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Sample records for mice developing atopic

  1. Morus alba L. suppresses the development of atopic dermatitis induced by the house dust mite in NC/Nga mice

    Science.gov (United States)

    2014-01-01

    Background Morus alba, a medicinal plant in Asia, has been used traditionally to treat diabetes mellitus and hypoglycemia. However, the effects of M. alba extract (MAE) on atopic dermatitis have not been verified scientifically. We investigated the effects of MAE on atopic dermatitis through in vitro and in vivo experiments. Methods We evaluated the effects of MAE on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7, as well as thymus and activation-regulated chemokine (TARC/CCL17) in HaCaT cells. In an in vivo experiment, atopic dermatitis was induced by topical application of house dust mites for four weeks, and the protective effects of MAE were investigated by measuring the severity of the skin reaction on the back and ears, the plasma levels of immunoglobulin E (IgE) and histamine, and histopathological changes in the skin on the back and ears. Results MAE suppressed the production of NO and PGE2 in RAW 264.7 cells, as well as TARC in HaCaT cells, in a dose-dependent manner. MAE treatment of NC/Nga mice reduced the severity of dermatitis and the plasma levels of IgE and histamine. MAE also reduced the histological manifestations of atopic dermatitis-like skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration in the skin on the back and ears. Conclusion Our results suggest that MAE has potent inhibitory effects on atopic dermatitis-like lesion and may be a beneficial natural resource for the treatment of atopic dermatitis. PMID:24755250

  2. Inhibitory Effect of Valencene on the Development of Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice

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    In Jun Yang

    2016-01-01

    Full Text Available Valencene (VAL isolated from Cyperus rotundus possesses various biological effects such as antiallergic and antimelanogenesis activity. We investigated the effect of VAL on atopic dermatitis (AD skin lesions and their molecular mechanisms. We topically applied VAL to 1-chloro-2,4-dinitrobenzene (DNCB sensitized NC/Nga mice. Modified scoring atopic dermatitis index, scratching behavior, and histological/immunohistochemical staining were used to monitor disease severity. RT-PCR, western blotting, and enzyme-linked immunosorbent assay were used to determine the level of IgE, proinflammatory cytokines/chemokines production, and skin barrier proteins expression. Topical application of VAL significantly reduced AD-like symptoms and recovered decreased expression of filaggrin in DNCB-sensitized NC/Nga mice. The levels of serum IgE, IL-1β, IL-6, and IL-13 in skin/splenic tissue were reduced. In vitro studies using TNF-α and IFN-γ treated HaCaT cells revealed that VAL inhibited the exaggerated expression of Th2 chemokines including TARC/CCL17, MDC/CCL22, and proinflammatory chemokines such as CXCL8, GM-CSF, and I-CAM through blockade of the NF-κB pathway. In addition, expression of the skin barrier protein, involucrin, was also increased by VAL treatment. VAL inhibited the production and expression of proinflammatory cytokines IL-1β and IL-6 in LPS-stimulated RAW 264.7 cells. These results suggest that VAL may serve as a potential therapeutic option for AD.

  3. 7,3′,4′-Trihydroxyisoflavone Ameliorates the Development of Dermatophagoides farinae-Induced Atopic Dermatitis in NC/Nga Mice

    Directory of Open Access Journals (Sweden)

    Bo-Bae Kim

    2013-01-01

    Full Text Available Atopic dermatitis is an inflammatory and chronically relapsing skin disorder that commonly occurs in children; the number of atopic dermatitis patients is increasing. The cause and mechanism of atopic dermatitis have not been defined clearly, although many studies are ongoing. Epidemiological studies suggest that soybean and its isoflavones have immunoregulatory activities. Here, we report that 7,3′,4′-trihydroxyisoflavone (7,3′,4′-THIF, a major metabolite of daidzin, effectively inhibited lipopolysaccharide (LPS-induced nitric oxide (NO, tumor necrosis factor (TNF-α, and interleukin (IL-6 production in RAW 264.7 cells, and also reduced β-hexosaminidase secretion in RBL-2H3 cells. Moreover, 7,3′,4′-THIF significantly reduced scratching time, transepidermal water loss, and mast cell infiltration. It also decreased protease-activated receptor (PAR-2 and IL-4 expression and increased filaggrin expression in skin lesions of NC/Nga mice. These results suggest that 7,3′,4′-THIF improves Dermatophagoides farina body extract-induced atopic dermatitis in NC/Nga mice.

  4. Effect of the topical application of an ethanol extract of quince seeds on the development of atopic dermatitis-like symptoms in NC/Nga mice.

    Science.gov (United States)

    Kawahara, Takeshi; Tsutsui, Kanako; Nakanishi, Eri; Inoue, Toshifumi; Hamauzu, Yasunori

    2017-01-31

    Quince (Cydonia oblonga Miller) is a deciduous shrub belonging to the Rosaceae family. Quince seed extract has long been used as a cosmetic ingredient for its moisturizing effect. However, little is known about whether quince seed extract has therapeutic effects on keratinocyte-associated skin inflammation. In the present study, we investigated the effect of the topical application of ethanol extract of quince seeds (QSEtE) on atopic dermatitis (AD) symptoms in NC/Nga mice. The direct effect of QSEtE on keratinocytes was evaluated using the human keratinocyte cell line HaCaT. The preliminary application of QSEtE markedly reduced house dust mite allergen-induced skin lesions. The expression of thymus- and activation-regulated chemokine (TARC) in dorsal skin was downregulated. QSEtE directly suppressed the expression and production of TARC in HaCaT cells. The results suggest that the topical application of QSEtE is effective in preventing the onset of and ameliorating the atopic symptoms of keratinocyte-associated skin inflammation by suppressing TARC production in keratinocytes.

  5. Inhibitory effect of Psidium guajava water extract in the development of 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice.

    Science.gov (United States)

    Choi, Jae Ho; Park, Bong Hwan; Kim, Hyung Gyun; Hwang, Yong Pil; Han, Eun Hee; Jin, Sun Woo; Seo, Jong Kwon; Chung, Young Chul; Jeong, Hye Gwang

    2012-08-01

    Atopic dermatitis (AD) is a chronic, relapsing, and inflammatory skin disease associated with eczematous symptoms and IgE hyperproduction. Psidium guajava is an important food crop and medicinal plant with anti-oxidant, anti-inflammatory, and anti-allergic activities, supporting its traditional uses. Our previous studies have shown that P. guajava extract inhibits Th2 chemokine expression by suppressing the activation of NF-κB and STAT1 co-stimulated with TNF-α and INF-γ. In this study, we investigated the inhibitory effect of P. guajava water extract (PGW) on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in NC/Nga mice. Treatment of cream containing PGW onto DNCB-induced AD-like skin lesions in NC/Nga mice ameliorated lesion intensity scores, levels of IgE, thymus and activation-regulated chemokine (TARC), TNF-α, and IL-4 in serum and ears. In contrast, PGW increased level of the immunosuppressive cytokine IL-10. Histological analyses demonstrated decreased thickening of the epidermis/dermis as well as dermal infiltration by inflammatory cells. These results suggest that cream containing PGW may be a potential therapeutic modality for AD and adjunctive agent to control pruritus in AD. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. The inhibitory effect of Duchesnea chrysantha extract on the development of atopic dermatitis-like lesions by regulating IgE and cytokine production in Nc/Nga mice.

    Science.gov (United States)

    Lee, Ji-Sook; Kim, In Sik; Ryu, Ji-Sun; Kim, Joo-Hwan; Kim, Jin Sook; Kim, Dong-Hee; Yun, Chi-Young

    2012-02-01

    Duchesnea chrysantha belongs to the Rosaceae family and has been used traditionally for the treatment of various diseases in Korea and other parts of East Asia. This study examined the antiinflammatory effect of Duchesnea chrysantha extract (DcE) on atopic dermatitis in vitro and in vivo. DcE inhibited the production of IL-6, IL-8 and MCP-1 in THP-1 cells and the release of IL-6 and MCP-1 in EoL-1 cells after treatment with house dust mite extract. In the in vivo experiment, Nc/Nga mice were sensitized to DNCB and then orally and dorsally administered DcE (50 mg/kg in PBS) for 3 weeks. The DcE administration significantly reduced the skin severity score when compared with the control group and inhibited the thickening of the epidermis and infiltration of inflammatory cells into the dermis. In addition, the serum IgE levels decreased markedly in the DcE-treated mice when compared with the control group. The synthesis of IL-5, IL-13, MCP-1 and eotaxin was also decreased in splenocytes of the DcE-treated group, while IFN-γ was increased in the Dc-administered group. These results may indicate that DcE attenuates the development of atopic dermatitis-like lesions by lowering the IgE and inflammatory cytokine levels, and that it is useful in drug development for the treatment of atopic dermatitis. Copyright © 2011 John Wiley & Sons, Ltd.

  7. Oral administration of Uncariae rhynchophylla inhibits the development of DNFB-induced atopic dermatitis-like skin lesions via IFN-gamma down-regulation in NC/Nga mice.

    Science.gov (United States)

    Kim, Dong-Young; Jung, Jung-A; Kim, Tae-Ho; Seo, Sang-Wan; Jung, Sung-Ki; Park, Cheung-Seog

    2009-04-21

    Uncariae rhynchophylla (UR) is an herb which has blood pressure lowering and anti-inflammatory effects and has been prescribed traditionally to treat stroke and vascular dementia. In the present study, we examined whether UR suppress Atopic dermatitis (AD)-like skin lesions in NC/Nga mice treated with 2, 4-dinitrofluorobenzene (DNFB) under SPF conditions. The effect of UR in DNFB- treated NC/Nga mice was determined by measuring the skin symptom severity, levels of serum IgE, and of the amounts of IL-4 and IFN-gamma secreted by activated T cells in draining lymph nodes. Oral administration of UR to DNFB-treated NC/Nga mice was found to inhibit ear thickness increases and the skin lesions induced by DNFB. IFN-gamma production by CD4+ T cells from the lymph nodes of DNFB-treated NC/Nga mice was significantly inhibited by UR treatment, although levels of IL-4 and total IgE in serum were not. UR may suppress the development of AD-like dermatitis in DNFB-treated NC/Nga mice by reducing IFN-gamma production.

  8. Diospyros lotus leaf and grapefruit stem extract synergistically ameliorate atopic dermatitis-like skin lesion in mice by suppressing infiltration of mast cells in skin lesions.

    Science.gov (United States)

    Cho, Byoung Ok; Che, Denis Nchang; Yin, Hong Hua; Shin, Jae Young; Jang, Seon Il

    2017-05-01

    Atopic dermatitis, a chronic relapsing and pruritic inflammation of the skin also thought to be involved in, or caused by immune system destruction is an upsetting health problem due to its continuously increasing incidence especially in developed countries. Mast cell infiltration in atopic dermatitis skin lesions and its IgE-mediated activation releases various cytokines and chemokines that have been implicated in the pathogenesis of atopic dermatitis. This study was aimed at investigating synergistic anti-inflammatory, anti-pruritic and anti-atopic dermatitis effects of Diospyros lotus leaf extract (DLE) and Muscat bailey A grapefruit stem extract (GFSE) in atopic dermatitis-like induced skin lesions in mice. Combinations of DLE and GFSE inhibited TNF-α and IL-6 production more than DLE or GFSE in PMA plus calcium ionophore A23187-activated HMC-1 cells. DLE and GFSE synergistically inhibited compound 48/80-induced dermal infiltration of mast cells and reduced scratching behavior than DLE or GFSE. Furthermore, DLE and GFSE synergistically showed a stronger ameliorative effect in skin lesions by reducing clinical scores; dermal infiltration of mast cells; ear and dorsal skin thickness; serum IgE and IL-4 production in atopic dermatitis-like mice. Collectively, these results suggest that DLE and GFSE synergistically exhibit anti-atopic dermatitis effects in atopic dermatitis-like skin lesions in mice. Copyright © 2017. Published by Elsevier Masson SAS.

  9. Di-(2-ethylhexyl) phthalate affects immune cells from atopic prone mice in vitro

    International Nuclear Information System (INIS)

    Koike, Eiko; Inoue, Ken-ichiro; Yanagisawa, Rie; Takano, Hirohisa

    2009-01-01

    Phthalate esters as plasticizers have been widespread in the environment and may be associated with development of allergic diseases such as asthma and atopic dermatitis. However, the underlying mechanisms have not been fully elucidated. The present study investigated the effects of di-(2-ethylhexyl) phthalate (DEHP) on immune cells from atopic prone NC/Nga mice in vitro. Bone marrow-derived dendritic cells (BMDC) as a professional antigen-presenting cell and splenocytes as mixture of immune cells were used. BMDC were differentiated by culture with granulocyte macrophage-colony stimulating factor (GM-CSF) in the presence of DEHP (0.1-10 μM) for 6 days. In another experiments, BMDC were differentiated by culture with GM-CSF for 8 days then these BMDC were exposed to DEHP (0.1-100 μM) for 24 h. Splenocytes were exposed to DEHP for 24 h (0.1-100 μM) or 72 h (0.1-1000 nM). After the culture, the phenotypic markers and the function of BMDC and splenocytes were evaluated. BMDC differentiated in the presence of DEHP showed enhancement in the expression of MHC class II, CD86, CD11c and DEC205, and in their antigen-presenting activity. On the other hand, the function of the differentiated BMDC was not activated by DEHP although DEHP partly enhanced their expression of DEC205. DEHP-exposed splenocytes showed increases in their TCR and CD3 expression, interleukin-4 production, and antigen-stimulated proliferation. These results demonstrate that DEHP enhances BMDC differentiation but not activation and also enhances Th2 response in splenocytes from atopic prone mice. The enhancement might contribute to the aggravating effect of DEHP on allergic disorders.

  10. Theobroma cacao extract attenuates the development of Dermatophagoides farinae-induced atopic dermatitis-like symptoms in NC/Nga mice.

    Science.gov (United States)

    Kang, Heerim; Lee, Chang Hyung; Kim, Jong Rhan; Kwon, Jung Yeon; Son, Myoung-Jin; Kim, Jong-Eun; Lee, Ki Won

    2017-02-01

    Cacao beans from Theobroma cacao are an abundant source of polyphenols, particularly flavonoids. Previous studies demonstrated that cacao flavanols decrease pro-inflammatory cytokines resulting in the alleviation of allergic symptoms. We sought to investigate the effects of cacao extract (CE) on Dermatophagoides farinae extract (DFE)-induced atopic dermatitis (AD)-like symptoms. CE attenuated DFE-induced AD-like symptoms as assessed by skin lesion analyses, dermatitis score, and skin thickness. Histopathological analysis revealed that CE suppressed DFE-induced immune cell infiltration into the skin. These observations occurred concomitantly with the downregulation of inflammatory markers including serum immunoglobulin (Ig) E, chemokine; thymus and activation-regulated chemokine and macrophage-derived chemokine as well as the skin-derived cytokines interleukin (IL)-4, IL-5, and interferon-γ. CE also significantly alleviated transepidermal water loss and increased skin hydration. These results suggest that CE, a natural phytochemical-rich food, has potential therapeutic efficacy for the treatment of AD. Copyright © 2016. Published by Elsevier Ltd.

  11. Apgar score is related to development of atopic dermatitis

    DEFF Research Database (Denmark)

    Naeser, Vibeke; Kahr, Niklas; Stensballe, Lone Graff

    2013-01-01

    . We cross-linked with data from the Danish National Birth Registry and performed cotwin control analysis in order to test the impact of birth characteristics on the risk of atopic dermatitis. Results. Apgar score, OR (per unit) = 1.23 (1.06-1.44), P = 0.008, and female sex, OR = 1.31 (1.06-1.61), P...... = 0.012, were risk factors for atopic dermatitis in cotwin control analysis, whereas birth anthropometric factors were not significantly related to disease development. Risk estimates in monozygotic and dizygotic twins were not significantly different for the identified risk factors. Conclusions......Aim. To study the impact of birth characteristics on the risk of atopic dermatitis in a twin population. Methods. In a population-based questionnaire study of 10,809 twins, 3-9 years of age, from the Danish Twin Registry, we identified 907 twin pairs discordant for parent-reported atopic dermatitis...

  12. Lol p I-specific IgE and IgG synthesis by peripheral blood mononuclear cells from atopic subjects in SCID mice.

    Science.gov (United States)

    Gagnon, R; Boutin, Y; Hébert, J

    1995-06-01

    The development of an animal model representative of the in vivo situation of human atopic diseases is always of interest for a better understanding of IgE production and regulation. Along these lines, mice with severe combined immunodeficiency (SCID mice) engrafted with lymphocytes from atopic subjects might be a suitable model for such studies. This study aims to analyze the production of Lol p I-specific IgE and IgG antibodies in SCID mice after transplantation of human peripheral blood mononuclear cells from atopic patients sensitive to grass pollens and from nonatopic donors. Peripheral blood mononuclear cells were transplanted into SCID mice, which were then challenged with Lol p I, and antibody responses (IgG and IgE) were analyzed over a 6-week period. Total IgG antibody was measured in each mouse serum after transplantation. Also, most mice (regardless of whether donors were atopic) that were challenged with Lol p I produced specific IgG antibody. Total IgE antibody production was observed only in mice grafted with cells from atopic patients. Lol p I-specific IgE antibodies were also produced after immunization with Lol p I. Although IgG antibody/response tended to plateau, the IgE antibody response increased until it peaked and declined thereafter. Interferon-gamma was detected in sera from mice producing IgE antibody, which supports a possible role of interferon-gamma in the decrease of IgE response. This study suggests that the SCID mouse model could represent an interesting approach to studying specific, total IgG and IgE antibody production, and ultimately their regulation.

  13. Immunomodulatory effects of ultraviolet B irradiation on atopic dermatitis in NC/NGA mice

    International Nuclear Information System (INIS)

    Yasuko Mutou; Shuji Kojima; Yuko Ibuki

    2007-01-01

    Complete text of publication follows. Background: Atopic dermatitis (AD) is a common pruritic inflammatory skin disease with severe itching which occurs primarily in childhood. Overexpression of serum IgE are also a characteristic feature in many patient. Furthermore, Th2-type T cell cytokine, such as IL-4, IL-5, and Il-10, are produced in AD lesions. Recently, ultraviolet B (UVB) irradiation may increase according to depletion of the ozone layer. Furthermore, phototherapy is used to treat AD patient, but the mechanism involved is unknown. In this study, we investigated whether UVB irradiation influences atopic dermatitis in the NC/Nga mouse model. Methods: The mice were separated into 3 groups, control, AD-control (immunized with mite antigens), and AD + UVB-irradiated (immunized with mite antigens and UVB irradiation) groups. The mice of the irradiation group were exposed to 1 kJ/m 2 /day twice a week from 6 to 12 weeks of age. Animals of the control and AD-control groups were shaved, but not irradiated. Results: In the AD + UVB-irradiated group, the atopy score, ear thickness, and total IgE were increased in comparison with the AD-control group. On day 40, the levels of IL-4, IL-5, and IL-10 in the spleen lymphocytes were significantly increased compared with the AD-control group, resulting in a marked decrease of the IFN-Γ/IL-4 ratio compared with the AD-control group. In addition, the levels of IL-6, TNF-α, and NO X production by peritoneal macrophages were significantly elevated. Conclusion: These results indicate that UVB irradiation promotes the development of AD-like symptoms in NC/Nga mice, with an increased inflammatory response owing to increases of both IgE and NO X . In addition, systemic immune responses to local UVB were observed. It is possible that upstream proteins involved in IL-4, IL-5, IL-6, IL-10, and TNF-α, and NO X production play roles in the UVB-induced inflammatory responses. Our results also suggest that sunlight may aggravate the

  14. Risk Factors for Developing Atopic Dermatitis

    DEFF Research Database (Denmark)

    G. Carson, Charlotte

    2013-01-01

    The aim of this thesis was to investigate possible risk factors affecting the development of AD. AD is a frequent disease among children and has a substantial impact on the lives of both the child and its family. A better understanding of the disease would enable better treatment, prevention...... and information to the families involved. Previous risk factor studies have been hampered by an unsuitable study design and/or difficulties in standardization when diagnosing AD, which limit their conclusions. In paper I, we conducted a traditional cross-sectional analysis testing 40 possible risk factors...... exposure to dog was the only environmental exposure that significantly reduced the disease manifestation, suggesting other, yet unknown environmental factors affecting the increasing prevalence of AD in children. Length at birth was shown to be inversely associated with the risk of later developing AD...

  15. Effect of German chamomile oil application on alleviating atopic dermatitis-like immune alterations in mice

    Science.gov (United States)

    Lee, Soon-Hee; Heo, Yong

    2010-01-01

    Historically, German chamomile (GC) oil has been used for treatment of skin disorders. BALB/c mice were sensitized twice a week with 100 µL of 1% 2,4-dinitrochlorobenzene (DNCB) and challenged twice the following week with 100 µL of 0.2% DNCB for atopic dermatitis induction. Thereafter, 3% GC oil was applied daily (70 µL, 6 times week) on the dorsal skin for 4 weeks. Saline or jojoba oil was used for the control mice. Blood was collected after second DNCB challenge, and at 2 and 4 weeks after initiating oil application. Serum IgE levels were significantly lowered in the GC oil application group at the end of the 4-week application period. The GC oil application for 4 weeks resulted in reduction in serum IgG1 level compared with that after 2-week application. The GC oil application group showed a significantly lower serum histamine level than the control group 2 weeks after oil application. Scratching frequency of the GC oil application group was significantly lower than either control groups. This study is to demonstrate GC oil's immunoregulatory potential for alleviating atopic dermatitis through influencing of Th2 cell activation. PMID:20195063

  16. Development of atopic dermatitis and its association with prenatal and early life exposures

    OpenAIRE

    Roduit, Caroline

    2015-01-01

    Over 20% of children in industrialized countries are affected by atopic dermatitis. From epidemiological studies, it is quite obvious that the worldwide prevalence of atopic dermatitis has considerably increased over the past decades and constitutes a major public health problem. Atopic dermatitis is a chronic inflammatory skin disease that occurs in very early life and frequently precedes the development of asthma and allergic rhinitis during the first several years of life. Although a large...

  17. Early-life rotavirus and norovirus infections in relation to development of atopic manifestation in infants.

    NARCIS (Netherlands)

    Reimerink, J.; Stelma, F.F.; Rockx, B.; Brouwer, D.; Stobberingh, E.E.; Ree, R. van; Dompeling, E.; Mommers, M.; Thijs, C.; Koopmans, M.

    2009-01-01

    BACKGROUND: The increase in incidence of atopic diseases (ADs) in the developed world over the past decades has been associated with reduced exposure of childhood infections. OBJECTIVE: To investigate the relation between early intestinal viral infections in relation to the development of atopic

  18. Atopic diseases and the risk of developing ulcerative colitis

    NARCIS (Netherlands)

    Azim, Samman; Hak, Eelko; Bos, Jens H.J.; Schuiling-Veninga, Catharina C.M.

    2016-01-01

    Background: Although auto-immune diseases and atopic diseases seem to be caused by different malfunctions in the immunological pathways, there is an increasing body of evidence for cross regulation between the two pathways. Research showed that patients suffering from atopic diseases are at greater

  19. Bee Venom Phospholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice

    Directory of Open Access Journals (Sweden)

    Kyung-Hwa Jung

    2017-02-01

    Full Text Available Atopic dermatitis (AD is a biphasic inflammatory skin disease that is provoked by epidermal barrier defects, immune dysregulation, and increased skin infections. Previously, we have demonstrated that bvPLA2 evoked immune tolerance by inducing regulatory T cells (Treg, and thus alleviated Th2 dominant allergic asthma in mice. Here, we would like to determine whether treatment with bvPLA2 exacerbates the AD-like allergic inflammations induced by house dust mite extract (DFE in a murine model. Epidermal thickness, immune cell infiltration, serum immunoglobulin, and cytokines were measured. Ear swelling, skin lesions, and the levels of total serum IgE and Th1/Th2 cytokines were elevated in DFE/DNCB-induced AD mice. Topical application of bvPLA2 elicited significant suppression of the increased AD symptoms, including ear thickness, serum IgE concentration, inflammatory cytokines, and histological changes. Furthermore, bvPLA2 treatment inhibited mast cell infiltration into the ear. On the other hand, Treg cell depletion abolished the anti-atopic effects of bvPLA2, suggesting that the effects of bvPLA2 depend on the existence of Tregs. Taken together, the results revealed that topical exposure to bvPLA2 aggravated atopic skin inflammation, suggesting that bvPLA2 might be a candidate for the treatment of AD.

  20. Bee Venom Phospholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice.

    Science.gov (United States)

    Jung, Kyung-Hwa; Baek, Hyunjung; Kang, Manho; Kim, Namsik; Lee, Seung Young; Bae, Hyunsu

    2017-02-18

    Atopic dermatitis (AD) is a biphasic inflammatory skin disease that is provoked by epidermal barrier defects, immune dysregulation, and increased skin infections. Previously, we have demonstrated that bvPLA2 evoked immune tolerance by inducing regulatory T cells (Treg), and thus alleviated Th2 dominant allergic asthma in mice. Here, we would like to determine whether treatment with bvPLA2 exacerbates the AD-like allergic inflammations induced by house dust mite extract (DFE) in a murine model. Epidermal thickness, immune cell infiltration, serum immunoglobulin, and cytokines were measured. Ear swelling, skin lesions, and the levels of total serum IgE and Th1/Th2 cytokines were elevated in DFE/DNCB-induced AD mice. Topical application of bvPLA2 elicited significant suppression of the increased AD symptoms, including ear thickness, serum IgE concentration, inflammatory cytokines, and histological changes. Furthermore, bvPLA2 treatment inhibited mast cell infiltration into the ear. On the other hand, Treg cell depletion abolished the anti-atopic effects of bvPLA2, suggesting that the effects of bvPLA2 depend on the existence of Tregs. Taken together, the results revealed that topical exposure to bvPLA2 aggravated atopic skin inflammation, suggesting that bvPLA2 might be a candidate for the treatment of AD.

  1. Fluoxetine ameliorates atopic dermatitis-like skin lesions in BALB/c mice through reducing psychological stress and inflammatory response

    Directory of Open Access Journals (Sweden)

    Yanxi Li

    2016-09-01

    Full Text Available Atopic dermatitis (AD is a common chronic inflammatory skin disorder, and patients with AD suffer from severe psychological stress, which markedly increases the prevalence rate of depression and anxiety disorders in later life. Fluoxetine, a selective serotonin reuptake inhibitor, has recently been reported to exert anti-inflammatory and immunosuppressive effects. However, it is unclear whether fluoxetine is effective in the treatment of AD through reducing psychological stress and inflammatory reaction. Here, we reported that a BALB/c mouse model of AD was induced by application of 2,4‑dinitrochlorobenzene (DNCB onto hairless dorsal skin. Chronic fluoxetine treatment (10 mg/kg per day, i.p. significantly attenuated AD-like symptoms, as reflected by a dramatic decrease in scratching bouts, as well as a decrease in anxiety- and depressive-like behaviors. Furthermore, these behavioral changes were accompanied by a significant decrease in epidermal thickness, the number of mast cells in skin tissue, mRNA levels of interleukin-4 (IL-4 and IL-13 in the spleen, as well as serum immunoglobulin E (IgE in the DNCB-treated mice by treatment with fluoxetine. Taken together, these results indicate that fluoxetine may suppress psychological stress and inflammatory response during AD development, and subsequently ameliorate AD symptoms, suggesting that fluoxetine may be a potential therapeutic agent against AD in clinic.

  2. Protein Linked to Atopic Dermatitis

    Science.gov (United States)

    ... Research Matters NIH Research Matters January 14, 2013 Protein Linked to Atopic Dermatitis Normal skin from a ... in mice suggests that lack of a certain protein may trigger atopic dermatitis, the most common type ...

  3. Infant feeding and the development of food allergies and atopic eczema: An update.

    Science.gov (United States)

    Gamboni, Sarah E; Allen, Katrina J; Nixon, Rosemary L

    2013-05-01

    There is an increasing awareness of food allergies in the community. Dermatologists frequently see patients with atopic eczema, where parents are extremely concerned about the role of food allergy. Advice given to parents regarding the timing of introduction of solid foods has changed markedly over the past decade. Whereas previous advice advocated delaying the introduction of solid foods until the infant's gastrointestinal system had matured, recent studies suggest that the introduction of solids from around 4 to 6 months may actually prevent the development of allergies. Studies on maternal dietary restrictions during pregnancy and lactation have led researchers to believe that antigen avoidance does not play a significant role in the prevention of atopic disease. Breastfeeding exclusively for 4 to 6 months has multiple benefits for mother and child, however, it does not convincingly prevent food allergies or decrease atopic eczema. New evidence suggests that the use of hydrolysed formulas does not delay or prevent atopic eczema or food allergy. This article aims to highlight current evidence and provide an update for dermatologists on the role of food exposure in the development of atopic disease, namely atopic eczema. © 2012 The Authors. Australasian Journal of Dermatology © 2012 The Australasian College of Dermatologists.

  4. Effect of Acer tegmentosum bark on atopic dermatitis-like skin lesions in NC/Nga mice.

    Science.gov (United States)

    Yang, Gabsik; An, Duckgun; Lee, Mi-Hwa; Lee, Kyungjin; Kim, Bumjung; Suman, Chinannai Khanita; Ham, Inhye; Choi, Ho-Young

    2016-01-11

    Atopic dermatitis (AD) is a chronic and relapsing inflammatory condition characterized by pruritic and eczematous skin lesions that requires safe and effective pharmacological therapy. The bark of Acer tegmentosum Maxim trees has been used in Korean folk and traditional medicine to treat abscesses, surgical bleeding, liver diseases, and AD. To investigate the therapeutic effect of A. tegmentosum, on a mouse model of Dermatophagoides farinae (Df)-induced AD. Development of AD-like skin lesions was induced by repetitive skin contact with barrier-disrupted backs of NC/Nga mice with Df body ointment, and the effects of A. tegmentosum were evaluated on the basis of histopathological skin assessment results, ear swelling, and cytokine production in the dorsal skin. The component of A. tegmentosum, salidroside, inhibited the production of TSLP in KCMH-1 cells, which indicated that its production could be pharmacologically regulated. Topical application of A. tegmentosum for 1 week after Df body ointment challenge significantly reduced ear swelling and improved dorsal skin lesions. Suppression of dermatitis by combined therapy was accompanied by a decrease in the skin level of Th2 cytokines, such as interleukin (IL)-4, IL-5 and IL-13, plasma levels of thymus and activation-regulated chemokine, and IgE. Induction of thymic stromal lymphopoietin, which leads to a systemic Th2 response, was also reduced in in vivo and in vitro by A. tegmentosum and salidroside. Our findings suggest that A. tegmentosum treatment has a significant therapeutic effect on Df-induced AD-like skin lesions on NC/Nga mice through inhibition of thymic stromal lymphopoietin and IgE via a mechanism that may inhibit Th2-mediated immune responses. These results suggest that A. tegmentosum and salidroside may be useful tools for the treatment of AD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Effect of repeated small-dose γ-ray irradiation on atopic dermatitis in NC/Nga mice

    International Nuclear Information System (INIS)

    Fang, Su-Ping; Muto, Yasuko; Tago, Fumitoshi; Simura, Noriko; Kojima, Shuji

    2006-01-01

    We previously showed that several small-dose 0.5 Gy whole-body γ-ray irradiation inhibits tumor growth in mice via elevation of the interferon (IFN)-γ/interleukin 4 (IL-4) ratio concomitantly with a decrease in the percentage of B cells. Here, we examined whether repeated small-dose (0.5 Gy, 10 times) γ-ray irradiation influences atopic dermatitis in an NC/Nga mouse model. It was found that repeated γ-ray irradiation increased total IgE in comparison with the disease-control group. Levels of IL-4 and IL-5 were increased versus the disease-control group, while IFN-γ was slightly decreased, resulting in a further decrease of the IFN-γ/IL-4 ratio compared with the disease-control group. These results indicate that repeated small-dose γ-ray irradiation may exacerbate atopic dermatitis. This may be because the irradiation induces not helper T lymphocyte 1 (Th1), but Th2 polarization in this atopic mouse model, i.e., the effects of small-dose irradiation may be different in conditions involving immune hypersensitivity and impaired immunity. (author)

  6. Risk of developing major depression and bipolar disorder among adolescents with atopic diseases: A nationwide longitudinal study in Taiwan.

    Science.gov (United States)

    Wei, Han-Ting; Lan, Wen-Hsuan; Hsu, Ju-Wei; Huang, Kai-Lin; Su, Tung-Ping; Li, Cheng-Ta; Lin, Wei-Chen; Chen, Tzeng-Ji; Bai, Ya-Mei; Chen, Mu-Hong

    2016-10-01

    Previous studies have found an increased prevalence of atopic diseases among patients with major depression and bipolar disorder. But the temporal association between atopic diseases in adolescence and the subsequent risk of developing mood disorders has been rarely investigated. Using the Taiwan National Health Insurance Research Databases, 5075 adolescents with atopic diseases (atopic cohort) and 44,729 without (non-atopic cohort) aged between 10 and 17 in 2000 were enrolled into our study and followed to the end of 2010. Subjects who developed major depression or bipolar disorder during the follow-up were identified. The atopic cohort had an increased risk of developing major depression (HR: 2.45, 95% CI: 1.93~3.11) and bipolar disorder (HR: 2.51, 95% CI: 1.71~3.67) compared to the non-atopic cohort, with a dose-dependent relationship between having a greater number of atopic comorbidities and a greater likelihood of major depression (1 atopic disease: HR: 1.80, 95% CI: 1.29~2.50; 2 atopic comorbidities: HR: 2.42, 95% CI: 1.93~3.04;≥3 atopic comorbidities: HR: 3.79, 95% CI: 3.05~4.72) and bipolar disorder (HR: 1.40, 95% CI: 0.57~3.44; HR: 2.81, 95% CI: 1.68~4.68; HR: 3.02, 95% CI: 1.69~5.38). Having atopic diseases in adolescence increased the risk of developing major depression and bipolar disorder in later life. Further studies may be required to clarify the underlying mechanism between atopy and mood disorders, and to investigate whether prompt intervention may decrease the risk of subsequent mood disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Risk assessment of bronchial asthma development in children with atopic dermatitis

    Science.gov (United States)

    Vуsotska, Olena V.; Klymenko, Viktoriia A.; Trubitcin, Alexei A.; Pecherska, Anna I.; Savchuk, Tamara O.; Kolimoldayev, Maksat; Wójcik, Waldemar; Szatkowska, Małgorzata; Burlibay, Aron

    2017-08-01

    This article offers a risk assessment of bronchial asthma development in children with atopic dermatitis by applying fuzzy-set theory to accumulated statistical data. It is shown that with a view to executing the said task one should exercise a complex approach involving factors such as "IgE level", "existence of obstructions" and "burdened bronchial asthma heredity of immediate relatives". The obtained results will assist in making adequate and well-informed medical decisions as well as facilitate the decrease of the risk of developing bronchial asthma in children with atopic dermatitis.

  8. Vitamin E improves biochemical indices associated with symptoms of atopic dermatitis-like inflammation in NC/Nga mice.

    Science.gov (United States)

    Hayashi, Daisuke; Sugaya, Hotaka; Ohkoshi, Takayuki; Sekizawa, Kaori; Takatsu, Hirokatsu; Shinkai, Tadashi; Urano, Shiro

    2012-01-01

    We aimed to define whether vitamin E improves biochemical indices associated with symptoms of atopic dermatitis-like inflammation in NC/Nga mice. After picryl chloride (PC) application to their backs, changes in the content of thiobarbituric acid reactive substances (TBARS) and vitamin E, as well as the activity of antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase) were analyzed in the serum and skin of NC/Nga mice during a symptomatic cycle. The levels of inflammatory factors were also assessed, including IgE, cyclooxigenase-2 (COX-2), tumor necrosis factor (TNF-α) and nuclear factor-κB (NF-κB). When allergic dermatitis was induced by the application of PC to the skin of the mice, skin inflammation appeared 2 wk after PC application, with the peak severity of inflammation observed 5 wk after PC application. Subsequently, the animals recovered from the inflammation by 9 wk after PC application. The TBARS content in the skin and serum increased markedly when the symptoms were the most severe, and decreased to levels near those in control mice by 9 wk after PC application. The activities of SOD and GSHPx in the skin and serum were also positively correlated with symptomatic changes; however, no change in catalase activity was observed 5 wk after PC application. Conversely, vitamin E content decreased at the stage of peak severity. The levels of all inflammatory factors analyzed in this study were altered in a manner similar to other indices. Additionally, vitamin E treatment markedly inhibited these PC-induced alterations. On the basis of these results, it is expected that the observed alterations in biochemical indices, which reflect the symptomatic cycle, may be applicable to objective diagnosis and treatment for atopic dermatitis, and that vitamin E may improve the symptoms of AD.

  9. Early-life rotavirus and norovirus infections in relation to development of atopic manifestation in infants

    NARCIS (Netherlands)

    Reimerink, J.; Stelma, F.; Rockx, B.; Brouwer, D.; Stobberingh, E.; van Ree, R.; Dompeling, E.; Mommers, M.; Thijs, C.; Koopmans, M.

    2009-01-01

    Summary Background The increase in incidence of atopic diseases (ADs) in the developed world over the past decades has been associated with reduced exposure of childhood infections. Objective To investigate the relation between early intestinal viral infections in relation to the development of

  10. Development of atopic dermatitis during the first 3 years of life

    DEFF Research Database (Denmark)

    Halkjær, Liselotte Brydensholt; Loland, Lotte; Buchvald, Frederik F

    2006-01-01

    , followed up for 3 years with scheduled visits every 6 months as well as visits for onset or acute exacerbations of skin symptoms. SETTING: The cohort was recruited from greater Copenhagen, Denmark, and followed up at a clinical research unit, which controlled all diagnoses and treatment of skin diseases....... PARTICIPANTS: A total of 411 infants were enrolled in the cohort; 55 had incomplete follow-up and were excluded from certain analyses. MAIN OUTCOME MEASURES: Atopic dermatitis was defined based on the criteria of Hanifin and Rajka, and severity was assessed by the SCORAD (Scoring Atopic Dermatitis) index...... predicted AD at age 3 years. CONCLUSIONS: Atopic dermatitis begins at the scalp, forehead, ear, and neck in a balaclava-like pattern. Eczema at the arms and joints provides the highest predictive value for the development of AD at age 3 years. This may be used for early prediction and intervention of AD....

  11. Cesarean section delivery and development of food allergy and atopic dermatitis in early childhood.

    Science.gov (United States)

    Papathoma, Evangelia; Triga, Maria; Fouzas, Sotirios; Dimitriou, Gabriel

    2016-06-01

    Delivery by Cesarean section (CS) may predispose to allergic disorders, presumably due to alterations in the establishment of normal gut microbiota in early infancy. In this study, we sought to investigate the association between CS and physician-diagnosed food allergy and atopic dermatitis during the first 3 years of life, using data from a homogeneous, population-based, birth cohort. A total of 459 children born and cared for in the same tertiary maternity unit were examined at birth and followed up at 1, 6, 12, 18, 24, 30 and 36 months of age. Participants with symptoms suggestive of food allergy or atopic dermatitis were evaluated by a pediatric allergy specialist to confirm the diagnosis based on well-defined criteria. The rate of CS was 50.8% (n = 233). Food allergy was diagnosed in 24 participants (5.2%) while atopic dermatitis was diagnosed in 62 children (13.5%). Cesarean section (OR 3.15; 95% CI 1.14-8.70), atopic dermatitis of the child (OR 3.01; 95% CI 1.18-7.80), parental atopy (OR 4.33; 95% CI 1.73-12.1), and gestational age (OR 1.57; 95% CI 1.07-2.37) were significant and independent predictors of food allergy. Children with at least one allergic parent delivered by CS had higher probability of developing food allergy compared with vaginally delivered children of non-allergic parents (OR 10.0; 95% CI 3.06-32.7). Conversely, the effect of CS on atopic dermatitis was not significant (OR 1.35; 95% CI 0.74-2.47). Delivery by CS predisposes to the development of food allergy but not atopic dermatitis in early childhood. Cesarean section delivery seems to upregulate the immune response to food allergens, especially in children with allergic predisposition. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Development of human skin equivalents to unravel the impaired skin barrier in atopic dermatitis skin

    NARCIS (Netherlands)

    Eweje, M.O.

    2016-01-01

    The studies in this thesis describes the barrier defects in Atopic Dermatitis (AD) skin and various techniques to develop AD Human Skin Equivalents (HSEs) which can be used to better understand the role of several factors in the pathogenesis of AD skin. The results described show that Inflammation

  13. The Drinking Effect of Hydrogen Water on Atopic Dermatitis Induced by Dermatophagoides farinae Allergen in NC/Nga Mice

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    Rosa Mistica C. Ignacio

    2013-01-01

    Full Text Available Hydrogen water (HW produced by electrolysis of water has characteristics of extremely low oxidation-reduction potential (ORP value and high dissolved hydrogen (DH. It has been proved to have various beneficial effects including antioxidant and anti-inflammatory effects; however, HW effect on atopic dermatitis (AD, an inflammatory skin disorder, is poorly documented. In the present study, we examined the immunological effect of drinking HW on Dermatophagoides farinae-induced AD-like skin in NC/Nga mice. Mice were administered with HW and purified water (PW for 25 days. We evaluated the serum concentration of pro-inflammatory (TNF-α, Th1 (IFN-γ, IL-2, and IL-12p70, Th2 (IL-4, IL-5, and IL-10, and cytokine expressed by both subsets (GM-CSF to assess their possible relationship to the severity of AD. The serum levels of cytokines such as IL-10, TNF-α, IL-12p70, and GM-CSF of mice administered with HW was significantly reduced as compared to PW group. The results suggest that HW affects allergic contact dermatitis through modulation of Th1 and Th2 responses in NC/Nga mice. This is the first note on the drinking effect of HW on AD, clinically implying a promising potential remedy for treatment of AD.

  14. Atopic dermatitis

    DEFF Research Database (Denmark)

    Thomsen, Simon Francis

    2014-01-01

    Atopic dermatitis is an inflammatory skin disease with early onset and with a lifetime prevalence of approximately 20%. The aetiology of atopic dermatitis is unknown, but the recent discovery of filaggrin mutations holds promise that the progression of atopic dermatitis to asthma in later childhood...... may be halted. Atopic dermatitis is not always easily manageable and every physician should be familiar with the fundamental aspects of treatment. This paper gives an overview of the natural history, clinical features, and treatment of atopic dermatitis....

  15. Immunosuppressive effects of fisetin against dinitrofluorobenzene-induced atopic dermatitis-like symptoms in NC/Nga mice.

    Science.gov (United States)

    Kim, Gun-Dong; Lee, Seung Eun; Park, Yong Seek; Shin, Dong-Hoon; Park, Gwi Gun; Park, Cheung-Seog

    2014-04-01

    Atopic dermatitis (AD) is a multifactorial chronic skin disorder that is increasing in prevalence globally. In NC/Nga mice, repetitive epicutaneous applications of 2-4-dinitrofluorobenzene (DNFB) induces AD-like clinical symptoms. Bioflanonol fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary component found in plants, fruits and vegetables. Fisetin has various physiological effects that include anti-oxidation, anti-angiogenesis, anti-carcinogenesis and anti-inflammation. In this study, we investigated whether fisetin relieves AD-like clinical symptoms induced by repeated DNFB treatment in NC/Nga mice. Fisetin significantly inhibited infiltration of inflammatory cells including eosinophils, mast cells and CD4(+) T and CD8(+) T cells, and suppressed the expressions of cytokines and chemokines associated with dermal infiltrates in AD-like skin lesions. Total serum immunoglobulin E (IgE) levels and the ratio of phospho-NF-κB p65 to total NF-κB p65 were markedly reduced by fisetin. Fisetin also reduced the production of interferon-gamma and interleukin-4 by activated CD4(+) T cells in a dose-dependent manner, whereas the anti-inflammatory cytokine, interleukin-10 was increased. These results implicate fisetin as a potential therapeutic for AD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Aspartame Attenuates 2, 4-Dinitrofluorobenzene-Induced Atopic Dermatitis-Like Clinical Symptoms in NC/Nga Mice.

    Science.gov (United States)

    Kim, Gun-Dong; Park, Yong Seek; Ahn, Hyun-Jong; Cho, Jeong-Je; Park, Cheung-Seog

    2015-11-01

    Atopic dermatitis (AD) is a common multifactorial chronic skin disease that has a multiple and complex pathogenesis. AD is gradually increasing in prevalence globally. In NC/Nga mice, repetitive applications of 2, 4-dinitrofluorobenzene (DNFB) evoke AD-like clinical symptoms similar to human AD. Aspartame (N-L-α-aspartyl-L-phenylalanine 1-methyl ester) is a methyl ester of a dipeptide, which is used as an artificial non-nutritive sweetener. Aspartame has analgesic and anti-inflammatory functions that are similar to the function of nonsteroidal anti-inflammatory drugs such as aspirin. We investigated whether aspartame can relieve AD-like clinical symptoms induced by DNFB treatment in NC/Nga mice. Sucrose did not relieve AD-like symptoms, whereas aspartame at doses of 0.5 μg kg(-1) and 0.5 mg kg(-1) inhibited ear swelling and relieved AD-like clinical symptoms. Aspartame inhibited infiltration of inflammatory cells including eosinophils, mast cells, and CD4(+) T cells, and suppressed the expression of cytokines including IL-4 and IFN-γ, and total serum IgE levels. Aspartame may have therapeutic value in the treatment of AD.

  17. THE ROLE OF IMMUNOLOGICAL DISORDERS IN THE DEVELOPMENT OF ATOPIC DERMATITIS

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    E. E. Zhiltsova

    2018-01-01

    Full Text Available The basis for the development of atopic dermatitis (AtD is a complex interaction between genetic disorders, environmental factors, lack of the skin barrier and immunological disorders. In view of the importance of immunological disorders in the etiopathogenesis of atopic dermatitis, the study of these parameters in patients with AtD is a necessary aspect to assess the severity of the course, prognosis of complications and recurrence.Purpose. Comprehensive assessment of clinical and immunological parameters in adolescents with atopic dermatitis.Materials and methods. The study included examination of 28 patients with atopic dermatitis aged from 12 to 16 years, with disease duration from 10 to 15 years, which included analysis of complaints and anamnesis data, evaluation of disease severity on the SCORAD scale, General clinical and immunological studies. The peculiarities of cellular and humoral immunity in the relapse stage were determined. The main indicators of phagocytic activity of blood neutrophils were also investigated.Results. In the analysis of anamnestic data of patients, a history of diseases associated with atopia in 16 (57.1% of 28 adolescents (AtD, bronchial asthma in relatives of the first and second line of kinship was revealed. When assessing the disease severity on a scale of SCORAD, prevailed patients with moderate to severe atopic dermatitis over — 19 (67,9% patients, the average score of the assessment of the severity of AtD amounted to 29.3 ± 1,25. The conducted immunological examination with assessment of cellular and humoral immunity showed significant changes in immunological reactivity in patients with AtD. On the part of the cellular immunity level it is necessary to note a clear decrease in CD3+ and CD8+, as well as an increase in the subpopulation of T-lymphocytes — CD4+ and b-lymphocytes — CD20+ in most patients compared to normal indicators characteristic of this age group. Compared to healthy adolescents

  18. Chlorella vulgaris Attenuates Dermatophagoides Farinae-Induced Atopic Dermatitis-Like Symptoms in NC/Nga Mice

    Science.gov (United States)

    Kang, Heerim; Lee, Chang Hyung; Kim, Jong Rhan; Kwon, Jung Yeon; Seo, Sang Gwon; Han, Jae Gab; Kim, Byung Gon; Kim, Jong-Eun; Lee, Ki Won

    2015-01-01

    Atopic dermatitis (AD) is a chronic and inflammatory skin disease that can place a significant burden on quality of life for patients. AD most frequently appears under the age of six and although its prevalence is increasing worldwide, therapeutic treatment options are limited. Chlorella vulgaris (CV) is a species of the freshwater green algae genus chlorella, and has been reported to modulate allergy-inducible factors when ingested. Here, we examined the effect of CV supplementation on AD-like symptoms in NC/Nga mice. CV was orally administrated for six weeks while AD-like symptoms were induced via topical application of Dermatophagoides farinae extract (DFE). CV treatment reduced dermatitis scores, epidermal thickness, and skin hydration. Histological analysis also revealed that CV treatment reduced DFE-induced eosinophil and mast cell infiltration into the skin, while analysis of serum chemokine levels indicated that CV treatment downregulated thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) levels. In addition, CV treatment downregulated mRNA expression levels of IL-4 and IFN-γ. Taken together, these results suggest that CV extract may have potential as a nutraceutical ingredient for the prevention of AD. PMID:26404252

  19. Chlorella vulgaris Attenuates Dermatophagoides Farinae-Induced Atopic Dermatitis-Like Symptoms in NC/Nga Mice

    Directory of Open Access Journals (Sweden)

    Heerim Kang

    2015-09-01

    Full Text Available Atopic dermatitis (AD is a chronic and inflammatory skin disease that can place a significant burden on quality of life for patients. AD most frequently appears under the age of six and although its prevalence is increasing worldwide, therapeutic treatment options are limited. Chlorella vulgaris (CV is a species of the freshwater green algae genus chlorella, and has been reported to modulate allergy-inducible factors when ingested. Here, we examined the effect of CV supplementation on AD-like symptoms in NC/Nga mice. CV was orally administrated for six weeks while AD-like symptoms were induced via topical application of Dermatophagoides farinae extract (DFE. CV treatment reduced dermatitis scores, epidermal thickness, and skin hydration. Histological analysis also revealed that CV treatment reduced DFE-induced eosinophil and mast cell infiltration into the skin, while analysis of serum chemokine levels indicated that CV treatment downregulated thymus- and activation-regulated chemokine (TARC and macrophage-derived chemokine (MDC levels. In addition, CV treatment downregulated mRNA expression levels of IL-4 and IFN-γ. Taken together, these results suggest that CV extract may have potential as a nutraceutical ingredient for the prevention of AD.

  20. Long Term Development of Gut Microbiota Composition in Atopic Children: Impact of Probiotics

    Science.gov (United States)

    Rutten, N. B. M. M.; Gorissen, D. M. W.; Eck, A.; Niers, L. E. M.; Vlieger, A. M.; Besseling-van der Vaart, I.; Budding, A. E.; Savelkoul, P. H. M.; van der Ent, C. K.; Rijkers, G. T.

    2015-01-01

    Introduction Imbalance of the human gut microbiota in early childhood is suggested as a risk factor for immune-mediated disorders such as allergies. With the objective to modulate the intestinal microbiota, probiotic supplementation during infancy has been used for prevention of allergic diseases in infants, with variable success. However, not much is known about the long-term consequences of neonatal use of probiotics on the microbiota composition. The aim of this study was to assess the composition and microbial diversity in stool samples of infants at high-risk for atopic disease, from birth onwards to six years of age, who were treated with probiotics or placebo during the first year of life. Methods In a double-blind, randomized, placebo-controlled trial, a probiotic mixture consisting of B. bifidum W23, B. lactis W52 and Lc. Lactis W58 (Ecologic® Panda) was administered to pregnant women during the last 6 weeks of pregnancy and to their offspring during the first year of life. During follow-up, faecal samples were collected from 99 children over a 6-year period with the following time points: first week, second week, first month, three months, first year, eighteen months, two years and six years. Bacterial profiling was performed by IS-pro. Differences in bacterial abundance and diversity were assessed by conventional statistics. Results The presence of the supplemented probiotic strains in faecal samples was confirmed, and the probiotic strains had a higher abundance and prevalence in the probiotic group during supplementation. Only minor and short term differences in composition of microbiota were found between the probiotic and placebo group and between children with or without atopy. The diversity of Bacteroidetes was significantly higher after two weeks in the placebo group, and at the age of two years atopic children had a significantly higher Proteobacteria diversity (p < 0.05). Gut microbiota development continued between two and six years, whereby

  1. Effects of Scutellariae radix and Aloe vera gel extracts on immunoglobulin E and cytokine levels in atopic dermatitis NC/Nga mice.

    Science.gov (United States)

    Kim, Jinkyung; Lee, In seok; Park, Soojin; Choue, Ryowon

    2010-11-11

    The present study aimed to investigate the effects of Scutellariae radix (SR) and Aloe vera gel (AV), alone or in combination, on levels of immunoglobulin E (IgE) and inflammatory cytokines in spontaneous atopic dermatitis(AD)-like skin lesions. After spontaneous AD-like skin lesion was developed by adaptation to conventional conditions, mice were randomly assigned to control, SR (50 mg/kg, p.o.), AV (0.8 mg/kg, p.o.) and SRAV (50 mg of SR and 0.8 mg of AV/kg, p.o.) groups, and were treated for 6 weeks. SR and SRAV suppressed IL-5 levels compared with control, but had no effects on IgE levels (P<0.05). AV increased IgE levels, but decreased both IL-5 and IL-10 compared with control (P<0.05). These results suggest that SR and AV modulate immunological responses in AD, mainly through influencing IL-5 or IL-10 levels. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  2. Pseudolaric acid B extracted from the Chinese medicinal herb Cortex Pseudolaricis ameliorates DNFB-induced atopic dermatitis-like skin lesions in BALB/c mice

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    Yi-Teng Wang

    2017-10-01

    Full Text Available Objective: Pseudolaric acid B (PB is a newly identified diterpenoid isolated from Tujinpi (Cortex Pseudolaricis. In the present study, we aimed to explore the anti-inflammatory effects of PB on atopic dermatitis (AD, as well as the molecular mechanisms underlying its effects. Methods: BALB/c mice treated with 2,4-dinitrofluorobenzene were orally administered with PB (10 mg∙kg-1∙d-1. After evaluating the AD score, serum levels of IgE and the mRNA expression of NLRP3 inflammasome and IL-1β were measured by ELISA and qRT-PCR respectively. Results: The results showed that PB treatment significantly ameliorated the development of AD-like clinical symptoms and effectively suppressed the infiltration of inflammatory cells. Furthermore, PB inhibited the expression of NLRP3 inflammasome and IL-1β in skin lesions, and downregulated serum IgE levels. Conclusion: The anti-inflammatory properties of PB were demonstrated using the 2,4-dinitrofluorobenzene-induced mouse model of AD-like skin lesions. Our study highlighted the potential use of PB as a novel therapeutic agent for the treatment of inflammation-associated skin diseases.

  3. Atopic dermatitis.

    Science.gov (United States)

    Weidinger, Stephan; Novak, Natalija

    2016-03-12

    Atopic dermatitis (also known as atopic eczema) is a chronic inflammatory skin disease that is characterised by intense itching and recurrent eczematous lesions. Although it most often starts in infancy and affects two of ten children, it is also highly prevalent in adults. It is the leading non-fatal health burden attributable to skin diseases, inflicts a substantial psychosocial burden on patients and their relatives, and increases the risk of food allergy, asthma, allergic rhinitis, other immune-mediated inflammatory diseases, and mental health disorders. Originally regarded as a childhood disorder mediated by an imbalance towards a T-helper-2 response and exaggerated IgE responses to allergens, it is now recognised as a lifelong disposition with variable clinical manifestations and expressivity, in which defects of the epidermal barrier are central. Present prevention and treatment focus on restoration of epidermal barrier function, which is best achieved through the use of emollients. Topical corticosteroids are still the first-line therapy for acute flares, but they are also used proactively along with topical calcineurin inhibitors to maintain remission. Non-specific immunosuppressive drugs are used in severe refractory cases, but targeted disease-modifying drugs are being developed. We need to improve understanding of the heterogeneity of the disease and its subtypes, the role of atopy and autoimmunity, the mechanisms behind disease-associated itch, and the comparative effectiveness and safety of therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Pre-natal and post-natal exposure to respiratory infection and atopic diseases development: a historical cohort study

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    Gehring Ulrike

    2006-05-01

    Full Text Available Abstract Background According to the hygiene hypothesis, infections in early life protect from allergic diseases. However, in earlier studies surrogate measures of infection rather than clinical infections were associated with decreased frequencies of atopic diseases. Exposure to infection indicating sub-clinical infection rather than clinical infection might protect from atopic diseases. Objective: to investigate whether exposure to acute respiratory infections within pregnancy and the first year of life is associated with atopic conditions at age 5–14 years and to explore when within pregnancy and the first year of life this exposure is most likely to be protective. Methods Historical cohort study: Population level data on acute respiratory infections from the routine reporting system of the former German Democratic Republic were linked with individual data from consecutive surveys on atopic diseases in the same region (n = 4672. Statistical analyses included multivariate logistic regression analysis and polynomial distributed lag models. Results High exposure to acute respiratory infection between pregnancy and age one year was associated with overall reduced odds of asthma, eczema, hay fever, atopic sensitization and total IgE. Exposure in the first 9 months of life showed the most pronounced effect. Adjusted odds ratio's for asthma, hay fever, inhalant sensitization and total IgE were statistical significantly reduced up to around half. Conclusion Exposure to respiratory infection (most likely indicating sub-clinical infection within pregnancy and the first year of life may be protective in atopic diseases development. The post-natal period thereby seems to be particularly important.

  5. Atopic dermatitis induces the expansion of thymus-derived regulatory T cells exhibiting a Th2-like phenotype in mice

    NARCIS (Netherlands)

    Moosbrugger-Martinz, Verena; Tripp, Christoph H.; Clausen, Björn E.; Schmuth, Matthias; Dubrac, Sandrine

    2016-01-01

    Atopic dermatitis (AD) is a widespread inflammatory skin disease with an early onset, characterized by pruritus, eczematous lesions and skin dryness. This chronic relapsing disease is believed to be primarily a result of a defective epidermal barrier function associated with genetic susceptibility,

  6. Atopic dermatitis

    Science.gov (United States)

    ... People with atopic dermatitis often have asthma or seasonal allergies. There is often a family history of ... and solvents Sudden changes in body temperature and stress, which may ... your skin to water for as short a time as possible. Short, ...

  7. Risk factors for the development of atopic disease in infancy and early childhood

    NARCIS (Netherlands)

    L.P. Koopman (Laurens)

    2002-01-01

    textabstractThe etiology of allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis, is multifactorial, involving interaction of both genetic and environmental factors [1]. The prevalence of allergic diseases has doubled in the last 3 decades. especially in Western

  8. Measurement of Health Care Quality in Atopic Dermatitis - Development and Application of a Set of Quality Indicators.

    Science.gov (United States)

    Steinke, S; Beikert, F C; Langenbruch, A; Fölster-Holst, R; Ring, J; Schmitt, J; Werfel, T; Hintzen, S; Franzke, N; Augustin, M

    2018-05-15

    Quality indicators are essential tools for the assessment of health care, in particular for guideline-based procedures. 1) Development of a set of indicators for the evaluation of process and outcomes quality in atopic dermatitis (AD) care. 2) Application of the indicators to a cross-sectional study and creation of a global process quality index. An expert committee consisting of 10 members of the German guideline group on atopic dermatitis condensed potential quality indicators to a final set of 5 outcomes quality and 12 process quality indicators using a Delphi panel. The outcomes quality and 7 resp. 8 process quality indicators were retrospectively applied to a nationwide study on 1,678 patients with atopic dermatitis (AtopicHealth). Each individual process quality indicator score was then summed up to a global index (ranges from 0 (no quality achieved) to 100 (full quality achieved)) displaying the quality of health care. In total, the global process quality index revealed a median value of 62.5 and did not or only slightly correlate to outcome indicators as the median SCORAD (SCORing Atopic Dermatitis; rp =0.08), Dermatology Life Quality Index (DLQI; rp = 0.256), and Patient Benefit Index (PBI; rp = -0.151). Process quality of AD care is moderate to good. The health care process quality index does not substantially correlate to the health status of AD patients measured by 5 different outcomes quality indicators. Further research should include the investigation of reliability, responsiveness, and feasibility of the proposed quality indicators for AD. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. Qualitative vs. quantitative atopic dermatitis criteria

    DEFF Research Database (Denmark)

    Andersen, R M; Thyssen, J P; Maibach, H I

    2016-01-01

    This review summarizes historical aspects, clinical expression and pathophysiology leading to coining of the terms atopy and atopic dermatitis, current diagnostic criteria and further explore the possibility of developing quantitative diagnostic criteria of atopic dermatitis (AD) based on the imp...

  10. Natural History of Food-Triggered Atopic Dermatitis and Development of Immediate Reactions in Children.

    Science.gov (United States)

    Chang, Angela; Robison, Rachel; Cai, Miao; Singh, Anne Marie

    2016-01-01

    Case reports suggest that children with food-triggered atopic dermatitis (AD) on elimination diets may develop immediate reactions on accidental ingestion or reintroduction of an avoided food. The objective of this study was to systematically study the incidence and risk factors associated with these immediate reactions. A retrospective chart review of 298 patients presenting to a tertiary-care allergy-immunology clinic based on concern for food-triggered AD was performed. Data regarding triggering foods, laboratory testing, and clinical reactions were collected prospectively from the initial visit. Food-triggered AD was diagnosed by an allergist-immunologist with clinical evaluation and laboratory testing. We identified immediate reactions as any reaction to a food for which there was evidence of sIgE and for which patients developed timely allergic signs and symptoms. Differences between children with and without new immediate reactions were determined by a Mann-Whitney, χ(2), or Fisher's exact test as appropriate. A total of 19% of patients with food-triggered AD and no previous history of immediate reactions developed new immediate food reactions after initiation of an elimination diet. Seventy percent of reactions were cutaneous but 30% were anaphylaxis. Cow's milk and egg were the most common foods causing immediate-type reactions. Avoidance of a food was associated with increased risk of developing immediate reactions to that food (P food. A significant number of patients with food-triggered AD may develop immediate-type reactions. Strict elimination diets need to be thoughtfully prescribed as they may lead to decreased oral tolerance. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  11. Spontaneous atopic dermatitis-like symptoms in a/a ma ft/ma ft/J flaky tail mice appear early after birth.

    Directory of Open Access Journals (Sweden)

    Magdalini Kypriotou

    Full Text Available Loss-of-function mutations in human profilaggrin gene have been identified as the cause of ichthyosis vulgaris (IV, and as a major predisposition factor for atopic dermatitis (AD. Similarly, flaky tail (a/a ma ft/ma ft/J mice were described as a model for IV, and shown to be predisposed to eczema. The aim of this study was to correlate the flaky tail mouse phenotype with human IV and AD, in order to dissect early molecular events leading to atopic dermatitis in mice and men, suffering from filaggrin deficiency. Thus, 5-days old flaky tail pups were analyzed histologically, expression of cytokines was measured in skin and signaling pathways were investigated by protein analysis. Human biopsies of IV and AD patients were analyzed histologically and by real time PCR assays. Our data show acanthosis and hyperproliferation in flaky tail epidermis, associated with increased IL1β and thymic stromal lymphopoietin (TSLP expression, and Th2-polarization. Consequently, NFκB and Stat pathways were activated, and IL6 mRNA levels were increased. Further, quantitative analysis of late epidermal differentiation markers revealed increased Small proline-rich protein 2A (Sprr2a synthesis. Th2-polarization and Sprr2a increase may result from high TSLP expression, as shown after analysis of 5-days old K14-TSLP tg mouse skin biopsies. Our findings in the flaky tail mouse correlate with data obtained from patient biopsies of AD, but not IV. We propose that proinflammatory cytokines are responsible for acanthosis in flaky tail epidermis, and together with the Th2-derived cytokines lead to morphological changes. Accordingly, the a/a ma ft/ma ft/J mouse model can be used as an appropriate model to study early AD onset associated with profilaggrin deficiency.

  12. Therapeutic effect of tyndallized Lactobacillus rhamnosus IDCC 3201 on atopic dermatitis mediated by down-regulation of immunoglobulin E in NC/Nga mice.

    Science.gov (United States)

    Lee, Seung-Hun; Yoon, Jong-Min; Kim, Young-Hoo; Jeong, Dong-Gu; Park, Soobong; Kang, Dae-Jung

    2016-07-01

    The therapeutic effect of oral administration of Lactobacillus rhamnosus IDCC 3201 tyndallizate (RHT3201) on atopic dermatitis (AD)-like skin lesions in NC/Nga mice were investigated. After induction of dermatitis in NC/Nga mice with house-dust mite extract, each group was fed RHT3201 with 1 × 10(8) , 1 × 10(9) , or 1 × 10(10) cells orally once a day for 8 weeks. Dermatitis scores and frequency of scratching were improved by oral feeding with RHT3201. In contrast to the control group, RHT3201-fed mice showed significantly down-regulated mast cell numbers and serum immunoglobulin E (IgE) concentrations had significantly less IL4 in their axillary lymph node cells. The therapeutic effect of RHT3201 was found to be dose-dependent. These findings indicate that RHT3201 has potential for treating AD. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

  13. Amelioration of atopic-like skin conditions in NC/Tnd mice by topical application with distilled Alpinia intermedia Gagnep extracts.

    Science.gov (United States)

    Amagai, Yosuke; Katsuta, Chihiro; Nomura, Yoshihiro; Oida, Kumiko; Matsuda, Kenshiro; Jang, Hyosun; Ahn, Ginnae; Hamasaki, Tetsuyoshi; Matsuda, Hiroshi; Tanaka, Akane

    2017-11-01

    Alpinia intermedia, a perennial plant that belongs to the Zingiberaceae family, has been used in folk medicine for a long time in the southern region of Japan. Because skin care is an effective approach that enables patients to manage their atopic dermatitis (AD), various herbal ingredients with few adverse effects have been evaluated for use in AD patients in recent years. In this study, we examined whether distilled extracts obtained from A. intermedia were beneficial for AD-like skin conditions in NC/Tnd mice. Topical application with the A. intermedia extracts significantly reduced the severity of AD, transepidermal water loss and scratching behavior in the mice. Supplementation of the extracts to cell cultures suppressed the expression of Tslp mRNA in PAM212 keratinocytes, degranulation in bone marrow-derived cultured mast cells (BMCMC), and neurite outgrowth in PC12 cells and dorsal root ganglia. In addition, the component analysis revealed that β-pinene was a major constituent of the A. intermedia extracts. The inhibitory effects of β-pinene both in vivo and in vitro were also demonstrated. These results indicate that topical application with the A. intermedia extract to the skin of NC/Tnd mice improved the condition of the skin by suppressing multiple inflammatory responses. The extracts may become novel skin-care remedies for AD patients. © 2017 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

  14. Hypersensitivity to aeroallergens in adult patients with atopic dermatitis develops due to the different immunological mechanisms.

