limits within 30 days of the study. REC-2001 in combination with pkre holds promise for further studies to achieve radioprotection against lethal radiation by oral administration.

  14. Per-oral immunization with antigen-conjugated nanoparticles followed by sub-cutaneous boosting immunization induces long-lasting mucosal and systemic antibody responses in mice.

    Directory of Open Access Journals (Sweden)

    Savannah E Howe

    Full Text Available Food or water-borne enteric pathogens invade their hosts via intestinal mucosal surfaces, thus developing effective oral vaccines would greatly reduce the burden of infectious diseases. The nature of the antigen, as well as the mode of its internalization in the intestinal mucosa affects the ensuing immune response. We show that model protein antigen ovalbumin (Ova given per-orally (p.o. induces oral tolerance (OT, characterized by systemic IgG1-dominated antibody response, which cannot be boosted by sub-cutaneous (s.c. immunization with Ova in complete Freund's adjuvant (CFA. Intestinal IgA generated in response to Ova feeding diminished over time and was abrogated by s.c. immunization with Ova+CFA. Humoral response to Ova was altered by administering Ova conjugated to 20 nm nanoparticles (NP-Ova. P.o. administration of NP-Ova induced systemic IgG1/IgG2c, and primed the intestinal mucosa for secretion of IgA. These responses were boosted by secondary s.c. immunization with Ova+CFA or p.o. immunization with NP-Ova. However, only in s.c.-boosted mice serum and mucosal antibody titers remained elevated for 6 months after priming. In contrast, s.c. priming with NP-Ova induced IgG1-dominated serum antibodies, but did not prime the intestinal mucosa for secretion of IgA, even after secondary p.o. immunization with NP-Ova. These results indicate that Ova conjugated to NPs reaches the internal milieu in an immunogenic form and that mucosal immunization with NP-Ova is necessary for induction of a polarized Th1/Th2 immune response, as well as intestinal IgA response. In addition, mucosal priming with NP-Ova, followed by s.c. boosting induces superior systemic and mucosal memory responses. These findings are important for the development of efficacious mucosal vaccines.

  15. Hymenolepis nana: immunity against oncosphere challenge in mice previously given viable or non-viable oncospheres of H. nana, H. diminuta, H. microstoma and Taenia taeniaeformis.

    Science.gov (United States)

    Ito, A; Onitake, K; Sasaki, J; Takami, T

    1991-04-01

    When mice, previously given oral inoculation with viable oncospheres of the heterologous cestode species (Hymenolepis diminuta, H. microstoma, Taenia taeniaeformis) and the homologous one (H. nana), were challenged with oncospheres of H. nana 4 days after the primary inoculation, they showed strong and complete resistance to H. nana challenge, respectively. However, the resistance was not evoked in mice given either infective eggs of Toxocara canis or non-viable oncospheres of all cestode species examined. Congenitally athymic nude mice given viable oncospheres did not show any resistance to H. nana either. Eosinophil infiltration around cysticercoids of H. nana in the intestinal villi appeared to be more prominent in mice previously given viable oncospheres of H. diminuta than in mice given non-viable oncospheres or PBS only. Some of the eosinophils in the villus harboring cysticercoid(s) of H. nana invaded the epithelia in the former, whereas all eosinophils remained in the lamina propria in the latter. There was almost no eosinophil infiltration in nude mice. Microscopic observations revealed that oncospheres of H. diminuta, which require beetles as the intermediate host like H. microstoma, could invade the mouse intestinal tissue. Therefore, it is strongly suggested that the strong cross resistance to H. nana in mice, induced by oncospheres of all heterologous cestode species, is thymus-dependent and due to oncospheral invasion into the intestinal tissue of mice.

  16. Klebsiella pneumoniae inoculants for enhancing plant growth

    Science.gov (United States)

    Triplett, Eric W [Middleton, WI; Kaeppler, Shawn M [Oregon, WI; Chelius, Marisa K [Greeley, CO

    2008-07-01

    A biological inoculant for enhancing the growth of plants is disclosed. The inoculant includes the bacterial strains Herbaspirillum seropedicae 2A, Pantoea agglomerans P101, Pantoea agglomerans P102, Klebsiella pneumoniae 342, Klebsiella pneumoniae zmvsy, Herbaspirillum seropedicae Z152, Gluconacetobacter diazotrophicus PA15, with or without a carrier. The inoculant also includes strains of the bacterium Pantoea agglomerans and K. pneumoniae which are able to enhance the growth of cereal grasses. Also disclosed are the novel bacterial strains Herbaspirillum seropedicae 2A, Pantoea agglomerans P101 and P102, and Klebsiella pneumoniae 342 and zmvsy.

  17. Bagaza virus is pathogenic and transmitted by direct contact in experimentally infected partridges, but is not infectious in house sparrows and adult mice.

    Science.gov (United States)

    Llorente, Francisco; Pérez-Ramírez, Elisa; Fernández-Pinero, Jovita; Elizalde, Maia; Figuerola, Jordi; Soriguer, Ramón C; Jiménez-Clavero, Miguel Ángel

    2015-09-04

    Bagaza virus (BAGV) is a mosquito-borne flavivirus belonging to the Ntaya serocomplex. In 2010, a disease outbreak was reported in Cádiz (Southern Spain) affecting game birds (red-legged partridges and common pheasants). In this work, red-legged partridges were inoculated experimentally with infectious BAGV isolated from this outbreak in order to make a complete clinical and analytical assessment of the disease caused by the pathogen in this species. Viral load (by real-time RT-PCR) in blood, oral and cloacal swabs, and feathers, and neutralizing antibody titres (by VNT) were measured. In order to determine direct contact transmission, non-inoculated partridges were caged together with the inoculated ones. To assess infectiousness in other species, house sparrows and mice were also inoculated with the virus. All the inoculated partridges were clinically affected, and 30% of them died. All the infected individuals lost weight, with larger losses being recorded in females. Conversely, no mortality or disease symptoms were observed in the sparrows or mice. Remarkably, all the contact partridges acquired the infection by direct (non-vectored) transmission. This study confirms that the red-legged partridge is a susceptible host for BAGV infection, and that this pathogen is transmitted by direct contact. Long-lasting viral loads detected in calami of immature feathers demonstrate that feather sampling could be a useful strategy in active surveillance programs for early detection of BAGV.

  18. Effect of a novel oral active iron chelator: 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) in iron-overloaded and non-overloaded mice.

    Science.gov (United States)

    Chansiw, Nittaya; Pangjit, Kanjana; Phisalaphong, Chada; Porter, John B; Evans, Patricia; Fucharoen, Suthat; Srichairatanakool, Somdet

    2014-09-01

    To evaluate efficacy and toxicity of a novel orally active bidentate iron chelator, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) in mice under normal and iron overload conditions. Wild type C57BL/6 mice were fed with normal and 0.2% (w/w) ferrocene-supplemented (Fe) diets, respectively for 240 d and orally given the CM1 (50, 100 and 200 mg/kg) for 180 d. Blood iron profiles, hematological indices, liver enzymes and histopathology were determined. CM1 treatment lowered plasma levels of labile plasma iron and non-transferrin bound iron, but not ferritin in the Fe-fed mice. However, the treatment did not impact blood hemoglobin level, white blood cell and platelet numbers in both normal diet and Fe diet-fed mice. Interestingly, CM1 treatment did not markedly elevate plasma aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities in the normal diet-fed mice but it tended to increase the levels of the liver enzymes slightly in the Fe-fed mice. Hematoxylin and eosin staining result showed no abnormal pathological changes in heart, liver and spleen tissues. It is clear that CM1 would not be toxic to bone marrow and liver cells under normal and iron-overload conditions. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  19. Antitumor activity of total flavonoids from Tetrastigma hemsleyanum Diels et Gilg is associated with the inhibition of regulatory T cells in mice.

    Science.gov (United States)

    Feng, Zhengquan; Hao, Wanrong; Lin, Xiaoyang; Fan, Daping; Zhou, Juhua

    2014-01-01

    To determine the antitumor activity of Radix tetrastigmae flavonoids and their inhibitory effect on regulatory T cells (Tregs) in mice. Total flavonoids were isolated from Radix tetrastigmae, the root of Tetrastigma hemsleyanum Diels et Gilg, and administered to C57BL/6 mice by oral gavage after inoculation with Lewis lung carcinoma (LLC) cells. The effects of total flavonoids on tumor growth in vivo were examined. Flow cytometry was used to study the effects on Tregs, and enzyme-linked immunosorbent assay was used to analyze the changes in the serum levels of transforming growth factor β, prostaglandin E2, and cyclooxygenase 2 after tumor inoculation and flavonoid administration. Total flavonoids from T. hemsleyanum Diels et Gilg significantly inhibited tumor growth in C57BL/6 mice inoculated with LLCs. These flavonoids dramatically suppressed regulatory T-cell development in tumor-bearing mice. Further studies revealed that total flavonoids significantly decreased the serum levels of transforming growth factor β, prostaglandin E2, and cyclooxygenase 2 in tumor-bearing mice, which may be responsible for the inhibition of Tregs. The antitumor activity of total flavonoids from T. hemsleyanum Diels et Gilg is associated with the inhibition of Tregs in a mouse tumor model. Total flavonoids from T. hemsleyanum Diels et Gilg may be used as antitumor agents in cancer prevention and treatment.

  20. Inoculating Students against Using Smokeless Tobacco.

    Science.gov (United States)

    Noland, Melody Powers; Riggs, Richard S.

    1989-01-01

    This article describes a teaching technique based on a method intended to develop skills among junior and senior high school youth to resist pressure to use smokeless tobacco. This method is referred to as "inoculation" and "resistance training." (IAH)

  1. The control of hyperglycemia by a novel trypsin resistant oral insulin preparation in alloxan induced type I diabetic mice

    OpenAIRE

    Sarbashri Bank; Arjun Ghosh; Suman Bhattacharya; Smarajit Maiti; Khan, Gausal A.; Sinha, Asru K.

    2016-01-01

    A trypsin resistant oral insulin preparation was made by incubating insulin for 2?h at 23??C with previously boiled cow milk at 100??C that was coagulated with 0.6?M acetic acid. The precipitate was resuspended in the same volume of milk. The immunoblot analysis of the suspended proteins treated with 200?ng of trypsin/ml for 3?h demonstrated that the 80.1% of the insulin in the suspension survived the proteolytic degradation compared to 0% of the hormone survived in the control. The feeding o...

  2. Inoculation of chromium white cast iron

    OpenAIRE

    D. Kopyciński

    2009-01-01

    It has been proved that an addition of boron carbide introduced as an inoculant to the chromium white cast iron changes the structureof castings. Castings after inoculation revealed a different structure with numerous grains. Primary precipitates of chromium carbide also appeared, reducing the mechanical properties of as-cast parts. Properly established heat treatment regime makes chromium iron castings regain their, originally high, mechanical properties.

  3. Inoculation of chromium white cast iron

    Directory of Open Access Journals (Sweden)

    D. Kopyciński

    2009-01-01

    Full Text Available It has been proved that an addition of boron carbide introduced as an inoculant to the chromium white cast iron changes the structureof castings. Castings after inoculation revealed a different structure with numerous grains. Primary precipitates of chromium carbide also appeared, reducing the mechanical properties of as-cast parts. Properly established heat treatment regime makes chromium iron castings regain their, originally high, mechanical properties.

  4. New inoculants on maize silage fermentation

    Directory of Open Access Journals (Sweden)

    Fábia Giovana do Val de Assis

    2014-08-01

    Full Text Available The objective of this study was to evaluate the effect of bacterial inoculants at two inoculation rates on chemical and biological characteristics of maize silage. The treatments consisted of two inoculating rates (5 and 6 log cfu g-1 of forage for each strain of lactic acid bacteria (LAB identified as Lactobacillus buchneri, L. hilgardii, or L. plantarum. The maize was ensiled in experimental PVC silos. Samples were taken for the determination of the contents of dry matter (DM, crude protein (CP, neutral detergent fiber (NDF, water-soluble carbohydrates (WSC, organic acids and alcohols, for the evaluation of the populations of lactic acid bacteria, yeasts, filamentous fungi, and for the determination of pH values during ensilage and after 30 or 90 days of fermentation. The doses of inoculants did not promote significant differences on the evaluated characteristics. There was effect of inoculants on acetic acid, 1.2-propanediol, LAB population, filamentous fungi, and pH value. No significant influence of the treatments with inoculants was observed in the variables DM, WSC, CP, lactic acid concentrations, or ethanol. The maximum temperature, i.e., the time to achieve the maximum temperature (TMT and aerobic stability (AS, was not influencied by treatments. However, a decrease in maximum temperature, an increase in TMT, and improvement in the AS were observed after 90 days of fermentation. These results proved the advantage of microbial inoculation. The treatments influenced LAB populations and filamentous fungi, but no effect was observed on the yeast population. The best inoculation dose is 6 cfu g-1 of forage because it provides higher reduction of filamentous fungi in maize silage, thereby decreasing the aerobic deterioration by these microorganisms.

  5. Automatic surface inoculation of agar trays.

    Science.gov (United States)

    Wilkins, J. R.; Mills, S. M.; Boykin, E. H.

    1972-01-01

    Description of a machine and technique for the automatic inoculation of a plastic tray containing agar media with a culture, using either a conventional inoculation loop or a cotton swab. The design of the machine is simple, it is easy to use, and it relieves the operator from the manual task of streaking cultures. The described technique makes possible the visualization of the overall qualitative and, to some extent, quantitative relationships of various bacterial types in a sample tested.

  6. Hymenolepis microstoma: direct life cycle in immunodeficient mice.

    Science.gov (United States)

    Andreassen, J; Ito, A; Ito, M; Nakao, M; Nakaya, K

    2004-03-01

    The mouse bile duct tapeworm Hymenolepis microstoma requires beetles as the obligatory intermediate host. However, when congenitally athymic NMRI-nu mice were infected with the mature tapeworm and allowed to eat their own faeces with tapeworm eggs, the oncospheres penetrated the intestinal tissue and developed to cysticercoids. After excysting, growth to adult worms occurs in the lumen of the small intestine and bile duct. Furthermore, the same happened when NMRI-nu mice, non-obese diabetic severe combined immunodeficiency (NOD/Shi-scid) mice and NOD/Shi-scid, IL-2 Rgamma(null) (NOG) mice were orally inoculated with shell-free eggs of this parasite. Differences between the cysticercoids of H. microstoma and H. nana developed in the mouse intestinal tissues were: (i) the time course for the development of fully matured cysticercoids of H. microstoma in mice was about 11 days but only 4 days for H. nana; and (ii) cysticercoids of H. microstoma developed in mice had a tail while those of H. nana had none.

  7. Artificial inoculation-perspectives in tailings phytostabilization.

    Science.gov (United States)

    Petrisor, Ioana G; Dobrota, Smaranda; Komnitsas, Kostas; Lazar, Ioan; Kuperberg, J Michael; Serban, Mihai

    2004-01-01

    Intensive mining and processing activities worldwide resulted in the generation of huge amounts of waste (tailings), generally characterized as toxic, radioactive, and/or hazardous. The exposure potential and, hence, the risk posed by such wastes is enhanced by a general lack of vegetation. Phytostabilization has proven to be efficient in reducing this risk. However, establishing vegetation on tailing dumps may be expensive due to the intensive use of amendments and chemical fertilizers. In this article, investigations on artificial inoculation of mine tailings with bacterial strains as a means to improve the development of vegetative covers and reduce application cost by eliminating chemical fertilization are presented and discussed. The development of plants and microbial communities from tailings, as well as the impact of inoculation on metal uptake in plants, were studied. Experiments were carried out in greenhouse using two types of mine tailings (phosphogypsum and sulphidic tailings) from the Romanian Black Sea coast. Indigenous herbaceous plants were cultivated on tailings with the addition of chemical fertilizers versus bacterial inoculation. After a 6-month experimental period, excellent plant growth, which is associated with a rich microbial community, was observed in all inoculated treatments, in contrast with poor plant growth and microbiota from the chemical fertilization treatments alone. Additionally, artificial inoculation improved plant resistance to heavy metals by reducing the uptake of some toxic metals. Once a rich microbial community is established, inoculation may be discontinued. Based on these results, efficient and cost-effective phytostabilization schemes can be proposed.

  8. Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation

    Science.gov (United States)

    Flores-Soto, Mario Eduardo; Chaparro-Huerta, Verónica; Soto-Rodríguez, Sofía; González-Perez, Oscar

    2016-01-01

    Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD) prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1) control, (2) REMSD, (3) melatonin (10 mg/kg) plus REMSD, (4) melatonin and intraperitoneal luzindole (once a day at 5 mg/kg) plus REMSD, and (5) luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU) and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P < 0.021). The melatonin-treated REMSD group also showed the highest expression of Bcl-2 and Bcl-xL as compared to the rest of the groups. Conclusion. The exogenous administration of melatonin restores the tissue levels of sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD. PMID:27579149

  9. Oral administration of potassium bromate induces neurobehavioral changes, alters cerebral neurotransmitters level and impairs brain tissue of swiss mice.

    Science.gov (United States)

    Ajarem, Jamaan; Altoom, Naif G; Allam, Ahmed A; Maodaa, Saleh N; Abdel-Maksoud, Mostafa A; Chow, Billy Kc

    2016-05-12

    Potassium bromate (KBrO3) is widely used as a food additive and is a major water disinfection by-product. The present study reports the side effects of KBrO3 administration on the brain functions and behaviour of albino mice. Animals were divided into three groups: control, low dose KBrO3 (100 mg/kg/day) and high dose KBrO3 (200 mg/kg/day) groups. Administration of KBrO3 led to a significant change in the body weight in the animals of the high dose group in the first, second and the last weeks while water consumption was not significantly changed. Neurobehavioral changes and a reduced Neurotransmitters levels were observed in both KBrO3 groups of mice. Also, the brain level of reduced glutathione (GSH) in KBrO3 receiving animals was decreased. Histological studies favoured these biochemical results showing extensive damage in the histological sections of brain of KBrO3-treated animals. These results show that KBrO3 has serious damaging effects on the central nervous system and therefore, its use should be avoided.

  10. Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation

    Directory of Open Access Journals (Sweden)

    Gabriela López-Armas

    2016-01-01

    Full Text Available Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1 control, (2 REMSD, (3 melatonin (10 mg/kg plus REMSD, (4 melatonin and intraperitoneal luzindole (once a day at 5 mg/kg plus REMSD, and (5 luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P<0.021. The melatonin-treated REMSD group also showed the highest expression of Bcl-2 and Bcl-xL as compared to the rest of the groups. Conclusion. The exogenous administration of melatonin restores the tissue levels of sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD.

  11. Experimental infection of Balb/c nude mice with Hepatitis E virus

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    Zhu Jianguo

    2009-06-01

    Full Text Available Abstract Background Several animal species can reportedly act as reservoirs for Hepatitis E virus (HEV, a zoonotic pathogen. HEV and antibody to the virus have been detected in a variety of animals including rodents. Pig and rat models for HEV have been established for HEV, but a nude mouse has not yet been developed. Methods Balb/c nude mice were inoculated with swine HEV, both orally and via intravenous injection to insure infection. Negative control and experimental contact-exposed groups of mice were also included in the study. The liver, spleen, kidney, jejunum, ileum, cecum and colon of each mouse from all three groups were collected for reverse transcription nested polymerase chain reaction (RT-nPCR detection, indirect immunofluorescence observation and histopathologic examination. The sera from nude mice were tested for anti-HEV IgG by enzyme linked immunosorbent assay (ELISA. Activities of liver enzymes, including alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP, as well as total bilirubin (TBIL were also measured in the sera of the nude mice. Results HEV antigens and HEV RNA were detected in liver, spleen, kidney, jejunum, ileum and colon both by indirect immunofluorescence and by RT-nPCR in all of the inoculated and in one of the contact-exposed nude mice. Histopathological changes were observed in the liver and spleen of these mice. Infected mice showed increased levels of AST, ALP, and anti-HEV IgG in sera. The livers of contact-exposed mice showed obvious histopathological damage. Conclusion Nude mice could be readily infected by HEV isolated from pigs. The nude mouse may therefore be a useful animal model for studying the pathogenesis of HEV.

  12. Metabolism and disposition of 2-ethylhexyl-p-methoxycinnamate following oral gavage and dermal exposure in Harlan Sprague Dawley rats and B6C3F1/N mice and in hepatocytes in vitro.

    Science.gov (United States)

    Fennell, Timothy R; Mathews, James M; Snyder, Rodney W; Hong, Yan; Watson, Scott L; Black, Sherry R; McIntyre, Barry S; Waidyanatha, Suramya

    2017-11-23

    1. 2-Ethylhexyl-p-methoxycinnamate (EHMC) is commonly used as an ingredient in sunscreens, resulting in potential oral and dermal exposure in humans. 2. Clearance and metabolism of EHMC in hepatocytes and disposition and metabolism of EHMC in rodents following oral (8-800 mg/kg) intravenous (IV) (8 mg/kg) or dermal (0.8-80 mg/kg representing 0.1-10% formulation concentration) exposure to [14C]EHMC were investigated in rats and mice. 3. EHMC was rapidly cleared from rat and mouse hepatocytes (half-life ≤3.16 min) and less rapidly (half-life ≤48 min) from human hepatocytes. 4. [14C]EHMC was extensively absorbed and excreted primarily in urine by 72 h after oral administration to rats (65-80%) and mice (63-72%). Oral doses to rats were excreted to a lesser extent (3-8%) in feces and as CO2 (1-4%). Radioactive residues in tissues were <1% of the dose. There were no sex or species differences in disposition in rats. 5. Following dermal application, 34-42% of an 8-mg/kg dose was absorbed in rats, and 54-62% in mice in 72-h. 6. Among numerous urinary metabolites associated with hydrolysis of the ester, two potential reproductive and developmental toxicants, 2-ethylhexanol and 2-ethylhexanoic acid were produced by metabolism of EHMC.

  13. Oral (Gavage) Combined Developmental and Perinatal/Postnatal Reproduction Toxicity Study of Ammonium Salt of Perfluorinated Hexanoic Acid in Mice.

    Science.gov (United States)

    Iwai, Hiroyuki; Hoberman, Alan M

    2014-05-01

    The reproductive toxicity potential of Ammonium Salt of Perfluorinated Hexanoic Acid (PFHxA Ammonium Salt) in pregnant Crl: CD1(ICR) mice was investigated. Twenty females/group were administered the test substance or vehicle once daily from gestation day 6 through 18. Phase 1 doses: 0, 100, 350, and 500 mg/kg/d; phase 2: 0, 7, 35, and 175 mg/kg/d. Parameters evaluated include mortality, viability, body weights, clinical signs, abortions, premature deliveries, pregnancy and fertility, litter observations, maternal behavior, and sexual maturity in the F1 generation. The level of PFHxA Ammonium Salt was measured in the liver of F0 and F1 mice. At doses of 350 and 500 mg/kg/d maternal mortalities, excess salivation and changes in body weight gains occurred. Pup body weights were reduced on postpartum day (PPD) 0 in all the dosage groups, but persisted only in the 350 and 500 mg/kg/d groups. Additional effects at 300 and 500 mg/kg/d included stillbirths, reductions in viability indices, and delays in physical development. Levels of PFHxA Ammonium Salt in the livers of the 100 mg/kg/d dams were all below the lower limit of quantization (0.02 µg/mL); in the 350 mg/kg/d group, 3 of the 8 samples had quantifiable analytical results. In phase 2 no PFHxA Ammonium Salt was found in the liver. Adverse effects occurred only in the 175 mg/kg/d group and consisted of increased stillborn pups, pups dying on PPD 1, and reduced pup weights on PPD 1. Based on these data, the maternal and reproductive no observable adverse effect level of PFHxA Ammonium Salt is 100 mg/kg/d. © The Author(s) 2014.

  14. Oral treatment with the herbal formula B401 protects against aging-dependent neurodegeneration by attenuating oxidative stress and apoptosis in the brain of R6/2 mice.

    Science.gov (United States)

    Wang, Sheue-Er; Lin, Ching-Lung; Hsu, Chih-Hsiang; Sheu, Shuenn-Jyi; Wu, Chung-Hsin

    2015-01-01

    Neurodegeneration is characterized by progressive neurological deficits due to selective neuronal loss in the nervous system. Huntington's disease (HD) is an incurable neurodegenerative disorder. Neurodegeneration in HD patients shows aging-dependent pattern. Our previous study has suggested that a herbal formula B401 may have neuroprotective effects in the brains of R6/2 mice. To clarify possible mechanisms for neurodegeneration, which improves the understanding the aging process. This study focuses on clarifying neurodegenerative mechanisms and searching potential therapeutic targets in HD patients. The oxidative stress and apoptosis were compared in the brain tissue between R6/2 HD mice with and without oral B401 treatment. Expressions of proteins for oxidative stress and apoptosis in the brain tissue of R6/2 HD mice were examined by using immunostaining and Western blotting techniques. R6/2 HD mice with oral B401 treatment significantly reduced reactive oxygen species levels in the blood, but markedly increased expressions of superoxide dismutase 2 in the brain tissue. Furthermore, R6/2 HD mice with oral B401 treatment significantly increased expressions of B-cell lymphoma 2 (Bcl-2), but significantly reduced expressions of Bcl-2-associated X protein (Bax), calpain, and caspase-3 in the brain tissue. Our findings provide evidence that the herbal formula B401 can remedy for aging-dependent neurodegeneration of R6/2 mice via suppressing oxidative stress and apoptosis in the brain. We suggest that the herbal formula B401 can be developed as a potential health supplement for ameliorating aging-dependent neurodegeneration.

  15. Short-term effects of oral administration of Pistacia lentiscus oil on tissue-specific toxicity and drug metabolizing enzymes in mice.

    Science.gov (United States)

    Attoub, Samir; Karam, Sherif M; Nemmar, Abderrahim; Arafat, Kholoud; John, Annie; Al-Dhaheri, Wafa; Al Sultan, Mahmood Ahmed; Raza, Haider

    2014-01-01

    Pistacia lentiscus (Anacardiaceae) is a flowering plant traditionally used in the treatment of various skin, respiratory, and gastrointestinal disorders. The aim of this study was to assess whether Pistacia lentiscus oil has any short term toxic effects in vivo and in vitro. Pistacia lentiscus oil (100µl) was administered orally into mice for 5 days. Measurements of body weight did not show any weight loss. Serum concentration of LDH did not show any significant statistical difference when compared to control mice. Similarly, blood, kidney or liver function tests showed no toxicity with Pistacia lentiscus oil when compared to the control group. Examination of gastrointestinal tissues sections revealed similar structural features with no difference in cell proliferation. In this context, pharmacological dilutions of Pistacia lentiscus oil (10(-6) - 10(-3)) did not affect the viability (cell death and proliferation) of mouse gastric stem cells, human colorectal cancer cells HT29, human hepatoma cells HepG2. However, it appears that at the dose and time point studied, Pistacia lentiscus oil treatment has targeted various cytochrome P450s and has specifically inhibited the activities and the expression of CYP2E1, CYP3A4, CYP1A1 and CYP1A2 differentially in different tissues. Our results also demonstrate that there is no appreciable effect of Pistacia lentiscus oil on the GSH-dependent redox homoeostasis and detoxification mechanism in the tissues. These data suggest a good safety profile of short term oral use of Pistacia lentiscus oil as a monotherapy in the treatment of various skin, respiratory, and gastrointestinal disorders. However, due to its inhibitory effect of various cytochrome P450s and mainly CYP3A4, this might have implications on the bioavailability and metabolism of drugs taken in combination with Pistacia lentiscus oil. More attention is needed when Pistacia lentiscus oil is intended to be uses in combination with other pharmacological agents in order

  16. Short-Term Effects of Oral Administration of Pistacia Lentiscus Oil on Tissue-Specific Toxicity and Drug Metabolizing Enzymes in Mice

    Directory of Open Access Journals (Sweden)

    Samir Attoub

    2014-05-01

    Full Text Available Background: Pistacia lentiscus (Anacardiaceae is a flowering plant traditionally used in the treatment of various skin, respiratory, and gastrointestinal disorders. The aim of this study was to assess whether Pistacia lentiscus oil has any short term toxic effects in vivo and in vitro. Methods: Pistacia lentiscus oil (100µl was administered orally into mice for 5 days. Results: Measurements of body weight did not show any weight loss. Serum concentration of LDH did not show any significant statistical difference when compared to control mice. Similarly, blood, kidney or liver function tests showed no toxicity with Pistacia lentiscus oil when compared to the control group. Examination of gastrointestinal tissues sections revealed similar structural features with no difference in cell proliferation. In this context, pharmacological dilutions of Pistacia lentiscus oil (10-6 - 10-3 did not affect the viability (cell death and proliferation of mouse gastric stem cells, human colorectal cancer cells HT29, human hepatoma cells HepG2. However, it appears that at the dose and time point studied, Pistacia lentiscus oil treatment has targeted various cytochrome P450s and has specifically inhibited the activities and the expression of CYP2E1, CYP3A4, CYP1A1 and CYP1A2 differentially in different tissues. Our results also demonstrate that there is no appreciable effect of Pistacia lentiscus oil on the GSH-dependent redox homoeostasis and detoxification mechanism in the tissues. Conclusion: These data suggest a good safety profile of short term oral use of Pistacia lentiscus oil as a monotherapy in the treatment of various skin, respiratory, and gastrointestinal disorders. However, due to its inhibitory effect of various cytochrome P450s and mainly CYP3A4, this might have implications on the bioavailability and metabolism of drugs taken in combination with Pistacia lentiscus oil. More attention is needed when Pistacia lentiscus oil is intended to be uses in

  17. Results from oral gavage carcinogenicity studies of ruxolitinib in Tg.rasH2 mice and Sprague-Dawley (Crl:CD) rats.

    Science.gov (United States)

    Shuey, Dana L; Oliver, Julian; Zhou, Gongfu; Roberts, Alan

    2016-11-01

    Ruxolitinib is a selective and potent inhibitor of Janus kinase (JAK) 1 and JAK2. It is approved for the treatment of patients with intermediate or high-risk myelofibrosis, or those with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea. To investigate its carcinogenic potential, ruxolitinib was administered by oral gavage once daily to Tg.rasH2 mice for 6 months at doses of 15, 45 or 125 mg/kg/day, and to Sprague-Dawley (Crl:CD) rats for 2 years at 10, 20 or 60 mg/kg/day. Ruxolitinib had no effect on survival, and did not increase the incidence of any neoplastic findings in either species. Exposure (AUC) was similar to or exceeded that associated with therapeutic use. Lymphoid depletion and a decrease in extramedullary hematopoiesis in the spleen occurred in rats, which were attributed to the pharmacologic activity of ruxolitinib. In Tg.rasH2 mice, increased inflammation in the nasal cavity was observed. Dose-dependent decreases in a number of spontaneous neoplastic/preneoplastic lesions were observed in rats, including mammary tumors in females, adrenal pheochromocytomas in males, hepatocellular adenomas/carcinomas in males, and hepatic basophilic (males and females) and eosinophilic (males) foci. Peribiliary fibrosis was also decreased. Clear cell foci in the liver were increased in females. Based on the results of these studies, ruxolitinib is not considered to be carcinogenic. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Effects of Morinda lucida leaf extract on Trypanosoma brucei brucei infection in mice.

    Science.gov (United States)

    Asuzu, I U; Chineme, C N

    1990-10-01

    The dried leaves of Morinda lucida were extracted with 50% methanol and the extract was recovered in a 9.7% w/w yield. Acute toxicity tests were performed in mice and the intraperitoneal LD50 of the extract was 2000 mg/kg. The extract induced purgation in mice from the first hour after oral administration and reached its peak between the third and fourth hour. The purgation was not dose-dependent. M. lucida leaf extract i.p. significantly suppressed the level of parasitemia after Trypanosoma brucei infection in mice. Suppression of existing parasitemia appeared dose-dependent with 1000 mg/kg i.p. producing the maximum effect. The best trypanocidal activity was obtained when treatment with M. lucida extract commenced simultaneously with trypanosome inoculation.

  19. Effects of daily oral administration of quercetin chalcone and modified citrus pectin on implanted colon-25 tumor growth in Balb-c mice.

    Science.gov (United States)

    Hayashi, A; Gillen, A C; Lott, J R

    2000-12-01

    The health benefits of fruits and vegetables have been the subject of numerous investigations over many years. Two natural substances, quercetin (a flavonoid) and citrus pectin (a polysaccharide found in the cell wall of plants) are of particular interest to cancer researchers. Two modified versions of these substances - quercetin chalcone (QC) and a pH-modified citrus pectin (MCP) - are the focus of this study. Previous research has confirmed that quercetin exhibits antitumor properties, likely due to immune stimulation, free radical scavenging, alteration of the mitotic cycle in tumor cells, gene expression modification, anti-angiogenesis activity, or apoptosis induction, or a combination of these effects. MCP has inhibited metastases in animal studies of prostate cancer and melanoma. To date, no study has demonstrated a reduction in solid tumor growth with MCP, and there is no research into the antitumor effect of QC. This study examines the effects of MCP and QC on the size and weight of colon-25 tumors implanted in balb-c mice. Fifty mice were orally administered either 1 ml distilled water (controls), low-dose QC (0.8 mg/ml), high-dose QC (1.6 mg/ml), low-dose MCP (0. 8 mg/ml) or high-dose MCP (1.6 mg/ml) on a daily basis, beginning the first day of tumor palpation (usually eight days post-implantation). A significant reduction in tumor size was noted at day 20 in all groups compared to controls. The groups given low-dose QC and MCP had a 29-percent (NS) and 38-percent (p<0.02) decrease in size, respectively. The high-dose groups had an even more impressive reduction in size; 65 percent in the QC group and 70 percent in the mice given MCP (both p<0.001). This is the first evidence that MCP can reduce the growth of solid primary tumors, and the first research showing QC has antitumor activity. Additional research on these substances and their effect on human cancers is warranted.

  20. Oral exposure of mice to cadmium (II), chromium (VI) and their mixture induce oxidative- and endoplasmic reticulum-stress mediated apoptosis in the livers.

    Science.gov (United States)

    Jin, Yuanxiang; Zhang, Songbin; Tao, Runhua; Huang, Jie; He, Xingzhi; Qu, Lanya; Fu, Zhengwei

    2016-06-01

    Health concerns regarding the environmental heavy metals in wildlife and humans have increased in recent years. We evaluated the effects of exposure of mice to low doses of cadmium (Cd), chromium (Cr) and their mixtures on oxidative- and ER-stress. Male adult mice were orally exposed to Cd (0.5 and 2 mg kg(-1) ), Cr (1 and 4 mg kg(-1) ) and binary Cd+Cr mixtures (0.25 + 05 and 1 + 2 mg kg(-1) ) daily for 36 days. We observed that the bioaccumulation of Cd and Cr in the liver in a dose-dependent manner, and the Cd and Cr contents in the 2 mg kg(-1) Cd and 4 mg kg(-1) Cr treated groups reached 2.43 and 3.46 µg g(-1) liver weight. In addition, treatments with 2 mg kg(-1) Cd, 4 mg kg(-1) Cr or their mixture (1 + 2 mg kg(-1) ) significantly decreased body and liver weights, increased the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and activities of catalase (CAT) and glutathione peroxidase (GPX) in the liver. Moreover, Cd and Cr exposures also elevated the transcription of the oxidative- and endoplasmic reticulum (ER)-stress related genes including Cat, Gpx, heme oxygenase 1 (Ho-1), regulated protein 78 (Grp78), activating transcription factor 6 (Atf6) and proaoptotic CCAAT/-enhancer-binding protein homologous protein (Chop) in a dose dependent manner in the liver. And hepatic cytochrome c levels increased in all Cd, Cr or their mixture treated groups. Furthermore, the transcriptional status and the activities of Caspase 9 and Caspase 3 were increased significantly in the liver when exposed to high doses of Cd, Cr or their mixture. These results suggested that a long period exposure of mice to Cd or Cr has the potential to elicit oxidative- and ER-stress mediated apoptosis in their livers. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 693-705, 2016. © 2014 Wiley Periodicals, Inc.

  1. Parenteral vs. oral iron: influence on hepcidin signaling pathways through analysis of Hfe/Tfr2-null mice.

    Science.gov (United States)

    McDonald, Cameron J; Wallace, Daniel F; Ostini, Lesa; Subramaniam, V Nathan

    2014-01-01

    Treatment for iron deficiency anemia can involve iron supplementation via dietary or parenteral routes that result in different cellular iron distributions. The effect of the administered iron on the iron regulatory system and hepcidin in the liver has not been well studied. Hepcidin, the liver-expressed central iron-regulatory peptide, is itself regulated through the bone morphogenetic protein (BMP)/SMAD signaling pathway. Specifically, Bmp6 expression is upregulated in response to iron and induces hepcidin through phosphorylation of Smad1/5/8. The hemochromatosis-associated proteins Hfe and transferrin receptor 2 (Tfr2) are known upstream regulators of hepcidin, although their precise roles are still unclear. To investigate the mechanisms of this regulation and the roles of the Hfe and Tfr2, we subjected wild-type, Hfe(-/-), Tfr2(-/-), and Hfe(-/-)/Tfr2(-/-) mice to iron loading via dietary or parenteral routes. Systematic analysis demonstrated that Tfr2 is required for effective upregulation of Bmp6 in response to hepatocyte iron, but not nonparenchymal iron. Hfe is not required for Bmp6 upregulation, regardless of iron localization, but rather, is required for efficient downstream transmission of the regulatory signal. Our results demonstrate that Hfe and Tfr2 play separate roles in the regulatory responses to iron compartmentalized in different cell types and further elucidates the regulatory mechanisms controlling iron homeostasis.

  2. Attenuation of allergic immune response phenotype by mannosylated egg white in orally induced allergy in BALB/c mice.

    Science.gov (United States)

    Rupa, Prithy; Nakamura, Soichiro; Katayama, Shigeru; Mine, Yoshinori

    2014-10-01

    Food allergies are attributed to an imbalance in immune response to ubiquitous antigens. A previous study demonstrated that mannose glycation (mannosylation) of ovalbumin decreased allergenicity in vivo. The proposed research targets mannosylation of various common allergens that may help prevent food allergy. Balb/c mice (n = 8) were sensitized toxin egg white, peanut, and whey and treated with mannosylated forms of the test antigens. Glucosylated peanut and cholera toxins were used as controls. Allergic status was assessed as clinical signs, serum histamine, mouse mast cell protease (MMCP), antibody activity, cytokines, and T regulatory cells (T-regs). Significant preventative effects were observed with mannosylated egg white treatment such as reduced clinical signs, histamine, MMCP, specific G, G1, and E antibody activities, and IL-4 and increased IL-10 and CD25(+) Foxp3(+) cells. Other groups did not differ significantly. It was concluded that mannosylated egg white provides a powerful tool to prevent allergic phenotypes with possible relevance to control human egg allergy.

  3. Kinetic analysis of antibody responses to Blastocystis hominis in sera and intestinal secretions of orally infected mice.

    Science.gov (United States)

    Santos, Herbert J; Rivera, Windell L

    2009-10-01

    The kinetics of antibody production against Blastocystis hominis, an emerging infectious protozoan parasite which causes intestinal disorder in humans and animals, was studied. Sera and intestinal secretions were collected from B. hominis-immunized Balb/C mice for 8 weeks. Flow cytometry was used to monitor the levels of immunoglobulins A (IgA), G (IgG), and M (IgM) from both types of biological samples. The kinetic profile derived from flow cytometry analysis revealed that IgM led the early immune action against B. hominis infection in immune sera while IgA was the predominant antibody isotype in intestinal secretions. Western blotting revealed an array of antigens recognized by both serum and intestinal secretion antibodies. Immunoreactive B. hominis soluble proteins with molecular weights ranging from 28.2 to 77.6 kDa were detected by serum antibodies and 15.1 to 117.5 kDa by secretory antibodies. These antigens may be cytoplasmic or membrane-bound as determined through indirect fluorescent antibody test. Moreover, two immunogens (39.8 and 77.6 kDa) were commonly recognized by serum antibodies, one (70.8 kDa) by secretory antibodies and two (55.0 and 56.2 kDa) by both serum and secretory antibodies, suggesting a possible target in the further understanding of B. hominis pathogenicity, discovery of virulence factors, and development of immunology-based diagnostic protocols and alternative modes of treatment.

  4. Antipruritic effect of the single oral administration of German chamomile flower extract and its combined effect with antiallergic agents in ddY mice.

    Science.gov (United States)

    Kobayashi, Yoshinori; Takahashi, Ria; Ogino, Fumiko

    2005-10-03

    The single peroral administration of the ethyl acetate extract or essential oil of German chamomile (Matricaria recutita L.) showed remarkable antipruritic effects in the compound 48/80-induced itch-scratching test in ddY mice, if suitable vehicle was used. The ethyl acetate extract or essential oil of German chamomile dissolved in the vehicle of 10% ethanol, 10% Tween 80 and 80% physiological saline was orally administrated 2 h before pruritus provocation by compound 48/80 subcutaneous injection. The ethyl acetate extract or essential oil of German chamomile showed significant dose-dependent inhibition of the compound 48/80-induced scratching without affecting spontaneous motor activity. The antipruritic effects of antihistamine H1 antagonists, oxatomide (10 mg/kg) and fexofenadine (10 mg/kg), were only partial in this test. However, the antipruritic effects of these agents were remarkably enhanced by the combined administration of the ethyl acetate extract of German chamomile (300 mg/kg). Thus, the co-medication with the ethyl acetate extract, or essential oil of German chamomile and antihistamines might be effective for the pruritus which could not be perfectly resolved alone by conventional antihistamines.

  5. Inhibition of Carrageenan-Induced Acute Inflammation in Mice by Oral Administration of Anthocyanin Mixture from Wild Mulberry and Cyanidin-3-Glucoside

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    Neuza Mariko Aymoto Hassimotto

    2013-01-01

    Full Text Available Anthocyanins are flavonoids which demonstrated biological activities in in vivo and in vitro models. Here in the anti-inflammatory properties of an anthocyanin-enriched fraction (AF extracted from wild mulberry and the cyanidin-3-glucoside (C3G, the most abundant anthocyanin in diet, were studied in two acute inflammation experimental models, in the peritonitis and in the paw oedema assays, both of which were induced by carrageenan (cg in mice. In each trial, AF and C3G (4 mg/100 g/animal were orally administered in two distinct protocols: 30 min before and 1 h after cg stimulus. The administration of both AF and C3G suppresses the paw oedema in both administration times (P<0.05. In the peritonitis, AF and C3G reduced the polymorphonuclear leukocytes (PMN influx in the peritoneal exudates when administered 1 h after cg injection. AF was more efficient reducing the PMN when administered 30 min before cg. Both AF and C3G were found to suppress mRNA as well as protein levels of COX-2 upregulated by cg in both protocols, but the inhibitory effect on PGE2 production in the peritoneal exudates was observed when administered 30 min before cg (P<0.05. Our findings suggest that AF and C3G minimize acute inflammation and they present positive contributions as dietary supplements.

  6. Legume bioactive compounds: influence of rhizobial inoculation

    Directory of Open Access Journals (Sweden)

    Luis R. Silva

    2017-04-01

    Full Text Available Legumes consumption has been recognized as beneficial for human health, due to their content in proteins, fiber, minerals and vitamins, and their cultivation as beneficial for sustainable agriculture due to their ability to fix atmospheric nitrogen in symbiosis with soil bacteria known as rhizobia. The inoculation with these baceria induces metabolic changes in the plant, from which the more studied to date are the increases in the nitrogen and protein contents, and has been exploited in agriculture to improve the crop yield of several legumes. Nevertheless, legumes also contain several bioactive compounds such as polysaccharides, bioactive peptides, isoflavones and other phenolic compounds, carotenoids, tocopherols and fatty acids, which makes them functional foods included into the nutraceutical products. Therefore, the study of the effect of the rhizobial inoculation in the legume bioactive compounds content is gaining interest in the last decade. Several works reported that the inoculation of different genera and species of rhizobia in several grain legumes, such as soybean, cowpea, chickpea, faba bean or peanut, produced increases in the antioxidant potential and in the content of some bioactive compounds, such as phenolics, flavonoids, organic acids, proteins and fatty acids. Therefore, the rhizobial inoculation is a good tool to enhance the yield and quality of legumes and further studies on this field will allow us to have plant probiotic bacteria that promote the plant growth of legumes improving their functionality.

  7. Persistence of Rhizobium Inoculants originating from Leucaena ...

    African Journals Online (AJOL)

    TonukariJ

    Ten core soil samples were collected from experimental plots at IITA, SW Nigeria that were previously inoculated with Rhizobium ... pot experiment and plant reinfection experiment in the greenhouse. At 0–15 cm and ... agricultural practice and environmental pollution abatement for non-use of chemical nitrogen fertilizers.

  8. Persistence of Rhizobium inoculants originating from Leucaena ...

    African Journals Online (AJOL)

    Ten core soil samples were collected from experimental plots at IITA, SW Nigeria that were previously inoculated with Rhizobium strains (IRC1045 and IRC 1050) specific for Leucaena leucocephala at two depths; 0—15 cm and 15—30 cm. The control soil samples were collected at similar depths from an adjacent field with ...

  9. Mice develop effective but delayed protective immune responses when immunized as neonates either intranasally with nonliving VP6/LT(R192G) or orally with live rhesus rotavirus vaccine candidates.

    Science.gov (United States)

    VanCott, John L; Prada, Anne E; McNeal, Monica M; Stone, Susan C; Basu, Mitali; Huffer, Bert; Smiley, Kristi L; Shao, Mingyuan; Bean, Judy A; Clements, John D; Choi, Anthony H-C; Ward, Richard L

    2006-05-01

    Rotavirus vaccines are delivered early in life, when the immune system is immature. To determine the effects of immaturity on responses to candidate vaccines, neonatal (7 days old) and adult mice were immunized with single doses of either Escherichia coli-expressed rotavirus VP6 protein and the adjuvant LT(R192G) or live rhesus rotavirus (RRV), and protection against fecal rotavirus shedding following challenge with the murine rotavirus strain EDIM was determined. Neonatal mice immunized intranasally with VP6/LT(R192G) were unprotected at 10 days postimmunization (dpi) and had no detectable rotavirus B-cell (antibody) or CD4(+) CD8(+) T-cell (rotavirus-inducible, Th1 [gamma interferon and interleukin-2 {IL-2}]-, Th2 [IL-5 and IL-4]-, or ThIL-17 [IL-17]-producing spleen cells) responses. However, by 28 and 42 dpi, these mice were significantly (P >or= 0.003) protected and contained memory rotavirus-specific T cells but produced no rotavirus antibody. In contrast, adult mice were nearly fully protected by 10 dpi and contained both rotavirus immunoglobulin G and memory T cells. Neonates immunized orally with RRV were also less protected (P=0.01) than adult mice by 10 dpi and produced correspondingly less rotavirus antibody. Both groups contained few rotavirus-specific memory T cells. Protection levels by 28 dpi for neonates or adults were equal, as were rotavirus antibody levels. This report introduces a neonatal mouse model for active protection studies with rotavirus vaccines. It indicates that, with time, neonatal mice develop full protection after intranasal immunization with VP6/LT(R192G) or oral immunization with a live heterologous rotavirus and supports reports that protection depends on CD4(+) T cells or antibody, respectively.

  10. Performance of broilers experimentally inoculated with Salmonella Typhimurium and fed diets with addition of lactulosis

    Directory of Open Access Journals (Sweden)

    Eliete Souza Santana

    2012-08-01

    Full Text Available The objective of this experiment was to evaluate the influence of lactulose on performance as well as its ability to prevent colonization by Salmonella Typhimurium in broilers orally inoculated with this pathogen. The design adopted was completely randomized, with 630 one-day-old male chicks distributed into six treatments, with seven replications and 15 birds per experimental unit. The treatments comprised the following procedures: T1 (control group - no S. Typhimurium inoculation or supply of lactulosis; T2 - only inoculation of S. Typhimurium; T3 - only lactulosis supply; T4 supply of lactulosis and S. Typhimurium inoculation on the first day of life; T5 - supply of lactulosis 48 hours before S. Typhimurium inoculation; and T6 - supply of lactulosis 48 hours after inoculation of S. Typhimurium. Performance variables were evaluated on the seventh, 14th, 21st and 28th days of age; fragments of the duodenum and jejunum were collected and sent to histomorphometric assessment at 14 days of age, and S. Typhimurium excretion was verified in cloacal swabs on the 10th, 24th and 35th days of age. Performance data were analyzed by ANOVA and Tukey's test (5% and fecal excretion data were assessed by non-parametric chi-square test. Better weight gain and feed conversion were observed in groups fed lactulosis with or without challenge of S. Typhimurium up to 21 days of age. Reduced duodenum villous height was verified on the 14th day in groups challenged with the pathogen. Reduction of S. Typhimurium fecal excretion was verified in broilers fed lactulosis from the first day of life on and 48 hours before receiving S. Typhimurium directly into the crop. Lactulosis increases broiler performance up to one week after its inoculation, influences duodenum villous height and reduces the fecal excretion of Salmonella Typhimurium.

  11. Role of interferon in homologous and heterologous rotavirus infection in the intestines and extraintestinal organs of suckling mice.

    Science.gov (United States)

    Feng, N; Kim, B; Fenaux, M; Nguyen, H; Vo, P; Omary, M B; Greenberg, H B

    2008-08-01

    Recent studies demonstrated that viremia and extraintestinal rotavirus infection are common in acutely infected humans and animals, while systemic diseases appear to be rare. Intraperitoneal infection of newborn mice with rhesus rotavirus (RRV) results in biliary atresia (BA), and this condition is influenced by the host interferon response. We studied orally inoculated 5-day-old suckling mice that were deficient in interferon (IFN) signaling to evaluate the role of interferon on the outcome of local and systemic infection after enteric inoculation. We found that systemic replication of RRV, but not murine rotavirus strain EC, was greatly enhanced in IFN-alpha/beta and IFN-gamma receptor double-knockout (KO) or STAT1 KO mice but not in mice deficient in B- or T-cell immunity. The enhanced replication of RRV was associated with a lethal hepatitis, pancreatitis, and BA, while no systemic disease was observed in strain EC-infected interferon-deficient mice. In IFN-alpha/beta receptor KO mice the extraintestinal infection and systemic disease were only moderately increased, while RRV infection was not augmented and systemic disease was not present in IFN-gamma receptor KO mice. The increase of systemic infection in IFN-deficient mice was also observed during simian strain SA11 infection but not following bovine NCDV, porcine OSU, or murine strain EW infection. Our data indicate that the requirements for the interferon system to inhibit intestinal and extraintestinal viral replication in suckling mice vary among different heterologous and homologous rotavirus strains, and this variation is associated with lethal systemic disease.

  12. Immunological and clinical response of coyotes (Canis latrans) to experimental inoculation with Yersinia pestis.

    Science.gov (United States)

    Baeten, Laurie A; Pappert, Ryan; Young, John; Schriefer, Martin E; Gidlewski, Thomas; Kohler, Dennis; Bowen, Richard A

    2013-10-01

    Multiple publications have reported the use of coyotes (Canis latrans) in animal-based surveillance efforts for the detection of Yersinia pestis. Coyotes are likely exposed via flea bite or oral routes and are presumed to be resistant to the development of clinical disease. These historic data have only been useful for the evaluation of the geographic distribution of Y. pestis in the landscape. Because the canid immunologic response to Y. pestis has not been thoroughly characterized, we conducted experimental inoculation of captive-reared, juvenile coyotes (n = 8) with Y. pestis CO92 via oral or intradermal routes. We measured the humoral response to Y. pestis fraction 1 capsular protein (anti-F1) and found a significant difference between inoculation groups in magnitude and duration of antibody production. The anti-F1 titers in animals exposed intradermally peaked at day 10 postinoculation (PI; range = 1∶32 to 1∶128) with titers remaining stable at 1∶32 through week 12. In contrast, orally inoculated animals developed higher titers (range = 1∶256 to 1∶1,024) that remained stable at 1∶256 to 1∶512 through week 6. No clinical signs of disease were observed, and minimal changes were noted in body temperature, white blood cell counts, and acute phase proteins during the 7 days PI. Gross pathology was unremarkable, and minimal changes were noted in histopathology at days 3 and 7 PI. Rechallenge at 14 wk PI via similar dosage and routes resulted in marked differences in antibody response between groups. Animals in the orally inoculated group produced a striking increase in anti-F1 titers (up to 1∶4,096) within 3 days, whereas there was minimal to no increase in antibody response in the intradermal group. Information gathered from this experimental trial may provide additional insight into the spatial and temporal evaluation of coyote plague serology.

  13. Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes tumor-cell infiltration into multiple organs and improves survival period for ATL model mice.