    Science.gov (United States)

    Samochocki, Zbigniew; Owczarek, Witold; Rujna, Paweł; Raczka, Alicja

    2007-01-01

    Atopic dermatitis (AD) is a disease with a complex pathomechanism, it is very difficult to establish the exact factors which can either trigger or exacerbate the disease. Knowledge of the mechanisms involved in AD development can be increased by, among others, applying new diagnostic tests and careful assessment of the results obtained. The aim of this study was to determine the allergic mechanisms of hypersensitivity to selected aeroallergens in patients with AD. The study comprised 109 AD patients. In all the patients the total IgE level was measured and atopy patch tests and skin prick tests were performed. We also assessed the presence of specific IgE against house dust mite, birch-tree, mixed grass pollen and cat dander. The highest incidence of positive results was found for house dust mite allergens, irrespective of the test employed. Analysing hypersensitivity to all the examined allergens we revealed the presence of allergic mechanisms in 85.3% of the patients. In 30.2% of the examined individuals we proved a type I immunological response, in 45.9% -- both types I and IV in 9.2% -- only type IV in one patient. In 14.7% of the patients the results of all the tests performed were negative. Analysing hypersensitivity to particular aeroallergens, negative test results to house dust mite were observed in 25.8% of the patients. The percentage of positive results for birch pollen, grass pollen and cat dander were 45.0, 44.1 and 53.2, respectively. Analysis of the results showed that allergic reactions to the same aeroallergens may develop via different mechanisms. We also revealed that the coexistence of various mechanisms involved in the development of hypersensitivity to a particular aeroallergen may occur in individual patients.

  15. Bathing Effects of Various Seawaters on Allergic (Atopic Dermatitis-Like Skin Lesions Induced by 2,4-Dinitrochlorobenzene in Hairless Mice

    Directory of Open Access Journals (Sweden)

    Choong Gon Kim

    2015-01-01

    Full Text Available We evaluated the preventive effects of four types of seawater collected in Republic of Korea on hairless mice with 2,4-dinitrochlorobenzene- (DNCB- induced allergic/atopic dermatitis (AD. The anti-inflammatory effects were evaluated by measuring tumor necrosis factor- (TNF- α and interleukins (ILs. Glutathione (GSH, malondialdehyde (MDA, superoxide anion, and inducible nitric oxide synthase (iNOS were measured to evaluate the antioxidant effects. Caspase-3 and poly (ADP-ribose polymerase (PARP were observed to measure the antiapoptotic effects; matrix metalloproteinase- (MMP- 9 levels were also evaluated. Mice with AD had markedly higher clinical skin severity scores and scratching behaviors; higher TNF-α and ILs (1β, 10, 4, 5, and 13 levels; higher MDA, superoxide anion, caspase-3, PARP, and MMP-9 levels; and greater iNOS activity. However, the severity of AD was significantly decreased by bathing in seawaters, but it did not influence the dermal collagen depositions and skin tissue antioxidant defense systems. These results suggest that bathing in all four seawaters has protective effects against DNCB-induced AD through their favorable systemic and local immunomodulatory effects, active cytoprotective antiapoptotic effects, inhibitory effects of MMP activity and anti-inflammatory and antioxidative effects.

  16. A comparison of the leaf gel extracts of Aloe ferox and Aloe vera in the topical treatment of atopic dermatitis in Balb/c mice.

    Science.gov (United States)

    Finberg, M J; Muntingh, G L; van Rensburg, C E J

    2015-12-01

    Aloe vera gel is widely used in the treatment of an array of disturbances, especially skin disorders. The wound-healing effects have been attributed to its moisturizing and anti-inflammatory effects as well as its beneficial effect on the maturation of collagen. The aim of the present study is to compare the effects of topically applied extracts of Aloe ferox with that of Aloe vera on the symptoms as well as IgE levels of a mouse model of atopic dermatitis (AD). Mice were sensitized and challenged with 2,4-dinitrochlorobenzene and treated afterwards for 10 consecutive days with the gels of either A. ferox or A. vera applied topically to the affected areas. A placebo gel was used for the control mice. Blood was collected at the beginning and end of the treatment period to measure serum IgE levels. Although the gels of both the Aloe species inhibited the cutaneous inflammatory response as well as serum IgE levels in the rats, the extracts of A. ferox were superior to that of A. vera in reducing IgE levels. The gels of A. ferox and A. vera, applied topically, may be a safe and useful alternative to antihistamines and topical corticosteroids, for the treatment of patients suffering from recurring chronic AD.

  17. Hataedock treatment has preventive therapeutic effects for atopic dermatitis through skin barrier protection in Dermatophagoides farinae-induced NC/Nga mice.

    Science.gov (United States)

    Cha, Ho-Yeol; Ahn, Sang-Hyun; Cheon, Jin-Hong; Park, Sun-Young; Kim, Kibong

    2017-07-12

    Hataedock treatment is traditionally used for the purpose of preventing the future skin disease by feeding herbal extracts to the newborn in traditional Chinese and Korean medicine. This study investigated the preventive therapeutic effects of Hataedock (HTD) treatment for atopic dermatitis (AD) through skin barrier protection in Dermatophagoides farinae-induced NC/Nga mice. To the HTD treatment group, the extract of Coptis japonica Makino and Glycyrrhiza uralensis Fischer, which analyzed with High Performance Liquid Chromatography (HPLC)-fingerprint for quality consistency, was administered orally to the 3-week-old mice before inducing AD. After that, Dermatophagoides farinae was applied except the control group to induce AD-like skin lesions. We confirmed the effects of HTD on morphological changes, protection of skin barrier, regulation of Th2 differentiation, inflammation regulation and induction of apoptosis through histochemistry, immunohistochemistry, and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. HTD effectively reduced edema, angiogenesis and skin lesion. HTD also increased the levels of liver X receptor (LXR) and filaggrin but decreased the level of protein kinase C (PKC) (pprotection of skin barrier. Therefore, HTD may have potential applications for alternative and preventive treatment in the management of AD. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  18. Atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Watson Wade

    2011-11-01

    Full Text Available Abstract Atopic dermatitis (AD is a common, chronic skin disorder that can significantly impact the quality of life of affected individuals as well as their families. Although the pathogenesis of the disorder is not completely understood, it appears to result from the complex interplay between defects in skin barrier function, environmental and infectious agents, and immune abnormalities. There are no specific diagnostic tests for AD; therefore, the diagnosis is based on specific clinical criteria that take into account the patient’s history and clinical manifestations. Successful management of the disorder requires a multifaceted approach that involves education, optimal skin care practices, anti-inflammatory treatment with topical corticosteroids and/or topical calcineurin inhibitors (TCIs, the use of first-generation antihistamines to help manage sleep disturbances, and the treatment of skin infections. Systemic corticosteroids may also be used, but are generally reserved for the acute treatment of severe flare-ups. Topical corticosteroids are the first-line pharmacologic treatments for AD, and evidence suggests that these agents may also be beneficial for the prophylaxis of disease flare-ups. Although the prognosis for patients with AD is generally favourable, those patients with severe, widespread disease and concomitant atopic conditions, such as asthma and allergic rhinitis, are likely to experience poorer outcomes.

  19. [Atopic dermatitis and domestic animals].

    Science.gov (United States)

    Song, M

    2000-09-01

    Several arguments are raised attributing to aeroallergens an important role in atopic dermatitis. The aeroallergens that penetrate the epidermis could be fixed by IgE on the Langerhans cells and then induce a cellular mediator reaction comparable to that of allergic contact eczema. Patch tests have been developed to evaluate the role of aeroallergens (dust mites, animal dander, etc.). Preventive anti-dust mites measures in the home of atopic patients are recommended. Eviction of domestic animals (cat, dog, etc.) or avoidance measures for animal dander in the home can produce improvement in atopic dermatitis. Oral specific immunotherapy is being validated as a treatment for this disease.

  20. A prospective birth cohort study of different risk factors for development of allergic diseases in offspring of non-atopic parents.

    Science.gov (United States)

    Lee, Ming-Tsung; Wu, Chih-Chiang; Ou, Chia-Yu; Chang, Jen-Chieh; Liu, Chieh-An; Wang, Chih-Lu; Chuang, Hau; Kuo, Ho-Chang; Hsu, Te-Yao; Chen, Chie-Pein; Yang, Kuender D

    2017-02-14

    Allergic diseases are thought to be inherited. Prevalence of allergic diseases has, however, increased dramatically in last decades, suggesting environmental causes for the development of allergic diseases. We studied risk factors associated with the development of atopic dermatitis (AD), allergic rhinitis (AR) and asthma (AS) in children of non-atopic parents in a subtropical country. In a birth cohort of 1,497 newborns, parents were prenatally enrolled and validated for allergic diseases by questionnaire, physician-verified and total or specific Immunoglobulin E (IgE) levels; 1,236 and 756 children, respectively, completed their 3-year and 6-year follow-up. Clinical examination, questionnaire, and blood samples for total and specific IgE of the children were collected at each follow-up visit. Prevalence of AD, AR and AS was, respectively, 8.2%, 30.8% and 12.4% in children of non-atopic parents. Prevalence of AR (pchildren of parents who were both atopic. A combination of Cesarean section (C/S) and breastfeeding for more than 1 month showed the highest risk for AD (OR=3.111, p=.006). Infants living in homes with curtains and no air filters had the highest risk for AR (OR=2.647, pparents living in homes without air filters had the highest risk for AS (OR=1.930, p=.039). Breastfeeding and C/S affect development of AD. Gender, use of curtains and/or air filters affect AR and AS, suggesting that control of the perinatal environment is necessary for the prevention of atopic diseases in children of non-atopic parents.

  1. Comorbidity in Atopic Dermatitis.

    Science.gov (United States)

    Simpson, Eric L

    2012-03-01

    The negative impact of atopic dermatitis (AD) often extends beyond the skin. Children with AD experience increased rates of infectious, mental health, and allergic diseases compared to their non-atopic peers. The mechanisms underlying these associations remain elusive. New insights from genetic and epidermal research pinpoint the skin barrier as a primary initiator of AD. Epicutaneous sensitization represents an intriguing new model which links a disrupted skin barrier to the later development of IgE-mediated diseases in patients with AD. Recent epidemiological studies have identified new comorbidities linked to AD as well, including several mental health disorders and obesity. This manuscript reviews the recent literature regarding both classic and newly described AD comorbidities.

  2. Risk of developing major depressive disorder and anxiety disorders among adolescents and adults with atopic dermatitis: a nationwide longitudinal study.

    Science.gov (United States)

    Cheng, Chih-Ming; Hsu, Ju-Wei; Huang, Kai-Lin; Bai, Ya-Mei; Su, Tung-Ping; Li, Cheng-Ta; Yang, Albert C; Chang, Wen-Han; Chen, Tzeng-Ji; Tsai, Shih-Jen; Chen, Mu-Hong

    2015-06-01

    Previous cross-sectional studies have suggested a comorbid association between atopic dermatitis (AD) and depressive disorder as well as anxiety disorders, but the temporal relationship was not determined. Using the Taiwan National Health Insurance Research Database, 8208 AD patients aged 12 and older without psychiatric history and age-/sex-matched (1:1) controls between 1998 and 2008 were enrolled in our study and followed to the end of 2011. Subjects who developed major depression, any depressive disorder, and anxiety disorders during the follow-up were identified. The Cox regression analysis after adjusting for demographic data and atopic comorbidities demonstrated that patients with AD had an elevated risk of developing major depression (hazard ratio [HR]: 6.56, 95% confidence interval [CI]: 3.64-11.84), any depressive disorder (HR: 5.44, 95% CI: 3.99-7.44), and anxiety disorders (HR: 3.57, 95% CI: 2.55-4.98). Stratified by age group, both adolescents and adults with AD were prone to developing major depression (HR: 4.26, 95% CI: 1.39-13.13; HR: 7.56, 95% CI: 3.75-15.23), any depressive disorder (HR: 4.38, 95% CI: 2.09-9.18; HR: 5.66, 95% CI: 4.01-7.99), and anxiety disorders (HR: 5.40, 95% CI: 2.02-14.39; HR: 3.36, 95% CI: 2.38-4.80). AD in both adolescence and adulthood increased the risk of developing major depression, any depressive disorder, and anxiety disorders in later life. Further studies would be required to clarify the possible underlying mechanism between AD and depression as well as anxiety disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Epidemiology and natural history of atopic diseases

    DEFF Research Database (Denmark)

    Thomsen, Simon F

    2015-01-01

    The atopic diseases - atopic dermatitis, asthma, and hay fever - pose a great burden to the individual and society, not least, since these diseases have reached epidemic proportions during the past decades in industrialized and, more recently, in developing countries. Whereas the prevalence...... of the atopic diseases now seems to have reached a plateau in many Western countries, they are still on the increase in the developing world. This emphasizes continuing research aimed at identifying the causes, risk factors, and natural history of these diseases. Herein, the fundamental aspects of the natural...... history and epidemiology of the atopic diseases are reviewed....

  4. Developing drugs for treatment of atopic dermatitis in children (≥3 months to <18 years of age): Draft guidance for industry.

    Science.gov (United States)

    Siegfried, Elaine C; Jaworski, Jennifer C; Eichenfield, Lawrence F; Paller, Amy; Hebert, Adelaide A; Simpson, Eric L; Altman, Emily; Arena, Charles; Blauvelt, Andrew; Block, Julie; Boguniewicz, Mark; Chen, Suephy; Cordoro, Kelly; Hanna, Diane; Horii, Kimberly; Hultsch, Thomas; Lee, James; Leung, Donald Y; Lio, Peter; Milner, Joshua; Omachi, Theodore; Schneider, Christine; Schneider, Lynda; Sidbury, Robert; Smith, Timothy; Sugarman, Jeffrey; Taha, Sharif; Tofte, Susan; Tollefson, Megha; Tom, Wynnis L; West, Dennis P; Whitney, Lucinda; Zane, Lee

    2018-05-01

    Atopic dermatitis is the most common chronic skin disease, and it primarily affects children. Although atopic dermatitis (AD) has the highest effect on burden of skin disease, no high-level studies have defined optimal therapy for severe disease. Corticosteroids have been used to treat AD since the 1950s and remain the only systemic medication with Food and Drug Administration approval for this indication in children, despite published guidelines of care that recommend against this option. Several clinical trials with level 1 evidence have supported the use of topical treatments for mild to moderate atopic dermatitis in adults and children, but these trials have had little consistency in protocol design. Consensus recommendations will help standardize clinical development and trial design for children. The Food and Drug Administration issues guidance documents for industry as a source for "the Agency's current thinking on a particular subject." Although they are nonbinding, industry considers these documents to be the standard for clinical development and trial design. Our consensus group is the first to specifically address clinical trial design in this population. We developed a draft guidance document for industry, Developing Drugs for Treatment of Atopic Dermatitis in Children (≥3 months to <18 years of age). This draft guidance has been submitted to the Food and Drug Administration based on a provision in the Federal Register (Good Guidance Practices). © 2018 Wiley Periodicals, Inc.

  5. Eczema, Atopic Dermatitis, or Atopic Eczema

    DEFF Research Database (Denmark)

    Xu, Shuai; Thyssen, Jacob P; Paller, Amy S

    2017-01-01

    BACKGROUND: The lack of standardized nomenclature for atopic dermatitis (AD) creates challenges for scientific communication, patient education, and advocacy. OBJECTIVE: We sought to determine the relative popularity of the terms eczema, AD, and atopic eczema (AE) using global search engine volumes...

  6. Exploring Immune Development in Infants With Moderate to Severe Atopic Dermatitis

    Directory of Open Access Journals (Sweden)

    Lies Hulshof

    2018-03-01

    Full Text Available BackgroundAtopic dermatitis (AD is the most common chronic inflammatory skin disease in infancy with a complex pathology. In adults, the clinical severity of AD has been associated with increases in T helper cell type (Th 2, Th22, and Th17 serum markers, including high levels of CC chemokine ligand (CCL 17 and CCL22 chemokines.ObjectiveTo explore the possible association between serum chemokine levels and AD severity in infants with moderate-to-severe AD and elevated immunoglobulin E (IgE.Subjects and methodsSerum samples (n = 41 obtained from a randomized, double-blind, and clinical dietary intervention study were used to study biomarkers in infants with AD. Baseline- and post-intervention samples (4 months were used, six chemokines and nine ratios thereof were analyzed using Luminex and correlated to AD severity. In the initial study, the infants were randomized to receive extensively hydrolyzed whey-based formula without (control or with short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides (9:1 and Bifidobacterium breve M-16V (active.Results31 Infants up to 11 months of age, with an objective-SCORAD score (oSCORAD ≥ 20 and elevated total-IgE and/or specific-IgE levels were included. In time, the median oSCORAD decreased in both groups by −8 (control, p < 0.05; active, p < 0.01. Irrespective of dietary intervention, several changes in Th2 chemokines (CCL17 and CCL22, inflammatory chemokine (CCL20, and the Th1 chemokine, CXC chemokine ligand (CXCL 9, were detected over time. Overall CCL17 correlated to oSCORAD (r = 0.446, p < 0.01. After 4 months of dietary intervention, CXCL9 was higher (p < 0.01 in the active group compared with control [active, 2.33 (1.99–2.89; controls, 1.95 (1.77–2.43 log 10 median (range]. In addition, a reduction in Th2/Th1 chemokine ratios for CCL17/CXCL9, CCL22/CXCL9, CCL20/CXCL10, and CCL20/CXCL11 was detected associated with the active intervention

  7. Differential Effects of Peptidoglycan Recognition Proteins on Experimental Atopic and Contact Dermatitis Mediated by Treg and Th17 Cells

    Science.gov (United States)

    Park, Shin Yong; Gupta, Dipika; Kim, Chang H.; Dziarski, Roman

    2011-01-01

    Skin protects the body from the environment and is an important component of the innate and adaptive immune systems. Atopic dermatitis and contact dermatitis are among the most frequent inflammatory skin diseases and are both determined by multigenic predisposition, environmental factors, and aberrant immune response. Peptidoglycan Recognition Proteins (Pglyrps) are expressed in the skin and we report here that they modulate sensitivity to experimentally-induced atopic dermatitis and contact dermatitis. Pglyrp3 −/− and Pglyrp4 −/− mice (but not Pglyrp2 −/− mice) develop more severe oxazolone-induced atopic dermatitis than wild type (WT) mice. The common mechanism underlying this increased sensitivity of Pglyrp3 −/− and Pglyrp4 −/− mice to atopic dermatitis is reduced recruitment of Treg cells to the skin and enhanced production and activation Th17 cells in Pglyrp3 −/− and Pglyrp4 −/− mice, which results in more severe inflammation and keratinocyte proliferation. This mechanism is supported by decreased inflammation in Pglyrp3 −/− mice following in vivo induction of Treg cells by vitamin D or after neutralization of IL-17. By contrast, Pglyrp1 −/− mice develop less severe oxazolone-induced atopic dermatitis and also oxazolone-induced contact dermatitis than WT mice. Thus, Pglyrp3 and Pglyrp4 limit over-activation of Th17 cells by promoting accumulation of Treg cells at the site of chronic inflammation, which protects the skin from exaggerated inflammatory response to cell activators and allergens, whereas Pglyrp1 has an opposite pro-inflammatory effect in the skin. PMID:21949809

  8. Gene-environment interaction in atopic diseases

    DEFF Research Database (Denmark)

    Kahr, Niklas; Naeser, Vibeke; Stensballe, Lone Graff

    2015-01-01

    INTRODUCTION: The development of atopic diseases early in life suggests an important role of perinatal risk factors. OBJECTIVES: To study whether early-life exposures modify the genetic influence on atopic diseases in a twin population. METHODS: Questionnaire data on atopic diseases from 850....... Significant predictors of atopic diseases were identified with logistic regression and subsequently tested for genetic effect modification using variance components analysis. RESULTS: After multivariable adjustment, prematurity (gestational age below 32 weeks) [odds ratio (OR) = 1.93, confidence interval (CI...... stratified by exposure status showed no significant change in the heritability of asthma according to the identified risk factors. CONCLUSION: In this population-based study of children, there was no evidence of genetic effect modification of atopic diseases by several identified early-life risk factors...

  9. Skin microbiome before development of atopic dermatitis: Early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year.

    LENUS (Irish Health Repository)

    Kennedy, Elizabeth A

    2017-01-01

    Disease flares of established atopic dermatitis (AD) are generally associated with a low-diversity skin microbiota and Staphylococcus aureus dominance. The temporal transition of the skin microbiome between early infancy and the dysbiosis of established AD is unknown.

  10. Hypothetical atopic dermatitis-myeloproliferative neoplasm (AD-MPN syndrome

    Directory of Open Access Journals (Sweden)

    Toshiaki eKawakami

    2015-08-01

    Full Text Available Atopic dermatitis (AD is a chronic inflammatory skin disease. Myeloproliferative neoplasms (MPNs are hematopoietic malignancies caused by uncontrolled proliferation of hematopoietic stem/progenitor cells. Recent studies have described several mutant mice exhibiting both AD-like skin inflammation and MPN. Common pathways for skin inflammation encompass overexpression of thymic stromal lymphopoietin and reduced signaling of epidermal growth factor receptor in the epidermis, while overproduction of granulocyte-colony stimulating factor by keratinocytes and constitutive activation of Stat5 in hematopoietic stem cells are important for the development of MPN. The murine studies suggest the existence of a similar human disease tentatively termed the AD-MPN syndrome.

  11. The Lavender Ceiling atop the Global Closet: Human Resource Development and Lesbian Expatriates

    Science.gov (United States)

    Gedro, Julie

    2010-01-01

    This literature review will examine international assignments as career development opportunities and uncover multiple issues and considerations with respect to lesbians and international assignments. There is a clear interest in the fields of management and human resource management in the privileges, challenges, and opportunities of…

  12. Comorbidities of Atopic Dermatitis

    DEFF Research Database (Denmark)

    Andersen, Yuki M F; Egeberg, Alexander; Skov, Lone

    2017-01-01

    PURPOSE OF REVIEW: In this review article, we summarize the current evidence about atopic dermatitis (AD)-associated comorbidities, beyond the traditional atopic and allergic conditions. RECENT FINDINGS: Patients with AD may have an increased risk of cardiovascular diseases, certain malignancies...

  13. Atopic dermatitis 2017

    DEFF Research Database (Denmark)

    No, Daniel J; Amin, Mina; Egeberg, Alexander

    2018-01-01

    Novel and innovative treatment options for atopic dermatitis (AD) are underway. The recent advancements in understanding AD are reminiscent of the progress made in psoriasis research over a decade ago.......Novel and innovative treatment options for atopic dermatitis (AD) are underway. The recent advancements in understanding AD are reminiscent of the progress made in psoriasis research over a decade ago....

  14. Hypereosinophilic Atopic Transverse Myelitis

    African Journals Online (AJOL)

    2018-06-11

    4 days ago ... Atopic transverse myelitis is a rare disorder that is defined as a ... was commenced on prednisolone and had good response to treatment. .... Atopic myelitis is more common in male sex such as .... their identity, but anonymity cannot be guaranteed. ... useful diagnostic clue in surgical neuropathology.

  15. Andrographolide suppresses thymic stromal lymphopoietin in phorbol myristate acetate/calcium ionophore A23187-activated mast cells and 2,4-dinitrofluorobenzene-induced atopic dermatitis-like mice model

    Directory of Open Access Journals (Sweden)

    Li CX

    2016-02-01

    Full Text Available Chun-xiao Li,* Hua-guo Li,* Hui Zhang,* Ru-hong Cheng, Ming Li, Jian-ying Liang, Yan Gu, Bo Ling, Zhi-rong Yao, Hong Yu Department of Dermatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Atopic dermatitis (AD is one of the most common inflammatory cutaneous diseases. Thymic stromal lymphopoietin (TSLP has been demonstrated to be an important immunologic factor in the pathogenesis of AD. The production of TSLP can be induced by a high level of intracellular calcium concentration and activation of the receptor-interacting protein 2/caspase-1/NF-κB pathway. Andrographolide (ANDRO, a natural bicyclic diterpenoid lactone, has been found to exert anti-inflammatory effects in gastrointestinal inflammatory disorders through suppressing the NF-κB pathway. Objective: To explore the effect of ANDRO on the production of TSLP in human mast cells and AD mice model. Methods: We utilized enzyme-linked immunosorbent assay, real-time reverse transcription polymerase chain reaction analysis, Western blot analysis, and immunofluorescence staining assay to investigate the effects of ANDRO on AD. Results: ANDRO ameliorated the increase in the intracellular calcium, protein, and messenger RNA levels of TSLP induced by phorbol myristate acetate/calcium ionophore A23187, through the blocking of the receptor-interacting protein 2/caspase-1/NF-κB pathway in human mast cell line 1 cells. ANDRO, via oral or local administration, also attenuated clinical symptoms in 2,4-dinitrofluorobenzene-induced AD mice model and suppressed the levels of TSLP in lesional skin. Conclusion: Taken together, ANDRO may be a potential therapeutic agent for AD through suppressing the expression of TSLP. Keywords: atopic dermatitis, thymic stromal lymphopoietin, andrographolide, human mast cell

  16. Effects of the Fruit Extract of Tribulus terrestris on Skin Inflammation in Mice with Oxazolone-Induced Atopic Dermatitis through Regulation of Calcium Channels, Orai-1 and TRPV3, and Mast Cell Activation

    Directory of Open Access Journals (Sweden)

    Seok Yong Kang

    2017-01-01

    Full Text Available Ethnopharmacological Relevance. In this study, we investigated the effects of Tribulus terrestris fruit (Leguminosae, Tribuli Fructus, TF extract on oxazolone-induced atopic dermatitis in mice. Materials and Methods. TF extract was prepared with 30% ethanol as solvent. The 1% TF extract with or without 0.1% HC was applied to the back skin daily for 24 days. Results. 1% TF extract with 0.1% HC improved AD symptoms and reduced TEWL and symptom scores in AD mice. 1% TF extract with 0.1% HC inhibited skin inflammation through decrease in inflammatory cells infiltration as well as inhibition of Orai-1 expression in skin tissues. TF extract inhibited Orai-1 activity in Orai-1-STIM1 cooverexpressing HEK293T cells but increased TRPV3 activity in TRPV3-overexpressing HEK293T cells. TF extract decreased β-hexosaminidase release in RBL-2H3 cells. Conclusions. The present study demonstrates that the topical application of TF extract improves skin inflammation in AD mice, and the mechanism for this effect appears to be related to the modulation of calcium channels and mast cell activation. This outcome suggests that the combination of TF and steroids could be a more effective and safe approach for AD treatment.

  17. Effects of the Fruit Extract of Tribulus terrestris on Skin Inflammation in Mice with Oxazolone-Induced Atopic Dermatitis through Regulation of Calcium Channels, Orai-1 and TRPV3, and Mast Cell Activation

    Science.gov (United States)

    Kang, Seok Yong; Jung, Hyo Won; Nam, Joo Hyun; Kim, Woo Kyung; Kang, Jong-Seong; Kim, Young-Ho; Cho, Cheong-Weon; Cho, Chong Woon

    2017-01-01

    Ethnopharmacological Relevance In this study, we investigated the effects of Tribulus terrestris fruit (Leguminosae, Tribuli Fructus, TF) extract on oxazolone-induced atopic dermatitis in mice. Materials and Methods TF extract was prepared with 30% ethanol as solvent. The 1% TF extract with or without 0.1% HC was applied to the back skin daily for 24 days. Results 1% TF extract with 0.1% HC improved AD symptoms and reduced TEWL and symptom scores in AD mice. 1% TF extract with 0.1% HC inhibited skin inflammation through decrease in inflammatory cells infiltration as well as inhibition of Orai-1 expression in skin tissues. TF extract inhibited Orai-1 activity in Orai-1-STIM1 cooverexpressing HEK293T cells but increased TRPV3 activity in TRPV3-overexpressing HEK293T cells. TF extract decreased β-hexosaminidase release in RBL-2H3 cells. Conclusions The present study demonstrates that the topical application of TF extract improves skin inflammation in AD mice, and the mechanism for this effect appears to be related to the modulation of calcium channels and mast cell activation. This outcome suggests that the combination of TF and steroids could be a more effective and safe approach for AD treatment. PMID:29348776

  18. Skin absorption through atopic dermatitis skin

    DEFF Research Database (Denmark)

    Halling-Overgaard, A-S; Kezic, S; Jakasa, I

    2017-01-01

    Patients with atopic dermatitis have skin barrier impairment in both lesional and non-lesional skin. They are typically exposed to emollients daily and topical anti-inflammatory medicaments intermittently, hereby increasing the risk of developing contact allergy and systemic exposed to chemicals...... ingredients found in these topical preparations. We systematically searched for studies that investigated skin absorption of various penetrants, including medicaments, in atopic dermatitis patients, but also animals with experimentally induced dermatitis. We identified 40 articles, i.e. 11 human studies...... examining model penetrants, 26 human studies examining atopic dermatitis drugs and 3 animal studies. We conclude that atopic dermatitis patients have nearly two-fold increased skin absorption when compared to healthy controls. There is a need for well-designed epidemiological and dermato...

  19. Stressors in Atopic Dermatitis.

    Science.gov (United States)

    Barilla, Steven; Felix, Kayla; Jorizzo, Joseph L

    2017-01-01

    As with other inflammatory skin disorders, atopic dermatitis has a tendency to cause stress and also be exacerbated by it. Patients with atopic dermatitis have several disease-associated stressors, some of which include physical discomfort due to itching and altered appearance due to flare-ups. These stressors have been shown to effect patients psychosocially by altering sleep patterns, decreasing self-esteem and interfering with interpersonal relationships. In combination with its direct effect on patients, atopic dermatitis also causes stress for parents and caregivers. Studies suggest that atopic dermatitis is strongly correlated with co-sleeping habits, which can negatively impact the health and mood of parents or caregivers. It has also been reported to interfere with the formation of a strong mother-child relationship. In order to optimize treatment for patients with atopic dermatitis, it is important to note the impact that it has on quality of life. By implementing patient counseling, sleep-targeted therapies, and the use of quality of life (QoL) indices, atopic dermatitis patients and caregivers have the potential to experience greater satisfaction with treatment.

  20. Childhood Atopic Dermatitis in Taiwan

    Directory of Open Access Journals (Sweden)

    I-Jen Wang

    2016-04-01

    Full Text Available The prevalence of atopic dermatitis (AD appears to have increased dramatically over the past decades. It is generally believed that such rapid increase in prevalence cannot be explained fully by genetic factors. Environmental factors might play a role in such an increment. Children with AD are most likely to suffer considerable school absences, family stress, and health care expenditures. Because the onset of AD occurs relatively early in life, identification of early life risk factors and early management for AD to prevent the development of atopic march are of critical importance. However, there is still no consensus on coordinated prevention and management for AD in Taiwan. In this review, we discuss the specific risk factors of AD and important results of recent articles on AD from Taiwan. The management and prevention strategies of AD for Asian skin are also discussed.

  1. Flexural eczema versus atopic dermatitis.

    Science.gov (United States)

    Jacob, Sharon E; Goldenberg, Alina; Nedorost, Susan; Thyssen, Jacob P; Fonacier, Luz; Spiewak, Radoslaw

    2015-01-01

    Flexural eczema and atopic dermatitis are frequently synonymized. As respiratory atopy is rarely tested for and found in these patients, systematically equating a flexural distribution of dermatitis with atopic dermatitis may too frequently result in misclassified diagnoses and potentially missed opportunity for intervention toward improving patients' symptoms and quality of life. We present a critical review of the available evidence for the atopic dermatitis diagnosis and discuss the similarities between atopic dermatitis and allergic contact dermatitis. Because neither flexural predilection nor atopy is specific for atopic dermatitis, we conclude that the term atopic dermatitis is a misnomer and propose an etymologic reclassification of atopic dermatitis to "atopy-related" dermatitis. Allergic contact dermatitis can induce an atopic dermatitis-like phenotype, and thus, flexural dermatitis cannot be assumed as atopic without further testing. Patch testing should at least be considered in cases of chronic or recurrent eczema regardless of the working diagnosis.

  2. Flexural eczema versus atopic dermatitis

    DEFF Research Database (Denmark)

    Jacob, Sharon E; Goldenberg, Alina; Nedorost, Susan

    2015-01-01

    Flexural eczema and atopic dermatitis are frequently synonymized. As respiratory atopy is rarely tested for and found in these patients, systematically equating a flexural distribution of dermatitis with atopic dermatitis may too frequently result in misclassified diagnoses and potentially missed...... opportunity for intervention toward improving patients' symptoms and quality of life. We present a critical review of the available evidence for the atopic dermatitis diagnosis and discuss the similarities between atopic dermatitis and allergic contact dermatitis. Because neither flexural predilection nor...... atopy is specific for atopic dermatitis, we conclude that the term atopic dermatitis is a misnomer and propose an etymologic reclassification of atopic dermatitis to "atopy-related" dermatitis. Allergic contact dermatitis can induce an atopic dermatitis-like phenotype, and thus, flexural dermatitis...

  3. [Atopic dermatitis physiopathology].

    Science.gov (United States)

    Waton, J

    2017-12-01

    Our understanding of the physiopathology of atopic dermatitis has much improved over the recent years. Epidermal barrier alterations are integrated into 2 theories called inside out and outside in. They are related to complex immune abnormalities. Understanding their mechanism makes it possible to foresee new therapeutics. Moreover, environmental biodiversity, the diversity of cutaneous microbiota and genetic predispositions in atopic dermatitis lead to a new, more comprehensive theory, « the biodiversity theory », integrating epigenetics. © 2017 Elsevier Masson SAS. Tous droits réservés.

  4. Japanese Guideline for Atopic Dermatitis

    Directory of Open Access Journals (Sweden)

    Ichiro Katayama

    2011-01-01

    The basics of treatment discussed in this guideline are based on the “Guidelines for the Treatment of Atopic Dermatitis 2008” prepared by the Health and Labour Sciences Research and the “Guidelines for the Management of Atopic Dermatitis 2009 (ADGL2009” prepared by the Atopic Dermatitis Guidelines Advisory Committee, Japanese Society of Allergology in principle.

  5. Ultra-pure soft water ameliorates atopic skin disease by preventing metallic soap deposition in NC/Tnd mice and reduces skin dryness in humans.

    Science.gov (United States)

    Tanaka, Akane; Matsuda, Akira; Jung, Kyungsook; Jang, Hyosun; Ahn, Ginnae; Ishizaka, Saori; Amagai, Yosuke; Oida, Kumiko; Arkwright, Peter D; Matsuda, Hiroshi

    2015-09-01

    Mineral ions in tap water react with fatty acids in soap, leading to the formation of insoluble precipitate (metallic soap) on skin during washing. We hypothesised that metallic soap might negatively alter skin conditions. Application of metallic soap onto the skin of NC/Tnd mice with allergic dermatitis further induced inflammation with elevation of plasma immunoglobulin E and proinflammatory cytokine expression. Pruritus and dryness were ameliorated when the back of mice was washed with soap in Ca2+- and Mg2+-free ultra-pure soft water (UPSW). Washing in UPSW, but not tap water, also protected the skin of healthy volunteers from the soap deposition. Furthermore, 4 weeks of showering with UPSW reduced dryness and pruritus of human subjects with dry skin. Washing with UPSW may be therapeutically beneficial in patients with skin troubles.

  6. Daily intake of Jeju groundwater improves the skin condition of the model mouse for human atopic dermatitis.

    Science.gov (United States)

    Tanaka, Akane; Jung, Kyungsook; Matsuda, Akira; Jang, Hyosun; Kajiwara, Naoki; Amagai, Yosuke; Oida, Kumiko; Ahn, Ginnae; Ohmori, Keitaro; Kang, Kyung-goo; Matsuda, Hiroshi

    2013-03-01

    Drinking water is an important nutrient for human health. The mineral ingredients included in drinking water may affect the physical condition of people. Various kinds of natural water are in circulation as bottled water in developed countries; however, its influence on clinical conditions of patients with certain diseases has not been fully evaluated. In this study, effects of the natural groundwater from Jeju Island on clinical symptoms and skin barrier function in atopic dermatitis (AD) were evaluated. NC/Tnd mice, a model for human AD, with moderate to severe dermatitis were used. Mice were given different natural groundwater or tap water for 8 weeks from 4 weeks of age. Clinical skin severity scores were recorded every week. Scratching analysis and measurement of transepidermal water loss were performed every other week. The pathological condition of the dorsal skin was evaluated histologically. Real-time polymerase chain reaction analysis was performed for cytokine expression in the affected skin. The epidermal hyperplasia and allergic inflammation were reduced in atopic mice supplied with Jeju groundwater when compared to those supplied with tap water or other kinds of natural groundwater. The increase in scratching behavior with the aggravation of clinical severity of dermatitis was favorably controlled. Moreover, transepidermal water loss that reflects skin barrier function was recovered. The early inflammation and hypersensitivity in the atopic skin was alleviated in mice supplied with Jeju groundwater, suggesting its profitable potential on the daily care of patients with skin troubles including AD. © 2013 Japanese Dermatological Association.

  7. Omalizumab for atopic dermatitis

    DEFF Research Database (Denmark)

    Holm, Jesper Grønlund; Agner, Tove; Sand, Carsten

    2017-01-01

    Omalizumab is a recombinant humanized monoclonal antibody targeting the high-affinity Fc receptor of IgE, registered for the treatment of chronic spontaneous urticaria and severe allergic asthma. We present a case series of nine patients with atopic dermatitis (AD) treated off-label with omalizumab...

  8. Advances in pediatric asthma and atopic dermatitis.

    Science.gov (United States)

    Foroughi, Shabnam; Thyagarajan, Ananth; Stone, Kelly D

    2005-10-01

    Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, food allergy, and urticaria are common in general pediatric practice. This review highlights several significant advances in pediatric allergy over the past year, focusing on asthma and atopic dermatitis. With increasing options for the treatment of allergic diseases, much work is now focused on methods for individualizing treatments to a patient's phenotype and genotype. Progress over the past year includes the characterization of effects of regular albuterol use in patients with genetic variations in the beta-adrenergic receptor. Maintenance asthma regimens for children in the first years of life are also an ongoing focus. The relation between upper airway allergic inflammation and asthma has continued to accumulate support and now extends to the middle ear. Environmental influences on asthma and interventions have been described, including environmental controls for asthma and the role of air pollution on lung development in children. Finally, concerns have been raised regarding the use of topical immunomodulators in young children with atopic dermatitis. Progress continues in the care of children with atopic diseases. Attention to treatment with appropriate medications, patient-individualized environmental controls, and extensive education are the keys to successfully treating atopic children. This review highlights several recent advances but is not intended to be a comprehensive review.

  9. Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among low-atopy-risk infants

    NARCIS (Netherlands)

    Grueber, Christoph; van Stuijvenberg, Margriet; Mosca, Fabio; Moro, Guido; Chirico, Gaetano; Braegger, Christian P.; Riedler, Josef; Boehm, Guenther; Wahn, Ulrich

    2010-01-01

    Background: Most infants developing atopic dermatitis have a low risk for atopy. Primary prevention of atopic dermatitis is difficult. Objective: To assess the effect of supplementation of an infant and follow-on formula with prebiotic and immunoactive oligosaccharides on the occurrence of atopic

  10. Tartrazine in atopic eczema.

    OpenAIRE

    Devlin, J; David, T J

    1992-01-01

    Multiple double blind placebo controlled challenges with tartrazine 50 mg (three challenges) and glucose placebo (three challenges) were performed in 12 children with atopic eczema aged 1 to 6 years. The children were selected on the basis of severity (regular clinic attenders) and a parental history that tartrazine provoked worsening of the eczema. In only one patient did the three tartrazine challenge periods correspond with the highest symptom scores or the highest physician observer score...

  11. Therapeutic benefits of enhancing permeability barrier for atopic eczema

    Directory of Open Access Journals (Sweden)

    George Man

    2015-06-01

    Full Text Available The regulatory role of epidermal permeability barrier function in cutaneous inflammation has been well appreciated. While barrier disruption induces cutaneous inflammation, improvement of permeability barrier function alleviates inflammation. Studies have demonstrated that improvement of epidermal permeability barrier function not only prevents the development of atopic eczema, but also delays the relapse of these diseases. Moreover, enhancing the epidermal permeability barrier also alleviates atopic eczema. Furthermore, co-applications of barrier enhancing products with glucocorticoids can increase the therapeutic efficacy and reduce the adverse effects of glucocorticoids in the treatment of atopic eczema. Therefore, utilization of permeability barrier enhancing products alone or in combination with glucocorticoids could be a valuable approach in the treatment of atopic eczema. In this review, we discuss the benefits of improving the epidermal permeability barrier in the management of atopic eczema.

  12. Mice lacking major brain gangliosides develop parkinsonism.

    Science.gov (United States)

    Wu, Gusheng; Lu, Zi-Hua; Kulkarni, Neil; Amin, Ruchi; Ledeen, Robert W

    2011-09-01

    Parkinson's disease (PD) is the second most prevalent late-onset neurodegenerative disorder that affects nearly 1% of the global population aged 65 and older. Whereas palliative treatments are in use, the goal of blocking progression of motor and cognitive disability remains unfulfilled. A better understanding of the basic pathophysiological mechanisms underlying PD would help to advance that goal. The present study provides evidence that brain ganglioside abnormality, in particular GM1, may be involved. This is based on use of the genetically altered mice with disrupted gene Galgt1 for GM2/GD2 synthase which depletes GM2/GD2 and all the gangliotetraose gangliosides that constitute the major molecular species of brain. These knockout mice show overt motor disability on aging and clear indications of motor impairment with appropriate testing at an earlier age. This disability was rectified by L-dopa administration. These mice show other characteristic symptoms of PD, including depletion of striatal dopamine (DA), loss of DA neurons of the substantia nigra pars compacta, and aggregation of alpha synuclein. These manifestations of parkinsonism were largely attenuated by administration of LIGA-20, a membrane permeable analog of GM1 that penetrates the blood brain barrier and enters living neurons. These results suggest that perturbation of intracellular mechanisms mediated by intracellular GM1 may be a contributing factor to PD.

  13. Can atopic dermatitis be prevented?

    Science.gov (United States)

    Gómez-de la Fuente, E

    2015-05-01

    Atopic dermatitis has become a health problem in our setting due to its rising prevalence, impact on quality of life, associated costs, and role in the progression to other atopic diseases. Furthermore, atopic dermatitis has no definitive cure and therefore preventive measures are important. In this article, we review the latest advances in both primary prevention (reduction of the incidence of atopic dermatitis) and secondary prevention (reduction of associated morbidity and reduction of the atopic march). We analyze the different preventive strategies available, including modification of the immune system through microbial exposure, induction of immune tolerance through antigen exposure, and restoration of skin barrier function to halt the atopic march. Dermatologists need to be familiar with these strategies in order to apply them where necessary and to accurately inform patients and their relatives to prevent misguided or inappropriate actions. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

  14. Activated Natural Killer Cells Mediate the Suppressive Effect of Interleukin-4 on Tumor Development via STAT6 Activation in an Atopic Condition Melanoma Model

    OpenAIRE

    Dong Ju Son; Yu Yeon Jung; Mi Hee Park; Hye Lim Lee; Min Ji Song; Hwan-Soo Yoo; Dae Youn Hwang; Sang Bae Han; Jin Tae Hong

    2017-01-01

    A protective effect of allergy for cancer has been suggested, but the results are somewhat conflicting, and the mechanism remains elusive. Interleukin-4 (IL-4) signaling has been identified as a potentially important pathway in the development of allergies and the suppression of cancer development. To evaluate the allergy responses in IL-4?mediated tumor development, we compared the growth of B16F10 melanoma cells in 4% phthalic anhydride (PA)-treated IL-4/Luc/CNS-1 transgenic mice (IL-4 mice...

  15. Novel investigational therapies for atopic dermatitis

    DEFF Research Database (Denmark)

    Ibler, Kristina Sophie; Jemec, Gregor Be

    2015-01-01

    Introduction: Atopic dermatitis (AD) is a common skin disease. Although most patients are well served by existing therapies, a subset of patients with severe AD are still not adequately treated. An improved understanding of the pathogenic mechanisms behind the disease has led to the development...

  16. Cell-extrinsic defective lymphocyte development in Lmna(-/- mice.

    Directory of Open Access Journals (Sweden)

    J Scott Hale

    2010-04-01

    Full Text Available Mutations in the LMNA gene, which encodes all A-type lamins, result in a variety of human diseases termed laminopathies. Lmna(-/- mice appear normal at birth but become runted as early as 2 weeks of age and develop multiple tissue defects that mimic some aspects of human laminopathies. Lmna(-/- mice also display smaller spleens and thymuses. In this study, we investigated whether altered lymphoid organ sizes are correlated with specific defects in lymphocyte development.Lmna(-/- mice displayed severe age-dependent defects in T and B cell development which coincided with runting. Lmna(-/- bone marrow reconstituted normal T and B cell development in irradiated wild-type recipients, driving generation of functional and self-MHC restricted CD4(+ and CD8(+ T cells. Transplantation of Lmna(-/- neonatal thymus lobes into syngeneic wild-type recipients resulted in good engraftment of thymic tissue and normal thymocyte development.Collectively, these data demonstrate that the severe defects in lymphocyte development that characterize Lmna(-/- mice do not result directly from the loss of A-type lamin function in lymphocytes or thymic stroma. Instead, the immune defects in Lmna(-/- mice likely reflect indirect damage, perhaps resulting from prolonged stress due to the striated muscle dystrophies that occur in these mice.

  17. Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: first results of ETAC. Early Treatment of the Atopic Child.

    Science.gov (United States)

    1998-08-01

    There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (> or = 30 kU/l) or specific IgE (> or = 0.35 kUA/l) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the

  18. Tartrazine in atopic eczema.

    Science.gov (United States)

    Devlin, J; David, T J

    1992-06-01

    Multiple double blind placebo controlled challenges with tartrazine 50 mg (three challenges) and glucose placebo (three challenges) were performed in 12 children with atopic eczema aged 1 to 6 years. The children were selected on the basis of severity (regular clinic attenders) and a parental history that tartrazine provoked worsening of the eczema. In only one patient did the three tartrazine challenge periods correspond with the highest symptom scores or the highest physician observer scores, and the probability of this occurring by chance in one or more patients out of 12 was 0.46. In this sample we were unable to confirm intolerance to tartrazine in 11 out of 12 patients.

  19. Effects of prenatal cocaine exposure on social development in mice.

    Science.gov (United States)

    Kabir, Zeeba D; Kennedy, Bruce; Katzman, Aaron; Lahvis, Garet P; Kosofsky, Barry E

    2014-01-01

    Prenatal cocaine exposure (PCE) in humans and animals has been shown to impair social development. Molecules that mediate synaptic plasticity and learning in the medial prefrontal cortex (mPFC), specifically brain-derived neurotrophic factor (BDNF) and its downstream signaling molecule, early growth response protein 1 (egr1), have been shown to affect the regulation of social interactions (SI). In this study we determined the effects of PCE on SI and the corresponding ultrasonic vocalizations (USVs) in developing mice. Furthermore, we studied the PCE-induced changes in the constitutive expression of BDNF, egr1 and their transcriptional regulators in the mPFC as a possible molecular mechanism mediating the altered SI. In prenatal cocaine-exposed (PCOC) mice we identified increased SI and USV production at postnatal day (PD) 25, and increased SI but not USVs at PD35. By PD45 the expression of both social behaviors normalized in PCOC mice. At the molecular level, we found increased BDNF exon IV and egr1 mRNA in the mPFC of PCOC mice at PD30 that normalized by PD45. This was concurrent with increased EGR1 protein in the mPFC of PCOC mice at PD30, suggesting a role of egr1 in the enhanced SI observed in juvenile PCOC mice. Additionally, by measuring the association of acetylation of histone 3 at lysine residues 9 and 14 (acH3K9,14) and MeCP2 at the promoters of BDNF exons I and IV and egr1, our results provide evidence of promoter-specific alterations in the mPFC of PCOC juvenile mice, with increased association of acH3K9,14 only at the BDNF exon IV promoter. These results identify a potential PCE-induced molecular alteration as the underlying neurobiological mechanism mediating the altered social development in juvenile mice. © 2014 S. Karger AG, Basel.

  20. Pregnancy alters the circulating B cell compartment in atopic asthmatic women, and transitional B cells are positively associated with the development of allergy manifestations in their progeny.

    Science.gov (United States)

    Martins, Catarina; Lima, Jorge; Nunes, Glória; Borrego, Luís Miguel

    2016-12-01

    Maternal atopy is a risk factor for allergy. B cells are poorly studied in reproduction and atopy. We aimed to assess how pregnancy affects B cells in atopic women and whether B cells relate to allergic manifestations in offspring. Women with and without atopic asthma, pregnant and non-pregnant were enrolled for the study, and circulating B cells were evaluated by flow cytometry, using CD19, CD27, CD38, IgD, and IgM. Compared to healthy non-pregnant, atopic asthmatic non-pregnant (ANP) women presented increased B cell counts, enlarged memory subsets, less transitional cells, and plasmablasts. Atopic asthmatic pregnant (AP) and healthy pregnant (HP) women showed similarities: reduced B cell counts and percentages, fewer memory cells, especially switched, and higher plasmablast percentages. Transitional B cell percentages were increased in AP women with allergic manifestations in their progeny. Atopic asthmatic non-pregnant women have a distinctive B cell compartment. B cells change in pregnancy, similarly in AP and HP women. The recognition that AP women with allergy in their progeny have a typical immune profile may help, in the future, the adoption of preventive measures to avoid the manifestation of allergic diseases in their newborns. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Evaluation of FITC-induced atopic dermatitis-like disease in NC/Nga mice and BALB/c mice using computer-assisted stereological toolbox, a computer-aided morphometric system

    DEFF Research Database (Denmark)

    Hvid, Malene; Jensen, Helene Kofoed; Deleuran, Bent

    2009-01-01

    Stereological Toolbox as a stereological method, the mice were sensitized to FITC and the histological efficiency of disease induction with regard to inflammation and CD4+ and CD8+ lymphocytes, in addition to mast cells, was evaluated. The method was validated by comparison to a conventional semiquantitative...

  2. Management of Atopic Hand Dermatitis

    DEFF Research Database (Denmark)

    Halling-Overgaard, Anne-Sofie; Zachariae, Claus; Thyssen, Jacob P

    2017-01-01

    This article provides an overview of clinical aspects of hand eczema in patients with atopic dermatitis. Hand eczema can be a part of atopic dermatitis itself or a comorbidity, for example, as irritant or allergic contact dermatitis. When managing hand eczema, it is important to first categorize...

  3. Allergenic food introduction and risk of childhood atopic diseases

    NARCIS (Netherlands)

    N.J. Elbert (Niels); J.C. Kiefte-de Jong (Jessica); R.G. Voortman (Trudy); T.E.C. Nijsten (Tamar); N.W. de Jong (Nicolette); V.W.V. Jaddoe (Vincent); J.C. de Jongste (Johan); R. Gerth van Wijk (Roy); Duijts, L. (Liesbeth); S.G.M.A. Pasmans (Suzanne)

    2017-01-01

    textabstractBackground: The role of timing and diversity of allergenic food introduction in the development of childhood allergic sensitization and atopic diseases is controversial. Objective: To examine whether timing and diversity of allergenic food introduction are associated with allergic

  4. Atopic diseases in twins born after assisted reproduction.

    Science.gov (United States)

    Jäderberg, Ida; Thomsen, Simon F; Kyvik, Kirsten O; Skytthe, Axel; Backer, Vibeke

    2012-03-01

    We examined the risk of atopic diseases in twins born after assisted reproduction. Data on atopic diseases and assisted reproduction in 9694 twin pairs, 3-20 years of age, from the Danish Twin Registry were collected via multidisciplinary questionnaires. The risk of atopic diseases in twins born after assisted reproduction was compared with the risk in twins born after spontaneous conception using logistic regression and variance components analysis. Children born after assisted reproduction did not have a different risk of atopic outcomes (adjusted odds ratios [95% confidence intervals] for asthma: 0.95 [0.85, 1.07], P = 0.403; hay fever: 1.01 [0.86, 1.18], P = 0.918; and atopic dermatitis: 1.02 [0.81, 1.11], P = 0.773 respectively) compared with children born after spontaneous conception. Assisted reproduction did not modify the heritability of atopic diseases. This study does not support an association between assisted reproduction and development of atopic diseases. This result must be confirmed in subsequent studies, preferably of singleton populations. © 2011 Blackwell Publishing Ltd.

  5. [The role of the innate immune system in atopic dermatitis].

    Science.gov (United States)

    Volz, T; Kaesler, S; Skabytska, Y; Biedermann, T

    2015-02-01

    The mechanisms how the innate immune system detects microbes and mounts a rapid immune response have been more and more elucidated in the past years. Subsequently it has been shown that innate immunity also shapes adaptive immune responses and determines their quality that can be either inflammatory or tolerogenic. As atopic dermatitis is characterized by disturbances of innate and adaptive immune responses, colonization with pathogens and defects in skin barrier function, insight into mechanisms of innate immunity has helped to understand the vicious circle of ongoing skin inflammation seen in atopic dermatitis patients. Elucidating general mechanisms of the innate immune system and its functions in atopic dermatitis paves the way for developing new therapies. Especially the novel insights into the human microbiome and potential functional consequences make the innate immune system a very fundamental and promising target. As a result atopic dermatitis manifestations can be attenuated or even resolved. These currently developed strategies will be introduced in the current review.

  6. An Improved Mouse Model of Atopic Dermatitis and Suppression of Skin Lesions by an Inhibitor of Tec Family Kinases

    Directory of Open Access Journals (Sweden)

    Yuko Kawakami

    2007-01-01

    Conclusions: We established a highly efficient, highly reproducible protocol to induce skin lesions in NC/Nga mice and successfully applied it to show the efficacy of terreic acid in treating skin lesions. This mouse model of atopic dermatitis will be useful to study the pathogenetic processes of atopic dermatitis and to evaluate the efficacy of drug candidates.

  7. Tartrazine in atopic eczema.

    Science.gov (United States)

    Devlin, J; David, T J

    1992-01-01

    Multiple double blind placebo controlled challenges with tartrazine 50 mg (three challenges) and glucose placebo (three challenges) were performed in 12 children with atopic eczema aged 1 to 6 years. The children were selected on the basis of severity (regular clinic attenders) and a parental history that tartrazine provoked worsening of the eczema. In only one patient did the three tartrazine challenge periods correspond with the highest symptom scores or the highest physician observer scores, and the probability of this occurring by chance in one or more patients out of 12 was 0.46. In this sample we were unable to confirm intolerance to tartrazine in 11 out of 12 patients. PMID:1626990

  8. Aldose Reductase-Deficient Mice Develop Nephrogenic Diabetes Insipidus

    Science.gov (United States)

    Ho, Horace T. B.; Chung, Sookja K.; Law, Janice W. S.; Ko, Ben C. B.; Tam, Sidney C. F.; Brooks, Heddwen L.; Knepper, Mark A.; Chung, Stephen S. M.

    2000-01-01

    Aldose reductase (ALR2) is thought to be involved in the pathogenesis of various diseases associated with diabetes mellitus, such as cataract, retinopathy, neuropathy, and nephropathy. However, its physiological functions are not well understood. We developed mice deficient in this enzyme and found that they had no apparent developmental or reproductive abnormality except that they drank and urinated significantly more than their wild-type littermates. These ALR2-deficient mice exhibited a partially defective urine-concentrating ability, having a phenotype resembling that of nephrogenic diabetes insipidus. PMID:10913167

  9. Atopic dermatitis -- self-care

    Science.gov (United States)

    ... C. Evolution of conventional therapy in atopic dermatitis. Immunology and Allergy Clinics of North America . 2010;30( ... D.A.M. Editorial team. Related MedlinePlus Health Topics Eczema Browse the Encyclopedia A.D.A.M., ...

  10. Difficult to control atopic dermatitis

    NARCIS (Netherlands)

    U. Darsow (U.); A. Wollenberg (A.); D. Simon; A. Taieb; T. Werfel; A.P. Oranje (Arnold); C. Gelmetti (C.); Ã. Svensson (Ãke); M. Deleuran (M.); A.M. Calza; F. Giusti; J. Lübbe (Jann); S. Seidenari (Stefania); J. Ring (J.)

    2013-01-01

    textabstractDifficult to control atopic dermatitis (AD) presents a therapeutic challenge and often requires combinations of topical and systemic treatment. Anti-inflammatory treatment of severe AD most commonly includes topical glucocorticosteroids and topical calcineurin antagonists used for

  11. Aberrant Wound Healing in an Epidermal Interleukin-4 Transgenic Mouse Model of Atopic Dermatitis

    Science.gov (United States)

    Zhao, Yan; Bao, Lei; Chan, Lawrence S.; DiPietro, Luisa A.; Chen, Lin

    2016-01-01

    Wound healing in a pre-existing Th2-dominated skin milieu was assessed by using an epidermal specific interleukin-4 (IL-4) transgenic (Tg) mouse model, which develops a pruritic inflammatory skin condition resembling human atopic dermatitis. Our results demonstrated that IL-4 Tg mice had delayed wound closure and re-epithelialization even though these mice exhibited higher degrees of epithelial cell proliferation. Wounds in IL-4 Tg mice also showed a marked enhancement in expression of inflammatory cytokines/chemokines, elevated infiltration of inflammatory cells including neutrophils, macrophages, CD3+ lymphocytes, and epidermal dendritic T lymphocytes. In addition, these mice exhibited a significantly higher level of angiogenesis as compared to wild type mice. Furthermore, wounds in IL-4 Tg mice presented with larger amounts of granulation tissue, but had less expression and deposition of collagen. Taken together, an inflamed skin condition induced by IL-4 has a pronounced negative influence on the healing process. Understanding more about the pathogenesis of wound healing in a Th2- dominated environment may help investigators explore new potential therapeutic strategies. PMID:26752054

  12. The development of lower respiratory tract microbiome in mice.

    Science.gov (United States)

    Singh, Nisha; Vats, Asheema; Sharma, Aditi; Arora, Amit; Kumar, Ashwani

    2017-06-21

    Although culture-independent methods have paved the way for characterization of the lung microbiome, the dynamic changes in the lung microbiome from neonatal stage to adult age have not been investigated. In this study, we tracked changes in composition and diversity of the lung microbiome in C57BL/6N mice, starting from 1-week-old neonates to 8-week-old mice. Towards this, the lungs were sterilely excised from mice of different ages from 1 to 8 weeks. High-throughput DNA sequencing of the 16S rRNA gene followed by composition and diversity analysis was utilized to decipher the microbiome in these samples. Microbiome analysis suggests that the changes in the lung microbiome correlated with age. The lung microbiome was primarily dominated by phyla Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria in all the stages from week 1 to week 8 after birth. Although Defluvibacter was the predominant genus in 1-week-old neonatal mice, Streptococcus became the dominant genus at the age of 2 weeks. Lactobacillus, Defluvibacter, Streptococcus, and Achromobacter were the dominant genera in 3-week-old mice, while Lactobacillus and Achromobacter were the most abundant genera in 4-week-old mice. Interestingly, relatively greater diversity (at the genus level) during the age of 5 to 6 weeks was observed as compared to the earlier weeks. The diversity of the lung microbiome remained stable between 6 and 8 weeks of age. In summary, we have tracked the development of the lung microbiome in mice from an early age of 1 week to adulthood. The lung microbiome is dominated by the phyla Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria. However, dynamic changes were observed at the genus level. Relatively higher richness in the microbial diversity was achieved by age of 6 weeks and then maintained at later ages. We believe that this study improves our understanding of the development of the mice lung microbiome and will facilitate further analyses of the role of

  13. IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice.

    Directory of Open Access Journals (Sweden)

    Polyxeni T Mantani

    Full Text Available IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice.Administration of 1 μg IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apoE deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 μg IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease.The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses.

  14. EFFECTS OF VITEX AGNUS CASTUS ON MICE FETUS DEVELOPMENT

    OpenAIRE

    M. Azarnia; S. Ejtemaee-Mehr; A. Shakoor A. Ansari

    2007-01-01

    Vitex agnus castus (chasteberry) is a popular treatment for the management of female reproductive disorders including corpus luteum insufficiency, premenstrual syndrome (PMS), menopausal symptoms, and insufficient milk production. According to developing situation of complementary medicine, and frequent use of this herb, it is important to examine its effects during pregnancy. In this research we studied its effects on mice development, and we focused on macroscopic parameters, such as CRL (C...

  15. Morphological study of tooth development in podoplanin-deficient mice.

    Directory of Open Access Journals (Sweden)

    Kenyo Takara

    Full Text Available Podoplanin is a mucin-type highly O-glycosylated glycoprotein identified in several somatyic cells: podocytes, alveolar epithelial cells, lymphatic endothelial cells, lymph node stromal fibroblastic reticular cells, osteocytes, odontoblasts, mesothelial cells, glia cells, and others. It has been reported that podoplanin-RhoA interaction induces cytoskeleton relaxation and cell process stretching in fibroblastic cells and osteocytes, and that podoplanin plays a critical role in type I alveolar cell differentiation. It appears that podoplanin plays a number of different roles in contributing to cell functioning and growth by signaling. However, little is known about the functions of podoplanin in the somatic cells of the adult organism because an absence of podoplanin is lethal at birth by the respiratory failure. In this report, we investigated the tooth germ development in podoplanin-knockout mice, and the dentin formation in podoplanin-conditional knockout mice having neural crest-derived cells with deficiency in podoplanin by the Wnt1 promoter and enhancer-driven Cre recombinase: Wnt1-Cre;PdpnΔ/Δmice. In the Wnt1-Cre;PdpnΔ/Δmice, the tooth and alveolar bone showed no morphological abnormalities and grow normally, indicating that podoplanin is not critical in the development of the tooth and bone.

  16. Morphological study of tooth development in podoplanin-deficient mice.

    Science.gov (United States)

    Takara, Kenyo; Maruo, Naoki; Oka, Kyoko; Kaji, Chiaki; Hatakeyama, Yuji; Sawa, Naruhiko; Kato, Yukinari; Yamashita, Junro; Kojima, Hiroshi; Sawa, Yoshihiko

    2017-01-01

    Podoplanin is a mucin-type highly O-glycosylated glycoprotein identified in several somatyic cells: podocytes, alveolar epithelial cells, lymphatic endothelial cells, lymph node stromal fibroblastic reticular cells, osteocytes, odontoblasts, mesothelial cells, glia cells, and others. It has been reported that podoplanin-RhoA interaction induces cytoskeleton relaxation and cell process stretching in fibroblastic cells and osteocytes, and that podoplanin plays a critical role in type I alveolar cell differentiation. It appears that podoplanin plays a number of different roles in contributing to cell functioning and growth by signaling. However, little is known about the functions of podoplanin in the somatic cells of the adult organism because an absence of podoplanin is lethal at birth by the respiratory failure. In this report, we investigated the tooth germ development in podoplanin-knockout mice, and the dentin formation in podoplanin-conditional knockout mice having neural crest-derived cells with deficiency in podoplanin by the Wnt1 promoter and enhancer-driven Cre recombinase: Wnt1-Cre;PdpnΔ/Δmice. In the Wnt1-Cre;PdpnΔ/Δmice, the tooth and alveolar bone showed no morphological abnormalities and grow normally, indicating that podoplanin is not critical in the development of the tooth and bone.

  17. Human atopic dermatitis skin-derived T cells can induce a reaction in mouse keratinocytes in vivo

    DEFF Research Database (Denmark)

    Martel, Britta C; Blom, Lars; Dyring-Andersen, Beatrice

    2015-01-01

    . In comparison, blood -derived in vitro differentiated Th2 cells only induced a weak response in a few of the mice. Thus, we conclude that human AD skin-derived T cells can induce a reaction in mouse skin through induction of a proliferative response in the mouse keratinocytes. This article is protected......In atopic dermatitis (AD), the inflammatory response between skin infiltrating T cells and keratinocytes is fundamental to the development of chronic lesional eczema. The aim of this study was to investigate whether skin-derived T cells from AD patients could induce an inflammatory response in mice...... through keratinocyte activation and consequently cause development of eczematous lesions. Punch biopsies of lesional skin from AD patients were used to establish skin-derived T cell cultures and which were transferred into NOD.Cg-Prkd(scid) Il2rg(tm1Sug) /JicTac (NOG) mice. We found that subcutaneous...

  18. Atopic dermatitis in adolescence

    Directory of Open Access Journals (Sweden)

    Giampaolo Ricci

    2011-12-01

    Full Text Available Atopic dermatitis (AD is a chronic inflammatory skin disorder that typically occurs during childhood especially in the first year of life, with a variable frequency from 10% to 30%. Recent studies have shown that in Europe among 10-20% of children with AD suffer from this disorder also in adolescence. AD is a chronic inflammatory skin disease with a typical onset in the first years of life and with a 10- 30% prevalence among young children. AD prevalence in adolescence has been estimated around 5-15% in European countries. AD persists from childhood through adolescence in around 40% of cases and some risk factors have been identified: female sex, sensitization to inhalant and food allergens, allergic asthma and/or rhinoconjunctivitis, the practice of certain jobs. During adolescence, AD mainly appears on the face and neck, often associated with overinfection by Malassezia, and on the palms and soles. AD persistence during adolescence is correlated with psychological diseases such as anxiety; moreover, adolescents affected by AD might have problems in the relationship with their peers. Stress and the psychological problems represent a serious burden for adolescents with AD and cause a significant worsening of the patients’ quality of life (QoL. The pharmacological treatment is similar to other age groups. Educational and psychological approaches should be considered in the most severe cases.

  19. Homeopathy in paediatric atopic diseases: long-term results in children with atopic dermatitis.

    Science.gov (United States)

    Rossi, Elio; Bartoli, Paola; Bianchi, Alba; Da Frè, Monica

    2012-01-01

    To study the socio-demographic features, the prescribed remedies and the outcome of atopic diseases in children treated with homeopathy at the Homeopathic Clinic of Lucca (Italy), and the long-term outcome of children suffering from atopic dermatitis (AD) after an approximate 8-year period (range 5-10 years). Our data derive from an observational longitudinal study carried out on 213 children (38.6%) with atopic diseases out of 551 children consecutively examined from September 1998 to December 2008. We used the Glasgow Homeopathic Hospital Outcome Score to evaluate the results that were classified on the basis of a Likert scale. Eighty-three (39%) children were affected by asthma, 51 (24%) by allergic rhinoconjunctivitis, 76 (36%) by AD and 3 (1%) by food intolerance. Follow-up patients were 104 (48.8%), and 65 (62.5%) of them reported a major improvement or resolution. The parents of paediatric patients suffering from AD, who had started homeopathic treatment at homeopathy in atopic children. Furthermore, according to the data from the literature paediatric patients treated with homeopathy seem to show a reduced tendency to maintain AD and develop asthma (and allergic rhinitis) in adult age. Copyright © 2011 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  20. Effect of cat and daycare exposures on the risk of asthma in children with atopic dermatitis.