    Science.gov (United States)

    Ikebe, E; Kawaguchi, A; Tezuka, K; Taguchi, S; Hirose, S; Matsumoto, T; Mitsui, T; Senba, K; Nishizono, A; Hori, M; Hasegawa, H; Yamada, Y; Ueno, T; Tanaka, Y; Sawa, H; Hall, W; Minami, Y; Jeang, K T; Ogata, M; Morishita, K; Hasegawa, H; Fujisawa, J; Iha, H

    2013-08-16

    In the peripheral blood leukocytes (PBLs) from the carriers of the human T-lymphotropic virus type-1 (HTLV-1) or the patients with adult T-cell leukemia (ATL), nuclear factor kappaB (NF-κB)-mediated antiapoptotic signals are constitutively activated primarily by the HTLV-1-encoded oncoprotein Tax. Tax interacts with the I κB kinase regulatory subunit NEMO (NF-κB essential modulator) to activate NF-κB, and this interaction is maintained in part by a molecular chaperone, heat-shock protein 90 (HSP90), and its co-chaperone cell division cycle 37 (CDC37). The antibiotic geldanamycin (GA) inhibits HSP90's ATP binding for its proper interaction with client proteins. Administration of a novel water-soluble and less toxic GA derivative, 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG), to Tax-expressing ATL-transformed cell lines, C8166 and MT4, induced significant degradation of Tax. 17-DMAG also facilitated growth arrest and cellular apoptosis to C8166 and MT4 and other ATL cell lines, although this treatment has no apparent effects on normal PBLs. 17-DMAG also downregulated Tax-mediated intracellular signals including the activation of NF-κB, activator protein 1 or HTLV-1 long terminal repeat in Tax-transfected HEK293 cells. Oral administration of 17-DMAG to ATL model mice xenografted with lymphomatous transgenic Lck-Tax (Lck proximal promoter-driven Tax transgene) cells or HTLV-1-producing tumor cells dramatically attenuated aggressive infiltration into multiple organs, inhibited de novo viral production and improved survival period. These observations identified 17-DMAG as a promising candidate for the prevention of ATL progression.

  14. Fabrication of water-soluble polymer-encapsulated As4S4 to increase oral bioavailability and chemotherapeutic efficacy in AML mice

    Science.gov (United States)

    Ma, Qiang; Wang, Chuan; Li, Xiaojin; Guo, Hua; Meng, Jie; Liu, Jian; Xu, Haiyan

    2016-01-01

    Realgar (As4S4) has been demonstrated to be effective for the treatment of acute myeloid leukemia (AML); it has the advantages of no drug resistance and oral administration. Nevertheless, its poor solubility has been an obstacle to its bioavailability, requiring high-dose administration over a long period. We investigated whether crushing realgar crystals to the nanoscale and encapsulating the particles in a water-soluble polymer in one step using hot-melt extrusion would increase the bioavailability of As4S4. Raw As4S4 (r-As4S4) and water-soluble polymer were processed via co-rotating twin screw extrusion. The resulting product (e-As4S4) was characterized by SEM, XRD, and DLS. The cytotoxicity and therapeutic effects of e-As4S4 were evaluated in vivo and in vitro. The results show that e-As4S4 dissolved rapidly in water, forming a stable colloid solution. The average size of e-As4S4 particles was 680 nm, which was reduced by more than 40-fold compared with that of r-As4S4. The bioavailability of e-As4S4 was up to 12.6-fold higher than that of r-As4S4, and it inhibited the proliferation of HL-60 cells much more effectively than did r-As4S4, inducing apoptosis and significantly reducing the infiltration of HL-60 cells into the bone marrow, spleen, and liver. This in turn prolonged the survival of AML mice. PMID:27383126

  15. UV radiation-induced skin aging in hairless mice is effectively prevented by oral intake of sea buckthorn (Hippophae rhamnoides L.) fruit blend for 6 weeks through MMP suppression and increase of SOD activity.

    Science.gov (United States)

    Hwang, In Sik; Kim, Ji Eun; Choi, Sun Il; Lee, Hye Ryun; Lee, Young Ju; Jang, Min Ju; Son, Hong Ju; Lee, Hee Seob; Oh, Chung Hun; Kim, Bae Hwan; Lee, Sang Hak; Hwang, Dae Youn

    2012-08-01

    Oxidative stress and oxidative photodamage induced by UV radiation can cause serious skin damage that is characterized by wrinkling, roughness, laxity and pigmentation. The effects of a sea buckthorn (Hippophae rhamnoides L.) fruit blend (SFB) containing sea buckthorn fruit extract, blueberry extract and collagen on UV-induced skin aging were examined by treating hairless mice for 6 weeks with UV irradiation and SFB administered orally. The effects of SFB were measured in the skin of these mice by phenotypical and histological analysis and western blotting. According to wrinkle formation analysis, the oral intake of SFB induced a decrease in wrinkle formation in the damaged skin of UV-irradiated mice. The thickness of the epidermis and dermis in the vitamin extracts (Vit)- and SFB-treated group was lower than that in the vehicle-treated group, but the group treated with SFB50 was the most effective group. The mice treated with the Vit- or SFB solution maintained a normal moisture content through the inhibition of transdermal water loss (TEWL) and an increase in skin moisture content. Furthermore, the levels of matrix metalloproteinase (MMP) and collagen protein expression were assessed in five groups to examine the mechanisms underlying the effects of SFB oral intake. The application of SFB induced a decrease in MMP-1 and -9 expression to the levels observed in the vehicle-treated group, but MMP-9 expression showed a much larger decrease than MMP-1. Furthermore, the expression of collagen-1 in the skin corresponded to MMP expression except for the SFB30-treated group, whereas the superoxide dismutase (SOD) activity was increased dramatically in the SFB50-treated group. These results suggest that SFB has potential as a protective and therapeutic drug candidate against skin aging that functions by regulating the moisture content, MMP expression levels and SOD activity.

  16. Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), Δ⁹-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive-compulsive behaviour.

    Science.gov (United States)

    Deiana, Serena; Watanabe, Akihito; Yamasaki, Yuki; Amada, Naoki; Arthur, Marlene; Fleming, Shona; Woodcock, Hilary; Dorward, Patricia; Pigliacampo, Barbara; Close, Steve; Platt, Bettina; Riedel, Gernot

    2012-02-01

    Phytocannabinoids are useful therapeutics for multiple applications including treatments of constipation, malaria, rheumatism, alleviation of intraocular pressure, emesis, anxiety and some neurological and neurodegenerative disorders. Consistent with these medicinal properties, extracted cannabinoids have recently gained much interest in research, and some are currently in advanced stages of clinical testing. Other constituents of Cannabis sativa, the hemp plant, however, remain relatively unexplored in vivo. These include cannabidiol (CBD), cannabidivarine (CBDV), Δ(9)-tetrahydrocannabivarin (Δ(9)-THCV) and cannabigerol (CBG). We here determined pharmacokinetic profiles of the above phytocannabinoids after acute single-dose intraperitoneal and oral administration in mice and rats. The pharmacodynamic-pharmacokinetic relationship of CBD (120 mg/kg, ip and oral) was further assessed using a marble burying test in mice. All phytocannabinoids readily penetrated the blood-brain barrier and solutol, despite producing moderate behavioural anomalies, led to higher brain penetration than cremophor after oral, but not intraperitoneal exposure. In mice, cremophor-based intraperitoneal administration always attained higher plasma and brain concentrations, independent of substance given. In rats, oral administration offered higher brain concentrations for CBD (120 mg/kg) and CBDV (60 mg/kg), but not for Δ(9)-THCV (30 mg/kg) and CBG (120 mg/kg), for which the intraperitoneal route was more effective. CBD inhibited obsessive-compulsive behaviour in a time-dependent manner matching its pharmacokinetic profile. These data provide important information on the brain and plasma exposure of new phytocannabinoids and guidance for the most efficacious administration route and time points for determination of drug effects under in vivo conditions.

  17. Sequential inoculation versus co-inoculation in Cabernet Franc wine fermentation.

    Science.gov (United States)

    Cañas, Pedro Miguel Izquierdo; Romero, Esteban García; Pérez-Martín, Fátima; Seseña, Susana; Palop, María Llanos

    2015-04-01

    A study has been carried out in order to determine the effect of the lactic acid bacteria inoculation time on the kinetic of vinification and on chemical and sensory characteristics of Cabernet Franc wines. Traditional vinifications, with lactic acid bacteria inoculated after completion of alcoholic fermentation were compared with vinifications where yeast and bacteria were co-inoculated at the beginning of vinification. One commercial yeast strain and an autochthonous Oenococcus oeni strain (C22L9), previously identified and selected at our laboratory, were used. Monitoring of alcoholic and malolactic fermentations was carried out by yeast and lactic acid bacteria counts and by measuring l-malic acid concentration. Wines were chemically characterized and analysed for volatile compounds content. A sensory analysis, consisting of a descriptive and a triangular test, was also carried out. Results from this study showed that the concurrent yeast/bacteria inoculation of musts at the beginning of vinification produced a reduction in duration of the process without an excessive increase in volatile acidity. Differences in volatile compounds content and the corresponding impact on the sensorial profile of wines were also displayed. These results suggest that co-inoculation is a worthwhile alternative for winemaking of Cabernet Franc wines, if compared with traditional post-alcoholic fermentation lactic acid bacteria inoculation. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  18. Dose-response model of murine typhus (Rickettsia typhi: time post inoculation and host age dependency analysis

    Directory of Open Access Journals (Sweden)

    Tamrakar Sushil B

    2012-03-01

    Full Text Available Abstract Background Rickettsia typhi (R. mooseri is the causative agent of murine typhus. It is one of the most widely distributed flea-borne diseases with a relatively mild febrile initial illness with six to 14 days of incubation period. The bacterium is gram negative and an obligate intracellular pathogen. The disease is transmitted to humans and vertebrate host through fleabites or via contact with infected feces. This paper develops dose-response models of different routes of exposure for typhus in rodents. Methods Data from published articles were analyzed using parametric dose-response relationship models. Dose-response relationships were fit to data using the method of maximum likelihood estimation (MLE. Results Dose-response models quantifying the effects of different ages of rats and time post inoculation in BALB/c mice were analyzed in the study. Both the adult rats (inoculated intradermally and newborn rats (inoculated subcutaneously were best fit by exponential models and both distributions could be described by a single dose-response relationship. The BALB/C mice inoculated subcutaneously were best fit by Beta-Poisson models. The time post inoculation analysis showed that there was a definite time and response relationship existed in this case. Conclusions Intradermally or subcutaneously inoculated rats (adult and newborn models suggest that less than 1 plaque-forming unit (PFU (1.33 to 0.38 in 95% confidence limits of the pathogen is enough to seroconvert 50% of the exposed population on average. For the BALB/c mouse time post inoculation model, an average dose of 0.28 plaque-forming units (PFU (0.75 to 0.11 in 95% confidence limits will seroconvert 50% of the exposed mice.

  19. Oral therapy for type 1 diabetes mellitus using a novel immunomodulator, FTY720 (fingolimod), in combination with sitagliptin, a dipeptidyl peptidase-4 inhibitor, examined in non-obese diabetic mice.

    Science.gov (United States)

    Tsuji, Takumi; Yoshida, Yuya; Fujita, Tetsuro; Kohno, Takeyuki

    2012-10-18

    Aims/Introduction:  The therapeutic effectiveness against type 1 diabetes mellitus of a novel immunomodulator, FTY720 (fingolimod), in combination with sitagliptin, a dipeptidyl peptidase-4 inhibitor, was examined in the non-obese diabetic (NOD) mouse model.   Female NOD mice that had developed type 1 diabetes mellitus spontaneously were divided into four groups according to which therapy they received: (i) FTY720 (0.1 mg/kg, orally, six times a week) plus sitagliptin (1 mg/kg, orally, six times a week); (ii) FTY720 (0.1 mg/kg, orally, six times a week); (iii) sitagliptin (1 mg/kg, orally, six times a week); and (iv) the vehicle (water) alone. Therapeutic efficacy was evaluated in terms of survival rate, ratio of insulin-positive β-cells/total islet area, extent of islet inflammation (insulitis score) and blood-glucose level.   The therapeutic administration of FTY720 plus sitagliptin significantly improved survival (83% at 70 days after onset, P treatment, and might allow the treatment of type 1 diabetes mellitus with only oral agents. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00218.x, 2012).

  20. Different prion disease phenotypes result from inoculation of cattle with two temporally separated sources of sheep scrapie from Great Britain

    Directory of Open Access Journals (Sweden)

    Hawkins Steve AC

    2006-10-01

    Full Text Available Abstract Background Given the theoretical proposal that bovine spongiform encephalopathy (BSE could have originated from sheep scrapie, this study investigated the pathogenicity for cattle, by intracerebral (i.c. inoculation, of two pools of scrapie agents sourced in Great Britain before and during the BSE epidemic. Two groups of ten cattle were each inoculated with pools of brain material from sheep scrapie cases collected prior to 1975 and after 1990. Control groups comprised five cattle inoculated with sheep brain free from scrapie, five cattle inoculated with saline, and for comparison with BSE, naturally infected cattle and cattle i.c. inoculated with BSE brainstem homogenate from a parallel study. Phenotypic characterisation of the disease forms transmitted to cattle was conducted by morphological, immunohistochemical, biochemical and biological methods. Results Disease occurred in 16 cattle, nine inoculated with the pre-1975 inoculum and seven inoculated with the post-1990 inoculum, with four cattle still alive at 83 months post challenge (as at June 2006. The different inocula produced predominantly two different disease phenotypes as determined by histopathological, immunohistochemical and Western immunoblotting methods and biological characterisation on transmission to mice, neither of which was identical to BSE. Whilst the disease presentation was uniform in all scrapie-affected cattle of the pre-1975 group, the post-1990 inoculum produced a more variable disease, with two animals sharing immunohistochemical and molecular profile characteristics with animals in the pre-1975 group. Conclusion The study has demonstrated that cattle inoculated with different pooled scrapie sources can develop different prion disease phenotypes, which were not consistent with the phenotype of BSE of cattle and whose isolates did not have the strain typing characteristics of the BSE agent on transmission to mice.

  1. Comparison of artificial inoculation methods for studying ...

    African Journals Online (AJOL)

    divya

    2013-05-01

    May 1, 2013 ... value of number of initial disease lesions in drop plus agarose method was highest in all of the time intervals ... V-8 agar (10% V-8 juice, 0.02% CaCO3 and 2% agar) at 24°C for three to .... pathogen inoculation methods (spraying, infiltration, wounding, drop plus agarose and drop) at different time intervals ...

  2. Inoculation Stress Hypothesis of Environmental Enrichment

    Science.gov (United States)

    Crofton, Elizabeth J.; Zhang, Yafang; Green, Thomas A.

    2014-01-01

    One hallmark of psychiatric conditions is the vast continuum of individual differences in susceptibility vs. resilience resulting from the interaction of genetic and environmental factors. The environmental enrichment paradigm is an animal model that is useful for studying a range of psychiatric conditions, including protective phenotypes in addiction and depression models. The major question is how environmental enrichment, a non-drug and non-surgical manipulation, can produce such robust individual differences in such a wide range of behaviors. This paper draws from a variety of published sources to outline a coherent hypothesis of inoculation stress as a factor producing the protective enrichment phenotypes. The basic tenet suggests that chronic mild stress from living in a complex environment and interacting non-aggressively with conspecifics can inoculate enriched rats against subsequent stressors and/or drugs of abuse. This paper reviews the enrichment phenotypes, mulls the fundamental nature of environmental enrichment vs. isolation, discusses the most appropriate control for environmental enrichment, and challenges the idea that cortisol/corticosterone equals stress. The intent of the inoculation stress hypothesis of environmental enrichment is to provide a scaffold with which to build testable hypotheses for the elucidation of the molecular mechanisms underlying these protective phenotypes and thus provide new therapeutic targets to treat psychiatric/neurological conditions. PMID:25449533

  3. Humoral immune response of C57Bl/6j and BALB/c mice immunized with irradiated tachyzoites of Toxoplasma gondii RH strain and oral challenge with ME-49 strain

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez Galisteo Junior, Andres [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Centro de Biotecnologia; Instituto de Medicina Tropical de Sao Paulo, Sao Paulo, SP (Brazil). Lab. de Protozoologia; E-mail: galisteo@usp.br; Zorgi, Nahiara Esteves; Andrade Junior, Heitor Franco de [Instituto de Medicina Tropical de Sao Paulo, Sao Paulo, SP (Brazil). Lab. de Protozoologia; Alves, Janaina Baptista; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Centro de Biotecnologia; Hiramoto, Roberto Mitsuyoshi [instituto Adolfo Lutz, Sao Paulo, SP (Brazil)

    2007-07-01

    Toxoplasmosis, a prevalent widespread infection in man and animals, is mainly transmitted by oral route, through ingestion of oocysts from water and food contaminated with cat feces or infected animal tissue cysts in undercooked meat. Vaccine development implies in effective intestinal immunity, the first site of parasite entry. Radiation (255 Gy/{sup 60}Co) sterilized T. gondii RH strain tachyzoites (RST) induced significant protection when parentally administered, similar to chronically infected and acute disease protected animal. We study the humoral immune response in C57Bl/6j and BALB/c mice immunized with 10{sup 7} RST, by oral (with aluminium hydroxide 3%) or parenteral 3 biweekly administrations. T. gondii antigens specific ELISA for IgG, IgA, IgG1, IgG2a and IgG2b detection was performed in weekly blood samples during immunization. Also we evaluate of the intestinal epithelial of immunized mice the integrity of the radiated parasites by electronic microscopy. After 2 weeks, immunized and control animals were challenged with 10 cysts of ME-49 strain p.o. Protection was determined at the 30th day by brain cyst counting. As it was possible to observe in the intestinal mucosal, the aluminium hydroxide seems to maintain unchanged the parasite morphology and its mechanisms of invasion, probably due to keeping it safe from extreme pH condition of stomach. All immunized groups presented significant protection when challenged with ME-49; however, BALB/c mice showed better protection levels, with only one positive animal on brain microscopic analysis. IgG production in the serum of the animals was higher in groups immunized by i.p route, however, IgA and IgG1 levels were higher in BALB/c mice immunized by oral route. This higher protection found in BALB/c group could probably also be related to the Th2 response, demonstrated by higher IgG1 levels. All these data provide insights in oral immunization schedules for toxoplasmosis prevention, suggesting that oral

  4. The Effects of Stress Inoculation, Physical Relaxation and Skills ...

    African Journals Online (AJOL)

    ... the physical relaxation was more effective than the other treatment conditions in reducing psychophysiological symptoms, the stress inoculation was more effective in reducing the participants worry and emotionality reactions to evaluative situations. Keywords: Stress Inoculation; Physical Relaxation; Stress Management.

  5. FEASIBILITY STUDY OF BUSINESS IN AGARWOOD INOCULATION AT DIFFERENT STEM DIAMETERS AND INOCULATION PERIODS

    Directory of Open Access Journals (Sweden)

    Sri Suharti

    2011-12-01

    Full Text Available Indonesia signifies as the biggest agarwood producer country in the world. Its demand and price tend to increase and have brought about over exploitation of agarwood. Consequently, its population in nature has decreased significantly. To overcome the situation, since 1995, agarwood has been included in the CITES Appendix II. However, illegal exploitation remains persistent and reaches an excessive level. In order to deal with it, agarwood cultivation and its artificial production have been undertaken at several provinces in Indonesia. Some supporting factors for agarwood cultivation and artificial production are the availability of potential land for extensive cultivation, appropriate agro climate condition, simple cultivation technique and already being well adopted by farmers, the availability of necessary pathogen for agarwood inoculation, and the increasing demand with relatively high price. The research aims to analyze the feasibility study of agarwood inoculation business at several stem diameters (15 - 25 cm; 26 -35 cm and 36 - 40 cm and periods of inoculation (1 - 5 years. Data were collected through field observation and literature study. The results showed that inoculation on agarwood producer tree stands at 12.5% interest rate afforded positive net present value (NPV,  internal rate of return (IRR is much higher than market interest and benefit cost (B/C ratio >2 for those three diameter classes. Furthermore, if agarwood harvesting is delayed until five years after inoculation, NPV,  IRR and B/C ratio would be much higher. It can be concluded that inoculation on agarwood producer tree stands (at appropriate age for inoculation is feasible to be developed.

  6. Rapid Dissemination of SIV Follows Multisite Entry after Rectal Inoculation

    Science.gov (United States)

    Prétet, Jean-Luc; Michel-Salzat, Alice; Messent, Valérie; Bogdanova, Anna; Couëdel-Courteille, Anne; Souil, Evelyne; Cheynier, Rémi; Butor, Cécile

    2011-01-01

    Receptive ano-rectal intercourse is a major cause of HIV infection in men having sex with men and in heterosexuals. Current knowledge of the mechanisms of entry and dissemination during HIV rectal transmission is scarce and does not allow the development of preventive strategies. We investigated the early steps of rectal infection in rhesus macaques inoculated with the pathogenic isolate SIVmac251 and necropsied four hours to nine days later. All macaques were positive for SIV. Control macaques inoculated with heat-inactivated virus were consistently negative for SIV. SIV DNA was detected in the rectum as early as four hours post infection by nested PCR for gag in many laser-microdissected samples of lymphoid aggregates and lamina propria but never in follicle-associated epithelium. Scarce SIV antigen positive cells were observed by immunohistofluorescence in the rectum, among intraepithelial and lamina propria cells as well as in clusters in lymphoid aggregates, four hours post infection and onwards. These cells were T cells and non-T cells that were not epithelial cells, CD68+ macrophages, DC-SIGN+ cells or fascin+ dendritic cells. DC-SIGN+ cells carried infectious virus. Detection of Env singly spliced mRNA in the mucosa by nested RT-PCR indicated ongoing viral replication. Strikingly, four hours post infection colic lymph nodes were also infected in all macaques as either SIV DNA or infectious virus was recovered. Rapid SIV entry and dissemination is consistent with trans-epithelial transport. Virions appear to cross the follicle-associated epithelium, and also the digestive epithelium. Viral replication could however be more efficient in lymphoid aggregates. The initial sequence of events differs from both vaginal and oral infections, which implies that prevention strategies for rectal transmission will have to be specific. Microbicides will need to protect both digestive and follicle-associated epithelia. Vaccines will need to induce immunity in lymph nodes

  7. Arthritis-induced alveolar bone loss is associated with changes in the composition of oral microbiota.

    Science.gov (United States)

    Corrêa, Jôice Dias; Saraiva, Adriana Machado; Queiroz-Junior, Celso Martins; Madeira, Mila Fernandes Moreira; Duarte, Poliana Mendes; Teixeira, Mauro Martins; Souza, Danielle Glória; da Silva, Tarcília Aparecida

    2016-06-01

    Rheumatoid arthritis (RA) and periodontitis (PD) are chronic inflammatory disorders that cause bone loss. PD tends to be more prevalent and severe in RA patients. Previous experimental studies demonstrated that RA triggers alveolar bone loss similarly to PD. The aim of this study was to investigate if arthritis-induced alveolar bone loss is associated with modification in the oral microbiota. Checkerboard DNA-DNA hybridization was employed to analyze forty oral bacterial species in 3 groups of C57BL/6 mice: control (n = 12; without any challenge); Y4 (n = 8; received oral inoculation of Aggregatibacter Actinomycetemcomitans strain FDC Y4) and AIA group (n = 12; chronic antigen-induced arthritis). The results showed that AIA and Y4 group exhibited similar patterns of bone loss. The AIA group exhibited higher counts of most bacterial species analyzed with predominance of Gram-negative species similarly to infection-induced PD. Prevotella nigrescens and Treponema denticola were detected only in the Y4 group whereas Campylobacter showae, Streptococcus mitis and Streptococcus oralis were only found in the AIA group. Counts of Parvimonas micra, Selenomonas Noxia and Veillonella parvula were greater in the AIA group whereas Actinomyces viscosus and Neisseira mucosa were in large proportion in Y4 group. In conclusion, AIA is associated with changes in the composition of the oral microbiota, which might account for the alveolar bone loss observed in AIA mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Effects of genotype x bradyrhizobium inoculation or x fertilizer n ...

    African Journals Online (AJOL)

    symbiotic fixation). A set of 52 random lines from a broad-based reference population was evaluated for 2 years with and without B.japonicum inoculation in a split-plot design. Inoculation increased ... Genotype x: Inoculation Interactions, Nitrogen fixation ..... genotype x N treatment interaction was non significant each year ...

  9. 7 CFR 201.24a - Inoculated seed.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Inoculated seed. 201.24a Section 201.24a Agriculture..., Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Labeling Agricultural Seeds § 201.24a Inoculated seed. Seed claimed to be inoculated shall be...

  10. Comparative evaluation of commercial rhizobial inoculants of soybean

    African Journals Online (AJOL)

    Inoculation of soybean seeds with root-nodule bacteria results in a significant increase in nodulation and yield. Two commercial rhizobial inoculants available on the South African market were tested for their efficacy under standardised conditions in a short-term greenhouse experiment. The rhizobial inoculants used were: ...

  11. Comparison of bedside inoculation of culture media with ...

    African Journals Online (AJOL)

    Bedside inoculation of culture media with CSF may improve yields. Objective: To compare the culture yield of CSF inoculated onto culture medium at the bedside to that of CSF inoculated onto culture medium in the microbiology laboratory. Design: Cross-sectional comparative study. Setting: Accident and Emergency ...

  12. Pengaruh lama pemberian aspirin pada ekspresi protein KI-67 dan ketebalan epitel mukosa rongga mulut tikus Wistar jantan (The effect of aspirin administration period on KI-67 expression protein and oral epithelial mucosal thickness in male Wistar mice

    Directory of Open Access Journals (Sweden)

    Dian Yosi Arinawati

    2014-09-01

    Full Text Available Background: Aspirin has been widely used as an anti-inflammatory, antipyretic, and analgesics drugs. It has seriously side effects like gastrointestinal ulceration, delayed healing ulcer, and oral mucosal ulceration when Aspirin is administered for long time. Purpose: The aim of study was to examine the effect of Aspirin administration period on Kiehl-67 (KI-67 protein expressions and oral mucosal epithelial thickness in male Wistar mice. Methods: Experimental laboratory study with post-test only control group design was performed and 40 male Wistar mice were used in this experiment. The samples were divided into 2 groups. Group I was treated with Aspirin, whereas group II was receive aquadest. Each group was divided into 5 subgroups for assessment of the length administration effect. All of mice were sacrificed on day 1, 3, 5, 7 and 10 after treatment. Aspirin was orally administrated with doses of 9 mg/kg body weight. The buccal right of mice oral mucosal tissue was sliced and delivered for immunohistochemistry staining using anti-KI-67. Hematoxylin-eosin (HE staining was performed to measure the oral epithelial thickness. Examination of KI-67 expressions and oral epithelial thickness were performed by using ImageJ software. Two-way Anova and Kruskall-Wallis test were carried-out for data analysis with significant level of 95%. Results: The results revealed that the administration of Aspirin in mice on day 1, 3, 5, 7, and 10 was markedly decreased in the KI-67 protein expressions and oral epithelial thickness compared with that of control (p<0.05, otherwise the duration of Aspirin administration did not affect mucosal epithelial thickness. Conclusion: Aspirin administration period has the potential to suppress the KI-67 protein expression within 10 days; the effect in line with the length of duration. The epithelial thickness was not influenced by the length of Aspirin administration.Latar belakang: Aspirin digunakan sebagai anti inflamasi

  13. Replication of respiratory syncytial virus in lungs of immunodeficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Wyde, P.R.; Sun, C.S.; Knight, V.