    Science.gov (United States)

    Gaffin, Jonathan M; Spergel, Jonathan M; Boguniewicz, Mark; Eichenfield, Lawrence F; Paller, Amy S; Fowler, Joseph F; Dinulos, James G; Tilles, Stephen A; Schneider, Lynda C; Phipatanakul, Wanda

    2012-01-01

    Atopic dermatitis (AD) in young children is often followed by the development of asthma (atopic march). The role of environmental exposures is unclear in this high-risk population. We aimed to determine the predictive relationship between indoor allergen exposures, particularly pets, rodents, and cockroaches, to the development of asthma in a prospective pediatric cohort. Children with AD and a family history of allergy were followed prospectively with questionnaire ascertainment of environmental exposure to cats, dogs, cockroaches, rats, and mice. Asthma was diagnosed by study physicians based on caregiver reports of symptoms continually assessed over the course of the study period. Fifty-five of the 299 children developed asthma by the end of the study. Cat exposure had a strong and independent effect to reduce the risk of developing asthma across all analyses (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.05-0.53). Dog, mouse, rat, and cockroach exposures did not significantly influence the development of asthma. Daycare exposure had the largest risk reduction for the development of asthma (OR, 0.08; 95% CI, 0.03-0.19). Maternal asthma (OR, 2.93; 95% CI, 1.29-6.67), baseline body mass index (OR, 1.23; 95% CI, 1.08-1.42), and specific immunoglobulin E to house-dust mix at 3 years were each independent risk factors for the development of asthma. In children with AD, cat and daycare exposure may reduce the risk of developing early childhood asthma.

  1. EFFECTS OF VITEX AGNUS CASTUS ON MICE FETUS DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    M. Azarnia; S. Ejtemaee-Mehr; A. Shakoor A. Ansari

    2007-07-01

    Full Text Available Vitex agnus castus (chasteberry is a popular treatment for the management of female reproductive disorders including corpus luteum insufficiency, premenstrual syndrome (PMS, menopausal symptoms, and insufficient milk production. According to developing situation of complementary medicine, and frequent use of this herb, it is important to examine its effects during pregnancy. In this research we studied its effects on mice development, and we focused on macroscopic parameters, such as CRL (Crown-Rump length and the weight of embryos, and diameter and the weight of placenta, and microscopic parameters such as the diameters of eye and lens of embryos. We found that Vitex has special effects during different stages of mice development, for example it can improve the growth of embryos in 8th and 9th day of pregnancy (it causes significant increase in CRL and weight of embryos. Also, it may changes some microscopic parameters. These founding suggest that it should be used more cautiously during pregnancy.

  2. Probiotics and infantile atopic eczema

    Directory of Open Access Journals (Sweden)

    Akelma AZ

    2015-09-01

    Full Text Available Ahmet Zülfikar Akelma,1 Aziz Alper Biten2 1Pediatric Allergy and Immunology Unit, Ankara Kecioren Teaching and Research Hospital, Ankara, Turkey; 2General Directorate of Management Services, Republic of Turkey Ministry of Health, Ankara, Turkey Abstract: Pediatric eczema is a common disease which causes economic and social burden. Its incidence differs among the societies, with an incidence reported to reach up to 20% in developed countries. Eczema is the first allergic disease seen in the childhood, and it is recognized as a precursor for the development of atopic diseases such as asthma, allergic rhinitis, and food allergy in the forthcoming years of children. Increased incidence of eczema in recent years has led to new research in epidemiology, prevention, and intervention of this disease. It is no doubt important to treat itching, rash, and excoriation of the skin; however, treatment of pediatric eczema should not be considered only as a treatment of skin lesions. Considering skin treatment as the tip of the iceberg, proper management of the allergic processes can be accepted as the rest of the iceberg. The role of probiotics in the prevention of atopic eczema is yet to be clarified. Evidence presented by existing studies suggesting that probiotics may prevent pediatric eczema is not strong enough. A positive effect, if any, may be related with onset time, dose, duration, and use of specific probiotics. To date, there is no strong evidence for use of probiotics in the treatment of eczema; however, administration of probiotics in breast-feeding mothers in the prenatal period and in infants in the postnatal period can be accepted as a safe and helpful option in the prevention of eczema. Nevertheless, there are still questions to be answered in the future about probiotic administration for eczema. Clinical use of probiotics will gradually become more widespread when these questions are answered. Based on current information, the administration

  3. Development of an Allergic Conjunctivitis Model in Mice

    Directory of Open Access Journals (Sweden)

    Tolga Kocatürk

    2012-12-01

    Full Text Available Pur po se: To develop an animal model that simulates human allergic conjunctivitis to understand the physiopathogenesis of allergic diseases and for developing novel therapeutic interventions. Ma te ri al and Met hod: BALB/c mice (12 males were divided into two groups each comprised of six mice. For sensitization, on the 1st and 8th days, a 0.2 ml mixed solution, adjusted to a concentration to 5mg/ml of ovalbumin (OVA and 15mg/ml of aluminium hydroxide, was administered intraperitoneally to the mice in Group 1 and 0.2 ml saline solution to the mice in Group 2. To induce experimental allergic conjunctivitis, an antigen challenge was made on days 15 and 18, using an OVA solution (5mg/ml instilled into both eyes of the mice in Group 1; while the mice in Group 2 received Human Balanced Salt Solution instead of OVA. For the clinical evaluation, the occurrence of conjunctival and palpebral oedema, conjunctival hyperaemia, and lacrimation were observed. For the histological examination, eyeballs, eyelids, and lacrimal glands were removed and prepared according to the routine processing method of the tissue laboratory. Immunohistochemical examination was made with mast cell tryptase using the labeled streptavidin–biotin amplification method and 3.3´-diaminobenzidine, in addition to hematoxylin-eosin (HE, and toluidine blue (TB staining. Re sults: Evident conjunctival oedema, palpebral oedema, conjunctival hyperaemia, and lacrimation were observed in Group 1. Mean mast cell density in cells/mm2, infiltrating the subconjunctival tissue was significantly high in Group 1 (allergy group, 23.17±7.46, p<0.0001 when compared to Group 2 (5.58±3.12. There was no increase in eosinophil and lymphocyte counts as well as vascular intensity in the subconjunctival tissue in any group. Dis cus si on: The murine model developed is similar to the human allergic conjunctivitis both clinically and histopathologically and can be used as a template for future studies

  4. sirt1-null mice develop an autoimmune-like condition

    International Nuclear Information System (INIS)

    Sequeira, Jedon; Boily, Gino; Bazinet, Stephanie; Saliba, Sarah; He Xiaohong; Jardine, Karen; Kennedy, Christopher; Staines, William; Rousseaux, Colin; Mueller, Rudi; McBurney, Michael W.

    2008-01-01

    The sirt1 gene encodes a protein deacetylase with a broad spectrum of reported substrates. Mice carrying null alleles for sirt1 are viable on outbred genetic backgrounds so we have examined them in detail to identify the biological processes that are dependent on SIRT1. Sera from adult sirt1-null mice contain antibodies that react with nuclear antigens and immune complexes become deposited in the livers and kidneys of these animals. Some of the sirt1-null animals develop a disease resembling diabetes insipidus when they approach 2 years of age although the relationship to the autoimmunity remains unclear. We interpret these observations as consistent with a role for SIRT1 in sustaining normal immune function and in this way delaying the onset of autoimmune disease

  5. Risk factors for atopic dermatitis in infants at high risk of allergy : the PIAMA study

    NARCIS (Netherlands)

    Kerkhof, M; Koopman, LP; van Strien, RT; Wijga, A; Smit, HA; Aalberse, RC; Neijens, HJ; Brunekreef, B; Postma, DS; Gerritsen, J

    2003-01-01

    Background It has been suggested that the period immediately after birth is a sensitive period for the development of atopic disease. Objective We investigated whether birth characteristics and environmental factors are associated with the development of atopic dermatitis in the first year of life.

  6. Risk factors for atopic dermatitis in infants at high risk of allergy: the PIAMA study

    NARCIS (Netherlands)

    Kerkhof, M.; Koopman, L. P.; van Strien, R. T.; Wijga, A.; Smit, H. A.; Aalberse, R. C.; Neijens, H. J.; Brunekreef, B.; Postma, D. S.; Gerritsen, J.

    2003-01-01

    It has been suggested that the period immediately after birth is a sensitive period for the development of atopic disease. We investigated whether birth characteristics and environmental factors are associated with the development of atopic dermatitis in the first year of life. Seventy-six children

  7. Development of mice without Cip/Kip CDK inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Tateishi, Yuki; Matsumoto, Akinobu; Kanie, Tomoharu [Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582 (Japan); CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan); Hara, Eiji [Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Nakayama, Keiko [Department of Developmental Genetics, Center for Translational and Advanced Animal Research, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 (Japan); Nakayama, Keiichi I., E-mail: nakayak1@bioreg.kyushu-u.ac.jp [Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582 (Japan); CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Mice lacking Cip/Kip CKIs (p21, p27, and p57) survive until embryonic day 13.5. Black-Right-Pointing-Pointer Proliferation of MEFs lacking all three Cip/Kip CKIs appears unexpectedly normal. Black-Right-Pointing-Pointer CDK2 kinase activity of the triple mutant MEFs is increased in G0 phase. -- Abstract: Timely exit of cells from the cell cycle is essential for proper cell differentiation during embryogenesis. Cyclin-dependent kinase (CDK) inhibitors (CKIs) of the Cip/Kip family (p21, p27, and p57) are negative regulators of cell cycle progression and are thought to be essential for development. However, the extent of functional redundancy among Cip/Kip family members has remained largely unknown. We have now generated mice that lack all three Cip/Kip CKIs (TKO mice) and compared them with those lacking each possible pair of these proteins (DKO mice). We found that the TKO embryos develop normally until midgestation but die around embryonic day (E) 13.5, slightly earlier than p27/p57 DKO embryos. The TKO embryos manifested morphological abnormalities as well as increased rates of cell proliferation and apoptosis in the placenta and lens that were essentially indistinguishable from those of p27/p57 DKO mice. Unexpectedly, the proliferation rate and cell cycle profile of mouse embryonic fibroblasts (MEFs) lacking all three Cip/Kip CKIs did not differ substantially from those of control MEFs. The abundance and kinase activity of CDK2 were markedly increased, whereas CDK4 activity and cyclin D1 abundance were decreased, in both p27/p57 DKO and TKO MEFs during progression from G{sub 0} to S phase compared with those in control MEFs. The extents of the increase in CDK2 activity and the decrease in CDK4 activity and cyclin D1 abundance were greater in TKO MEFs than in p27/p57 DKO MEFs. These results suggest that p27 and p57 play an essential role in mouse development after midgestation, and that p21 plays only an auxiliary role in

  8. Atopic Dermatitis (Eczema): An Appraisal

    Science.gov (United States)

    Hudson, Arthur L.

    1962-01-01

    Atopic (spontaneous) allergies and nonatopic (induced) allergies are often confused. The meaning of these terms is definite, but the occurrence of either (in a given individual) may depend upon his autonomic nervous system control. The evidence that allergens produce the cutaneous changes in atopic dermatitis is flimsy, and neurodermatitis would be a more appropriate term since the entity falls into that pattern of skin changes. Treatment carried out, from infancy sometimes to old age, consists of careful management of the patient in the physical and emotional spheres, avoidance of external irritation and the use of a multiplicity of anti-pruritic, anti-inflammatory and sedative agents. PMID:13955448

  9. Mice null for the deubiquitinase USP18 spontaneously develop leiomyosarcomas

    International Nuclear Information System (INIS)

    Chinyengetere, Fadzai; Sekula, David J.; Lu, Yun; Giustini, Andrew J.; Sanglikar, Aarti; Kawakami, Masanori; Ma, Tian; Burkett, Sandra S.; Eisenberg, Burton L.; Wells, Wendy A.; Hoopes, Paul J.; Demicco, Elizabeth G.; Lazar, Alexander J; Torres, Keila E.; Memoli, Vincent; Freemantle, Sarah J.; Dmitrovsky, Ethan

    2015-01-01

    USP18 (ubiquitin-specific protease 18) removes ubiquitin-like modifier interferon stimulated gene 15 (ISG15) from conjugated proteins. USP18 null mice in a FVB/N background develop tumors as early as 2 months of age. These tumors are leiomyosarcomas and thus represent a new murine model for this disease. Heterozygous USP18 +/− FVB/N mice were bred to generate wild-type, heterozygous and homozygous cohorts. Tumors were characterized immunohistochemically and two cell lines were derived from independent tumors. Cell lines were karyotyped and their responses to restoration of USP18 activity assessed. Drug testing and tumorigenic assays were also performed. USP18 immunohistochemical staining in a large series of human leiomyosacomas was examined. USP18 −/− FVB/N mice spontaneously develop tumors predominantly on the back of the neck with most tumors evident between 6–12 months (80 % penetrance). Immunohistochemical characterization of the tumors confirmed they were leiomyosarcomas, which originate from smooth muscle. Restoration of USP18 activity in sarcoma-derived cell lines did not reduce anchorage dependent or independent growth or xenograft tumor formation demonstrating that these cells no longer require USP18 suppression for tumorigenesis. Karyotyping revealed that both tumor-derived cell lines were aneuploid with extra copies of chromosomes 3 and 15. Chromosome 15 contains the Myc locus and MYC is also amplified in human leiomyosarcomas. MYC protein levels were elevated in both murine leiomyosarcoma cell lines. Stabilized P53 protein was detected in a subset of these murine tumors, another feature of human leiomyosarcomas. Immunohistochemical analyses of USP18 in human leiomyosarcomas revealed a range of staining intensities with the highest USP18 expression in normal vascular smooth muscle. USP18 tissue array analysis of primary leiomyosarcomas from 89 patients with a clinical database revealed cases with reduced USP18 levels had a significantly

  10. Early-life risk factors for occurrence of atopic dermatitis during the first year.

    Science.gov (United States)

    Sugiyama, Mikio; Arakawa, Hirokazu; Ozawa, Kiyoshi; Mizuno, Takahisa; Mochizuki, Hiroyuki; Tokuyama, Kenichi; Morikawa, Akihiro

    2007-03-01

    In a prospective birth cohort study, we sought to identify perinatal predictors of the occurrence of atopic dermatitis in the first year of life. Associations of family history, infection during pregnancy, cord blood cytokine concentrations, and skin function parameters with atopic dermatitis were analyzed. Stratum corneum hydration was measured with an impedance meter until 5 days after delivery and again at 1 month. Complete data were obtained for 213 infants, including 27 diagnosed by a physician as having atopic dermatitis during their first year and 26 diagnosed as having infantile eczema during their first month. The risk of atopic dermatitis during the first year of life was related to maternal atopic dermatitis, lower concentrations of macrophage inflammatory protein-1beta in cord blood, and greater skin moisture in the surface and stratum corneum of the forehead and cheek at 1 month of age but not to viral or bacterial infection during pregnancy or breastfeeding. Paternal hay fever was associated negatively with the development of atopic dermatitis. High concentrations of interleukin-5, interleukin-17, and macrophage chemotactic protein-1 and only surface moisture in the cheek were associated with greater risk of infantile eczema in the first month. The association of atopic dermatitis in infancy with reduced neonatal macrophage inflammatory protein-1beta levels suggests a link with immature immune responses at birth. Stratum corneum barrier disruption in atopic dermatitis may involve impairment of cutaneous adaptation to extrauterine life. The majority of risk factors had different effects on infant eczema and atopic dermatitis, indicating different causes.

  11. Effect of healthcare associated infections and broad spectrum antibiotic use in newborn period on development of asthma, allergic rhinitis and atopic dermatitis in early childhood

    Directory of Open Access Journals (Sweden)

    Hacer Yapicioglu Yildizdas

    2017-03-01

    Full Text Available Purpose: The iam of this study was to investigate the effect of healthcare associated infections (HAIs and broad spectrum antibiotic use in newborn period on asthma, allergic rhinitis and atopic dermatitis. Material and Methods: Seventy three children treated for HAIs in newborn period in Neonatal Intesive Care Unitin a 6 years period, and their 41 siblings who were healthy in newborn period were included in the study. Parents answered a detailed questionnaire, children were examined and complete blood count, serum total Ig E and specific Ig E levels were studied. Results: Ventilator associated pneumonia was observed in 32 (45.2%, blood stream infection in 28 (38.4% and clinic sepsis in 12 (16.4% of 73 children with HAIs. Asthma was significantly higher in HAIs group compared to sibling group (32.9% vs. 4.9, whereas there was no significant difference in allergic rhinitis (4.1% vs.2.4% and atopic dermatitis (6.8% vs. 0% among groups. When non-allergic 85 subjects and allergic 29 children compared, children who had been hospitalised and treated with broad-spectrum antibiotics in newborn period were almost 11.5 times as likely to have an allergic disease. Conclusion: Asthma was significantly higher in HAI group, and allergic disease risk seems to increase in children treated with broad-spectrum antibiotics for HAIs in newborn period. [Cukurova Med J 2017; 42(1.000: 132-139

  12. Pro-inflammatory interleukins in middle ear effusions from atopic and non-atopic children with chronic otitis media with effusion.

    Science.gov (United States)

    Zielnik-Jurkiewicz, Beata; Stankiewicz-Szymczak, Wanda

    2016-06-01

    Chronic otitis media with effusion (OME) is associated with irreversible changes in the middle ear, sometimes leading to hearing loss and abnormal language development in children. While the pathogenesis of OME is not fully understood, inflammatory and allergic factors are thought to be involved. The study aimed to investigate the role of cytokines in the local development of chronic OME, and assess differences in the cytokine profiles between atopic and non-atopic children. 84 atopic and non-atopic children with chronic OME (mean age of 6 years 7 months) were studied. Age-matched children with hypertrophy of the adenoids and Eustachian tube dysfunction served as the control group. The number of past acute otitis media (AOM) episodes, their age, and the type of effusion were recorded for all children. Pro-inflammatory cytokine concentrations (TNF-α, IL-1β, IL-6 and IL-8) were determined and the presence of pathogenic bacteria in the patients' effusions was examined. High concentrations of TNF-α, IL-1β, IL-6 and IL-8 were found in the effusions in all children with chronic OME, with the highest levels observed in the non-atopic group. The atopic group showed persistently high IL-1β levels, while in the non-atopic children, IL-1β and TNF-α levels positively correlated with the patient's age and the number of past AOM episodes. Pathogenic bacteria were more frequently isolated from effusions in non-atopic children. In both atopic and non-atopic children, pro-inflammatory cytokines are found at high concentrations. This argues in favor of instituting anti-inflammatory management for treating OME, regardless of atopy.

  13. Psychological interventions in atopic dermatitis

    NARCIS (Netherlands)

    Jaspers, Jan P. C.

    Atopic dermatitis is a common skin disease that places a large burden on patients and their families. It is characterized as a chronic inflammatory disease that most commonly begins in early childhood. Prevalence is high, especially in children, and increases in western countries. Originally,

  14. Recall Bias in Childhood Atopic Diseases Among Adults in The Odense Adolescence Cohort Study

    DEFF Research Database (Denmark)

    Mortz, Charlotte G; Andersen, Klaus E; Bindslev-Jensen, Carsten

    2015-01-01

    Atopic dermatitis (AD) is a common disease in childhood and an important risk factor for the later development of other atopic diseases. Many publications on childhood AD use questionnaires based on information obtained in adulthood, which introduce the possibility of recall bias. In a prospectiv...

  15. Atopic dermatitis in children: prospects of using innovation products as an external therapy

    Directory of Open Access Journals (Sweden)

    M. M. Tlish

    2016-01-01

    Full Text Available Goal of the research: to determine the efficacy of a new line of Atopic cosmetic products for skin care in children suffering from atopic dermatitis. Materials and methods: The study involved three groups of 15 children aged 3-12 suffering from atopic dermatitis in each group. Subjects from Group 1 were treated with Atopic Soothing Cream, from Group 2 with Atopic Soothing Stick Cream and from Group 3 with Atopic Everyday Care Cream. Different inclusion and exclusion criteria were developed for each group, and the algorithm for the product application and efficacy criteria were determined. According to recommendations, Atopic Soothing Cream and Atopic Soothing Stick Cream were applied to clean and dry skin in the morning and in the evening for the study period of 14 days. The patients’ skin condition was assessed prior to the study and on Day 14 of the therapy; the assessment covered parameters necessary for calculating the SCORAD Index. Atopic Everyday Care Cream was applied to clean and dry skin in the morning and in the evening for 28 days. The patients’ skin condition was assessed prior to the study and on Days 14 and 28 of the therapy including the SCORAD Index and assessments of the skin hydration level of the epidermal corneous layer and transepidermal waster loss (TEWL using the DermaLabCombo CORTEX device. According to the study results, the line of Atopic cosmetic products fully complies with the properties specified by the manufacturer, reliably improves the skin condition in children suffering from atopic dermatitis, has no irritant or sensitizing effect, and can be recommended for the complex treatment and rehabilitation of patients suffering from the pathology.

  16. HSP: bystander antigen in atopic diseases?

    Directory of Open Access Journals (Sweden)

    Joost A Aalberse

    2012-05-01

    Full Text Available Over the last years insight in the complex interactions between innate and adaptive immunity in the regulation of an inflammatory response has increased enormously. This has revived the interest in stress proteins; proteins that are expressed during cell stress. As these proteins can attract and trigger an immunological response they can act as important mediators in this interaction. In this respect, of special interest are proteins that may act as modulators of both innate and adaptive immunity. Heat shock proteins (HSPs are stress proteins that have these, and more, characteristics. More than two decades of studies on HSPs has revealed that they are part of intrinsic, natural mechanisms that steer inflammation. This has provoked comprehensive explorations of the role of HSPs in various human inflammatory diseases.Most studies have focused on classical autoimmune diseases. This has led to the development of clinical studies with HSPs that have shown promise in Phase II/III clinical trials. Remarkably, only very little is yet known of the role of HSPs in atopic diseases. In allergic disease a number of studies have investigated the possibility that allergen-specific regulatory T cell (Treg function is defective in individuals with allergic diseases. This raises the question whether methods can be identified to improve the Treg repertoire. Studies from other inflammatory diseases have suggested HSPs may have such a beneficial effect on the T cell repertoire. Based on the immune mechanisms of atopic diseases, in this review we will argue that, as in other human inflammatory conditions, understanding immunity to HSPs is likely also relevant for atopic diseases. Specifically, we will discuss why certain HSPs such as HSP60 connect the immune response to environmental antigens with regulation of the inflammatory response.Thus they provide a molecular link that may eventually even help to better understand the immune pathological basis of the hygiene

  17. Multifactorial skin barrier deficiency and atopic dermatitis: Essential topics to prevent the atopic march.

    Science.gov (United States)

    Egawa, Gyohei; Kabashima, Kenji

    2016-08-01

    Atopic dermatitis (AD) is the most common inflammatory skin disease in the industrialized world and has multiple causes. Over the past decade, data from both experimental models and patients have highlighted the primary pathogenic role of skin barrier deficiency in patients with AD. Increased access of environmental agents into the skin results in chronic inflammation and contributes to the systemic "atopic (allergic) march." In addition, persistent skin inflammation further attenuates skin barrier function, resulting in a positive feedback loop between the skin epithelium and the immune system that drives pathology. Understanding the mechanisms of skin barrier maintenance is essential for improving management of AD and limiting downstream atopic manifestations. In this article we review the latest developments in our understanding of the pathomechanisms of skin barrier deficiency, with a particular focus on the formation of the stratum corneum, the outermost layer of the skin, which contributes significantly to skin barrier function. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. [A guide for education programs in atopic dermatitis].

    Science.gov (United States)

    Barbarot, S; Gagnayre, R; Bernier, C; Chavigny, J-M; Chiaverini, C; Lacour, J-P; Dupre-Goetghebeur, D; Misery, L; Piram, M; Cuny, J-F; Dega, H; Stalder, J-F

    2007-02-01

    Education about therapy applies to many chronic diseases. The aim is to improve patient management through the development of certain skills by patients themselves. Atopic dermatitis is an area amenable to the development of therapeutic education. The purpose of this study was to define the skills required for management of atopic dermatitis suitable for therapeutic education and to bring together these skills in a handbook suitable for use. Thirty caregivers were involved in the drafting of the handbook (dermatologists, a doctor specialising in therapeutic education, a psychologist and nurses), each of whom has experience of therapeutic education in atopic dermatitis. Four age groups were selected (under 5 years, 6 to 10 years, pre-teens/adults, parents of children aged under 5 years). For each age group, different levels of skill were identified for patients or parents of children and suitable learning methods were selected. Skills were classed according to 3 levels: (i) knowledge about the disease, treatments, triggering factors, (ii) knowledge about provision of care by patients or their parents, (iii) knowledge in terms of explaining the disease and treatment methods to family, and knowing who to contact and when. Finally, a 10-question evaluation guide was drawn up. In this paper we report the method of production and content of the handbook of skills for atopic dermatitis patients. The aim is not to impose all skills listed in this work on patients but rather to provide caregivers with a complete handbook covering therapeutic education. The book is intended for patients with moderate to severe forms of atopic dermatitis currently in therapeutic failure. It may be used by anyone treating such patients, whether doctors, nurses or psychologists, depending on the items chosen. It is intended for use as a support for the elaboration, diffusion and evaluation of a therapeutic education programme for atopic dermatitis.

  19. Abnormal megakaryocyte development and platelet function in Nbeal2(-/-) mice.

    Science.gov (United States)

    Kahr, Walter H A; Lo, Richard W; Li, Ling; Pluthero, Fred G; Christensen, Hilary; Ni, Ran; Vaezzadeh, Nima; Hawkins, Cynthia E; Weyrich, Andrew S; Di Paola, Jorge; Landolt-Marticorena, Carolina; Gross, Peter L

    2013-11-07

    Gray platelet syndrome (GPS) is an inherited bleeding disorder associated with macrothrombocytopenia and α-granule-deficient platelets. GPS has been linked to loss of function mutations in NEABL2 (neurobeachin-like 2), and we describe here a murine GPS model, the Nbeal2(-/-) mouse. As in GPS, Nbeal2(-/-) mice exhibit splenomegaly, macrothrombocytopenia, and a deficiency of platelet α-granules and their cargo, including von Willebrand factor (VWF), thrombospondin-1, and platelet factor 4. The platelet α-granule membrane protein P-selectin is expressed at 48% of wild-type levels and externalized upon platelet activation. The presence of P-selectin and normal levels of VPS33B and VPS16B in Nbeal2(-/-) platelets suggests that NBEAL2 acts independently of VPS33B/VPS16B at a later stage of α-granule biogenesis. Impaired Nbeal2(-/-) platelet function was shown by flow cytometry, platelet aggregometry, bleeding assays, and intravital imaging of laser-induced arterial thrombus formation. Microscopic analysis detected marked abnormalities in Nbeal2(-/-) bone marrow megakaryocytes, which when cultured showed delayed maturation, decreased survival, decreased ploidy, and developmental abnormalities, including abnormal extracellular distribution of VWF. Our results confirm that α-granule secretion plays a significant role in platelet function, and they also indicate that abnormal α-granule formation in Nbeal2(-/-) mice has deleterious effects on megakaryocyte survival, development, and platelet production.

  20. The history of atopic dermatitis.

    Science.gov (United States)

    Kramer, Owen N; Strom, Mark A; Ladizinski, Barry; Lio, Peter A

    Fred Wise (1881-1950) and Marion Sulzberger (1895-1983) are often credited with introducing the term atopic dermatitis to dermatology in 1933. This definition was based on atopy, a term first created by Arthur Coca (1875-1959) and Robert Cooke (1880-1960) in 1923, when they recognized an association between allergic rhinitis and asthma. Despite its recent introduction into our medical lexicon, historical precursors of atopic dermatitis date back to at least as early as 69-140 ce. In this contribution, we highlight both the prominent individuals credited with shaping the disorder into our current interpretation and the suspected historical precursors of this disease and reported treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. First observation of the decay $\\bar{B}$$0\\atop{s}$ →; D$+\\atop{s}$ K and measurement of B($\\bar{B}$$0\\atop{s}$ →; D$±\\atop{s}$K)/Br($\\bar{B}$$0\\atop{s}$→; D$+\\atop{s}$ π-)

    Energy Technology Data Exchange (ETDEWEB)

    Muelmenstaedt, Johannes [Univ. of California, Berkeley, CA (United States)

    2007-01-01

    We present the first observation of the decay $\\bar{B}$$0\\atop{s}$ → D$+\\atop{s}$ K and measure the relative branching fraction of $\\bar{B}$$0\\atop{s}$ → D$+\\atop{s}$ K to $\\bar{B}$$0\\atop{s}$ → D$+\\atop{s}$ π-. The measurement of the relative branching fraction is performed by applying a fit in invariant mass and specific ionization to 1.2 fb-1 of Ds(φπ)X data collected with the CDF II detector in pp collisions at √s = 1.96 TeV at the Fermilab Tevatron collider. We measure B($\\bar{B}$$0\\atop{s}$ → D± s K∓¢/B($\\bar{B}$$0\\atop{s}$ → D$+\\atop{s}$ π-) = 0.107±0.019(stat)±0.008(sys). The statistical significance of the $\\bar{B}$$0\\atop{s}$ → D$+\\atop{s}$ K signal is 7.9σ. To cross-check our analysis method, we also measure B($\\bar{B0}$ → D+K-)/B($\\bar{B0}$ → D+π-) and B($\\bar{B0}$ → D*+K-)/B($\\bar{B0}$ → D*+π-) and verify that our results are in agreement with the world average.

  2. Prebiotics and probiotics: the prevention and reduction in severity of atopic dermatitis in children.

    Science.gov (United States)

    Foolad, N; Armstrong, A W

    2014-06-01

    The purpose of this review was to identify whether supplementation with prebiotics and/or probiotics help prevent the development or reduce the severity of atopic dermatitis in children less than three years of age. Since 1997, immunostimulatory supplements, such as prebiotics and probiotics, have been investigated. Various supplementations include probiotics (single strain or mix), probiotics with formula, probiotics mix with prebiotics, and prebiotics. In this narrative review, we examined 13 key articles on prebiotics and/or probiotics, and their effects on infant atopic dermatitis. Among the selected studies, a total of 3,023 participants received supplements or placebo. Eight out of the 13 (61.5%) studies reported a significant effect on the prevention of atopic dermatitis after supplementation with probiotics and/or prebiotics. Five out of the 13 (38.5%) studies indicated significant reduction in the severity of atopic dermatitis after supplementation. Based on the available studies, supplementation with certain probiotics (Lactobacillus rhamnosus GG) appears to be an effective approach for the prevention and reduction in severity of atopic dermatitis. A mix of specific probiotic strains prevented atopic dermatitis among infants. Based on studies with prebiotics, there was a long-term reduction in the incidence of atopic dermatitis. Supplementation with prebiotics and probiotics appears useful for the reduction in the severity of atopic dermatitis. Additional interventional studies exploring prebiotics and probiotics are imperative before recommendations can be made.

  3. Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting.

    Science.gov (United States)

    Schmitt, Jochen; Spuls, Phyllis; Boers, Maarten; Thomas, Kim; Chalmers, Joanne; Roekevisch, Evelien; Schram, Mandy; Allsopp, Richard; Aoki, Valeria; Apfelbacher, Christian; Bruijnzeel-Koomen, Carla; Bruin-Weller, Marjolein; Charman, Carolyn; Cohen, Arnon; Dohil, Magdalene; Flohr, Carsten; Furue, Masutaka; Gieler, Uwe; Hooft, Lotty; Humphreys, Rosemary; Ishii, Henrique Akira; Katayama, Ichiro; Kouwenhoven, Willem; Langan, Sinéad; Lewis-Jones, Sue; Merhand, Stephanie; Murota, Hiroyuki; Murrell, Dedee F; Nankervis, Helen; Ohya, Yukihiro; Oranje, Arnold; Otsuka, Hiromi; Paul, Carle; Rosenbluth, Yael; Saeki, Hidehisa; Schuttelaar, Marie-Louise; Stalder, Jean-Francois; Svensson, Ake; Takaoka, Roberto; Wahlgren, Carl-Fredrik; Weidinger, Stephan; Wollenberg, Andreas; Williams, Hywel

    2012-09-01

    The use of nonstandardized and inadequately validated outcome measures in atopic eczema trials is a major obstacle to practising evidence-based dermatology. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international multiprofessional group dedicated to atopic eczema outcomes research. In June 2011, the HOME initiative conducted a consensus study involving 43 individuals from 10 countries, representing different stakeholders (patients, clinicians, methodologists, pharmaceutical industry) to determine core outcome domains for atopic eczema trials, to define quality criteria for atopic eczema outcome measures and to prioritize topics for atopic eczema outcomes research. Delegates were given evidence-based information, followed by structured group discussion and anonymous consensus voting. Consensus was achieved to include clinical signs, symptoms, long-term control of flares and quality of life into the core set of outcome domains for atopic eczema trials. The HOME initiative strongly recommends including and reporting these core outcome domains as primary or secondary endpoints in all future atopic eczema trials. Measures of these core outcome domains need to be valid, sensitive to change and feasible. Prioritized topics of the HOME initiative are the identification/development of the most appropriate instruments for the four core outcome domains. HOME is open to anyone with an interest in atopic eczema outcomes research. © 2012 John Wiley & Sons A/S.

  4. Alcohol during pregnancy and atopic dermatitis in the offspring

    DEFF Research Database (Denmark)

    Linneberg, A; Petersen, Janne; Grønbaek, M

    2004-01-01

    BACKGROUND: There is evidence that antenatal factors play a role in the development of atopic dermatitis (AD). However, little is known about the effects of maternal lifestyle factors during pregnancy on the risk of AD in the offspring. OBJECTIVE: To investigate the effect of alcohol consumption...

  5. Evaluation of self-esteem and dermatological quality of life in adolescents with atopic dermatitis

    Directory of Open Access Journals (Sweden)

    İjlal Erturan

    2013-03-01

    Full Text Available Background and Design: Atopic dermatitis is a chronic, inflammatory skin disease characterized by itchy skin lesions. Since adolescents are intensely interested in their physical appearance, chronic skin diseases in this period can adversely affect the development of self esteem. Atopic dermatitis is a skin disease that affects the appearance and there is an heightened attention to the body image in adolescence which is an important period of time in the development of self-esteem. Therefore, we aimed to investigate self-esteem and dermatological quality of life in adolescents with atopic dermatitis. Materials and Methods: Thirty-three patients with atopic dermatitis and 33 healthy controls were included in the study. The Piers-Harris Children’s Self-Concept Scale and the Children’s Dermatology Life Quality Index (CDLQI were used for determining self-esteem and quality of life. The Scoring of Atopic Dermatitis (SCORAD Index was used to assess the severity of atopic dermatitis. Results: It was found that patient group had lower self-esteem than healthy controls according to the Piers-Harris Children’s Self-Concept Scale. A statistically significant difference was observed in happiness/satisfaction and anxiety subscale scores between the patients and healthy controls while there was no significant difference between the other sub-scale scores. Mean value of dermatological quality of life in patients with atopic dermatitis was significantly lower than in healthy controls. A moderate negative correlation was found between self-esteem and CDLQI scores among adolescents with atopic dermatitis. Discussion: This study results have shown that self-esteem and dermatological quality of life were adversely affected in adolescents with atopic dermatitis irrespective of gender. These patients should be examined psychiatrically besides dermatological examination and treatment. We suggest that improvement will be observed in self-esteem and quality of

  6. Treating pediatric atopic dermatitis: current perspectives

    Directory of Open Access Journals (Sweden)

    Dimitriades VR

    2015-06-01

    Full Text Available Victoria R Dimitriades, Elizabeth Wisner Division of Allergy/Immunology, Department of Pediatrics, Louisiana State University Health Sciences Center, Children's Hospital of New Orleans, New Orleans, LA, USAAbstract: Atopic dermatitis (AD is a chronic, inflammatory skin condition which affects millions of people worldwide. It is most commonly seen in children but may also progress into adulthood. Management of this complex disease requires a multi-pronged approach which can address the myriad of issues which underscore its development. Avoidance of triggering factors is imperative in establishing consistent control of skin irritation while daily moisturization can be very effective in skin barrier repair and maintenance. Judicious use of anti-inflammatory medications has been shown to make a significant impact on both treatment as well as prevention of disease. Unfortunately, pruritus, a key feature of AD, has proven much harder to control. Finally, awareness of the risks of colonization and infection in patients with AD should be incorporated into their surveillance and management plans. While our understanding has progressed greatly regarding this disease, further research is still needed regarding future directions for both treatment and prevention. Keywords: atopic dermatitis, eczema, treatment, corticosteroids, antipruritic

  7. Japanese guidelines for atopic dermatitis 2017

    Directory of Open Access Journals (Sweden)

    Ichiro Katayama

    2017-04-01

    The basics of treatment discussed in this guideline are based on the “Guidelines for the Treatment of Atopic Dermatitis 2008” prepared by the Health and Labour Sciences Research and the “Guidelines for the Management of Atopic Dermatitis 2015 (ADGL2015” prepared by the Atopic Dermatitis Guidelines Advisory Committee, Japanese Society of Allergology in principle. The guidelines for the treatment of atopic dermatitis are summarized in the “Japanese Guideline for the Diagnosis and Treatment of Allergic Disease 2016” together with those for other allergic diseases.

  8. Japanese Guideline for Atopic Dermatitis 2014

    Directory of Open Access Journals (Sweden)

    Ichiro Katayama

    2014-01-01

    The basics of treatment discussed in this guideline are based on the "Guidelines for the Treatment of Atopic Dermatitis 2008" prepared by the Health and Labour Sciences Research and the "Guidelines for the Management of Atopic Dermatitis 2012 (ADGL2012" prepared by the Atopic Dermatitis Guidelines Advisory Committee, Japanese Society of Allergology in principle. The guidelines for the treatment of atopic dermatitis are summarized in the "Japanese Guideline for the Diagnosis and Treatment of Allergic Disease 2013" together with those for other allergic diseases.

  9. Th17-cells in atopic dermatitis stimulate orthodontic root resorption.

    Science.gov (United States)

    Yamada, K; Yamaguchi, M; Asano, M; Fujita, S; Kobayashi, R; Kasai, K

    2013-10-01

    The aim of this study was to investigate how atopic dermatitis (AD) contributes to root resorption during orthodontic tooth movement. Atopic dermatitis model mice and wild-type mice were subjected to an excessive orthodontic force (OF) to induce movement of the upper first molars. The expression levels of the tartrate-resistant acid phosphatase (TRAP), IL-17, IL-6, and RANKL proteins were determined in the periodontal ligament (PDL) by an immunohistochemical analysis. Furthermore, the effects of the compression force on co-cultures of CD4(+) cells from AD patients or healthy individuals and human PDL cells were investigated with regard to the levels of secretion and mRNA expression of IL-17, IL-6, RANKL, and osteoprotegerin. The immunoreactivities for TRAP, IL-17, IL-6, and RANKL in the AD group were found to be significantly increased. The double immunofluorescence analysis for IL-17/CD4 detected immunoreaction. The secretion of IL-17, IL-6, and RANKL, and the mRNA levels of IL-6 and RANKL in the AD patients were increased compared with those in healthy individuals. Th17 cells may therefore be associated with the deterioration of root resorption of AD mice, and may explain why AD patients are more susceptible to root resorption than healthy individuals when an excessive OF is applied. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Importance of genetic factors in the etiology of atopic dermatitis: a twin study

    DEFF Research Database (Denmark)

    Thomsen, Simon F; Ulrik, Charlotte S; Kyvik, Kirsten O

    2007-01-01

    The susceptibility to develop atopic dermatitis can be attributed both to genetic and environmental causes. We estimated the relative impact of genetic and environmental factors in the etiology of atopic dermatitis in a population-based sample of twins. From the birth cohorts of 1953-1982 who wer...... dermatitis both in male and female patients (p = 0.98). The estimates were adjusted for age. The susceptibility to develop atopic dermatitis is attributable to mainly genetic differences between people. However, differences in environmental exposures also are of importance......The susceptibility to develop atopic dermatitis can be attributed both to genetic and environmental causes. We estimated the relative impact of genetic and environmental factors in the etiology of atopic dermatitis in a population-based sample of twins. From the birth cohorts of 1953-1982 who were...... with a threefold increased risk among cotwins of an affected fraternal twin, relative to the general population. Genes accounted for 82% and nonshared environmental factors accounted for 18% of the individual susceptibility to develop atopic dermatitis. The same genes contributed to the susceptibility to atopic...

  11. Breastfeeding and atopic eczema in Japanese infants: The Osaka Maternal and Child Health Study.

    Science.gov (United States)

    Miyake, Yoshihiro; Tanaka, Keiko; Sasaki, Satoshi; Kiyohara, Chikako; Ohya, Yukihiro; Fukushima, Wakaba; Yokoyama, Tetsuji; Hirota, Yoshio

    2009-05-01

    Epidemiological studies associated with breastfeeding have provided conflicting results about whether it is preventive or a risk factor for atopic eczema in children. The current prospective study investigated the relationship between breastfeeding and the risk of atopic eczema in Japan. A birth cohort of 763 infants was followed. The first survey during pregnancy and the second survey between 2 and 9 months postpartum collected information on potential confounding factors and atopic eczema status. Data on breastfeeding and symptoms of atopic eczema were obtained from questionnaires in the third survey from 16 to 24 months postpartum. The following variables were a priori selected as potential confounders: maternal age, maternal and paternal history of asthma, atopic eczema, and allergic rhinitis, indoor domestic pets (cats, dogs, birds, or hamsters), family income, maternal and paternal education, maternal smoking during pregnancy, baby's sex, baby's birth weight, baby's older siblings, household smoking in the same room as the infant, and time of delivery before the third survey. In the third survey, 142 infants (18.6%) were revealed to have developed atopic eczema based on criteria of the International Study of Asthma and Allergies in Childhood. In an overall analysis, neither exclusive nor partial breastfeeding was significantly related to the risk of atopic eczema. After excluding 64 infants identified with suspected atopic eczema in the second survey, both exclusive breastfeeding for 4 months or more and partial breastfeeding for 6 months or more were independently associated with an increased risk of atopic eczema only among infants with no parental history of allergic disorders [multivariate odds ratios were 2.41 (95% confidence interval, 1.10-5.55) and 3.39 (95% confidence interval, 1.20-12.36), respectively]. The authors found that, overall, neither exclusive nor partial breastfeeding had a strong impact on the risk of atopic eczema. However, a parental

  12. Topical cyclosporine for atopic keratoconjunctivitis.

    Science.gov (United States)

    González-López, Julio J; López-Alcalde, Jesús; Morcillo Laiz, Rafael; Fernández Buenaga, Roberto; Rebolleda Fernández, Gema

    2012-09-12

    Atopic keratoconjunctivitis (AKC) is a chronic ocular surface non-infectious inflammatory condition that atopic dermatitis patients may suffer at any time point in the course of their dermatologic disease and is independent of its degree of severity. AKC is usually not self resolving and it poses a higher risk of corneal injuries and severe sequelae. Management of AKC should prevent or treat corneal damage. Although topical corticosteroids remain the standard treatment for patients with AKC, prolonged use may lead to complications. Topical cyclosporine A (CsA) may improve AKC signs and symptoms, and be used as a corticosteroid sparing agent. To determine the efficacy and gather evidence on safety from randomised controlled trials (RCTs) of topical CsA in patients with AKC. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1946 to July 2012), EMBASE (January 1980 to July 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2012), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to July 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en), the IFPMA Clinical Trials Portal (http://clinicaltrials.ifpma.org/no_cache/en/myportal/index.htm) and Web of Science Conference Proceedings Citation Index- Science (CPCI-S). We did not use any date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 9 July 2012. We also handsearched the following conference proceedings: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, International Council of Opthalmology and Societas

  13. Acquisition of vernal and atopic keratoconjunctivitis after bone marrow transplantation.

    Science.gov (United States)

    Tabbara, Khalid F; Nassar, Amr; Ahmed, Syed Osman; Al Mohareb, Fahad; Aljurf, Mahmoud

    2008-09-01

    Vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) result from genetic and environmental factors. We present patients who had no history of atopic disorders before bone marrow transplantation (BMT) and who seem to have acquired VKC or AKC from their donors, who had atopic disorders. Observational case series. The patients in this study were part of a cohort of patients who had undergone allogeneic hemapoietic stem cell transplantation (HSCT) from January 1997 through December 2007. Of 621 HSCT recipients, four recipients who were free of allergic disorders acquired VKC or AKC from their afflicted donors after HSCT. Each patient underwent complete ophthalmologic examination, determination of the total serum immunoglobulin (Ig) E, and conjunctival scrapings. Four (0.64%) of 621 patients who had undergone HSCT acquired VKC or AKC after BMT. The donors had VKC or atopic dermatitis. In addition, in two of these four patients, asthma developed. One patient had elevated total serum IgE. Conjunctival scrapings of all four patients revealed the presence of eosinophils. One patient had concurrent graft-versus-host disease. VKC and AKC are systemic allergic disorders characterized by local ocular manifestations. This report suggests the possibility of the acquisition of VKC or AKC after BMT by adoptive transfer.

  14. Allergic contact dermatitis: A comparison between atopic and non-atopic individuals

    International Nuclear Information System (INIS)

    Rani, Z.; Hussain, I.; Haroon, T.S.

    2002-01-01

    Objective: To determine the prevalence of ACD in atopics in comparison to non-atopics in our community. Design: Cross sectional study. Place and Duration of Study: Departments of Dermatology, King Edward Medical College/Mayo Hospital, Lahore, from May 1998 to July 1999. Subjects and Methods: Two hundred and fifty patients, 34 with past or present atopic dermatitis (Group I), 88 with personal or familial atopy (Group II) and 128 non-atopic with contact dermatitis (Group III) were subjected to patch testing with European standard series. The results were interpreted according to International Contact Dermatitis Research Group guidelines. Results: Positive reactions were seen in 50%, 70.4% and 67.8% of patients in the respective groups (p>0.05). Conclusion: Our results suggest that atopics are equally affected with contact dermatitis as compared with non-atopics and recalcitrant cases of atopic dermatitis should be patch tested to find out aggravating factors. (author)

  15. Effect of radiophosphorus on hematology of mice during postnatal development

    International Nuclear Information System (INIS)

    Malhotra, N.; Srivastava, P.N.

    1975-01-01

    Swiss albino mice at different stages of their postnatal development (one day, one week, two weeks,three weeks, four weeks age groups) were injected intraperitoneally with radioactive phosphorus (P-32) at the dose of 1.0 μCi/g body weight and studied for their hematological response at weekly intervals up to six weeks of age when they attain sexual maturity. In all the treated groups in both males and females, the radiation injury was evident after injection of radioactive phosphorus. Animals showed reduction in blood cell number and fall in hemoglobin and hematocrit levels after injection. Reparation was also evident in the animals after some lapse of time following P-32 administration. Morphological changes in different white blood cells were not observed. No radiation sickness symptoms were observed in any of the treated groups during the study. There was no radiation mortality. The radiation damage to blood forming organs was moderate. It was observed that the females showed a greater hematological damage than the males. (orig.) [de

  16. Ghrelin treatment prevents development of activity based anorexia in mice.

    Science.gov (United States)

    Legrand, Romain; Lucas, Nicolas; Breton, Jonathan; Azhar, Saïda; do Rego, Jean-Claude; Déchelotte, Pierre; Coëffier, Moïse; Fetissov, Sergueï O

    2016-06-01

    Stimulation of feeding is necessary for treatment of pathological conditions of chronic malnutrition due to anorexia. Ghrelin, a hunger hormone, is one of the candidate for pharmacological treatments of anorexia, but because of its instability in plasma has limited efficacy. We previously showed that plasmatic IgG protect ghrelin from degradation and that IgG from obese subjects and mice may increase ghrelin׳s orexigenic effect. In this study we tested if ghrelin alone or combined with IgG may improve feeding in chronically food-restricted mice with or without physical activity-based anorexia (ABA) induced by free access to a running wheel. Mice received a single daily intraperitoneal injection of ghrelin (1nM) together or not with total IgG (1nM) from obese ob/ob or lean mice before access to food during 8 days of 3h/day feeding time. We found that both ghrelin and ghrelin combined with IgG from obese, but not lean mice, prevented ABA, however, they were not able to diminish body weight loss. Physical activity was lower during the feeding period and was increased shortly after feeding in mice receiving ghrelin together with IgG from obese mice. In food-restricted mice without ABA, ghrelin treatments did not have significant effects on food intake. Thus, this study supports pharmacological use of ghrelin or ghrelin combined with IgG from obese animals for treatment of anorexia accompanied by elevated physical activity. The utility of combining ghrelin with protective IgG should be further determined in animal models of anorexia with unrestricted access to food. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  17. Contact allergy in children with atopic dermatitis

    DEFF Research Database (Denmark)

    Simonsen, A B; Johansen, J D; Deleuran, M

    2017-01-01

    The importance of contact allergy in children with atopic dermatitis is frequently debated. Previously, patients with atopic dermatitis were believed to have a reduced ability to produce a type IV immunological response. However, this belief has been challenged and authors have highlighted the risk...... of underestimating and overlooking allergic contact dermatitis in children with atopic dermatitis. Several studies have been published aiming to shed light on this important question but results are contradictory. To provide an overview of the existing knowledge, we systematically reviewed studies that report...... frequencies of positive patch test reactions in children with atopic dermatitis. We identified 436 manuscripts of which 31 met the inclusion criteria. Although the literature is conflicting, it is evident that contact allergy is a common problem in children with atopic dermatitis....

  18. THE ROLE OF EPIDERMAL BARRIER IMPAIRMENTS IN ATOPIC DERMATITIS: MODERN CONCEPTS OF DISEASE PATHOGENESIS

    Directory of Open Access Journals (Sweden)

    Nikolay N. Murashkin

    2018-01-01

    Full Text Available Atopic dermatitis is a common chronic inflammatory skin disease characterized by a recurring course and progressive decrease in the quality of life. Recent studies in this area demonstrate the multifaceted pathogenesis of atopic dermatitis. Interaction of such factors as epidermal dysfunction, immune system disorders, and the consequences of genetic mutations contributes not only to the development of the disease but also to its progression and chronic course. The article presents various components of the etiopathogenesis of atopic dermatitis, describes the role of lipids, thereby the new therapeutic targets are revealed to specialists.

  19. THE CASE OF HERPETIC ECZEMA IN A CHILD WITH CONGENITAL ICHTHYOSIS AND ATOPIC DERMATITIS

    Directory of Open Access Journals (Sweden)

    A. S. Stadnikova

    2017-01-01

    Full Text Available The case of the development of herpetic eczema (Kaposi's eczema is presented against the background of congenital ichthyosis and atopic dermatitis. It has been shown that the presence of atopic diseases such as allergic rhinitis and pollinosis, sensitization to many common allergens, and a positive family history of atopic dermatitis are factors of a more severe course of Kaposi's eczema. The presented clinical observation of the child with Kaposi's eczema showed that early diagnosis and timely initiated complex  therapy are the determining factors of a favorable prognosis of the disease.

  20. Lithosphere erosion atop mantle plumes

    Science.gov (United States)

    Agrusta, R.; Arcay, D.; Tommasi, A.

    2012-12-01

    Mantle plumes are traditionally proposed to play an important role in lithosphere erosion. Seismic images beneath Hawaii and Cape Verde show a lithosphere-asthenosphere-boundary (LAB) up to 50 km shallower than the surroundings. However, numerical models show that unless the plate is stationary the thermo-mechanical erosion of the lithosphere does not exceed 30 km. We use 2D petrological-thermo-mechanical numerical models based on a finite-difference method on a staggered grid and marker in cell method to study the role of partial melting on the plume-lithosphere interaction. A homogeneous peridotite composition with a Newtonian temperature- and pressure-dependent viscosity is used to simulate both the plate and the convective mantle. A constant velocity, ranging from 5 to 12.5 cm/yr, is imposed at the top of the plate. Plumes are created by imposing a thermal anomaly of 150 to 350 K on a 50 km wide domain at the base of the model (700 km depth); the plate right above the thermal anomaly is 40 Myr old. Partial melting is modeled using batch-melting solidus and liquidus in anhydrous conditions. We model the progressive depletion of peridotite and its effect on partial melting by assuming that the melting degree only strictly increases through time. Melt is accumulated until a porosity threshold is reached and the melt in excess is then extracted. The rheology of the partially molten peridotite is determined using viscous constitutive relationship based on a contiguity model, which enables to take into account the effects of grain-scale melt distribution. Above a threshold of 1%, melt is instantaneously extracted. The density varies as a function of partial melting degree and extraction. Besides, we analyze the kinematics of the plume as it impacts a moving plate, the dynamics of time-dependent small-scale convection (SSC) instabilities developing in the low-viscosity layer formed by spreading of hot plume material at the lithosphere base, and the resulting thermal

  1. First measurement of the B$0\\atop{2}$ semileptonic branching ratio to an orbitally excited d$**\\atop{s}$ state, Br(B$0\\atop{2}$ → D$-\\atop{s1}$(2536)μ+vX)

    Energy Technology Data Exchange (ETDEWEB)

    Rieger, Jason [Indiana Univ., Bloomington, IN (United States)

    2007-12-08

    In a data sample of approximately 1.3 fb-1 collected with the D0 detector between 2002 and 2006, the orbitally excited charm state D$±\\atop{s1}$(2536)has been observed with a measured mass of 2535.7 ± 0.6(stat) ± 0.5(syst) MeV/c2 via the decay mode B$0\\atop{s}$ → D$-\\atop{s1}$(2536)μ+vX followed by D$±\\atop{s1}$(2536) → DK$0\\atop{S}$. By normalizing to the known branching ratio Br($\\bar{b}$ → D*- μ+vX) and to the number of reconstructed D* mesons with an associated identified muon, a first-ever measurement is made of the product branching ratio ($\\bar{b}$ →} D$-\\atop{s1}$(2536)μ+vX) • Br(D$-\\atop{s1}$ → D*-K$0\\atop{S}$). Assuming that D$-\\atop{s1}$(2536) production in semileptonic decay is entirely from B$0\\atop{s}$, an extraction of the semileptonic branching ratio Br(B$0\\atop{s}$ → D$-\\atop{s1}$(2536)μ+vX) is made. Comparisons are made with theoretical expectations.

  2. Development of resistance to serotonin-induced itch in bile duct ligated mice.

    Science.gov (United States)

    Ostadhadi, Sattar; Haddadi, Nazgol-Sadat; Foroutan, Arash; Azimi, Ehsan; Elmariah, Sarina; Dehpour, Ahmad-Reza

    2017-06-01

    Cholestatic itch can be severe and significantly impair the quality of life of patients. The serotonin system is implicated in cholestatic itch; however, the pruritogenic properties of serotonin have not been evaluated in cholestatic mice. Here, we investigated the serotonin-induced itch in cholestatic mice which was induced by bile duct ligation (BDL). Serotonin, sertraline or saline were administered intradermally to the rostral back area in BDL and sham operated (SHAM) mice, and the scratching behaviour was videotaped for 1 hour. Bile duct ligated mice had significantly increased scratching responses to saline injection on the seventh day after surgery. Additionally, serotonin or sertraline significantly induced scratching behaviour in BDL mice compared to saline at day 7 after surgery, while it did not induce itch at day 5. The scratching behaviour induced by serotonin or sertraline was significantly less in BDL mice compared to SHAM mice. Likewise, the locomotor activity of BDL or SHAM mice was not significantly different from unoperated (UNOP) mice on the fifth and seventh day, suggesting that the scratching behaviour was not affected by motor dysfunctions. Our data suggest that despite the potentiation of evoked itch, a resistance to serotonin-induced itch is developed in cholestatic mice. © 2017 John Wiley & Sons Australia, Ltd.

  3. Psychosocial adjustment in preschool children with atopic eczema.

    Science.gov (United States)

    Daud, L R; Garralda, M E; David, T J

    1993-12-01

    Atopic eczema is a chronic skin disorder that is most common in early childhood, an important stage in the child's social and emotional development. The psychiatric adjustment and mother-child attachment in 30 preschool children with severe atopic eczema was compared with 20 matched controls. Patients with eczema had a significant increase in behaviour symptoms, 7/30 (23%) v 1/20 (5%); with significant excess of dependency/clinginess, 15/30 (50%) v 2/20 (10%); fearfulness, 12/30 (40%) v 2/20 (10%); and sleep difficulty, 19/30 (63%) v 9/20 (45%), but there was no significant difference between the two groups in the security of attachments, 25/29 (86%) v 14/20 (70%). Significantly fewer mothers of children with atopic eczema were in outside employment, 8/29 (27%) v 13/20 (65%), or felt supported socially, 10/29 (34%) v 13/20 (65%). Significantly more of them, 9/30 (30%) v 1/20 (5%), felt particularly stressed in relation to their parenting and less efficient in their disciplining of the affected child. In spite of this and at variance with earlier reports in the literature, they did not display negative attitudes towards their child. On the contrary mothers had a positive empathic attitude towards the child, 7/14 (50%) v 2/16 (12%). Child behaviour problems, 7/14 (50%) v 2/16 (12%), and maternal distress, 12/14 (85%) v 5/16 (31%), were significantly more common in the more severely affected children. Minor behaviour problems and parenting distress are important features of severe atopic eczema in early childhood but atopic eczema does not lead to insecurity of the mother-child attachment.

  4. Use of textiles in atopic dermatitis: care of atopic dermatitis.

    Science.gov (United States)

    Ricci, G; Patrizi, A; Bellini, F; Medri, M

    2006-01-01

    Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease which usually starts during the first years of life. In the management of AD, the correct approach requires a combination of multiple treatments to identify and eliminate trigger factors, and to improve the alteration of the skin barrier. In this article we try to explain the importance of skin care in the management of AD in relation to the use of textiles: they may be useful to improve disrupted skin but they are also a possible cause of triggering or worsening the lesions. Garments are in direct contact with the skin all day long, and for this reason it is important to carefully choose suitable fabrics in atopic subjects who have disrupted skin. Owing to their hygienic properties fabrics produced from natural fibres are preferential. Wool fibres are frequently used in human clothes but are irritant in direct contact with the skin. Wool fibre has frequently been shown to be irritant to the skin of atopic patients, and for this reason wool intolerance was included as a minor criterion in the diagnostic criteria of AD by Hanifin and Rajka in 1980. Cotton is the most commonly used textile for patients with AD; it has wide acceptability as clothing material because of its natural abundance and inherent properties like good folding endurance, better conduction of heat, easy dyeability and excellent moisture absorption. Silk fabrics help to maintain the body temperature by reducing the excessive sweating and moisture loss that can worsen xerosis. However, the type of silk fabric generally used for clothes is not particularly useful in the care and dressing of children with AD since it reduces transpiration and may cause discomfort when in direct contact with the skin. A new type of silk fabric made of transpiring and slightly elastic woven silk is now commercially available (Microair Dermasilk) and may be used for the skin care of children with AD. The presence of increased bacterial colonization

  5. Maternal mental health and social support: effect on childhood atopic and non-atopic asthma symptoms.

    Science.gov (United States)

    Marques dos Santos, Letícia; Neves dos Santos, Darci; Rodrigues, Laura Cunha; Barreto, Maurício Lima

    2012-11-01

    Atopic and non-atopic asthma have distinct risk factors and immunological mechanisms, and few studies differentiate between the impacts of psychosocial factors on the prevalence of these disease phenotypes. The authors aimed to identify whether the effect of maternal mental health on prevalence of asthma symptoms differs between atopic and non-atopic children, taking into account family social support. This is a cross-sectional study of 1013 children participating in the Social Change Allergy and Asthma in Latin America project. Psychosocial data were collected through a household survey utilising Self-Reporting Questionnaire and Medical Outcome Study Social Support Scale. Socioeconomic and wheezing information was obtained through the questionnaire of the International Study of Allergy and Asthma in Childhood, and level of allergen-specific IgE was measured to identify atopy. Polytomous logistic regression was used to estimate the association between maternal mental health, social support and atopic and non-atopic wheezing. Effect modification was evaluated through stratified polytomous regression according to social support level. Maternal mental disorder had the same impact on atopic and non-atopic wheezing, even after adjusting for confounding variables. Affective, material and informational supports had protective effects on non-atopic asthma, and there is some evidence that social supports may act as a buffer for the impact of maternal mental disorder on non-atopic wheezing. Poor maternal mental health is positively associated with wheezing, independent of whether asthma is atopic or non-atopic, but perception of high levels of social support appears to buffer this relationship in non-atopic wheezers only.

  6. Mice deficient in PAPP-A show resistance to the development of diabetic nephropathy.

    Science.gov (United States)

    Mader, Jessica R; Resch, Zachary T; McLean, Gary R; Mikkelsen, Jakob H; Oxvig, Claus; Marler, Ronald J; Conover, Cheryl A

    2013-10-01

    We investigated pregnancy-associated plasma protein-A (PAPP-A) in diabetic nephropathy. Normal human kidney showed specific staining for PAPP-A in glomeruli, and this staining was markedly increased in diabetic kidney. To assess the possible contribution of PAPP-A in the development of diabetic nephropathy, we induced diabetes with streptozotocin in 14-month-old WT and Papp-A knockout (KO) mice. Renal histopathology was evaluated after 4 months of stable hyperglycemia. Kidneys from diabetic WT mice showed multiple abnormalities including thickening of Bowman's capsule (100% of mice), increased glomerular size (80% of mice), tubule dilation (80% of mice), and mononuclear cell infiltration (90% of mice). Kidneys of age-matched non-diabetic WT mice had similar evidence of tubule dilation and mononuclear cell infiltration to those of diabetic WT mice, indicating that these changes were predominantly age-related. However, thickened Bowman's capsule and increased glomerular size appeared specific for the experimental diabetes. Kidneys from diabetic Papp-A KO mice had significantly reduced or no evidence of changes in Bowman's capsule thickening and glomerular size. There was also a shift to larger mesangial area and increased macrophage staining in diabetic WT mice compared with Papp-A KO mice. In summary, elevated PAPP-A expression in glomeruli is associated with diabetic nephropathy in humans and absence of PAPP-A is associated with resistance to the development of indicators of diabetic nephropathy in mice. These data suggest PAPP-A as a potential therapeutic target for diabetic nephropathy.

  7. The dual role of scavenger receptor class A in development of diabetes in autoimmune NOD mice.

    Directory of Open Access Journals (Sweden)

    Mami Shimizu

    Full Text Available Human type 1 diabetes is an autoimmune disease that results from the autoreactive destruction of pancreatic β cells by T cells. Antigen presenting cells including dendritic cells and macrophages are required to activate and suppress antigen-specific T cells. It has been suggested that antigen uptake from live cells by dendritic cells via scavenger receptor class A (SR-A may be important. However, the role of SR-A in autoimmune disease is unknown. In this study, SR-A-/- nonobese diabetic (NOD mice showed significant attenuation of insulitis, lower levels of insulin autoantibodies, and suppression of diabetes development compared with NOD mice. We also found that diabetes progression in SR-A-/- NOD mice treated with low-dose polyinosinic-polycytidylic acid (poly(I:C was significantly accelerated compared with that in disease-resistant NOD mice treated with low-dose poly(I:C. In addition, injection of high-dose poly(I: C to mimic an acute RNA virus infection significantly accelerated diabetes development in young SR-A-/- NOD mice compared with untreated SR-A-/- NOD mice. Pathogenic cells including CD4+CD25+ activated T cells were increased more in SR-A-/- NOD mice treated with poly(I:C than in untreated SR-A-/- NOD mice. These results suggested that viral infection might accelerate diabetes development even in diabetes-resistant subjects. In conclusion, our studies demonstrated that diabetes progression was suppressed in SR-A-/- NOD mice and that acceleration of diabetes development could be induced in young mice by poly(I:C treatment even in SR-A-/- NOD mice. These results suggest that SR-A on antigen presenting cells such as dendritic cells may play an unfavorable role in the steady state and a protective role in a mild infection. Our findings imply that SR-A may be an important target for improving therapeutic strategies for type 1 diabetes.

  8. Association of atopic diseases and attention-deficit/hyperactivity disorder : A systematic review and meta-analyses

    NARCIS (Netherlands)

    van der Schans, Jurjen; Cicek, Rukiye; de Vries, Tjalling W.; Hak, Eelko; Hoekstra, Pieter J.

    Over the last decades, the hypothesis has been raised that an atopic response could lead to the development of attention-deficit/hyperactivity disorder (ADHD). This study systematically reviews the observational cross-sectional and longitudinal studies that assessed the association between atopic

  9. Difficult to control atopic dermatitis

    Science.gov (United States)

    2013-01-01

    Difficult to control atopic dermatitis (AD) presents a therapeutic challenge and often requires combinations of topical and systemic treatment. Anti-inflammatory treatment of severe AD most commonly includes topical glucocorticosteroids and topical calcineurin antagonists used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, the topical calcineurin inhibitors tacrolimus and pimecrolimus are preferred in certain locations. Systemic anti-inflammatory treatment is an option for severe refractory cases. Microbial colonization and superinfection contribute to disease exacerbation and thus justify additional antimicrobial / antiseptic treatment. Systemic antihistamines (H1) may relieve pruritus but do not have sufficient effect on eczema. Adjuvant therapy includes UV irradiation preferably of UVA1 wavelength. “Eczema school” educational programs have been proven to be helpful. PMID:23663504

  10. Defining intrinsic vs. extrinsic atopic dermatitis.

    Science.gov (United States)

    Karimkhani, Chante; Silverberg, Jonathan I; Dellavalle, Robert P

    2015-06-16

    Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition characterized by eczematous lesions, i.e. ill-demarcated erythematous patches and plaques. AD is commonly associated with elevated immunoglobulin E (IgE) and atopic disorders, such as asthma, hay fever, and food allergies. Rackemann and Mallory were some of the first to distinguish between asthma based on the presence ("extrinsic") or absence ("intrinsic") of allergy. This distinction has subsequently been applied to AD based on the presence ("extrinsic") or absence ("intrinsic") of increased IgE and atopic disease. Although the distinction between intrinsic and extrinsic AD is widely used, it remains controversial.

  11. Rate of lens lesion development and the age of mice at time of irradiation

    International Nuclear Information System (INIS)

    Gajewski, A.K.; Majewska, K.; Slowikowska, M.G.

    1976-01-01

    The rate of lens lesion development has been studied in mice irradiated at different age ranging from one day up to one year old mice. The time needed for the first appearance of lens lesion was shortest in groups of mice irradiated at the age of one, two and three days of life, and longest in groups of mice irradiated at the age of 5 days, 1 week and 2 weeks of life. The time needed for the first appearance of lens lesion for mice irradiated between the third week and one year of life was constant. It was longer than for mice irradiated during the first three days of life and shorter than for mice irradiated at 5 up to 14 days of life. In all but one irradiated groups the age at which the first lens lesion occurred differed significantly from the age at which the first senile changes occurred in the lens of control mice. The one exception was the group of mice irradiated at the age of one year. (author)

  12. Sox9 induces testis development in XX transgenic mice

    NARCIS (Netherlands)

    Vidal, V. P.; Chaboissier, M. C.; de rooij, D. G.; Schedl, A.

    2001-01-01

    Mutations in SOX9 are associated with male-to-female sex reversal in humans. To analyze Sox9 function during sex determination, we ectopically expressed this gene in XX gonads. Here, we show that Sox9 is sufficient to induce testis formation in mice, indicating that it can substitute for the

  13. Management of Children with Atopic Dermatitis: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Masoud Golpour

    2016-11-01

    Full Text Available Context Atopic dermatitis is a chronic, relapsing skin disorder that affects all ages including infancy and childhood. There are many proved and unproved treatments for atopic dermatitis. Evidence Acquisition Data sources of this narrative review included studies about pediatric atopic dermatitis with the following keywords, pediatric, atopic dermatitis, immunity, acute, chronic, pruritic inflammatory skin disorder, infancy, childhood, diagnosis, management and treatment. All of the articles were written in English language with full text on management or treatment. Results Innate and adaptive immune system involved atopic dermatitis. Major characteristics of atopic dermatitis include pruritus, chronic or relapsing lesions and personal or family history of atopic disease. There is no specific treatment for atopic dermatitis. The treatment included rehydration, emollients, topical steroid, calcineurin inhibitors and immunosuppressant. Crisaborole topical ointment, a PDE4 anti-inflammatory topical agent (phase three of the research could be effective in atopic dermatitis. Conclusions Avoidance from trigger factors and emollients are basic treatments of atopic dermatitis.

  14. IMMUNOLOGIC CHARACTERISTICS OF BREAST MILK IN WOMEN, WHO HAVE CHILDREN WITH ATOPIC DERMATITIS

    Directory of Open Access Journals (Sweden)

    M.Yu. Belitskaya

    2008-01-01

    Full Text Available 100 mothers and children in couple were observed in this trial. All children had atopic dermatitis, developed against breast feeding. Analysis of immunologic characteristics of breast milk in 53 women showed a presence of allergencpecific Ide and Igg antybodies and common Ige in it. The level of those characteristics was lower if mothers were consistent with diet with goat's milk «amaltea».Key words: children, atopic dermatitis, breast feeding, dietotherapy.

  15. TAP1-deficiency does not alter atherosclerosis development in Apoe-/- mice.

    Directory of Open Access Journals (Sweden)

    Daniel Kolbus

    Full Text Available Antigen presenting cells (APC have the ability to present both extra-cellular and intra-cellular antigens via MHC class I molecules to CD8(+ T cells. The cross presentation of extra-cellular antigens is reduced in mice with deficient Antigen Peptide Transporter 1 (TAP1-dependent MHC class I antigen presentation, and these mice are characterized by a diminished CD8(+ T cell population. We have recently reported an increased activation of CD8(+ T cells in hypercholesterolemic Apoe(-/- mice. Therefore, this study included TAP1-deficient Apoe(-/- mice (Apoe(-/-Tap1(-/- to test the atherogenicity of CD8(+ T cells and TAP1-dependent cross presentation in a hypercholesterolemic environment. As expected the CD8(+ T cell numbers were low in Apoe(-/-Tap1(-/- mice in comparison to Apoe(-/- mice, constituting ~1% of the lymphocyte population. In spite of this there were no differences in the extent of atherosclerosis as assessed by en face Oil Red O staining of the aorta and cross-sections of the aortic root between Apoe(-/-Tap1(-/- and Apoe(-/- mice. Moreover, no differences were detected in lesion infiltration of macrophages or CD3(+ T cells in Apoe(-/-Tap1(-/- compared to Apoe(-/- mice. The CD3(+CD4(+ T cell fraction was increased in Apoe(-/-Tap1(-/- mice, suggesting a compensation for the decreased CD8(+ T cell population. Interestingly, the fraction of CD8(+ effector memory T cells was increased but this appeared to have little impact on the atherosclerosis development.In conclusion, Apoe(-/-Tap1(-/- mice develop atherosclerosis equal to Apoe(-/- mice, indicating a minor role for CD8(+ T cells and TAP1-dependent antigen presentation in the disease process.

  16. FTO is a relevant factor for the development of the metabolic syndrome in mice.

    Directory of Open Access Journals (Sweden)

    Kathrin Ikels

    Full Text Available The metabolic syndrome is a worldwide problem mainly caused by obesity. FTO was found to be a obesity-risk gene in humans and FTO deficiency in mice led to reduction in adipose tissue. Thus, FTO is an important factor for the development of obesity. Leptin-deficient mice are a well characterized model for analysing the metabolic syndrome. To determine the relevance of FTO for the development of the metabolic syndrome we analysed different parameters in combined homozygous deficient mice (Lep(ob/ob;Fto(-/-. Lep(ob/ob;Fto(-/- mice showed an improvement in analysed hallmarks of the metabolic syndrome in comparison to leptin-deficient mice wild type or heterozygous for Fto. Lep(ob/ob;Fto(-/- mice did not develop hyperglycaemia and showed an improved glucose tolerance. Furthermore, extension of beta-cell mass was prevented in Lep(ob/ob;Fto(-/-mice and accumulation of ectopic fat in the liver was reduced. In conclusion this study demonstrates that FTO deficiency has a protective effect not only on the development of obesity but also on the metabolic syndrome. Thus, FTO plays an important role in the development of metabolic disorders and is an interesting target for therapeutic agents.

  17. Development of Murine Cyp3a Knockout Chimeric Mice with Humanized Liver.

    Science.gov (United States)

    Kato, Kota; Ohbuchi, Masato; Hamamura, Satoko; Ohshita, Hiroki; Kazuki, Yasuhiro; Oshimura, Mitsuo; Sato, Koya; Nakada, Naoyuki; Kawamura, Akio; Usui, Takashi; Kamimura, Hidetaka; Tateno, Chise

    2015-08-01

    We developed murine CYP3A knockout ko chimeric mice with humanized liver expressing human P450S similar to those in humans and whose livers and small intestines do not express murine CYP3A this: approach may overcome effects of residual mouse metabolic enzymes like Cyp3a in conventional chimeric mice with humanized liver, such as PXB-mice [urokinase plasminogen activator/severe combined immunodeficiency (uPA/SCID) mice repopulated with over 70% human hepatocytes] to improve the prediction of drug metabolism and pharmacokinetics in humans. After human hepatocytes were transplanted into Cyp3a KO/uPA/SCID host mice, human albumin levels logarithmically increased until approximately 60 days after transplantation, findings similar to those in PXB-mice. Quantitative real-time-polymerase chain reaction analyses showed that hepatic human P450s, UGTs, SULTs, and transporters mRNA expression levels in Cyp3a KO chimeric mice were also similar to those in PXB-mice and confirmed the absence of Cyp3a11 mRNA expression in mouse liver and intestine. Findings for midazolam and triazolam metabolic activities in liver microsomes were comparable between Cyp3a KO chimeric mice and PXB-mice. In contrast, these activities in the intestine of Cyp3a KO chimeric mice were attenuated compared with PXB-mice. Owing to the knockout of murine Cyp3a, hepatic Cyp2b10 and 2c55 mRNA levels in Cyp3a KO/uPA/SCID mice (without hepatocyte transplants) were 8.4- and 61-fold upregulated compared with PXB-mice, respectively. However, human hepatocyte transplantation successfully restored Cyp2b10 level nearly fully and Cyp2c55 level partly (still 13-fold upregulated) compared with those in PXB-mice. Intestinal Cyp2b10 and 2c55 were also repressed by human hepatocyte transplantation in Cyp3a KO chimeric mice. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  18. Alcohol Intake During Pregnancy and Offspring's Atopic Eczema Risk.

    Science.gov (United States)

    Wada, Keiko; Konishi, Kie; Tamura, Takashi; Shiraki, Makoto; Iwasa, Shinichi; Nagata, Chisato

    2016-05-01

    Although alcohol consumption has been suggested to have an effect on the immune system, it is unknown whether alcohol consumption has a role in developing allergic diseases. We aimed to examine the associations of total alcohol intake during pregnancy with the risks of childhood asthma and atopic eczema in a birth cohort in Japan. Pregnant women were recruited at a maternal clinic from May 2000 to October 2001. The children who were born to these mothers were followed until November 2007. Total alcohol intake, including alcohol as a cooking ingredient, was assessed using 5-day dietary records. Mother reports of physician-diagnosed asthma and atopic eczema were annually obtained from the questionnaires. Asthma assessed by the American Thoracic Society Division of Lung Diseases questionnaire and atopic eczema assessed by International Study of Asthma and Allergies in Childhood questions were also obtained in 2007. A total of 350 children participated in the follow-up survey. Maternal total alcohol intake during pregnancy was associated with increased risks of atopic eczema before age 3. The positive association with atopic eczema was also observed when it was defined as before age 5. In the high versus the low tertile of maternal total alcohol intake, the estimated hazard ratios (HRs) of child's eczema were 1.90 (95% CI: 0.96 to 3.76) before age 3 and 1.74 (95% CI: 0.93 to 3.24) before age 5, respectively. The estimated HRs of child's asthma before age 3 was 1.61 (95% CI: 0.70 to 3.69) in the high versus the low of maternal total alcohol intake and 2.11 (95% CI: 0.93 to 4.81) among children having drinking mothers versus nondrinking mothers in pregnancy, although maternal alcohol intake during pregnancy was not significantly associated with the risk of asthma before age 5. Alcohol consumption during pregnancy might have an effect on developing atopic eczema in offspring. Copyright © 2016 by the Research Society on Alcoholism.

  19. Lack of association between the MTHFR (C677T) polymorphism and atopic disease

    DEFF Research Database (Denmark)

    Thuesen, Betina Heinsbaek; Husemoen, Lise Lotte Nystrup; Fenger, Mogens

    2009-01-01

    -tetrahydrofolate reductase (MTHFR)-gene, a well-known marker of impaired folate metabolism. OBJECTIVES: The aim of this study was to investigate the association between the MTHFR (C677T) polymorphism and different outcome variables of asthma and atopic disease. METHODS: This study was a population-based study of 1189...... and symptoms of allergy and asthma. In addition, participants were genotyped for the MTHFR (C677T) polymorphism. RESULTS: None of the examined outcomes were significantly associated with the MTHFR (C677T) polymorphism. CONCLUSIONS: The results of this study using detailed objective markers of atopic disease do......BACKGROUND: Impaired folate metabolism has been suggested as a potential risk factor for the development of asthma and atopic disease. However, there have been conflicting reports on the potential association between atopic disease and a common polymorphism of the methylene...

  20. IMMUNOLOGICAL MARKERS OF UNCONTROLLED ATOPIC BRONCHIAL ASTHMA IN CHILDREN

    Directory of Open Access Journals (Sweden)

    M. V. Smolnikova

    2017-01-01

    Full Text Available Bronchial asthma is a prevalent chronic allergic disease of lungs at early ages. A priority  task in allergology  is to search  biological  markers  related  to uncontrolled atopic  bronchial asthma. Cytokines fulfill their distinct function in pathogenesis of atopic  bronchial asthma, participating at the initiation, development and persistence of allergic inflammation in airways, causing different  variations of clinical course of the disease (with  respect  to its acuteness, severity, frequency of exacerbations. The  present  work has studied  indices  of cellular  and  humoral links of immunity, as well as levels of some  pro and  anti-inflammatory cytokines in peripheral blood serum (IL-4, IL-10, IL-2 and TNFα, aiming to determine potential markers of uncontrolled atopic bronchial asthma in children. A group of Caucasian (European children was involved into the research: Cohort 1, moderate atopic  bronchial asthma with controlled course during the last 3 months (n = 59; Cohort 2, severe/moderate-severe atopic bronchial asthma with uncontrolled course of the disease within last 3 months (n = 51,  Cohort 3 – control, practically healthy  children without signs of atopy  (n = 33. All the  children included in the group with atopic  bronchial asthma underwent regular mono/combined basic therapy  at high/ intermediate therapeutic doses.  We performed a comparative analysis  of cell  population indices  reflecting certain cellular  immunity links,  and  determined significantly  lower  levels of CD3+   lymphocytes, as well as decrease in relative  and  absolute  contents of CD4+  and  CD8+  cells in the  cohort with  uncontrolled course of atopic  bronchial asthma, as compared with controlled-course cohort. When  evaluating concentrations  of cytokines in peripheral blood serum of the patients with controlled and uncontrolled atopic  bronchial asthma, we revealed  significantly  higher

  1. Atopic dermatitis: tacrolimus vs. topical corticosteroid use

    African Journals Online (AJOL)

    Atopic dermatitis (AD) is an inflammatory skin disease that is characterised .... effective in the treatment of AD.5. Although ..... original steroid preparations,20 the cost-effectiveness of ... Topical corticosteroids [homepage on the Internet]. c2010.

  2. Atopic eczema and the filaggrin story.

    Science.gov (United States)

    Brown, Sara J; Irvine, Alan D

    2008-06-01

    The discovery that null mutations in the filaggrin gene (FLG) are associated with atopic eczema represents the single most significant breakthrough in understanding the genetic basis of this complex disorder. The association has been replicated in multiple independent studies during the past 2 years with the use of various methodologies, from populations in Europe, the United States, and Japan. Filaggrin plays a key role in epidermal barrier function, and its association with atopic eczema emphasizes the importance of barrier dysfunction in eczema pathogenesis. This review aims to summarize the current state of knowledge regarding the role of FLG mutations in ichthyosis vulgaris, atopic eczema, and other skin disorders, with an emphasis on potential clinical applications. Further research is needed to clarify the precise role of filaggrin in skin and systemic atopic disease, to pave the way for novel therapeutic interventions.

  3. Current understanding in pathogenesis of atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Tess McPherson

    2016-01-01

    Full Text Available There have been advances in our understanding of the complex pathogenesis of atopic eczema over the past few decades. This article examines the multiple factors which are implicated in this process.

  4. Tetranectin Knockout Mice Develop Features of Parkinson Disease

    Directory of Open Access Journals (Sweden)

    Er-song Wang

    2014-07-01

    Full Text Available Background/Aims: Aggregation of insoluble α-synuclein to form Lewy bodies (LBs may contribute to the selective loss of midbrain dopaminergic neurons in Parkinson disease (PD. Lack of robust animal models has impeded elucidation of the molecular mechanisms of LB formation and other critical aspects of PD pathogenesis. Methods: We established a mouse model with targeted deletion of the plasminogen-binding protein tetranectin (TN gene (TN-/- and measured the behavioral and histopathological features of PD. Results: Aged (15-to 20-month-old TN-/- mice displayed motor deficits resembling PD symptoms, including limb rigidity and both slower ambulation (bradykinesia and reduced rearing activity in the open field. In addition, these mice exhibited more numerous α-synuclein-positive LB-like inclusions within the substantia nigra pars compacta (SNc and reduced numbers of SNc dopaminergic neurons than age-matched wild type (WT mice. These pathological changes were also accompanied by loss of dopamine terminals in the dorsal striatum. Conclusion: The TN-/- mouse exhibits several key features of PD and so may be a valuable model for studying LB formation and testing candidate neuroprotective therapies for PD and other synucleinopathies.

  5. The growth and development of Schistosoma mansoni in mice exposed to sublethal doses of radiation

    International Nuclear Information System (INIS)

    Aitken, R.; Wilson, R.A.

    1989-01-01

    The maturation of Schistosoma mansoni was studied in mice exposed to various sublethal doses of radiation. Although the treatment of mice with 500 rads of radiation prior to infection did not alter parasite maturation, doses in excess of 500 rads led to a reduction in worm burden. This could not be attributed to a delay in the arrival of parasites in the hepatic portal system. Worms developing in mice treated with 800 rads commenced egg-laying about 1 wk later than worms in intact mice, and the rate of egg deposition appeared to be lower in irradiated hosts. The data demonstrate that exposure of C57BL/6 mice to doses of radiation in excess of 500 rads impairs their ability to carry infections of S. mansoni. The findings do not support the hypothesis that primary worm burdens in the mouse are controlled by a host immune response

  6. ATOPIC DERMATITIS: NEW ASPECTS OF TREATMENT

    Directory of Open Access Journals (Sweden)

    D. Sh. Macharadze

    2013-01-01

    Full Text Available Atopic dermatitis is a chronic inflammatory cutaneous disease, which demands a prolonged treatment. A modern views on the main approaches to treatment of atopic dermatitis in children and adults are analyzed in this article. The treatment is based on the permanent use of emollients in order to achieve an anti-inflammatory effect — topical calcineurin inhibitors (tacrolimus and pimecrolimus, and short courses (5 days of topical corticosteroids during relapses. For the 10-year period of topical calcineurin inhibitors usage in treatment of atopic dermatitis a great amount of experimental and clinical data have been accumulated. Two the most important changes and additions in the treatment of atopic dermatitis in recent times were related to a new hypothesis of proactive therapy with the use of topical tacrolimus and closing of «black box» warnings, associated to malignization risk due to the long-term usage of topical calcineurin inhibitors. Since atopic dermatitis is characterized by relapsing course, nowadays topical tacrolimus should be considered the most appropriate treatment approach, both in adults and children. The results of investigations confirmed more than 6-times decrease in relapse rate, as well as the significant improvement of quality of life, when the above-mentioned treatment scheme is used, both in children and adults.Key words: children, atopic dermatitis, emollients, treatment, tacrolimus.

  7. SAP Suppresses the Development of Experimental Autoimmune Encephalomyelitis in C57BL6 Mice

    Science.gov (United States)

    Ji, Zhe; Ke, Zun-Ji; Geng, Jian-Guo

    2012-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated disease of the CNS. Serum amyloid P component (SAP) is a highly conserved plasma protein named for its universal presence in amyloid deposits. Here we report SAP transgenic mice had unexpectedly attenuated EAE due to impaired encephalitogenic responses. Following induction with myelin oligodendroglial glycoprotein (MOG) peptide 35–55 in CFA, SAP transgenic mice showed reduced spinal cord inflammation with lower severity of EAE attacks as compared with control C57BL/6 mice. However in SAP-KO mice, the severity of EAE is enhanced. Adoptive transfer of Ag-restimulated T cells from wild-type to SAP transgenic mice or transfer of SAP transgenic Ag-restimulated T cells to control mice induced milder EAE. T cells from MOG-primed SAP transgenic mice showed weak proliferative responses. Furthermore, in SAP transgenic mice, there is little infiltration of CD45-positive cells in the spinal cord. In vitro, SAP suppressed the secretion of IL-2 stimulated by P-selectin, and blocked P-selectin binding to T cells. Moreover, SAP could change the affinity between α4-integrin and T cells. These data suggested that SAP could antagonize the development of the acute phase of inflammation accompanying EAE by modulating the function of P-selectin. PMID:21647172

  8. Deletion of Foxp3+ regulatory T cells in genetically targeted mice supports development of intestinal inflammation

    Directory of Open Access Journals (Sweden)

    Boehm Franziska

    2012-07-01

    Full Text Available Abstract Background Mice lacking Foxp3+ regulatory T (Treg cells develop severe tissue inflammation in lung, skin, and liver with premature death, whereas the intestine remains uninflamed. This study aims to demonstrate the importance of Foxp3+ Treg for the activation of T cells and the development of intestinal inflammation. Methods Foxp3-GFP-DTR (human diphtheria toxin receptor C57BL/6 mice allow elimination of Foxp3+ Treg by treatment with Dx (diphtheria toxin. The influence of Foxp3+ Treg on intestinal inflammation was tested using the CD4+ T-cell transfer colitis model in Rag−/− C57BL/6 mice and the acute DSS-colitis model. Results Continuous depletion of Foxp3+ Treg in Foxp3-GFP-DTR mice led to dramatic weight loss and death of mice by day 28. After 10 days of depletion of Foxp3+ Treg, isolated CD4+ T-cells were activated and produced extensive amounts of IFN-γ, IL-13, and IL-17A. Transfer of total CD4+ T-cells isolated from Foxp3-GFP-DTR mice did not result in any changes of intestinal homeostasis in Rag−/− C57BL/6 mice. However, administration of DTx between days 14 and 18 after T-cell reconstitution, lead to elimination of Foxp3+ Treg and to immediate weight loss due to intestinal inflammation. This pro-inflammatory effect of Foxp3+ Treg depletion consecutively increased inflammatory cytokine production. Further, the depletion of Foxp3+ Treg from Foxp3-GFP-DTR mice increased the severity of acute dSS-colitis accompanied by 80% lethality of Treg-depleted mice. CD4+ effector T-cells from Foxp3+ Treg-depleted mice produced significantly more pro-inflammatory cytokines. Conclusion Intermittent depletion of Foxp3+ Treg aggravates intestinal inflammatory responses demonstrating the importance of Foxp3+ Treg for the balance at the mucosal surface of the intestine.

  9. Mitochondrial DNA mutations in mutator mice confer respiration defects and B-cell lymphoma development.

    Directory of Open Access Journals (Sweden)

    Takayuki Mito

    Full Text Available Mitochondrial DNA (mtDNA mutator mice are proposed to express premature aging phenotypes including kyphosis and hair loss (alopecia due to their carrying a nuclear-encoded mtDNA polymerase with a defective proofreading function, which causes accelerated accumulation of random mutations in mtDNA, resulting in expression of respiration defects. On the contrary, transmitochondrial mito-miceΔ carrying mtDNA with a large-scale deletion mutation (ΔmtDNA also express respiration defects, but not express premature aging phenotypes. Here, we resolved this discrepancy by generating mtDNA mutator mice sharing the same C57BL/6J (B6J nuclear background with that of mito-miceΔ. Expression patterns of premature aging phenotypes are very close, when we compared between homozygous mtDNA mutator mice carrying a B6J nuclear background and selected mito-miceΔ only carrying predominant amounts of ΔmtDNA, in their expression of significant respiration defects, kyphosis, and a short lifespan, but not the alopecia. Therefore, the apparent discrepancy in the presence and absence of premature aging phenotypes in mtDNA mutator mice and mito-miceΔ, respectively, is partly the result of differences in the nuclear background of mtDNA mutator mice and of the broad range of ΔmtDNA proportions of mito-miceΔ used in previous studies. We also provided direct evidence that mtDNA abnormalities in homozygous mtDNA mutator mice are responsible for respiration defects by demonstrating the co-transfer of mtDNA and respiration defects from mtDNA mutator mice into mtDNA-less (ρ(0 mouse cells. Moreover, heterozygous mtDNA mutator mice had a normal lifespan, but frequently developed B-cell lymphoma, suggesting that the mtDNA abnormalities in heterozygous mutator mice are not sufficient to induce a short lifespan and aging phenotypes, but are able to contribute to the B-cell lymphoma development during their prolonged lifespan.

  10. Adverse reactions to food additives in children with atopic symptoms

    DEFF Research Database (Denmark)

    Fuglsang, G.; Madsen, Charlotte Bernhard; Halken, S.

    1994-01-01

    and 335 were subjected to open challenge. A total of 23 children developed positive reactions after the open challenge. Sixteen of these patients accepted the double-blind challenge, and six showed a positive reaction to preservatives (atopic dermatitis, asthma, rhinitis), coloring agents (atopic......, rhinitis, or urticaria. After a 2-week period on an additive-free diet, the children were challenged with the eliminated additives. The food additives investigated were coloring agents, preservatives, citric acid, and flavoring agents. Carbonated ''lemonade'' containing the dissolved additives was used...... for the open challenge. Two doses were used: a low dose and a 10-fold higher dose. Gelatin capsules were used for a double-blind challenge. The children were 4-15 years old, and they were attending an outpatient pediatric clinic for the first time. Of the 379 patients who entered the study, 44 were excluded...

  11. The role of vitamin D in atopic dermatitis.

    Science.gov (United States)

    Dębińska, Anna; Sikorska-Szaflik, Hanna; Urbanik, Magdalena; Boznański, Andrzej

    2015-01-01

    Vitamin D has been suggested to have an important impact on a much wider aspects on human health than calcium homeostasis and mineral metabolism, specifically in the field of human immunology. It has been reported that vitamin D influences the regulation of both innate and adaptive immune systems, which makes the association between vitamin D and allergic diseases a field of interest. Although many studies have sought to determine whether vitamin D has an influence on progression of allergic disease, the impact of vitamin D on atopic dermatitis development and severity remains unclear. In this review, we summarize recent studies relating vitamin D to atopic dermatitis and discuss its possible role in the pathogenesis of allergic skin diseases, emphasizing the need for well-designed, prospective trials on vitamin D supplementation in the context of prevention and treatment for allergic conditions.

  12. CYCLOSPORINE IN TREATMENT OF SEVERE ATOPIC DERMATITIS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    A.A. Alekseeva

    2010-01-01

    Full Text Available Atopic dermatitis (AtD is one of the most widespread types of allergic lesions of skin in children. Increase of severe types of AtD with lesion of big parts of skin, high frequency of exacerbations, presence of concomitant atopic diseases, and inefficiency of standard therapeutic approaches, torpid clinical course and early development of disability, causes an anxiety. Present standard approaches can be ineffective in children with severe clinical course of AtD and they are not able to prevent progression of disease, development of severe exacerbations and child’s disability. One of therapeutic alternatives for these patients is treatment with immunosuppressive agents. The article describes questions of treatment with cyclosporine in systemic therapy of severe resistant forms of AtD in children. Author discusses effectiveness and safety of a drug, formulated rules of treatment of severe AtD with cyclosporine. Key words: children, atopic dermatitis, cyclosporine, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(5:117-120

  13. Chemokine RANTES in atopic dermatitis.

    Science.gov (United States)

    Glück, J; Rogala, B

    1999-01-01

    Chemokines play a key role in inflammatory diseases. The aim of this study was to estimate chemokine RANTES in the sera of patients with atopic dermatitis (AD) and to analyze the correlation between RANTES serum level and the immunological and clinical parameters of the disease. Serum levels of RANTES (ELISA; R&D Systems), total IgE and specific IgE (FEIA; Pharmacia CAP System) were estimated in 24 patients with AD, 28 patients with pollinosis (PL) and 22 healthy nonatopic subjects (HC). The division of the AD group into a pure AD (pAD) subgroup, without a coexisting respiratory allergy, and a subgroup of patients with AD and a respiratory allergy (AD+AO) was done according to Wütrich. Levels of RANTES were higher in the AD group than in the HC group and the PL group. RANTES levels did not differ among subgroups with various clinical scores and between the pAD and AD+AO subgroups. There were no correlations between levels of RANTES and total IgE. Significant positive correlations between serum levels of RANTES and Dermatophagoides farinae and cat dander-specific IgE were found in the AD group. We conclude that the serum level of chemokine RANTES differs patients with AD from patients with PL. The increase of RANTES concentration in the serum of patients with AD depends neither on a clinical picture nor an IgE system.

  14. Probiotics and Atopic Dermatitis: An Overview

    Directory of Open Access Journals (Sweden)

    Irfan A. Rather

    2016-04-01

    Full Text Available Atopic dermatitis (AD is a common, recurrent, chronic inflammatory skin disease that is a cause of considerable economic and social burden. Its prevalence varies substantially among different countries with an incidence rate proclaimed to reach up to 20% of children in developed countries and continues to escalate in developing nations. This increased rate of incidence has changed the focus of research on AD toward epidemiology, prevention, and treatment. The effects of probiotics in the prevention and treatment of AD remain elusive. However, evidence from different research groups show that probiotics could have positive effect on AD treatment, if any, that depend on multiple factors, such as specific probiotic strains, time of administration (onset time, duration of exposure, and dosage. However, till date we still lack strong evidence to advocate the use of probiotics in the treatment of AD, and questions remain to be answered considering its clinical use in future. Based on updated information, the processes that facilitate the development of AD and the topic of the administration of probiotics are addressed in this review.

  15. Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice

    International Nuclear Information System (INIS)

    Li, Guodong; Kong, Bo; Zhu, Yan; Zhan, Le; Williams, Jessica A.; Tawfik, Ossama; Kassel, Karen M.; Luyendyk, James P.; Wang, Li; Guo, Grace L.

    2013-01-01

    Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis. Induction of SHP serves as a major mechanism of FXR in suppressing gene expression. Both FXR −/− and SHP −/− mice develop spontaneous hepatocellular carcinoma (HCC). SHP is one of the most strongly induced genes by FXR in the liver and is a tumor suppressor, therefore, we hypothesized that deficiency of SHP contributes to HCC development in the livers of FXR −/− mice and therefore, increased SHP expression in FXR −/− mice reduces liver tumorigenesis. To test this hypothesis, we generated FXR −/− mice with overexpression of SHP in hepatocytes (FXR −/− /SHP Tg ) and determined the contribution of SHP in HCC development in FXR −/− mice. Hepatocyte-specific SHP overexpression did not affect liver tumor incidence or size in FXR −/− mice. However, SHP overexpression led to a lower grade of dysplasia, reduced indicator cell proliferation and increased apoptosis. All tumor-bearing mice had increased serum bile acid levels and IL-6 levels, which was associated with activation of hepatic STAT3. In conclusion, SHP partially protects FXR −/− mice from HCC formation by reducing tumor malignancy. However, disrupted bile acid homeostasis by FXR deficiency leads to inflammation and injury, which ultimately results in uncontrolled cell proliferation and tumorigenesis in the liver. - Highlights: • SHP does not prevent HCC incidence nor size in FXR KO mice but reduces malignancy. • Increased SHP promotes apoptosis. • Bile acids and inflammation maybe critical for HCC formation with FXR deficiency

  16. Persistent Salmonella enterica serovar Typhimurium Infection Increases the Susceptibility of Mice to Develop Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Bárbara M. Schultz

    2018-05-01

    Full Text Available Chronic intestinal inflammations are triggered by genetic and environmental components. However, it remains unclear how specific changes in the microbiota, host immunity, or pathogen exposure could promote the onset and exacerbation of these diseases. Here, we evaluated whether Salmonella enterica serovar Typhimurium (S. Typhimurium infection increases the susceptibility to develop intestinal inflammation in mice. Two mouse models were used to evaluate the impact of S. Typhimurium infection: the chemical induction of colitis by dextran sulfate sodium (DSS and interleukin (IL-10−/− mice, which develop spontaneous intestinal inflammation. We observed that S. Typhimurium infection makes DSS-treated and IL-10−/− mice more susceptible to develop intestinal inflammation. Importantly, this increased susceptibility is associated to the ability of S. Typhimurium to persist in liver and spleen of infected mice, which depends on the virulence proteins secreted by Salmonella Pathogenicity Island 2-encoded type three secretion system (TTSS-2. Although immunization with a live attenuated vaccine resulted in a moderate reduction of the IL-10−/− mice susceptibility to develop intestinal inflammation due to previous S. Typhimurium infection, it did not prevent bacterial persistence. Our results suggest that persistent S. Typhimurium infection may increase the susceptibility of mice to develop inflammation in the intestine, which could be associated with virulence proteins secreted by TTSS-2.

  17. Effects of gamma radiation on fetal development in mice

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    Tahere Dehghan

    2016-04-01

    Full Text Available Background: Many cancer patients receive radiotherapy which may lead to serious damages to the ovary storage and the matrix muscle state. Some of these patients may admit to infertility clinics for having pregnancy and on the other hand hormonal administration for superovulation induction is a routine procedure in assisted reproduction technology (ART clinics. Objective: This study aimed to investigate fertility and fetuses of hormone treated super ovulated female mice who had received whole-body gamma irradiation before mating. Materials and Methods: Female mice were randomly categorized into a control group and 3 experimental groups including: Group I (Irradiation, Group II (Superovulation, and Group III (Superovulation and Irradiation. In hormone treated groups, mice were injected with different doses of 59Tpregnant mare's serum gonadotropin59T (PMSG followed with human chorionic gonadotropin (HCG. Irradiation was done using a Co-60 gamma ray generator with doses of 2 and 4 Gy. Number of fetuses counted and the fetus’s weight, head circumference, birth height, the number of live healthy fetuses, the number of fetuses with detected anomalies in the body, the sum of resorption and arrested fetuses were all recorded as outcome of treatments. Results: In the group I and group II, increased radiation and hormone dose led to a decrease in the number of survived fetuses (45 in 2 Gy vs. 29 in 4 Gy for irradiated group as well as from 76 in 10 units into 48 in 15 units. In the group III, a higher dose of hormone in the presence of a 2 Gy irradiation boosted the slink rate; i.e. the number of aborted fetuses reached 21 cases while applying the dose of 15 Iu, whereas 6 cases of abortion were reported applying the hormone with a lower dose. Among different parameters studied, there was a significant difference in parameters of weight and height in the mouse fetuses (p=0.01. Conclusion: The data indicated that use of ovarian stimulating hormones in mice

  18. Early childhood environment related to microbial exposure and the occurrence of atopic disease at school age.

    Science.gov (United States)

    de Meer, G; Janssen, N A H; Brunekreef, B

    2005-05-01

    There is a growing body of evidence that the early childhood environment with respect to day care attendance, older siblings, pet ownership, and early life airway infections may protect from developing atopic disease. Few studies have distinguished between atopic sensitization and symptoms, and none have evaluated independent contributions for all of these different environmental conditions. Examine independent effects on atopic sensitization and symptoms of day care attendance, older siblings, pet ownership, and early infancy's airway disease. A cross-sectional survey among 8-13-year-old school children with complete data for 1555 children. After adjustment for confounders, atopic sensitization occurred less frequently in children that had attended a day care centre (OR: 0.73, 95% CI: 0.55-0.98) or had a cat or dog before 2 years of age (OR: 0.78, 95% CI: 0.61-0.99). Having older siblings yielded a nonsignificant trend towards protection (OR: 0.88, 95% CI: 0.70-1.11). For symptoms, there was no relation with having older sibs, day care attendance and pet ownership, although there was a trend towards protection for the combination of atopy and symptoms. In contrast, children with doctors' treated airway disease before age 2, more frequently reported recent symptoms of wheeze, asthma, rhinitis, or dermatitis (all P atopic sensitization. Protection against symptoms only occurred if atopic sensitization was present as well.

  19. Topical tacrolimus for atopic dermatitis.

    Science.gov (United States)

    Cury Martins, Jade; Martins, Ciro; Aoki, Valeria; Gois, Aecio F T; Ishii, Henrique A; da Silva, Edina M K

    2015-07-01

    Atopic dermatitis (AD) (or atopic eczema) is a chronic inflammatory skin condition that affects children and adults and has an important impact on quality of life. Topical corticosteroids (TCS) are the first-line therapy for this condition; however, they can be associated with significant adverse effects when used chronically. Tacrolimus ointment (in its 2 manufactured strengths of 0.1% and 0.03%) might be an alternative treatment. Tacrolimus, together with pimecrolimus, are drugs called topical calcineurin inhibitors (TCIs). To assess the efficacy and safety of topical tacrolimus for moderate and severe atopic dermatitis compared with other active treatments. We searched the following databases up to 3 June 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 5, 2015), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), and the Global Resource of Eczema Trials (GREAT database). We searched six trials registers and checked the bibliographies of included studies for further references to relevant trials. We contacted specialists in the field for unpublished data.A separate search for adverse effects of topical tacrolimus was undertaken in MEDLINE and EMBASE on 30 July 2013. We also scrutinised the U.S. Food and Drug Administration (FDA) websites for adverse effects information. All randomised controlled trials (RCTs) of participants with moderate to severe atopic dermatitis (both children and adults) using topical tacrolimus at any dose, course duration, and follow-up time compared with other active treatments. Two authors independently screened and examined the full text of selected studies for compliance with eligibility criteria, risk of bias, and data extraction. Our three prespecified primary outcomes were physician's assessment, participant's self-assessment of improvement, and adverse effects. Our secondary outcomes included assessment of improvement of the disease by validated or objective measures, such as

  20. Esculetin from Fraxinus rhynchophylla attenuates atopic skin inflammation by inhibiting the expression of inflammatory cytokines.

    Science.gov (United States)

    Jeong, Na-Hee; Yang, Eun-Ju; Jin, Meiling; Lee, Jong Yeong; Choi, Young-Ae; Park, Pil-Hoon; Lee, Sang-Rae; Kim, Sun-Uk; Shin, Tae-Yong; Kwon, Taeg Kyu; Jang, Yong Hyun; Song, Kyung-Sik; Kim, Sang-Hyun

    2018-06-01

    Atopic dermatitis (AD) is a common chronic inflammatory skin disorder afflicting from infancy to adults with itching, scratching, and lichenification. We aimed to investigate the effects of esculetin from Fraxinus rhynchophylla on atopic skin inflammation. For induction of atopic skin inflammation, we exposed the ears of female BALB/c mice to house dust mite (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB) for 4 weeks. Oral administration of esculetin reduced the symptoms of DFE/DNCB-induced atopic skin inflammation, which were evaluated based on ear swelling and number of scratch bouts. The immunoglobulin (Ig) E, IgG2a, and histamine levels in serum were decreased and inflammatory cell infiltration in skin tissue was reduced by the esculetin. It suppressed production of Th1, Th2 and Th17-related cytokines such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-4, IL-13, IL-31 and IL-17 in the ear tissue. Furthermore, we investigated the effects of esculetin on activated keratinocytes, which are representative cells used for studying the pathogenesis of acute and chronic atopic skin inflammation. As results, esculetin suppressed gene expression of Th1, Th2 and Th17 cytokines and the activation of nuclear factor-κB and signal transducer and activator of transcription 1 in TNF-α/IFN-γ-stimulated keratinocytes. Taken together, these results imply that esculetin attenuated atopic skin inflammation, suggesting that esculetin could be a potential therapeutic candidate for the treatment of AD. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Helicobacter bilis Infection Alters Mucosal Bacteria and Modulates Colitis Development in Defined Microbiota Mice.

    Science.gov (United States)

    Atherly, Todd; Mosher, Curtis; Wang, Chong; Hostetter, Jesse; Proctor, Alexandra; Brand, Meghan W; Phillips, Gregory J; Wannemuehler, Michael; Jergens, Albert E

    2016-11-01

    Helicobacter bilis infection of C3H/HeN mice harboring the altered Schaedler flora (ASF) triggers progressive immune responsiveness and the development of colitis. We sought to investigate temporal alterations in community structure of a defined (ASF-colonized) microbiota in normal and inflamed murine intestines and to correlate microbiota changes to histopathologic lesions. The colonic mucosal microbiota of healthy mice and ASF mice colonized with H. bilis for 3, 6, or 12 weeks were investigated by fluorescence in situ hybridization targeting the 16S ribosomal RNA genes of total bacteria, group-specific organisms, and individual ASF bacterial species. Microbial profiling of ASF and H. bilis abundance was performed on cecal contents. Helicobacter bilis-colonized mice developed colitis associated with temporal changes in composition and spatial distribution of the mucosal microbiota. The number of total bacteria, ASF519, and helicobacter-positive bacteria were increased (P attachment, or by invasion, and this interaction is differentially expressed over time.

  2. NFC Evaluation in the Development of Mobile Applications for MICE in Tourism

    Directory of Open Access Journals (Sweden)

    David Silva-Pedroza

    2017-10-01

    Full Text Available This paper presents an analysis and implementation of a service for the deployment of events in the Meetings, Incentives, Conferences, and Exhibitions (MICE category, to answer the question: how can Near Field Communication (NFC and mobile applications contribute to the development of tourism in the MICE category? First is an analysis of the applications that are currently on the market and an extraction of the features of greater relevance; later, we define the functionalities for our service, and finally we provide a performance test in a MICE-type event, the seventh Seminar on Emerging Technologies in Telecommunications “TET 2016” developed in Popayán, Colombia and the results of the experience are analyzed. The use of NFC technology with a mobile application allows the experience to be improved when a MICE event was made, for both the user and the organizer.

  3. The role of melatonin in autoimmune and atopic diseases

    Directory of Open Access Journals (Sweden)

    J.R. Calvo

    2016-04-01

    Full Text Available Melatonin is the main secretory product synthesized and secreted by the pineal gland during the night. Melatonin is a pleitropic molecule with a wide distribution within phylogenetically distant organisms and has a great functional versatility, including the regulation of circadian and seasonal rhythms and antioxidant and anti-inflammatory properties. It also possesses the capacity to modulate immune responses by regulation of the TH1/TH2 balance and cytokine production. Immune system eradicates infecting organisms without serious injury to host tissues, but sometimes these responses are inadequately controlled, giving rise to called hypersensitivity diseases, or inappropriately targeted to host tissues, causing the autoimmune diseases. In clinical medicine, the hypersensitivity diseases include the allergic or atopic diseases and the hallmarks of these diseases are the activation of TH2 cells and the production of IgE antibody. Regarding autoimmunity, at the present time we know that the key events in the development of autoimmunity are a failure or breakdown of the mechanisms normally responsible for maintaining self-tolerance in B lymphocytes, T lymphocytes, or both, the recognition of self-antigens by autoreactive lymphocytes, the activation of these cells to proliferate and differentiate into effector cells, and the tissue injury caused by the effector cells and their products. Melatonin treatment has been investigated in atopic diseases, in several animal models of autoimmune diseases, and has been also evaluated in clinical autoimmune diseases. This review summarizes the role of melatonin in atopic diseases (atopic dermatitis and asthma and in several autoimmune diseases, such as arthritis rheumatoid, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes mellitus, and inflammatory bowel diseases.

  4. Sex differences in obesity development in pair-fed neuronal lipoprotein lipase deficient mice

    Directory of Open Access Journals (Sweden)

    Hong Wang

    2016-10-01

    Full Text Available Objective: Compared to men, postmenopausal women suffer from a disproportionate burden of many co-morbidities associated with obesity, e.g. cardiovascular disease, cancer, and dementia. The underlying mechanism for this sex difference is not well understood but is believed to relate to absence of the protective effect of estrogen through the action of estrogen receptor alpha (ERα in the central nervous system. With the recently developed neuron-specific lipoprotein lipase deficient mice (NEXLPL−/− (Wang et al., Cell Metabolism, 2011 [15], we set to explore the possible role of lipid sensing in sex differences in obesity development. Methods: Both male and female NEXLPL−/− mice and littermate WT controls were subjected to pair feeding (pf where daily food amount given was adjusted according to body weight to match the food intake of ad libitum (ad fed control WT mice. Food intake and body weight were measured daily, and pair feeding was maintained to 42 wk in male mice and to 38 wk in female mice. Various brain regions of the mice were harvested, and ERα gene expression was examined in both male and female NEXLPL−/− and WT control mice under both ad- and pf-fed conditions. Results: Although both male and female NEXLPL−/− mice developed obesity similarly on standard chow, male NEXLPL−/− mice still developed obesity under with pair feeding, but on a much delayed time course, while female NEXLPL−/− mice were protected from extra body weight and fat mass gain compared to pair-fed WT control mice. Pair feeding alone induced extra fat mass gain in both male and female WT mice, and this was mostly driven by the reduction in physical activity. LPL deficiency resulted in an increase in ERα mRNA in the hypothalamus of ad-fed female mice, while pair feeding alone also resulted in an increase of ERα in both female WT control and NEXLPL−/− mice. The effect on increasing ERα by pair feeding and LPL deficiency was additive in

  5. Development of infection with Streptococcus bovis and Aspergillus sp. in irradiated mice after glycopeptide therapy

    International Nuclear Information System (INIS)

    Brook, I.; Tom, S.P.; Ledney, G.D.

    1993-01-01

    The use of ofloxacin and glycopeptides was evaluated for the treatment of infections arising in C3H/HeN female mice irradiated with 8.3 Gy from a 60 Co source. The 21 day regimen began 72 h after irradiation when each of five sets of experimental animals received three antimicrobial therapy regimens and a saline-treated control group. With 40 mice in each group, 20 were used to monitor survival, 20 for the recovery of bacteria from the liver culture. Treatment groups were oral ofloxacin; oral or intramuscular vancomycin oral teicoplanin, ofloxacin and vancomycin; ofloxacin and teicoplanin; or saline. Bacteria recovered from saline treated mice were Enterobacteriaceae and Streptococcus spp. By comparison, fewer Enterobacteriaceae were isolated from ofloxacin treated mice and fewer Streptococcus spp. in both vancomycin and teicoplanin treated mice. However, glycopeptide-treated mice developed infection with Aspergillis fumigatus and glycopeptide resistant Streptococcus bovis. Mortality rates within 60 days of irradiation were 100% in all treatment and control groups with the exception of ofloxacin which was 25%-35%. These data suggest that glycopeptide therapy increases rates of systemic infection with fungi and antibiotic resistant bacteria in irradiated mice. (Author)

  6. Development of infection with Streptococcus bovis and Aspergillus sp. in irradiated mice after glycopeptide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Brook, I.; Tom, S.P.; Ledney, G.D. (Armed Forces Radiobiology Research Inst., Bethesda, MD (United States))

    1993-11-01

    The use of ofloxacin and glycopeptides was evaluated for the treatment of infections arising in C3H/HeN female mice irradiated with 8.3 Gy from a [sup 60]Co source. The 21 day regimen began 72 h after irradiation when each of five sets of experimental animals received three antimicrobial therapy regimens and a saline-treated control group. With 40 mice in each group, 20 were used to monitor survival, 20 for the recovery of bacteria from the liver culture. Treatment groups were oral ofloxacin; oral or intramuscular vancomycin oral teicoplanin, ofloxacin and vancomycin; ofloxacin and teicoplanin; or saline. Bacteria recovered from saline treated mice were Enterobacteriaceae and Streptococcus spp. By comparison, fewer Enterobacteriaceae were isolated from ofloxacin treated mice and fewer Streptococcus spp. in both vancomycin and teicoplanin treated mice. However, glycopeptide-treated mice developed infection with Aspergillis fumigatus and glycopeptide resistant Streptococcus bovis. Mortality rates within 60 days of irradiation were 100% in all treatment and control groups with the exception of ofloxacin which was 25%-35%. These data suggest that glycopeptide therapy increases rates of systemic infection with fungi and antibiotic resistant bacteria in irradiated mice. (Author).

  7. RIPK3 Mediates Necroptosis during Embryonic Development and Postnatal Inflammation in Fadd-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Qun Zhao

    2017-04-01

    Full Text Available RIPK3 mediates cell death and regulates inflammatory responses. Although genetic studies have suggested that RIPK3-MLKL-mediated necroptosis leads to embryonic lethality in Fadd or Caspase-8-deficient mice, the exact mechanisms are not fully understood. Here, we generated Ripk3 mutant mice by altering the RIPK3 kinase domain (Ripk3Δ/Δ mice, thus abolishing its kinase activity. Ripk3Δ/Δ cells were resistant to necroptosis stimulation in vitro, and Ripk3Δ/Δ mice were protected from necroptotic diseases. Although the Ripk3Δ/Δ mutation rescued embryonic lethality in Fadd−/− embryos, Fadd−/− Ripk3Δ/Δ mice died within 1 day after birth due to massive inflammation. These results indicate that Ripk3 ablation rescues embryonic lethality in Fadd-deficient mice by suppressing two RIPK3-mediating processes: necroptosis during embryogenesis and inflammation during postnatal development in Fadd−/− mice.

  8. Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH.

    Directory of Open Access Journals (Sweden)

    Mikael Bjursell

    Full Text Available Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1, the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.

  9. Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH.

    Science.gov (United States)

    Bjursell, Mikael; Wedin, Marianne; Admyre, Therése; Hermansson, Majlis; Böttcher, Gerhard; Göransson, Melker; Lindén, Daniel; Bamberg, Krister; Oscarsson, Jan; Bohlooly-Y, Mohammad

    2013-01-01

    Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR) is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1), the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH) and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.

  10. Mice do not develop conditioned taste aversion because of immunity loss.

    Science.gov (United States)

    Vidal, Jose

    2011-01-01

    This study intends to test the generation of conditioned taste aversion and conditioned immunodepression by daily paired administration of saccharin solution with cyclophosphamide, 15 mg/kg, for 4 days. One group of male mice of the outbred CD1 strain drank 0.15% saccharin and received 1 injection of cyclophosphamide, 15 mg/kg, for 4 days (paired group), another group (unpaired group) received the same doses of saccharin and cyclophosphamide noncontingently, the third group (cy60) received saccharin paired with cyclophosphamide, 60 mg/kg, and the fourth group (placebo) received saccharin in the absence of cyclophosphamide. All mice were immunized with keyhole limpet hemocyanin (KLH), 0.2 mg, 1 day before the treatments. Mice of the paired, unpaired and cy60 groups displayed a similarly decreased antibody response to KLH, but mice of the paired group did not develop an aversion to saccharin while mice of the cy60 group did. Besides, repeat presentation of saccharin to mice of the paired group did not alter their antibody response to ovalbumin compared with mice of the unpaired or placebo group. Taste aversion was not elicited in response to impaired immunity and the conditioned stimulus (saccharin) did not impair the antibody response. 2011 S. Karger AG, Basel.

  11. Mixing and CP violation in the B$0\\atop{s}$ meson system at CDF; Mélange et violation de CP dans le système des mésons B$0\\atop{s}$ à CDF

    Energy Technology Data Exchange (ETDEWEB)

    Di Giovanni, Gian Piero [Univ. of Paris VI-VII (France)

    2008-01-01

    The two analyses presented in the thesis, the B$0\\atop{s}$ mixing analysis and the B$0\\atop{s}$ → J/ψφ angular analysis, share most of the technical implementations and features. Thus, my choice was to pursue in parallel the common aspects of the analyses, avoiding, whenever possible, repetitions. Each Chapter is split in two parts, the first one dedicated to the B$0\\atop{s}$ mixing analysis and the second one describing the angular analysis on the B$0\\atop{s}$ → J/ψφ decay mode. They are organized as follows. In Chapter 1 we present the theoretical framework of the B$0\\atop{s}$ neutral mesons system. After a general introduction on the Standard Model, we focus on the quantities which are relevant to the Δms measurement and the CP violation phenomena, underlying the details concerning the study of pseudo-scalar to vector vector decays, P → VV, which allow to carry out an angular analysis. A discussion on the implication of the measurements performed in the search of physics beyond the Standard Model is presented. The accelerator facilities and the CDF-II detector are reported in Chapter 2. While describing the detector, more emphasis is given to the components fundamental to perform B physics analyses at CDF. The Chapter 3 is focused on the reconstruction and selection of the data samples. The Chapter starts with a description of the on-line trigger requirements, according to the B$0\\atop{s}$ sample considered, followed by the offline selection criteria implemented to reconstruct B$0\\atop{s}$ semileptonic and hadronic decays, fully and partially reconstructed, for the B$0\\atop{s}$ mixing analysis, as well as the B$0\\atop{s}$ → J/ψφ decay mode for the angular analysis. The subsequent Chapter 4 is dedicated to the revision of the technical ingredients needed in the final analyses. The B$0\\atop{s}$ mixing elements are firstly described. The methodology historically used in the oscillation searches, the 'amplitude scan', is here

  12. Food restriction affects Y-maze spatial recognition memory in developing mice.

    Science.gov (United States)

    Fu, Yu; Chen, Yanmei; Li, Liane; Wang, Yumei; Kong, Xiangyang; Wang, Jianhong

    2017-08-01

    The ambiguous effects of food restriction (FR) on cognition in rodents have been mostly explored in the aged brain by a variety of paradigms, in which either rewards or punishments are involved. This study aims to examine the effects of chronic and acute FR with varying intensities on spatial recognition memory in developing mice. We have used a Y-maze task that is based on the innate tendency of rodents to explore novel environments. In chronic FR, mice had 70-30% chow of control for seven weeks. In acute FR, mice were food restricted for 12-48h before the tests. We found that chronic FR had no effect on the preference of mice for novelty in the Y-maze, but severe FR (50-30% of control) caused impairment on spatial recognition memory. The impairment significantly correlated with the slow weight growth induced by FR. Acute FR also did not affect the novelty preference of mice, but either improved or impaired the memory retention. These data suggest chronic FR impairs Y-maze spatial recognition memory in developing mice depending on FR intensity and individual tolerability of the FR. Moreover, acute FR exerts diverse effects on the memory, either positive or negative. Our findings have revealed new insights on the effects of FR on spatial recognition memory in developing animals. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

  13. The role of the skin microbiome in atopic dermatitis

    DEFF Research Database (Denmark)

    Bjerre, R. D.; Bandier, J.; Skov, L.

    2017-01-01

    Dysbiosis is a hallmark of atopic dermatitis (AD). The composition of skin microbiome communities and the causality of dysbiosis in eczema have not been well established. The objective of this review is to describe the skin microbiome profile in AD and address whether there is a causal relationship...... between dysbiosis and AD. The protocol is registered in PROSPERO (CRD42016035813). We searched PubMed, Embase, Scopus and ClinicalTrials.gov for primary research studies applying culture-independent analysis on the microbiome on AD skin of humans and animal models. Two authors independently screened...... of dysbiosis in eczema in mice should encourage future studies to investigate if this also applies to humans. Other important aspects are temporal dynamics and the influence of methodology on microbiome data....

  14. Effects of a 4.7 T static magnetic field on fetal development in ICR mice

    International Nuclear Information System (INIS)

    Okazaki, Ryuji; Ootsuyama, Akira; Uchida, Soshi; Norimura, Toshiyuki

    2001-01-01

    In order to determine the effects of a 4.7 T static magnetic field (SMF) on fetal development in mice, we evaluated fetal teratogenesis and endochondral ossification following exposure in utero. Pregnant ICR mice were exposed to a 4.7 T SMF from day 7.5 to 9.5 of gestation in a whole-body dose, and sacrificed on day 18.5 of gestation. We examined with incidence of prenatal death, external malformations and fetal skeletal malformations. There were no significant differences observed in the incidence of prenatal death and/or malformations between SMF-exposed mice and control mice. Further, we evaluated the immunoreactivity for the vascular endothelial growth factor (VEGF), which is implicated in angiogenesis and osteogenesis, in the sternum of fetal mice following magnetic exposure. Our studies also indicated that on day 16.5 of gestation following SMF exposure, the immunoreactivity for VEGF was increased compared to unexposed controls. However, it was decreased in the exposed group compared to the control group on day 18.5 of gestation. DNA and proteoglycan (PG) synthesis were also measured in rabbit costal growth plate chondrocytes in vitro. No significant differences were observed in DNA synthesis between the SMF exposed chondrocytes and the control chondrocytes; however, PG synthesis in SMF exposed chondrocytes increased compared to the controls. Based on these results, we suggest that while SMF exposure promoted the endochondral ossification of chondrocytes, it did not induce any harmful effects on fetal development in ICR mice. (author)

  15. Effects of a 4.7 T static magnetic field on fetal development in ICR mice

    Energy Technology Data Exchange (ETDEWEB)

    Okazaki, Ryuji; Ootsuyama, Akira; Uchida, Soshi; Norimura, Toshiyuki [Univ. of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan). School of Medicine

    2001-09-01

    In order to determine the effects of a 4.7 T static magnetic field (SMF) on fetal development in mice, we evaluated fetal teratogenesis and endochondral ossification following exposure in utero. Pregnant ICR mice were exposed to a 4.7 T SMF from day 7.5 to 9.5 of gestation in a whole-body dose, and sacrificed on day 18.5 of gestation. We examined with incidence of prenatal death, external malformations and fetal skeletal malformations. There were no significant differences observed in the incidence of prenatal death and/or malformations between SMF-exposed mice and control mice. Further, we evaluated the immunoreactivity for the vascular endothelial growth factor (VEGF), which is implicated in angiogenesis and osteogenesis, in the sternum of fetal mice following magnetic exposure. Our studies also indicated that on day 16.5 of gestation following SMF exposure, the immunoreactivity for VEGF was increased compared to unexposed controls. However, it was decreased in the exposed group compared to the control group on day 18.5 of gestation. DNA and proteoglycan (PG) synthesis were also measured in rabbit costal growth plate chondrocytes in vitro. No significant differences were observed in DNA synthesis between the SMF exposed chondrocytes and the control chondrocytes; however, PG synthesis in SMF exposed chondrocytes increased compared to the controls. Based on these results, we suggest that while SMF exposure promoted the endochondral ossification of chondrocytes, it did not induce any harmful effects on fetal development in ICR mice. (author)

  16. Hydrolyzed whey protein prevents the development of food allergy to β-lactoglobulin in sensitized mice.

    Science.gov (United States)

    Gomes-Santos, Ana Cristina; Fonseca, Roberta Cristelli; Lemos, Luisa; Reis, Daniela Silva; Moreira, Thaís Garcias; Souza, Adna Luciana; Silva, Mauro Ramalho; Silvestre, Marialice Pinto Coelho; Cara, Denise Carmona; Faria, Ana Maria Caetano

    2015-01-01

    Food allergy is an adverse immune response to dietary proteins. Hydrolysates are frequently used for children with milk allergy. However, hydrolysates effects afterwards are poorly studied. The aim of this study was to investigate the immunological consequences of hydrolyzed whey protein in allergic mice. For that, we developed a novel model of food allergy in BALB/c mice sensitized with alum-adsorbed β-lactoglobulin. These mice were orally challenged with either whey protein or whey hydrolysate. Whey-challenged mice had elevated levels of specific IgE and lost weight. They also presented gut inflammation, enhanced levels of SIgA and IL-5 as well as decreased production of IL-4 and IL-10 in the intestinal mucosa. Conversely, mice challenged with hydrolyzate maintained normal levels of IgE, IL-4 and IL-5 and showed no sign of gut inflammation probably due to increased IL-12 production in the gut. Thus, consumption of hydrolysate prevented the development of clinical signs of food allergy in mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Prenatal exposure to fenugreek impairs sensorimotor development and the operation of spinal cord networks in mice.

    Directory of Open Access Journals (Sweden)

    Loubna Khalki

    Full Text Available Fenugreek is a medicinal plant whose seeds are widely used in traditional medicine, mainly for its laxative, galactagogue and antidiabetic effects. However, consumption of fenugreek seeds during pregnancy has been associated with a range of congenital malformations, including hydrocephalus, anencephaly and spina bifida in humans. The present study was conducted to evaluate the effects of prenatal treatment of fenugreek seeds on the development of sensorimotor functions from birth to young adults. Pregnant mice were treated by gavage with 1 g/kg/day of lyophilized fenugreek seeds aqueous extract (FSAE or distilled water during the gestational period. Behavioral tests revealed in prenatally treated mice a significant delay in righting, cliff avoidance, negative geotaxis responses and the swimming development. In addition, extracellular recording of motor output in spinal cord isolated from neonatal mice showed that the frequency of spontaneous activity and fictive locomotion was reduced in FSAE-exposed mice. On the other hand, the cross-correlation coefficient in control mice was significantly more negative than in treated animals indicating that alternating patterns are deteriorated in FSAE-treated animals. At advanced age, prenatally treated mice displayed altered locomotor coordination in the rotarod test and also changes in static and dynamic parameters assessed by the CatWalk automated gait analysis system. We conclude that FSAE impairs sensorimotor and coordination functions not only in neonates but also in adult mice. Moreover, spinal neuronal networks are less excitable in prenatally FSAE-exposed mice suggesting that modifications within the central nervous system are responsible, at least in part, for the motor impairments.

  18. Risk factors for atopic and non-atopic asthma in a rural area of Ecuador.

    Science.gov (United States)

    Moncayo, Ana Lucia; Vaca, Maritza; Oviedo, Gisela; Erazo, Silvia; Quinzo, Isabel; Fiaccone, Rosemeire L; Chico, Martha E; Barreto, Mauricio L; Cooper, Philip J

    2010-05-01

    BACKGROUND Asthma has emerged as an important public health problem of urban populations in Latin America. Epidemiological data suggest that a minority of asthma cases in Latin America may be associated with allergic sensitisation and that other mechanisms causing asthma have been overlooked. The aim of the present study was to investigate risk factors for atopic and non-atopic asthma in school-age children. METHODS A cross-sectional study was conducted among 3960 children aged 6-16 years living in Afro-Ecuadorian rural communities in Esmeraldas province in Ecuador. Allergic diseases and risk factors were assessed by questionnaire and allergic sensitisation by allergen skin prick reactivity. RESULTS A total of 390 (10.5%) children had wheeze within the previous 12 months, of whom 14.4% had at least one positive skin test. The population-attributable fraction for recent wheeze associated with atopy was 2.4%. Heavy Trichuris trichiura infections were strongly inversely associated with atopic wheeze. Non-atopic wheeze was positively associated with maternal allergic symptoms and sedentarism (watching television (>3 h/day)) but inversely associated with age and birth order. CONCLUSIONS The present study showed a predominance of non-atopic compared with atopic wheeze among schoolchildren living in a poor rural region of tropical Latin America. Distinct risk factors were associated with the two wheeze phenotypes and may indicate different causal mechanisms. Future preventive strategies in such populations may need to be targeted at the causes of non-atopic wheeze.

  19. Systematic review of treatments for atopic eczema.

    Science.gov (United States)

    Hoare, C; Li Wan Po, A; Williams, H

    2000-01-01

    Atopic eczema is the commonest inflammatory skin disease of childhood, affecting 15-20% of children in the UK at any one time. Adults make up about one-third of all community cases. Moderate-to-severe atopic eczema can have a profound effect on the quality of life for both sufferers and their families. In addition to the effects of intractable itching, skin damage, soreness, sleep loss and the social stigma of a visible skin disease, other factors such as frequent visits to doctors, special clothing and¿the need to constantly apply messy topical applications all add to the burden of disease. The cause of atopic eczema is unknown, though a genetic pre-disposition and a combination of allergic and non-allergic factors appear to be important in determining disease expression. Treatment of atopic eczema in the UK is characterised by a profusion of treatments aimed at disease control. The evidential basis of these treatments is often unclear. Most people with atopic eczema are managed in primary care where the least research has been done. The objectives of this scoping review are two-fold. To produce an up-to-date coverage 'map' of randomised controlled trials (RCTs) of treatments of atopic eczema. To assist in making treatment recommendations by summarising the available RCT evidence using qualitative and quantitative methods. Data sources included electronic searching of MEDLINE, EMBASE, the Cochrane Controlled Clinical Trials Register, the Cochrane Skin Group specialised register of trials, hand-searching of atopic eczema conference proceedings, follow-up of references in retrieved articles, contact with leading researchers and requests to relevant pharmaceutical companies. Only RCTs of therapeutic agents used in the prevention and treatment of people with atopic eczema of any age were considered for inclusion. Only studies where a physician diagnosed atopic eczema or atopic dermatitis were included. Data extraction was conducted by two observers onto abstraction

  20. Family interaction and a supportive social network as salutogenic factors in childhood atopic illness.

    Science.gov (United States)

    Gustafsson, Per A; Kjellman, N-I Max; Björkstén, Bengt

    2002-02-01

    The role of psycho-social factors in the development of allergy was studied prospectively in 82 infants with a family history of atopy. The family participated in a standardized family test when the children were 18 months old. The ability to adjust to demands of the situation ('adaptability'), and the balance between emotional closeness and distance ('cohesion'), were assessed from videotapes by independent raters. Families rated as functional in both of these aspects were classified as 'functional', otherwise as 'dysfunctional'. The social network, life events, atopic symptoms (based on postal inquiries regarding symptoms answered by the parents, and on physical examinations), psychiatric symptoms, and socio-economic circumstances of the families were evaluated when the children were 18 months and 3 years of age. The children were classified as atopic (asthmatic symptoms or eczema) or as non-atopic. All but two children with atopic disease at 3 years of age had atopic disease before 18 months of age, while 32 of 60 children with atopic disease at 18 months of age had no problems by 3 years of age. An unbalanced family interplay at 18 months was associated with a relative risk (RR) of 1.99 for continuing atopic illness at 3 years of age (1.18 eczema on three or more localizations (RR reduced by 4.5%), and the amount of cat allergen in household dust (RR reduced by 3%). Recovery from atopic illness between 18 months and 3 years of age was four times as probable in families with functional interaction and a good social supportive network when children were 18 months of age, than in dysfunctional families with a poor social network (74% versus 20% p emotional distress than did healthy children (p = 0.02). Dysfunctional family interaction patterns were more commonly observed in families of children who at 3 years of age still had atopic symptoms, than in children who had recovered. The patterns included expression of emotion and reaction to the needs of others

  1. [Effect of Huanglian Jiedu Decoction on Monocyte Development in apoE Gene Knockout Mice].