    1983-08-01

    Respiratory syncytial virus was frequently isolated during a 10-day test period from the lungs of 4- to 6-week-old immunodeficient nude (nu/nu) mice and from gamma-irradiated C3H mice inoculated intranasally with this virus, but not from similar aged and comparably inoculated normal littermates of these mice. Virus isolation rates and levels of virus in lungs in both groups of immunodeficient mice were similar. No extrapulmonary dissemination of virus was observed in any test group of mice.

  14. Effect of selenium (Se) deficiency on the anti-malarial action of Qinghaosu (QHS) in mice

    Energy Technology Data Exchange (ETDEWEB)

    Levander, O.A.; Ager, A.L.; May, R.

    1986-03-01

    QHS is an endoperoxide, so it occurred to the authors that its anti-malarial action might be potentiated by low glutathione peroxidase (GSH-Px) activity. Weanling female mice were fed 1 of 4 diets: chow or a Torula yeast-based diet supplemented with 0, 0.1 or 0.5 ppm Se as Na/sub 2/SeO/sub 3/. After 6 weeks, mean hepatic GSH-Px activities and plasma Se levels in these 4 dietary groups were 17.3, 0.1, 5.4, and 14.5 munits/mg protein and 242, 4, 230, and 532 ng/ml, respectively. At this time, all mice were inoculated i.p. with asexual blood stages of Plasmodium yoelii. Then groups of 7 or 8 mice fed each diet were given 0, 4, 16, or 64 mg QHS/kg orally bid at 3, 4, and 5 days post inoculation. On the 6th day, blood films were taken and antimalarial activity was assessed by determining % parasitemia (% PARA). Mice given 0 or 4 mg QHS/kg averaged 47% PARA and this was not affected by diet. Mice receiving 64 mg QHS/kg averaged about 1% PARA irrespective of diet. However, mice given 16 mg QHS/kg had 25% PARA when fed chow but only 8 to 11% PARA when fed the Torula diet, regardless of Se intake. Thus, while Se status did not appear to influence the antimalarial potency of QHS, some factor(s) in the Torula diet enhanced its activity at intermediate doses vs. the chow diet.

  15. The inoculation method affects colonization and performance of bacterial inoculant strains in the phytoremediation of soil contaminated with diesel oil.

    Science.gov (United States)

    Afzal, Muhammad; Yousaf, Sohail; Reichenauer, Thomas G; Sessitsch, Angela

    2012-01-01

    Plants in combination with microorganisms can remediate soils, which are contaminated with organic pollutants such as petroleum hydrocarbons. Inoculation of plants with degrading bacteria is one approach to improve remediation processes, but is often not successful due to the competition with resident microorganisms. It is therefore of high importance to address the persistence and colonization behavior of inoculant strains. The objective of this study was to determine whether the inoculation method (seed imbibement and soil inoculation) influences bacterial colonization, plant growth promotion and hydrocarbon degradation. Italian ryegrass was grown in non-sterilized soil polluted with diesel and inoculated with different alkane-degrading strains Pantoea sp. ITSI10, Pantoea sp. BTRH79 and Pseudomonas sp. MixRI75 individually as well as in combination. Inoculation generally had a beneficial effect on plant biomass production and hydrocarbon degradation, however, strains inoculated in soil performed better than applied by seed imbibement. Performance correlated with the colonization efficiency of the inoculated strains. The highest hydrocarbon degradation was observed in the treatment, in which all three strains were inoculated in combination into soil. Our study revealed that besides the degradation potential and competitive ability of inoculant strains the inoculation method plays an important role in determining the success of microbial inoculation.

  16. Treatment of Oral Candidiasis Using Photodithazine®- Mediated Photodynamic Therapy In Vivo.

    Directory of Open Access Journals (Sweden)

    Juliana Cabrini Carmello

    Full Text Available This study evaluated the effectiveness of antimicrobial photodynamic therapy (aPDT in the treatment of oral candidiasis in a murine model using Photodithazine® (PDZ. This model of oral candidiasis was developed to allow the monitoring of the infection and the establishment of the aPDT treatment. Six-week-old female mice were immunosuppressed and inoculated with C. albicans to induce oral candidiasis. PDZ-mediated aPDT and nystatin treatment were carried out for 5 consecutive days with one application per day. The macroscopic evaluation of oral lesions was performed. After each treatment, the tongue was swabbed to recover C. albicans cells. Viable colonies were quantified and the number of CFU/ml determined. The animals were sacrificed 24 hours and 7 days after treatment and the tongues were surgically removed for histological analysis and analysis of inflammatory cytokines expression (IL-1, TNF-α and IL-6 by RT-qPCR. Data were analyzed by two-way ANOVA. PDZ-mediated aPDT was as effective as Nystatin (NYS group in the inactivation of C. albicans, reducing 3 and 3.2 logs10 respectively, 24 h after treatment (p<0.05. Animals underwent PDZ-mediated aPDT showed complete remission of oral lesions, while animals treated with NYS presented partial remission of oral lesions in both periods assessed. Histological evaluation revealed mild inflammatory infiltrate in the groups treated with aPDT and NYS in both periods assessed. The aPDT induced the TNF-α expression when compared with the control (P-L- (p<0.05, 24 h and 7 days after treatment. In summary, the murine model developed here was able to mimic the infection and PDZ-mediated aPDT was effective to treat mice with oral candidiasis.

  17. Effects of oral Lactobacillus administration on antioxidant activities and CD4+CD25+forkhead box P3 (FoxP3)+ T cells in NZB/W F1 mice.

    Science.gov (United States)

    Tzang, Bor-Show; Liu, Chung-Hsien; Hsu, Kuo-Ching; Chen, Yi-Hsing; Huang, Chih-Yang; Hsu, Tsai-Ching

    2017-09-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterised by a dysregulation of the immune system, which causes inflammation responses, excessive oxidative stress and a reduction in the number of cluster of differentiation (CD)4+CD25+forkhead box P3 (FoxP3)+ T cells. Supplementation with certain Lactobacillus strains has been suggested to be beneficial in the comprehensive treatment of SLE. However, little is known about the effect and mechanism of certain Lactobacillus strains on SLE. To investigate the effects of Lactobacillus on SLE, NZB/W F1 mice were orally gavaged with Lactobacillus paracasei GMNL-32 (GMNL-32), Lactobacillus reuteri GMNL-89 (GMNL-89) and L. reuteri GMNL-263 (GMNL-263). Supplementation with GMNL-32, GMNL-89 and GMNL-263 significantly increased antioxidant activity, reduced IL-6 and TNF-α levels and significantly decreased the toll-like receptors/myeloid differentiation primary response gene 88 signalling in NZB/W F1 mice. Notably, supplementation with GMNL-263, but not GMNL-32 and GMNL-89, in NZB/W F1 mice significantly increased the differentiation of CD4+CD25+FoxP3+ T cells. These findings reveal beneficial effects of GMNL-32, GMNL-89 and GMNL-263 on NZB/W F1 mice and suggest that these specific Lactobacillus strains can be used as part of a comprehensive treatment of SLE patients.

  18. Acute liver effects, disposition and metabolic fate of [14C]-fenclozic acid following oral administration to normal and bile-cannulated male C57BL/6J mice.

    Science.gov (United States)

    Pickup, Kathryn; Martin, Scott; Partridge, Elizabeth A; Jones, Huw B; Wills, Jonathan; Schulz-Utermoehl, Tim; McCarthy, Alan; Rodrigues, Alison; Page, Chris; Ratcliffe, Kerry; Sarda, Sunil; Wilson, Ian D

    2017-07-01

    The distribution, metabolism, excretion and hepatic effects of the human hepatotoxin fenclozic acid were investigated following single oral doses of 10 mg/kg to normal and bile duct-cannulated male C57BL/6J mice. Whole body autoradiography showed distribution into all tissues except the brain, with radioactivity still detectable in blood, kidney and liver at 72 h post-dose. Mice dosed with [14C]-fenclozic acid showed acute centrilobular hepatocellular necrosis, but no other regions of the liver were affected. The majority of the [14C]-fenclozic acid-related material recovered was found in the urine/aqueous cage wash, (49%) whilst a smaller portion (13%) was eliminated via the faeces. Metabolic profiles for urine, bile and faecal extracts, obtained using liquid chromatography and a combination of mass spectrometric and radioactivity detection, revealed extensive metabolism of fenclozic acid in mice that involved biotransformations via both oxidation and conjugation. These profiling studies also revealed the presence of glutathione-derived metabolites providing evidence for the production of reactive species by mice administered fenclozic acid. Covalent binding to proteins from liver, kidney and plasma was also demonstrated, although this binding was relatively low (less than 50 pmol eq./mg protein).

  19. Antitumor HPV E7-specific CTL activity elicited by in vivo engineered exosomes produced through DNA inoculation.

    Science.gov (United States)

    Di Bonito, Paola; Chiozzini, Chiara; Arenaccio, Claudia; Anticoli, Simona; Manfredi, Francesco; Olivetta, Eleonora; Ferrantelli, Flavia; Falcone, Emiliana; Ruggieri, Anna; Federico, Maurizio

    2017-01-01

    We recently proved that exosomes engineered in vitro to deliver high amounts of HPV E7 upon fusion with the Nef(mut) exosome-anchoring protein elicit an efficient anti-E7 cytotoxic T lymphocyte immune response. However, in view of a potential clinic application of this finding, our exosome-based immunization strategy was faced with possible technical difficulties including industrial manufacturing, cost of production, and storage. To overcome these hurdles, we designed an as yet unproven exosome-based immunization strategy relying on delivery by intramuscular inoculation of a DNA vector expressing Nef(mut) fused with HPV E7. In this way, we predicted that the expression of the Nef(mut)/E7 vector in muscle cells would result in a continuous source of endogenous (ie, produced by the inoculated host) engineered exosomes able to induce an E7-specific immune response. To assess this hypothesis, we first demonstrated that the injection of a Nef(mut)/green fluorescent protein-expressing vector led to the release of fluorescent exosomes, as detected in plasma of inoculated mice. Then, we observed that mice inoculated intramuscularly with a vector expressing Nef(mut)/E7 developed a CD8(+) T-cell immune response against both Nef and E7. Conversely, no CD8(+) T-cell responses were detected upon injection of vectors expressing either the wild-type Nef isoform of E7 alone, most likely a consequence of their inefficient exosome incorporation. The production of immunogenic exosomes in the DNA-injected mice was formally demonstrated by the E7-specific CD8(+) T-cell immune response we detected in mice inoculated with exosomes isolated from plasma of mice inoculated with the Nef(mut)/E7 vector. Finally, we provide evidence that the injection of Nef(mut)/E7 DNA led to the generation of effective antigen-specific cytotoxic T lymphocytes whose activity was likely part of the potent, therapeutic antitumor effect we observed in mice implanted with TC-1 tumor cells. In summary, we

  20. Influence of inoculation route on the course of infection of Trichomonas gallinae in nonimmune pigeons

    Science.gov (United States)

    Kocan, R.M.

    1971-01-01

    The Jones' Barn strain of Trichomonas gallinae was given to nonimmune pigeons by five different routes: (I) oral; (2) pulmonary; (3) intravenous; (4) intramuscular; (5) subcutaneous. The birds infected by the oral and pulmonarv routes succumbed to typical trichomoniasis involving the liver and lungs respectively. The pulmonary route also produced air sac lesions resulting from trichomonads passing through the lungs via the mesobronchi. Intramuscular and subcutaneous introduction of the parasite resulted in transient infections involving small lesions which were resorbed in I to 2 weeks. The intravenous introductions resulted only in large lesions at the site of inoculation, presumably from perivascular leakage at the time of parasite entry. No other internal lesions were found and cultures made from liver and lung tissue were negative for T. gallinae. The results of infection by the oral and pulmonary routes were not surprising, since these are essentially normal routes of infection. The inhibition of parasite development at the intramuscular and subcutaneous sites of parasite introduction may have resulted from inhibition of the mobility of the parasite by connective tissue or these substrates may have been unsuitable for parasite development. The results of intravenous inoculation are surprising, since it has been stated that T. gallinae reaches the viscera via the circulation. If this were true, lesions should have occurred at least in the lungs where the parasites would have lodged following introduction into a vein. Recovery from infection at any site is apparently sufficient to produce an immunity to the parasite when subsequently introduced via the oral route.

  1. Oral vaccination with a recombinant Salmonella vaccine vector provokes systemic HIV-1 subtype C Gag-specific CD4+ Th1 and Th2 cell immune responses in mice

    Directory of Open Access Journals (Sweden)

    Williamson Anna-Lise

    2009-06-01

    Full Text Available Abstract Background Recombinant Salmonella vaccine vectors may potentially be used to induce specific CD4+ T cell responses against foreign viral antigens. Such immune responses are required features of vaccines against pathogens such as human immunodeficiency virus type 1 (HIV-1. The aim of this study was to investigate the induction of systemic HIV-1-specific CD4+ T helper (Th responses in mice after oral immunization with a live attenuated Salmonella vaccine vector that expressed HIV-1 subtype C Gag. Groups of BALB/c mice were vaccinated orally three times (4 weeks apart with this recombinant Salmonella. At sacrifice, 28 days after the last immunization, systemic CD4+ Th1 and Th2 cytokine responses were evaluated by enzyme-linked immunospot assay and cytometric bead array. HIV-1 Gag-specific IgG1 and IgG2a humoral responses in the serum were determined by enzyme-linked immunosorbent assay. Results Mice vaccinated with the recombinant Salmonella elicited both HIV-1-specific Th1 (interferon-gamma (IFN-γ and tumour necrosis factor-alpha (TNF-α and Th2 (interleukin-4 (IL-4 and interleukin-5 (IL-5 cytokine responses. The vaccine induced 70 (IFN-γ spot-forming units (SFUs/10e6 splenocytes and 238 IL-4 SFUs/10e6 splenocytes. Splenocytes from vaccinated mice also produced high levels of Th1 and Th2 cytokines upon stimulation with a Gag CD4 peptide. The levels of IFN-γ, TNF-α, IL-4 and IL-5 were 7.5-, 29.1-, 26.2- and 89.3-fold above the background, respectively. Both HIV-1 Gag-specific IgG1 and IgG2a antibodies were detected in the sera of vaccinated mice. Conclusion The study highlights the potential of orally-delivered attenuated Salmonella as mucosal vaccine vectors for HIV-1 Subtype C Gag to induce Gag-specific CD4+ Th1 and Th2 cellular immune responses and antibodies which may be important characteristics required for protection against HIV-1 infection.

  2. Increased intake of vegetable oil rich in n-6 PUFA enhances allergic symptoms and prevents oral tolerance induction in whey-allergic mice

    NARCIS (Netherlands)

    van den Elsen, Lieke W J; van Esch, Betty C A M; Dingjan, Gemma M; Hofman, Gerard A; Garssen, Johan; Willemsen, Linette E M

    2015-01-01

    Increased intake of vegetable oils rich in n-6 PUFA, including soyabean oil, has been associated with an increase in allergic disease. The present study aimed to determine the effect of an increasing dose of dietary vegetable oil on allergic outcomes in mice. To study this, mice received a 7 v. 10 %

  3. Oral Herpes

    Science.gov (United States)

    ... Dry Mouth Burning Mouth Tooth Decay See All Oral Complications of Systemic Diseases Cancer Treatment Developmental Disabilities ... care. NIDCR > Image Gallery > Oral Health > Oral Herpes Oral Herpes Main Content Title: Oral Herpes Description: Herpes ( ...

  4. Oral Warts

    Science.gov (United States)

    ... Dry Mouth Burning Mouth Tooth Decay See All Oral Complications of Systemic Diseases Cancer Treatment Developmental Disabilities ... care. NIDCR > Image Gallery > Oral Health > Oral Warts Oral Warts Main Content Title: Oral Warts Description: Warts ...

  5. Encystation--survival of Blastocystis hominis in immunocompetent mice abdomen cavity.

    Science.gov (United States)

    Zhou, Xiao Bo; Zhang, Xu; Qiao, Ji Ying; Cai, Juan; Cheng, Shaoli; Yuan, Yukang; Li, Jun

    2010-05-01

    Human Blastocystis hominis were isolated from diarrhea patients' feces and cultured in vitro. Then the cultures were inoculated intraperitoneally to laboratory mice. The B. hominis in living mice were collected and inoculated again to healthy mice. The B. hominis showed dose-dependent pathogenicity in the primary inoculation. No pathogenicity was observed in the secondary inoculation. The protozoan existed in the living mice abdomen cavity for more than 6 months and the cyst was the only form. These results showed that encystation enable the parasite to avoid the immune attack in competent host and simultaneously decrease the pathogenicity to host. Intraperitoneal inoculation to laboratory mice is a good method to maintain and propagate B. hominis. This is also a good model to study the interaction of B. hominis and immune system.

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

    Directory of Open Access Journals (Sweden)

    Lynn Soong

    2016-08-01

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

  7. Yeast interactions in inoculated wine fermentation

    Directory of Open Access Journals (Sweden)

    Maurizio eCiani

    2016-04-01

    Full Text Available The use of selected starter culture is widely diffused in winemaking. In pure fermentation, the ability of inoculated Saccharomyces cerevisiae to suppress the wild microflora is one of the most important feature determining the starter ability to dominate the process. Since the wine is the result of the interaction of several yeast species and strains, many studies are available on the effect of mixed cultures on the final wine quality. In mixed fermentation the interactions between the different yeasts composing the starter culture can led the stability of the final product and the analytical and aromatic profile. In the present review, we will discuss the recent developments regarding yeast interactions in pure and in mixed fermentation, focusing on the influence of interactions on growth and dominance in the process.

  8. Guillain Barré Syndrome is induced in Non-Obese Diabetic (NOD) mice following Campylobacter jejuni infection and is exacerbated by antibiotics.

    Science.gov (United States)

    St Charles, J L; Bell, J A; Gadsden, B J; Malik, A; Cooke, H; Van de Grift, L K; Kim, H Y; Smith, E J; Mansfield, L S

    2017-02-01

    Campylobacter jejuni is a leading cause of bacterial gastroenteritis linked to several serious autoimmune sequelae such as the peripheral neuropathies Guillain Barré syndrome (GBS) and Miller Fisher syndrome (MFS). We hypothesized that GBS and MFS can result in NOD wild type (WT) mice or their congenic interleukin (IL)-10 or B7-2 knockouts secondary to C. jejuni infection. Mice were gavaged orally with C. jejuni strains HB93-13 and 260.94 from patients with GBS or CF93-6 from a patient with MFS and assessed for clinical neurological signs and phenotypes, anti-ganglioside antibodies, and cellular infiltrates and lesions in gut and peripheral nerve tissues. Significant increases in autoantibodies against single gangliosides (GM1, GQ1b, GD1a) occurred in infected NOD mice of all genotypes, although the isotypes varied (NOD WT had IgG1, IgG3; NOD B7-2-/- had IgG3; NOD IL-10-/- had IgG1, IgG3, IgG2a). Infected NOD WT and NOD IL-10-/- mice also produced anti-ganglioside antibodies of the IgG1 isotype directed against a mixture of GM1/GQ1b gangliosides. Phenotypic tests showed significant differences between treatment groups of all mouse genotypes. Peripheral nerve lesions with macrophage infiltrates were significantly increased in infected mice of NOD WT and IL-10-/- genotypes compared to sham-inoculated controls, while lesions with T cell infiltrates were significantly increased in infected mice of the NOD B7-2-/- genotype compared to sham-inoculated controls. In both infected and sham inoculated NOD IL-10-/- mice, antibiotic treatment exacerbated neurological signs, lesions and the amount and number of different isotypes of antiganglioside autoantibodies produced. Thus, inducible mouse models of post-C. jejuni GBS are feasible and can be characterized based on evaluation of three factors-onset of GBS clinical signs/phenotypes, anti-ganglioside autoantibodies and nerve lesions. Based on these factors we characterized 1) NOD B-7-/- mice as an acute inflammatory

  9. Co-inoculation effects of Bradyrhizobium japonicum and ...

    African Journals Online (AJOL)

    Co-inoculation effects of Bradyrhizobium japonicum and Azospirillum sp. on competitive nodulation and rhizosphere eubacterial community structures of soybean under rhizobia-established soil conditions.

  10. Evaluation of Colicin Effect on the Induction of Treated Mice in Prevention of Infection Caused by Escherichia coli K99

    Directory of Open Access Journals (Sweden)

    Yahya Tahamtan

    2016-11-01

    Full Text Available Background. Colicin produce by colicinogenic E. coli (CEC arenarrow limited spectrum antimicrobial agents that are able to kill or prevent close related strains. Objective. The objective of this study was to evaluation effect of Colicin to induce immunized mice to prevent infection caused by E. coliK99. Patient and Methods. The experiment was conducted into two mice groups (30 in each group with two weeks old. All mice were administered by streptomycin sulfate prior to treatment to eliminate resident E. coli. Group one was orally inoculated with PBS as control and the second was immunized by Colicin solution as immunize group. Both control and immunized group were challenged by 3 LD 50 of E. coli K99 and follow a week. Results. Immunized mice group were not showed severe clinical signs. While diarrhea with different sings of colibaccillosis was established in control group and infected mice was died. Conclusion. Overuse antibiotics developed serious new types of multi drug resistance in human medicine and therefore has limited their use in farm animals. The study indicates the use of Colicin and biotherapy instead of antibiotic is more safe and efficient for control of E. coliK99 infection. Immunized mice by Colicin solution protected E. coli K99 colonization and reduce fecal shedding. Investigation in livestock for applying Colicin in farm animal is recommended.

  11. Efficacy of oral administration of heat-killed probiotics from Mongolian dairy products against influenza infection in mice: alleviation of influenza infection by its immunomodulatory activity through intestinal immunity.

    Science.gov (United States)

    Takeda, Shiro; Takeshita, Masahiko; Kikuchi, Yukiharu; Dashnyam, Bumbein; Kawahara, Satoshi; Yoshida, Hiroki; Watanabe, Wataru; Muguruma, Michio; Kurokawa, Masahiko

    2011-12-01

    Some probiotics possess immunomodulatory activities and have been used as complementary and alternative medicines. We previously found that 10 lactic acid bacteria (LAB) strains isolated from traditional Mongolian dairy products showed probiotic potential in vitro. In this study, we assessed the immunomodulatory activity of 10 LABs on influenza virus (IFV) infection in relation to their efficacies in IFV-infected mice. In an intranasal IFV infection model in mice, oral administration of boiled Lactobacillus plantarum 06CC2 strain (20mg/mouse), one of the 10 LABs, twice daily for 10 days starting two days before infection was significantly effective in protecting the body weight loss of infected mice, reducing virus yields in the lungs on days 2, 4, and 6 after infection, and prolonging survival times without toxicity. The total numbers of infiltrated cells in the bronchoalveolar lavage fluid (BALF), especially macrophages and neutrophils, were significantly reduced by 06CC2 administration on day 2. On day 2, tumor necrosis factor (TNF)-α production in BALF was also reduced significantly, but interferon-α, interleukin-12, and interferon-γ productions were augmented and natural killer (NK) cell activity was significantly elevated. Furthermore, the gene expressions of interleukin-12 receptor and interferon-γ in Peyer's patches were augmented by 06CC2 administration on day 2. Thus, 06CC2 was suggested to alleviate influenza symptoms in mice in correlation with the augmentation of NK cell activity associated with the enhancement of interferon-α and Th1 cytokine productions through intestinal immunity and the reduction of TNF-α in the early stage of infection. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Prevotella intermedia induces severe bacteremic pneumococcal pneumonia in mice with upregulated platelet-activating factor receptor expression.

    Science.gov (United States)

    Nagaoka, Kentaro; Yanagihara, Katsunori; Morinaga, Yoshitomo; Nakamura, Shigeki; Harada, Tatsuhiko; Hasegawa, Hiroo; Izumikawa, Koichi; Ishimatsu, Yuji; Kakeya, Hiroshi; Nishimura, Masaharu; Kohno, Shigeru

    2014-02-01

    Streptococcus pneumoniae is the leading cause of respiratory infection worldwide. Although oral hygiene has been considered a risk factor for developing pneumonia, the relationship between oral bacteria and pneumococcal infection is unknown. In this study, we examined the synergic effects of Prevotella intermedia, a major periodontopathic bacterium, on pneumococcal pneumonia. The synergic effects of the supernatant of P. intermedia (PiSup) on pneumococcal pneumonia were investigated in mice, and the stimulation of pneumococcal adhesion to human alveolar (A549) cells by PiSup was assessed. The effects of PiSup on platelet-activating factor receptor (PAFR) transcript levels in vitro and in vivo were analyzed by quantitative real-time PCR, and the differences between the effects of pneumococcal infection induced by various periodontopathic bacterial species were verified in mice. Mice inoculated with S. pneumoniae plus PiSup exhibited a significantly lower survival rate, higher bacterial loads in the lungs, spleen, and blood, and higher inflammatory cytokine levels in the bronchoalveolar lavage fluid (macrophage inflammatory protein 2 and tumor necrosis factor alpha) than those infected without PiSup. In A549 cells, PiSup increased pneumococcal adhesion and PAFR transcript levels. PiSup also increased lung PAFR transcript levels in mice. Similar effects were not observed in the supernatants of Porphyromonas gingivalis or Fusobacterium nucleatum. Thus, P. intermedia has the potential to induce severe bacteremic pneumococcal pneumonia with enhanced pneumococcal adhesion to lower airway cells.

  13. Oral Biology, Oral Pathology, and Oral Treatments

    National Research Council Canada - National Science Library

    Nammour, Samir; Zeinoun, Toni; Yoshida, Kenji; Brugnera Junior, Aldo

    2016-01-01

    ..., and reproduction in any medium, provided the original work is properly cited. Oral biology, oral pathology, and oral treatments are interesting fields in dentistry. The rapid evolution of technologies ...

  14. Hymenolepis diminuta and H. nana: cross immunity against the lumen phase in BALB/c mice.

    Science.gov (United States)

    Ito, A; Onitake, K

    1987-08-01

    When BALB/c mice initially given cysticercoids of Hymenolepis diminuta orally (Day 0) were challenged with eggs or cysticercoids of H. nana, almost all the mice became completely resistant to H. nana challenges from Day 30 onward, and no luminal adults of H. nana were established. There was a tendency for the number of tissue cysticercoids recovered 4 days after egg challenge in immunized mice to be much less than that in control mice (P less than 0.001, Student's t test). However, when these cysticercoids recovered from immune group mice were inoculated into uninfected mice, they matured in the lumen. Thus, the cross immunity to H. nana challenge evoked by an initial prepatent infection with H. diminuta appeared to be directed not against the tissue phase but against the lumen phase of H. nana. When BALB/c mice initially given eggs of H. nana were challenged with H. diminuta, they became resistant to H. diminuta from Day 15 onward. When the mice given eggs of H. nana were treated with a cestocide, praziquantel, at the beginning of the expected luminal development of H. nana and experienced a tissue phase only before challenge with H. diminuta, they showed no resistance to H. diminuta. Thus, the cross immunity to H. diminuta challenge evoked by an initial patent infection with H. nana appeared to be due to the immunogens of the lumen phase of H. nana but not those of the tissue phase. The cross immunity may be, therefore, essentially evoked by the lumen phase of these two phylogenetically closely related species and not by or against the tissue phase of H. nana.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Effects of single and combined inoculations of selected Trichoderma ...

    African Journals Online (AJOL)

    Effects of single and combined inoculations of selected Trichoderma and Bacillus isolates on growth of dry bean and biological control of Rhizoctonia solani damping-off. ... Greenhouse trials showed that combined inoculations of T. atroviride strain 6 and B. subtilis B69 gave the highest growth promotion of bean in terms of ...

  16. Biolistic inoculation of cassava ( Manihot esculenta Crantz) with ...

    African Journals Online (AJOL)

    We report for the first time successful infection, induced by SACMV DNA A and B dimer, of cassava cultivar TMS60444 using biolistic inoculation. Typical mosaic symptoms started to show at 14 days post-inoculation (dpi) in infected cassava plants, and SACMV replication was confirmed using PCR. Potential applications of ...

  17. Potential woodpecker nest trees through artificial inoculation of heart rots

    Science.gov (United States)

    Richard N. Conner; James G. Dickson; J. Howard Williamson

    1983-01-01

    We suggest that the fungus Spongipellis pachyodon might be used to artificially create suitable hardwood nest trees for woodpeckers in both young and older trees and when supplies of potential nest trees are limited. Sizes of trees suitable for inoculation, inoculation heights, and densities of snags are suggested for six species of woodpeckers.

  18. Effect of plant-growth-promoting rhizobacteria inoculation on plant ...

    African Journals Online (AJOL)

    Effect of plant-growth-promoting rhizobacteria inoculation on plant growth, productivity and economics of Basmati rice. ... Egyptian Journal of Biology ... Abstract. A field experiment was conducted in a wet season (Kharif) to study the effects of plant growth-promoting rhizobacteria(PGPR) inoculation on agronomic traits and ...

  19. Effects of rhizobium inoculation, sulfur and phosphorus applications ...

    African Journals Online (AJOL)

    SERVER

    2008-03-18

    Mar 18, 2008 ... This study was carried out to determine the effects of sulfur and phosphorus application and rhizobium inoculation ... they were obtained from 80 kg ha-1 P with 879 kg ha-1 from 100 kg ha-1 S with 818 and from inoculation with 784 kg ... Fertilizer P was applied in bands 3 cm below rows sown to chick pea.

  20. Oral administration of soluble β-glucans extracted from Grifola frondosa induces systemic antitumor immune response and decreases immunosuppression in tumor-bearing mice.

    Science.gov (United States)

    Masuda, Yuki; Inoue, Hiroko; Ohta, Hiroya; Miyake, Ayumi; Konishi, Morichika; Nanba, Hiroaki

    2013-07-01

    Maitake D (MD)-Fraction is a highly purified soluble β-glucan derived from Grifola frondosa (an oriental edible mushroom). Intraperitoneal (i.p.) injection of MD-Fraction has been reported to inhibit tumor growth via enhancement of the host immune system. In this study, we demonstrated that oral administration of MD-Fraction as well as i.p. injection significantly inhibited tumor growth in murine tumor models. After oral administration, MD-Fraction was not transferred to the blood in its free form but was captured by antigen-presenting cells such as macrophages and dendritic cells (DCs) present in the Peyer's patch. The captured MD-Fraction was then transported to the spleen, thereby inducing the systemic immune response. Our study showed that MD-Fraction directly induced DC maturation via a C-type lectin receptor dectin-1 pathway. The therapeutic response of orally administered MD-Fraction was associated with (i) induced systemic tumor-antigen specific T cell response via dectin-1-dependent activation of DCs, (ii) increased infiltration of the activated T cells into the tumor and (iii) decreased number of tumor-caused immunosuppressive cells such as regulatory T cells and myeloid-derived suppressor cells. Our preclinical study suggests that MD-Fraction is a useful oral therapeutic agent in the management of patients with cancer. Copyright © 2012 UICC.

  1. EVALUATION OF THE THERAPEUTIC EFFICACY OF LEVAMISOLE HYDROCHLORIDE ON THIRD-STAGE LARVAE OF Lagochilascaris minor IN EXPERIMENTALLY INFECTED MICE

    Directory of Open Access Journals (Sweden)

    Dulcinéa Maria Barbosa CAMPOS

    2016-01-01

    Full Text Available Lagochilascariosis, a disease caused by Lagochilascaris minor, affects the neck, sinuses, tonsils, lungs, the sacral region, dental alveoli, eyeballs and the central nervous system of humans. A cycle of autoinfection may occur in human host tissues characterized by the presence of eggs, larvae and adult worms. This peculiarity of the cycle hinders therapy, since there are no drugs that exhibit ovicidal, larvicidal and vermicidal activity. Given these facts, we studied the action of levamisole hydrochloride on third-stage larvae in the migration phase (G1 and on encysted larvae (G3 of L. minor. To this end, 87 inbred mice of the C57BL/6 strain were divided into test groups comprising 67 animals (G1-37; G3-30 and a control group (G2-10; G4-10 with 20 animals. Each animal was inoculated orally with 2,000 infective eggs of the parasite. The animals of the test groups were treated individually with a single oral dose of levamisole hydrochloride at a concentration of 0.075 mg. The drug was administered either 30 minutes prior to the parasite inoculation (G1 animals or 120 days after the inoculation (G3 animals. The mice in the control groups were not treated with the drug. After the time required for the migration and the encysting of L. minor larvae, all the animals were euthanized and their tissues examined. The data were analyzed using the Student's unpaired t-test and the Levene test. The groups showed no statistically significant difference. Levamisole hydrochloride was ineffective on third-stage larvae of L. minor. These findings explain the massive expulsion of live adult worms, as well as the use of long treatment schemes, owing to the persistence of larvae and eggs in human parasitic lesions.

  2. EVALUATION OF THE THERAPEUTIC EFFICACY OF LEVAMISOLE HYDROCHLORIDE ON THIRD-STAGE LARVAE OF Lagochilascaris minor IN EXPERIMENTALLY INFECTED MICE.

    Science.gov (United States)

    Campos, Dulcinéa Maria Barbosa; Barbosa, Alverne Passos; Oliveira, Jayrson Araújo; Barbosa, Carlos Augusto Lopes; Lobo, Tamara Flavia Correa; Silva, Luana Gabriella; Thomaz, Douglas Vieira; Peixoto, Josana de Castro

    2016-01-01

    Lagochilascariosis, a disease caused by Lagochilascaris minor, affects the neck, sinuses, tonsils, lungs, the sacral region, dental alveoli, eyeballs and the central nervous system of humans. A cycle of autoinfection may occur in human host tissues characterized by the presence of eggs, larvae and adult worms. This peculiarity of the cycle hinders therapy, since there are no drugs that exhibit ovicidal, larvicidal and vermicidal activity. Given these facts, we studied the action of levamisole hydrochloride on third-stage larvae in the migration phase (G1) and on encysted larvae (G3) of L. minor. To this end, 87 inbred mice of the C57BL/6 strain were divided into test groups comprising 67 animals (G1-37; G3-30) and a control group (G2-10; G4-10) with 20 animals. Each animal was inoculated orally with 2,000 infective eggs of the parasite. The animals of the test groups were treated individually with a single oral dose of levamisole hydrochloride at a concentration of 0.075 mg. The drug was administered either 30 minutes prior to the parasite inoculation (G1 animals) or 120 days after the inoculation (G3 animals). The mice in the control groups were not treated with the drug. After the time required for the migration and the encysting of L. minor larvae, all the animals were euthanized and their tissues examined. The data were analyzed using the Student's unpaired t-test and the Levene test. The groups showed no statistically significant difference. Levamisole hydrochloride was ineffective on third-stage larvae of L. minor. These findings explain the massive expulsion of live adult worms, as well as the use of long treatment schemes, owing to the persistence of larvae and eggs in human parasitic lesions.

  3. Microbial inoculants for small scale composting of putrescible kitchen wastes.

    Science.gov (United States)

    Nair, J; Okamitsu, K

    2010-06-01

    This research looked at the need for ligno-cellulolytic inoculants (EM bacteria and Trichoderma sp.) in small to medium scale composting of household wastes. A mixture of household organic waste comprised of kitchen waste, paper, grass clippings and composted material was subjected to various durations of thermo composting followed by vermicomposting with and without microbial inoculants for a total of 28days. The results revealed that ligno-celluloytic inoculants are not essential to speed up the process of composting for onsite small scale household organic waste treatment as no significant difference was observed between the control and those inoculated with Trichoderma and EM in terms of C:N ratio of the final product. However, it was observed that EM inoculation enhanced reproductive rate of earthworms, and so probably created the best environment for vermicomposting, in all treatment groups. Copyright 2010 Elsevier Ltd. All rights reserved.

  4. Intranasal inoculation of white-tailed deer (Odocoileus virginianus with lyophilized chronic wasting disease prion particulate complexed to montmorillonite clay.

    Directory of Open Access Journals (Sweden)

    Tracy A Nichols

    Full Text Available Chronic wasting disease (CWD, the only known prion disease endemic in wildlife, is a persistent problem in both wild and captive North American cervid populations. This disease continues to spread and cases are found in new areas each year. Indirect transmission can occur via the environment and is thought to occur by the oral and/or intranasal route. Oral transmission has been experimentally demonstrated and although intranasal transmission has been postulated, it has not been tested in a natural host until recently. Prions have been shown to adsorb strongly to clay particles and upon oral inoculation the prion/clay combination exhibits increased infectivity in rodent models. Deer and elk undoubtedly and chronically inhale dust particles routinely while living in the landscape while foraging and rutting. We therefore hypothesized that dust represents a viable vehicle for intranasal CWD prion exposure. To test this hypothesis, CWD-positive brain homogenate was mixed with montmorillonite clay (Mte, lyophilized, pulverized and inoculated intranasally into white-tailed deer once a week for 6 weeks. Deer were euthanized at 95, 105, 120 and 175 days post final inoculation and tissues examined for CWD-associated prion proteins by immunohistochemistry. Our results demonstrate that CWD can be efficiently transmitted utilizing Mte particles as a prion carrier and intranasal exposure.

  5. Oral treatment with essential oil of Hyptis spicigera Lam. (Lamiaceae) reduces acute pain and inflammation in mice: Potential interactions with transient receptor potential (TRP) ion channels.

    Science.gov (United States)

    Simões, Róli Rodrigues; Coelho, Igor Dos Santos; Junqueira, Stella Célio; Pigatto, Glauce Regina; Salvador, Marcos José; Santos, Adair Roberto Soares; de Faria, Felipe Meira

    2017-03-22

    The genus Hyptis comprehends almost 400 species widespread in tropical and temperate regions of America. The use of Hyptis spicigera Lam. (Lamiaceae) is reported in traditional medicine due to its gastroprotective, anti-inflammatory and analgesic properties. The rationale of this study was to investigate the potential use of the essential oil of H. spicigera (EOHs) as analgesic. The antinociceptive effect of EOHs was verified analyzing acute nocifensive behavior of mice induced by chemical noxious stimuli [i.e., formalin and transient receptor potential (TRP) channels agonists]. We also verified the effects of EOHs on locomotor activity and motor performance in mice. Finally, we investigate the involvement of central afferent C-fibers with EOHs analgesic effect. EOHs presented antinociceptive effect at 300 and 1000mg/kg on formalin-induced pain behavior model, presenting 50% and 72% of inhibition during the first phase (ED50 =292mg/kg), and 85% and 100% during de second phase (ED50 =205mg/kg), respectively. Temperature of the hind paw was reduced by EOHs treatment in a dose-dependent manner; oedema was diminished only by EOHs 1000mg/kg. EOHs does not impaired locomotor activity or motor performance. For mice injected with capsaicin, a TRPV1 activator, EOHs (1000mg/kg, ED50 =660mg/kg) showed decreased (63%) nociceptive behavior. When injected with cinnamaldehyde (TRPA1 activator), mice treated with EOHs showed 23%, 43% and 66% inhibition on nociceptive behavior (100, 300 and 1000mg/kg, respectively; ED50 402mg/kg). When mice were injected with menthol (TRPM8 activator), EOHs showed 29%, 59% and 98% inhibition of nociceptive behavior (100, 300 and 1000mg/kg, respectively; with ED50 =198mg/kg. Finally, when desensitized mice were injected with menthol, EOHs (300mg/kg) does not show antinociceptive effect. This study demonstrated the efficacy of EOHs on experimental models of nociception. We have found the involvement of TRP channels V1, A1 and M8 with EOHs activity

  6. Experimentally induced lameness in turkeys inoculated with a newly emergent turkey reovirus.

    Science.gov (United States)

    Sharafeldin, Tamer A; Mor, Sunil K; Bekele, Aschalew Z; Verma, Harsha; Noll, Sally L; Goyal, Sagar M; Porter, Robert E

    2015-02-24

    Newly emergent turkey arthritis reoviruses (TARVs) have been isolated from cases of lameness in male turkeys over 10 weeks of age. In a previous study, experimental inoculation of TARV in one-week-old turkey poults produced lymphocytic tenosynovitis at four weeks post inoculation but without causing clinical lameness. This study was undertaken to determine if TARV infection at an early age can lead to clinical lameness in birds as they age. One-week-old male turkeys were inoculated orally with a TARV (strain TARV-O'Neil) and monitored for the development of gait defects until 16 weeks of age. At 4, 8, 12 and 16 weeks of age, a subset of birds was euthanized followed by the collection of gastrocnemius tendon, digital flexor tendon, and intestines for virus detection by rRT-PCR and for histologic inflammation scoring. Clinical lameness was first displayed in TARV-infected turkeys at 8 weeks of age and ruptured gastrocnemius tendons with progressive lameness were also seen at 12-16 weeks of age. The virus was detected in gastrocnemius tendon of 4- 8- and 12-week-old turkeys but not in 16-week-old turkeys. Histologic inflammation scores of tendons at each of the four time points were significantly higher in the virus-inoculated group than in the control group (p < 0.01). Lesions began as lymphocytic tenosynovitis with mild synoviocyte hyperplasia at four weeks of age and progressed to fibrosis as the birds aged. These results demonstrate the potential of TARV to infect young turkeys and to produce subclinical tenosynovitis that becomes clinically demonstrable as the turkeys age.

  7. Pathogenesis of Escherichia coli O157:H7 Strain 86-24 Following Oral Infection of BALB/c Mice with an Intact Commensal Flora

    Science.gov (United States)

    2010-01-01

    fur. lethargy, tremors , etc.) and succumbed to infection. To more closely examine the systemic effects of E. coli 0157:H7 infection in mice with an...ataxia, tremor , and convulsions), yet had no detectable bacteria in their blood. The final two animals from the bacteremia-assessment group were...607-25. (2) Rangel jM, Sparling PH, Crowe C, Griffin PM, Swerdlow DL Epidemiology of Escherichia coli 0157:H7 ourbreaks, Unired Srares, 1982-2002

  8. Evaluation of Plaque Stability of Advanced Atherosclerotic Lesions in Apo E-Deficient Mice after Treatment with the Oral Factor Xa Inhibitor Rivaroxaban

    Directory of Open Access Journals (Sweden)

    Qianxing Zhou

    2011-01-01

    Full Text Available Aim. Thrombin not only plays a central role in thrombus formation and platelet activation, but also in induction of inflammatory processes. Activated factor X (FXa is traditionally known as an important player in the coagulation cascade responsible for thrombin generation. We assessed the hypothesis that rivaroxaban, a direct FXa inhibitor, attenuates plaque progression and promotes stability of advanced atherosclerotic lesions in an in vivo model. Methods and Results. Rivaroxaban (1 or 5 mg/kg body weight/day or standard chow diet was administered for 26 weeks to apolipoprotein E-deficient mice (n=20 per group with already established atherosclerotic lesions. There was a nonsignificant reduction of lesion progression in the high-concentration group, compared to control mice. FXa inhibition with 5 mg Rivaroxaban/kg/day resulted in increased thickness of the protective fibrous caps (12.3±3.8 μm versus 10.1±2.7 μm; P<.05, as well as in fewer medial erosions and fewer lateral xanthomas, indicating plaque stabilizing properties. Real time-PCR from thoracic aortas revealed that rivaroxaban (5 mg/kg/day treatment reduced mRNA expression of inflammatory mediators, such of IL-6, TNF-α, MCP-1, and Egr-1 (P<.05. Conclusions. Chronic administration of rivaroxaban does not affect lesion progression but downregulates expression of inflammatory mediators and promotes lesion stability in apolipoprotein E-deficient mice.

  9. DNA Vaccines: Protective Immunizations by Parenteral, Mucosal, and Gene-Gun Inoculations

    Science.gov (United States)

    Fynan, Ellen F.; Webster, Robert G.; Fuller, Deborah H.; Haynes, Joel R.; Santoro, Joseph C.; Robinson, Harriet L.

    1993-12-01

    Plasmid DNAs expressing influenza virus hemagglutinin glycoproteins have been tested for their ability to raise protective immunity against lethal influenza challenges of the same subtype. In trials using two inoculations of from 50 to 300 μg of purified DNA in saline, 67-95% of test mice and 25-63% of test chickens have been protected against a lethal influenza challenge. Parenteral routes of inoculation that achieved good protection included intramuscular and intravenous injections. Successful mucosal routes of vaccination included DNA drops administered to the nares or trachea. By far the most efficient DNA immunizations were achieved by using a gene gun to deliver DNA-coated gold beads to the epidermis. In mice, 95% protection was achieved by two immunizations with beads loaded with as little as 0.4 μg of DNA. The breadth of routes supporting successful DNA immunizations, coupled with the very small amounts of DNA required for gene-gun immunizations, highlight the potential of this remarkably simple technique for the development of subunit vaccines.

  10. Effects of orally administered Actinidia arguta (Hardy Kiwi) fruit extract on 2-chloro-1,3,5-trinitrobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice.

    Science.gov (United States)

    Kim, Ji-Yun; Lee, In-Ki; Son, Mi-Won; Kim, Kyu-Han

    2009-10-01

    Atopic dermatitis (AD) is characterized by highly pruritic, chronic, relapsing inflammatory skin lesions. Furthermore, therapeutic choices are limited, especially in long-standing cases, despite its increasing prevalence. This study was performed to examine the clinical efficacy and the therapeutic mechanism underlying the effects of Actinidia arguta (hardy kiwi) fruit extract in an animal model of AD. To examine the effects of A. arguta extract on AD, 2-chloro-1,3,5-trinitrobenzene-treated NC/Nga mice were orally administered A. arguta extract (100 mg/kg/day), tacrolimus (1 mg/kg/day), or dexamethasone (3 mg/kg/day) for 8 weeks. Skin severity scores, epidermal thickening, mast cell infiltration and degranulation, total serum immunoglobulin (Ig) isotypes (IgE, IgG(1)), and cytokine (interleukin [IL]-4 and interferon [IFN]-gamma) and Toll-like receptor (TLR) (TLR-2, TLR-4, and TLR-9) expressions were examined in each of the study groups. Orally administered A. arguta extract significantly reduced clinical dermatitis severity, epidermal thickness, mast cell dermal infiltration and degranulation, and total levels of serum IgE and IgG(1). Furthermore, this suppression of total serum IgE and IgG(1) levels was accompanied by a decrease in IL-4 and an increase in IFN-gamma expression in skin and splenocytes. Interestingly, TLR-9 expression was increased by oral A. arguta extract. This study confirms that A. arguta extract has potential as a dietary therapeutic agent for the treatment of AD. Furthermore, our findings suggest that its clinical efficacy and mode of action against AD are associated with the modulation of biphasic T-helper (Th) 1/Th2 cytokines, with the inhibition of Th2-mediated IgE overproduction, and possibly with the up-regulation of TLR-9.

  11. Mycorrhizal inoculation affects the phytochemical content in strawberry fruits

    Directory of Open Access Journals (Sweden)

    Ana Paula Cecatto

    2016-04-01

    Full Text Available The aim of this research was to evaluate the effect of the inoculation date of arbuscular mycorrhizal fungi on the fruit quality and the content of phytochemicals in a strawberry soilless growing system. The experiment was performed in Huelva (Spain and was conducted in a greenhouse on the La Rábida Campus of Huelva University under natural light and temperature from October 2013 to June 2014. Three short-day strawberry cultivars (‘Splendor’, ‘Sabrina’ and ‘Fortuna’ were grown in polyethylene bags filled with coconut fibres. Randomized block design, with 3 repetitions and factorial arrangement (3 cultivars x 3 treatments, was established. Each replicate consisted of one bag with 12 plants supporting structures at 40 cm height. The treatments were: T1 = mycorrhizal inoculation in the transplantation; T2 = mycorrhizal inoculation 30 days after transplantation (DAT; and T0 = control treatment, without inoculation. Arbuscular mycorrhizal fungi inoculation significantly affected the contents of anthocyanin and phenolics. When the inoculation is performed in the transplantation, the fruits showed a high content of anthocyanin and total phenolics. The mycorrhizal inoculation influences decreasing the acidity in fruit throughout the growing season and increase firmness only during the early stage of production.

  12. Inoculation message treatments for curbing noncommunicable disease development.

    Science.gov (United States)

    Mason, Alicia M; Miller, Claude H

    2013-07-01

    To study the effect of various types of inoculation message treatments on resistance to persuasive and potentially deceptive health- and nutrition-related (HNR) content claims of commercial food advertisers. A three-phase experiment was conducted among 145 students from a Midwestern U.S. university. Quantitative statistical analyses were used to interpret the results. RESULTS provide clear evidence that integrating regulatory focus/fit considerations enhances the treatment effectiveness of inoculation messages. Inoculation messages that employed a preventative, outcome focus with concrete language were most effective at countering HNR advertising claims. The findings indicate that inoculation fosters resistance equally across the most common types of commercially advertised HNR product claims (e.g., absolute, general, and structure/function claims). As the drive to refine the inoculation process model continues, further testing and application of this strategy in a public health context is needed to counter ongoing efforts by commercial food advertisers to avoid government regulations against deceptive practices such as dubious health/nutrition claims. This research advances inoculation theory by providing evidence that 1) good regulatory fit strengthens the effect of refutational preemption and 2) an inoculation approach is highly effective at fostering resistance to commercial advertisers' HNR content claims. This macro approach appears far superior to education or information-based promotional health campaigns targeted solely at specific populations demonstrating rising rates of noncommunicable disease.

  13. Genetically modified rabies virus ERA strain is safe and induces long-lasting protective immune response in dogs after oral vaccination.

    Science.gov (United States)

    Shuai, Lei; Feng, Na; Wang, Xijun; Ge, Jinying; Wen, Zhiyuan; Chen, Weiye; Qin, Lide; Xia, Xianzhu; Bu, Zhigao

    2015-09-01

    Oral immunization in free-roaming dogs is one of the most practical approaches to prevent rabies for developing countries. The safe, efficient and long-lasting protective oral rabies vaccine for dogs is highly sought. In this study, rabies virus (RABV) Evelyn-Rokitnicki-Abelseth (ERA) strain wild-type (rERA) and a genetically modified type (rERAG333E) containing a mutation from arginine to glutamic acid at residue 333 of glycoprotein (G333E) were generated by reverse genetic. The recombinant virus rERAG333E retained growth properties of similar to the parent strain rERA in BHK-21 cell culture. The G333E mutation showed genetic stability during passage into neuroblastoma cells and in the brains of suckling mice and was significantly reduced the virulence of rERA in mice. rERAG333E was immunogenic in dogs by intramuscular inoculation. Mice orally vaccinated with rERAG333E induced strong and one year longer virus neutralizing antibodies (VNA) to RABV, and were completely protected from challenge with lethal street virus at 12months after immunization. Dogs received oral vaccination with rERAG333E induced strong protective RABV VNA response, which lasted for over 3years, and moderate saliva RABV-specific IgA. Moreover, sizeable booster responses to RABV VNA were induced by a second oral dose 1year after the first dose. These results demonstrated that the genetically modified ERA vaccine strain has the potential to serve as a safe and efficient oral live vaccine against rabies in dogs. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Influence of indigenous microbiota on experimental toxoplasmosis in conventional and germ-free mice.

    Science.gov (United States)

    Nascimento, Bruna B; Cartelle, Christiane T; Noviello, Maria de L; Pinheiro, Breno V; de Almeida Vitor, Ricardo W; Souza, Danielle da G; de Vasconcelos Generoso, Simone; Cardoso, Valbert N; Martins, Flaviano Dos S; Nicoli, Jacques R; Arantes, Rosa M E

    2017-08-01

    Toxoplasmosis represents one of the most common zoonoses worldwide. Its agent, Toxoplasma gondii, causes a severe innate pro-inflammatory response. The indigenous intestinal microbiota promotes host animal homoeostasis and may protect the host against pathogens. Germ-free (GF) animals provide an important tool for the study of interactions between host and microbiota. In this study, we assessed the role of indigenous microorganisms in disease development utilizing a murine toxoplasmosis model, which includes conventional (CV) and GF NIH Swiss mice. CV and GF mice orally inoculated with T. gondii had similar survival curves. However, disease developed differently in the two animal groups. In CV mice, intestinal permeability increased and levels of intestinal pro-inflammatory cytokines were altered. In GF animals, there were discrete epithelial degenerative changes and mucosal oedema, but the liver and lungs displayed significant lesions. We conclude that, despite similar survival curves, CV animals succumb to an exaggerated inflammatory response, whereas GF mice fail to produce an adequate systemic response. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

  15. Virological and serological findings in Rousettus aegyptiacus experimentally inoculated with vero cells-adapted hogan strain of Marburg virus.

    Science.gov (United States)

    Paweska, Janusz T; Jansen van Vuren, Petrus; Masumu, Justin; Leman, Patricia A; Grobbelaar, Antoinette A; Birkhead, Monica; Clift, Sarah; Swanepoel, Robert; Kemp, Alan

    2012-01-01

    The Egyptian fruit bat, Rousettus aegyptiacus, is currently regarded as a potential reservoir host for Marburg virus (MARV). However, the modes of transmission, the level of viral replication, tissue tropism and viral shedding pattern remains to be described. Captive-bred R. aegyptiacus, including adult males, females and pups were exposed to MARV by different inoculation routes. Blood, tissues, feces and urine from 9 bats inoculated by combination of nasal and oral routes were all negative for the virus and ELISA IgG antibody could not be demonstrated for up to 21 days post inoculation (p.i.). In 21 bats inoculated by a combination of intraperitoneal/subcutaneous route, viremia and the presence of MARV in different tissues was detected on days 2-9 p.i., and IgG antibody on days 9-21 p.i. In 3 bats inoculated subcutaneously, viremia was detected on days 5 and 8 (termination of experiment), with virus isolation from different organs. MARV could not be detected in urine, feces or oral swabs in any of the 3 experimental groups. However, it was detected in tissues which might contribute to horizontal or vertical transmission, e.g. lung, intestines, kidney, bladder, salivary glands, and female reproductive tract. Viremia lasting at least 5 days could also facilitate MARV mechanical transmission by blood sucking arthropods and infections of susceptible vertebrate hosts by direct contact with infected blood. All bats were clinically normal and no gross pathology was identified on post mortem examination. This work confirms the susceptibility of R. aegyptiacus to infection with MARV irrespective of sex and age and contributes to establishing a bat-filovirus experimental model. Further studies are required to uncover the mode of MARV transmission, and to investigate the putative role of R. aegyptiacus as a reservoir host.