    Science.gov (United States)

    Chen, Bing; Kong, Ya-xian; Ll, Yu-mei; Xue, Xin; Zhang, Jian-ping; Zeng, Hui; Hu, Jing- qing; Ma, Ya-luan

    2016-01-01

    To observe monocyte (Mo) development in wild type C57BL/6 mice and apoE gene knockout (apoE(-/-)) mice, and to evaluate the immuno-regulatory effect of Huanglian Jiedu Decoction (HJD) on peripheral Mo development in apoE(-/-) mice. Four, 8, 12, and 16 weeks old female C57BL/6 mice were set up as control groups of different ages, while 4, 8, 12, and 16 weeks old female apoE(-/-) mice were set up as hyperlipidemia groups of different ages. Four-week old female C57BL/6 mice were recruited as a blank group. Four-week old female apoE(-/-) mice were randomly divided into the control group, the Western medicine group, and the Chinese medicine group by paired comparison, 5 in each group. Equivalent clinical dose was administered to mice according to body weight. Mice in the Western medicine group were administered with Atrovastatin at the daily dose of 10 mg/kg by gastrogavage, while those in the Chinese medicine group were administered with HJD at the daily dose of 5 g/kg by gastrogavage. Body weight was detected each week. After 4 weeks blood lipids levels (such as TG, TC, LDL-C, and HDL-C), and the proportions of Mo and Ly6c(hi) were detected. Compared with 4-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05). Levels of TC and TG, and the proportion of Ly6c(hi) subtype increased, but the proportion of Mo de- creased in 8-week-old apoE(-/-) mice (P <0. 05). Levels of TC, TG, and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05). Levels of TC, TG, LDL-C, and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with 8-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05); levels of TC and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05); levels of TC and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with C57BL/6 mice of the same age, TC and TG increased, HDL-C decreased (P < 0.01) in 4-and 8-week-old apoE(-/-) mice (P

  2. Junctional Adhesion Molecule (JAM)-C Deficient C57BL/6 Mice Develop a Severe Hydrocephalus

    Science.gov (United States)

    Liebner, Stefan; Mittelbronn, Michel; Deutsch, Urban; Enzmann, Gaby; Adams, Ralf H.; Aurrand-Lions, Michel; Plate, Karl H.; Imhof, Beat A.; Engelhardt, Britta

    2012-01-01

    The junctional adhesion molecule (JAM)-C is a widely expressed adhesion molecule regulating cell adhesion, cell polarity and inflammation. JAM-C expression and function in the central nervous system (CNS) has been poorly characterized to date. Here we show that JAM-C−/− mice backcrossed onto the C57BL/6 genetic background developed a severe hydrocephalus. An in depth immunohistochemical study revealed specific immunostaining for JAM-C in vascular endothelial cells in the CNS parenchyma, the meninges and in the choroid plexus of healthy C57BL/6 mice. Additional JAM-C immunostaining was detected on ependymal cells lining the ventricles and on choroid plexus epithelial cells. Despite the presence of hemorrhages in the brains of JAM-C−/− mice, our study demonstrates that development of the hydrocephalus was not due to a vascular function of JAM-C as endothelial re-expression of JAM-C failed to rescue the hydrocephalus phenotype of JAM-C−/− C57BL/6 mice. Evaluation of cerebrospinal fluid (CSF) circulation within the ventricular system of JAM-C−/− mice excluded occlusion of the cerebral aqueduct as the cause of hydrocephalus development but showed the acquisition of a block or reduction of CSF drainage from the lateral to the 3rd ventricle in JAM-C−/− C57BL/6 mice. Taken together, our study suggests that JAM-C−/− C57BL/6 mice model the important role for JAM-C in brain development and CSF homeostasis as recently observed in humans with a loss-of-function mutation in JAM-C. PMID:23029139

  3. Overactivation of Hedgehog Signaling Alters Development of the Ovarian Vasculature in Mice1

    Science.gov (United States)

    Ren, Yi; Cowan, Robert G.; Migone, Fernando F.; Quirk, Susan M.

    2012-01-01

    ABSTRACT The hedgehog (HH) signaling pathway is critical for ovarian function in Drosophila, but its role in the mammalian ovary has not been defined. Previously, expression of a dominant active allele of the HH signal transducer protein smoothened (SMO) in Amhr2cre/+SmoM2 mice caused anovulation in association with a lack of smooth muscle in the theca of developing follicles. The current study examined events during the first 2 wk of life in Amhr2cre/+SmoM2 mice to gain insight into the cause of anovulation. Expression of transcriptional targets of HH signaling, Gli1, Ptch1, and Hhip, which are used as measures of pathway activity, were elevated during the first several days of life in Amhr2cre/+SmoM2 mice compared to controls but were similar to controls in older mice. Microarray analysis showed that genes with increased expression in 2-day-old mutants compared to controls were enriched for the processes of vascular and tube development and steroidogenesis. The density of platelet endothelial cell adhesion molecule (PECAM)-labeled endothelial tubes was increased in the cortex of newborn ovaries of mutant mice. Costaining of preovulatory follicles for PECAM and smooth muscle actin showed that muscle-type vascular support cells are deficient in theca of mutant mice. Expression of genes for steroidogenic enzymes that are normally expressed in the fetal adrenal gland were elevated in newborn ovaries of mutant mice. In summary, overactivation of HH signaling during early life alters gene expression and vascular development and this is associated with the lifelong development of anovulatory follicles in which the thecal vasculature fails to mature appropriately. PMID:22402963

  4. Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice.

    Science.gov (United States)

    Zhang, Hongsheng; Kang, Eunchai; Wang, Yaqing; Yang, Chaojuan; Yu, Hui; Wang, Qin; Chen, Zheyu; Zhang, Chen; Christian, Kimberly M; Song, Hongjun; Ming, Guo-Li; Xu, Zhiheng

    2016-06-01

    Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown of crmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.

  5. Hypertension is a conditional factor for the development of cardiac hypertrophy in type 2 diabetic mice.

    Directory of Open Access Journals (Sweden)

    Marc van Bilsen

    Full Text Available BACKGROUND: Type 2 diabetes is frequently associated with co-morbidities, including hypertension. Here we investigated if hypertension is a critical factor in myocardial remodeling and the development of cardiac dysfunction in type 2 diabetic db/db mice. METHODS: Thereto, 14-wks-old male db/db mice and non-diabetic db/+ mice received vehicle or angiotensin II (AngII for 4 wks to induce mild hypertension (n = 9-10 per group. Left ventricular (LV function was assessed by serial echocardiography and during a dobutamine stress test. LV tissue was subjected to molecular and (immunohistochemical analysis to assess effects on hypertrophy, fibrosis and inflammation. RESULTS: Vehicle-treated diabetic mice neither displayed marked myocardial structural remodeling nor cardiac dysfunction. AngII-treatment did not affect body weight and fasting glucose levels, and induced a comparable increase in blood pressure in diabetic and control mice. Nonetheless, AngII-induced LV hypertrophy was significantly more pronounced in diabetic than in control mice as assessed by LV mass (increase +51% and +34%, respectively, p<0.01 and cardiomyocyte size (+53% and +31%, p<0.001. This was associated with enhanced LV mRNA expression of markers of hypertrophy and fibrosis and reduced activation of AMP-activated protein kinase (AMPK, while accumulation of Advanced Glycation End products (AGEs and the expression levels of markers of inflammation were not altered. Moreover, AngII-treatment reduced LV fractional shortening and contractility in diabetic mice, but not in control mice. CONCLUSIONS: Collectively, the present findings indicate that type 2 diabetes in its early stage is not yet associated with adverse cardiac structural changes, but already renders the heart more susceptible to hypertension-induced hypertrophic remodeling.

  6. TRAF3IP2 mediates atherosclerotic plaque development and vulnerability in ApoE−/− mice

    Science.gov (United States)

    Prasad, Sakamuri Siva Sankara Vara; Higashi, Yusuke; Sukhanov, Sergiy; Siddesha, Jalahalli M; Delafontaine, Patrice; Siebenlist, Ulrich; Chandrasekar, Bysani

    2016-01-01

    Background and aims Atherosclerosis is a major cause of heart attack and stroke. Inflammation plays a critical role in the development of atherosclerosis. Since the cytoplasmic adaptor molecule TRAF3IP2 (TRAF3-Interacting Protein 2) plays a causal role in various autoimmune and inflammatory diseases, we hypothesized that TRAF3IP2 mediates atherosclerotic plaque development. Methods TRAF3IP2/ApoE double knockout (DKO) mice were generated by crossing TRAF3IP2−/− and ApoE−/− mice. ApoE−/− mice served as controls. Both DKO and control mice were fed a high-fat diet for 12 weeks. Plasma lipids were measured by ELISA, atherosclerosis by en face analysis of aorta and plaque cross-section measurements at the aortic valve region, plaque necrotic core area, collagen and smooth muscle cell content by histomorphometry, and aortic gene expression by RT-qPCR. Results The plasma lipoprotein profile was not altered by TRAF3IP2 gene deletion in ApoE−/− mice. While total aortic plaque area was decreased in DKO female, but not male mice, the plaque necrotic area was significantly decreased in DKO mice of both genders. Plaque collagen and smooth muscle cell contents were increased significantly in both female and male DKO mice compared to respective controls. Aortic expression of proinflammatory cytokine (Tumor necrosis factor α, TNFα), chemokine (Chemokine (C-X-C motif) Ligand 1, CXCL1) and adhesion molecule (Vascular cell adhesion molecule 1, VCAM1; and Intercellular adhesion molecule 1, ICAM1) gene expression were decreased in both male and female DKO mice. In addition, the male DKO mice showed a markedly reduced expression of extracellular matrix (ECM)-related genes, including TIMP1 (Tissue inhibitor of metalloproteinase 1), RECK (Reversion-Inducing- Cysteine-Rich Protein with Kazal Motifs) and ADAM17 (A Disintegrin And Metalloproteinase 17). Conclusions TRAF3IP2 plays a causal role in atherosclerotic plaque development and vulnerability, possibly by inducing the

  7. Development of electrocardiogram intervals during growth of FVB/N neonate mice

    Science.gov (United States)

    2010-01-01

    Background Electrocardiography remains the best diagnostic tool and therapeutic biomarker for a spectrum of pediatric diseases involving cardiac or autonomic nervous system defects. As genetic links to these disorders are established and transgenic mouse models produced in efforts to understand and treat them, there is a surprising lack of information on electrocardiograms (ECGs) and ECG abnormalities in neonate mice. This is likely due to the trauma and anaesthesia required of many legacy approaches to ECG recording in mice, exacerbated by the fragility of many mutant neonates. Here, we use a non-invasive system to characterize development of the heart rate and electrocardiogram throughout the growth of conscious neonate FVB/N mice. Results We examine ECG waveforms as early as two days after birth. At this point males and females demonstrate comparable heart rates that are 50% lower than adult mice. Neonatal mice exhibit very low heart rate variability. Within 12 days of birth PR, QRS and QTc interval durations are near adult values while heart rate continues to increase until weaning. Upon weaning FVB/N females quickly develop slower heart rates than males, though PR intervals are comparable between sexes until a later age. This suggests separate developmental events may contribute to these gender differences in electrocardiography. Conclusions We provide insight with a new level of detail to the natural course of heart rate establishment in neonate mice. ECG can now be conveniently and repeatedly used in neonatal mice. This should serve to be of broad utility, facilitating further investigations into development of a diverse group of diseases and therapeutics in preclinical mouse studies. PMID:20735846

  8. Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

    International Nuclear Information System (INIS)

    Zhang, Pengpeng; Shan, Tizhong; Liang, Xinrong; Deng, Changyan; Kuang, Shihuan

    2014-01-01

    Highlights: • mTOR is a critical regulator of many biological processes yet its function in heart is not well understood. • MCK-Cre/Mtor flox/flox mice were established to delete Mtor in cardiomyocytes. • The mTOR-mKO mice developed normally but die prematurely within 5 weeks after birth due to heart disease. • The mTOR-mKO mice had dilated myocardium and increased cell death. • mTOR-mKO hearts had reduced expression of metabolic genes and activation of mTOR target proteins. - Abstract: Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor flox/flox mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function

  9. Probiotic bacteria for prevention of atopic diseases: design and application

    NARCIS (Netherlands)

    Niers, L.E.M.

    2009-01-01

    Atopic diseases such as (atopic) eczema, food allergy, asthma, and allergic rhinitis are common diseases. The cumulative incidence during childhood is estimated to be 20 to 30%. In countries with a so called ‘’Western lifestyle’’ an increase in the prevalence of atopic diseases has been observed

  10. Contact sensitization in Dutch children and adolescents with and without atopic dermatitis - a retrospective analysis.

    Science.gov (United States)

    Lubbes, Stefanie; Rustemeyer, Thomas; Sillevis Smitt, Johannes H; Schuttelaar, Marie Louise; Middelkamp-Hup, Maritza A

    2017-03-01

    Allergic contact dermatitis is known to occur in children with and without atopic dermatitis, but more data are needed on contact sensitization profiles in these two groups. To identify frequent allergens in children with and without atopic dermatitis suspected of having allergic contact dermatitis. A retrospective analysis of children aged 0-17 years patch tested between 1996 and 2013 was performed. Of all 1012 children tested because of suspected contact dermatitis, 46% developed one or more positive reactions, the proportions for children with (n = 526) and without (n = 395) atopic dermatitis being 48% and 47%, respectively. Children with atopic dermatitis reacted more often to lanolin alcohol (30% pet., p = 0.030), Amerchol L-101 (p = 0.030), and fragrances [fragrance mix I (p = 0.048) and Myroxylon pereirae (p = 0.005)]. Allergens outside the European baseline series that frequently gave positive reactions in these groups included cocamidopropyl betaine and Amerchol L-101. Reactivity to these allergens was significantly more common in atopic dermatitis children. Sensitization prevalences in children with and without atopic dermatitis were similar, but children with atopic dermatitis reacted significantly more often to lanolin alcohol and fragrances. Testing with additional series besides the European baseline series may be necessary, as reactions to, for example, cocamidopropyl betaine and Amerchol L-101 may otherwise be missed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Psychological disturbance in atopic eczema: the extent of the problem in school-aged children.

    Science.gov (United States)

    Absolon, C M; Cottrell, D; Eldridge, S M; Glover, M T

    1997-08-01

    Although psychological factors are widely considered to be important in atopic eczema, there have been few controlled studies to assess the extent of disturbance in affected children and the problems experienced by their parents. This study was designed to find out the degree of psychological difficulty experienced by children with atopic eczema, whether their mothers show higher levels of mental distress than a comparison group, and whether the families of children with atopic eczema have less social support than the comparison group. We investigated 30 school-aged children with atopic eczema for psychological problems using the Rutter parent scale and compared them with 30 children with relatively minor skin lesions such as viral warts. Mental distress in mothers was assessed using the General Health Questionnaire. The Family Support Scale was used to get a measure of the social support experienced by the families. We found twice the rate of psychological disturbance in children in the eczema group compared with the control group. This difference was statistically significant for children with moderately severe eczema and severe eczema, but not for children with very mild eczema. Levels of mental distress were no greater in mothers of children with eczema than in parents of the control group and there was no difference in the degree of social support experienced by their families. These findings indicate that school-aged children with moderate and severe atopic eczema are at high risk of developing psychological difficulties, which may have implications for their academic and social development.

  12. Suppressive effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Natsume, Midori; Baba, Seigo

    2014-01-01

    Previous studies in humans have shown that the cacao polyphenols, (-)-epicatechin and its oligomers, prevent in vitro and ex vivo low-density lipoprotein oxidation mediated by free radical generators and metal ions and also reduce plasma LDL-cholesterol levels. The aim of this study was to examine the effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice. Mice aged 8 weeks (n = 90) were randomized into three groups, and fed either normal mouse chow (controls) or chow supplemented with 0.25 or 0.40 % cacao polyphenols for 16 weeks. The mean plaque area in cross-sections of the brachiocephalic trunk was measured and found to be lower in the 0.25 % cacao polyphenol group than in the control group (p cacao polyphenol group (p cacao polyphenols inhibit the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice by reducing oxidative stress and inflammatory responses.

  13. Excess TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate.

    Science.gov (United States)

    Endo, Toyoshi; Kobayashi, Tetsuro

    2013-09-01

    Hypothyroidism in the young leads to irreversible growth failure. hyt/hyt Mice have a nonfunctional TSH receptor (TSHR) and are severely hypothyroid, but growth retardation was not observed in adult mice. We found that epiphysial cartilage as well as cultured chondrocytes expressed functional TSHR at levels comparable to that seen in the thyroid, and that addition of TSH to cultured chondrocytes suppressed expression of chondrocyte differentiation marker genes such as Sox-9 and type IIa collagen. Next, we compared the long bone phenotypes of two distinct mouse models of hypothyroidism: thyroidectomized (THYx) mice and hyt/hyt mice. Although both THYx and hyt/hyt mice were severely hypothyroid and had similar serum Ca(2+) and growth hormone levels, the tibia was shorter and the proliferating and hypertrophic zones in the growth plate was significantly narrower in THYx mice than in hyt/hyt mice. Supplementation of hyt/hyt mice thyroid hormone resulted in a wider growth plate compared with that of wild-type mice. Expressions of chondrocyte differentiation marker genes Sox-9 and type IIa collagen in growth plate from THYx mice were 52 and 60% lower than those of hyt/hyt mice, respectively. High serum TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate.

  14. Types and rate of cataract development in mice irradiated at different ages

    International Nuclear Information System (INIS)

    Gajewski, A.K.; Majewska, K.; Slowikowska, M.G.; Chomiczewski, K.; Kulig, A.

    1977-01-01

    The effect of age on the development of radiation cataract has been investigated in an inbred A strain of mice and, as a result, the patterns of age dependence and senile mice cataract development were obtained. In general, the lenses of mice 1 to 3 days old were the most sensitive to radiation; the maximum resistance was noted in 5-day-old mice, and from this age up to 3 to 7 weeks of life there was a period of increasing sensitivity. In older animals the lens sensitivity tends to level off. The early stages of cataract occurred in all irradiated groups at a younger age than in the control group, but the late stages occurred in irradiated groups at the same age as the senile cataract occurred in the control group. Two types of cataract were observed. One was typical for young irradiated mice 1 to 5 days of age and the other was typical for all remaining irradiated groups and for a control group. Also, an attempt was made to correlate the obtained results with the cell kinetics in normal lens epithelium

  15. Lgl1 Is Required for Olfaction and Development of Olfactory Bulb in Mice

    Science.gov (United States)

    Li, Zhenzu; Zhang, Tingting; Lin, Zhuchun; Hou, Congzhe; Zhang, Jian; Men, Yuqin; Li, Huashun

    2016-01-01

    Lethal giant larvae 1 (Lgl1) was initially identified as a tumor suppressor in Drosophila and functioned as a key regulator of epithelial polarity and asymmetric cell division. In this study, we generated Lgl1 conditional knockout mice mediated by Pax2-Cre, which is expressed in olfactory bulb (OB). Next, we examined the effects of Lgl1 loss in the OB. First, we determined the expression patterns of Lgl1 in the neurogenic regions of the embryonic dorsal region of the LGE (dLGE) and postnatal OB. Furthermore, the Lgl1 conditional mutants exhibited abnormal morphological characteristics of the OB. Our behavioral analysis exhibited greatly impaired olfaction in Lgl1 mutant mice. To elucidate the possible mechanisms of impaired olfaction in Lgl1 mutant mice, we investigated the development of the OB. Interestingly, reduced thickness of the MCL and decreased density of mitral cells (MCs) were observed in Lgl1 mutant mice. Additionally, we observed a dramatic loss in SP8+ interneurons (e.g. calretinin and GABAergic/non-dopaminergic interneurons) in the GL of the OB. Our results demonstrate that Lgl1 is required for the development of the OB and the deletion of Lgl1 results in impaired olfaction in mice. PMID:27603780

  16. Prenatal animal contact and gene expression of innate immunity receptors at birth are associated with atopic dermatitis.

    Science.gov (United States)

    Roduit, Caroline; Wohlgensinger, Johanna; Frei, Remo; Bitter, Sondhja; Bieli, Christian; Loeliger, Susanne; Büchele, Gisela; Riedler, Josef; Dalphin, Jean-Charles; Remes, Sami; Roponen, Marjut; Pekkanen, Juha; Kabesch, Michael; Schaub, Bianca; von Mutius, Erika; Braun-Fahrländer, Charlotte; Lauener, Roger

    2011-01-01

    Cross-sectional studies have suggested that prenatal farm exposures might protect against allergic disease and increase the expression of receptors of the innate immune system. However, epidemiologic evidence supporting the association with atopic dermatitis remains inconsistent. To study the association between prenatal farm-related exposures and atopic dermatitis in a prospective study. We further analyzed the association between the expression of innate immune genes at birth and atopic dermatitis. A total of 1063 children who participated in a birth cohort study, Protection against Allergy-Study in Rural Environments, were included in this study. Doctor diagnosis of atopic dermatitis was reported by the parents from 1 to 2 years of age by questionnaire. Gene expression of Toll-like receptors (TLRs) and CD14 was assessed in cord blood leukocytes by quantitative PCR. Maternal contact with farm animals and cats during pregnancy had a significantly protective effect on atopic dermatitis in the first 2 years of life. The risk of atopic dermatitis was reduced by more than half among children with mothers having contact with 3 or more farm animal species during pregnancy compared with children with mothers without contact (adjusted odds ratio, 0.43; 95% CI, 0.19-0.97). Elevated expression of TLR5 and TLR9 in cord blood was associated with decreased doctor diagnosis of atopic dermatitis. A significant interaction between polymorphism in TLR2 and prenatal cat exposure was observed in atopic dermatitis. Maternal contact with farm animals and cats during pregnancy has a protective effect on the development of atopic dermatitis in early life, which is associated with a lower expression of innate immune receptors at birth. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  17. Association of atopic dermatitis with smoking

    DEFF Research Database (Denmark)

    Kantor, Robert; Kim, Ashley; Thyssen, Jacob P

    2016-01-01

    BACKGROUND: Tobacco exposure might be a modifiable risk factor for atopic dermatitis (AD). OBJECTIVE: We examine the association between AD and exposure to tobacco smoke. METHODS: We performed a systematic review and meta-analysis of observational studies (n = 86) in MEDLINE, EMBASE, Scopus...

  18. Autoimmune diseases in adults with atopic dermatitis

    DEFF Research Database (Denmark)

    Andersen, Yuki M.F.; Egeberg, Alexander; Gislason, Gunnar H.

    2017-01-01

    Background An increased susceptibility to autoimmune disease has been shown in patients with atopic dermatitis (AD), but data remain scarce and inconsistent. Objective We examined the co-occurrence of selected autoimmune diseases in adult patients with AD. Methods Nationwide health registers were...

  19. Use of systemic corticosteroids for atopic dermatitis

    DEFF Research Database (Denmark)

    Drucker, A M; Eyerich, K; de Bruin-Weller, M S

    2018-01-01

    BACKGROUND: Guidelines discourage the use of systemic corticosteroids for atopic dermatitis (AD), but their use remains widespread. OBJECTIVES: To reach consensus among an international group of AD experts on the use of systemic corticosteroids for AD. METHODS: A survey consisting of statements...

  20. Is atopic dermatitis associated with obesity?

    DEFF Research Database (Denmark)

    Ali, Zarqa; Suppli Ulrik, Charlotte; Agner, Tove

    2018-01-01

    Obesity has been associated with atopic dermatitis (AD), however the results have been conflicting. Our aim was to provide an update on current knowledge from observational studies addressing the possible association between obesity and AD. Systematic literature review was performed by identifying...

  1. A study of atopic diseases in Basrah

    African Journals Online (AJOL)

    STORAGESEVER

    2008-11-19

    Nov 19, 2008 ... The patients were divided into three age stages as shown in. Table 1. RESULTS AND DISCUSSION. From 174 patients 68 (39.08%) patients suffer with atopic dermatitis followed by bronchial asthma with 59 cases. (33.90%) and allergic rhinitis with 47 cases (27.01%). (Table 2). Table 3 shows that more ...

  2. [Allergy testing in atopic dermatitis: often unnecessary

    NARCIS (Netherlands)

    Thijs, J.L.; Damoiseaux, R.A.; Lucassen, P.L.; Pasmans, S.G.; Bruin-Weller, M. de; Bruijnzeel-Koomen, C.A.

    2013-01-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease from which many children and adults suffer. In the Netherlands, the majority of patients with AD are treated in the primary health care setting. There is no clear consensus about whether or not to conduct allergy testing in patients with

  3. Effects of Resistance Exercise Intensity on Cytokine and Chemokine Gene Expression in Atopic Dermatitis Mouse Model

    Directory of Open Access Journals (Sweden)

    Eun-Ju Choi

    2018-04-01

    Full Text Available Background and Objective: Although the evidence is unclear, literature indicates that resistance exercise reduces inflammation in colorectal disease. The purpose of this study was to identify the effects of colon tissue on cytokine and chemokine gene expression with changes in resistance exercise intensity. Material and Methods: We divided male BABL/c mice into 6 groups (each group n=10, total=60 (control group: CON, low resistance exercise group: EX_L, high resistance exercise group: EX_H, atopic dermatitis group: AD, atopic dermatitis+low resistance exercise group: AD+EX_L, atopic dermatitis+high resistance exercise group: AD+EX_H and subjected them to ladder climbing resistance exercise for 4 weeks. After 24 h of each exercise schedule, a real-time polymerase chain reaction was performed to determine mRNA expression of interleukin-6 (IL-6 and chemokine ligand 20 (CCL20. Results: The AD group showed significantly higher mRNA expression of IL-6 and CCL20 compared with the CON, EX_L, EX_H, AD+EX_L, and AD+EX_H groups (p<0.05. Conclusion: In conclusion, both high and low resistance exercise effectively decreases the concentration of IL-6 and CCL20 in mice with and without AD.

  4. p120-Catenin Is Critical for the Development of Invasive Lobular Carcinoma in Mice.

    Science.gov (United States)

    Tenhagen, Milou; Klarenbeek, Sjoerd; Braumuller, Tanya M; Hofmann, Ilse; van der Groep, Petra; Ter Hoeve, Natalie; van der Wall, Elsken; Jonkers, Jos; Derksen, Patrick W B

    2016-12-01

    Loss of E-cadherin expression is causal to the development of invasive lobular breast carcinoma (ILC). E-cadherin loss leads to dismantling of the adherens junction and subsequent translocation of p120-catenin (p120) to the cytosol and nucleus. Although p120 is critical for the metastatic potential of ILC through the regulation of Rock-dependent anoikis resistance, it remains unknown whether p120 also contributes to ILC development. Using genetically engineered mouse models with mammary gland-specific inactivation of E-cadherin, p120 and p53, we demonstrate that ILC formation induced by E-cadherin and p53 loss is severely impaired upon concomitant inactivation of p120. Tumors that developed in the triple-knockout mice were mostly basal sarcomatoid carcinomas that displayed overt nuclear atypia and multinucleation. In line with the strong reduction in ILC incidence in triple-knockout mice compared to E-cadherin and p53 double-knockout mice, no functional redundancy of p120 family members was observed in mouse ILC development, as expression and localization of ARVCF, p0071 or δ-catenin was unaltered in ILCs from triple-knockout mice. In conclusion, we show that loss of p120 in the context of the p53-deficient mouse models is dominant over E-cadherin inactivation and its inactivation promotes the development of basal, epithelial-to-mesenchymal-transition (EMT)-type invasive mammary tumors.

  5. EVALUATION OF EFFECTIVENESS OF HYPOALLERGENIC COMPOUND, ENRICHED WITH PREBIOTICS, FOR THE PROPHYLACTICS OF ATOPIC DERMATITIS

    Directory of Open Access Journals (Sweden)

    A.A. Dzhumagaziyev

    2010-01-01

    Full Text Available The article presents a study of prophylactic effectiveness of hypoallergenic compound «Nutrilon Hypoallergenic 1», fortified with prebiotics «IMMUNOFORTIS», in children from group of risk of development of atopic dermatitis. Anthropometric rates of children after 8 weeks of observation corresponded with average age rates; their physical development was estimated as harmonious. The compound was well-tolerated. Its use resulted in increase of bifido- and lactobacteria of intestinal micro flora and decrease of acute respiratory infections in infants.Key words: infants, alimentary allergy, atopic dermatitis, artificial feeding, prebiotics, hypoallergenic compound.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(1:37-43

  6. GUIDELINES OF CARE FOR THE MANAGEMENT OF ATOPIC DERMATITIS

    Science.gov (United States)

    Eichenfield, Lawrence F.; Tom, Wynnis L.; Chamlin, Sarah L.; Feldman, Steven R.; Hanifin, Jon M.; Simpson, Eric L.; Berger, Timothy G.; Bergman, James N.; Cohen, David E.; Cooper, Kevin D.; Cordoro, Kelly M.; Davis, Dawn M.; Krol, Alfons; Margolis, David J.; Paller, Amy S.; Schwarzenberger, Kathryn; Silverman, Robert A.; Williams, Hywel C.; Elmets, Craig A.; Block, Julie; Harrod, Christopher G.; Begolka, Wendy Smith; Sidbury, Robert

    2014-01-01

    Atopic dermatitis (AD) is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2–3% of adults. This guideline addresses important clinical questions that arise in AD management and care, providing updated and expanded recommendations based on the available evidence. In this first of four sections, methods for diagnosis and monitoring of disease, outcomes measures for assessment and common clinical associations that affect patients with AD are discussed. Known risk factors for the development of disease are also reviewed. PMID:24290431

  7. A comparison between criteria for diagnosing atopic eczema in infants

    DEFF Research Database (Denmark)

    Jøhnke, H; Vach, W; Norberg, L A

    2005-01-01

    Research Centre (DARC) criteria developed for this study and doctor-diagnosed visible eczema with typical morphology and atopic distribution. Additionally, the U.K. diagnostic criteria based on a questionnaire were used at 1 year of age. Agreement between the four criteria was analysed at each time point...... the four criteria demonstrated that cumulative incidences showed better agreement than point prevalence values. CONCLUSIONS: Agreement between different criteria for diagnosing AE was acceptable, but the mild cases constituted a diagnostic problem, although they were in the minority. Repeated examinations...

  8. Testicular development in mice lacking receptors for follicle stimulating hormone and androgen.

    Directory of Open Access Journals (Sweden)

    Peter J O'Shaughnessy

    Full Text Available Post-natal testicular development is dependent on gonadotrophin and androgen stimulation. Follicle stimulating hormone (FSH acts through receptors (FSHR on the Sertoli cell to stimulate spermatogenesis while androgens promote testis growth through receptors (AR on the Sertoli cells, Leydig cells and peritubular myoid cells. In this study we have examined the effects on testis development of ablating FSHRs (FSHRKO mice and/or ARs ubiquitously (ARKO mice or specifically on the Sertoli cells (SCARKO mice. Cell numbers were measured using stereological methods. In ARKO mice Sertoli cell numbers were reduced at all ages from birth until adulthood. FSHR ablation also caused small reductions in Sertoli cell numbers up to day 20 with more marked effects seen in the adult. Germ cell numbers were unaffected by FSHR and/or AR ablation at birth. By day 20 ubiquitous AR or FSHR ablation caused a marked reduction in germ cell numbers with a synergistic effect of losing both receptors (germ cell numbers in FSHRKO.ARKO mice were 3% of control. Germ cell numbers in SCARKO mice were less affected. By adulthood, in contrast, clear synergistic control of germ cell numbers had become established between the actions of FSH and androgen through the Sertoli cells. Leydig cell numbers were normal on day 1 and day 5 in all groups. By day 20 and in adult animals total AR or FSHR ablation significantly reduced Leydig cell numbers but Sertoli cell specific AR ablation had no effect. Results show that, prior to puberty, development of most testicular parameters is more dependent on FSH action than androgen action mediated through the Sertoli cells although androgen action through other cells types is crucial. Post-pubertally, germ cell numbers and spermatogenesis are dependent on FSH and androgen action through the Sertoli cells.

  9. Sodium meta-arsenite prevents the development of autoimmune diabetes in NOD mice

    International Nuclear Information System (INIS)

    Lee, Y.S.; Kim, D.; Lee, E.K.; Kim, S.; Choi, C.S.; Jun, H.S.

    2015-01-01

    Sodium meta-arsenite (SA) is an orally available arsenic compound. We investigated the effects of SA on the development of autoimmune type 1 diabetes. Female non-obese diabetic (NOD) mice were orally intubated with SA (5 mg/kg/day) from 8 weeks of age for 8 weeks. The cumulative incidence of diabetes was monitored until 30 weeks of age, islet histology was examined, and lymphocytes including T cells, B cells, CD4+ IFN-γ+ cells, CD8+ IFN-γ+ cells, CD4+ IL-4+ cells, and regulatory T cells were analyzed. We also investigated the diabetogenic ability of splenocytes using an adoptive transfer model and the effect of SA on the proliferation, activation, and expression of glucose transporter 1 (Glut1) in splenocytes treated with SA in vitro and splenocytes isolated from SA-treated mice. SA treatment decreased the incidence of diabetes and delayed disease onset. SA treatment reduced the infiltration of immunocytes in islets, and splenocytes from SA-treated mice showed a reduced ability to transfer diabetes. The number of total splenocytes and T cells and both the number and the proportion of CD4+ IFN-γ+ and CD8+ IFN-γ+ T cells in the spleen were significantly reduced in SA-treated NOD mice compared with controls. The number, but not the proportion, of regulatory T cells was decreased in SA-treated NOD mice. Treatment with SA either in vitro or in vivo inhibited proliferation of splenocytes. In addition, the expression of Glut1 and phosphorylated ERK1/2 was decreased by SA treatment. These results suggest that SA reduces proliferation and activation of T cells, thus preventing autoimmune diabetes in NOD mice. - Highlights: • SA prevents the development of diabetes and delays the age of onset in NOD mice. • SA decreases the number but not the proportion of T lymphocytes in NOD mice. • SA reduces IFN-γ-producing T lymphocytes in NOD mice. • SA reduces proliferation and activation of T lymphocytes in vitro and in vivo. • SA reduces the expression of glucose

  10. Sodium meta-arsenite prevents the development of autoimmune diabetes in NOD mice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y.S.; Kim, D.; Lee, E.K. [Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); Kim, S. [Komipharm International Co. Ltd., 3188, Seongnam-dong, Jungwon-gu, Seongnam-si, Gyeonggi-do 462-827 (Korea, Republic of); Choi, C.S. [Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); Endocrinology, Internal Medicine, Gachon University Gil Medical Center, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760 (Korea, Republic of); Gachon Medical Research Institute, Gil Hospital, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760 (Korea, Republic of); Jun, H.S., E-mail: hsjun@gachon.ac.kr [Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); Gachon Medical Research Institute, Gil Hospital, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760 (Korea, Republic of)

    2015-04-15

    Sodium meta-arsenite (SA) is an orally available arsenic compound. We investigated the effects of SA on the development of autoimmune type 1 diabetes. Female non-obese diabetic (NOD) mice were orally intubated with SA (5 mg/kg/day) from 8 weeks of age for 8 weeks. The cumulative incidence of diabetes was monitored until 30 weeks of age, islet histology was examined, and lymphocytes including T cells, B cells, CD4+ IFN-γ+ cells, CD8+ IFN-γ+ cells, CD4+ IL-4+ cells, and regulatory T cells were analyzed. We also investigated the diabetogenic ability of splenocytes using an adoptive transfer model and the effect of SA on the proliferation, activation, and expression of glucose transporter 1 (Glut1) in splenocytes treated with SA in vitro and splenocytes isolated from SA-treated mice. SA treatment decreased the incidence of diabetes and delayed disease onset. SA treatment reduced the infiltration of immunocytes in islets, and splenocytes from SA-treated mice showed a reduced ability to transfer diabetes. The number of total splenocytes and T cells and both the number and the proportion of CD4+ IFN-γ+ and CD8+ IFN-γ+ T cells in the spleen were significantly reduced in SA-treated NOD mice compared with controls. The number, but not the proportion, of regulatory T cells was decreased in SA-treated NOD mice. Treatment with SA either in vitro or in vivo inhibited proliferation of splenocytes. In addition, the expression of Glut1 and phosphorylated ERK1/2 was decreased by SA treatment. These results suggest that SA reduces proliferation and activation of T cells, thus preventing autoimmune diabetes in NOD mice. - Highlights: • SA prevents the development of diabetes and delays the age of onset in NOD mice. • SA decreases the number but not the proportion of T lymphocytes in NOD mice. • SA reduces IFN-γ-producing T lymphocytes in NOD mice. • SA reduces proliferation and activation of T lymphocytes in vitro and in vivo. • SA reduces the expression of glucose

  11. Elastin-derived peptides are new regulators of insulin resistance development in mice

    DEFF Research Database (Denmark)

    Blaise, Sébastien; Romier, Béatrice; Kawecki, Charlotte

    2013-01-01

    . In the current study, we show that elastin-derived peptides (EDPs) may be involved in the development of insulin resistance (IRES) in mice. In chow-fed mice, acute or chronic intravenous injections of EDPs induced hyperglycemic effects associated with glucose uptake reduction and IRES in skeletal muscle, liver......, and adipose tissue. Based on in vivo, in vitro, and in silico approaches, we propose that this IRES is due to interaction between the insulin receptor (IR) and the neuraminidase-1 subunit of the elastin receptor complex triggered by EDPs. This interplay was correlated with decreased sialic acid levels...

  12. Development of Schistosoma incognitum in mice upon intraperitoneal inoculation with irradiated schistosomula

    International Nuclear Information System (INIS)

    Bhilegaonkar, N.G.; Sahasrabudhe, V.K.

    1987-01-01

    As a prelude to the study of the immunizing potential of gamma-irradiated Schistosoma incognitum schistosomula, experiments were conducted to study the effect of different doses of gamma irradiation (1,3,5 and 10 kr) on the development and survival of S. incognitum in mice, and its attendant pathology. The present experiments suggested that 3 and 5 kr irradiation doses can be safely used for irradiating schistosomula for immunization experiments in mice as the worms will not mature and therefore no harm will be caused which is mainly due to the eggs. (author). 7 refs

  13. Pituitary mammosomatotroph adenomas develop in old mice transgenic for growth hormone-releasing hormone

    DEFF Research Database (Denmark)

    Asa, S L; Kovacs, K; Stefaneanu, L

    1990-01-01

    It has been shown that mice transgenic for human growth hormone-releasing hormone (GRH) develop hyperplasia of pituitary somatotrophs and mammosomatotrophs, cells capable of producing both growth hormone and prolactin, by 8 months of age. We now report for the first time that old GRH-transgenic...

  14. Mice deficient in CD38 develop an attenuated form of collagen type II-induced arthritis.

    Science.gov (United States)

    Postigo, Jorge; Iglesias, Marcos; Cerezo-Wallis, Daniela; Rosal-Vela, Antonio; García-Rodríguez, Sonia; Zubiaur, Mercedes; Sancho, Jaime; Merino, Ramón; Merino, Jesús

    2012-01-01

    CD38, a type II transmembrane glycoprotein expressed in many cells of the immune system, is involved in cell signaling, migration and differentiation. Studies in CD38 deficient mice (CD38 KO mice) indicate that this molecule controls inflammatory immune responses, although its involvement in these responses depends on the disease model analyzed. Here, we explored the role of CD38 in the control of autoimmune responses using chicken collagen type II (col II) immunized C57BL/6-CD38 KO mice as a model of collagen-induced arthritis (CIA). We demonstrate that CD38 KO mice develop an attenuated CIA that is accompanied by a limited joint induction of IL-1β and IL-6 expression, by the lack of induction of IFNγ expression in the joints and by a reduction in the percentages of invariant NKT (iNKT) cells in the spleen. Immunized CD38 KO mice produce high levels of circulating IgG1 and low of IgG2a anti-col II antibodies in association with reduced percentages of Th1 cells in the draining lymph nodes. Altogether, our results show that CD38 participates in the pathogenesis of CIA controlling the number of iNKT cells and promoting Th1 inflammatory responses.

  15. Mice deficient in CD38 develop an attenuated form of collagen type II-induced arthritis.

    Directory of Open Access Journals (Sweden)

    Jorge Postigo

    Full Text Available CD38, a type II transmembrane glycoprotein expressed in many cells of the immune system, is involved in cell signaling, migration and differentiation. Studies in CD38 deficient mice (CD38 KO mice indicate that this molecule controls inflammatory immune responses, although its involvement in these responses depends on the disease model analyzed. Here, we explored the role of CD38 in the control of autoimmune responses using chicken collagen type II (col II immunized C57BL/6-CD38 KO mice as a model of collagen-induced arthritis (CIA. We demonstrate that CD38 KO mice develop an attenuated CIA that is accompanied by a limited joint induction of IL-1β and IL-6 expression, by the lack of induction of IFNγ expression in the joints and by a reduction in the percentages of invariant NKT (iNKT cells in the spleen. Immunized CD38 KO mice produce high levels of circulating IgG1 and low of IgG2a anti-col II antibodies in association with reduced percentages of Th1 cells in the draining lymph nodes. Altogether, our results show that CD38 participates in the pathogenesis of CIA controlling the number of iNKT cells and promoting Th1 inflammatory responses.

  16. Environmental change during postnatal development alters behaviour, cognitions and neurogenesis of mice.

    Science.gov (United States)

    Iso, Hiroyuki; Simoda, Shigero; Matsuyama, Tomohiro

    2007-04-16

    Four groups of male C57BL/6 mice were reared differing combinations of the two environments from 3 to 11 weeks after birth. At 12 and 13 weeks they were assessed by measures of behaviour and learning: open-field activity, auditory startle reflex and prepulse inhibition, water maze learning, and passive avoidance. Another four groups of mice reared under these varying conditions were examined for generation of neurons in hippocampus and cerebral cortex using bromodeoxyuridine (BrdU) at 12 weeks. Enriched (EE) and impoverished (PP) groups were housed in their respective environment for 8 weeks, enriched-impoverished (EP) and impoverished-enriched (PE) mice respectively were reared for 6 weeks in the first-mentioned environment and then for 2 weeks in the second. PP and EP mice showed hyperactivity, greater startle amplitude and significantly slower learning in a water maze than EE or PE animals, and also showed a memory deficit in a probe test, avoidance performance did not differ. Neural generation was greater in the EE and PE than PP and EP groups, especially in the hippocampus. These results suggest that environmental change critically affects behavioural and anatomic brain development, even if brief. In these mice, the effect of unfavourable early experience could be reversed by a later short of favourable experience.

  17. Fancf-deficient mice are prone to develop ovarian tumours

    NARCIS (Netherlands)

    Bakker, S.T.; van der Vrugt, H.J.; Visser, J.A.; Delzenne-Goette, E.; van der Wal, A.; Berns, M.A.D.; van de Ven, M.; Oostra, A.B.; de Vries, S.; Kramer, P.; Arwert, F.; van de Valk, M; de Winter, J.P.; te Riele, H.P.J.

    2012-01-01

    Fanconi anaemia (FA) is a rare recessive disorder marked by developmental abnormalities, bone marrow failure, and a high risk for the development of leukaemia and solid tumours. The inactivation of FA genes, in particular FANCF, has also been documented in sporadic tumours in non-FA patients. To

  18. In vitro skin permeation and anti-atopic efficacy of lipid nanocarriers containing water soluble extracts of Houttuynia cordata.

    Science.gov (United States)

    Kwon, Taek Kwan; Kim, Jin-Chul

    2014-10-01

    The aims of this work are to enhance the in vitro skin permeation of Houttuynia cordata (water-soluble extract of H. cordata; HCWSE) and to boost the efficacy of HCWSE against atopic dermatitis (AD) - like skin lesion in hairless mice using lipid nano-carriers (liposome and cubosome). HCWSE was obtained by a hot water extraction. Monoolein cubosomal suspension containing HCWSE and egg phosphatidylcholine liposomal suspension containing the same was prepared by a sonication and a film hydration method, respectively. The lipid nano-carriers, especially cubosome, enhanced the in vitro skin permeation of HCWSE. The inhibitory effects of HCWSE-containing lipid carrier suspensions on the development of 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like skin lesion in hairless mice were investigated by observing appearance of skin surface, serum immunoglobulin E (IgE) level and cytokine expression. HCWSE-containing preparations suppressed IgE production and interleukin 4 expression, whereas they promoted interferon gamma expression. The order of lymphocyte (B-cell, Th1 cell and Th2 cell) modulating effect was HCWSE-containing cubosomal suspension > HCWSE-containing liposomal suspension > HCWSE solution in phosphate buffered saline, indicating that the cubosomal suspension, among the preparations, was the most efficacious in inhibiting the development of DNCB-induced AD-like skin lesion. It is believed that the cubosomal suspension containing HCWSE would be an efficacious preparation for the treatment of AD.

  19. Tritium toxicity on postnatally developing mice testes: a qualitative and quantitative evaluation

    International Nuclear Information System (INIS)

    Bhatia, A.L.

    1982-01-01

    The present study is an attempt to evaluate the possible radiobiological effects of tritiated water (HTO) on the testes of Swiss albino mice during postnatal development. Mice were continuously irradiated with different doses providing 46, 93 and 185 kBq of HTO per ml drinking water (after a priming injection) from day 1 after brith up to 6 weeks of age. Qualitative and quantitative studies were made at 6 weeks old mice testes and were compared with the sham-irradiated controls. A dose-dependent damage is noticed in the testes in the form of various radiopathological lesions such as intertubular edema, necrotic and pycnotic cells at various stages, mild cytoplasmic vacuolation, fibrosis, sclerosis, cellular edema etc. The number of various germ cells at their different phases were greatly reduced. 185 kBq/ml affect severely the spermatogonia and spermatid populations. The primary spermatocyte level was maintained at the range 64 +- 3.5%

  20. Tritium toxicity on postnatally developing mice testes: a qualitative and quantitative evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Bhatia, A.L. (Rajasthan Univ., Jaipur (India). Radiation Biology Lab.)

    1982-11-01

    The present study is an attempt to evaluate the possible radiobiological effects of tritiated water (HTO) on the testes of Swiss albino mice during postnatal development. Mice were continuously irradiated with different doses providing 46, 93 and 185 kBq of HTO per ml drinking water (after a priming injection) from day 1 after brith up to 6 weeks of age. Qualitative and quantitative studies were made at 6 weeks old mice testes and were compared with the sham-irradiated controls. A dose-dependent damage is noticed in the testes in the form of various radiopathological lesions such as intertubular edema, necrotic and pycnotic cells at various stages, mild cytoplasmic vacuolation, fibrosis, sclerosis, cellular edema etc. The number of various germ cells at their different phases were greatly reduced. 185 kBq/ml affect severely the spermatogonia and spermatid populations. The primary spermatocyte level was maintained at the range 64 +- 3.5%.

  1. Akt2/LDLr double knockout mice display impaired glucose tolerance and develop more complex atherosclerotic plaques than LDLr knockout mice

    NARCIS (Netherlands)

    Rensing, Katrijn L.; de Jager, Saskia C. A.; Stroes, Erik S.; Vos, Mariska; Twickler, Marcel Th B.; Dallinga-Thie, Geesje M.; de Vries, Carlie J. M.; Kuiper, Johan; Bot, Ilze; von der Thüsen, Jan H.

    2014-01-01

    To characterize the phenotype of Akt2/low-density-lipoprotein receptor double knockout (dKO) (Akt2/LDLr dKO) mice with respect to insulin resistance and features of atherosclerotic plaque progression. Metabolic profile and atherosclerotic plaque progression were compared between LDLr KO mice and

  2. Gromwell (Lithospermum erythrorhizon) Supplementation Enhances Epidermal Levels of Ceramides, Glucosylceramides, β-Glucocerebrosidase, and Acidic Sphingomyelinase in NC/Nga Mice

    OpenAIRE

    Kim, Jungmin; Cho, Yunhi

    2013-01-01

    We have previously reported that dietary gromwell (Lithospermum erythrorhizon; LE) prevents the development of atopic dermatitis (AD) with increased epidermal levels of total ceramide (Cer), the major lipid maintaining epidermal barrier. In this study, we investigated whether the increased level of total Cer induced by dietary LE would be related to the altered metabolism of glucosylceramide (GlcCer) and sphingomyelin (SM), two major precursor lipids in Cer generation. NC/Nga mice, an animal ...

  3. Effects of Cymbidium Root Ethanol Extract on Atopic Dermatitis

    Directory of Open Access Journals (Sweden)

    Wan-Joong Kim

    2016-01-01

    Full Text Available Cymbidium has known antibacterial and antiedema activity and has been used as an ingredient in cosmetics and fragrances. The effects of Cymbidium ethanol extract (CYM on allergic response and the underlying mechanisms of action have not been reported. Therefore, the purpose of this study was to determine the effect of CYM on allergic responses. Topical application of CYM was effective against immunoglobulin E (IgE/dinitrophenyl-conjugated bovine serum albumin- (DNP-BSA- induced degranulation of RBL-2H3 cells and anaphylaxis in ICR mice. An allergic dermatitis-like mouse model was used to evaluate the therapeutic potential of CYM in vivo. Continuous application of 2,4-dinitrochlorobenzene (DNCB not only induced dermatitis in ICR mice but also aggravated the skin lesioning. However, the application of CYM decreased skin lesion severity, scratching behavior, and IgE levels. In addition, CYM downregulated the expression of the proinflammatory cytokines interleukin- (IL- 4, IL-13, and tumor necrosis factor- (TNF- α. Studies of signal transduction pathways showed that CYM suppressed the phosphorylation of spleen tyrosine kinase (Syk, an upstream molecule. It also inhibited the phosphorylation of Akt, phospholipase C- (PLC- γ, and mitogen-activated protein kinase kinase kinase (MEKK. These results indicate that CYM may be effective in preventing and reducing allergic response and may have therapeutic potential as an antiallergic agent in disorders such as atopic dermatitis.

  4. Effects of Dim Light at Night on Food Intake and Body Mass in Developing Mice.

    Science.gov (United States)

    Cissé, Yasmine M; Peng, Juan; Nelson, Randy J

    2017-01-01

    Appropriately timed light is critical for circadian organization; exposure to dim light at night (dLAN) disrupts temporal organization of endogenous biological timing. Exposure to dLAN in adult mice is associated with elevated body mass and changes in metabolism putatively driven by voluntary changes in the time of food intake. We predicted that exposure of young mice to LAN could affect adult metabolic function. At 3 weeks (Experiment 1) or 5 weeks (Experiment 2) of age, mice were either maintained in standard light-dark (DARK) cycles or exposed to nightly dLAN (5 lux). In the first two experiments, food intake and locomotor activity were assessed after 4 weeks and a glucose tolerance test was administered after 6 weeks in experimental lighting conditions. In Experiment 3, tissues were collected around the clock at 6 h intervals to investigate rhythmic hepatic clock gene expression in mice exposed to dLAN from 3 or 5 weeks of age. Male and female mice exposed to dLAN beginning at 3 weeks of age displayed similar growth rates and body mass to DARK-reared offspring, despite increasing day-time food intake. Exposure to dLAN beginning at 5 weeks of age increased body mass and daytime food intake in male, but not female, mice. Consistent with the body mass phenotype, clock gene expression was unaltered in the liver. In contrast to adults, dLAN exposure during the development of the peripheral circadian system has sex- and development-dependent effects on body mass gain.

  5. Effects of Dim Light at Night on Food Intake and Body Mass in Developing Mice

    Directory of Open Access Journals (Sweden)

    Yasmine M. Cissé

    2017-05-01

    Full Text Available Appropriately timed light is critical for circadian organization; exposure to dim light at night (dLAN disrupts temporal organization of endogenous biological timing. Exposure to dLAN in adult mice is associated with elevated body mass and changes in metabolism putatively driven by voluntary changes in the time of food intake. We predicted that exposure of young mice to LAN could affect adult metabolic function. At 3 weeks (Experiment 1 or 5 weeks (Experiment 2 of age, mice were either maintained in standard light-dark (DARK cycles or exposed to nightly dLAN (5 lux. In the first two experiments, food intake and locomotor activity were assessed after 4 weeks and a glucose tolerance test was administered after 6 weeks in experimental lighting conditions. In Experiment 3, tissues were collected around the clock at 6 h intervals to investigate rhythmic hepatic clock gene expression in mice exposed to dLAN from 3 or 5 weeks of age. Male and female mice exposed to dLAN beginning at 3 weeks of age displayed similar growth rates and body mass to DARK-reared offspring, despite increasing day-time food intake. Exposure to dLAN beginning at 5 weeks of age increased body mass and daytime food intake in male, but not female, mice. Consistent with the body mass phenotype, clock gene expression was unaltered in the liver. In contrast to adults, dLAN exposure during the development of the peripheral circadian system has sex- and development-dependent effects on body mass gain.

  6. Asic3(-/- female mice with hearing deficit affects social development of pups.

    Directory of Open Access Journals (Sweden)

    Wei-Li Wu

    Full Text Available BACKGROUND: Infant crying is an important cue for mothers to respond adequately. Inappropriate response to infant crying can hinder social development in infants. In rodents, the pup-mother interaction largely depends on pup's calls. Mouse pups emit high frequency to ultrasonic vocalization (2-90 kHz to communicate with their dam for maternal care. However, little is known about how the maternal response to infant crying or pup calls affects social development over the long term. METHODOLOGY/PRINCIPAL FINDINGS: Here we used mice lacking acid-sensing ion channel 3 (Asic3(-/- to create a hearing deficit to probe the effect of caregiver hearing on maternal care and adolescent social development. Female Asic3(-/- mice showed elevated hearing thresholds for low to ultrasonic frequency (4-32 kHz on auditory brain stem response, which thus hindered their response to their pups' wriggling calls and ultrasonic vocalization, as well as their retrieval of pups. In adolescence, pups reared by Asic3(-/- mice showed a social deficit in juvenile social behaviors as compared with those reared by wild-type or heterozygous dams. The social-deficit phenotype in juvenile mice reared by Asic3(-/- mice was associated with the reduced serotonin transmission of the brain. However, Asic3(-/- pups cross-fostered to wild-type dams showed rescued social deficit. CONCLUSIONS/SIGNIFICANCE: Inadequate response to pups' calls as a result of ASIC3-dependent hearing loss confers maternal deficits in caregivers and social development deficits in their young.

  7. Sdhd and SDHD/H19 knockout mice do not develop paraganglioma or pheochromocytoma.

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Bayley

    Full Text Available BACKGROUND: Mitochondrial succinate dehydrogenase (SDH is a component of both the tricarboxylic acid cycle and the electron transport chain. Mutations of SDHD, the first protein of intermediary metabolism shown to be involved in tumorigenesis, lead to the human tumors paraganglioma (PGL and pheochromocytoma (PC. SDHD is remarkable in showing an 'imprinted' tumor suppressor phenotype. Mutations of SDHD show a very high penetrance in man and we postulated that knockout of Sdhd would lead to the development of PGL/PC, probably in aged mice. METHODOLOGY/PRINCIPAL FINDINGS: We generated a conventional knockout of Sdhd in the mouse, removing the entire third exon. We also crossed this mouse with a knockout of H19, a postulated imprinted modifier gene of Sdhd tumorigenesis, to evaluate if loss of these genes together would lead to the initiation or enhancement of tumor development. Homozygous knockout of Sdhd results in embryonic lethality. No paraganglioma or other tumor development was seen in Sdhd KO mice followed for their entire lifespan, in sharp contrast to the highly penetrant phenotype in humans. Heterozygous Sdhd KO mice did not show hyperplasia of paraganglioma-related tissues such as the carotid body or of the adrenal medulla, or any genotype-related pathology, with similar body and organ weights to wildtype mice. A cohort of Sdhd/H19 KO mice developed several cases of profound cardiac hypertrophy, but showed no evidence of PGL/PC. CONCLUSIONS: Knockout of Sdhd in the mouse does not result in a disease phenotype. H19 may not be an initiator of PGL/PC tumorigenesis.

  8. Atopic Dermatitis in Children: Current Clinical Guidelines for Diagnosis and Therapy

    Directory of Open Access Journals (Sweden)

    Leyla S. Namazova-Baranova

    2016-01-01

    Full Text Available Atopic dermatitis is a chronic multifactorial skin disease that is common enough in childhood. The article presents the current data on epidemiology and dynamics of incidence of pathological symptoms, pathogenesis basics, and key factors of the disease development, shows the current classification of the disease. The authors consider in detail the key principles of the diagnosis and peculiarities of a clinical aspect depending on age. Algorithms of a therapeutic approach, as well as basics of an individual hypoallergenic diet are proposed. General recommendations and possible prognosis for pediatric patients with atopic dermatitis are given.

  9. Effects of in Utero Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Epidermal Permeability Barrier Development and Function

    Science.gov (United States)

    Muenyi, Clarisse S.; Carrion, Sandra Leon; Jones, Lynn A.; Kennedy, Lawrence H.; Slominski, Andrzej T.

    2014-01-01

    Background: Development of the epidermal permeability barrier (EPB) is essential for neonatal life. Defects in this barrier are found in many skin diseases such as atopic dermatitis. Objective: We investigated the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development and function of the EPB. Methods: Timed-pregnant C57BL/6J mice were gavaged with corn oil or TCDD (10 μg/kg body weight) on gestation day 12. Embryos were harvested on embryonic day (E) 15, E16, E17, and postnatal day (PND) 1. Results: A skin permeability assay showed that TCDD accelerated the development of the EPB, beginning at E15. This was accompanied by a significant decrease in transepidermal water loss (TEWL), enhanced stratification, and formation of the stratum corneum (SC). The levels of several ceramides were significantly increased at E15 and E16. PND1 histology revealed TCDD-induced acanthosis and epidermal hyperkeratosis. This was accompanied by disrupted epidermal tight junction (TJ) function, with increased dye leakage at the terminal claudin-1–staining TJs of the stratum granulosum. Because the animals did not have enhanced rates of TEWL, a commonly observed phenotype in animals with TJ defects, we performed tape-stripping. Removal of most of the SC resulted in a significant increase in TEWL in TCDD-exposed PND1 pups compared with their control group. Conclusions: These findings demonstrate that in utero exposure to TCDD accelerates the formation of an abnormal EPB with leaky TJs, warranting further study of environmental exposures, epithelial TJ integrity, and atopic disease. Citation: Muenyi CS, Leon Carrion S, Jones LA, Kennedy LH, Slominski AT, Sutter CH, Sutter TR. 2014. Effects of in utero exposure of C57BL/6J mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin on epidermal permeability barrier development and function. Environ Health Perspect 122:1052–1058; http://dx.doi.org/10.1289/ehp.1308045 PMID:24904982

  10. Study of Sperm Parameters and Sperm Fertility in Mice were Exposed to Tamoxifen during Embryonic Development

    Directory of Open Access Journals (Sweden)

    J Soleimanirad

    2017-05-01

    Full Text Available Introduction: Tamoxifen is steroidal drug, which mainly treats breast cancer and also used to stimulate ovulation. The purpose of the present study was the evaluation of sperm parameters and fertility of mice whose mothers had received tamoxifen during pregnancy. Methods: In this study, 30 female and 15 male mice of NMRI were selected for mating. After mating female mice were randomly divided into two groups, the first group (control and second group (experimental. All of which contained 15 mice. From the day 13th day of pregnancy, experimental group has received tamoxifen with the dosage of 5 mg/kg for 7 days. After childbirth of the mated mice, male infants were selected. After reaching the age of puberty (6-8Weeks, adult mice were sacrificed by the cervical dislocation. After take sperm, sperm parameters (count, normality and motility, and sperm fertility was performed. In this study SPSS software and statistical t-test was used (p <0.001. Results: Studies showed that sperm parameters and sperm fertilization were significantly different. The number of sperm in the control group was 83.50±28.20 million, and in the experimental group was 60±14.14 million. There was a decrease in average sperm count in the experimental group compared with the control group (p <0.001. Our findings from in vitro fertilization culture media showed that embryos formation and oocyte disruption between control and experimental groups significantly different (p <0.001. Conclusion: The results showed that tamoxifen exposure during development can cause histological changes in the seminiferous tubules, which can lead to infertility.

  11. Development of an experimental model of neutrophilic pulmonary response induction in mice

    Directory of Open Access Journals (Sweden)

    Leonardo Araújo Pinto

    2003-08-01

    Full Text Available BACKGROUND: Several lung diseases are characterized by a predominantly neutrophilic inflammation. A better understanding of the mechanisms of action of some drugs on the airway inflammation of such diseases may bring advances to the treatment. OBJECTIVE: To develop a method to induce pulmonary neutrophilic response in mice, without active infection. METHODS: Eight adult Swiss mice were used. The study group (n = 4 received an intranasal challenge with 1 x 10(12 CFU/ml of Pseudomonas aeruginosa (Psa, frozen to death. The control group (n = 4 received an intranasal challenge with saline solution. Two days after the intranasal challenge, a bron­choalveolar lavage (BAL was performed with total cell and differential cellularity counts. RESULTS: The total cell count was significantly higher in the group with Psa, as compared to the control group (median of 1.17 x 10(6 and 0.08 x 10(6, respectively, p = 0.029. In addition to this, an absolute predominance of neutrophils was found in the differential cellularity of the mice that had received the Psa challenge. CONCLUSIONS: The model of inducing a neutrophilic pulmonary disease using frost-dead bacteria was successfully developed. This neutrophilic inflammatory response induction model in Swiss mice lungs may be an important tool for testing the anti-inflammatory effect of some antimicrobial drugs on the inflammation of the lower airways.

  12. Excessive Sensory Stimulation during Development Alters Neural Plasticity and Vulnerability to Cocaine in Mice.

    Science.gov (United States)

    Ravinder, Shilpa; Donckels, Elizabeth A; Ramirez, Julian S B; Christakis, Dimitri A; Ramirez, Jan-Marino; Ferguson, Susan M

    2016-01-01

    Early life experiences affect the formation of neuronal networks, which can have a profound impact on brain function and behavior later in life. Previous work has shown that mice exposed to excessive sensory stimulation during development are hyperactive and novelty seeking, and display impaired cognition compared with controls. In this study, we addressed the issue of whether excessive sensory stimulation during development could alter behaviors related to addiction and underlying circuitry in CD-1 mice. We found that the reinforcing properties of cocaine were significantly enhanced in mice exposed to excessive sensory stimulation. Moreover, although these mice displayed hyperactivity that became more pronounced over time, they showed impaired persistence of cocaine-induced locomotor sensitization. These behavioral effects were associated with alterations in glutamatergic transmission in the nucleus accumbens and amygdala. Together, these findings suggest that excessive sensory stimulation in early life significantly alters drug reward and the neural circuits that regulate addiction and attention deficit hyperactivity. These observations highlight the consequences of early life experiences and may have important implications for children growing up in today's complex technological environment.

  13. Recent studies of cutaneous nociception in atopic and non-atopic subjects.

    Science.gov (United States)

    Heyer, G R; Hornstein, O P

    1999-02-01

    Itching reflects a distinct quality of cutaneous nociception elicited by chemical or other stimuli to neuronal receptors at the superficial layers of the skin and muco-cutaneous orifices. Although recent experimental studies of the conduction and perception of itch have yielded deeper insight into the physiology of this sensory quality, little is known about the neuromechanisms involved in pruritus accompanying many inflammatory skin diseases, in particular, in atopic eczema. Previous case-control studies of our research group with patients suffering from atopic eczema (AE) revealed significantly diminished itch perception after iontophoretic application of different doses of histamine as well as substance P (i.c. injected). Further experiments using acetylcholine (ACh, i.c.) clearly demonstrated that ACh elicits pruritus instead of pain in patients with AE. The first part of the present review deals with the results of our most recent case-control studies on histamine-induced itch perception in atopics devoid of eczema as well as in patients with urticaria or psoriasis compared to atopics with or without manifest eczema. We demonstrated that both focal itch and perifocal alloknesis (i.e., itch elicited by a slight mechanical, otherwise non-itching stimulus) were significantly reduced in eczema-free atopics yet were normal in non-atopics suffering from urticaria or psoriasis. In further studies using ACh i.c. injected into the uninvolved skin of patients with AE, lichen ruber, psoriasis, type IV contact eczema, or non-specific nummular eczema (n = 10/each group), all the atopics and 6/10 psoriatics felt itch instead of burning pain, but none of the others did. Different doses of vasoactive intestinal peptide (VIP) i.c. applied to the controls and the atopics with or without eczema did not markedly increase the intensity of nociceptive sensations. However, ACh induced pain in the controls, pure pruritus in the atopics with acute eczema, and a 'mixture' of pain and

  14. Development of a model for marburgvirus based on severe-combined immunodeficiency mice

    Directory of Open Access Journals (Sweden)

    Kalina Warren V

    2007-10-01

    Full Text Available Abstract The filoviruses, Ebola (EBOV and Marburg (MARV, cause a lethal hemorrhagic fever. Human isolates of MARV are not lethal to immmunocompetent adult mice and, to date, there are no reports of a mouse-adapted MARV model. Previously, a uniformly lethal EBOV-Zaire mouse-adapted virus was developed by performing 9 sequential passages in progressively older mice (suckling to adult. Evaluation of this model identified many similarities between infection in mice and nonhuman primates, including viral tropism for antigen-presenting cells, high viral titers in the spleen and liver, and an equivalent mean time to death. Existence of the EBOV mouse model has increased our understanding of host responses to filovirus infections and likely has accelerated the development of countermeasures, as it is one of the only hemorrhagic fever viruses that has multiple candidate vaccines and therapeutics. Here, we demonstrate that serially passaging liver homogenates from MARV-infected severe combined immunodeficient (scid mice was highly successful in reducing the time to death in scid mice from 50–70 days to 7–10 days after MARV-Ci67, -Musoke, or -Ravn challenge. We performed serial sampling studies to characterize the pathology of these scid mouse-adapted MARV strains. These scid mouse-adapted MARV models appear to have many similar properties as the MARV models previously developed in guinea pigs and nonhuman primates. Also, as shown here, the scid-adapted MARV mouse models can be used to evaluate the efficacy of candidate antiviral therapeutic molecules, such as phosphorodiamidate morpholino oligomers or antibodies.

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

    Directory of Open Access Journals (Sweden)

    Kate Kosmac

    2013-03-01

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

  16. What Should General Practice Trainees Learn about Atopic Eczema?

    Directory of Open Access Journals (Sweden)

    Deepani Munidasa

    2015-02-01

    Full Text Available Effective atopic eczema (AE control not only improves quality of life but may also prevent the atopic march. The Royal College of General Practitioners’ (RCGP curriculum does not currently provide specific learning outcomes on AE management. We aimed to gain consensus on learning outcomes to inform curriculum development. A modified Delphi method was used with questionnaires distributed to gather the views of a range of health care professionals (HCPs including general practitioners (GPs, dermatologists, dermatology nurses and parents of children with AE attending a dedicated paediatric dermatology clinic. Ninety-one questionnaires were distributed to 61 HCPs and 30 parents; 81 were returned. All agreed that learning should focus on the common clinical features, complications and management of AE and the need to appreciate its psychosocial impact. Areas of divergence included knowledge of alternative therapies. Parents felt GPs should better understand how to identify, manage and refer severe AD and recognized the value of the specialist eczema nurse. Dermatologists and parents highlighted inconsistencies in advice regarding topical steroids. This study identifies important areas for inclusion as learning outcomes on AE management in the RCGP curriculum and highlights the importance of patients and parents as a valuable resource in the development of medical education.

  17. Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Pengpeng [Key Laboratory of Swine Genetics and Breeding, Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Shan, Tizhong; Liang, Xinrong [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Deng, Changyan [Key Laboratory of Swine Genetics and Breeding, Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Kuang, Shihuan, E-mail: skuang@purdue.edu [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States)

    2014-09-12

    Highlights: • mTOR is a critical regulator of many biological processes yet its function in heart is not well understood. • MCK-Cre/Mtor{sup flox/flox} mice were established to delete Mtor in cardiomyocytes. • The mTOR-mKO mice developed normally but die prematurely within 5 weeks after birth due to heart disease. • The mTOR-mKO mice had dilated myocardium and increased cell death. • mTOR-mKO hearts had reduced expression of metabolic genes and activation of mTOR target proteins. - Abstract: Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor{sup flox/flox} mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function.