  16. Immunomodulatory efficacy of ethanol extract of propolis on tumor-bearing mice with disseminated candidiasis.

    Science.gov (United States)

    Khosravi, A R; Shokri, H; Darvishi, S; Taghavi, M

    2014-12-01

    This study was aimed at investigating the effect of propolis on immunosurveillance by measuring the levels of serum interleukin (IL)-4, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in tumor-bearing mice with disseminated candidiasis. The ethanol extract of propolis was selected for this study. Balb/C female mice were infected with Candida albicans (C. albicans) and inoculated with spontaneous mouse mammary tumor (SMMT). The serum levels of tissue inhibitor of metalloproteinase-1(TIMP-1) were assessed by enzyme- linked immunosorbent assay (ELISA). Mice were treated daily with propolis solution (100mg/kg, 0.1 mL, orally) for 3 days before IV challenge with C. albicans and SC challenge with SMMT and continued for 10 days. The rates of survival and tumor growth of understudy mice were investigated as well. The levels of TNF-α, IFN-γ, IL-4, IL-10 and IL-17 cytokines in culture supernatants were determined by ELISA. The mean tumor size was significantly increased in tumor-bearing mice infected with C. albicans (16.98 ± 0.49 mm(2)) as compared to other mice groups (P<0.05). The results showed a significant decline of IL-4 and IL-10 levels after propolis administration to tumor-bearing mice infected with C. albicans (53.41 pg/mL, 156.81 pg/mL and 63.45 pg/mL) (P < 0.05). The increment of TNF-α (433.85 pg/mL) and IFN-γ (120.43 pg/mL) levels were also observed. Data revealed that propolis has remarkable immunomodulatory effect, which provides a scientific validation for the popular use of this natural substance, and further investigation will help to understand propolis usefulness during immunosuppressive conditions. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  17. Sarcocystis jamaicensis n. sp., from Red-Tailed Hawks (Buteo jamaicensis) Definitive Host and IFN-γ Gene Knockout Mice as Experimental Intermediate Host.

    Science.gov (United States)

    Verma, S K; von Dohlen, A Rosypal; Mowery, J D; Scott, D; Rosenthal, B M; Dubey, J P; Lindsay, D S

    2017-10-01

    Here, we report a new species of Sarcocystis with red-tailed hawk (RTH, Buteo jamaicensis) as the natural definitive host and IFN-γ gene knockout (KO) mice as an experimental intermediate host in which sarcocysts form in muscle. Two RTHs submitted to the Carolina Raptor Center, Huntersville, North Carolina, were euthanized because they could not be rehabilitated and released. Fully sporulated 12.5 × 9.9-μm sized sporocysts were found in intestinal scrapings of both hawks. Sporocysts were orally fed to laboratory-reared outbred Swiss Webster mice (SW, Mus musculus) and also to KO mice. The sporocysts were infective for KO mice but not for SW mice. All SW mice remained asymptomatic, and neither schizonts nor sarcocysts were found in any SW mice euthanized on days 54, 77, 103 (n = 2) or 137 post-inoculation (PI). The KO mice developed neurological signs and were necropsied between 52 to 68 days PI. Schizonts/merozoites were found in all KO mice euthanized on days 52, 55 (n = 3), 59, 61 (n = 2), 66, and 68 PI and they were confined to the brain. The predominant lesion was meningoencephalitis characterized by perivascular cuffs, granulomas, and necrosis of the neural tissue. The schizonts/merozoites were located in neural tissue and were apparently extravascular. Brain homogenates from infected KO mice were infective to KO mice by subcutaneous inoculation and when seeded on to CV-1 cells. Microscopic sarcocysts were found in skeletal muscles of 5 of 8 KO mice euthanized between 55-61 days PI. Only a few sarcocysts were detected. Sarcocysts were microscopic, up to 3.5 mm long. When viewed with light microscopy, the sarcocyst wall appeared thin (<1 μm thick) and smooth. By transmission electron microscopy, the sarcocyst wall classified as "type 1j" (new designation). Molecular characterization using 18S rRNA, 28S rRNA, ITS-1, and cox1 genes revealed a close relationship with Sarcocystis microti and Sarcocystis glareoli; both species infect birds as definitive hosts

  18. Oral Cancer

    Science.gov (United States)

    ... NIDCR Home Oral Health Diseases and Conditions Gum Disease TMJ Disorders Oral Cancer Dry Mouth Burning Mouth Tooth Decay See All Oral Complications of Systemic Diseases Cancer Treatment Developmental Disabilities Diabetes Heart Disease HIV/ ...

  19. Oral Cancer

    Science.gov (United States)

    Oral cancer can form in any part of the mouth. Most oral cancers begin in the flat cells that cover the ... your mouth, tongue, and lips. Anyone can get oral cancer, but the risk is higher if you are ...

  20. Investigation of the Mode of Action Underlying the Tumorigenic Response Induced in B6C3F1 Mice Exposed Orally to Hexavalent Chromium

    Science.gov (United States)

    Thompson, Chad M.; Proctor, Deborah M.; Haws, Laurie C.; Hébert, Charles D.; Grimes, Sheila D.; Shertzer, Howard G.; Kopec, Anna K.; Hixon, J.Gregory; Zacharewski, Timothy R.; Harris, Mark A.

    2011-01-01

    Chronic ingestion of high concentrations of hexavalent chromium [Cr(VI)] in drinking water induces intestinal tumors in mice. To investigate the mode of action (MOA) underlying these tumors, a 90-day drinking water study was conducted using similar exposure conditions as in a previous cancer bioassay, as well as lower (heretofore unexamined) drinking water concentrations. Tissue samples were collected in mice exposed for 7 or 90 days and subjected to histopathological, biochemical, toxicogenomic, and toxicokinetic analyses. Described herein are the results of toxicokinetic, biochemical, and pathological findings. Following 90 days of exposure to 0.3–520 mg/l of sodium dichromate dihydrate (SDD), total chromium concentrations in the duodenum were significantly elevated at ≥ 14 mg/l. At these concentrations, significant decreases in the reduced-to-oxidized glutathione ratio (GSH/GSSG) were observed. Beginning at 60 mg/l, intestinal lesions were observed including villous cytoplasmic vacuolization. Atrophy, apoptosis, and crypt hyperplasia were evident at ≥ 170 mg/l. Protein carbonyls were elevated at concentrations ≥ 4 mg/l SDD, whereas oxidative DNA damage, as assessed by 8-hydroxydeoxyguanosine, was not increased in any treatment group. Significant decreases in the GSH/GSSG ratio and similar histopathological lesions as observed in the duodenum were also observed in the jejunum following 90 days of exposure. Cytokine levels (e.g., interleukin-1β) were generally depressed or unaltered at the termination of the study. Overall, the data suggest that Cr(VI) in drinking water can induce oxidative stress, villous cytotoxicity, and crypt hyperplasia in the mouse intestine and may underlie the MOA of intestinal carcinogenesis in mice. PMID:21712504

  1. Toll-like Receptor 5 Agonist Protects Mice From Dermatitis and Oral Mucositis Caused by Local Radiation: Implications for Head-and-Neck Cancer Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Burdelya, Lyudmila G. [Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY (United States); Gleiberman, Anatoli S.; Toshkov, Ilia [Cleveland BioLabs, Inc., Buffalo, NY (United States); Aygun-Sunar, Semra [Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY (United States); Bapardekar, Meghana [Cleveland BioLabs, Inc., Buffalo, NY (United States); Manderscheid-Kern, Patricia; Bellnier, David [Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY (United States); Krivokrysenko, Vadim I.; Feinstein, Elena [Cleveland BioLabs, Inc., Buffalo, NY (United States); Gudkov, Andrei V., E-mail: andrei.gudkov@roswellpark.org [Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY (United States); Cleveland BioLabs, Inc., Buffalo, NY (United States)

    2012-05-01

    Purpose: Development of mucositis is a frequent side effect of radiotherapy of patients with head-and-neck cancer. We have recently reported that bacterial flagellin, an agonist of Toll-like receptor 5 (TLR5), can protect rodents and primates from acute radiation syndrome caused by total body irradiation. Here we analyzed the radioprotective efficacy of TLR5 agonist under conditions of local, single dose or fractionated radiation treatment. Methods and Materials: Mice received either single-dose (10, 15, 20, or 25 Gy) or fractioned irradiation (cumulative dose up to 30 Gy) of the head-and-neck area with or without subcutaneous injection of pharmacologically optimized flagellin, CBLB502, 30 min before irradiation. Results: CBLB502 significantly reduced the severity of dermatitis and mucositis, accelerated tissue recovery, and reduced the extent of radiation induced weight loss in mice after a single dose of 15 or 20 Gy but not 25 Gy of radiation. CBLB502 was also protective from cumulative doses of 25 and 30 Gy delivered in two (10 + 15 Gy) or three (3 Multiplication-Sign 10 Gy) fractions, respectively. While providing protection to normal epithelia, CBLB502 did not affect the radiosensitivity of syngeneic squamous carcinoma SCCVII grown orthotopically in mice. Use of CBLB502 also elicited a radiation independent growth inhibitory effect upon TLR5-expressing tumors demonstrated in the mouse xenograft model of human lung adenocarcinoma A549. Conclusion: CBLB502 combines properties of supportive care (radiotherapy adjuvant) and anticancer agent, both mediated via activation of TLR5 signaling in the normal tissues or the tumor, respectively.

  2. Oral administration of whole dihomo-γ-linolenic acid-producing Saccharomyces cerevisiae suppresses cutaneous inflammatory responses induced by croton oil application in mice.

    Science.gov (United States)

    Watanabe, Naoko; Masubuchi, Daiki; Itoh, Maki; Teradu, Soichiro; Yazawa, Hisashi; Uemura, Hiroshi

    2014-10-01

    Polyunsaturated fatty acids have been attracting considerable interest because of their many biological activities and important roles in human health and nutrition. Dihomo-γ-linolenic acid (DGLA; C20: 3n-6) is known to have an anti-inflammatory activity, but its range of effects was not well studied because of its limited natural sources. Taking advantage of genetic tractability and increasing wealth of accessible data of Saccharomyces cerevisiae, we have previously constructed a DGLA-producing yeast strain by introducing two types of desaturase and one elongase genes to convert endogenous oleic acid (C18:1n-9) to DGLA. In this study, we investigated the efficacy of oral intake of heat-killed whole DGLA-producing yeast cells in the absence of lipid purification on cutaneous inflammation. Topical application of croton oil to mouse ears induces ear swelling in parallel with the increased production of chemokines and accumulation of infiltrating cells into the skin sites. These inflammatory reactions were significantly suppressed in a dose-dependent manner by oral intake of the DGLA-producing yeast cells for only 7 days. This suppression was not observed by the intake of the γ-linolenic acid-producing (C18:3n-6, an immediate precursor of DGLA) yeast, indicating DGLA itself suppressed the inflammation. Further analysis demonstrated that DGLA exerted an anti-inflammatory effect via prostaglandin E1 formation because naproxen, a cyclooxygenase inhibitor, attenuated the suppression. Since 25-fold of purified DGLA compared with that provided as a form of yeast was not effective, oral administration of the whole DGLA-producing yeast is considered to be a simple but efficient method to suppress inflammatory responses.

  3. Evaluation of self-emulsified DIM-14 in dogs for oral bioavailability and in Nu/nu mice bearing stem cell lung tumor models for anticancer activity.

    Science.gov (United States)

    Patel, Apurva R; Doddapaneni, Ravi; Andey, Terrick; Wilson, Heather; Safe, Stephen; Singh, Mandip

    2015-09-10

    3, 3-Diindolylmethane-14 (DIM-14), a novel lipophilic derivative of DIM, has demonstrated anticancer activity in different types of cancers. However, poor solubility and low oral bioavailability of DIM-14 limit its translational benefits in vivo. This study was carried out to improve the oral bioavailability of DIM-14 via self-emulsifying drug (SED) delivery system in dogs and to evaluate pharmacodynamic characteristics of SED against H1650 stem cell tumor models. DIM-14 was incorporated into an oil, surfactant, and co-surfactant mixture using labrafil and tween-80 to obtain SED. SED were characterized by droplet size, polydispersitiy index (PDI), zeta potential, entrapment efficiency (EE), in vitro permeability and drug release (investigated with Caco-2 monolayers and dissolution apparatus respectively). Pharmacokinetic parameters in dogs were evaluated and analyzed using Winonlin. Anti-tumor activity was carried out in H1650 lung tumor model. Particle size of SED was between 230 and 246 nm and surface charge was negative and ranged from 26.50 to 28.69 mV. Entrapment efficiency of SED was 85%. Pharmacokinetic evaluation in dogs showed increased Cmax (39.18 ± 7.34 vs 21.68 ± 6.3 μg·dL-1), higher AUC0-t (34,481.34 ± 1125.46 vs 14,159.53 ± 702.20 μg·min·dL-1) and improved absorption with 3 times more bioavailability of SED compared to DIM-14 solution. SED showed ~30-59% tumor volume/weight reduction in H1650 tumor model compared to DIM-P solution. Our studies demonstrate the potential application of self-emulsifying drug delivery system (SEDDS), that enhances oral absorption of DIM-14 and increased anti-tumor activity against lung tumor models. Published by Elsevier B.V.

  4. Oral drug self-administration in the home cage of mice: alcohol-heightened aggression and inhibition by the 5-HT1B agonist anpirtoline.

    Science.gov (United States)

    Miczek, K A; de Almeida, R M

    2001-10-01

    In order to model heightened aggression after alcohol consumption and to study the inhibitory influence of 5-HT1B receptors on drinking and fighting, an experimental procedure should enable self-administration of precise amounts of alcohol in a limited period of time before an aggressive confrontation. To design a new device that can reinforce operant responding by the delivery of sweet alcohol in the resident mouse home cage, where aggressive behavior toward an intruder can subsequently be examined, and to demonstrate inhibition of alcohol-heightened aggression by 5-HT1B receptor agonist treatment. Within one experimental session, all singly housed CFW male mice (n=26) performed a nose-poke response that was reinforced by 0.05 ml sucrose. Using the sucrose fading technique, eventually the mice consumed a 6% ethanol/4% sucrose solution after each fifth nose poke during daily 15-min experimental sessions. The number of ethanol reinforcements was adjusted so that 0.6, 1.0, 1.7, and 3.0-g/kg doses were consumed in 15 min or less. Assays confirmed blood alcohol levels at 68.1 mg/dl for intake of 1.0 g/kg. After consuming a specific dose of ethanol in the form of a fixed number of response-dependent deliveries, the response panel was removed from the home cage and, 15 min later, the resident confronted a male intruder. Anpirtoline was administered either before alcohol self-administration or before the aggressive confrontation. After being reinforced with 1.0 g/kg or 1.7 g/kg sweet ethanol, the mice significantly increased attack and threat behavior relative to their aggressive behavior following sucrose or water consumption only. Treatment with the 5-HT1B receptor agonist anpirtoline (0.125, 0.25, 0.5 mg/kg, i.p.) before the confrontation decreased alcohol-heightened aggression and species-typical aggression in the absence of changes in other elements of the behavioral repertoire. Anpirtoline affected ethanol-reinforced behavior only at doses that were 5-10 times

  5. Role of iron in Trypanosoma cruzi infection of mice.

    OpenAIRE

    Lalonde, R G; Holbein, B E

    1984-01-01

    The role of iron in experimental infection of mice with Trypanosoma cruzi was investigated. B6 mice had a transient parasitemia and a transient anemia, both of maximal intensity 28 d after the inoculation of T. cruzi. There was a biphasic hypoferremic host response to infection with T. cruzi with the peak hypoferremia also occurring 28 d after inoculation of the parasite. The mortality rate from infection was increased from 23% in phosphate-buffered saline-treated B6 mice to 50% in a group of...

  6. Interleukin-10 Production by T and B Cells Is a Key Factor to Promote Systemic Salmonella enterica Serovar Typhimurium Infection in Mice

    Directory of Open Access Journals (Sweden)

    Geraldyne A. Salazar

    2017-08-01

    Full Text Available Salmonella enterica serovar Typhimurium (S. Typhimurium is a Gram-negative bacterium that produces disease in numerous hosts. In mice, oral inoculation is followed by intestinal colonization and subsequent systemic dissemination, which leads to severe pathogenesis without the activation of an efficient anti-Salmonella immune response. This feature suggests that the infection caused by S. Typhimurium may promote the production of anti-inflammatory molecules by the host that prevent efficient T cell activation and bacterial clearance. In this study, we describe the contribution of immune cells producing the anti-inflammatory cytokine interleukin-10 (IL-10 to the systemic infection caused by S. Typhimurium in mice. We observed that the production of IL-10 was required by S. Typhimurium to cause a systemic disease, since mice lacking IL-10 (IL-10−/− were significantly more resistant to die after an infection as compared to wild-type (WT mice. IL-10−/− mice had reduced bacterial loads in internal organs and increased levels of pro-inflammatory cytokines in serum at 5 days of infection. Importantly, WT mice showed high bacterial loads in tissues and no increase of cytokines in serum after 5 days of S. Typhimurium infection, except for IL-10. In WT mice, we observed a peak of il-10 messenger RNA production in ileum, spleen, and liver after 5 days of infection. Importantly, the adoptive transfer of T or B cells from WT mice restored the susceptibility of IL-10−/− mice to systemic S. Typhimurium infection, suggesting that the generation of regulatory cells in vivo is required to sustain a systemic infection by S. Typhimurium. These findings support the notion that IL-10 production from lymphoid cells is a key process in the infective cycle of S. Typhimurium in mice due to generation of a tolerogenic immune response that prevents bacterial clearance and supports systemic dissemination.

  7. Effects of Rhizobuim leguminosarum inoculation on the growth and ...

    African Journals Online (AJOL)

    g per plant in 2008 and 2009 seasons, respectively. The findings suggested that inoculation of Mucuna flagellipies with Rhizobium is beneficial and produced high seed yield and could be use as biofertilizer an alternative to nitrogen fertilizer.

  8. Formation of ectomycorrhizae following inoculation of containerized Sitka spruce seedlings.

    Science.gov (United States)

    C.G. Shaw; R. Molina

    1980-01-01

    Containerized Sitka spruce, [Picea sitchensis (Bong.) Carr.] were inoculated at sowing with pure cultures of either Pisolithus tinctorius (Pers.) Coker & Couch, Laccaria laccata (Scop. ex Fr.) Berk. & Br., Astraeus pteridis (Shear) Feller, Amanita pantherina...

  9. Effect of bradyrhizobial inoculation and n fertilization on ...

    African Journals Online (AJOL)

    Effect of bradyrhizobial inoculation and n fertilization on promiscuous soybean and subsequent maize yield grown in degraded “terre de barre” in Benin. P Houngnandan, F Zapata, P Boekx, O Van Cleemput ...

  10. Inoculation of Ceratonia siliqua L. with native arbuscular mycorrhizal ...

    African Journals Online (AJOL)

    Inoculation of Ceratonia siliqua L. with native arbuscular mycorrhizal fungi mixture improves seedling establishment under greenhouse conditions. Ouahmane Lahcen, Ndoye Ibrahima, Morino Abdessadek, Ferradous Abderrahim, Sfairi Youssef, Al Faddy Mohamed Najib, Abourouh Mohamed ...

  11. Effect of Bifidobacterium animalis on mice infected with Strongyloides venezuelensis.

    Science.gov (United States)

    Oliveira-Sequeira, Teresa Cristina Goulart; David, Érica Boarato; Ribeiro, Cláudia; Guimarães, Semíramis; Masseno, Ana Paula Batista; Katagiri, Satie; Sequeira, Julio Lopes

    2014-01-01

    The administration of viable Bifidobacterium animalis was tested to induce resistance against Strongyloides venezuelensis infection in mice. Effects on parasite burden, worm length, egg output, and intestinal mucosal histology were evaluated. The oral administration of B. animalis, strain 04450B, starting 14 days before the inoculation of nematode larvae significantly decreased the worm burden and egg output. In probiotic treated animals, the percent reduction of adult worms in the intestine was of 33% and the reduction of egg production was of 21%, compared with those of the control group. The duodenum villous height and villous/crypt ratio were significantly higher in probiotic-treated mice, indicating that this group could be experiencing less intestinal damage. The present findings revealed that the administration of B. animalis for the amelioration of host response to nematode infections is biologically plausible and could have some potential for impacting public health. Meanwhile, further study is needed to delineate the nature and identity of the factor(s) involved in these beneficial effects.

  12. Involvement of miR-518c-5p to growth and metastasis in oral cancer.

    Directory of Open Access Journals (Sweden)

    Makoto Kinouchi

    Full Text Available We have previously demonstrated that a stromal cell-derived factor-1 (SDF-1; CXCL12/CXCR4 system is involved in the establishment of metastasis in oral cancer. Recently, small non coding RNAs, microRNAs (miRNAs have been shown to be involved in the metastatic process of several types of cancers. However, the miRNAs that contribute to metastases induced by the SDF-1/CXCR4 system in oral cancer are largely unknown. In this study, we examined the metastasis-related miRNAs induced by the SDF-1/CXCR4 system using B88-SDF-1 oral cancer cells, which exhibit functional CXCR4 and distant metastatic potential in vivo. Through miRNA microarray analysis, we identified the upregulation of miR-518c-5p in B88-SDF-1 cells, and confirmed the induction by real-time PCR analysis. Although an LNA-based miR-518c-5p inhibitor did not affect cell growth of B88-SDF-1 cells, it did significantly inhibit the migration of the cells. Next, we transfected a miR-518c expression vector into parental B88 cells and CAL27 oral cancer cells and isolated stable transfectants, B88-518c and CAL27-518c cells, respectively. The anchorage-dependent and -independent growth of miR-518c transfectants was significantly enhanced compared with the growth of mock cells. Moreover, we detected the enhanced migration of these cells. The LNA-based miR-518c-5p inhibitor significantly impaired the enhanced cell growth and migration of miR-518c transfectants, indicating that these phenomena were mainly dependent on the expression of miR-518c-5p. Next, we examined the function of miR-518c-5p in vivo. miR-518c transfectants or mock transfectants were inoculated into the masseter muscle or the blood vessels of nude mice. Tumor volume, lymph nodes metastasis, and lung metastasis were significantly increased in the mice inoculated with the miR-518c transfectants. These results indicated that miR-518c-5p regulates the growth and metastasis of oral cancer as a downstream target of the SDF-1/CXCR4 system.

  13. 3,4-Dicaffeoylquinic Acid, a Major Constituent of Brazilian Propolis, Increases TRAIL Expression and Extends the Lifetimes of Mice Infected with the Influenza A Virus

    Directory of Open Access Journals (Sweden)

    Tomoaki Takemura

    2012-01-01

    Full Text Available Brazilian green propolis water extract (PWE and its chemical components, caffeoylquinic acids, such as 3,4-dicaffeoylquinic acid (3,4-diCQA, act against the influenza A virus (IAV without influencing the viral components. Here, we evaluated the anti-IAV activities of these compounds in vivo. PWE or PEE (Brazilian green propolis ethanol extract at a dose of 200 mg/kg was orally administered to Balb/c mice that had been inoculated with IAV strain A/WSN/33. The lifetimes of the PWE-treated mice were significantly extended compared to the untreated mice. Moreover, oral administration of 3,4-diCQA, a constituent of PWE, at a dose of 50 mg/kg had a stronger effect than PWE itself. We found that the amount of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL mRNA in the mice that were administered 3,4-diCQA was significantly increased compared to the control group, while H1N1 hemagglutinin (HA mRNA was slightly decreased. These data indicate that PWE, PEE or 3,4-diCQA possesses a novel and unique mechanism of anti-influenza viral activity, that is, enhancing viral clearance by increasing TRAIL.

  14. Plant Inoculation with the Fungal Leaf Pathogen Colletotrichum higginsianum.

    Science.gov (United States)

    Hiruma, Kei; Saijo, Yusuke

    2016-01-01

    After Colletotrichum storage methods in Chapter 23 , we describe here experimental methods for the inoculation of Colletotrichum higginsianum (C.h.) on Arabidopsis leaves. We put a particular focus on the methods for lesion measurements after the drop-inoculation of the leaves and on C.h. biomass measurements in the leaves by RT-qPCR analysis. As an option, we also briefly describe methods for counting C.h. entry ratio.

  15. Experimental infections of mice and guinea pigs with Haemophilus parasuis.

    Science.gov (United States)

    Morozumi, T; Hiramune, T; Kobayashi, K

    1982-01-01

    The pathogenicity of Haemophilus parasuis for mice and guinea pigs was examined. Mice were inoculated intraperitoneally with 2 X 10(7) to 2 X 10(9) organisms suspended in saline or in broth containing fresh yeast extract. Most of them survived after inoculation. Death occurred only in mice inoculated with 2 X 10(9) organisms suspended in broth. The recovery rate of H. parasuis from all the dead mice varied from 28.9% of the brains to 71.4% of the lungs. There were no lesions observed in any mouse, except one. Guinea pigs were inoculated intraperitoneally with 1 X 10(8) to 1.6 X 10(10) organisms suspended in saline. Many of them died after showing septicemia and serofibrinous serositis, which were associated with purulent leptomeningitis or meningoencephalitis in some of them. H. parasuis was recovered abundantly from many organs, including the brain, in the guinea pigs. It was also recovered from guinea pigs inoculated with 1.8 X 10(9) organisms by various routes. Serositis was observed in guinea pigs inoculated intramuscularly or intrapulmonarily. These results suggested that guinea pigs might be available for investigation of the pathogenicity of H. parasuis.

  16. Immune response elicited by the oral administration of an intermediate strain of IBDV in chickens

    OpenAIRE

    Juan Manuel Carballeda; Silvina Chimeno Zoth; Evangelina Gómez; María Soledad Lucero; María José Gravisaco; Analía Berinstein

    2015-01-01

    The immune response elicited by the oral inoculation of an intermediate strain of infectious bursal disease virus was studied in chickens. A strong over expression of IL-6, IL-8, IFNα and IFNγ was observed in bursa at 3 days post inoculation together with an increase in splenic NO2 release. An influx of T-lymphocytes was also detected.

  17. Immune response elicited by the oral administration of an intermediate strain of IBDV in chickens

    Directory of Open Access Journals (Sweden)

    Juan Manuel Carballeda

    2014-12-01

    Full Text Available The immune response elicited by the oral inoculation of an intermediate strain of infectious bursal disease virus was studied in chickens. A strong over expression of IL-6, IL-8, IFNα and IFNγ was observed in bursa at 3 days post inoculation together with an increase in splenic NO2 release. An influx of T-lymphocytes was also detected.

  18. Diagnostic efficacy of Brucella abortus strain RB51 in experimentally inoculated Sprague-Dawley rats using western blot assay.

    Science.gov (United States)

    Rahman, Siddiqur; Baek, Byeong Kirl

    2008-10-01

    To investigate the diagnosis and efficacy of Brucella abortus strain RB51 (SRB51) in experimentally inoculated Sprague-Dawley (SD) rat using western blot assay. Female SD rats were orally administered with 1.0 x 10(7) colony forming unit (cfu) suspension of SRB51 and half of these SD rats were challenged at 4 weeks post inoculation with 1.0 x 10(9) cfu suspension of B. abortus biotype 1 isolated in South Korea. Sera of SD rats were monitored at regular intervals by western blot assay using whole cell antigen of B. abortus strain 1119-3 (S1119-3). The bacteriological examination of blood and clinical examination of the rats were also performed. There were several bands at 120, 70, 45, 30, 20 kDa and clear specific bands were found after vaccination (20, 70 kDa) and challenge (15, 20, 45, 70, 120 kDa). The highest immune response was observed in sera 4 weeks post SRB51 vaccination. SRB51 was recovered from the blood of all of SRB51 inoculated rats until one week post vaccination and there were no clinical signs in that inoculated rats. It is concluded that the SRB51 elicits antigen specific immunity in SD rats based on western blot assay.

  19. Genetic diversity of symbiotic Bradyrhizobium elkanii populations recovered from inoculated and non-inoculated Acacia mangium field trials in Brazil.

    Science.gov (United States)

    Perrineau, M M; Le Roux, C; de Faria, S M; de Carvalho Balieiro, F; Galiana, A; Prin, Y; Béna, G

    2011-07-01

    Acacia mangium is a legume tree native to Australasia. Since the eighties, it has been introduced into many tropical countries, especially in a context of industrial plantations. Many field trials have been set up to test the effects of controlled inoculation with selected symbiotic bacteria versus natural colonization with indigenous strains. In the introduction areas, A. mangium trees spontaneously nodulate with local and often ineffective bacteria. When inoculated, the persistence of inoculants and possible genetic recombination with local strains remain to be explored. The aim of this study was to describe the genetic diversity of bacteria spontaneously nodulating A. mangium in Brazil and to evaluate the persistence of selected strains used as inoculants. Three different sites, several hundred kilometers apart, were studied, with inoculated and non-inoculated plots in two of them. Seventy-nine strains were isolated from nodules and sequenced on three housekeeping genes (glnII, dnaK and recA) and one symbiotic gene (nodA). All but one of the strains belonged to the Bradyrhizobium elkanii species. A single case of housekeeping gene transfer was detected among the 79 strains, suggesting an extremely low rate of recombination within B. elkanii, whereas the nodulation gene nodA was found to be frequently transferred. The fate of the inoculant strains varied depending on the site, with a complete disappearance in one case, and persistence in another. We compared our results with the sister species Bradyrhizobium japonicum, both in terms of population genetics and inoculant strain destiny. Copyright © 2011 Elsevier GmbH. All rights reserved.

  20. Oral administration of live exopolysaccharide-producing Pediococcus parvulus, but not purified exopolysaccharide, suppressed Enterobacteriaceae without affecting bacterial diversity in ceca of mice.

    Science.gov (United States)

    Lindström, Cecilia; Xu, Jie; Oste, Rickard; Holst, Olle; Molin, Göran

    2013-08-01

    Growing evidence indicates that the gut microbiota could have an important role in the development of diet- and lifestyle-induced diseases. It has been shown that modulation of the gut microbiota by means of probiotics and prebiotics could improve host health. An oat-based product fermented by the exopolysaccharide (EPS)-producing organism Pediococcus parvulus 2.6 has been reported to have a bifidogenic effect. To find out whether the effect could be attributed to the EPS or the bacterium, mice were fed a diet supplemented with 2% purified EPS or 10(8) CFU/g of live P. parvulus 2.6 for 6 weeks. Both supplementations altered the gut microbiota composition but in different directions. Purified EPS not only significantly lowered the microbial diversity (P producing bacterium P. parvulus 2.6 antagonized Enterobacteriaceae without disturbing the homeostasis of the cecal microbiota.

  1. Oral exposure of Kunming mice to diisononyl phthalate induces hepatic and renal tissue injury through the accumulation of ROS. Protective effect of melatonin.

    Science.gov (United States)

    Ma, Ping; Yan, Biao; Zeng, Qiang; Liu, Xudong; Wu, Yang; Jiao, Ming; Liu, Chao; Wu, Jiliang; Yang, Xu

    2014-06-01

    Diisononyl phthalate (DINP) has been widely used in polyvinyl chloride (PVC) products and is ubiquitous as a substitute; however, its toxicity due to exposure remains to be determined. This study investigated the oxidative damage induced by DINP and the induced production of the pro-inflammation cytokines interleukin-1 (IL-1) and tumour necrosis factor-α (TNF-α). Oral exposure to DINP induced oxidative damage and inflammatory responses in liver and kidney tissues through the accumulation of ROS, which may be an underlying mechanism for its toxicity. These changes may contribute to hepatic and renal histopathological alterations. Our data suggest that oxidative stress is involved in DINP-induced toxicity and that the co-administration of melatonin exerts a protective effect against DINP-induced toxicity. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. An oral Salmonella-based vaccine inhibits liver metastases by promoting tumor-specific T cell-mediated immunity in celiac & portal lymph nodes. A preclinical study.

    Directory of Open Access Journals (Sweden)

    Alejandrina eVendrell

    2016-03-01

    Full Text Available Primary tumor excision is one of the therapies of cancer most widely used. However, the risk of metastases development still exists following tumor resection. The liver is a common site of metastatic disease for numerous cancers. Breast cancer is one of the most frequent source of metastases to the liver. The aim of this work was to evaluate the efficacy of the orally-administered Salmonella Typhi vaccine strain CVD 915 on the development of liver metastases in a mouse model of breast cancer. To this end, one group of BALB/c mice was immunized with CVD 915 via o.g. while another received PBS as a control. After 24 h, mice were injected with LM3 mammary adenocarcinoma cells into the spleen and subjected to splenectomy. This oral Salmonella-based vaccine produced an antitumor effect, leading to a decrease in the number and volume of liver metastases. Immunization with Salmonella induced an early cellular immune response in mice. This innate stimulation rendered a large production of IFN-γ by intrahepatic immune cells (IHIC detected within 24 h. An antitumor adaptive immunity was found in the liver and celiac & portal lymph nodes (LDLN 21 days after oral bacterial inoculation. The antitumor immune response inside the liver was associated with increased CD4+ and DC cell populations as well as with an inflammatory infiltrate located around liver metastatic nodules. Enlarged levels of inflammatory cytokines (IFN-γ and TNF were also detected in IHIC. Furthermore, a tumor-specific production of IFN-γ and TNF as well as tumor-specific IFN-γ-producing CD8 T cells (CD8+IFN-γ+ were found in the celiac & portal lymph nodes of Salmonella-treated mice. This study provides first evidence for the involvement of LDLN in the development of an efficient cellular immune response against hepatic tumors, which resulted in the elimination of liver metastases after oral Salmonella-based vaccination.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    . aeruginosa, with and without simultaneous inoculation with RSV. Lung function measurements were undertaken using Whole Body Plethysmography and lungs were harvested 24 hr after inoculation. Mice exposed to RSV and P. aeruginosa showed 2,000 times higher colony-forming units (CFU) counts of P. aeruginosa...

  4. Infection cycle of Salmonella enterica serovar Enteritidis in latent carrier mice.

    Science.gov (United States)

    Maciel, Bianca Mendes; Sriranganathan, Nammalwar; Romano, Carla Cristina; dos Santos, Thalis Ferreira; Teixeira Dias, João Carlos; Gross, Eduardo; Rezende, Rachel Passos

    2012-12-01

    This work reports the distribution of an oral dose of Salmonella enterica serovar Enteritidis (SE) in C57Bl/6-Bcgr mice, to study its pathogenesis in a latent carrier animal. Mice orally inoculated with a high dose of SE developed a latent infection characterized by the absence of clinical symptoms in which the cecum is functioning as a "strategic site" of SE proliferation, releasing bacteria into feces intermittently over the 4-week study. A sequence of disruptions occurred in the small intestine at 1 day postinculation (PI). The microvilli exhibited different degrees of degeneration, which were reversible as the cells became vacuolated. From 2 days PI, SE was detected in the mononuclear phagocytic system, and an exponential growth of the remaining bacteria in tissues was observed until 4 days PI. The production of interferon gamma from 3 days PI is restricting the SE growth, and a plateau phase was observed from 4 to 15 days PI. A recurrence of the bacterial growth in tissue occurred from 15 to 28 days PI, especially in the cecum. Increasing our knowledge about the host-pathogen interaction of adapted pathogens with the ability to develop latency is essential for the development of an efficient strategy for Salmonella control.

  5. A 28-day oral gavage toxicity study of 3-monochloropropane-1,2-diol (3-MCPD) in CB6F1-non-Tg rasH2 mice.

    Science.gov (United States)

    Lee, Byoung-Seok; Park, Sang-Jin; Kim, Yong-Bum; Han, Ji-Seok; Jeong, Eun-Ju; Moon, Kyoung-Sik; Son, Hwa-Young

    2015-12-01

    3-Monochloro-1,2-propanediol (3-MCPD) is a well-known contaminant of foods containing hydrolyzed vegetable protein. However, limited toxicity data are available for the risk assessment of 3-MCPD and its carcinogenic potential is controversial. To evaluate the potential toxicity and determine the dose levels for a 26-week carcinogenicity test using Tg rasH2 mice, 3-MCPD was administered once daily by oral gavage at doses of 0, 25, 50, and 100 mg/kg body weight (b.w.)/day for 28 days to male and female CB6F1-non-Tg rasH2 mice (N = 5 males and females per dose). The standard toxicological evaluations were conducted during the in-life and post-mortem phase. In the 100 mg/kg b.w./day group, 3 males and 1 female died during the study and showed clinical signs such as thin appearance and subdued behavior accompanied by significant decreases in mean b.w. Microscopy revealed tubular basophilia in the kidneys, exfoliated degenerative germ cells in the lumen of the seminiferous tubule of the testes, vacuolation in the brain, axonal degeneration of the sciatic nerve, and cardiomyopathy in the 100, ≥25, ≥50, 100, and 100 mg/kg b.w./day groups, respectively. In conclusion, 3-MCPD's target organs were the kidneys, testes, brain, sciatic nerve, and heart. The "no-observed-adverse-effect level" (NOAEL) of 3-MCPD was ≤25 and 25 mg/kg b.w./day in males and females, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Oral treatment with methanolic extract of the root bark of Condalia buxifolia Reissek alleviates acute pain and inflammation in mice: Potential interactions with PGE2, TRPV1/ASIC and PKA signaling pathways.

    Science.gov (United States)

    Simões, Róli Rodrigues; Dos Santos Coelho, Igor; do Espírito Santo, Caroline Cunha; Morel, Ademir Farias; Zanchet, Eliane Maria; Santos, Adair Roberto Soares

    2016-06-05

    The Condalia buxifolia root bark infusion is used in traditional medicine in Brazil as antipyretic, anti-inflammatory and anti-dysentery. Previous data from our group showed that methanolic extract of Condalia buxifolia (MECb) produced a marked antinociceptive effect in animal models of acute pain. The purpose of this study was to investigate the mechanisms of MECb-induced antinociception as measured by nocifensive behavior in pain induced by endogenous (prostaglandin E2) or exogenous (TRPs and ASIC agonist, and protein kinase A and C activators) chemical stimuli, and the potential role of PKA signaling and capsaicin-sensitive central C-fiber afferents. The effect of MECb administered orally (0.1-300mg/kg, i.g.) to mice on nociception induced by capsaicin (TRPV1 agonist), cinnamaldehyde (TRPA1 agonist), menthol (TRPM8 agonist), acidified saline (ASIC agonist), PMA (protein kinase C activator), PGE2 and forskolin (protein kinase A activator) was assessed. Moreover, this study also investigated the role of C-fibers desensitizing mice with a high dose of intrathecal capsaicin. Furthermore, this study performed the western blot to PKA phosphorylated on nocifensive behavior induced by forskolin. MECb was able to reduce the nociception and paw edema induced by capsaicin, acidified saline, PMA, PGE2 and forskolin, but not by cinnamaldehyde or menthol. Western blot analyses showed that MECb reduced the levels of PKA phosphorylation induced by forskolin in hind paws. Finally, ablating central afferent C-fibers abolished MECb antinociception. In accordance with its use in traditional medicine, these findings provide new evidence indicating that Condalia buxifolia reduces the acute painful behavior of animals caused by chemical stimuli. The precise mechanism of MECb antinociceptive activity is not completely understood but the results suggest involvement of PGE2, TRPV1/ASIC and PKA signaling pathways, and require integrity of the capsaicin-sensitive central C-fiber afferents

  7. Simultaneous determination of six short-chain fatty acids in colonic contents of colitis mice after oral administration of polysaccharides from Chrysanthemum morifolium Ramat by gas chromatography with flame ionization detector.

    Science.gov (United States)

    Tao, Jin-Hua; Duan, Jin-Ao; Jiang, Shu; Guo, Jian-Ming; Qian, Yi-Yun; Qian, Da-Wei

    2016-09-01

    Short-chain fatty acids (SCFAs) produced by the intestinal bacteria are very critical for the intestinal barrier, mucosal cytoprotection and normal intestinal biology. However, accumulation of SCFAs promoted by the polysaccharides from Chrysanthemum morifolium Ramat remains unknown. Thus, it is necessary to investigate SCFAs in the colonic contents of dextran sulfate sodium (DSS) induced colitis mice after oral administration of the polysaccharides from C. morifolium Ramat which is very helpful to unravel how it works. In this study, a rapid and reliable gas chromatographic method with flame ionization detector (GC-FID) for simultaneous determination of six SCFAs such as acetic acid (AA), propionic acid (PA), butyric acid (BA), isobutyric acid (IBA), valeric acid (VA) and isovaleric acid (IVA) has been developed and validated. Under the optimized chromatographic conditions and sample extraction procedure, good separation for 6 target compounds was obtained on a HP-INNOWAX column within 12min. Results revealed that polysaccharides from C. morifolium Ramat positively affected the SCFAs intestinal production. The polysaccharides group had greater SCFAs concentration in colonic content than the DSS-treated group (P<0.05), which was decreased remarkably compared to the normal group (P<0.01). With the decrease of the polysaccharides dosage, the contents of AA, PA and VA increased gradually, while the change of BA concentration was the opposite. There was no significant difference in the content of IBA at the different administration concentrations. And the content of IVA reached the highest concentration 0.953mg/g at lower dose of the polysaccharides. Additionally, oral administration of the polysaccharides prominently attenuated the body weight loss, reduced the disease activity index, rectal bleeding and stool consistency, improved colon shortening and macroscopic score of colitis. Our results indicated that the polysaccharides of C. morifolium Ramat might be used as

  8. Endogenous expression of CD80 co-stimulatory molecule facilitates in vivo tumor regression of oral squamous carcinoma.

    Science.gov (United States)

    Thomas, Giovana R; Wen, Judy

    2006-01-01

    Most tumor tissues, especially those of non-hematopoietic origin, do not express CD80 co-stimulatory molecules, possibly as a mechanism to evade immune surveillance. The objective of this study was to determine whether abundant endogenous CD80 expression on oral squamous cell carcinoma (SCC) early during tumor progression can facilitate immune elimination and reverse immune tolerance. The growth of regressor and progressor oral SCC lines with differing endogenous CD80 expression were examined in immune-competent and -deficient mice. Immune effectors were determined by T-cell depletion experiments and immunohistochemistry. Our studies show regression of early tumor growth when immunocompetent animals are inoculated with oral SCC progressor cell lines expressing abundant endogenous CD80. The CD80-induced antitumor response was due largely to induced T-cell responses. Our findings suggest that inadequate CD80 expression during early oral SCC formation may contribute to the escape of tumors from immune elimination. This information can be useful in the design of new approaches to generate more effective immunotherapy against this disease.

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

    Science.gov (United States)

    Somsak, Voravuth; Polwiang, Natsuda; Chachiyo, Sukanya

    2016-01-01

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

  10. Simultaneous determination of three flavonoid C-glycosides in mice biosamples by HPLC-ESI-MS method after oral administration of Abrus mollis extract and its application to biodistribution studies.

    Science.gov (United States)

    Wang, Hao; Jiang, Zhenzhou; Du, Huibing; Liang, Chunyi; Wang, Yuanchao; Zhang, Mohan; Zhang, Luyong; Ye, Wencai; Li, Ping

    2012-08-15

    A simple HPLC-ESI-MS method was developed for the determination of vicenin-2 (1), isoschaftoside (2), and schaftoside (3) of Abrus mollis extract in mice plasma and tissues (heart, liver, spleen, lungs, and kidneys). The separation was achieved by HPLC on a Shim-Pack CLC-ODS column with a mobile phase composed of 0.1% formic acid (mobile phase A, 72%) and methanol-isopropanol (9:1) (mobile phase B, 28%). The electrospray source of the MS was operated in the selective ion monitoring (SIM) mode at m/z 593 ([M-H]⁻) for 1, and 563 ([M-H]⁻) for 2 and 3, respectively. The limit of detection (LOD) of 1-3 was in the range of 8.5-12.6 ng/mL for plasma, and 32.5-49.4 ng/g for tissue tested. The limit of quantification (LOQ) was found to be 25 ng/mL for plasma, and 100 ng/g for tissue. The calibration curves were linear in all matrices (r² > 0.994) in the concentration range of 25-500 ng/mL in plasma or 100-1250 ng/g in tissue, respectively. Intra-day and inter-day precision studies demonstrate that the method is precise with coefficients of variation intra-day and inter-day below 5.9 and 7.4% for all the samples, respectively. The recoveries of three flavonoid C-glycosides ranged from 95.3 to 106.4% for plasma, and 92.6 to 107.3% for tissues. Following oral administration of A. mollis extract to mice at a dose of 72 mg/kg, the concentrations of 1-3 in plasma and tissues were quantifiable in bio-samples collected up to 180 min. The method described is suitable for studies on the distribution of three flavonoid C-glycosides of A. mollis extract in plasma and different tissues of mice. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. GERMINATION OF GRASSES DUE TO INOCULATION DIAZOTROPHIC BACTERIA

    Directory of Open Access Journals (Sweden)

    C. D. A. Moreira

    2014-07-01

    Full Text Available The germination of forage grasses suffers from numbness and a natural tendency to low quality. The use of microorganisms inoculated in seeds with the purpose of increasing and meet the demand of some nutrient has been shown to be efficient, but the role of the microorganism in germination and rate of force is still unknown. Therefore the goal as study was to evaluate the germination rate of seeds of three cultivars of Brachiaria brizantha CV. Marandu, b., b. brizantha CV. Xaraés and b. humidícola cv Tupi and a cultivar of millet, P. hybrid cv Massai depending on the bacterium Azospirillum brasilense diazotrofic inoculation (nitrogen-fixing. Germination test was used in seed dispersal to assess the effect of first count (VPC in the treatments with and without inoculation. It was done also conducted further tests of electrical conductivity, weight of thousand seeds and water content. The delineation used was randomized entirely (DIC and the statistical analysis carried out through the analysis of variance and comparison of means using the Tukey test, the 5% probability. Massai grass seeds have the highest rate of force of first count in both treatments. Inoculation of bacterium Azospirillum brasilense did not affect the values of force of first count on seeds of the cultivars Marandu, Xaraés, Tupi and Massai. The seeds of the massai have higher germination speed relative the other cultivars evaluated when inoculated.

  12. Key factors to inoculate Botrytis cinerea in tomato plants

    Directory of Open Access Journals (Sweden)

    Álefe Vitorino Borges

    2014-09-01

    Full Text Available Studies addressing the biological control of Botrytis cinerea have been unsuccessful because of fails in inoculating tomato plants with the pathogen. With the aim of establishing a methodology for inoculation into stems, experiments were designed to assess: i. the aggressiveness of pathogen isolates; ii. the age at which tomato plants should be inoculated; iii. the susceptibility of tissues at different stem heights; iv. the need for a moist chamber after inoculation; and v. the effectiveness of gelatin regarding inoculum adhesion. Infection with an isolate from tomato plants that was previously inoculated into petioles and then re-isolated was successful. An isolate from strawberry plants was also aggressive, although less than that from tomato plants. Tomato plants close to flowering, at 65 days after sowing, and younger, middle and apical stem portions were more susceptible. There was positive correlation between lesion length and sporulation and between lesion length and broken stems. Lesion length and the percentage of sporulation sites were reduced by using a moist chamber and were not affected by adding gelatin to the inoculum suspension. This methodology has been adopted in studies of B. cinerea in tomato plants showing reproducible results. The obtained results may assist researchers who study the gray mold.

  13. Plant growth-promoting bacteria as inoculants in agricultural soils

    Directory of Open Access Journals (Sweden)

    Rocheli de Souza

    2015-01-01

    Full Text Available AbstractPlant-microbe interactions in the rhizosphere are the determinants of plant health, productivity and soil fertility. Plant growth-promoting bacteria (PGPB are bacteria that can enhance plant growth and protect plants from disease and abiotic stresses through a wide variety of mechanisms; those that establish close associations with plants, such as the endophytes, could be more successful in plant growth promotion. Several important bacterial characteristics, such as biological nitrogen fixation, phosphate solubilization, ACC deaminase activity, and production of siderophores and phytohormones, can be assessed as plant growth promotion (PGP traits. Bacterial inoculants can contribute to increase agronomic efficiency by reducing production costs and environmental pollution, once the use of chemical fertilizers can be reduced or eliminated if the inoculants are efficient. For bacterial inoculants to obtain success in improving plant growth and productivity, several processes involved can influence the efficiency of inoculation, as for example the exudation by plant roots, the bacterial colonization in the roots, and soil health. This review presents an overview of the importance of soil-plant-microbe interactions to the development of efficient inoculants, once PGPB are extensively studied microorganisms, representing a very diverse group of easily accessible beneficial bacteria.

  14. Sunflower growth according to seed inoculation with endophytic bacteria

    Directory of Open Access Journals (Sweden)

    Juliana Fernandes dos Santos

    2014-06-01

    Full Text Available The sunflower crop has a great importance worldwide, due to the oil of excellent quality extracted from its seeds and in natura grains that are consumed in various ways. However, drought is one of the main environmental factors that limit its yield. An experiment was carried out under controlled greenhouse conditions, in a completely randomized experimental design, in order to determine the effect of endophytic bacteria inoculation (Bacillus sp. and Enterobacter cloacae on the growth and contents of nutrients and organic solutes, in sunflower leaves and roots under water deficit. Plant height, stem diameter, fresh and dry biomass of shoot and roots, as well as contents of N, P, K, soluble carbohydrates, free proline, free amino acids and soluble proteins, were determined at 35 days after the plant emergence. The water deficit reduced plant growth regardless inoculation. However, under optimum conditions of soil moisture, the combination of both endophytic bacteria increased the sunflower growth. The water deficit also increased the N and K contents in leaves, as well as the organic solutes content in shoots, especially in inoculated plants. These results suggest that the inoculation of endophytic bacteria may increase the capacity of drought stressed plants to perform the osmotic adjustment through a higher accumulation of organic solutes, when compared to plants not inoculated.

  15. Oral Administration of Oleuropein and Its Semisynthetic Peracetylated Derivative Prevents Hepatic Steatosis, Hyperinsulinemia, and Weight Gain in Mice Fed with High Fat Cafeteria Diet

    Directory of Open Access Journals (Sweden)

    Saverio Massimo Lepore

    2015-01-01

    Full Text Available The high consumption of olive tree products in the Mediterranean diet has been associated with a lower incidence of metabolic disorders and cardiovascular diseases. In particular, the protective effects of olive oil have been attributed to the presence of polyphenols such as oleuropein (Ole and its derivatives. We have synthesized a peracetylated derivative of Ole (Ac-Ole which has shown in vitro antioxidant and growth-inhibitory activity higher than the natural molecule. In this study, male C57BL/6JOlaHsd mice were fed with a standard (std, cafeteria (caf diet, and caf diet supplemented with Ole (0.037 mmol/kg/day and Ac-Ole (0.025 mmol/kg/day for 15 weeks. We observed a significant reduction in the caf diet-induced body weight gain and increase of abdominal adipose tissue. Also, Ole and Ac-Ole prevented the development of hepatic steatosis. Finally, Ole and Ac-Ole determined a lower increase of HDL and LDL-cholesterol levels and corrected caf diet-induced elevation of plasma glucose concentrations by improving insulin sensitivity. The observed beneficial properties of Ole and Ac-Ole make these compounds and in particular Ac-Ole promising candidates for a potential pharmaceutic use in metabolic disorders.

  16. Delayed O-methylation of l-DOPA in MB-COMT-deficient mice after oral administration of l-DOPA and carbidopa.

    Science.gov (United States)

    Tammimäki, Anne; Aonurm-Helm, Anu; Männistö, Pekka T

    2018-04-01

    1. Catechol-O-methyltransferase (COMT) is involved in the O-methylation of l-DOPA, dopamine, and other catechols. The enzyme is expressed in two isoforms: soluble (S-COMT), which resides in the cytoplasm, and membrane-bound (MB-COMT), which is anchored to intracellular membranes. 2. To obtain specific information on the functions of COMT isoforms, we studied how a complete MB-COMT deficiency affects the total COMT activity in the body, peripheral l-DOPA levels, and metabolism after l-DOPA (10 mg kg -1 ) plus carbidopa (30 mg kg -1 ) administration by gastric tube in wild-type (WT) and MB-COMT-deficient mice. l-DOPA and 3-O-methyl-l-DOPA (3-OMD) levels were assayed in plasma, duodenum, and liver. 3. We showed that the selective lack of MB-COMT did not alter the total COMT activity, COMT enzyme kinetics, l-DOPA levels, or the total O-methylation of l-DOPA but delayed production of 3-OMD in plasma and peripheral tissues.

  17. Effect of a Ropy Exopolysaccharide-Producing Bifidobacterium animalis subsp. lactis Strain Orally Administered on DSS-Induced Colitis Mice Model.