  18. Gender-specific impairments on cognitive and behavioral development in mice exposed to fenvalerate during puberty.

    Science.gov (United States)

    Meng, Xiu-Hong; Liu, Ping; Wang, Hua; Zhao, Xian-Feng; Xu, Zhong-Mei; Chen, Gui-Hai; Xu, De-Xiang

    2011-06-24

    In human and rodent models, endocrine disrupting chemicals (EDCs) interfere with the development of cognition and behaviors. Fenvalerate is a potential EDC. The purpose of this study was to examine whether pubertal fenvalerate exposure altered behavioral development. Mice were orally administered with either vehicle or fenvalerate (7.5 or 30 mg/kg/day) from postnatal day (PND) 28 to PND56. Learning and memory were assessed by Morris Water Maze. Aggressive performance was evaluated by aggressive behavior test. Anxiety-related activities were detected by three tests: open-field, plus-maze and black-white alley. Sensorimotor function was analyzed using beam walking and tightrope. Results found that the impairment for spatial learning and memory was more severe in fenvalerate-exposed female mice than in male mice. In addition, pubertal fenvalerate exposure inhibited aggressive behavior in males. Moreover, pubertal fenvalerate exposure increased anxiety activities in females. Altogether, these results suggest that pubertal fenvalerate exposure impairs spatial cognition and behavioral development in a gender-dependent manner. These findings identify fenvalerate as candidate environmental risk factors for cognitive and behavioral development, especially in the critical period of development. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Potential contribution of progesterone receptors to the development of sexual behavior in male and female mice.

    Science.gov (United States)

    Desroziers, Elodie; Brock, Olivier; Bakker, Julie

    2017-04-01

    We previously showed that estradiol can have both defeminizing and feminizing effects on the developing mouse brain. Pre- and early postnatal estradiol defeminized the ability to show lordosis in adulthood, whereas prepubertal estradiol feminized this ability. Furthermore, we found that estradiol upregulates progesterone receptors (PR) during development, inducing both a male-and female-typical pattern of PR expression in the mouse hypothalamus. In the present study, we took advantage of a newly developed PR antagonist (ZK 137316) to determine whether PR contributes to either male- or female-typical sexual differentiation. Thus groups of male and female C57Bl/6j mice were treated with ZK 137316 or OIL as control: males were treated neonatally (P0-P10), during the critical period for male sexual differentiation, and females were treated prepubertally (P15-P25), during the critical period for female sexual differentiation. In adulthood, mice were tested for sexual behavior. In males, some minor effects of neonatal ZK treatment on sexual behavior were observed: latencies to the first mount, intromission and ejaculation were decreased in neonatally ZK treated males; however, this effect disappeared by the second mating test. By contrast, female mice treated with ZK during the prepubertal period showed significantly less lordosis than OIL-treated females. Mate preferences were not affected in either males or females treated with ZK during development. Taken together, these results suggest a role for PR and thus perhaps progesterone in the development of lordosis behavior in female mice. By contrast, no obvious role for PR can be discerned in the development of male sexual behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Impairment of T-regulatory cells in cord blood of atopic mothers.

    Science.gov (United States)

    Schaub, Bianca; Liu, Jing; Höppler, Sabine; Haug, Severine; Sattler, Christine; Lluis, Anna; Illi, Sabina; von Mutius, Erika

    2008-06-01

    Maternal atopy is a strong predictor for the development of childhood allergic diseases. The underlying mechanisms are ill defined, yet regulatory T (Treg) and T(H)17 cells may play a key role potentially shaping the early immune system toward a proallergic or antiallergic immune regulation. We examined T(H)1/T(H)2, Treg, and T(H)17 cell responses to innate (lipid A/peptidoglycan) and mitogen/adaptive (phytohemagglutinin/Dermatophagoides pteronyssinus 1) immune stimulation in cord blood from offspring of atopic/nonatopic mothers. Cord blood mononuclear cells from 161 healthy neonates (59% nonatopic, 41% atopic mothers) were investigated regarding Treg and T(H)17 cells (mRNA/surface markers), suppressive function, and proliferation/cytokine secretion. Cord blood from offspring of atopic mothers showed fewer innate-induced Treg cells (CD4(+)CD25(+)high), lower mRNA expression of associated markers (glucocorticoid-induced tumor necrosis factor receptor-related protein/lymphocyte activation gene 3; P cell function was impaired in mitogen-induced suppression of T effector cells in cord blood of offspring from atopic mothers (P = .03). Furthermore, IL-10 and IFN-gamma secretion were decreased in innate-stimulated cord blood of offspring from atopic mothers (P = .04/.05). Innate-induced IL-17 was independent of maternal atopy and highly correlated with IL-13 secretion. In offspring of atopic mothers, Treg cell numbers, expression, and function were impaired at birth. T(H)17 cells were correlated with T(H)2 cells, independently of maternal atopy.

  1. First observation of the decay $\\bar{B}$$0\\atop{s}$ → D$±\\atop{s}$ K and measurement of the relative branching fraction B($\\bar{B}$$0\\atop{s}$→ D$±\\atop{s}$ K)/B($\\bar{B}$$0\\atop{s}$→ D$+\\atop{s}$ π-).

    Energy Technology Data Exchange (ETDEWEB)

    Muelmenstaedt, Johannes [Univ. of California, Berkeley, CA (United States)

    2007-01-01

    We present the first observation of the decay $\\bar{B}$$0\\atop{s}$→ D$±\\atop{s}$ K∓ and measure the relative branching fraction of $\\bar{B}$$0\\atop{s}$ → D$±\\atop{s}$ K∓ to $\\bar{B}$$0\\atop{s}$ → D$+\\atop{s}$ π-. The measurement of the relative branching fraction is performed by applying a fit in invariant mass and specific ionization to 1.2 fb-1 of Ds(φπ)X data collected with the CDF II detector in pp collisions at √ s = 1.96 TeV at the Fermilab Tevatron collider. We measure B $\\bar{B}$$0\\atop{s}$ → D$±\\atop{s}$ K∓ /B $\\bar{B}$$0\\atop{s}$ → D$+\\atop{s}$ π- = 0.107±0.019(stat)±0.008(sys). The statistical significance of the $\\bar{B}$$0\\atop{s}$ → D$±\\atop{s}$ K signal is 7.9σ. To cross-check our analysis method, we also measure B $\\bar{B0}$→ D+K- /B $\\bar{B0}$ → D+π- and B $\\bar{B0}$ → D+*K- /B $\\bar{B0}$ → D*+π- and verify that our results are in agreement with the world average.

  2. New function for an old enzyme: NEP deficient mice develop late-onset obesity.

    Directory of Open Access Journals (Sweden)

    Matthias Becker

    Full Text Available BACKGROUND: According to the World Health Organization (WHO there is a pandemic of obesity with approximately 300 million people being obese. Typically, human obesity has a polygenetic causation. Neutral endopeptidase (NEP, also known as neprilysin, is considered to be one of the key enzymes in the metabolism of many active peptide hormones. METHODOLOGY/PRINCIPAL FINDINGS: An incidental observation in NEP-deficient mice was a late-onset excessive gain in body weight exclusively from a ubiquitous accumulation of fat tissue. In accord with polygenetic human obesity, mice were characterized by deregulation of lipid metabolism, higher blood glucose levels, with impaired glucose tolerance. The key role of NEP in determining body mass was confirmed by the use of the NEP inhibitor candoxatril in wild-type mice that increased body weight due to increased food intake. This is a peripheral and not a central NEP action on the switch for appetite control, since candoxatril cannot cross the blood-brain barrier. Furthermore, we demonstrated that inhibition of NEP in mice with cachexia delayed rapid body weight loss. Thus, lack in NEP activity, genetically or pharmacologically, leads to a gain in body fat. CONCLUSIONS/SIGNIFICANCE: In the present study, we have identified NEP to be a crucial player in the development of obesity. NEP-deficient mice start to become obese under a normocaloric diet in an age of 6-7 months and thus are an ideal model for the typical human late-onset obesity. Therefore, the described obesity model is an ideal tool for research on development, molecular mechanisms, diagnosis, and therapy of the pandemic obesity.

  3. A neurorobotic platform for locomotor prosthetic development in rats and mice

    Science.gov (United States)

    von Zitzewitz, Joachim; Asboth, Leonie; Fumeaux, Nicolas; Hasse, Alexander; Baud, Laetitia; Vallery, Heike; Courtine, Grégoire

    2016-04-01

    Objectives. We aimed to develop a robotic interface capable of providing finely-tuned, multidirectional trunk assistance adjusted in real-time during unconstrained locomotion in rats and mice. Approach. We interfaced a large-scale robotic structure actuated in four degrees of freedom to exchangeable attachment modules exhibiting selective compliance along distinct directions. This combination allowed high-precision force and torque control in multiple directions over a large workspace. We next designed a neurorobotic platform wherein real-time kinematics and physiological signals directly adjust robotic actuation and prosthetic actions. We tested the performance of this platform in both rats and mice with spinal cord injury. Main Results. Kinematic analyses showed that the robotic interface did not impede locomotor movements of lightweight mice that walked freely along paths with changing directions and height profiles. Personalized trunk assistance instantly enabled coordinated locomotion in mice and rats with severe hindlimb motor deficits. Closed-loop control of robotic actuation based on ongoing movement features enabled real-time control of electromyographic activity in anti-gravity muscles during locomotion. Significance. This neurorobotic platform will support the study of the mechanisms underlying the therapeutic effects of locomotor prosthetics and rehabilitation using high-resolution genetic tools in rodent models.

  4. Targeting surface nucleolin with a multivalent pseudopeptide delays development of spontaneous melanoma in RET transgenic mice

    International Nuclear Information System (INIS)

    El Khoury, Diala; Courty, José; Hovanessian, Ara G; Prévost-Blondel, Armelle; Destouches, Damien; Lengagne, Renée; Krust, Bernard; Hamma-Kourbali, Yamina; Garcette, Marylène; Niro, Sandra; Kato, Masashi; Briand, Jean-Paul

    2010-01-01

    The importance of cell-surface nucleolin in cancer biology was recently highlighted by studies showing that ligands of nucleolin play critical role in tumorigenesis and angiogenesis. By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, we recently reported that HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in the athymic nude mice without apparent toxicity. The in vivo antitumoral action of HB-19 treatment was assessed on the spontaneous development of melanoma in the RET transgenic mouse model. Ten days old RET mice were treated with HB-19 in a prophylactic setting that extended 300 days. In parallel, the molecular basis for the action of HB-19 was investigated on a melanoma cell line (called TIII) derived from a cutaneous nodule of a RET mouse. HB-19 treatment of RET mice caused a significant delay in the onset of cutaneous tumors, several-months delay in the incidence of large tumors, a lower frequency of cutaneous nodules, and a reduction of visceral metastatic nodules while displaying no toxicity to normal tissue. Moreover, microvessel density was significantly reduced in tumors recovered from HB-19 treated mice compared to corresponding controls. Studies on the melanoma-derived tumor cells demonstrated that HB-19 treatment of TIII cells could restore contact inhibition, impair anchorage-independent growth, and reduce their tumorigenic potential in mice. Moreover, HB-19 treatment caused selective down regulation of transcripts coding matrix metalloproteinase 2 and 9, and tumor necrosis factor-α in the TIII cells and in melanoma tumors of RET mice. Although HB-19 treatment failed to prevent the development of spontaneous melanoma in the RET mice, it delayed for several months the onset and frequency of cutaneous tumors, and exerted a significant inhibitory effect on visceral metastasis. Consequently, HB-19 could provide a novel therapeutic agent by itself or

  5. Hand eczema, atopic dermatitis and filaggrin mutations in adult Danes: a registry-based study assessing risk of disability pension.

    Science.gov (United States)

    Heede, Nina G; Thuesen, Betina H; Thyssen, Jacob P; Linneberg, Allan; Szecsi, Pal B; Stender, Steen; Menné, Torkil; Johansen, Jeanne D

    2017-08-01

    Atopic dermatitis and hand eczema often impair the ability of people to work. Only a few studies have investigated whether individuals with loss-of-function filaggrin gene (FLG) mutations, who often have severe and early onset of dermatitis, experience occupational consequences. To investigate the personal consequences of having atopic dermatitis and/or hand eczema and FLG mutations. Adult Danes from the general population (n = 3247) and patients with atopic dermatitis and/or hand eczema (n = 496) were genotyped for common FLG mutations, and completed a questionnaire about skin symptoms and hand eczema. Socioeconomic variables, including disability pension, and information on work in risk occupations were retrieved from national registries. The reasons for granting disability pension were unknown. Disability pension was associated with hand eczema in the general population, especially among individuals with a history of atopic dermatitis. Moreover, self-reported hand eczema and atopic dermatitis were associated with particularly high risk of disability pension among FLG mutation carriers [odds ratio (OR) 4.02 and 95% confidence interval (CI): 1.15-14.11; and OR 6.01 and 95%CI: 2.37-15.34, respectively]. Furthermore, 60% of the FLG mutation carriers with atopic dermatitis who developed hand eczema had experienced symptoms before adulthood. In the general population, self-reported hand eczema and atopic dermatitis, particularly in individuals with a genetically impaired skin barrier, were associated with disability pension, suggesting that FLG mutations carriers with a history of atopic dermatitis and hand eczema could benefit from early attention with respect to choice of occupation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Comparison of serum concentrations of environmental allergen-specific IgE in atopic and healthy (nonatopic) horses.

    Science.gov (United States)

    Wilkołek, P; Sitkowski, W; Szczepanik, M; Adamek, Ł; Pluta, M; Taszkun, I; Gołyński, M; Malinowska, A

    2017-12-01

    Allergic responses in humans, horses and other species are mediated by immunoglobulin E (IgE) antibodies. Serum testing to detect allergen-specific IgE antibodies has been developed for dogs, cats and horses; this allows for the identification of allergens and determination of appropriate allergen- specific immunotherapies. This study compared serum allergen-specific IgE concentrations in atopic and healthy horses. The study was performed on Malopolski breed atopic (n=21) and nonatopic (n=21) clinically healthy horses. Allergen-specific IgE serum concentrations were measured in summer seasons of 2008-2015 using a monoclonal anti-IgE antibody. A Northern and Central European allergen panel containing mite, insect, mould and plant pollen allergens, including 15 tests of individual allergens and 5 tests of allergen mixtures was used. The mean allergen-specific IgE concentrations in the atopic and normal horse populations were compared. Among the atopic horses, the strongest positive reactions occurred against the storage mites Tyrophagus putrescentiae and the domestic mite Dermatophagoides farinae. The atopic horses also demonstrated high IgE concentrations against insects, particularly Tabanus sp., the plant pollens colza, cultivated rye and the mould pollen mixture Aspergillus/Penicillium. No horses in the atopic group were IgE-negative. Among all mite, insect, mould and some plant allergen groups the differences in mean specific IgE concentrations between allergic and healthy horses were significant. The mean IgE concentrations for most allergen groups were significantly higher in the atopic horses than in the healthy animals. However, a high incidence of positive reactions was observed in both healthy and allergic horses. Our results showed a high frequency of polysensitization in atopic horses. Copyright© by the Polish Academy of Sciences.

  7. A high-fat diet activates oncogenic Kras and COX2 to induce development of pancreatic ductal adenocarcinoma in mice.

    Science.gov (United States)

    Philip, Bincy; Roland, Christina L; Daniluk, Jaroslaw; Liu, Yan; Chatterjee, Deyali; Gomez, Sobeyda B; Ji, Baoan; Huang, Haojie; Wang, Huamin; Fleming, Jason B; Logsdon, Craig D; Cruz-Monserrate, Zobeida

    2013-12-01

    Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), but it is not clear how obesity contributes to pancreatic carcinogenesis. The oncogenic form of KRAS is expressed during early stages of PDAC development and is detected in almost all of these tumors. However, there is evidence that mutant KRAS requires an additional stimulus to activate its full oncogenic activity and that this stimulus involves the inflammatory response. We investigated whether the inflammation induced by a high-fat diet, and the accompanying up-regulation of cyclooxygenase-2 (COX2), increases Kras activity during pancreatic carcinogenesis in mice. We studied mice with acinar cell-specific expression of KrasG12D (LSL-Kras/Ela-CreERT mice) alone or crossed with COX2 conditional knockout mice (COXKO/LSL-Kras/Ela-CreERT). We also studied LSL-Kras/PDX1-Cre mice. All mice were fed isocaloric diets with different amounts of fat, and a COX2 inhibitor was administered to some LSL-Kras/Ela-CreERT mice. Pancreata were collected from mice and analyzed for Kras activity, levels of phosphorylated extracellular-regulated kinase, inflammation, fibrosis, pancreatic intraepithelial neoplasia (PanIN), and PDACs. Pancreatic tissues from LSL-Kras/Ela-CreERT mice fed high-fat diets (HFDs) had increased Kras activity, fibrotic stroma, and numbers of PanINs and PDACs than LSL-Kras/Ela-CreERT mice fed control diets; the mice fed the HFDs also had shorter survival times than mice fed control diets. Administration of a COX2 inhibitor to LSL-Kras/Ela-CreERT mice prevented these effects of HFDs. We also observed a significant reduction in survival times of mice fed HFDs. COXKO/LSL-Kras/Ela-CreERT mice fed HFDs had no evidence for increased numbers of PanIN lesions, inflammation, or fibrosis, as opposed to the increases observed in LSL-Kras/Ela-CreERT mice fed HFDs. In mice, an HFD can activate oncogenic Kras via COX2, leading to pancreatic inflammation and fibrosis and development of PanINs and PDAC. This

  8. Atopic diseases in twins born after assisted reproduction

    DEFF Research Database (Denmark)

    Jäderberg, Ida; Thomsen, Simon F; Kyvik, Kirsten Ohm

    2012-01-01

    Jäderberg I, Thomsen SF, Kyvik KO, Skytthe A, Backer V. Atopic diseases in twins born after assisted reproduction. Paediatric and Perinatal Epidemiology 2012; 26: 140-145. We examined the risk of atopic diseases in twins born after assisted reproduction. Data on atopic diseases and assisted...... reproduction in 9694 twin pairs, 3-20 years of age, from the Danish Twin Registry were collected via multidisciplinary questionnaires. The risk of atopic diseases in twins born after assisted reproduction was compared with the risk in twins born after spontaneous conception using logistic regression...... and variance components analysis. Children born after assisted reproduction did not have a different risk of atopic outcomes (adjusted odds ratios [95% confidence intervals] for asthma: 0.95 [0.85, 1.07], P = 0.403; hay fever: 1.01 [0.86, 1.18], P = 0.918; and atopic dermatitis: 1.02 [0.81, 1.11], P = 0...

  9. Ultrastructural analysis of development of myocardium in calreticulin-deficient mice

    Directory of Open Access Journals (Sweden)

    Michalak Marek

    2006-11-01

    Full Text Available Abstract Background Calreticulin is a Ca2+ binding chaperone of the endoplasmic reticulum which influences gene expression and cell adhesion. The levels of both vinculin and N-cadherin are induced by calreticulin expression, which play important roles in cell adhesiveness. Cardiac development is strictly dependent upon the ability of cells to adhere to their substratum and to communicate with their neighbours. Results We show here that the levels of N-cadherin are downregulated in calreticulin-deficient mouse embryonic hearts, which may lead to the disarray and wavy appearance of myofibrils in these mice, which we detected at all investigated stages of cardiac development. Calreticulin wild type mice exhibited straight, thick and abundant myofibrils, which were in stark contrast to the thin, less numerous, disorganized myofibrils of the calreticulin-deficient hearts. Interestingly, these major differences were only detected in the developing ventricles while the atria of both calreticulin phenotypes were similar in appearance at all developmental stages. Glycogen also accumulated in the ventricles of calreticulin-deficient mice, indicating an abnormality in cardiomyocyte metabolism. Conclusion Calreticulin is temporarily expressed during heart development where it is required for proper myofibrillogenesis. We postulate that calreticulin be considered as a novel cardiac fetal gene.

  10. Meta-analysis identifies seven susceptibility loci involved in the atopic March

    NARCIS (Netherlands)

    I. Marenholz (Ingo); J. Esparza-Gordillo (Jorge); F. Rüschendorf (Franz); A. Bauerfeind (Anja); D.P. Strachan (David P.); B.D. Spycher (Ben D.); H. Baurecht (Hansjörg); P. Margaritte-Jeannin (Patricia); A. Sääf (Annika); M. Kerkhof (Marjan); M. Ege (Markus); S. Baltic (Svetlana); J. Matheson; J. Li (Jin); S. Michel (Sven); W.Q. Ang (Wei Q.); W.L. McArdle (Wendy); A. Arnold (Andreas); G. Homuth (Georg); F. Demenais (Florence); E. Bouzigon (Emmanuelle); C. Söderhäll (Cilla); G. Pershagen (Göran); J.C. de Jongste (Johan); D.S. Postma (Dirkje); C. Braun-Fahrländer (Charlotte); E. Horak (Elisabeth); L.M. Ogorodova (Ludmila M.); V.P. Puzyrev (Valery P.); E.Y. Bragina (Elena Yu); T.J. Hudson (Thomas); C. Morin (Charles); D.L. Duffy (David); G.B. Marks (Guy B.); C. Robertson; G.W. Montgomery (Grant); A.W. Musk (Arthur); P.J. Thompson (Philip); N.G. Martin (Nicholas); A.L. James (Alan); P.M.A. Sleiman (Patrick); E. Toskala (Elina); P.M. Rodríguez; R. Fölster-Holst (R.); A. Franke (Andre); W. Lieb (Wolfgang); C. Gieger (Christian); A. Heinzmann (Andrea); E. Rietschel (Ernst); M. Keil (Mark); S. Cichon (Sven); M.M. Nöthen (Markus M.); C.E. Pennell (Craig); P.D. Sly; C.O. Schmidt (Carsten Oliver); A. Matanovic (Anja); V. Schneider (Valentin); M. Heinig (Matthias); N. Hübner (Norbert); P.G. Holt (Patrick); S. Lau (Susanne); M. Kabesch (Michael); S. Weidinger (Stefan); H. Hakonarson (Hakon); M.A. Ferreira (Manuel); C. Laprise (Catherine); M.B. Freidin (M.); J. Genuneit (Jon); G.H. Koppelman (Gerard); E. Melén (Erik); M.-H. Dizier; A.J. Henderson (A. John); Y.-A. Lee (Young-Ae)

    2015-01-01

    textabstractEczema often precedes the development of asthma in a disease course called the a 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12

  11. Heritability of hand eczema is not explained by comorbidity with atopic dermatitis

    DEFF Research Database (Denmark)

    Lerbaek, Anne; Kyvik, Kirsten O; Mortensen, Jakob

    2007-01-01

    Genetic factors have been shown to influence the risk of hand eczema, and may theoretically influence the frequency of eruptions as well as age at onset of the disease. However, the result may be confounded by atopic dermatitis, which is a major risk factor for development of hand eczema and is k...

  12. Allergic disease and atopic sensitization in children in relation to measles vaccination and measles infection.

    NARCIS (Netherlands)

    Rosenlund, H.; Bergstrom, A.; Alm, J.; Swartz, J.; Scheynius, A.; van Hage, M.; Johansen, K.; Brunekreef, B.|info:eu-repo/dai/nl/067548180; von Mutius, E.; Ege, M.; Riedler, J.; Braun-Fahrlander, C.; Waser, M.; Pershagen, G.

    2009-01-01

    OBJECTIVE: Our aim was to investigate the role of measles vaccination and measles infection in the development of allergic disease and atopic sensitization. METHODS: A total of 14 893 children were included from the cross-sectional, multicenter Prevention of Allergy-Risk Factors for Sensitization in

  13. Allergic Disease and Atopic Sensitization in Children in Relation to Measles Vaccination and Measles Infection

    NARCIS (Netherlands)

    Rosenlund, Helen; Bergstrom, Anna; Alm, Johan S.; Swartz, Jackie; Scheynius, Annika; van Hage, Marianne; Johansen, Kari; Brunekreef, Bert; von Mutius, Erika; Ege, Markus J.; Riedler, Josef; Braun-Fahrlaender, Charlotte; Waser, Marco; Pershagen, Goran

    OBJECTIVE. Our aim was to investigate the role of measles vaccination and measles infection in the development of allergic disease and atopic sensitization. METHODS. A total of 14 893 children were included from the cross-sectional, multicenter Prevention of Allergy-Risk Factors for Sensitization in

  14. Lack of efficacy of topical cyclosporin A in atopic dermatitis and allergic contact dermatitis

    NARCIS (Netherlands)

    de Rie, M. A.; Meinardi, M. M.; Bos, J. D.

    1991-01-01

    Since oral cyclosporin A (CsA) has demonstrated its effectiveness in psoriasis and atopic dermatitis, efforts have been made to develop a topical CsA formulation, thus avoiding systemic adverse events. A limited number of publications are available on the use of topical CsA in allergic contact

  15. Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hypercholesterolaemic mice.

    Science.gov (United States)

    Dorighello, Gabriel G; Rovani, Juliana C; Luhman, Christopher J F; Paim, Bruno A; Raposo, Helena F; Vercesi, Anibal E; Oliveira, Helena C F

    2014-03-28

    Different regimens of food restriction have been associated with protection against obesity, diabetes and CVD. In the present study, we hypothesised that food restriction would bring benefits to atherosclerosis- and diabetes-prone hypercholesterolaemic LDL-receptor knockout mice. For this purpose, 2-month-old mice were submitted to an intermittent fasting (IF) regimen (fasting every other day) over a 3-month period, which resulted in an overall 20 % reduction in food intake. Contrary to our expectation, epididymal and carcass fat depots and adipocyte size were significantly enlarged by 15, 72 and 68 %, respectively, in the IF mice compared with the ad libitum-fed mice. Accordingly, plasma levels of leptin were 50 % higher in the IF mice than in the ad libitum-fed mice. In addition, the IF mice showed increased plasma levels of total cholesterol (37 %), VLDL-cholesterol (195 %) and LDL-cholesterol (50 %). As expected, in wild-type mice, the IF regimen decreased plasma cholesterol levels and epididymal fat mass. Glucose homeostasis was also disturbed by the IF regimen in LDL-receptor knockout mice. Elevated levels of glycaemia (40 %), insulinaemia (50 %), glucose intolerance and insulin resistance were observed in the IF mice. Systemic inflammatory markers, TNF-α and C-reactive protein, were significantly increased and spontaneous atherosclerosis development were markedly increased (3-fold) in the IF mice. In conclusion, the IF regimen induced obesity and diabetes and worsened the development of spontaneous atherosclerosis in LDL-receptor knockout mice. Although being efficient in a wild-type background, this type of food restriction is not beneficial in the context of genetic hypercholesterolaemia.

  16. Effects of catechins and caffeine on the development of atherosclerosis in mice.

    Science.gov (United States)

    Liu, Litong; Nagai, Izumi; Gao, Ying; Matsushima, Yoshibumi; Kawai, Yoshichika; Sayama, Kazutoshi

    2017-10-01

    Atherosclerosis is one of the diseases related to metabolic syndrome which is caused by obesity. Previous reports have shown that green tea and its components have anti-obesity effect. We examined whether catechins and caffeine can prevent the development of atherosclerosis by oral administration, singly or in combination to the atherosclerosis model mice. Results demonstrated that the number of atherosclerotic regions in the aorta was significantly reduced by the combined treatment, and the atherosclerotic area was also improved. Serum HDL-C increased by caffeine single treatment, but no effect on the TG and TC by any treatments. Moreover, ECG illuviated to atheromatous lesions in aorta and the illuviation was enhanced by caffeine. The mRNA expression levels of LOX-1 and TNF-α showed a tendency to suppress by the combined treatment. These results indicated that the combined administration of catechins and caffeine has the inhibitory effect on the development of atherosclerosis in mice.

  17. Isoflurane Damages the Developing Brain of Mice and Induces Subsequent Learning and Memory Deficits through FASL-FAS Signaling

    Directory of Open Access Journals (Sweden)

    Xiuwen Yi

    2015-01-01

    Full Text Available Background. Isoflurane disrupts brain development of neonatal mice, but its mechanism is unclear. We explored whether isoflurane damaged developing hippocampi through FASL-FAS signaling pathway, which is a well-known pathway of apoptosis. Method. Wild type and FAS- or FASL-gene-knockout mice aged 7 days were exposed to either isoflurane or pure oxygen. We used western blotting to study expressions of caspase-3, FAS (CD95, and FAS ligand (FASL or CD95L proteins, TUNEL staining to count apoptotic cells in hippocampus, and Morris water maze (MWM to evaluate learning and memory. Result. Isoflurane increased expression of FAS and FASL proteins in wild type mice. Compared to isoflurane-treated FAS- and FASL-knockout mice, isoflurane-treated wild type mice had higher expression of caspase-3 and more TUNEL-positive hippocampal cells. Expression of caspase-3 in wild isoflurane group, wild control group, FAS/FASL-gene-knockout control group, and FAS/FASL-gene-knockout isoflurane group showed FAS or FASL gene knockout might attenuate increase of caspase-3 caused by isoflurane. MWM showed isoflurane treatment of wild type mice significantly prolonged escape latency and reduced platform crossing times compared with gene-knockout isoflurane-treated groups. Conclusion. Isoflurane induces apoptosis in developing hippocampi of wild type mice but not in FAS- and FASL-knockout mice and damages brain development through FASL-FAS signaling.

  18. Early-Onset Diabetic E1-DN Mice Develop Albuminuria and Glomerular Injury Typical of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Mervi E. Hyvönen

    2015-01-01

    Full Text Available The transgenic E1-DN mice express a kinase-negative epidermal growth factor receptor in their pancreatic islets and are diabetic from two weeks of age due to impaired postnatal growth of β-cell mass. Here, we characterize the development of hyperglycaemia-induced renal injury in the E1-DN mice. Homozygous mice showed increased albumin excretion rate (AER at the age of 10 weeks; the albuminuria increased over time and correlated with blood glucose. Morphometric analysis of PAS-stained histological sections and electron microscopy images revealed mesangial expansion in homozygous E1-DN mice, and glomerular sclerosis was observed in the most hyperglycaemic mice. The albuminuric homozygous mice developed also other structural changes in the glomeruli, including thickening of the glomerular basement membrane and widening of podocyte foot processes that are typical for diabetic nephropathy. Increased apoptosis of podocytes was identified as one mechanism contributing to glomerular injury. In addition, nephrin expression was reduced in the podocytes of albuminuric homozygous E1-DN mice. Tubular changes included altered epithelial cell morphology and increased proliferation. In conclusion, hyperglycaemic E1-DN mice develop albuminuria and glomerular and tubular injury typical of human diabetic nephropathy and can serve as a new model to study the mechanisms leading to the development of diabetic nephropathy.

  19. Current management of atopic dermatitis and interruption of the atopic march.

    Science.gov (United States)

    Boguniewicz, Mark; Eichenfield, Lawrence F; Hultsch, Thomas

    2003-12-01

    Treatment of atopic dermatitis requires a comprehensive approach that includes evaluation of potential triggers and education of the patient and family regarding proper avoidance measures. Hydration of the skin and maintenance of an intact skin barrier remain integral to proper management. Although topical corticosteroids have been a mainstay of anti-inflammatory therapy, the newer topical calcineurin inhibitors offer advantages for treatment of this chronic, relapsing disease. Studies aimed at defining optimal combination therapy and early intervention might change the treatment paradigm for atopic dermatitis.

  20. Abnormal placental development and early embryonic lethality in EpCAM-null mice.

    Directory of Open Access Journals (Sweden)

    Keisuke Nagao

    Full Text Available BACKGROUND: EpCAM (CD326 is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. METHODOLOGY/PRINCIPAL FINDINGS: To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts, eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. CONCLUSION: EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

  1. Abnormal placental development and early embryonic lethality in EpCAM-null mice.

    Science.gov (United States)

    Nagao, Keisuke; Zhu, Jianjian; Heneghan, Mallorie B; Hanson, Jeffrey C; Morasso, Maria I; Tessarollo, Lino; Mackem, Susan; Udey, Mark C

    2009-12-31

    EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

  2. Neurobehavioral development of CD-1 mice after combined gestational and postnatal exposure to ozone

    Energy Technology Data Exchange (ETDEWEB)

    Dell` Omo, G [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Fiore, M [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Petruzzi, S [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Alleva, E [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Bignami, G [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy)

    1995-09-01

    Outbred CD-1 mice were exposed continuously to ozone (O{sub 3}, 0.6 ppm) from 6 days prior to the formation of breeding pairs to the time of weaning of the offspring on postnatal day 22 (PND 22) or to PND 26. One half of the mice in each of eight O{sub 3} and eight control litters were subjected on PND 24 to a 20-min open-field test after IP treatment by either saline or scopolamine (2 mg/kg). The remaining mice (those exposed until PND 26) were subjected on PNDs 28-31 to a conditioned place preference (CPP) test, using a short schedule with a single IP injection on PND 29 of either d-amphetamine (3.3 mg/kg) or saline. Subsequently, the saline mice of the open-field experiment were used on PND 59 for an activity test in one of the CPP apparatus compartments after IP treatment by either d-amphetamine (same dose) or saline. In addition, the saline mice of the CPP experiment underwent a multitrial, step-through passive avoidance (PA) acquisition test on PND 59 or 60, followed 24 h later by a single-trial retention test. In the absence of effects on reproductive performance (proportion of successful pregnancies, litter size, offspring viability, and sex ratio), O{sub 3} offspring showed a long-lasting reduction in body weight without modification of sec differences. Ozone effects on neurobehavioral development were not large and quite selective, including: attenuation of the sex differences in several responses (rearing and sniffing in the open-field, activity in the final CPP test session); a change in response choices in the final CPP test, in the absence of a main effect on conditioning; a reduction of grooming in the activity test on PND 29; and impairment of PA acquisition limited to the initial period of training. (orig.)

  3. Neurobehavioral development of CD-1 mice after combined gestational and postnatal exposure to ozone.

    Science.gov (United States)

    Dell'Omo, G; Fiore, M; Petruzzi, S; Alleva, E; Bignami, G

    1995-01-01

    Outbred CD-1 mice were exposed continuously to ozone (O3, 0.6 ppm) from 6 days prior to the formation of breeding pairs to the time of weaning of the offspring on postnatal day 22 (PND 22) or to PND 26. One half of the mice in each of eight O3 and eight control litters were subjected on PND 24 to a 20-min open-field test after IP treatment by either saline or scopolamine (2 mg/kg). The remaining mice (those exposed until PND 26) were subjected on PNDs 28-31 to a conditioned place preference (CPP) test, using a short schedule with a single IP injection on PND 29 of either d-amphetamine (3.3 mg/kg) or saline. Subsequently, the saline mice of the open-field experiment were used on PND 59 for an activity test in one of the CPP apparatus compartments after IP treatment by either d-amphetamine (same dose) or saline. In addition, the saline mice of the CPP experiment underwent a multi-trial, step-through passive avoidance (PA) acquisition test on PND 59 or 60, followed 24 h later by a single-trial retention test. In the absence of effects on reproductive performance (proportion of successful pregnancies, litter size, offspring viability, and sex ratio), O3 offspring showed a long-lasting reduction in body weight without modification of sex differences. Ozone effects on neurobehavioral development were not large and quite selective, including: attenuation of the sex differences in several responses (rearing and sniffing in the open-field, activity in the final CPP test session); a change in response choices in the final CPP test, in the absence of a main effect on conditioning; a reduction of grooming in the activity test on PND 29; and impairment of PA acquisition limited to the initial period of training.

  4. Complete Plasmodium falciparum liver-stage development in liver-chimeric mice

    Science.gov (United States)

    Vaughan, Ashley M.; Mikolajczak, Sebastian A.; Wilson, Elizabeth M.; Grompe, Markus; Kaushansky, Alexis; Camargo, Nelly; Bial, John; Ploss, Alexander; Kappe, Stefan H.I.

    2012-01-01

    Plasmodium falciparum, which causes the most lethal form of human malaria, replicates in the host liver during the initial stage of infection. However, in vivo malaria liver-stage (LS) studies in humans are virtually impossible, and in vitro models of LS development do not reconstitute relevant parasite growth conditions. To overcome these obstacles, we have adopted a robust mouse model for the study of P. falciparum LS in vivo: the immunocompromised and fumarylacetoacetate hydrolase–deficient mouse (Fah–/–, Rag2–/–, Il2rg–/–, termed the FRG mouse) engrafted with human hepatocytes (FRG huHep). FRG huHep mice supported vigorous, quantifiable P. falciparum LS development that culminated in complete maturation of LS at approximately 7 days after infection, providing a relevant model for LS development in humans. The infections allowed observations of previously unknown expression of proteins in LS, including P. falciparum translocon of exported proteins 150 (PTEX150) and exported protein-2 (EXP-2), components of a known parasite protein export machinery. LS schizonts exhibited exoerythrocytic merozoite formation and merosome release. Furthermore, FRG mice backcrossed to the NOD background and repopulated with huHeps and human red blood cells supported reproducible transition from LS infection to blood-stage infection. Thus, these mice constitute reliable models to study human LS directly in vivo and demonstrate utility for studies of LS–to–blood-stage transition of a human malaria parasite. PMID:22996664

  5. Development of a Murine Model for Aerosolized Ebolavirus Infection Using a Panel of Recombinant Inbred Mice

    Directory of Open Access Journals (Sweden)

    Malak Kotb

    2012-12-01

    Full Text Available Countering aerosolized filovirus infection is a major priority of biodefense research.  Aerosol models of filovirus infection have been developed in knock-out mice, guinea pigs and non-human primates; however, filovirus infection of immunocompetent mice by the aerosol route has not been reported.  A murine model of aerosolized filovirus infection in mice should be useful for screening vaccine candidates and therapies.  In this study, various strains of wild-type and immunocompromised mice were exposed to aerosolized wild-type (WT or mouse-adapted (MA Ebola virus (EBOV.  Upon exposure to aerosolized WT-EBOV, BALB/c, C57BL/6 (B6, and DBA/2 (D2 mice were unaffected, but 100% of severe combined immunodeficiency (SCID and 90% of signal transducers and activators of transcription (Stat1 knock-out (KO mice became moribund between 7–9 days post-exposure (dpe.  Exposure to MA-EBOV caused 15% body weight loss in BALB/c, but all mice recovered.  In contrast, 10–30% lethality was observed in B6 and D2 mice exposed to aerosolized MA-EBOV, and 100% of SCID, Stat1 KO, interferon (IFN-γ KO and Perforin KO mice became moribund between 7–14 dpe. In order to identify wild-type, inbred, mouse strains in which exposure to aerosolized MA-EBOV is uniformly lethal, 60 BXD (C57BL/6 crossed with DBA/2 recombinant inbred (RI and advanced RI (ARI mouse strains were exposed to aerosolized MA-EBOV, and monitored for disease severity. A complete spectrum of disease severity was observed. All BXD strains lost weight but many recovered. However, infection was uniformly lethal within 7 to 12 days post-exposure in five BXD strains.  Aerosol exposure of these five BXD strains to 10-fold less MA-EBOV resulted in lethality ranging from 0% in two strains to 90–100% lethality in two strains.  Analysis of post-mortem tissue from BXD strains that became moribund and were euthanized at the lower dose of MA-EBOV, showed liver damage in all mice as well as lung lesions in

  6. In vitro development of embryos from experimentally Kerack-addicted Mice

    Directory of Open Access Journals (Sweden)

    Elham Mohammadzadeh

    2017-08-01

    Full Text Available Background: Prenatal drug exposure, as a common public health concern, is associated with an increased risk of adverse effects on early embryo development. Objective: To investigate the in vitro development of - embryo from experimentally Kerack-addicted mice. Materials and Methods: Twenty-five female mice were studied in five groups: control, vehicle, and three experimental groups of Kerack-dependent mice (I, II, and III which received different doses of Kerack for 14 days. After the establishment of addiction model (7 days, experimental groups I, II, and III were given Kerack intraperitoneally at the doses of 5, 35, and 70 mg/kg, twice a day for a period of 7 days, respectively. The vehicle group received normal saline and lemon juice whilst the control group just received water and food. Morulae were obtained through oviduct flashing. The survived embryos were cultured in T6+ 5mg/ml bovine serum albumin. The developmental rates up to hatched stage daily and embryo quality (differential staining and Tunnel staining were also assessed Results: The developmental potential of embryos obtained from the addicted mother was significantly decreased in comparison with control group. There was a significant reduction in the rate of blastocyst formation in the high dose Kerack dependent group. However, in addicted mice there was reduction in the total cell number (40.92% vs. 65.08% in control and, inner cell mass percentage (17.17% vs. 26.15% in control while apoptotic cells numbers were increased (7.17 vs. 1.46 in control (p<0.05. Conclusion: The Kerack addiction during pregnancy retards preimplantation development and induces apoptosis.

  7. Characterization of a sensitive mouse Aβ40 PD biomarker assay for Alzheimer's disease drug development in wild-type mice.

    Science.gov (United States)

    Lu, Yanmei; Hoyte, Kwame; Montgomery, William H; Luk, Wilman; He, Dongping; Meilandt, William J; Zuchero, Y Joy Yu; Atwal, Jasvinder K; Scearce-Levie, Kimberly; Watts, Ryan J; DeForge, Laura E

    2016-05-01

    Transgenic mice that overexpress human amyloid precursor protein with Swedish or London (APPswe or APPlon) mutations have been widely used for preclinical Alzheimer's disease (AD) drug development. AD patients, however, rarely possess these mutations or overexpress APP. We developed a sensitive ELISA that specifically and accurately measures low levels of endogenous Aβ40 in mouse plasma, brain and CSF. In wild-type mice treated with a bispecific anti-TfR/BACE1 antibody, significant Aβ reductions were observed in the periphery and the brain. APPlon transgenic mice showed a slightly less reduction, whereas APPswe mice did not have any decrease. This sensitive and well-characterized mouse Aβ40 assay enables the use of wild-type mice for preclinical PK/PD and efficacy studies of potential AD therapeutics.

  8. Effects of perinatal coexposure to methylmercury and polychlorinated biphenyls on neurobehavioral development in mice

    Energy Technology Data Exchange (ETDEWEB)

    Sugawara, Norio [Tohoku University School of Medicine, Environmental Health Sciences, Aoba-ku, Sendai (Japan); Hirosaki University Graduate School of Medicine, Department of Neuropsychiatry, Hirosaki (Japan); Ohba, Takashi; Nakai, Kunihiko; Nakamura, Tomoyuki; Suzuki, Keita; Kameo, Satomi; Shimada, Miyuki; Kurokawa, Naoyuki; Satoh, Chieko; Satoh, Hiroshi [Tohoku University School of Medicine, Environmental Health Sciences, Aoba-ku, Sendai (Japan); Kakita, Akiyoshi [Niigata University, Department of Pathological Neuroscience, Resource Branch for Brain Disease Research, Brain Research Institute, Niigata (Japan)

    2008-06-15

    Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are environmental pollutants that cause neurobehavioral deficits in humans. Because exposures to MeHg and PCBs occur through fish consumption, it is necessary to clarify the effects of the interaction of the two pollutants. Therefore, we investigated the effects of perinatal exposure to MeHg and PCBs on the neurobehavioral development in mice. Female mice (C57BL/6Cr) were divided into four groups according to the type of exposure: (1) vehicle control, (2) MeHg alone, (3) PCBs alone, and (4) MeHg + PCBs. The MeHg-exposed groups were fed with a diet containing 5 ppm MeHg (as Hg), from 4 weeks before mating, throughout pregnancy, and lactation. The PCB-exposed groups were given a commercial mixture of PCBs, Aroclor 1254, at 18 mg/kg body weight in corn oil by gavage every 3 days from day 5 after breeding and continued until postnatal day (PND) 20. Before weaning, an assessment of eye opening showed the interactive effects between MeHg and PCBs on PND 12: The coexposure group showed a similar response to the control group, whereas the MeHg- and PCB-exposed groups showed a high response than the former two groups. We also observed delay in development of grasp reflex by MeHg exposure on PNDs 12 and 14. When the offspring mice were 8 weeks old, the group exposed to PCBs alone showed increases in the frequencies of excrement defecation and urine traces in an open-field test. Analysis of the latency revealed the antagonistic interaction between the MeHg and PCBs: The latency increased by either MeHg or PCB exposure was decreased by coexposure. Treatment with MeHg decreased the distance walked by the mice, and MeHg interacted with PCBs. Moris' water maze test showed that the MeHg-treated mice took a long time to reach the submerged platform; however, this MeHg exposure showed no interaction with PCB exposure. The spontaneous locomotion activity of the mice was not affected by the chemical exposure at 9 weeks of

  9. Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

    Science.gov (United States)

    Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela

    2016-03-15

    Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life. Copyright © 2016 by The American Association of Immunologists, Inc.

  10. Rush allergen specific immunotherapy protocol in feline atopic dermatitis: a pilot study of four cats.

    Science.gov (United States)

    Trimmer, Ann M; Griffin, Craig E; Boord, Mona J; Rosenkrantz, Wayne S

    2005-10-01

    Rush immunotherapy has been shown to be as safe as conventional immunotherapy in canine atopic patients. Rush immunotherapy has not been reported in the feline atopic patient. The purpose of this pilot study was to determine a safe protocol for rush immunotherapy in feline atopic patients. Four atopic cats diagnosed by history, physical examination and exclusion of appropriate differential diagnoses were included in the study. Allergens were identified via liquid phase immunoenzymatic testing (VARL: Veterinary Allergy Reference Labs, Pasadena, CA). Cats were premedicated with 1.5 mg triamcinolone orally 24 and 2 h prior to first injection and 10 mg hydroxyzine PO 24, 12 and 2 h prior to first injection. An intravenous catheter was placed prior to first injection. Allergen extracts (Greer Laboratories, Lenoir, North Carolina) were all administered subcutaneously at increasing protein nitrogen units (pnu) every 30 minutes for 5 h to maintenance dose of 15,000 pnus ml-1. Vital signs were assessed every 15 minutes. Two cats developed mild pruritus and the subsequent injection was delayed 30 minutes. No changes in either cat's vital signs were noted, nor was there any further pruritus. All four cats successfully completed rush immunotherapy. Two cats developed a dermal swelling on the dorsal neck one week later. In these four cats, this protocol appeared to be a safe regimen to reach maintenance therapy. A larger sample of feline patients is needed to determine the incidence of adverse reactions and to follow the success of ASIT based upon this method of induction.

  11. Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

    LENUS (Irish Health Repository)

    Zagozdzon, Agnieszka M

    2012-05-30

    AbstractBackgroundNumerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study.ResultsA new mouse strain (MMTV-Luc2 mice) expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal.ConclusionsWe have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and\\/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques.

  12. Development of a physiologically based pharmacokinetic model for bisphenol A in pregnant mice

    International Nuclear Information System (INIS)

    Kawamoto, Yuko; Matsuyama, Wakoto; Wada, Masahiro; Hishikawa, Junko; Chan, Melissa Pui Ling; Nakayama, Aki; Morisawa, Shinsuke

    2007-01-01

    Bisphenol A (BPA) is a weakly estrogenic monomer used to produce polymers for food contact and other applications, so there is potential for oral exposure of humans to trace amounts via ingestion. To date, no physiologically based pharmacokinetic (PBPK) model has been located for BPA in pregnant mice with or without fetuses. An estimate by a mathematical model is essential since information on humans is difficult to obtain experimentally. The PBPK model was constructed based on the pharmacokinetic data of our experiment following single oral administration of BPA to pregnant mice. The risk assessment of bisphenol A (BPA) on the development of human offspring is an important issue. There have been limited data on the exposure level of human fetuses to BPA (e.g. BPA concentration in cord blood) and no information is available on the pharmacokinetics of BPA in humans with or without fetuses. In the present study, we developed a physiologically based pharmacokinetic (PBPK) model describing the pharmacokinetics of BPA in a pregnant mouse with the prospect of future extrapolation to humans. The PBPK model was constructed based on the pharmacokinetic data of an experiment we executed on pregnant mice following single oral administration of BPA. The model could describe the rapid transfer of BPA through the placenta to the fetus and the slow disappearance from fetuses. The simulated time courses after three-time repeated oral administrations of BPA by the constructed model fitted well with the experimental data, and the simulation for the 10 times lower dose was also consistent with the experiment. This suggested that the PBPK model for BPA in pregnant mice was successfully verified and is highly promising for extrapolation to humans who are expected to be exposed more chronically to lower doses

  13. Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

    Directory of Open Access Journals (Sweden)

    Zagozdzon Agnieszka M

    2012-05-01

    Full Text Available Abstract Background Numerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study. Results A new mouse strain (MMTV-Luc2 mice expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal. Conclusions We have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques.

  14. Vitamin K2 biosynthetic enzyme, UBIAD1 is essential for embryonic development of mice.

    Science.gov (United States)

    Nakagawa, Kimie; Sawada, Natsumi; Hirota, Yoshihisa; Uchino, Yuri; Suhara, Yoshitomo; Hasegawa, Tomoka; Amizuka, Norio; Okamoto, Tadashi; Tsugawa, Naoko; Kamao, Maya; Funahashi, Nobuaki; Okano, Toshio

    2014-01-01

    UbiA prenyltransferase domain containing 1 (UBIAD1) is a novel vitamin K2 biosynthetic enzyme screened and identified from the human genome database. UBIAD1 has recently been shown to catalyse the biosynthesis of Coenzyme Q10 (CoQ10) in zebrafish and human cells. To investigate the function of UBIAD1 in vivo, we attempted to generate mice lacking Ubiad1, a homolog of human UBIAD1, by gene targeting. Ubiad1-deficient (Ubiad1(-/-)) mouse embryos failed to survive beyond embryonic day 7.5, exhibiting small-sized body and gastrulation arrest. Ubiad1(-/-) embryonic stem (ES) cells failed to synthesize vitamin K2 but were able to synthesize CoQ9, similar to wild-type ES cells. Ubiad1(+/-) mice developed normally, exhibiting normal growth and fertility. Vitamin K2 tissue levels and synthesis activity were approximately half of those in the wild-type, whereas CoQ9 tissue levels and synthesis activity were similar to those in the wild-type. Similarly, UBIAD1 expression and vitamin K2 synthesis activity of mouse embryonic fibroblasts prepared from Ubiad1(+/-) E15.5 embryos were approximately half of those in the wild-type, whereas CoQ9 levels and synthesis activity were similar to those in the wild-type. Ubiad1(-/-) mouse embryos failed to be rescued, but their embryonic lifespans were extended to term by oral administration of MK-4 or CoQ10 to pregnant Ubiad1(+/-) mice. These results suggest that UBIAD1 is responsible for vitamin K2 synthesis but may not be responsible for CoQ9 synthesis in mice. We propose that UBIAD1 plays a pivotal role in embryonic development by synthesizing vitamin K2, but may have additional functions beyond the biosynthesis of vitamin K2.

  15. Effects of neonatal oxytocin manipulation on development of social behaviors in mice.

    Science.gov (United States)

    Mogi, Kazutaka; Ooyama, Rumi; Nagasawa, Miho; Kikusui, Takefumi

    2014-06-22

    The oxytocin (OT) neural system is thought to be involved in the underlying mechanisms that guide the development of social behaviors. In the present study, we examined the effects of neonatal oxytocin manipulation in mice. Within 24 hours after birth, pups in the treatment group randomly received an intraperitoneal injection of OT or OT antagonist (OTA), and those in the control group received a saline injection or handling only. Some of these mice underwent a test that counted the number of isolation-induced ultrasound vocalizations they made on postnatal day 6, and they were further tested for sociability at 8-9 weeks of age and for neuroendocrine stress response to novel environments at 19-20 weeks of age. Another group of mice was tested for alloparental responsiveness at 13-15 weeks of age. The OT injection affected sociability and alloparental responsiveness. In an approach/avoidance test, most of the mice made a social approach to an unfamiliar conspecific of the same sex, but females that had received a neonatal injection of 3 μg of OTA did not show this response. The neonatal OTA treatment appeared to inhibit females' sociability in a dose-dependent fashion. In a retrieving test, females that had received a neonatal injection of 3 μg of OT retrieved significantly more pups than did those that had received 3 μg of OTA, although neither of the treatments caused the females to behave significantly differently from control group females. Meanwhile, a neonatal injection of 3 μg of OTA increased the latency to retrieve pups in males. These results suggested that neonatal OT action may positively regulate alloparental responsiveness in adulthood. Considering that the organizational effects of OT have also been shown in voles and rats, the mechanism by which neonatal OT modifies the development of social behaviors appears to be common to all rodents. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Zinc Prevents the Development of Diabetic Cardiomyopathy in db/db Mice

    Directory of Open Access Journals (Sweden)

    Shudong Wang

    2017-03-01

    Full Text Available Diabetic cardiomyopathy (DCM is highly prevalent in type 2 diabetes (T2DM patients. Zinc is an important essential trace metal, whose deficiency is associated with various chronic ailments, including vascular diseases. We assessed T2DM B6.BKS(D-Leprdb/J (db/db mice fed for six months on a normal diet containing three zinc levels (deficient, adequate, and supplemented, to explore the role of zinc in DCM development and progression. Cardiac function, reflected by ejection fraction, was significantly decreased, along with increased left ventricle mass and heart weight to tibial length ratio, in db/db mice. As a molecular cardiac hypertrophy marker, atrial natriuretic peptide levels were also significantly increased. Cardiac dysfunction and hypertrophy were accompanied by significantly increased fibrotic (elevated collagen accumulation as well as transforming growth factor β and connective tissue growth factor levels and inflammatory (enhanced expression of tumor necrosis factor alpha, interleukin-1β, caspase recruitment domain family member 9, and B-cell lymphoma/leukemia 10, and activated p38 mitogen-activated protein kinase responses in the heart. All these diabetic effects were exacerbated by zinc deficiency, and not affected by zinc supplementation, respectively. Mechanistically, oxidative stress and damage, mirrored by the accumulation of 3-nitrotyrosine and 4-hydroxy-2-nonenal, was significantly increased along with significantly decreased expression of Nrf2 and its downstream antioxidants (NQO-1 and catalase. This was also exacerbated by zinc deficiency in the db/db mouse heart. These results suggested that zinc deficiency promotes the development and progression of DCM in T2DM db/db mice. The exacerbated effects by zinc deficiency on the heart of db/db mice may be related to further suppression of Nrf2 expression and function.

  17. Eμ/miR-125b transgenic mice develop lethal B-cell malignancies.

    Science.gov (United States)

    Enomoto, Y; Kitaura, J; Hatakeyama, K; Watanuki, J; Akasaka, T; Kato, N; Shimanuki, M; Nishimura, K; Takahashi, M; Taniwaki, M; Haferlach, C; Siebert, R; Dyer, M J S; Asou, N; Aburatani, H; Nakakuma, H; Kitamura, T; Sonoki, T

    2011-12-01

    MicroRNA-125b-1 (miR-125b-1) is a target of a chromosomal translocation t(11;14)(q24;q32) recurrently found in human B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This translocation results in overexpression of miR-125b controlled by immunoglobulin heavy chain gene (IGH) regulatory elements. In addition, we found that six out of twenty-one BCP-ALL patients without t(11;14)(q24;q32) showed overexpression of miR-125b. Interestingly, four out of nine patients with BCR/ABL-positive BCP-ALL and one patient with B-cell lymphoid crisis that had progressed from chronic myelogenous leukemia overexpressed miR-125b. To examine the role of the deregulated expression of miR-125b in the development of B-cell tumor in vivo, we generated transgenic mice mimicking the t(11;14)(q24;q32) (Eμ/miR-125b-TG mice). Eμ/miR-125b-TG mice overexpressed miR-125b driven by IGH enhancer and promoter and developed IgM-negative or IgM-positive lethal B-cell malignancies with clonal proliferation. B cells obtained from the Eμ/miR-125b-TG mice were resistant to apoptosis induced by serum starvation. We identified Trp53inp1, a pro-apoptotic gene induced by cell stress, as a novel target gene of miR-125b in hematopoietic cells in vitro and in vivo. Our results provide direct evidence that miR-125b has important roles in the tumorigenesis of precursor B cells.

  18. Topical Anti-Nuclear Factor-Kappa B Small Interfering RNA with Functional Peptides Containing Sericin-Based Hydrogel for Atopic Dermatitis

    Directory of Open Access Journals (Sweden)

    Takanori Kanazawa

    2015-09-01

    Full Text Available The small interfering RNA (siRNA is suggested to offer a novel means of treating atopic dermatitis (AD because it allows the specific silencing of genes related to AD pathogenesis. In our previous study, we found that siRNA targeted against RelA, an important nuclear factor-kappa B (NF-κB subdomain, with functional peptides, showed therapeutic effects in a mouse model of AD. In the present study, to develop a topical skin application against AD, we prepared a hydrogel containing anti-RelA siRNA and functional peptides and determined the intradermal permeation and the anti-AD effects in an AD mouse model. We selected the silk protein, sericin (SC, which is a versatile biocompatible biomaterial to prepare hydrogel as an aqueous gel base. We found that the siRNA was more widely delivered to the site of application in AD-induced ear skin of mice after topical application via the hydrogel containing functional peptides than via the preparation without functional peptides. In addition, the ear thickness and clinical skin severity of the AD-induced mice treated with hydrogel containing anti-RelA siRNA with functional peptides improved more than that of mice treated with the preparation formulated with negative siRNA.

  19. Trichostatin A suppresses lung adenocarcinoma development in Grg1 overexpressing transgenic mice

    International Nuclear Information System (INIS)

    Liu, Ju; Li, Yan; Dong, Fengyun; Li, Liqun; Masuda, Takahiro; Allen, Thaddeus D.; Lobe, Corrinne G.

    2015-01-01

    Trichostatin A (TSA) is a histone deacetylase inhibitor and a potential therapeutic for various malignancies. The in vivo effect of TSA, however, has not been investigated in a transgenic lung cancer model. Previously, we generated transgenic mice with overexpression of Groucho-related-gene 1 (Grg1) and these mice all developed mucinous lung adenocarcinoma. Grg1 is a transcriptional co-repressor protein, the function of which is thought to depend on HDAC activity. However, functions outside the nucleus have also been proposed. We tested the supposition that Grg1-induced tumorigenesis is HDAC-dependent by assaying the therapeutic effect of TSA in the Grg1 transgenic mouse model. We found that TSA significantly inhibited lung tumorigenesis in Grg1 transgenic mice (p < 0.01). TSA did not affect overall Grg1 protein levels, but instead reduced ErbB1 and ErbB2 expression, which are upregulated by Grg1 in the absence of TSA. We confirmed this effect in A549 cells. Furthermore, lapatinib, an inhibitor of both ErbB1 and ErbB2, effectively masked the effect of TSA on the inhibition of A549 cell proliferation and migration, suggesting TSA does work, at least in part, by downregulating ErbB receptors. We additionally found that TSA reduced the expression of VEGF and VEGFR2, but not basic FGF and FGFR1. Our findings indicate that TSA effectively inhibits Grg1-induced lung tumorigenesis through the down-regulation of ErbB1 and ErbB2, as well as reduced VEGF signaling. This suggests TSA and other HDAC inhibitors could have therapeutic value in the treatment of lung cancers with Grg1 overexpression. - Highlights: • TSA suppresses lung tumorigenesis in Grg1 overexpressing transgenic mice. • TSA does not affect overall Grg1 protein levels in the mice and in A549 cells. • TSA reduces ErbB1 and ErbB2 expression in the mice and in A549 cells. • Lapatinib masks TSA-induced inhibition of A549 cell proliferation and migration. • TSA inhibits VEGF signaling, but not basic FGF

  20. Trichostatin A suppresses lung adenocarcinoma development in Grg1 overexpressing transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ju, E-mail: ju.liu@sdu.edu.cn [Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan (China); Molecular and Cellular Biology Division, Sunnybrook Health Science Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5 (Canada); Li, Yan [Children' s Health Care Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014 (China); Dong, Fengyun; Li, Liqun [Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan (China); Masuda, Takahiro; Allen, Thaddeus D. [Molecular and Cellular Biology Division, Sunnybrook Health Science Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5 (Canada); Lobe, Corrinne G. [Molecular and Cellular Biology Division, Sunnybrook Health Science Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5 (Canada); Miami Mice Research Corp., MaRS Centre, Heritage Bldg., 101 College Street, Toronto, Ontario M5G 1L7 (Canada)

    2015-08-07

    Trichostatin A (TSA) is a histone deacetylase inhibitor and a potential therapeutic for various malignancies. The in vivo effect of TSA, however, has not been investigated in a transgenic lung cancer model. Previously, we generated transgenic mice with overexpression of Groucho-related-gene 1 (Grg1) and these mice all developed mucinous lung adenocarcinoma. Grg1 is a transcriptional co-repressor protein, the function of which is thought to depend on HDAC activity. However, functions outside the nucleus have also been proposed. We tested the supposition that Grg1-induced tumorigenesis is HDAC-dependent by assaying the therapeutic effect of TSA in the Grg1 transgenic mouse model. We found that TSA significantly inhibited lung tumorigenesis in Grg1 transgenic mice (p < 0.01). TSA did not affect overall Grg1 protein levels, but instead reduced ErbB1 and ErbB2 expression, which are upregulated by Grg1 in the absence of TSA. We confirmed this effect in A549 cells. Furthermore, lapatinib, an inhibitor of both ErbB1 and ErbB2, effectively masked the effect of TSA on the inhibition of A549 cell proliferation and migration, suggesting TSA does work, at least in part, by downregulating ErbB receptors. We additionally found that TSA reduced the expression of VEGF and VEGFR2, but not basic FGF and FGFR1. Our findings indicate that TSA effectively inhibits Grg1-induced lung tumorigenesis through the down-regulation of ErbB1 and ErbB2, as well as reduced VEGF signaling. This suggests TSA and other HDAC inhibitors could have therapeutic value in the treatment of lung cancers with Grg1 overexpression. - Highlights: • TSA suppresses lung tumorigenesis in Grg1 overexpressing transgenic mice. • TSA does not affect overall Grg1 protein levels in the mice and in A549 cells. • TSA reduces ErbB1 and ErbB2 expression in the mice and in A549 cells. • Lapatinib masks TSA-induced inhibition of A549 cell proliferation and migration. • TSA inhibits VEGF signaling, but not basic FGF

  1. Atopic and Contact Dermatitis of the Vulva.

    Science.gov (United States)

    Pichardo-Geisinger, Rita

    2017-09-01

    Pruritus, or itch, is a common vulvar complaint that is often treated empirically as a yeast infection; however, yeast infections are just one of the many conditions that can cause vulvar itch. Ignoring other conditions can prolong pruritus unnecessarily. Atopic dermatitis, irritant contact dermatitis, and allergic contact dermatitis are extremely common noninfectious causes of vulvar itch that are often underdiagnosed by nondermatologists. Identifying these conditions and treating them appropriately can significantly improve a patient's quality of life and appropriately decrease health care expenditures by preventing unnecessary additional referrals or follow-up visits and decreasing pharmaceutical costs. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Association between atopic dermatitis and contact sensitization

    DEFF Research Database (Denmark)

    Hamann, Carsten R; Hamann, Dathan; Egeberg, Alexander

    2017-01-01

    BACKGROUND: It is unclear whether patients with atopic dermatitis (AD) have an altered prevalence or risk for contact sensitization. Increased exposure to chemicals in topical products together with impaired skin barrier function suggest a higher risk, whereas the immune profile suggests a lower...... contact dermatitis is suspected....... risk. OBJECTIVE: To perform a systematic review and meta-analysis of the association between AD and contact sensitization. METHODS: The PubMed/Medline, Embase, and Cochrane databases were searched for articles that reported on contact sensitization in individuals with and without AD. RESULTS...

  3. Prenatal stress challenge impairs fetal lung development and asthma severity sex-specifically in mice.

    Science.gov (United States)

    Zazara, Dimitra E; Perani, Clara V; Solano, María E; Arck, Petra C

    2018-02-01

    Allergic asthma is an increasing health problem worldwide. Interestingly, prenatal challenges such as stress have been associated with an increased risk for asthma during childhood. The underlying pathogenesis of how prenatal stress increases the risk for asthma still remains unclear. Potential targets could be that the fetal immune ontogeny or fetal lung development are compromised by prenatal challenges. Here, we aimed to identify whether prenatal stress challenge affects fetal lung development in mice. C57BL/6 pregnant mice were challenged with sound stress and fetal lung development was assessed histologically. Whilst prenatal stress challenge did not profoundly affect lung development in male fetuses, it resulted in less extensive terminal sacs, surrounded by thicker mesenchymal tissue in female fetuses. Thus, prenatal stress disrupted fetal lung development sex-specifically. Interestingly, upon prenatal stress challenge, the airway hyperresponsiveness and eosinophilic inflammation- two hallmarks of asthma - were significantly increased in adult female offspring, whilst regulatory CD4+ T cells were reduced. These findings strongly underpin the sex-specific association between s challenged fetal development and a sex-specific altered severity of asthma in adult offspring. Our model now allows to identify maternal markers through which the risk for asthma and possible other diseases is vertically transferred before birth in response to challenges. Such identification then opens avenues for primary disease prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Development of a reactive stroma associated with prostatic intraepithelial neoplasia in EAF2 deficient mice.

    Directory of Open Access Journals (Sweden)

    Laura E Pascal

    Full Text Available ELL-associated factor 2 (EAF2 is an androgen-responsive tumor suppressor frequently deleted in advanced prostate cancer that functions as a transcription elongation factor of RNA Pol II through interaction with the ELL family proteins. EAF2 knockout mice on a 129P2/OLA-C57BL/6J background developed late-onset lung adenocarcinoma, hepatocellular carcinoma, B-cell lymphoma and high-grade prostatic intraepithelial neoplasia. In order to further characterize the role of EAF2 in the development of prostatic defects, the effects of EAF2 loss were compared in different murine strains. In the current study, aged EAF2(-/- mice on both the C57BL/6J and FVB/NJ backgrounds exhibited mPIN lesions as previously reported on a 129P2/OLA-C57BL/6J background. In contrast to the 129P2/OLA-C57BL/6J mixed genetic background, the mPIN lesions in C57BL/6J and FVB/NJ EAF2(-/- mice were associated with stromal defects characteristic of a reactive stroma and a statistically significant increase in prostate microvessel density. Stromal inflammation and increased microvessel density was evident in EAF2-deficient mice on a pure C57BL/6J background at an early age and preceded the development of the histologic epithelial hyperplasia and neoplasia found in the prostates of older EAF2(-/- animals. Mice deficient in EAF2 had an increased recovery rate and a decreased overall response to the effects of androgen deprivation. EAF2 expression in human cancer was significantly down-regulated and microvessel density was significantly increased compared to matched normal prostate tissue; furthermore EAF2 expression was negatively correlated with microvessel density. These results suggest that the EAF2 knockout mouse on the C57BL/6J and FVB/NJ genetic backgrounds provides a model of PIN lesions associated with an altered prostate microvasculature and reactive stromal compartment corresponding to that reported in human prostate tumors.