    Science.gov (United States)

    Hidalgo-Cantabrana, Claudio; Algieri, Francesca; Rodriguez-Nogales, Alba; Vezza, Teresa; Martínez-Camblor, Pablo; Margolles, Abelardo; Ruas-Madiedo, Patricia; Gálvez, Julio

    2016-01-01

    Exopolysaccharide (EPS)-producing bifidobacteria, particularly Bifidobacterium animalis subsp. lactis strains, are used in the functional food industry as promising probiotics with purported beneficial effects. We used three isogenic strains of B. animalis subsp. lactis, with different EPS producing phenotypes (mucoid-ropy and non-ropy), in order to determine their capability to survive the murine gastrointestinal tract transit, as well as to evaluate their role in improving clinical outcomes in a chemically-induced colitis model. The three strains were able to survive in the intestinal tract of C57BL/6J mice during the course of the intervention study. Furthermore, the disease activity index (DAI) of the animal group treated with the ropy strain was significantly lower than of the DAI of the placebo group at the end of the treatment. However, no significant differences were found among the three strains. The analysis of several immune parameters, such as TNFα and IL-10 quantified in blood plasma and lymphocyte populations enumerated in mesenteric nodes, showed some significant variations among the four experimental animal groups. Remarkably, a higher capability of the ropy strain to increase regulatory T-cells in mesenteric lymphoid nodes was demonstrated, suggesting a higher ability of this strain to regulate inflammatory responses at mucosal level. Our data indicate that strains of B. animalis subsp. lactis producing EPS that confer a mucoid-ropy phenotype could represent promising candidates to perform further studies targeting intestinal inflammatory processes.

  18. Oral Administration of a Seed-based Bivalent Rotavirus Vaccine Containing VP6 and NSP4 Induces Specific Immune Responses in Mice

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    Hao Feng

    2017-05-01

    Full Text Available Rotavirus is the leading cause of severe diarrheal disease among newborns. Plant-based rotavirus vaccines have been developed in recent years and have been proven to be effective in animal models. In the present study, we report a bivalent vaccine candidate expressing rotavirus subunits VP6 and NSP4 fused with the adjuvant subunit B of E. coli heat-labile enterotoxin (LTB in maize seeds. The RT-PCR and Western blot results showed that VP6 and LTB-NSP4 antigens were expressed and accumulated in maize seeds. The expression levels were as high as 0.35 and 0.20% of the total soluble protein for VP6 and LTB-NSP4, respectively. Oral administration of transgenic maize seeds successfully stimulated systemic and mucosal responses, with high titers of serum IgG and mucosal IgA antibodies, even after long-term storage. This study is the first to use maize seeds as efficient generators for the development of a bivalent vaccine against rotavirus.

  19. Oral Administration of a Seed-based Bivalent Rotavirus Vaccine Containing VP6 and NSP4 Induces Specific Immune Responses in Mice

    Science.gov (United States)

    Feng, Hao; Li, Xin; Song, Weibin; Duan, Mei; Chen, Hong; Wang, Tao; Dong, Jiangli

    2017-01-01

    Rotavirus is the leading cause of severe diarrheal disease among newborns. Plant-based rotavirus vaccines have been developed in recent years and have been proven to be effective in animal models. In the present study, we report a bivalent vaccine candidate expressing rotavirus subunits VP6 and NSP4 fused with the adjuvant subunit B of E. coli heat-labile enterotoxin (LTB) in maize seeds. The RT-PCR and Western blot results showed that VP6 and LTB-NSP4 antigens were expressed and accumulated in maize seeds. The expression levels were as high as 0.35 and 0.20% of the total soluble protein for VP6 and LTB-NSP4, respectively. Oral administration of transgenic maize seeds successfully stimulated systemic and mucosal responses, with high titers of serum IgG and mucosal IgA antibodies, even after long-term storage. This study is the first to use maize seeds as efficient generators for the development of a bivalent vaccine against rotavirus. PMID:28620404

  20. Oral infection of neonate gerbils by Neospora caninum tachyzoites

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    Maiara Sanitá Tafner Ferreira

    2015-01-01

    Full Text Available ABSTRACT: Neosporosis is a parasitic disease caused by the protozoan Neospora caninum which results in major economic losses for cattle breeding due to abortion and other reproductive disorders. Gerbils (Meriones unguiculatus are commonly used as experimental models for neosporosis due to their high susceptibility to N. caninum infection, both by oocysts ingestion as by tachyzoites/bradyzoites parenteral inoculation. However, the risk of transmission by tachyzoites ingestion is not fully elucidated. In this study, infection of neonate gerbils by N. caninum (NC-1 strain tachyzoites inoculated by the oral route and the parasite distribution in gerbils' tissues were evaluated by protozoan DNA detection. Seventeen neonate gerbils, aged 4-5 days, were inoculated with 4x105 tachyzoites by the oral route and one gerbil was kept as uninfected control. N. caninum DNA was detected in 100% of the inoculated gerbils, showing that the oral route is effective as a potential route of infection of neonates by N. caninum tachyzoites. N. caninum DNA was reported in all organs evaluated (heart, lungs, kidneys, liver, spleen and brain, with different frequencies. These results showed systemically distributed infection of neonate gerbils after oral inoculation of tachyzoites.

  1. Comparative study of the assay of Artemia salina L. and the estimate of the medium lethal dose (LD50 value) in mice, to determine oral acute toxicity of plant extracts.

    Science.gov (United States)

    Logarto Parra, A; Silva Yhebra, R; Guerra Sardiñas, I; Iglesias Buela, L

    2001-09-01

    Artemia salina L. (Artemiidae), the brine shrimp larva, is an invertebrate used in the alternative test to determine toxicity of chemical and natural products. In this study the Medium Lethal Concentrations (LC50 value) of 20 plant extracts, Aloe vera (L.) Burm. F. (Aloeaceae), Artemisia absinthium L. (Asteraceae); Citrus aurantium L. (Rutaceae); Cymbopogon citratus (DC. Ex Nees) Stapf (Poaceae); Datura stramonium L. (Solanaceae); Justicia pectoralis Jacq. (Acanthaceae); Musa x paradisiaca L. (Musaceae); Ocimum basilicum L.; O. gratissimum L.; O. tenuiflorum L. (Lamiaceae); Pimenta dioica (L.) Merr. (Myrtaceae); Piper auritum Kunth (Piperaceae); Plantago major L. (Plantaginaceae); Plectranthus amboinicus (Lour.) Spreng. (Lamiaceae); Ruta graveolens L. (Rutaceae); Senna alata (L.) Roxb. (Fabaceae); Stachytarpheta jamaicensis (L.) Vahl (Verbenaceae); and Thuja occidentalis L. (Cupressaceae), were determined using Artemia salina L. (Artemiidae), with the objective of relating the results to the LD50 values reported in mice (tested at three concentrations: 10, 100, and 1000 microg/mL, for each extract). We found good correlation between the in vivo and the in vitro tests (r = 0.85 p < 0.05), and this method is a useful tool for predicting oral acute toxicity in plant extracts.

  2. Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Hui-fang [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Takaoka, Munenori [Department of General Surgery, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505 (Japan); Bao, Xiao-hong [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Wang, Zhi-gang [College of Life Science, Inner Mongolia University, The Key Laboratory of Mammal Reproductive Biology and Biotechnology, Ministry of Education, Hohhot 010021 (China); Tomono, Yasuko [Division of Molecular and Cell Biology, Shigei Medical Research Institute, 2117 Yamada, Okayama 700-0202 (Japan); Sakurama, Kazufumi; Ohara, Toshiaki [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Fukazawa, Takuya; Yamatsuji, Tomoki [Department of General Surgery, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505 (Japan); Fujiwara, Toshiyoshi [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Naomoto, Yoshio, E-mail: ynaomoto@med.kawasaki-m.ac.jp [Department of General Surgery, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505 (Japan)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer A novel FAK inhibitor TAE226 suppressed FAK activity in HCT116 colon cancer cells. Black-Right-Pointing-Pointer TAE226 suppressed proliferation and migration, with a modest effect on adhesion. Black-Right-Pointing-Pointer Silencing of FAK by siRNA made no obvious difference on cancer cell attachment. Black-Right-Pointing-Pointer TAE226 treatment suppressed the progression of peritoneal dissemination. Black-Right-Pointing-Pointer Oral administration of TAE226 prolonged the survival of tumor-bearing mice. -- Abstract: Peritoneal dissemination is one of the most terrible types of colorectal cancer progression. Focal adhesion kinase (FAK) plays a crucial role in the biological processes of cancer, such as cell attachment, migration, proliferation and survival, all of which are essential for the progression of peritoneal dissemination. Since we and other groups have reported that the inhibition of FAK activity exhibited a potent anticancer effect in several cancer models, we hypothesized that TAE226, a novel ATP-competitive tyrosine kinase inhibitor designed to target FAK, can prevent the occurrence and progression of peritoneal dissemination. In vitro, TAE226 greatly inhibited the proliferation and migration of HCT116 colon cancer cells, while their adhesion on the matrix surface was minimally inhibited when FAK activity and expression was suppressed by TAE226 and siRNA. In vivo, when HCT116 cells were intraperitoneally inoculated in mice, the cells could attach to the peritoneum and begin to grow within 24 h regardless of the pretreatment of cells with TAE226 or FAK-siRNA, suggesting that FAK is not essential, at least for the initial integrin-matrix contact. Interestingly, the treatment of mice before and after inoculation significantly suppressed cell attachment to the peritoneum. Furthermore, oral administration of TAE226 greatly reduced the size of disseminated tumors and prolonged survival in tumor-bearing mice. Taken

  3. Inoculation of soil native cyanobacteria to restore arid degraded soils

    Science.gov (United States)

    Raúl Román Fernández, José; Roncero Ramos, Beatriz; Chamizo de la Piedra, Sonia; Rodríguez Caballero, Emilio; Ángeles Muñoz Martín, M.; Mateo, Pilar; Cantón Castilla, Yolanda

    2017-04-01

    Restoration projects in semiarid lands often yield poor results. Water scarcity, low soil fertility, and poor soil structure strongly limit the survival and growth of planted seedlings in these areas. Under these conditions, a previous stage that improves edaphic conditions would turn out to a successful plant restoration. By successfully colonizing arid soils, cyanobacteria naturally provide suitable edaphic conditions, enhancing water availability, soil fertility and soil stability. Furthermore, cyanobacteria can be easily isolated and cultured ex-situ to produce high quantities of biomass, representing a potential tool to restore large areas efficiently. The objective of this study was to test the effect of inoculated cyanobacteria on degraded soils at three different semiarid areas from southeast Spain: Tabernas badlands, a limestone quarry located in Gádor, and grazed grassland in Las Amoladeras (Cabo de Gata). Soil native cyanobacteria belonging to three representative N-fixing genera (Nostoc, Scytonema and Tolypothrix) were isolated from such soils and cultured in BG110 medium. Each strain was inoculated (6 g m-2), separately and mixed (all in the same proportion), on Petri dishes with 80 g of each soil. Biocrust development was monitored during 3 months in these soils under laboratory conditions, at a constant temperature of 25oC. During the experiment, two irrigation treatments were applied simulating a dry (180 mm) and a wet (360 mm) rainfall year (average recorded in the study sites). After 3 months, net CO2 flux, spectral response and soil surface microtopography (1 mm spatial resolution) of inoculated and control soils was measured under wet conditions, all of them as a surrogate of biocrust development. Samples of the surface crust were collected in order to determine total soil organic carbon (SOC) content. The inoculated soils showed positive values of net CO2 flux, thus indicating a net CO2 uptake, whereas control soils showed CO2 fluxes closed to

  4. Inoculation method could impact the outcome of microbiological experiments

    DEFF Research Database (Denmark)

    Kragh, Kasper Nørskov; Alhede, Maria; Rybtke, Morten

    2018-01-01

    characteristics with biofilms such as increased antibiotic tolerance. We have investigated how aggregates develop and what influences this development in LBC of Pseudomonas aeruginosa We focused on how the method of inoculation impacted aggregation by assessing aggregate frequency and size using confocal laser...... of biofilm aggregates in a LBC, with inoculation directly from a plate resulting in the most numerous and largest aggregates. These large aggregates had an overall impact on the cultures' subsequent tolerance towards tobramycin indicating that the inoculation method has a profound impact on antibiotic...... tolerance. We also observed a mechanism where pre-formed aggregates recruited single cells from the surrounding culture in a "snowball effect", building up aggregated biomass in the culture. This recruitment was found to rely heavily on the exopolysaccharide Psl. Additionally, we found that both Escherichia...

  5. Experimental inoculation study indicates swine as a potential host for Hendra virus

    Science.gov (United States)

    Li, Mingyi; Embury-Hyatt, Carissa; Weingartl, Hana M.

    2010-01-01

    Hendra virus (HeV) is a zoonotic virus from the family Paramyxoviridae causing fatal disease in humans and horses. Five-week-old Landrace pigs and 5-month-old Gottingen minipigs were inoculated with approximately 107 plaque forming units per animal. In addition to fever and depression exhibited in all infected pigs, one of the two Landrace pigs developed respiratory signs at 5 days post-inoculation (dpi) and one of the Gottingen minipigs developed respiratory signs at 5 dpi and mild neurological signs at 7 dpi. Virus was detected in all infected pigs at 2–5 dpi from oral, nasal, and rectal swabs and at 3–5 dpi from ocular swabs by real-time RT-PCR targeting the HeV M gene. Virus titers in nasal swab samples were as high as 104.6 TCID50/mL. The viral RNA was mainly distributed in tissues from respiratory and lymphoid systems at an early stage of infection and the presence of virus was confirmed by virus isolation. Pathological changes and immunohistochemical staining for viral antigen were consistent with the tissue distribution of the virus. This new finding indicates that pigs are susceptible to HeV infections and could potentially play a role as an intermediate host in transmission to humans. PMID:20167195

  6. Oral myiasis

    Directory of Open Access Journals (Sweden)

    Thalaimalai Saravanan

    2015-01-01

    Full Text Available Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy.

  7. [Oral ulcers].

    Science.gov (United States)

    Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

    2005-10-29

    Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology.

  8. Inducing Resistance to Conspiracy Theory Propaganda: Testing Inoculation and Metainoculation Strategies

    Science.gov (United States)

    Banas, John A.; Miller, Gregory

    2013-01-01

    This investigation examined the boundaries of inoculation theory by examining how inoculation can be applied to conspiracy theory propaganda as well as inoculation itself (called metainoculation). A 3-phase experiment with 312 participants compared 3 main groups: no-treatment control, inoculation, and metainoculation. Research questions explored…

  9. Experimental inoculation of equine coronavirus into Japanese draft horses.

    Science.gov (United States)

    Nemoto, Manabu; Oue, Yasuhiro; Morita, Yoshinori; Kanno, Toru; Kinoshita, Yuta; Niwa, Hidekazu; Ueno, Takanori; Katayama, Yoshinari; Bannai, Hiroshi; Tsujimura, Koji; Yamanaka, Takashi; Kondo, Takashi

    2014-12-01

    Recently, outbreaks associated with equine coronavirus (ECoV) have occurred in Japan and the United States. While ECoV is likely to be pathogenic to horses, it has not been shown that experimental inoculation of horses with ECoV produces clinical signs of disease. In this study, we inoculated three Japanese draft horses with an ECoV-positive diarrheic fecal sample to confirm infection after inoculation and to investigate the clinical course and virus shedding patterns of ECoV. Virus neutralization tests showed that all three horses became infected with ECoV. Two of the three horses developed clinical signs similar to those observed during ECoV outbreaks, including fever, anorexia, and gastrointestinal dysfunction. All horses excreted a large amount of virus into their feces for more than 9 days after inoculation regardless of the presence or absence of clinical signs, which suggests that feces are an important source of ECoV infection. ECoV was also detected in nasal swabs from all horses, suggesting that respiratory transmission of ECoV may occur. Both symptomatic horses developed viremia, while the asymptomatic horse did not. White blood cell counts and serum amyloid A concentrations changed relative to the clinical condition of the inoculated horses; these may be useful markers for monitoring the clinical status of horses infected with ECoV. This is the first report of induction of clinical signs of ECoV infection in horses by experimental inoculation. These clinical and virological findings should aid further investigation of the pathogenesis of ECoV.

  10. Effects of co-inoculation and sequential inoculation of Tetragenococcus halophilus and Zygosaccharomyces rouxii on soy sauce fermentation.

    Science.gov (United States)

    Devanthi, Putu Virgina Partha; Linforth, Robert; Onyeaka, Helen; Gkatzionis, Konstantinos

    2018-02-01

    The use of Tetragenococcus halophilus and Zygosaccharomyces rouxii as starter cultures is essential for desirable volatiles production during moromi stage of soy sauce fermentation. In this study, the effect of simultaneous and sequential inoculation of cultures in moromi fermentation models, with respect to viability, physicochemical changes, and volatiles formation (using SPME-GC/MS) was investigated. Interestingly, an antagonism was observed as T. halophilus only proliferated (3 log increase) in the presence of Z. rouxii, while Z. rouxii growth was suppressed by 4 log in concurrence with pH increase to 7.31. Final content of reducing sugars, ethanol, acetic acid, and amino nitrogen did not differ significantly (p<0.05) between co-inoculation and sequential inoculation. However, Z. rouxii promoted alcohols formation and produced a more complex aroma profile under suppression. According to Principal Component Analysis (PCA), the inoculation sequence (co-inoculation and sequential) has impacts on volatile compound profiles during moromi fermentation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. [D-Leu-4]-OB3, an orally bioavailable leptin-related synthetic peptide insulin sensitizer: a study comparing the efficacies of [D-Leu-4]-OB3 and metformin on energy balance and glycemic regulation in insulin-deficient male Swiss Webster mice.

    Science.gov (United States)

    Novakovic, Zachary M; Leinung, Matthew C; Grasso, Patricia

    2013-05-01

    The effects of oral delivery of exenatide or pramlintide acetate in dodecyl maltoside (DDM) on energy balance and glycemic control in insulin-resistant obese db/db mice are enhanced when given in combination with [D-Leu-4]-OB3. To examine the anti-hyperglycemic influence of [D-Leu-4]-OB3 in a non-obese insulin-deficient animal model, we compared the effects of metformin (200mg/kg) and [D-Leu-4]-OB3 (40 mg/kg) on energy balance and glycemic control in streptozotocin (STZ)-induced diabetic male Swiss Webster (SW) mice. Diabetic mice were given insulin (Levemir(®), sc) alone, or in combination with metformin or [D-Leu-4]-OB3 orally in DDM, for 14 days. Body weight and food and water intake were measured daily. Fasting blood glucose levels were determined every other day. Serum C-peptide was measured by ELISA. Diabetic mice receiving insulin alone for 14 days gained significantly more weight than DDM-treated control mice, or mice given insulin in combination with metformin or [D-Leu-4]-OB3. The weight gain seen in mice given insulin alone was accompanied by significant increases in both food and water intake. Mice treated with insulin in combination with metformin or [D-Leu-4]-OB3, consumed significantly less food and water. Blood glucose levels in STZ-treated mice receiving insulin alone were reduced to 65.3% of initial levels, while mice receiving insulin with metformin or [D-Leu-4]-OB3 were reduced to 44.5% and 38.9%, respectively. Our results indicate that [D-Leu-4]-OB3 is as effective as metformin in preventing the body weight gain associated with insulin therapy, and on a molar basis, that the efficacy of [D-Leu-4]-OB3 as an insulin sensitizer may equal or surpass that of metformin. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Protection by Lactobacillus acidophilus UFV-H2B20 against experimental oral infection with Salmonella enterica subsp. enterica Ser. Typhimurium in gnotobiotic and conventional mice Proteção por Lactobacillus acidophilus UFV-H2B20 contra o desafio oral experimental com Salmonella enterica subsp. enterica Ser. Typhimurium em camundongos gnotobióticos e convencionais

    Directory of Open Access Journals (Sweden)

    Lilian Nobre Moura

    2001-03-01

    Full Text Available The ability of Lactobacillus acidophilus UFV-H2B20 to antagonize Salmonella enterica subsp. enterica ser. Typhimurium and to reduce the pathological consequences for the host was determining using conventional and gnotobiotic animals. Conventional NIH mice received daily by gavage a 0.1 ml suspension containing about 10(8 cfu L. acidophilus UFV-H2B20 and germfree animals received a single 0.1 ml dose. The gnotobiotic and conventional groups were infected orally with 10² and 10(5 cfu of S. Typhimurium, respectively, 7 days after the beginning of treatment. Control groups were treated with sterile saline instead of Lactobacillus. Survival data showed a protective effect against the pathogenic bacteria in both conventional and gnotobiotic Lactobacillus-treated mice. L. acidophilus UFV-H2B20 colonized the digestive tract of gnotobiotic mice and the number of viable cells ranged from 10(9 to 10(10 cfu/g of faeces. In both experimental and control gnotobiotic animals, S. Typhimurium became rapidly established at a level ranging from 10(8 to 10(10 cfu/g of faeces and remained at high levels until the animals died or were sacrificed. In conclusion, the previous treatment of mice with L. acidophilus UFV-H2B20 protects the animals against the experimental infection with S. Typhimurium but this protection was not due to the reduction of the pathogenic populations in the intestines.A capacidade de Lactobacillus acidophilus UFV-H2B20 de antagonizar Salmonella enterica subsp. enterica ser. Typhimurium, e de reduzir as conseqüências patológicas para o hospedeiro foram determinadas em animais convencionais e gnotobióticos. Camundongos NIH convencionais receberam diariamente, por via oral, 0,1 ml de uma suspensão contendo em torno de 10(8 ufc de L. acidophilus UFV-H2B20 e os animais sem germes receberam uma única dose de 0,1 ml. Os grupos gnotobióticos e convencionais foram desafiados oralmente com, respectivamente, 10² e 10(5 ufc de S. Typhimurium 7

  13. BALB/c Mice resist infection with Bartonella bacilliformis

    Directory of Open Access Journals (Sweden)

    Manguiña Ciro

    2008-10-01

    Full Text Available Abstract Background Bartonellosis due to Bartonella bacilliformis is a highly lethal endemic and sometimes epidemic infectious disease in South America, and a serious public health concern in Perú. There is limited information on the immunologic response to B. bacilliformis infection. The objective of this research was to produce experimental infection of BALB/c mice to B. bacilliformis inoculation. Findings BALB/c mice were inoculated with 1.5, 3.0 or 4.5 × 108 live B. bacilliformis using different routes: intraperitoneal, intradermal, intranasal, and subcutaneous. Cultures of spleen, liver, and lymph nodes from one to 145 days yielded no cultivable organisms. No organs showed lesions at any time. Previously inoculated mice showed no changes in the reinoculation site. Conclusion Parenteral inoculation of live B. bacilliformis via different infection routes produced no macroscopic or microscopic organ lesions in BALB/c mice. It was not possible to isolate B. bacilliformis using Columbia blood agar from 1 to 15 days after inoculation.

  14. Oral thearubigins do not protect against acetaminopheninduced ...

    African Journals Online (AJOL)

    The drugs were given orally by gavage for seven days. On day 7, 1 h after the last dose of treatment, the mice (except control group) were given a single dose of acetaminophen (n-acetyl-p-aminophenol, APAP) orally by gavage (350 mg/kg) and then sacrificed 4 h post-APAP intake. Blood was collected for biochemical ...

  15. Erythema at BCG Inoculation Site in Kawasaki Disease Patients.

    Science.gov (United States)

    Rezai, Mohammad Sadegh; Shahmohammadi, Soheila

    2014-08-01

    Kawasaki disease is an acute, self-limiting childhood systemic vasculitis with unknown etiology. Because there is no diagnostic test for Kawasaki disease, the diagnosis is based on clinical criteria. An important clinical sign that is not included in the classical clinical criteria for Kawasaki disease is a reaction at the Bacille Calmette-Guérin inoculation site that are present in about 30-50% of Kawasaki disease patients. of this review was to highlight the usefulness of the inflammation at the Bacille Calmette-Guérin inoculation site for early diagnosis of Kawasaki disease, we conducted a literature review on Medline in PubMed area, Google scholar, Magiran and Scientific Information Database using the search terms "Kawasaki disease, Erythema, BCG, inoculation site, children, cardiac complications, coronary artery lesion, aneurysm, incomplete Kawasaki in 2013. A total of 15 articles had been found. Erythema at the Bacille Calmette-Guérin inoculation site was found in 49.87% of Kawasaki disease patients. Coronary artery abnormalities were found in 10.3% of cases. According to this review, BCGitis is more prevalent than cervical lymphadenopathy and rash and it can be a useful criterion in the diagnosis of incomplete Kawasaki disease in cases not fulfills the classic criteria of at least four of the five findings.

  16. New Inoculants Containing Lactic Bacteria Applied in Forage Ensiling

    Directory of Open Access Journals (Sweden)

    Teodor Vintila

    2010-05-01

    Full Text Available In a first study, the capacity of lactic bacteria to accumulate biomass in different culture media and temperatures was tested and the biosynthesis parameters were established. In the second study, the strains producing the highest quantity of biomass and determining the most rapid pH drop in culture medium were conditioned in solid supports. The obtained solid products containing lactic bacteria were used to inoculate different types of forages. Ensilage was carried out in laboratory silos made from O2-impermeable plastic flasks, vacuumed using a vacuum pump. The experiment was 2 x 2 factorial with two types of forage (alfalfa and sorghum, each of them inoculated and not inoculated with lactic bacteria. The evolution of lactic bacteria, pH value, and the concentration in volatile acids was verified. In the third experiment, lactic bacteria were used to inoculate silages in farm conditions. The obtained results recommend the tested strain for the improvement of preserving conditions and nutritive value in ensiled forages.

  17. Inoculation of peritoneal dialysate fluid into blood culture bottles ...

    African Journals Online (AJOL)

    Twenty conventional cultures (54%) were positive compared with 33 (89%) done according to the Bactec system (P < 0,002). In only 1 case did the former technique prove superior. Direct inoculation of peritoneal fluid into Bactec blood culture bottles is therefore superior to conventional methods and has obvious therapeutic ...

  18. Effect of tillage, rhizobium inoculation in maize-soybean based ...

    African Journals Online (AJOL)

    Field experiment was conducted at Research Farm of Institute for Agricultural Research, Ahmadu Bello University, Samaru, Nigeria, to investigate the effect of tillage, rhizobium inoculation in maize-soybeanbased cropping systems and nitrogen fertilizer application on chemical fertility status of a savanna Alfisol. The study ...

  19. Inoculation of Ceratonia siliqua L. with native arbuscular mycorrhizal ...

    African Journals Online (AJOL)

    Ouhmane

    In Morocco, the production of carob was estimated only to 8% of the world production. This production considered .... mycorrhizal maize roots were used for the control treatment. Mycorrhizal inoculation of C. siliqua seedlings and plant .... Hence the selection of efficient AM fungi is a key factor to ensure the success of soil.