  5. Embryonic Lethality Due to Arrested Cardiac Development in Psip1/Hdgfrp2 Double-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Hao Wang

    Full Text Available Hepatoma-derived growth factor (HDGF related protein 2 (HRP2 and lens epithelium-derived growth factor (LEDGF/p75 are closely related members of the HRP2 protein family. LEDGF/p75 has been implicated in numerous human pathologies including cancer, autoimmunity, and infectious disease. Knockout of the Psip1 gene, which encodes for LEDGF/p75 and the shorter LEDGF/p52 isoform, was previously shown to cause perinatal lethality in mice. The function of HRP2 was by contrast largely unknown. To learn about the role of HRP2 in development, we knocked out the Hdgfrp2 gene, which encodes for HRP2, in both normal and Psip1 knockout mice. Hdgfrp2 knockout mice developed normally and were fertile. By contrast, the double deficient mice died at approximate embryonic day (E 13.5. Histological examination revealed ventricular septal defect (VSD associated with E14.5 double knockout embryos. To investigate the underlying molecular mechanism(s, RNA recovered from ventricular tissue was subjected to RNA-sequencing on the Illumina platform. Bioinformatic analysis revealed several genes and biological pathways that were significantly deregulated by the Psip1 knockout and/or Psip1/Hdgfrp2 double knockout. Among the dozen genes known to encode for LEDGF/p75 binding factors, only the expression of Nova1, which encodes an RNA splicing factor, was significantly deregulated by the knockouts. However the expression of other RNA splicing factors, including the LEDGF/p52-interacting protein ASF/SF2, was not significantly altered, indicating that deregulation of global RNA splicing was not a driving factor in the pathology of the VSD. Tumor growth factor (Tgf β-signaling, which plays a key role in cardiac morphogenesis during development, was the only pathway significantly deregulated by the double knockout as compared to control and Psip1 knockout samples. We accordingly speculate that deregulated Tgf-β signaling was a contributing factor to the VSD and prenatal lethality

  6. Exposure to bisphenol A, but not phthalates, increases spontaneous diabetes type 1 development in NOD mice.

    Science.gov (United States)

    Bodin, Johanna; Kocbach Bølling, Anette; Wendt, Anna; Eliasson, Lena; Becher, Rune; Kuper, Frieke; Løvik, Martinus; Nygaard, Unni Cecilie

    2015-01-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA) accelerates the spontaneous development of diabetes in non-obese diabetic (NOD) mice. Here, we hypothesized that oral exposure to a mixture of the endocrine disruptors BPA and phthalates, relevant for human exposure, would accelerate diabetes development compared to BPA alone. NOD mice were exposed to BPA (1 mg/l), a mixture of phthalates (DEHP 1 mg/l, DBP 0.2 mg/l, BBP 10 mg/l and DiBP 20 mg/l) or a combination of BPA and the phthalate mixture through drinking water from conception and throughout life. Previous observations that BPA exposure increased the prevalence of diabetes and insulitis and decreased the number of tissue resident macrophages in pancreas were confirmed, and extended by demonstrating that BPA exposure also impaired the phagocytic activity of peritoneal macrophages. None of these effects were observed after phthalate exposure alone. The phthalate exposure in combination with BPA seemed to dampen the BPA effects on macrophage number and function as well as diabetes development, but not insulitis development. Exposure to BPA alone or in combination with phthalates decreased cytokine release (TNFα, IL-6, IL-10, IFNγ, IL-4) from in vitro stimulated splenocytes and lymph node cells, indicating systemic changes in immune function. In conclusion, exposure to BPA, but not to phthalates or mixed exposure to BPA and phthalates, accelerated diabetes development in NOD mice, apparently in part via systemic immune alterations including decreased macrophage function.

  7. Exposure to bisphenol A, but not phthalates, increases spontaneous diabetes type 1 development in NOD mice

    Directory of Open Access Journals (Sweden)

    Johanna Bodin

    2015-01-01

    Full Text Available Type 1 diabetes mellitus (T1DM is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA accelerates the spontaneous development of diabetes in non-obese diabetic (NOD mice. Here, we hypothesized that oral exposure to a mixture of the endocrine disruptors BPA and phthalates, relevant for human exposure, would accelerate diabetes development compared to BPA alone. NOD mice were exposed to BPA (1 mg/l, a mixture of phthalates (DEHP 1 mg/l, DBP 0.2 mg/l, BBP 10 mg/l and DiBP 20 mg/l or a combination of BPA and the phthalate mixture through drinking water from conception and throughout life. Previous observations that BPA exposure increased the prevalence of diabetes and insulitis and decreased the number of tissue resident macrophages in pancreas were confirmed, and extended by demonstrating that BPA exposure also impaired the phagocytic activity of peritoneal macrophages. None of these effects were observed after phthalate exposure alone. The phthalate exposure in combination with BPA seemed to dampen the BPA effects on macrophage number and function as well as diabetes development, but not insulitis development. Exposure to BPA alone or in combination with phthalates decreased cytokine release (TNFα, IL-6, IL-10, IFNγ, IL-4 from in vitro stimulated splenocytes and lymph node cells, indicating systemic changes in immune function. In conclusion, exposure to BPA, but not to phthalates or mixed exposure to BPA and phthalates, accelerated diabetes development in NOD mice, apparently in part via systemic immune alterations including decreased macrophage function.

  8. A study of B$0\\atop{s}$ → J/ΨΦ in the D0 experiment and an example of HEP technology transfer

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, Daniela Ursula [Imperial College, London (United Kingdom)

    2002-08-01

    After years of preparation, data taking with the upgraded D0 detector at the Tevatron proton-antiproton collider has begun. The large amount of data produced in a p$\\bar{p}$-collider requires sophisticated triggers to filter out the interesting events. Described in this thesis is the development of trigger software for the newly implemented Silicon Microstrip Tracker. D0 is a multi-purpose detector with a broad physics program. one area being studied at D0 is B mesons. An algorithm for reconstructing the B$0\\atop{s}$ and B$0\\atop{d}$ mesons and for measuring their lifetimes has been developed and is described in this thesis. The results suggest that an improvement of the current lifetime measurements can be achieved within the next two years. The reconstruction of a J/Ψ meson forms the basis for a wide range of b-physics. Data taken with the muon system during the commissioning period of the detector has been analyzed and a signal for the J/Ψ meson has been found. Systematic transfer of HEP technologies into other areas and their commercial exploitation plays an important role in the future of particle physics. An area of particular interest is DNA sequencing as shown by the recent completion of the sequencing of the human genome. The final part of this thesis details the development of a simulation for a high throughput sequencing device which is currently being developed at Imperial College.

  9. Portulaca Extract Attenuates Development of Dextran Sulfate Sodium Induced Colitis in Mice through Activation of PPARγ.

    Science.gov (United States)

    Kong, Rui; Luo, Hui; Wang, Nan; Li, Jingjing; Xu, Shizan; Chen, Kan; Feng, Jiao; Wu, Liwei; Li, Sainan; Liu, Tong; Lu, Xiya; Xia, Yujing; Shi, Yanhong; Zhou, Yingqun; He, Weigang; Dai, Qi; Zheng, Yuejuan; Lu, Jie

    2018-01-01

    Portulaca oleracea L. is a traditional Chinese medicine, which has been used as adjuvant therapy for inflammatory bowel disease (IBD). However, the mechanism of its activity in IBD still remains unclear. Since previous studies have documented the anti-inflammatory effect of peroxisome proliferator activated receptors- γ (PPAR- γ ), Portulaca regulation of PPAR- γ in inflammation was examined in current study. Ulcerative colitis (UC) was generated by 5% dextran sulfate sodium (DSS) in mice and four groups were established as normal control, DSS alone, DSS plus mesalamine, and DSS plus Portulaca . Severity of UC was evaluated by body weight, stool blood form, and length of colorectum. Inflammation was examined by determination of inflammatory cytokines (TNF-a, IL-6, and IL-1a). Portulaca extract was able to attenuate development of UC in DSS model similar to the treatment of mesalazine. Moreover, Portulaca extract inhibited proinflammatory cytokines release and reduced the level of DSS-induced NF- κ B phosphorylation. Furthermore, Portulaca extract restored PPAR- γ level, which was reduced by DSS. In addition, Portulaca extract protected DSS induced apoptosis in mice. In conclusion, Portulaca extract can alleviate colitis in mice through regulation of inflammatory reaction, apoptosis, and PPAR- γ level; therefore, Portulaca extract can be a potential candidate for the treatment of IBD.

  10. Sildenafil citrate (Viagra) impairs fertilization and early embryo development in mice.

    Science.gov (United States)

    Glenn, David R J; McClure, Neil; Cosby, S Louise; Stevenson, Michael; Lewis, Sheena E M

    2009-03-01

    To determine the effects of sildenafil citrate, a cyclic monophosphate-specific type 5 phosphodiesterase inhibitor known to affect sperm function, on fertilization and early embryo cleavage. This acute mammal study included male and female mice assigned randomly, the females sacrificed after mating and their oocytes/embryos evaluated at four time periods after treatment. Academic research environment. Male and female CBAB(6) mice. Female mice were injected intraperitoneally with 5 IU gonadotropin (hCG) to stimulate follicular growth and induce ovulation. They were each caged with a male that had been gavaged with sildenafil citrate (0.06 mg/0.05 mL) and allowed to mate. After 12, 36, 60, and 84 h, females were killed, their oviducts were dissected out, and retrieved embryos were assessed for blastomere number and quality. Fertilization rates and numbers of embryos were evaluated after treatment. Fertilization rates (day 1) were markedly reduced (-33%) in matings where the male had taken sildenafil citrate. Over days 2-4, the numbers of embryos developing in the treated group were significantly fewer than in the control group. There was also a trend for impaired cleavage rates within those embryos, although this did not reach significance. The impairments to fertility caused by sildenafil citrate have important implications for infertility centers and for couples who are using this drug precoitally while attempting to conceive.

  11. Mice lacking glutamate carboxypeptidase II develop normally, but are less susceptible to traumatic brain injury.

    Science.gov (United States)

    Gao, Yang; Xu, Siyi; Cui, Zhenwen; Zhang, Mingkun; Lin, Yingying; Cai, Lei; Wang, Zhugang; Luo, Xingguang; Zheng, Yan; Wang, Yong; Luo, Qizhong; Jiang, Jiyao; Neale, Joseph H; Zhong, Chunlong

    2015-07-01

    Glutamate carboxypeptidase II (GCPII) is a transmembrane zinc metallopeptidase found mainly in the nervous system, prostate and small intestine. In the nervous system, glia-bound GCPII mediates the hydrolysis of the neurotransmitter N-acetylaspartylglutamate (NAAG) into glutamate and N-acetylaspartate. Inhibition of GCPII has been shown to attenuate excitotoxicity associated with enhanced glutamate transmission under pathological conditions. However, different strains of mice lacking the GCPII gene are reported to exhibit striking phenotypic differences. In this study, a GCPII gene knockout (KO) strategy involved removing exons 3-5 of GCPII. This generated a new GCPII KO mice line with no overt differences in standard neurological behavior compared to their wild-type (WT) littermates. However, GCPII KO mice were significantly less susceptible to moderate traumatic brain injury (TBI). GCPII gene KO significantly lessened neuronal degeneration and astrocyte damage in the CA2 and CA3 regions of the hippocampus 24 h after moderate TBI. In addition, GCPII gene KO reduced TBI-induced deficits in long-term spatial learning/memory tested in the Morris water maze and motor balance tested via beam walking. Knockout of the GCPII gene is not embryonic lethal and affords histopathological protection with improved long-term behavioral outcomes after TBI, a result that further validates GCPII as a target for drug development consistent with results from studies using GCPII peptidase inhibitors. © 2015 International Society for Neurochemistry.

  12. Children and adolescents living with atopic eczema: an interpretive phenomenological study with Chinese mothers.

    Science.gov (United States)

    Cheung, Winnie K H; Lee, Regina L T

    2012-10-01

    This article is a report on a phenomenological study of Chinese mothers' experiences of caring for their children who were living with atopic eczema. A mother's attitude and personality may have a direct influence on her child's adherence to treatment for atopic eczema. Thus, good communication between healthcare professionals and the mother is essential. Treatment and care should also be culturally appropriate. Using an interpretive phenomenological method, 14 interviews were conducted in Hong Kong, China from September 2007 to August 2008, with nine mothers caring for their children who were living with atopic eczema. Crist and Tanner's circular process of hermeneutic interpretive phenomenology was chosen to guide the data analysis. Mothers' coping patterns involved persistently dealing with enduring demands and seeking alternative therapies that were aimed at curing the disease. Four themes finally emerged from the data: (1) dealing with extra mothering, (2) giving up their life, (3) becoming an expert and (4) living with blame and worry. Mothers' coping patterns involved persistently finding ways to relieve their children's suffering with the aim of curing the disease and dealing with their own emotions related to the frustration resulting from giving up their life and living with blame and worry. The study findings provide nurses with an empathic insight into mothers' feelings and the enduring demands of caring for children with atopic eczema, and help nurses to develop culturally sensitive interventions, reinforce positive coping strategies, increase family function and improve health outcomes. © 2011 Blackwell Publishing Ltd.

  13. Expression of truncated PITX3 in the developing lens leads to microphthalmia and aphakia in mice.

    Directory of Open Access Journals (Sweden)

    Kenta Wada

    Full Text Available Microphthalmia is a severe ocular disorder, and this condition is typically caused by mutations in transcription factors that are involved in eye development. Mice carrying mutations in these transcription factors would be useful tools for defining the mechanisms underlying developmental eye disorders. We discovered a new spontaneous recessive microphthalmos mouse mutant in the Japanese wild-derived inbred strain KOR1/Stm. The homozygous mutant mice were histologically characterized as microphthalmic by the absence of crystallin in the lens, a condition referred to as aphakia. By positional cloning, we identified the nonsense mutation c.444C>A outside the genomic region that encodes the homeodomain of the paired-like homeodomain transcription factor 3 gene (Pitx3 as the mutation responsible for the microphthalmia and aphakia. We examined Pitx3 mRNA expression of mutant mice during embryonic stages using RT-PCR and found that the expression levels are higher than in wild-type mice. Pitx3 over-expression in the lens during developmental stages was also confirmed at the protein level in the microphthalmos mutants via immunohistochemical analyses. Although lens fiber differentiation was not observed in the mutants, strong PITX3 protein signals were observed in the lens vesicles of the mutant lens. Thus, we speculated that abnormal PITX3, which lacks the C-terminus (including the OAR domain as a result of the nonsense mutation, is expressed in mutant lenses. We showed that the expression of the downstream genes Foxe3, Prox1, and Mip was altered because of the Pitx3 mutation, with large reductions in the lens vesicles in the mutants. Similar profiles were observed by immunohistochemical analysis of these proteins. The expression profiles of crystallins were also altered in the mutants. Therefore, we speculated that the microphthalmos/aphakia in this mutant is caused by the expression of truncated PITX3, resulting in the abnormal expression of

  14. In vivo evaluation of therapeutic options in atopic dermatitis

    NARCIS (Netherlands)

    Oldhoff, Jantje Maria

    2006-01-01

    Atopic dermatitis (AD, or atopic eczema) is an inflammatory itchy skin disease. AD patients often have high serum immunoglobulin E (IgE) levels, T-cell activation and eosinophilia in peripheral blood. The dermal infiltrate of AD contains mainly T-cells, eosinophils and dendritic cells. Epicutaneous

  15. Investigations on the immunopathogenesis of atopic dermatitis in cats

    NARCIS (Netherlands)

    Roosje, Pieternella Janna

    2002-01-01

    The term atopic dermatitis (AD) is commonly used in cats. At present, however, there is little known about the pathogenesis of feline AD. The aim was to investigate various aspects of the immunopathogenesis in a defined group of cats with signs and symptoms of atopic dermatitis and compare our

  16. Atopic dermatitis from adolescence to adulthood in the TOACS cohort

    DEFF Research Database (Denmark)

    Mørtz, Charlotte G; Andersen, K E; Dellgren, C

    2015-01-01

    allergic rhinitis and hand eczema. A close association was also found with allergic contact dermatitis and increased specific IgE to Malassezia furfur, but not with filaggrin gene defect. CONCLUSION: Persistence of atopic dermatitis in adulthood is common and affects quality of life. Persistent atopic...

  17. CD1d deficiency inhibits the development of abdominal aortic aneurysms in LDL receptor deficient mice.

    Directory of Open Access Journals (Sweden)

    Gijs H M van Puijvelde

    Full Text Available An abdominal aortic aneurysm (AAA is a dilatation of the abdominal aorta leading to serious complications and mostly to death. AAA development is associated with an accumulation of inflammatory cells in the aorta including NKT cells. An important factor in promoting the recruitment of these inflammatory cells into tissues and thereby contributing to the development of AAA is angiotensin II (Ang II. We demonstrate that a deficiency in CD1d dependent NKT cells under hyperlipidemic conditions (LDLr-/-CD1d-/- mice results in a strong decline in the severity of angiotensin II induced aneurysm formation when compared with LDLr-/- mice. In addition, we show that Ang II amplifies the activation of NKT cells both in vivo and in vitro. We also provide evidence that type I NKT cells contribute to AAA development by inducing the expression of matrix degrading enzymes in vSMCs and macrophages, and by cytokine dependently decreasing vSMC viability. Altogether, these data prove that CD1d-dependent NKT cells contribute to AAA development in the Ang II-mediated aneurysm model by enhancing aortic degradation, establishing that therapeutic applications which target NKT cells can be a successful way to prevent AAA development.

  18. How radiation influences atherosclerotic plaque development. A biophysical approach in ApoE{sup -/-} mice

    Energy Technology Data Exchange (ETDEWEB)

    Kloosterman, Astrid; Dillen, Teun van; Dekkers, Fieke [National Institute for Public Health and the Environment (RIVM), Centre for Environmental Safety and Security, Bilthoven (Netherlands); Bijwaard, Harmen [National Institute for Public Health and the Environment (RIVM), Centre for Environmental Safety and Security, Bilthoven (Netherlands); Inholland University of Applied Sciences, Medical Technology Research Group, Haarlem (Netherlands); Heeneman, Sylvia [Maastricht University Medical Center, Experimental Vascular Pathology group, Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht (Netherlands); Hoving, Saske; Stewart, Fiona A. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Biological Stress Response (H3), Amsterdam (Netherlands)

    2017-11-15

    Atherosclerosis is the development of lipid-laden plaques in arteries and is nowadays considered as an inflammatory disease. It has been shown that high doses of ionizing radiation, as used in radiotherapy, can increase the risk of development or progression of atherosclerosis. To elucidate the effects of radiation on atherosclerosis, we propose a mathematical model to describe radiation-promoted plaque development. This model distinguishes itself from other models by combining plaque initiation and plaque growth, and by incorporating information from biological experiments. It is based on two consecutive processes: a probabilistic dose-dependent plaque initiation process, followed by deterministic plaque growth. As a proof of principle, experimental plaque size data from carotid arteries from irradiated ApoE{sup -/-} mice was used to illustrate how this model can provide insight into the underlying biological processes. This analysis supports the promoting role for radiation in plaque initiation, but the model can easily be extended to include dose-related effects on plaque growth if available experimental data would point in that direction. Moreover, the model could assist in designing future biological experiments on this research topic. Additional biological data such as plaque size data from chronically-irradiated mice or experimental data sets with a larger variety in biological parameters can help to further unravel the influence of radiation on plaque development. To the authors' knowledge, this is the first biophysical model that combines probabilistic and mechanistic modeling which uses experimental data to investigate the influence of radiation on plaque development. (orig.)

  19. Development of myenteric cholinergic neurons in ChAT-Cre;R26R-YFP mice.

    Science.gov (United States)

    Hao, Marlene M; Bornstein, Joel C; Young, Heather M

    2013-10-01

    Cholinergic neurons are the major excitatory neurons of the enteric nervous system (ENS), and include intrinsic sensory neurons, interneurons, and excitatory motor neurons. Cholinergic neurons have been detected in the embryonic ENS; however, the development of these neurons has been difficult to study as they are difficult to detect prior to birth using conventional immunohistochemistry. In this study we used ChAT-Cre;R26R-YFP mice to examine the development of cholinergic neurons in the gut of embryonic and postnatal mice. Cholinergic (YFP+) neurons were first detected at embryonic day (E)11.5, and the proportion of cholinergic neurons gradually increased during pre- and postnatal development. At birth, myenteric cholinergic neurons comprised less than half of their adult proportions in the small intestine (25% of myenteric neurons were YFP+ at P0 compared to 62% in adults). The earliest cholinergic neurons appear to mainly project anally. Projections into the presumptive circular muscle were first observed at E14.5. A subpopulation of cholinergic neurons coexpress calbindin through embryonic and postnatal development, but only a small proportion coexpressed neuronal nitric oxide synthase. Our study shows that cholinergic neurons in the ENS develop over a protracted period of time. © 2013 Wiley Periodicals, Inc.

  20. Cell-cycle arrest in mature adipocytes impairs BAT development but not WAT browning, and reduces adaptive thermogenesis in mice.

    Science.gov (United States)

    Okamatsu-Ogura, Yuko; Fukano, Keigo; Tsubota, Ayumi; Nio-Kobayashi, Junko; Nakamura, Kyoko; Morimatsu, Masami; Sakaue, Hiroshi; Saito, Masayuki; Kimura, Kazuhiro

    2017-07-27

    We previously reported brown adipocytes can proliferate even after differentiation. To test the involvement of mature adipocyte proliferation in cell number control in fat tissue, we generated transgenic (Tg) mice over-expressing cell-cycle inhibitory protein p27 specifically in adipocytes, using the aP2 promoter. While there was no apparent difference in white adipose tissue (WAT) between wild-type (WT) and Tg mice, the amount of brown adipose tissue (BAT) was much smaller in Tg mice. Although BAT showed a normal cellular morphology, Tg mice had lower content of uncoupling protein 1 (UCP1) as a whole, and attenuated cold exposure- or β3-adrenergic receptor (AR) agonist-induced thermogenesis, with a decrease in the number of mature brown adipocytes expressing proliferation markers. An agonist for the β3-AR failed to increase the number of proliferating brown adipocytes, UCP1 content in BAT, and oxygen consumption in Tg mice, although the induction and the function of beige adipocytes in inguinal WAT from Tg mice were similar to WT mice. These results show that brown adipocyte proliferation significantly contributes to BAT development and adaptive thermogenesis in mice, but not to induction of beige adipocytes.

  1. Critical role of IFN-gamma in CFA-mediated protection of NOD mice from diabetes development.

    Science.gov (United States)

    Mori, Yoshiko; Kodaka, Tetsuro; Kato, Takako; Kanagawa, Edith M; Kanagawa, Osami

    2009-11-01

    IFN-gamma signaling-deficient non-obese diabetic (NOD) mice develop diabetes with similar kinetics to those of wild-type NOD mice. However, the immunization of IFN-gamma signaling-deficient NOD mice with CFA failed to induce long-term protection, whereas wild-type NOD mice receiving CFA remained diabetes-free. CFA also failed to protect IFN-gamma receptor-deficient (IFN-gammaR(-/-)) NOD mice from the autoimmune rejection of transplanted islets, as it does in diabetic NOD mice, and from disease transfer by spleen cells from diabetic NOD mice. These data clearly show that the pro-inflammatory cytokine IFN-gamma is necessary for the CFA-mediated protection of NOD mice from diabetes. There is no difference in the T(h)1/T(h)17 balance between IFN-gammaR(-/-) NOD and wild-type NOD mice. There is also no difference in the total numbers and percentages of regulatory T (Treg) cells in the lymph node CD4(+) T-cell populations between IFN-gammaR(-/-) NOD and wild-type NOD mice. However, pathogenic T cells lacking IFN-gammaR are resistant to the suppressive effect of Treg cells, both in vivo and in vitro. Therefore, it is likely that CFA-mediated protection against diabetes development depends on a change in the balance between Treg cells and pathogenic T cells, and IFN-gamma signaling seems to control the susceptibility of pathogenic T cells to the inhibitory activity of Treg cells.

  2. Diet-induced obesity promotes colon tumor development in azoxymethane-treated mice.

    Directory of Open Access Journals (Sweden)

    Iina Tuominen

    Full Text Available Obesity is an important risk factor for colon cancer in humans, and numerous studies have shown that a high fat diet enhances colon cancer development. As both increased adiposity and high fat diet can promote tumorigenesis, we examined the effect of diet-induced obesity, without ongoing high fat diet, on colon tumor development. C57BL/6J male mice were fed regular chow or high fat diet for 8 weeks. Diets were either maintained or switched resulting in four experimental groups: regular chow (R, high fat diet (H, regular chow switched to high fat diet (RH, and high fat diet switched to regular chow (HR. Mice were then administered azoxymethane to induce colon tumors. Tumor incidence and multiplicity were dramatically smaller in the R group relative to all groups that received high fat diet at any point. The effect of obesity on colon tumors could not be explained by differences in aberrant crypt foci number. Moreover, diet did not alter colonic expression of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, interleukin-1β, and interferon-γ, which were measured immediately after azoxymethane treatment. Crypt apoptosis and proliferation, which were measured at the same time, were increased in the HR relative to all other groups. Our results suggest that factors associated with obesity - independently of ongoing high fat diet and obesity - promote tumor development because HR group animals had significantly more tumors than R group, and these mice were fed the same regular chow throughout the entire carcinogenic period. Moreover, there was no difference in the number of aberrant crypt foci between these groups, and thus the effect of obesity appears to be on subsequent stages of tumor development when early preneoplastic lesions transition into adenomas.

  3. Dietary Heme Induces Gut Dysbiosis, Aggravates Colitis, and Potentiates the Development of Adenomas in Mice

    Directory of Open Access Journals (Sweden)

    Marco Constante

    2017-09-01

    Full Text Available Dietary heme can be used by colonic bacteria equipped with heme-uptake systems as a growth factor and thereby impact on the microbial community structure. The impact of heme on the gut microbiota composition may be particularly pertinent in chronic inflammation such as in inflammatory bowel disease (IBD, where a strong association with gut dysbiosis has been consistently reported. In this study we investigated the influence of dietary heme on the gut microbiota and inferred metagenomic composition, and on chemically induced colitis and colitis-associated adenoma development in mice. Using 16S rRNA gene sequencing, we found that mice fed a diet supplemented with heme significantly altered their microbiota composition, characterized by a decrease in α-diversity, a reduction of Firmicutes and an increase of Proteobacteria, particularly Enterobacteriaceae. These changes were similar to shifts seen in dextran sodium sulfate (DSS-treated mice to induce colitis. In addition, dietary heme, but not systemically delivered heme, contributed to the exacerbation of DSS-induced colitis and facilitated adenoma formation in the azoxymethane/DSS colorectal cancer (CRC mouse model. Using inferred metagenomics, we found that the microbiota alterations elicited by dietary heme resulted in non-beneficial functional shifts, which were also characteristic of DSS-induced colitis. Furthermore, a reduction in fecal butyrate levels was found in mice fed the heme supplemented diet compared to mice fed the control diet. Iron metabolism genes known to contribute to heme release from red blood cells, heme uptake, and heme exporter proteins, were significantly enriched, indicating a shift toward favoring the growth of bacteria able to uptake heme and protect against its toxicity. In conclusion, our data suggest that luminal heme, originating from dietary components or gastrointestinal bleeding in IBD and, to lesser extent in CRC, directly contributes to microbiota dysbiosis

  4. Topical steroid addiction in atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Fukaya M

    2014-10-01

    Full Text Available Mototsugu Fukaya,1 Kenji Sato,2 Mitsuko Sato,3 Hajime Kimata,4 Shigeki Fujisawa,5 Haruhiko Dozono,6 Jun Yoshizawa,7 Satoko Minaguchi8 1Tsurumai Kouen Clinic, Nagoya, 2Department of Dermatology, Hannan Chuo Hospital, Osaka, 3Sato Pediatric Clinic, Osaka, 4Kimata Hajime Clinic, Osaka, 5Fujisawa Dermatology Clinic, Tokyo, 6Dozono Medical House, Kagoshima, 7Yoshizawa Dermatology Clinic, Yokohama, 8Department of Dermatology, Kounosu Kyousei Hospital, Saitama, Japan Abstract: The American Academy of Dermatology published a new guideline regarding topical therapy in atopic dermatitis in May 2014. Although topical steroid addiction or red burning skin syndrome had been mentioned as possible side effects of topical steroids in a 2006 review article in the Journal of the American Academy of Dermatology, no statement was made regarding this illness in the new guidelines. This suggests that there are still controversies regarding this illness. Here, we describe the clinical features of topical steroid addiction or red burning skin syndrome, based on the treatment of many cases of the illness. Because there have been few articles in the medical literature regarding this illness, the description in this article will be of some benefit to better understand the illness and to spur discussion regarding topical steroid addiction or red burning skin syndrome. Keywords: topical steroid addiction, atopic dermatitis, red burning skin syndrome, rebound, corticosteroid, eczema

  5. Oral administration of Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1 suppresses inflammation by decreasing interleukin-6 responses in a murine model of atopic dermatitis.

    Science.gov (United States)

    Kano, Hiroshi; Kita, Junko; Makino, Seiya; Ikegami, Shuji; Itoh, Hiroyuki

    2013-06-01

    The oral intake of Lactobacillus spp. can provide beneficial effects to the host by modulating the immune response. Atopic dermatitis (AD) is an allergic inflammatory disease mediated by various immune responses. In this study, we examined the effect of a Lactobacillus strain, Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (OLL1073R-1), on AD development in a murine model of AD that was developed by the topical application of mite antigen in NC/Nga mice. The oral intake of heat-killed OLL1073R-1 cells inhibited both the development of dermatitis and the elevation of an acute inflammation marker, serum amyloid A. Another bacterial strain, Lactobacillus rhamnosus OLL2984, exerted no inhibitory effects on dermatitis. The oral intake of heat-killed OLL1073R-1 cells also attenuated secretion of IL-6 from lymph node cells in response to mite antigen and reduced IL-6 levels in inflamed tissues, such as auricles. Production of IFN-γ or IL-4 was not influenced by OLL1073R-1 intake. We also found that inhibition of IL-6 signaling by gp130-Fc (a fusion protein consisting of the extracellular portion of glycoprotein 130 fused to the Fc region of human IgG1) markedly decreased the severity of dermatitis in NC/Nga mice. Moreover, secretion of IL-6 by lymph node cells was augmented in NC/Nga mice compared with that in BALB/c mice. These results indicate that IL-6 plays an essential role in the development of dermatitis in the NC/Nga mouse model of AD, and that OLL1073R-1 inhibits dermatitis, at least in part, by suppressing the IL-6 response. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  6. Placental growth factor deficiency is associated with impaired cerebral vascular development in mice.

    Science.gov (United States)

    Luna, Rayana Leal; Kay, Vanessa R; Rätsep, Matthew T; Khalaj, Kasra; Bidarimath, Mallikarjun; Peterson, Nichole; Carmeliet, Peter; Jin, Albert; Croy, B Anne

    2016-02-01

    Placental growth factor (PGF) is expressed in the developing mouse brain and contributes to vascularization and vessel patterning. PGF is dynamically expressed in fetal mouse brain, particularly forebrain, and is essential for normal cerebrovascular development. PGF rises in maternal plasma over normal human and mouse pregnancy but is low in many women with the acute onset hypertensive syndrome, pre-eclampsia (PE). Little is known about the expression of PGF in the fetus during PE. Pgf  (-/-) mice appear normal but recently cerebral vascular defects were documented in adult Pgf  (-/-) mice. Here, temporal-spatial expression of PGF is mapped in normal fetal mouse brains and cerebral vasculature development is compared between normal and congenic Pgf  (-/-) fetuses to assess the actions of PGF during cerebrovascular development. Pgf/PGF, Vegfa/VEGF, Vegf receptor (Vegfr)1 and Vegfr2 expression were examined in the brains of embryonic day (E)12.5, 14.5, 16.5 and 18.5 C57BL/6 (B6) mice using quantitative PCR and immunohistochemistry. The cerebral vasculature was compared between Pgf  (-/-) and B6 embryonic and adult brains using whole mount techniques. Vulnerability to cerebral ischemia was investigated using a left common carotid ligation assay. Pgf/PGF and Vegfr1 are highly expressed in E12.5-14.5 forebrain relative to VEGF and Vegfr2. Vegfa/VEGF is relatively more abundant in hindbrain (HB). PGF and VEGF expression were similar in midbrain. Delayed HB vascularization was seen at E10.5 and 11.5 in Pgf  (-/-) brains. At E14.5, Pgf  (-/-) circle of Willis showed unilateral hypoplasia and fewer collateral vessels, defects that persisted post-natally. Functionally, adult Pgf  (-/-) mice experienced cerebral ischemia after left common carotid arterial occlusion while B6 mice did not. Since Pgf  (-/-) mice were used, consequences of complete absence of maternal and fetal PGF were defined. Therefore, the effects of maternal versus fetal PGF

  7. Histone demethylases UTX and JMJD3 are required for NKT cell development in mice.

    Science.gov (United States)

    Northrup, Daniel; Yagi, Ryoji; Cui, Kairong; Proctor, William R; Wang, Chaochen; Placek, Katarzyna; Pohl, Lance R; Wang, Rongfu; Ge, Kai; Zhu, Jinfang; Zhao, Keji

    2017-01-01

    Natural killer (NK)T cells and conventional T cells share phenotypic characteristic however they differ in transcription factor requirements and functional properties. The role of histone modifying enzymes in conventional T cell development has been extensively studied, little is known about the function of enzymes regulating histone methylation in NKT cells. We show that conditional deletion of histone demethylases UTX and JMJD3 by CD4-Cre leads to near complete loss of liver NKT cells, while conventional T cells are less affected. Loss of NKT cells is cell intrinsic and not due to an insufficient selection environment. The absence of NKT cells in UTX/JMJD3-deficient mice protects mice from concanavalin A-induced liver injury, a model of NKT-mediated hepatitis. GO-analysis of RNA-seq data indicates that cell cycle genes are downregulated in UTX/JMJD3-deleted NKT progenitors, and suggest that failed expansion may account for some of the cellular deficiency. The phenotype appears to be demethylase-dependent, because UTY, a homolog of UTX that lacks catalytic function, is not sufficient to restore their development and removal of H3K27me3 by deletion of EZH2 partially rescues the defect. NKT cell development and gene expression is sensitive to proper regulation of H3K27 methylation. The H3K27me3 demethylase enzymes, in particular UTX, promote NKT cell development, and are required for effective NKT function.

  8. Clonidine treatment delays postnatal motor development and blocks short-term memory in young mice.

    Directory of Open Access Journals (Sweden)

    Cristina Calvino-Núñez

    Full Text Available During the development of the nervous system, the perinatal period is particularly sensitive as neuronal connections are still forming in the brain of the neonate. Alpha2-adrenergic receptors are overexpressed temporarily in proliferative zones in the developing brain, reaching a peak during the first postnatal week of life. Both stimulation and blocking of these receptors during this period alter the development of neural circuits, affecting synaptic connectivity and neuronal responses. They even affect motor and cognitive skills later on in the adult. It's especially important to look for the early neurological consequences resulting from such modifications, because they may go unnoticed. The main objective of the present study has been to reaffirm the importance of the maturation of alpha-adrenergic system in mice, by carrying out a comprehensive examination of motor, behavioral and cognitive effects in neonates, during early postnatal development, following chronic administration of the drug Clonidine, an alpha2 adrenergic system agonist. Our study shows that mice treated postnatally with clonidine present a temporal delay in the appearance of developmental markers, a slow execution of vestibular reflexes during first postnatal week of life and a blockade of the short term memory in the novel object recognition task. Shortly after the treatment the startle response is hyperreactive.

  9. Atopic Dermatitis in Children: Clinical Features, Pathophysiology and Treatment

    Science.gov (United States)

    Lyons, Jonathan J.; Milner, Joshua D.; Stone, Kelly D.

    2014-01-01

    Atopic dermatitis (AD) is a chronic, relapsing, highly pruritic skin condition resulting from disruption of the epithelial barrier and associated immune dysregulation in the skin of genetically predisposed hosts. AD generally develops in early childhood, has a characteristic age-dependent distribution and is commonly associated with elevated IgE, peripheral eosinophilia and other allergic diseases. Staphylococcus aureus colonization is common and may contribute to disease progression and severity. Targeted therapies to restore both impaired skin barrier and control inflammation are required for optimal outcomes for patients with moderate to severe disease. Pruritus is universal among patients with AD and has a dominant impact on diminishing quality of life. Medications such as anti-histamines have demonstrated poor efficacy in controlling AD-associated itch. Education of patients regarding the primary underlying defects and provision of a comprehensive skin care plan is essential for disease maintenance and management of flares. PMID:25459583

  10. Alcohol during pregnancy and atopic dermatitis in the offspring

    DEFF Research Database (Denmark)

    Linneberg, A; Petersen, Janne; Grønbaek, M

    2004-01-01

    BACKGROUND: There is evidence that antenatal factors play a role in the development of atopic dermatitis (AD). However, little is known about the effects of maternal lifestyle factors during pregnancy on the risk of AD in the offspring. OBJECTIVE: To investigate the effect of alcohol consumption...... during pregnancy on the incidence of AD in the offspring. METHODS: A total of 24 341 mother-child pairs enrolled in the Danish National Birth Cohort were followed prospectively. Information about alcohol consumption was obtained by interview at 12 and 30 weeks of gestation. Information about symptoms......, time of onset, and doctor's diagnosis of AD in the offspring was obtained by interview at 18 months of age. The effect of alcohol consumption during pregnancy on the incidence of AD was analysed by Cox regression allowing for different effects of alcohol before (early infancy) and after 2 months (60...

  11. Alcohol during pregnacu and atopic dermatitis in the offspring

    DEFF Research Database (Denmark)

    Linneberg, a; Petersen, Janne; Grønbæk, M

    2005-01-01

    BACKGROUND: There is evidence that antenatal factors play a role in the development of atopic dermatitis (AD). However, little is known about the effects of maternal lifestyle factors during pregnancy on the risk of AD in the offspring. OBJECTIVE: To investigate the effect of alcohol consumption...... during pregnancy on the incidence of AD in the offspring. METHODS: A total of 24 341 mother-child pairs enrolled in the Danish National Birth Cohort were followed prospectively. Information about alcohol consumption was obtained by interview at 12 and 30 weeks of gestation. Information about symptoms......, time of onset, and doctor's diagnosis of AD in the offspring was obtained by interview at 18 months of age. The effect of alcohol consumption during pregnancy on the incidence of AD was analysed by Cox regression allowing for different effects of alcohol before (early infancy) and after 2 months (60...

  12. Atopic dermatitis: recent insight on pathogenesis and novel therapeutic target.

    Science.gov (United States)

    D'Auria, Enza; Banderali, Giuseppe; Barberi, Salvatore; Gualandri, Lorenzo; Pietra, Benedetta; Riva, Enrica; Cerri, Amilcare

    2016-06-01

    Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. It affects infancy, but it is also highly prevalent in adults and it is one of the disease burdens for the patients and their families. Nowadays, AD is recognized as a heterogenous disease with different subtypes with variable clinical manifestations which is affected by the impairments of the skin barrier. The severity of AD dictates the level of treatment. Current AD treatment focuses on restoration of the barrier function, mainly through the use of moisturizers and corticosteroids to control the inflammation, topical calcineurin inhibitors, and immunosuppresive drugs in the most severe cases. However, targeted disease-modifying therapies are under investigation. The most recent findings on the skin microbial dysbiosis is a promising future direction for the development of new treatments. We need to improve the understanding of the complex microbiome-host interactions, the role of autoimmunity, the comparative effectiveness of therapies and the ways to appropriately implement the educational strategies.

  13. Phenotypic analysis of perennial airborne allergen-specific CD4+ T cells in atopic and non-atopic individuals.

    Science.gov (United States)

    Crack, L R; Chan, H W; McPherson, T; Ogg, G S

    2011-11-01

    Accumulating evidence suggests that T cells play an important role in the pathogenesis of atopic dermatitis (AD); yet, little is known of the differentiation status of CD4+ T cells specific for common environmental allergens, such as the major cat allergen, Fel d 1. To determine the frequency, differentiation phenotype and function of circulating Fel d 1-specific CD4+ T cells in adult individuals with severe persistent AD in comparison with healthy controls. Using HLA class II tetrameric complexes based on a HLA-DPB1*0401-restricted Fel d 1 epitope, ex vivo and cultured T cell frequency and phenotype were analysed in individuals with AD and healthy controls. Cytokine secretion was measured by ex vivo and cultured IL-4 and IFN-γ ELISpots. Ex vivo Fel d 1-specific DPB1*0401-restricted CD4+ T cells in both atopics and non-atopics express high levels of CCR7, CD62L, CD27 and CD28, placing the cells largely within the central memory subgroup. However, the functional phenotype was distinct, with greater IL-4 production from the cells derived from atopics, which correlated with disease severity. Circulating Fel d 1-specific DPB1*0401-restricted CD4+ T cells in both atopic and non-atopic donors maintain a central memory phenotype; however in atopics, the cells had greater Th2 effector function, compatible with a disease model of altered antigen delivery in atopic individuals. © 2011 Blackwell Publishing Ltd.

  14. Measurement of the Λ$0\\atop{b}$ → Λ$+\\atop{c}$π- branching ratio

    Energy Technology Data Exchange (ETDEWEB)

    Le, Yi [Johns Hopkins Univ., Baltimore, MD (United States)

    2003-01-01

    The authors present a measurement of the Λ$0\\atop{b}$ → Λ$+\\atop{c}$π- branching ratio in p$\\bar{p}$ collisions at √s = 1.96 TeV using 65 pb-1 data collected by the Collider Detector at Fermilab (CDF).

  15. The validity of register data to identify children with atopic dermatitis, asthma or allergic rhinoconjunctivitis.

    Science.gov (United States)

    Stensballe, Lone Graff; Klansø, Lotte; Jensen, Andreas; Haerskjold, Ann; Thomsen, Simon Francis; Simonsen, Jacob

    2017-09-01

    The incidence of atopic dermatitis, wheezing, asthma and allergic rhinoconjunctivitis has been increasing. Register-based studies are essential for research in subpopulations with specific diseases and facilitate epidemiological studies to identify causes and evaluate interventions. Algorithms have been developed to identify children with atopic dermatitis, asthma or allergic rhinoconjunctivitis using register information on disease-specific dispensed prescribed medication and hospital contacts, but the validity of the algorithms has not been evaluated. This study validated the algorithms vs gold standard deep telephone interviews with the caretaker about physician-diagnosed atopic dermatitis, wheezing, asthma or allergic rhinoconjunctivitis in the child. The algorithms defined each of the three atopic diseases using register-based information on disease-specific hospital contacts and/or filled prescriptions of disease-specific medication. Confirmative answers to questions about physician-diagnosed atopic disease were used as the gold standard for the comparison with the algorithms, resulting in sensitivities and specificities and 95% confidence intervals. The interviews with the caretaker of the included 454 Danish children born 1997-2003 were carried out May-September 2015; the mean age of the children at the time of the interview being 15.2 years (standard deviation 1.3 years). For the algorithm capturing children with atopic dermatitis, the sensitivity was 74.1% (95% confidence interval: 66.9%-80.2%) and the specificity 73.0% (67.3%-78.0%). For the algorithm capturing children with asthma, both the sensitivity of 84.1% (78.0%-88.8%) and the specificity of 81.6% (76.5%-85.8%) were high compared with physician-diagnosed asthmatic bronchitis (recurrent wheezing). The sensitivity remained high when capturing physician-diagnosed asthma: 83.3% (74.3%-89.6%); however, the specificity declined to 66.0% (60.9%-70.8%). For allergic rhinoconjunctivitis, the sensitivity

  16. Knock-in mice harboring a Ca(2+) desensitizing mutation in cardiac troponin C develop early onset dilated cardiomyopathy.

    Science.gov (United States)

    McConnell, Bradley K; Singh, Sonal; Fan, Qiying; Hernandez, Adriana; Portillo, Jesus P; Reiser, Peter J; Tikunova, Svetlana B

    2015-01-01

    The physiological consequences of aberrant Ca(2+) binding and exchange with cardiac myofilaments are not clearly understood. In order to examine the effect of decreasing Ca(2+) sensitivity of cTnC on cardiac function, we generated knock-in mice carrying a D73N mutation (not known to be associated with heart disease in human patients) in cTnC. The D73N mutation was engineered into the regulatory N-domain of cTnC in order to reduce Ca(2+) sensitivity of reconstituted thin filaments by increasing the rate of Ca(2+) dissociation. In addition, the D73N mutation drastically blunted the extent of Ca(2+) desensitization of reconstituted thin filaments induced by cTnI pseudo-phosphorylation. Compared to wild-type mice, heterozygous knock-in mice carrying the D73N mutation exhibited a substantially decreased Ca(2+) sensitivity of force development in skinned ventricular trabeculae. Kaplan-Meier survival analysis revealed that median survival time for knock-in mice was 12 weeks. Echocardiographic analysis revealed that knock-in mice exhibited increased left ventricular dimensions with thinner walls. Echocardiographic analysis also revealed that measures of systolic function, such as ejection fraction (EF) and fractional shortening (FS), were dramatically reduced in knock-in mice. In addition, knock-in mice displayed electrophysiological abnormalities, namely prolonged QRS and QT intervals. Furthermore, ventricular myocytes isolated from knock-in mice did not respond to β-adrenergic stimulation. Thus, knock-in mice developed pathological features similar to those observed in human patients with dilated cardiomyopathy (DCM). In conclusion, our results suggest that decreasing Ca(2+) sensitivity of the regulatory N-domain of cTnC is sufficient to trigger the development of DCM.

  17. Stigmatization and self-perception in children with atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Chernyshov PV

    2016-07-01

    Full Text Available Pavel V Chernyshov Department of Dermatology and Venereology, National Medical University, Kiev, Ukraine Abstract: Atopic dermatitis (AD is one of the most common skin diseases. Prevalence of AD is highest in childhood. Because of chronicity and often visible lesions, AD may lead to stigmatization and problems with self-perception. However, problems of self-perception and stigmatization in AD children are poorly studied. Literature data on general tendencies of children’s development, clinical course, and epidemiologic tendencies of AD in different age groups make it possible to highlight three main periods in the formation of self-perception and stigmatization. The first period is from early infancy till 3 years of age. The child’s problems in this period depend on parental exhaustion, emotional distress, and security of the mother–child attachment. The child’s AD may form a kind of vicious circle in which severe AD causes parental distress and exhaustion that in turn lead to exacerbation of AD and psychological problems in children. The second period is from 3 till 10 years of age. During this period, development of AD children may be influenced by teasing, bullying, and avoiding by their peers. However, the majority of children in this age group are very optimistic. The third period is from 10 years till adulthood. Problems related to low self-esteem are characteristic during this period. It is important to identify children with AD and their parents who need psychological help and provide them with needs-based consultation and care. Appropriate treatment, medical consultations, and educational programs may help to reduce emotional problems in AD children and their parents. Keywords: atopic dermatitis, stigmatization, self-perception, quality of life, children, pediatric dermatology, skin disease

  18. Human CD4 restores normal T cell development and function in mice deficient in murine CD4

    OpenAIRE

    1994-01-01

    The ability of a human coreceptor to function in mice was investigated by generating human CD4 (hCD4)-expressing transgenic mice on a mouse CD4-deficient (mCD4-/-) background. From developing thymocyte to matured T lymphocyte functions, hCD4 was shown to be physiologically active. By examining the expansion and deletion of specific V beta T cell families in mutated mice with and without hCD4, it was found that hCD4 can participate in positive and negative selection. Mature hCD4 single positiv...

  19. PDK1 Deficit Impairs the Development of the Dentate Gyrus in Mice.

    Science.gov (United States)

    Xu, Min; Han, Xiaoning; Liu, Rui; Li, Yanjun; Qi, Cui; Yang, Zhongzhou; Zhao, Chunjie; Gao, Jun

    2018-02-06

    3-Phosphoinositide-dependent protein kinase-1 (PDK1) is crucial for the development of the dentate gyrus (DG), the first gateway receiving afferent inputs from the entorhinal cortex. However, the role of PDK1 in DG development is unclear. In the present study, by crossing Pdk1fl/fl mice with the Emx1-cre line, we identified that the ablation of PDK1 disrupted the development of DG via decreasing the proliferation, and increasing the differentiation of dentate neural progenitor cells, downregulating AKT activity and upregulating GSK3β signaling. Moreover, PDK1 deletion disrupted the distribution of Reelin+ cells and decreased the level of Reelin mRNA which may contribute to the defective migration of progenitor cells and the disrupted radial glial scaffolds. Furthermore, the inhibition of GSK3β activity partially restored the decreased proliferation of primary neural stem cells in vitro. Taken together, our data indicated that the ablation of PDK1 affected the proliferation and differentiation of dentate neural progenitor cells in mice. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Entire litters developed from transferred eggs in whole body x-irradiated female mice

    International Nuclear Information System (INIS)

    Lin, T.P.

    1980-01-01

    The sensitivity of mouse eggs to sublethal x-irradiation was determined in vitro and in vivo with regard to the development of donor litters in foster mothers. One thousand seven hundred fifty-eight unfertilized eggs of agouti dark-eyed donor mice were transferred into 293 unirradiated or x-irradiated, mated female pink-eyed mice. Two hundred thirty-nine recipients became pregnant; of these 35 produced litters containing solely dark-eyed fetuses. Sublethal doses of x-radiation administered to donor eggs in vitro before transferring into unirradiated recipients did not influence significantly the number of litters of exclusively dark-eyed fetuses produced. However, recipients irradiated by 250 roentgens (r) produced more solely dark-eyed litters than did those irradiated with 100 r. In 21 pregnant females irradiated by 100 r, only 3 (14%) developed solely dark-eyed fetuses as compared to 22 pregnant females irradiated by 250 r, of which 13 (59%) developed solely dark-eyed fetuses, all from unirradiated, transferred eggs. Of another group of 22 pregnant females which received 250 r body irradiation and subsequently received eggs also irradiated by 250 r, only 7 (32%) produced litters of dark-eyed fetuses. No one female of these three groups carried native fetuses. Such radiation-induced infertility resulting from damage of native eggs rather than loss of mother's ability to carry a pregnancy, is frequently remedied by egg transfer

  1. Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like Tumor Development in Mice.

    Science.gov (United States)

    Verhaegen, Monique E; Mangelberger, Doris; Harms, Paul W; Eberl, Markus; Wilbert, Dawn M; Meireles, Julia; Bichakjian, Christopher K; Saunders, Thomas L; Wong, Sunny Y; Dlugosz, Andrzej A

    2017-06-15

    Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a nonproliferative population of neuroendocrine cells that arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor's cell of origin, are unknown. Using a panel of preterm transgenic mice, we show that epidermis-targeted coexpression of sT and the cell fate-determinant atonal bHLH transcription factor 1 (ATOH1) leads to development of widespread cellular aggregates, with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Coexpression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with ATOH1. MCPyV sT, when coexpressed with ATOH1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. Cancer Res; 77(12); 3151-7. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. Deregulation of mTOR signaling is involved in thymic lymphoma development in Atm-/- mice

    International Nuclear Information System (INIS)

    Kuang, Xianghong; Shen, Jianjun; Wong, Paul K.Y.; Yan, Mingshan

    2009-01-01

    Abnormal thymocyte development with thymic lymphomagenesis inevitably occurs in Atm-/- mice, indicating that ATM plays a pivotal role in regulating postnatal thymocyte development and preventing thymic lymphomagenesis. The mechanism for ATM controls these processes is unclear. We have shown previously that c-Myc, an oncoprotein regulated by the mammalian target of rapamycin (mTOR), is overexpressed in Atm-/- thymocytes. Here, we show that inhibition of mTOR signaling with its specific inhibitor, rapamycin, suppresses normal thymocyte DNA synthesis by downregulating 4EBP1, but not S6K, and that 4EBP1 phosphorylation and cyclin D1 expression are coordinately increased in Atm-/- thymocytes. Administration of rapamycin to Atm-/- mice attenuates elevated phospho-4EBP1, c-Myc and cyclin D1 in their thymocytes, and delays thymic lymphoma development. These results indicate that mTOR downstream effector 4EBP1 is essential for normal thymocyte proliferation, but deregulation of 4EBP1 in Atm deficiency is a major factor driving thymic lymphomagenesis in the animals.

  3. Pathophysiological and behavioral deficits in developing mice following rotational acceleration-deceleration traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Guoxiang Wang

    2018-01-01

    Full Text Available Abusive head trauma (AHT is the leading cause of death from trauma in infants and young children. An AHT animal model was developed on 12-day-old mice subjected to 90° head extension-flexion sagittal shaking repeated 30, 60, 80 and 100 times. The mortality and time until return of consciousness were dependent on the number of repeats and severity of the injury. Following 60 episodes of repeated head shakings, the pups demonstrated apnea and/or bradycardia immediately after injury. Acute oxygen desaturation was observed by pulse oximetry during respiratory and cardiac suppression. The cerebral blood perfusion was assessed by laser speckle contrast analysis (LASCA using a PeriCam PSI system. There was a severe reduction in cerebral blood perfusion immediately after the trauma that did not significantly improve within 24 h. The injured mice began to experience reversible sensorimotor function at 9 days postinjury (dpi, which had completely recovered at 28 dpi. However, cognitive deficits and anxiety-like behavior remained. Subdural/subarachnoid hemorrhage, damage to the brain-blood barrier and parenchymal edema were found in all pups subjected to 60 insults. Proinflammatory response and reactive gliosis were upregulated at 3 dpi. Degenerated neurons were found in the cerebral cortex and olfactory tubercles at 30 dpi. This mouse model of repetitive brain injury by rotational head acceleration-deceleration partially mimics the major pathophysiological and behavioral events that occur in children with AHT. The resultant hypoxia/ischemia suggests a potential mechanism underlying the secondary rotational acceleration-deceleration-induced brain injury in developing mice.

  4. Thymic Stromal Lymphopoietin Attenuates the Development of Atherosclerosis in ApoE−/− Mice

    Science.gov (United States)

    Yu, Kunwu; Zhu, Pengfei; Dong, Qian; Zhong, Yucheng; Zhu, Zhengfeng; Lin, Yingzhong; Huang, Ying; Meng, Kai; Ji, Qingwei; Yi, Guiwen; Zhang, Wei; Wu, Bangwei; Mao, Yi; Cheng, Peng; Zhao, Xiaoqi; Mao, Xiaobo; Zeng, Qiutang

    2013-01-01

    Background Thymic stromal lymphopoietin (TSLP) is a cytokine with multiple effects on the body. For one thing, TSLP induces Th2 immunoreaction and facilitates allergic reaction; for another, it promotes the differentiation of naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) and maintains immune tolerance. However, the exact role of TSLP in atherosclerosis remains unknown. Methods and Results In vitro, we examined the phenotype of TSLP‐conditioned bone marrow dendritic cells (TSLP‐DCs) of apolipoprotein E–deficient (ApoE−/−) mice and their capacity to induce the differentiation of Tregs. Our results indicated that TSLP‐DCs obtained the characteristics of tolerogenic dendritic cells and increased a generation of CD4+ latency‐associated peptide (LAP)+ Tregs and nTregs when cocultured with naive T cells. In addition, the functional relevance of TSLP and TSLP‐DCs in the development of atherosclerosis was also determined. Interestingly, we found that TSLP was almost absent in cardiovascular tissue of ApoE−/− mice, and TSLP administration increased the levels of antioxidized low‐density lipoprotein IgM and IgG1, but decreased the levels of IgG2a in plasma. Furthermore, mice treated with TSLP and TSLP‐DCs developed significantly fewer (32.6% and 28.2%, respectively) atherosclerotic plaques in the aortic root compared with controls, along with increased numbers of CD4+LAP+ Tregs and nTregs in the spleen and decreased inflammation in the aorta, which could be abrogated by anti‐TGF‐β antibody. Conclusions Our results revealed a protective role for TSLP in atherosclerosis that is possibly mediated by reestablishing a tolerogenic immune response, which may represent a novel possibility for treatment or prevention of atherosclerosis. PMID:23985377

  5. Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice.

    Science.gov (United States)

    van der Sluis, Ronald J; Nahon, Joya E; Reuwer, Anne Q; Van Eck, Miranda; Hoekstra, Menno

    2015-05-01

    Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo. Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo. Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (-31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP-1 expression (-70%) and secretion (-28%) by peritoneal macrophages. Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis. © 2015 The British Pharmacological Society.

  6. GPR56 is essential for testis development and male fertility in mice.

    Science.gov (United States)

    Chen, Guangchun; Yang, Liquan; Begum, Shahinoor; Xu, Lei

    2010-12-01

    Testis development is critical for male fertility and continuation of the mammalian species. Essential structural components of testes are seminiferous tubules, which are lined by Sertoli cells and provide nutrients and physical protection for the maturation of sperm. Seminiferous tubule formation is initiated in embryos as testis cords and relies on their remodeling for maturation during development. Recently, three-dimensional image analyses showed that testis cords in different parts of embryonic gonads undergo distinct remodeling processes. How this asymmetric remodeling is regulated has not been investigated. We report here that the absence of an adhesion G protein-coupled receptor, GPR56, leads to partial disruption of seminiferous tubules and reduced fertility in male mice. The defects appear to originate asymmetrically in embryonic gonads, but subsequent to the initial establishment of testis cords, suggesting that GPR56 might act to establish a spatial and/or temporal cue for asymmetric cord remodeling during male gonad development. © 2010 Wiley-Liss, Inc.

  7. Alcohol intake in pregnancy increases the child's risk of atopic dermatitis. the COPSAC prospective birth cohort study of a high risk population.

    Directory of Open Access Journals (Sweden)

    Charlotte Giwercman Carson

    Full Text Available BACKGROUND: Atopic dermatitis has increased four-fold over the recent decades in developed countries, indicating that changes in environmental factors associated with lifestyle may play an important role in this epidemic. It has been proposed that alcohol consumption may be one contributing risk factor in this development. OBJECTIVE: To analyze the impact of alcohol intake during pregnancy on the development of atopic dermatitis during the first 7 years of life. METHOD: The COPSAC cohort is a prospective, longitudinal, birth cohort study of 411 children born to mothers with a history of asthma, followed up for 7 years with scheduled visits every 6 months as well as visits for acute exacerbations of atopic dermatitis. Risk of atopic dermatitis from any alcohol consumption during pregnancy was analyzed as time-to-diagnosis and adjusted for known risk factors. RESULTS: 177 of 411 children developed atopic dermatitis before age 7 years. We found a significant effect of alcohol intake during pregnancy on atopic dermatitis development (HR 1.44, 95% CI 1.05-1.99 p=0.024. This conclusion was unaffected after adjustment for smoking, mother's education and mother's atopic dermatitis. LIMITATIONS: The selection of a high-risk cohort, with all mothers suffering from asthma, and all children having a gestational age above 35 weeks with no congenital abnormality, systemic illness, or history of mechanical ventilation or lower airway infection. CONCLUSION: Alcohol intake by pregnant women with a history of asthma, is significantly associated with an increased risk for the child for developing atopic dermatitis during the first 7 years of life.

  8. The Endocannabinoid System across Postnatal Development in Transmembrane Domain Neuregulin 1 Mutant Mice

    Directory of Open Access Journals (Sweden)

    Rose Chesworth

    2018-02-01

    Full Text Available The use of cannabis is a well-established component risk factor for schizophrenia, particularly in adolescent individuals with genetic predisposition for the disorder. Alterations to the endocannabinoid system have been found in the prefrontal cortex of patients with schizophrenia. Thus, we assessed whether molecular alterations exist in the endocannabinoid signalling pathway during brain development in a mouse model for the schizophrenia risk gene neuregulin 1 (Nrg1. We analysed transcripts encoding key molecules of the endocannabinoid system in heterozygous transmembrane domain Nrg1 mutant mice (Nrg1 TM HET, which is known to have increased sensitivity to cannabis exposure. Tissue from the prelimbic cortex and hippocampus of male and female Nrg1 TM HET mice and wild type-like littermates was collected at postnatal days (PNDs 7, 10, 14, 21, 28, 35, 49, and 161. Quantitative polymerase chain reaction was conducted to assess mRNA levels of cannabinoid receptor 1 (CB1R and enzymes for the synthesis and breakdown of the endocannabinoid 2-arachidonoylglycerol [i.e., diacylglycerol lipase alpha (DAGLα, monoglyceride lipase (MGLL, and α/β-hydrolase domain-containing 6 (ABHD6]. No sex differences were found for any transcripts in either brain region; thus, male and female data were pooled. Hippocampal and cortical mRNA expression of DAGLα, MGLL, and ABHD6 increased until PND 21–35 and then decreased and stabilised for the rest of postnatal development. Hippocampal CB1R mRNA expression increased until PND 21 and decreased after this age. Expression levels of these endocannabinoid markers did not differ in Nrg1 TM HET compared to control mice at any time point. Here, we demonstrate dynamic changes in the developmental trajectory of several key endocannabinoid system transcripts in the mouse brain, which may correspond with periods of endocannabinoid system maturation. Nrg1 TM HET mutation did not alter the developmental trajectory of the

  9. Neurobehavioral effects of concurrent exposure to cesium-137 and paraquat during neonatal development in mice

    International Nuclear Information System (INIS)

    Heredia, Luis; Bellés, Montserrat; Llovet, Maria Isabel; Domingo, Jose L.; Linares, Victoria

    2015-01-01

    As a result of nuclear power plants accidents such as Chernobyl or Fukushima, some people were exposed to external and internal ionizing radiation (IR). Human brain is highly sensitive to IR during fetal and postnatal period when the molecular processes are not completely finished. Various studies have shown that exposure to low doses of IR causes a higher incidence of cognitive impairment. On the other hand, in industrialized countries, people are daily exposed to a number of toxicant pollutants. Exposure to environmental chemicals, such as paraquat (PQ), may potentiate the toxic effects induced by radiation on brain development. In this study, we evaluated the cognitive effects of concomitant exposure to low doses of internal radiation ( 137 Cs) and PQ during neonatal brain development. At the postnatal day 10 (PND10), two groups of mice (C57BL/6J) were exposed to 137 Cs (4000 and 8000 Bq/kg) and/or PQ (7 mg/kg). To investigate the spontaneous behavior, learning, memory capacities and anxiety, behavioral tests were conducted in the offspring at two months of age. The results showed that cognitive functions were not significantly affected when 137 Cs or PQ were administered alone. However, alterations in the working memory and anxiety were detected in mice exposed to 137 Cs combined with PQ

  10. Neurobehavioral effects of concurrent exposure to cesium-137 and paraquat during neonatal development in mice.

    Science.gov (United States)

    Heredia, Luis; Bellés, Montserrat; Llovet, Maria Isabel; Domingo, Jose L; Linares, Victoria

    2015-03-02

    As a result of nuclear power plants accidents such as Chernobyl or Fukushima, some people were exposed to external and internal ionizing radiation (IR). Human brain is highly sensitive to IR during fetal and postnatal period when the molecular processes are not completely finished. Various studies have shown that exposure to low doses of IR causes a higher incidence of cognitive impairment. On the other hand, in industrialized countries, people are daily exposed to a number of toxicant pollutants. Exposure to environmental chemicals, such as paraquat (PQ), may potentiate the toxic effects induced by radiation on brain development. In this study, we evaluated the cognitive effects of concomitant exposure to low doses of internal radiation ((137)Cs) and PQ during neonatal brain development. At the postnatal day 10 (PND10), two groups of mice (C57BL/6J) were exposed to (137)Cs (4000 and 8000 Bq/kg) and/or PQ (7 mg/kg). To investigate the spontaneous behavior, learning, memory capacities and anxiety, behavioral tests were conducted in the offspring at two months of age. The results showed that cognitive functions were not significantly affected when (137)Cs or PQ were administered alone. However, alterations in the working memory and anxiety were detected in mice exposed to (137)Cs combined with PQ. Copyright © 2015. Published by Elsevier Ireland Ltd.

  11. Patterns of Glycoconjugate Distribution during Molar Tooth Germ Development in Mice

    Directory of Open Access Journals (Sweden)

    AR. Varasteh

    2007-09-01

    Full Text Available Objective: The aim of the present study was to evaluate the structure and distribution of Glycoconjugates during molar tooth germ development in mice.Materials and Methods: Sixteen tooth germs were obtained from BALB/c mice embryos 15 to 18 days post-gestation and fixed in 10% formalin. After routine tissue processing, 5μm sections were cut and stained with BSA1-B4 and PNA using the lectin histochemical method. All slides were evaluated by light microscopy.Results: Both lectins showed positive reaction in the tooth germ but with spatiotemporal differences. During bell stage, the reaction was strong with BSA1-B4 but moderate with PNA. Strong PNA uptake was observed in the odontoblastic and ameloblastic nuclei alongwith the apical cytoplasm of the ameloblasts.Conclusion: Although the lectins that were used in the present study recognize the same terminal sugar residue, they reacted with different disaccharide sequences with various penaltomer sugars. Therefore it may be assumed that the pattern of affinity for different parts of the developing tooth germ such as ameloblasts and odontoblasts is different in various lectins.

  12. SMOC1 is essential for ocular and limb development in humans and mice.

    Science.gov (United States)

    Okada, Ippei; Hamanoue, Haruka; Terada, Koji; Tohma, Takaya; Megarbane, Andre; Chouery, Eliane; Abou-Ghoch, Joelle; Jalkh, Nadine; Cogulu, Ozgur; Ozkinay, Ferda; Horie, Kyoji; Takeda, Junji; Furuichi, Tatsuya; Ikegawa, Shiro; Nishiyama, Kiyomi; Miyatake, Satoko; Nishimura, Akira; Mizuguchi, Takeshi; Niikawa, Norio; Hirahara, Fumiki; Kaname, Tadashi; Yoshiura, Koh-Ichiro; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Furukawa, Takahisa; Matsumoto, Naomichi; Saitsu, Hirotomo

    2011-01-07

    Microphthalmia with limb anomalies (MLA) is a rare autosomal-recessive disorder, presenting with anophthalmia or microphthalmia and hand and/or foot malformation. We mapped the MLA locus to 14q24 and successfully identified three homozygous (one nonsense and two splice site) mutations in the SPARC (secreted protein acidic and rich in cysteine)-related modular calcium binding 1 (SMOC1) in three families. Smoc1 is expressed in the developing optic stalk, ventral optic cup, and limbs of mouse embryos. Smoc1 null mice recapitulated MLA phenotypes, including aplasia or hypoplasia of optic nerves, hypoplastic fibula and bowed tibia, and syndactyly in limbs. A thinned and irregular ganglion cell layer and atrophy of the anteroventral part of the retina were also observed. Soft tissue syndactyly, resulting from inhibited apoptosis, was related to disturbed expression of genes involved in BMP signaling in the interdigital mesenchyme. Our findings indicate that SMOC1/Smoc1 is essential for ocular and limb development in both humans and mice.

  13. In vivo imaging of the developing neuromuscular junction in neonatal mice.

    Science.gov (United States)

    Turney, Stephen G; Walsh, Mark K; Lichtman, Jeff W

    2012-11-01

    Although fluorescently labeled structures can be analyzed more easily at high resolution in fixed-tissue preparations than in living animals, some biological questions can only be answered by time-lapse imaging. Changes in nervous system wiring during development cannot be determined reliably by taking tissue from different animals at staggered time points. Rather, the same cells and connections must be viewed repeatedly. To study developmental synapse elimination, we image muscles in transgenic mice that express fluorescent proteins in motor neurons and follow the same neuromuscular junctions (NMJs) over multiple days. This protocol describes the use of confocal microscopy for in vivo imaging of developing NMJs in transgenic neonatal mice expressing cyan fluorescent protein (CFP) or yellow fluorescent protein (YFP). The sternomastoid, a flat, accessible neck muscle with large junctions, is imaged. A principal advantage of confocal microscopy is the ability to acquire multiple fluorescence channels simultaneously. If the channels are acquired sequentially, there is inevitably misalignment because of movement. Moreover, the total imaging time scales linearly with the number of channels. With simultaneous acquisition, only a single scan may be required. With perfect alignment between channels, irrespective of movement that might occur during a scan, color differences can be used to study interactions between axons over time. A limitation of this technique is that axons must be brightly labeled and at the muscle surface. NMJs that are more than one muscle fiber deep may be difficult to scan because of index of refraction changes that cause image blurring.

  14. Plasma and skin vitamin E concentrations in canine atopic dermatitis.

    Science.gov (United States)

    Plevnik Kapun, Alja; Salobir, Janez; Levart, Alenka; Tavčar Kalcher, Gabrijela; Nemec Svete, Alenka; Kotnik, Tina

    2013-01-01

    Altered homeostasis of vitamin E has been demonstrated in human atopic dermatitis. Data on plasma and skin vitamin E concentrations in canine atopic dermatitis (CAD) are not available. To determine vitamin E concentrations in plasma and skin of atopic dogs. Vitamin E concentrations in plasma and full-thickness skin biopsies of 15 atopic dogs were related to CAD extent and severity index (CADESI-03) scores and compared to the equivalent concentrations in 17 healthy dogs. Statistically significant differences of measured parameters between the two groups were determined by the nonparametric Mann Whitney U test and correlations between CADESI-03 scores and vitamin E concentrations were evaluated by the Spearman rank test. A value of P vitamin E were significantly lower in atopic dogs than in healthy dogs, with median values of 29.8 and 52.9 μmol/L, respectively. Skin vitamin E values did not differ significantly between patients and healthy controls. The median concentration of skin vitamin E in atopic dogs was higher than that in healthy dogs. No significant correlations were found between CADESI-03 score and plasma vitamin E or skin vitamin E concentrations. Significantly lower plasma vitamin E concentrations in atopic dogs than in healthy controls indicate altered homeostasis of vitamin E in CAD. Further investigation into vitamin E supplementation in CAD is warranted.

  15. New and emerging trends in the treatment of atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Christina M Gelbard

    2009-01-01

    Full Text Available Christina M Gelbard1, Adelaide A Hebert1,21Departments of Dermatology; 2Pediatrics, University of Texas-Houston, Houston, TX, USAAbstract: Atopic dermatitis is a chronic, inflammatory skin condition that affects 10% to 20% of children and 1% to 3% of adults in the US. Symptoms often result in sleeplessness, psychological stress, poor self-esteem, anxiety, and poor school or work performance. The cost of atopic dermatitis is estimated to be US$0.9 to 3.8 billion every year. Topical steroids are first-line treatment for atopic dermatitis, and recent advances in vehicle technologies have resulted in improved patient tolerability and compliance. Topical calcineurin inhibitors are also safe and effective topical treatments for atopic dermatitis, and provide an additional therapeutic option for patients with this disease. Systemic immunomodulators are used in the treatment of severe refractory disease. Cyclosporine, methotrexate, azathioprine, mycophenolate mofetil, and interferon gamma have been used in the management of severe atopic dermatitis. This review highlights the current and emerging trends in the treatment of atopic dermatitis.Keywords: atopic dermatitis, topical corticosteroids, calcineurin inhibitors, methotrexate, cyclosporine, mycophenolate mofetil, IFN-γ

  16. A different role of angiotensin II type 1a receptor in the development and hypertrophy of plantaris muscle in mice.

    Science.gov (United States)

    Zempo, Hirofumi; Suzuki, Jun-Ichi; Ogawa, Masahito; Watanabe, Ryo; Isobe, Mitsuaki

    2016-02-01

    The role of angiotensin II type 1 (AT1) receptors in muscle development and hypertrophy remains unclear. This study was designed to reveal the effects that a loss of AT1 receptors has on skeletal muscle development and hypertrophy in mice. Eight-week-old male AT1a receptor knockout (AT1a(-/-)) mice were used for this experiment. The plantaris muscle to body weight ratio, muscle fiber cross-sectional area, and number of muscle fibers of AT1a(-/-) mice was significantly greater than wild type (WT) mice in the non-intervention condition. Next, the functional overload (OL) model was used to induce plantaris muscle hypertrophy by surgically removing the two triceps muscles consisting of the calf, soleus, and gastrocnemius muscles in mice. After 14 days of OL intervention, the plantaris muscle weight, the amount of fiber, and the fiber area increased. However, the magnitude of the increment of plantaris weight was not different between the two strains. Agtr1a mRNA expression did not change after OL in WT muscle. Actually, the Agt mRNA expression level of WT-OL was lower than WT-Control (C) muscle. An atrophy-related gene, atrogin-1 mRNA expression levels of AT1a(-/-)-C, WT-OL, and AT1a(-/-)-OL muscle were lower than that of WT-C muscle. Our findings suggest that AT1 receptor contributes to plantaris muscle development via atrogin-1 in mice.

  17. When does atopic dermatitis warrant systemic therapy?

    DEFF Research Database (Denmark)

    Simpson, Eric L; Bruin-Weller, Marjolein; Flohr, Carsten

    2017-01-01

    -specific literature review, referred to guidelines when available, and provided interpretation and expert opinion. RESULTS: We recommend a systematic and holistic approach to assess patients with severe signs and symptoms of AD and impact on quality of life before systemic therapy. Steps taken before commencing......BACKGROUND: Although most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking. OBJECTIVE: To guide those considering use of systemic...... therapy in AD and provide a framework for evaluation before making this therapeutic decision with the patient. METHODS: A subgroup of the International Eczema Council determined aspects to consider before prescribing systemic therapy. Topics were assigned to expert reviewers who performed a topic...

  18. Molecular characterization and development of Sarcocystis speeri sarcocysts in gamma interferon gene knockout mice.

    Science.gov (United States)

    Dubey, J P; Verma, S K; Dunams, D; Calero-Bernal, R; Rosenthal, B M

    2015-11-01

    The North American opossum (Didelphis virginiana) is the definitive host for at least three named species of Sarcocystis: Sarcocystis falcatula, Sarcocystis neurona and Sarcocystis speeri. The South American opossums (Didelphis albiventris, Didelphis marsupialis and Didelphis aurita) are definitive hosts for S. falcatula and S. lindsayi. The sporocysts of these Sarcocystis species are similar morphologically. They are also not easily distinguished genetically because of the difficulties of DNA extraction from sporocysts and availability of distinguishing genetic markers. Some of these species can be distinguished by bioassay; S. neurona and S. speeri are infective to gamma interferon gene knockout (KO) mice, but not to budgerigars (Melopsittacus undulatus); whereas S. falcatula and S. lindsayi are infective to budgerigars but not to KO mice. The natural intermediate host of S. speeri is unknown. In the present study, development of sarcocysts of S. speeri in the KO mice is described. Sarcocysts were first seen at 12 days post-inoculation (p.i.), and they became macroscopic (up to 4 mm long) by 25 days p.i. The structure of the sarcocyst wall did not change from the time bradyzoites had formed at 50-220 days p.i. Sarcocysts contained unique villar protrusions, 'type 38'. The polymerase chain reaction amplifications and sequences analysis of three nuclear loci (18S rRNA, 28S rRNA and ITS1) and two mitochondrial loci (cox1 and cytb) of S. speeri isolate from an Argentinean opossum (D. albiventris) confirmed its membership among species of Sarcocystis and indicated an especially close relationship to another parasite in this genus that employs opossums as its definitive host, S. neurona. These results should be useful in finding natural intermediate host of S. speeri.

  19. Lysosome associated membrane proteins maintain pancreatic acinar cell homeostasis: LAMP-2 deficient mice develop pancreatitis.

    Science.gov (United States)

    Mareninova, Olga A; Sendler, Matthias; Malla, Sudarshan Ravi; Yakubov, Iskandar; French, Samuel W; Tokhtaeva, Elmira; Vagin, Olga; Oorschot, Viola; Lüllmann-Rauch, Renate; Blanz, Judith; Dawson, David; Klumperman, Judith; Lerch, Markus M; Mayerle, Julia; Gukovsky, Ilya; Gukovskaya, Anna S

    2015-11-01

    The pathogenic mechanism of pancreatitis is poorly understood. Recent evidence implicates defective autophagy in pancreatitis responses; however, the pathways mediating impaired autophagy in pancreas remain largely unknown. Here, we investigate the role of lysosome associated membrane proteins (LAMPs) in pancreatitis. We analyzed changes in LAMPs in experimental models and human pancreatitis, and the underlying mechanisms: LAMP de-glycosylation and degradation. LAMP cleavage by cathepsin B (CatB) was analyzed by mass spectrometry. We used mice deficient in LAMP-2 to assess its role in pancreatitis. Pancreatic levels of LAMP-1 and LAMP-2 greatly decrease across various pancreatitis models and in human disease. Pancreatitis does not trigger LAMPs' bulk de-glycosylation, but induces their degradation via CatB-mediated cleavage of LAMP molecule close to the boundary between luminal and transmembrane domains. LAMP-2 null mice spontaneously develop pancreatitis that begins with acinar cell vacuolization due to impaired autophagic flux, and progresses to severe pancreas damage characterized by trypsinogen activation, macrophage-driven inflammation, and acinar cell death. LAMP-2 deficiency causes a decrease in pancreatic digestive enzymes content, stimulates the basal and inhibits CCK-induced amylase secretion by acinar cells. The effects of LAMP-2 knockout and acute cerulein pancreatitis overlap, which corroborates the pathogenic role of LAMP decrease in experimental pancreatitis models. The results indicate a critical role for LAMPs, particularly LAMP-2, in maintaining pancreatic acinar cell homeostasis, and provide evidence that defective lysosomal function, resulting in impaired autophagy, leads to pancreatitis. Mice with LAMP-2 deficiency present a novel genetic model of human pancreatitis caused by lysosomal/autophagic dysfunction.

  20. Effects of pulsed magnetic stimulation on tumor development and immune functions in mice.

    Science.gov (United States)

    Yamaguchi, Sachiko; Ogiue-Ikeda, Mari; Sekino, Masaki; Ueno, Shoogo

    2006-01-01

    We investigated the effects of pulsed magnetic stimulation on tumor development processes and immune functions in mice. A circular coil (inner diameter = 15 mm, outer diameter = 75 mm) was used in the experiments. Stimulus conditions were pulse width = 238 micros, peak magnetic field = 0.25 T (at the center of the coil), frequency = 25 pulses/s, 1,000 pulses/sample/day and magnetically induced eddy currents in mice = 0.79-1.54 A/m(2). In an animal study, B16-BL6 melanoma model mice were exposed to the pulsed magnetic stimulation for 16 days from the day of injection of cancer cells. A tumor growth study revealed a significant tumor weight decrease in the stimulated group (54% of the sham group). In a cellular study, B16-BL6 cells were also exposed to the magnetic field (1,000 pulses/sample, and eddy currents at the bottom of the dish = 2.36-2.90 A/m(2)); however, the magnetically induced eddy currents had no effect on cell viabilities. Cytokine production in mouse spleens was measured to analyze the immunomodulatory effect after the pulsed magnetic stimulation. tumor necrosis factor (TNF-alpha) production in mouse spleens was significantly activated after the exposure of the stimulus condition described above. These results showed the first evidence of the anti-tumor effect and immunomodulatory effects brought about by the application of repetitive magnetic stimulation and also suggested the possible relationship between anti-tumor effects and the increase of TNF-alpha levels caused by pulsed magnetic stimulation.

  1. Atopic dermatitis-like disease and associated lethal myeloproliferative disorder arise from loss of Notch signaling in the murine skin.

    Directory of Open Access Journals (Sweden)

    Alexis Dumortier

    2010-02-01

    Full Text Available The Notch pathway is essential for proper epidermal differentiation during embryonic skin development. Moreover, skin specific loss of Notch signaling in the embryo results in skin barrier defects accompanied by a B-lymphoproliferative disease. However, much less is known about the consequences of loss of Notch signaling after birth.To study the function of Notch signaling in the skin of adult mice, we made use of a series of conditional gene targeted mice that allow inactivation of several components of the Notch signaling pathway specifically in the skin. We demonstrate that skin-specific inactivation of Notch1 and Notch2 simultaneously, or RBP-J, induces the development of a severe form of atopic dermatitis (AD, characterized by acanthosis, spongiosis and hyperkeratosis, as well as a massive dermal infiltration of eosinophils and mast cells. Likewise, patients suffering from AD, but not psoriasis or lichen planus, have a marked reduction of Notch receptor expression in the skin. Loss of Notch in keratinocytes induces the production of thymic stromal lymphopoietin (TSLP, a cytokine deeply implicated in the pathogenesis of AD. The AD-like associated inflammation is accompanied by a myeloproliferative disorder (MPD characterized by an increase in immature myeloid populations in the bone marrow and spleen. Transplantation studies revealed that the MPD is cell non-autonomous and caused by dramatic microenvironmental alterations. Genetic studies demontrated that G-CSF mediates the MPD as well as changes in the bone marrow microenvironment leading to osteopenia.Our data demonstrate a critical role for Notch in repressing TSLP production in keratinocytes, thereby maintaining integrity of the skin and the hematopoietic system.

  2. Complementary and alternative interventions in atopic dermatitis.

    Science.gov (United States)

    Lee, Joohee; Bielory, Leonard

    2010-08-01

    The burden of atopic diseases, including atopic dermatitis (AD), is significant and far-reaching. In addition to cost of care and therapies, it affects the quality of life for those affected as well as their caretakers. Complementary and alternative therapies are commonly used because of concerns about potential adverse effects of conventional therapies and frustration with the lack of response to prescribed medications, be it due to the severity of the AD or the lack of appropriate regular use. Despite the promising results reported with various herbal medicines and biologic products, the clinical efficacy of such alternative therapies remains to be determined. Physicians need to be educated about alternative therapies and discuss benefits and potential adverse effects or limitations with patients. A systematic approach and awareness of reputable and easily accessible resources are helpful in dealing with complementary and alternative medicine (CAM). The use of CAM interventions is common among individuals with AD. Epidemiologic data have been a motivating drive for better elucidation of the efficacy of CAM interventions for allergic disease. Herbal medicines and biologics for AD treatment and, more recently, prevention comprise a major area of clinical investigation. Potential mechanisms of therapeutic effect elucidated by animal models and human clinical studies implicate modulation of TH2-type allergic inflammation and induction of immune tolerance. Population-based research regarding the use of CAM for allergic diseases underscores the increasing challenge for care providers with respect to identifying CAM use and ensuring safe use of allopathic and complementary medicines in disease management. Copyright 2010. Published by Elsevier Inc.

  3. Investigations on the immunopathogenesis of atopic dermatitis in cats

    OpenAIRE

    Roosje, Pieternella Janna

    2002-01-01

    The term atopic dermatitis (AD) is commonly used in cats. At present, however, there is little known about the pathogenesis of feline AD. The aim was to investigate various aspects of the immunopathogenesis in a defined group of cats with signs and symptoms of atopic dermatitis and compare our findings with the immunoregulation of atopic dermatitis in humans. The presence of antigen-specific IgE in serum of AD cats was investigated by means of the Prausnitz-Küstner (PK) test and the passive c...

  4. RESULTS OF APPLYING POLYVITAMIN COMPLEX FOR CHILDREN WITH ATOPIC DERMATITIS

    Directory of Open Access Journals (Sweden)

    N.A. Ivanova

    2007-01-01

    Full Text Available The article presents findings of applying vitamin-and-mineral complex (VMC for children frequently suffering from diseases and children with atopic dermatitis. It shows that usage of VMC within a complex therapy promotes regression of subnormal vitamin provision symptoms, as well as symptoms of the core disease. This happens against heightened vitamin content in child's organism — which was proven with the test of A and E vitamins content in blood. The research has demonstrated a quite good tolerance of VMC by children suffering from atopic dermatitis.Key words: children frequently suffering from diseases, atopic dermatitis, vitamins, treatment.

  5. Regulatory T Cell Induced by Poria cocos Bark Exert Therapeutic Effects in Murine Models of Atopic Dermatitis and Food Allergy

    Directory of Open Access Journals (Sweden)

    Min-Jung Bae

    2016-01-01

    Full Text Available The prevalence of allergic disorders including atopic dermatitis (AD and food allergy (FA has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3+CD4+ regulatory T cells (Tregs. The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3+CD4+ Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3+CD4+ Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs.

  6. Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice

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    Mathieu Paul Rodero

    2013-06-01

    Full Text Available Expression of the CC chemokine receptor 1 (CCR1 by tumor cells has been associated with protumoral activity; however, its role in nontumoral cells during tumor development remains elusive. Here, we investigated the role of CCR1 deletion on stromal and hematopoietic cells in a liver metastasis tumor model. Metastasis development was strongly impaired in CCR1-deficient mice compared to control mice and was associated with reduced liver monocyte infiltration. To decipher the role of myeloid cells, sublethally irradiated mice were reconstituted with CCR1-deficient bone marrow (BM and showed better survival rates than the control reconstituted mice. These results point toward the involvement of CCR1 myeloid cell infiltration in the promotion of tumor burden. In addition, survival rates were extended in CCR1-deficient mice receiving either control or CCR1-deficient BM, indicating that host CCR1 expression on nonhematopoietic cells also supports tumor growth. Finally, we found defective tumor-induced neoangiogenesis (in vitro and in vivo in CCR1-deficient mice. Overall, our results indicate that CCR1 expression by both hematopoietic and nonhematopoietic cells favors tumor aggressiveness. We propose CCR1 as a potential therapeutical target for liver metastasis therapy.

  7. Development of hepatocellular adenomas and carcinomas in mice with liver-specific G6Pase-α deficiency

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    Roberta Resaz

    2014-09-01

    Full Text Available Glycogen storage disease type 1a (GSD-1a is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α, and is characterized by impaired glucose homeostasis and a high risk of developing hepatocellular adenomas (HCAs. A globally G6Pase-α-deficient (G6pc−/− mouse model that shows pathological features similar to those of humans with GSD-1a has been developed. These mice show a very severe phenotype of disturbed glucose homeostasis and rarely live beyond weaning. We generated liver-specific G6Pase-α-deficient (LS‑G6pc−/− mice as an alternative animal model for studying the long-term pathophysiology of the liver and the potential treatment strategies, such as cell therapy. LS‑G6pc−/− mice were viable and exhibited normal glucose profiles in the fed state, but showed significantly lower blood glucose levels than their control littermates after 6 hours of fasting. LS‑G6pc−/− mice developed hepatomegaly with glycogen accumulation and hepatic steatosis, and progressive hepatic degeneration. Ninety percent of the mice analyzed developed amyloidosis by 12 months of age. Finally, 25% of the mice sacrificed at age 10–20 months showed the presence of multiple HCAs and in one case late development of hepatocellular carcinoma (HCC. In conclusion, LS‑G6pc−/− mice manifest hepatic symptoms similar to those of human GSD-1a and, therefore, represent a valid model to evaluate long-term liver pathogenesis of GSD-1a.

  8. Maternal exposure to nanosized titanium dioxide suppresses embryonic development in mice

    Directory of Open Access Journals (Sweden)

    Hong F

    2017-08-01

    Full Text Available Fashui Hong,1–4 Yingjun Zhou,1–4 Xiaoyang Zhao,5 Lei Sheng,5 Ling Wang6 1Jiangsu Collaborative Innovation Center of Regional Modern Agriculture and Environmental Protection, 2Jiangsu Key Laboratory for Food Safety and Nutritional Function, 3Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, 4School of Life Sciences, Huaiyin Normal University, Huaian, 5Medical College of Soochow University, Suzhou, 6Library of Soochow University, Suzhou, Jiangsu, China Abstract: Although nanoscale titanium dioxide (nano-TiO2 has been extensively used in industrial food applications and daily products for pregnant women, infants, and children, its potential toxicity on fetal development has been rarely studied. The main objective of this investigation was to establish the effects of maternal exposure of nano-TiO2 on developing embryos. Female imprinting control region mice were orally administered nano-TiO2 from gestational day 0 to 17. Our findings showed that Ti concentrations in maternal serum, placenta, and fetus were increased in nano-TiO2-exposed mice when compared to controls, which resulted in reductions in the contents of calcium and zinc in maternal serum, placenta, and fetus, maternal weight gain, placental weight, fetal weight, number of live fetuses, and fetal crown–rump length as well as cauda length, and caused an increase in the number of both dead fetuses and resorptions. Furthermore, maternal nano-TiO2 exposure inhibited development of the fetal skeleton, suggesting a significant absence of cartilage, reduced or absent ossification, and an increase in the number of fetuses with dysplasia, including exencephaly, spina bifida, coiled tail, scoliosis, rib absence, and sternum absence. These findings indicated that nano-TiO2 can cross the blood–fetal barrier and placental barrier, thereby delaying the development of fetal mice and inducing skeletal malformation. These factors may be associated with reductions in

  9. Macrophage inhibitory cytokine-1 (MIC-1/GDF15 slows cancer development but increases metastases in TRAMP prostate cancer prone mice.

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    Yasmin Husaini

    Full Text Available Macrophage inhibitory cytokine-1 (MIC-1/GDF15, a divergent member of the TGF-β superfamily, is over-expressed by many common cancers including those of the prostate (PCa and its expression is linked to cancer outcome. We have evaluated the effect of MIC-1/GDF15 overexpression on PCa development and spread in the TRAMP transgenic model of spontaneous prostate cancer. TRAMP mice were crossed with MIC-1/GDF15 overexpressing mice (MIC-1(fms to produce syngeneic TRAMP(fmsmic-1 mice. Survival rate, prostate tumor size, histopathological grades and extent of distant organ metastases were compared. Metastasis of TC1-T5, an androgen independent TRAMP cell line that lacks MIC-1/GDF15 expression, was compared by injecting intravenously into MIC-1(fms and syngeneic C57BL/6 mice. Whilst TRAMP(fmsmic-1 survived on average 7.4 weeks longer, had significantly smaller genitourinary (GU tumors and lower PCa histopathological grades than TRAMP mice, more of these mice developed distant organ metastases. Additionally, a higher number of TC1-T5 lung tumor colonies were observed in MIC-1(fms mice than syngeneic WT C57BL/6 mice. Our studies strongly suggest that MIC-1/GDF15 has complex actions on tumor behavior: it limits local tumor growth but may with advancing disease, promote metastases. As MIC-1/GDF15 is induced by all cancer treatments and metastasis is the major cause of cancer treatment failure and cancer deaths, these results, if applicable to humans, may have a direct impact on patient care.

  10. Nepro is localized in the nucleolus and essential for preimplantation development in mice.

    Science.gov (United States)

    Hashimoto, Masakazu; Sato, Tatsuya; Muroyama, Yuko; Fujimura, Lisa; Hatano, Masahiko; Saito, Tetsuichiro

    2015-09-01

    We generated knockout (KO) mice of Nepro, which has been shown to be necessary to maintain neural progenitor cells downstream of Notch in the mouse developing neocortex by using knockdown experiments, to explore its function in embryogenesis. Nepro KO embryos were morphologically indistinguishable from wild type (WT) embryos until the morula stage but failed in blastocyst formation, and many cells of the KO embryos resulted in apoptosis. We found that Nepro was localized in the nucleolus at the blastocyst stage. The number of nucleolus precursor bodies (NPBs) and nucleoli per nucleus was significantly higher in Nepro KO embryos compared with WT embryos later than the 2-cell stage. Furthermore, at the morula stage, whereas 18S rRNA and ribosomal protein S6 (rpS6), which are components of the ribosome, were distributed to the cytoplasm in WT embryos, they were mainly localized in the nucleoli in Nepro KO embryos. In addition, in Nepro KO embryos, the amount of the mitochondria-associated p53 protein increased, and Cytochrome c was distributed in the cytoplasm. These findings indicate that Nepro is a nucleolus-associated protein, and its loss leads to the apoptosis before blastocyst formation in mice. © 2015 Japanese Society of Developmental Biologists.

  11. Effect of probiotics on the development of dimethylhydrazine-induced preneoplastic lesions in the mice colon

    Directory of Open Access Journals (Sweden)

    Juliana Costa Liboredo

    2013-05-01

    Full Text Available PURPOSE: To determine the effect of probiotics on the development of chemically induced (1, 2-dimethylhydrazine colonic preneoplastic lesions, in mice. METHODS: The animals were divided into five groups. The control group was injected with carcinogen alone and the other groups also received probiotics (1- Lactobacillus delbrueckii UFV-H2b20; 2- Bifidobacterium animalis var. lactis Bb12; 3- L. delbrueckii UFV-H2b20 plus B. animalis var. lactis Bb12; and 4- Saccharomyces boulardii administered orally in drinking water throughout fourteen weeks. RESULTS: Consumption of lactobacilli and bifidobacteria alone resulted in a significant reduction of the total number of aberrant crypt foci (55.7% and 45.1%, respectively. Significant reduction in the number of these small foci (3 aberrant crypts crypts had no significant reduction. CONCLUSION: L. delbrueckii UFV-H2b20 and B. animalis var. lactis Bb12 administered alone protect colonic preneoplastic lesions in mice, while the combined treatment of these bacteria and the administration of S.boulardii were not effective in reducing such colonic lesions.

  12. Increasing Hematopoietic Stem Cell Yield to Develop Mice with Human Immune Systems

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    Juan-Carlos Biancotti

    2013-01-01

    Full Text Available Hematopoietic stem cells (HSCs are unique in their capacity to give rise to all mature cells of the immune system. For years, HSC transplantation has been used for treatment of genetic and neoplastic diseases of the hematopoietic and immune systems. The sourcing of HSCs from human umbilical cord blood has salient advantages over isolation from mobilized peripheral blood. However, poor sample yield has prompted development of methodologies to expand HSCs ex vivo. Cytokines, trophic factors, and small molecules have been variously used to promote survival and proliferation of HSCs in culture, whilst strategies to lower the concentration of inhibitors in the culture media have recently been applied to promote HSC expansion. In this paper, we outline strategies to expand HSCs in vitro, and to improve engraftment and reconstitution of human immune systems in immunocompromised mice. To the extent that these “humanized” mice are representative of the endogenous human immune system, they will be invaluable tools for both basic science and translational medicine.

  13. BMPRIA mediated signaling is essential for temporomandibular joint development in mice.

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    Shuping Gu

    Full Text Available The central importance of BMP signaling in the development and homeostasis of synovial joint of appendicular skeleton has been well documented, but its role in the development of temporomandibular joint (TMJ, also classified as a synovial joint, remains completely unknown. In this study, we investigated the function of BMPRIA mediated signaling in TMJ development in mice by transgenic loss-of- and gain-of-function approaches. We found that BMPRIA is expressed in the cranial neural crest (CNC-derived developing condyle and glenoid fossa, major components of TMJ, as well as the interzone mesenchymal cells. Wnt1-Cre mediated tissue specific inactivation of BmprIa in CNC lineage led to defective TMJ development, including failure of articular disc separation from a hypoplastic condyle, persistence of interzone cells, and failed formation of a functional fibrocartilage layer on the articular surface of the glenoid fossa and condyle, which could be at least partially attributed to the down-regulation of Ihh in the developing condyle and inhibition of apoptosis in the interzone. On the other hand, augmented BMPRIA signaling by Wnt1-Cre driven expression of a constitutively active form of BmprIa (caBmprIa inhibited osteogenesis of the glenoid fossa and converted the condylar primordium from secondary cartilage to primary cartilage associated with ectopic activation of Smad-dependent pathway but inhibition of JNK pathway, leading to TMJ agenesis. Our results present unambiguous evidence for an essential role of finely tuned BMPRIA mediated signaling in TMJ development.

  14. The contribution of twin studies to the understanding of the aetiology of asthma and atopic diseases

    DEFF Research Database (Denmark)

    Thomsen, Simon F

    2015-01-01

    The prevalence of asthma and other atopic diseases has increased markedly during the past decades and the reasons for this are not fully understood. Asthma is still increasing in many parts of the world, notably in developing countries, and this emphasizes the importance of continuing research...... aimed at studying the aetiological factors of the disease and the causes of its increase in prevalence. Twin studies enable investigations into the genetic and environmental causes of individual variation in multifactorial diseases such as asthma. Thorough insight into these causes is important...... as this will ultimately guide the development of preventive strategies and targeted therapies. This review explores the contribution of twin studies to the understanding of the aetiology of asthma and atopic diseases....

  15. Development of ghrelin transgenic mice for elucidation of clinical implication of ghrelin.

    Science.gov (United States)

    Aotani, Daisuke; Ariyasu, Hiroyuki; Shimazu-Kuwahara, Satoko; Shimizu, Yoshiyuki; Nomura, Hidenari; Murofushi, Yoshiteru; Kaneko, Kentaro; Izumi, Ryota; Matsubara, Masaki; Kanda, Hajime; Noguchi, Michio; Tanaka, Tomohiro; Kusakabe, Toru; Miyazawa, Takashi; Nakao, Kazuwa

    2017-01-01

    To elucidate the clinical implication of ghrelin, we have been trying to generate variable models of transgenic (Tg) mice overexpressing ghrelin. We generated Tg mice overexpressing des-acyl ghrelin in a wide variety of tissues under the control of β-actin promoter. While plasma des-acyl ghrelin level in the Tg mice was 44-fold greater than that of control mice, there was no differences in the plasma ghrelin level between des-acyl ghrelin Tg and the control mice. The des-acyl ghrelin Tg mice exhibited the lower body weight and the shorter body length due to modulation of GH-IGF-1 axis. We tried to generate Tg mice expressing a ghrelin analog, which possessed ghrelin-like activity (Trp 3 -ghrelin Tg mice). The plasma Trp 3 -ghrelin concentration in Trp 3 -ghrelin Tg mice was approximately 85-fold higher than plasma ghrelin (acylated ghrelin) concentration seen in the control mice. Because Trp 3 -ghrelin is approximately 24-fold less potent than ghrelin, the plasma Trp 3 -ghrelin concentration in Trp 3 -ghrelin Tg mice was calculated to have approximately 3.5-fold biological activity greater than that of ghrelin (acylated ghrelin) in the control mice. Trp 3 -ghrelin Tg mice did not show any phenotypes except for reduced insulin sensitivity in 1-year old. After the identification of ghrelin O-acyltransferase (GOAT), we generated doubly Tg mice overexpressing both mouse des-acyl ghrelin and mouse GOAT in the liver by cross-mating the two kinds of Tg mice. The plasma ghrelin concentration of doubly Tg mice was approximately 2-fold higher than that of the control mice. No apparent phenotypic changes in body weight and food intake were observed in doubly Tg mice. Further studies are ongoing in our laboratory to generate Tg mice with the increased plasma ghrelin level to a greater extent. The better understanding of physiological and pathophysiological significance of ghrelin from experiments using an excellent animal model may provide a new therapeutic approach for human

  16. HPLC Analysis of nine corticosteroids in “natural creams” for atopic eczema

    OpenAIRE

    Ameti, Agim; Poposka, Zaklina; Memeti, Shaban; Shishovska, Maja; Mustafa, Zana; Starkoska, Katerina; Arsova-Sarafinovska, Zorica

    2013-01-01

    Purpose: The aim of the study was to determine whether “natural creams” sold for treatment of childhood atopic eczema illegally contain corticosteroids with a newly developed rapid and simple HPLC analysis with UV detection. Material and Methods: HPLC analysis was performed using a Schimadzu LC-2010 chromatographic system (Schimadzu, Kyoto, Japan) consisting of a LC-20AT Prominence liquid chromatography pump with DGU-20A5 Prominence degasser, a SPD-M20A Prominence Diode Array Detector, and...

  17. Evaluation of a Parental Questionnaire to Identify Atopic Dermatitis in Infants and Preschool Children

    OpenAIRE

    Laura B. von Kobyletzki; Staffan Janson; Mikael Hasselgren; Carl-Gustaf Bornehag; Åke Svensson

    2012-01-01

    Aim: To develop and validate a questionnaire for detecting atopic dermatitis in infants and small children from the age of 2 months. Methods: Parents to 60 children answered a written questionnaire prior to a physical examination and individual semistructured interview. Qualitative and quantitative analyses of validity, sensitivity, specificity, and predictive values of the questionnaire were performed. Results: A total of 27 girls and 33 boys, aged 2 to 71 months, 35 with and...

  18. ENTEROSORBENTS AS A PART OF COMPLEX THERAPY OF ATOPIC DERMATITIS

    Directory of Open Access Journals (Sweden)

    A. A. Alexeeva

    2012-01-01

    Full Text Available Atopic dermatitis (AD is one of the most common allergic diseases in children which is assuming ever greater medical and social importance. Risk factors of AD include gastro-intestinal tract disturbances, especially intestinal dysbiosis, which is revealed in 89–94,1% of children with atopic dermatitis. Both correlation of the dysbiosis and AD manifestations severity and increase of underlying disease treatment efficacy as a result of target influence on intestinal microflora confirm that. For many decades guidelines of atopic dermatitis treatment in children along with elimination diet, antihistamine drugs and topic medicines include enterosorbents. The most effective drugs are those ones, consisting of prebiotics and sorbents. The wide experience of prebiotic drug with sorbent action (Lactofiltrum in complex therapy of atopic dermatitis in children is reviewed in this article.

  19. Incidence of allergy and atopic disorders and hygiene hypothesis.

    Czech Academy of Sciences Publication Activity Database

    Bencko, V.; Šíma, Petr

    2017-01-01

    Roč. 2, 6 March (2017), č. článku 1244. ISSN 2474-1663 Institutional support: RVO:61388971 Keywords : allergy disorders * atopic disorders * hygiene hypothesis Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology

  20. Evidence-based treatment of atopic eczema in general practice

    African Journals Online (AJOL)

    banzi

    The exact cause is unknown but a ... Scratching may result in secondary infec- tion and associated ... general practice. Atopic eczema is a common chronic condition ... There was either insufficient or no .... itch and indirectly improving sleep.

  1. Cell surface fucosylation does not affect development of colon tumors in mice with germline Smad3 mutation

    Science.gov (United States)

    Domino, Steven E.; Karnak, David M.; Hurd, Elizabeth A.

    2006-01-01

    Background/Aims: Neoplasia-related alterations in cell surface α(1,2)fucosylated glycans have been reported in multiple tumors including colon, pancreas, endometrium, cervix, bladder, lung, and choriocarcinoma. Spontaneous colorectal tumors from mice with a germline null mutation of transforming growth factor-β signaling gene Smad3 (Madh3) were tested for α(1,2)fucosylated glycan expression. Methods: Ulex Europaeus Agglutinin-I lectin staining, fucosyltransferase gene northern blot analysis, and a cross of mutant mice with Fut2 and Smad3 germline mutations were performed. Results: Spontaneous colorectal tumors from Smad3 (-/-) homozygous null mice were found to express α(1,2)fucosylated glycans in an abnormal pattern compared to adjacent nonneoplastic colon. Northern blot analysis of α(1,2)fucosyltransferase genes Fut1 and Fut2 revealed that Fut2, but not Fut1, steady-state mRNA levels were significantly increased in tumors relative to adjacent normal colonic mucosa. Mutant mice with a Fut2-inactivating germline mutation were crossed with Smad3 targeted mice. In Smad3 (-/-)/Fut2 (-/-) double knock-out mice, UEA-I lectin staining was eliminated from colon and colon tumors, however, the number and size of tumors present by 24 weeks of age did not vary regardless of the Fut2 genotype. Conclusions: In this model of colorectal cancer, cell surface α(1,2)fucosylation does not affect development of colon tumors. PMID:17264540

  2. Incomplete development of the spleen and the deformity in the chimeras between asplenic mutant (Dominant hemimelia) and normal mice.

    Science.gov (United States)

    Suto, J; Wakayama, T; Imamura, K; Goto, S; Fukuta, K

    1995-08-01

    The semidominant gene Dh (Dominant hemimelia) induces skeletal and visceral abnormalities of various degrees and failure of the spleen in mice. The homozygous individual (Dh/Dh) seems to be lethal. The present experiment was designed to investigate the ability Dh cells to form a spleen and the genesis of the hind limb malformations by Dh/Dh and Dh/+ cells in chimeric mice. The Dh/Dh and Dh/+ embryos were produced in the F2 progeny of a cross between inbred strains of Dh/+ and DDD mice. They were aggregated with C3H/He or C57BL/6 embryos to make chimeras. Identification of Dh/Dh or Dh/+ embryos was carried out by Pep-3, and chimerism was analyzed by Gpi-1. Of 25 chimeras carrying the Dh gene, four mice formed a small spleen, two mice had a vestigial spleen, and the others no spleen. The tissues of the incompletely developed spleens were normal histologically and Dh cells were involved in the tissues of the spleen. In the chimeric mice, hindlimb malformation by the Dh gene was reduced in severity and the lethality of the homozygote (Dh/Dh) was rescued.

  3. Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With Different Susceptibility to Experimental Autoimmune Prostatitis.

    Science.gov (United States)

    Breser, Maria L; Motrich, Ruben D; Sanchez, Leonardo R; Rivero, Virginia E

    2017-01-01

    Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant. Tactile allodynia was assessed using Von Frey fibers as a measure of pelvic pain at baseline and at different time points after immunization. Using conventional histology, immunohistochemistry, FACS analysis, and protein arrays, an interstrain comparative study of prostate cell infiltration and inflammation was performed. Chronic pelvic pain development was similar between immunized NOD and C57BL/6 mice, although the severity of leukocyte infiltration was greater in the first case. Coversely, minimal prostate cell infiltration was observed in immunized BALB/c mice, who showed no pelvic pain development. Increased numbers of mast cells, mostly degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while lower total counts and resting were observed in BALB/c mice. Prostate tissue from NOD mice revealed markedly increased expression levels of inflammatory cytokines, chemokines, adhesion molecules, vascular endothelial growth factor, and metalloproteinases. Similar results, but to a lesser extent, were observed when analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of the above mediators was very low in prostate tissue from immunized BALB/c mice, showing significantly slight increments only for CXCL1 and IL4. Our results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice develop different degrees of chronic pelvic pain, type, and amount of prostate cell infiltration

  4. Changes in hippocampal synaptic functions and protein expression in monosodium glutamate-treated obese mice during development of glucose intolerance.

    Science.gov (United States)

    Sasaki-Hamada, Sachie; Hojo, Yuki; Koyama, Hajime; Otsuka, Hayuma; Oka, Jun-Ichiro

    2015-05-01

    Glucose is the sole neural fuel for the brain and is essential for cognitive function. Abnormalities in glucose tolerance may be associated with impairments in cognitive function. Experimental obese model mice can be generated by an intraperitoneal injection of monosodium glutamate (MSG; 2 mg/g) once a day for 5 days from 1 day after birth. MSG-treated mice have been shown to develop glucose intolerance and exhibit chronic neuroendocrine dysfunction associated with marked cognitive malfunctions at 28-29  weeks old. Although hippocampal synaptic plasticity is impaired in MSG-treated mice, changes in synaptic transmission remain unknown. Here, we investigated whether glucose intolerance influenced cognitive function, synaptic properties and protein expression in the hippocampus. We demonstrated that MSG-treated mice developed glucose intolerance due to an impairment in the effectiveness of insulin actions, and showed cognitive impairments in the Y-maze test. Moreover, long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal synapses in hippocampal slices was impaired, and the relationship between the slope of extracellular field excitatory postsynaptic potential and stimulus intensity of synaptic transmission was weaker in MSG-treated mice. The protein levels of vesicular glutamate transporter 1 and GluA1 glutamate receptor subunits decreased in the CA1 region of MSG-treated mice. These results suggest that deficits in glutamatergic presynapses as well as postsynapses lead to impaired synaptic plasticity in MSG-treated mice during the development of glucose intolerance, though it remains unknown whether impaired LTP is due to altered inhibitory transmission. It may be important to examine changes in glucose tolerance in order to prevent cognitive malfunctions associated with diabetes. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. Aging has small effects on initial ischemic acute kidney injury development despite changing intrarenal immunologic micromilieu in mice.

    Science.gov (United States)

    Jang, Hye Ryoun; Park, Ji Hyeon; Kwon, Ghee Young; Park, Jae Berm; Lee, Jung Eun; Kim, Dae Joong; Kim, Yoon-Goo; Kim, Sung Joo; Oh, Ha Young; Huh, Wooseong

    2016-02-15

    Inflammatory process mediated by innate and adaptive immune systems is a major pathogenic mechanism of renal ischemia-reperfusion injury (IRI). There are concerns that organ recipients may be at increased risk of developing IRI after receiving kidneys from elder donors. To reveal the effects of aging on the development of renal IRI, we compared the immunologic micromilieu of normal and postischemic kidneys from mice of three different ages (9 wk, 6 mo, and 12 mo). There was a higher number of total T cells, especially effector memory CD4/CD8 T cells, and regulatory T cells in the normal kidneys of old mice. On day 2 after IRI, the proportion of necrotic tubules and renal functional changes were comparable between groups although old mice had a higher proportion of damaged tubule compared with young mice. More T cells, but less B cells, trafficked into the postischemic kidneys of old mice. The infiltration of NK T cells was similar across the groups. Macrophages and neutrophils were comparable between groups in both normal kidneys and postischemic kidneys. The intrarenal expressions of TNF-α and VEGF were decreased in normal and postischemic kidneys of aged mice. These mixed effects of aging on lymphocytes and cytokines/chemokines were not different between the two groups of old mice. Our study demonstrates that aging alters the intrarenal micromilieu but has small effects on the development of initial renal injury after IRI. Further study investigating aging-dependent differences in the repair process of renal IRI may be required. Copyright © 2016 the American Physiological Society.

  6. Vitamin D in Atopic Dermatitis, Asthma and Allergic Diseases

    OpenAIRE

    Searing, Daniel A; Leung, Donald YM

    2010-01-01

    This review examines the scientific evidence behind the hypothesis that vitamin D plays a role in the pathogenesis of allergic diseases, with a particular focus on emerging data regarding vitamin D and atopic dermatitis. Both elucidated molecular interactions of vitamin D with components of the immune system, as well as clinical data regarding vitamin D deficiency and atopic diseases are discussed. The rationale behind the “sunshine hypothesis,” laboratory evidence supporting links between vi...

  7. Neuroticism, anxiety, and depression in Egyptian atopic bronchial asthma

    OpenAIRE

    Amal Fathy; Taha t Abd Algawad; Eman O. Arram; Hala Elboraei; Manal S. Arafat; Sherin S. Elmetwaly

    2014-01-01

    The association between allergic and psychological disorders had been reported, but whether the key mediating ingredients are predominantly biological, psychological, or mere artifacts remains unknown. We aim to examine the relationship between objectively measured atopic status and anxiety, depression, and neuroticism. Methods: This randomized case controlled trial was conducted on 50 atopic patients and 50 healthy controls. Atopy was determined by skin prick test and allergy related symp...

  8. Optimizing treatment of atopic dermatitis in infants using ursodeoxycholic acid

    Directory of Open Access Journals (Sweden)

    O.G. Shadrin

    2017-04-01

    Full Text Available The paper studied the rational for including of ursodeoxycholic acid suspension in complex therapy of atopic dermatitis for infants. The indication of ursodeoxycholic acid suspension for 25 infants with atopic dermatitis resulted in positive clinical dynamics of both dermic and gastrointestinal signs, that manifested as reduction of area of impaired skin, intensity of itch, sleep normalization and regression of pain abdominal syndrome, regurgitation.

  9. Erectile Dysfunction in Male Adults With Atopic Dermatitis and Psoriasis

    DEFF Research Database (Denmark)

    Egeberg, Alexander; Hansen, Peter R; Gislason, Gunnar H

    2017-01-01

    INTRODUCTION: Patients with psoriasis have increased risk of cardiovascular disease, but data on atopic dermatitis (AD) are less clear-cut. However, it is well-established that erectile dysfunction (ED) can serve as a risk marker for coronary disease. AIM: To investigate the incidence, prevalence...... population for men with AD. Egeberg A, Hansen PR, Gislason GH, et al. Erectile Dysfunction in Male Adults With Atopic Dermatitis and Psoriasis. J Sex Med 2017;14:380-386....

  10. Intraocular lens subluxation in a patient with facial atopic dermatitis.

    Science.gov (United States)

    Yamazaki, S; Nakamura, K; Kurosaka, D

    2001-02-01

    A 66-year-old Japanese man presented with subluxation of a posterior chamber intraocular lens (IOL) caused by a rupture of part of Zinn's zonule but no retinal break 2 years after phacoemulsification with IOL implantation. He had a history of atopic dermatitis since infancy. This case presents a rare ocular complication of scratching and rubbing the face and eyelids because of itching related to atopic dermatitis.

  11. Parents' reported preference scores for childhood atopic dermatitis disease states

    Directory of Open Access Journals (Sweden)

    Walter Emmanuel B

    2004-10-01

    Full Text Available Abstract Background We sought to elicit preference weights from parents for health states corresponding to children with various levels of severity of atopic dermatitis. We also evaluated the hypothesis that parents with children who had been diagnosed with atopic dermatitis would assign different preferences to the health state scenarios compared with parents who did not have a child with atopic dermatitis. Methods Subjects were parents of children aged 3 months to 18 years. The sample was derived from the General Panel, Mommies Sub-Panel, and Chronic Illness Sub-Panel of Harris Interactive. Participants rated health scenarios for atopic dermatitis, asthma, and eyeglasses on a visual analog scale, imagining a child was experiencing the described state. Results A total of 3539 parents completed the survey. Twenty-nine percent had a child with a history of atopic dermatitis. Mean preference scores for atopic dermatitis were as follows: mild, 91 (95% confidence interval [CI], 90.7 to 91.5; mild/moderate, 84 (95%CI, 83.5 to 84.4; moderate, 73 (95%CI, 72.5 to 73.6; moderate/severe, 61 (95%CI, 60.6 to 61.8; severe, 49 (95% CI, 48.7 to 50.1; asthma, 58 (95%CI, 57.4 to 58.8; and eyeglasses, 87(95%CI, 86.3 to 87.4. Conclusions Parents perceive that atopic dermatitis has a negative effect on quality of life that increases with disease severity. Estimates of parents' preferences can provide physicians with insight into the value that parents place on their children's treatment and can be used to evaluate new medical therapies for atopic dermatitis.

  12. Resveratrol ameliorates 2,4-dinitrofluorobenzene-induced atopic dermatitis-like lesions through effects on the epithelium

    Directory of Open Access Journals (Sweden)

    Sule Caglayan Sozmen

    2016-03-01

    Full Text Available Background. Resveratrol is a natural polyphenol that exhibits anti-inflammatory effects. The aim of this study was to investigate the effects of resveratrol treatment on epithelium-derived cytokines and epithelial apoptosis in a murine model of atopic dermatitis-like lesions. Material and Methods. Atopic dermatitis-like lesions were induced in BALB/c mice by repeated application of 2,4-dinitrofluorobenzene to shaved dorsal skin. Twenty-one BALB/c mice were divided into three groups: group I (control, group II (vehicle control, and group III (resveratrol. Systemic resveratrol (30 mg/kg/day was administered repeatedly during the 6th week of the experiment. After the mice had been sacrificed, skin tissues were examined histologically for epithelial thickness. Epithelial apoptosis (caspase-3 and epithelium-derived cytokines [interleukin (IL-25, IL-33, and thymic stromal lymphopoietin (TSLP] were evaluated immunohistochemically. Results. Epithelial thickness and the numbers of IL-25, IL-33, TSLP and caspase-3-positive cells were significantly higher in group II compared to group I mice. There was significant improvement in epithelial thickness in group III compared with group II mice (p < 0.05. The numbers of IL-25, IL-33, and TSLP-positive cells in the epithelium were lower in group III than in group II mice (p < 0.05. The number of caspase-3-positive cells, as an indicator of apoptosis, in the epithelium was significantly lower in group III than in group II mice (p < 0.05. Conclusion. Treatment with resveratrol was effective at ameliorating histological changes and inflammation by acting on epithelium-derived cytokines and epithelial apoptosis.

  13. Global analysis of gene expression in the developing brain of Gtf2ird1 knockout mice.

    Directory of Open Access Journals (Sweden)

    Jennifer O'Leary

    Full Text Available Williams-Beuren Syndrome (WBS is a neurodevelopmental disorder caused by a hemizygous deletion of a 1.5 Mb region on chromosome 7q11.23 encompassing 26 genes. One of these genes, GTF2IRD1, codes for a putative transcription factor that is expressed throughout the brain during development. Genotype-phenotype studies in patients with atypical deletions of 7q11.23 implicate this gene in the neurological features of WBS, and Gtf2ird1 knockout mice show reduced innate fear and increased sociability, consistent with features of WBS. Multiple studies have identified in vitro target genes of GTF2IRD1, but we sought to identify in vivo targets in the mouse brain.We performed the first in vivo microarray screen for transcriptional targets of Gtf2ird1 in brain tissue from Gtf2ird1 knockout and wildtype mice at embryonic day 15.5 and at birth. Changes in gene expression in the mutant mice were moderate (0.5 to 2.5 fold and of candidate genes with altered expression verified using real-time PCR, most were located on chromosome 5, within 10 Mb of Gtf2ird1. siRNA knock-down of Gtf2ird1 in two mouse neuronal cell lines failed to identify changes in expression of any of the genes identified from the microarray and subsequent analysis showed that differences in expression of genes on chromosome 5 were the result of retention of that chromosome region from the targeted embryonic stem cell line, and so were dependent upon strain rather than Gtf2ird1 genotype. In addition, specific analysis of genes previously identified as direct in vitro targets of GTF2IRD1 failed to show altered expression.We have been unable to identify any in vivo neuronal targets of GTF2IRD1 through genome-wide expression analysis, despite widespread and robust expression of this protein in the developing rodent brain.

  14. Mice deficient for ERAD machinery component Sel1L develop central diabetes insipidus.

    Science.gov (United States)

    Bichet, Daniel G; Lussier, Yoann

    2017-10-02

    Deficiency of the antidiuretic hormone arginine vasopressin (AVP) underlies diabetes insipidus, which is characterized by the excretion of abnormally large volumes of dilute urine and persistent thirst. In this issue of the JCI, Shi et al. report that Sel1L-Hrd1 ER-associated degradation (ERAD) is responsible for the clearance of misfolded pro-arginine vasopressin (proAVP) in the ER. Additionally, mice with Sel1L deficiency, either globally or specifically within AVP-expressing neurons, developed central diabetes insipidus. The results of this study demonstrate a role for ERAD in neuroendocrine cells and serve as a clinical example of the effect of misfolded ER proteins retrotranslocated through the membrane into the cytosol, where they are polyubiquitinated, extracted from the ER membrane, and degraded by the proteasome. Moreover, proAVP misfolding in hereditary central diabetes insipidus likely shares common physiopathological mechanisms with proinsulin misfolding in hereditary diabetes mellitus of youth.

  15. Studies on the influence of static magnetic fields on prenatal development of mice

    Energy Technology Data Exchange (ETDEWEB)

    Konermann, G.; Moenig, H.

    1986-10-01

    Developmental effects were studied in pregnant albino-mice after exposures to a static homogeneous magnetic field (1T) on days 7, 10 or 13 post conception. These days correspond approximately to the 16th, 28th or 42nd day p.c. in human development and represent stages of increased sensitivity. Intrauterine effects (after exposures on days 7 or 10 p.c.) were evaluated included lethality, external malformations, disoders in the fetal skeleton and fetal weights. The evaluation of postnatal effects (after exposure on day 13 p.c.) included body-weight, brain-weight, diameter of neocortex and commissures and the alignment of cortical neurons up to day 46 p.c. According to all these criteria, no developmental effects were observed after the exposures to the magnetic field. Transient effects, either being compensatable or biologically without relevance, cannot be excluded.

  16. Development of Ethanol Withdrawal-Related Sensitization and Relapse Drinking in Mice Selected for High or Low Ethanol Preference

    Science.gov (United States)

    Lopez, Marcelo F.; Grahame, Nicholas J.; Becker, Howard C.

    2010-01-01

    Background Previous studies have shown that high alcohol consumption is associated with low withdrawal susceptiblility, while at the same time, other studies have shown that exposure to ethanol vapor increases alcohol drinking in rats and mice. In the present studies, we sought to shed light on this seeming contradiction by using mice selectively bred for High- (HAP) and Low- (LAP) Alcohol Preference, first, assessing these lines for differences in signs of ethanol withdrawal and second, for differences in the efficacy of intermittent alcohol vapor exposure on elevating subsequent ethanol intake. Methods Experiment 1 examined whether these lines of mice differed in ethanol withdrawal-induced CNS hyperexcitability and the development of sensitization to this effect following intermittent ethanol vapor exposure. Adult HAP and LAP lines (replicates 1 and 2), and the C3H/HeNcr inbred strain (included as a control genotype for comparison purposes) received intermittent exposure to ethanol vapor and were evaluated for ethanol withdrawal-induced seizures assessed by scoring handling-induced convulsions (HIC). Experiment 2 examined the influence of chronic intermittent ethanol exposure on voluntary ethanol drinking. Adult male and female HAP-2 and LAP-2 mice, along with male C57BL/6J (included as comparative controls) were trained to drink 10% ethanol using a limited access (2 hr/day) 2-bottle choice paradigm. After stable baseline daily intake was established, mice received chronic intermittent ethanol vapor exposure in inhalation chambers. Ethanol intake sessions resumed 72 hr after final ethanol (or air) exposure for 5 consecutive days. Results Following chronic ethanol treatment, LAP mice exhibited overall greater withdrawal seizure activity compared to HAP mice. In Experiment 2, chronic ethanol exposure/withdrawal resulted in a significant increase in ethanol intake in male C57BL/6J, and modestly elevated intake in HAP-2 male mice. Ethanol intake for male control mice

  17. Parents' self-efficacy, outcome expectations, and self-reported task performance when managing atopic dermatitis in children: instrument reliability and validity.

    Science.gov (United States)

    Mitchell, Amy E; Fraser, Jennifer A

    2011-02-01

    Support and education for parents faced with managing a child with atopic dermatitis is crucial to the success of current treatments. Interventions aiming to improve parent management of this condition are promising. Unfortunately, evaluation is hampered by lack of precise research tools to measure change. To develop a suite of valid and reliable research instruments to appraise parents' self-efficacy for performing atopic dermatitis management tasks; outcome expectations of performing management tasks; and self-reported task performance in a community sample of parents of children with atopic dermatitis. The Parents' Eczema Management Scale (PEMS) and the Parents' Outcome Expectations of Eczema Management Scale (POEEMS) were developed from an existing self-efficacy scale, the Parental Self-Efficacy with Eczema Care Index (PASECI). Each scale was presented in a single self-administered questionnaire, to measure self-efficacy, outcome expectations, and self-reported task performance related to managing child atopic dermatitis. Each was tested with a community sample of parents of children with atopic dermatitis, and psychometric evaluation of the scales' reliability and validity was conducted. A community-based convenience sample of 120 parents of children with atopic dermatitis completed the self-administered questionnaire. Participants were recruited through schools across Australia. Satisfactory internal consistency and test-retest reliability was demonstrated for all three scales. Construct validity was satisfactory, with positive relationships between self-efficacy for managing atopic dermatitis and general perceived self-efficacy; self-efficacy for managing atopic dermatitis and self-reported task performance; and self-efficacy for managing atopic dermatitis and outcome expectations. Factor analyses revealed two-factor structures for PEMS and PASECI alike, with both scales containing factors related to performing routine management tasks, and managing the

  18. Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation.

    Science.gov (United States)

    Ciezka, Magdalena; Acosta, Milena; Herranz, Cristina; Canals, Josep M; Pumarola, Martí; Candiota, Ana Paula; Arús, Carles

    2016-08-01

    The initial aim of this study was to generate a transplantable glial tumour model of low-intermediate grade by disaggregation of a spontaneous tumour mass from genetically engineered models (GEM). This should result in an increased tumour incidence in comparison to GEM animals. An anaplastic oligoastrocytoma (OA) tumour of World Health Organization (WHO) grade III was obtained from a female GEM mouse with the S100β-v-erbB/inK4a-Arf (+/-) genotype maintained in the C57BL/6 background. The tumour tissue was disaggregated; tumour cells from it were grown in aggregates and stereotactically injected into C57BL/6 mice. Tumour development was followed using Magnetic Resonance Imaging (MRI), while changes in the metabolomics pattern of the masses were evaluated by Magnetic Resonance Spectroscopy/Spectroscopic Imaging (MRS/MRSI). Final tumour grade was evaluated by histopathological analysis. The total number of tumours generated from GEM cells from disaggregated tumour (CDT) was 67 with up to 100 % penetrance, as compared to 16 % in the local GEM model, with an average survival time of 66 ± 55 days, up to 4.3-fold significantly higher than the standard GL261 glioblastoma (GBM) tumour model. Tumours produced by transplantation of cells freshly obtained from disaggregated GEM tumour were diagnosed as WHO grade III anaplastic oligodendroglioma (ODG) and OA, while tumours produced from a previously frozen sample were diagnosed as WHO grade IV GBM. We successfully grew CDT and generated tumours from a grade III GEM glial tumour. Freezing and cell culture protocols produced progression to grade IV GBM, which makes the developed transplantable model qualify as potential secondary GBM model in mice.

  19. Transmaternal bisphenol A exposure accelerates diabetes type 1 development in NOD mice.

    Science.gov (United States)

    Bodin, Johanna; Bølling, Anette Kocbach; Becher, Rune; Kuper, Frieke; Løvik, Martinus; Nygaard, Unni Cecilie

    2014-02-01

    Diabetes mellitus type 1 is an autoimmune disease with a genetic predisposition that is triggered by environmental factors during early life. Epidemiological studies show that bisphenol A (BPA), an endocrine disruptor, has been detected in about 90% of all analyzed human urine samples. In this study, BPA was found to increase the severity of insulitis and the incidence of diabetes in female non obese diabetic (NOD) mice offspring after transmaternal exposure through the dams' drinking water (0, 0.1, 1, and 10mg/l). Both the severity of insulitis in the pancreatic islets at 11 weeks of age and the diabetes prevalence at 20 weeks were significantly increased for female offspring in the highest exposure group compared to the control group. Increased numbers of apoptotic cells, a reduction in tissue resident macrophages and an increase in regulatory T cells were observed in islets prior to insulitis development in transmaternally exposed offspring. The detectable apoptotic cells were identified as mostly glucagon producing alpha-cells but also tissue resident macrophages and beta-cells. In the local (pancreatic) lymph node neither regulatory T cell nor NKT cell populations were affected by maternal BPA exposure. Maternal BPA exposure may have induced systemic immune changes in offspring, as evidenced by alterations in LPS- and ConA-induced cytokine secretion in splenocytes. In conclusion, transmaternal BPA exposure, in utero and through lactation, accelerated the spontaneous diabetes development in NOD mice. This acceleration appeared to be related to early life modulatory effects on the immune system, resulting in adverse effects later in life.

  20. K-Ras(V14I) -induced Noonan syndrome predisposes to tumour development in mice.

    Science.gov (United States)

    Hernández-Porras, Isabel; Schuhmacher, Alberto J; Garcia-Medina, Raquel; Jiménez, Beatriz; Cañamero, Marta; de Martino, Alba; Guerra, Carmen

    2016-06-01

    The Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, craniofacial dysmorphism, and congenital heart defects. A significant proportion of NS patients may also develop myeloproliferative disorders (MPDs), including juvenile myelomonocytic leukaemia (JMML). Surprisingly, scarce information is available in relation to other tumour types in these patients. We have previously developed and characterized a knock-in mouse model that carries one of the most frequent KRAS-NS-related mutations, the K-Ras(V14I) substitution, which recapitulates most of the alterations described in NS patients, including MPDs. The K-Ras(V14I) mutation is a mild activating K-Ras protein; thus, we have used this model to study tumour susceptibility in comparison with mice expressing the classical K-Ras(G12V) oncogene. Interestingly, our studies have shown that these mice display a generalized tumour predisposition and not just MPDs. In fact, we have observed that the K-Ras(V14I) mutation is capable of cooperating with the p16Ink4a/p19Arf and Trp53 tumour suppressors, as well as with other risk factors such as pancreatitis, thereby leading to a higher cancer incidence. In conclusion, our results illustrate that the K-Ras(V14I) activating protein is able to induce cancer, although at a much lower level than the classical K-Ras(G12V) oncogene, and that it can be significantly modulated by both genetic and non-genetic events. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  1. Development of a DIPG Orthotopic Model in Mice Using an Implantable Guide-Screw System.

    Directory of Open Access Journals (Sweden)

    Miguel Marigil

    Full Text Available In this work we set to develop and to validate a new in vivo frameless orthotopic Diffuse Intrinsic Pontine Glioma (DIPG model based in the implantation of a guide-screw system.It consisted of a guide-screw also called bolt, a Hamilton syringe with a 26-gauge needle and an insulin-like 15-gauge needle. The guide screw is 2.6 mm in length and harbors a 0.5 mm central hole which accepts the needle of the Hamilton syringe avoiding a theoretical displacement during insertion. The guide-screw is fixed on the mouse skull according to the coordinates: 1mm right to and 0.8 mm posterior to lambda. To reach the pons the Hamilton syringe is adjusted to a 6.5 mm depth using a cuff that serves as a stopper. This system allows delivering not only cells but also any kind of intratumoral chemotherapy, antibodies or gene/viral therapies.The guide-screw was successfully implanted in 10 immunodeficient mice and the animals were inoculated with DIPG human cell lines during the same anesthetic period. All the mice developed severe neurologic symptoms and had a median overall survival of 95 days ranging the time of death from 81 to 116 days. Histopathological analysis confirmed tumor into the pons in all animals confirming the validity of this model.Here we presented a reproducible and frameless DIPG model that allows for rapid evaluation of tumorigenicity and efficacy of chemotherapeutic or gene therapy products delivered intratumorally to the pons.

  2. SPECIAL CHARACTERISTICS OF TREATMENT OF SEVERE ATOPIC DERMATITIS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    D. Sh. Macharadze

    2013-01-01

    Full Text Available The article analyzes modern data on risk factors of severe course of atopic dermatitis in children: the role of alimentary and inhalant allergens, cutaneous infections, allergic reactions to drugs used in the treatment of disease. The most important questions of differential diagnosis of atopic dermatitis in children and the distinctive features of the illness, which may be mistaken for atopic dermatitis (primary immunodeficiencies, keratosis pilaris, psoriasis, enteropatic acrodermatitis; cutaneous bacterial and fungal infections, and drug-induced contact dermatitis to topical creams and ointments are discussed. Treatment of atopic dermatitis is based on modern approaches and includes recommendations on the use of emolents, anti-inflammatory drugs (topical glucocorticoids and calcineurin inhibitors. The article provides indications and contraindications to the administration of anti-inflammatory drugs. Special recommendations for use of cleansers and emolents at all degrees of severity of atopic dermatitis, which helps reduce the risk of side effects of topical corticosteroids, complications such as cutaneous infections and helps to maintain remission of disease are given. The importance of training programs patients is emphasized. Compliance of patients and/or their parents contributes to the achievement of the desired effect of the treatment of atopic dermatitis, which will improve the patients’ quality of life.

  3. Efficacy of Astaxanthin for the Treatment of Atopic Dermatitis in a Murine Model.

    Directory of Open Access Journals (Sweden)

    Yoko Yoshihisa

    Full Text Available Atopic dermatitis (AD is a common chronic inflammatory skin disease associated with various factors, including immunological abnormalities and exposure to allergens. Astaxanthin (AST is a xanthophyll carotenoid that has recently been demonstrated to have anti-inflammatory effects and to regulate the expression of inflammatory cytokines. Thus, we investigated whether AST could improve the dermatitis and pruritus in a murine model of AD using NC/Nga mice. In addition to a behavioral evaluation, the effects of AST on the AD were determined by the clinical skin severity score, serum IgE level, histological analyses of skin, and by reverse transcription-PCR and Western blotting analyses for the expression of inflammation-related factors. AST (100 mg/kg or vehicle (olive oil was orally administered once day and three times a week for 26 days. When compared with vehicle-treated group, the administration of AST significantly reduced the clinical skin severity score. In addition, the spontaneous scratching in AD model mice was reduced by AST administration. Moreover, the serum IgE level was markedly decreased by the oral administration of AST compared to that in vehicle-treated mice. The number of eosinophils, total and degranulated mast cells all significantly decreased in the skin of AST-treated mice compared with vehicle-treated mice. The mRNA and protein levels of eotaxin, MIF, IL-4, IL-5 and L-histidine decarboxylase were significantly decreased in the skin of AST-treated mice compared with vehicle-treated mice. These results suggest that AST improves the dermatitis and pruritus in AD via the regulation of the inflammatory effects and the expression of inflammatory cytokines.

  4. Effects of Dim Light at Night on Food Intake and Body Mass in Developing Mice

    OpenAIRE

    Ciss?, Yasmine M.; Peng, Juan; Nelson, Randy J.

    2017-01-01

    Appropriately timed light is critical for circadian organization; exposure to dim light at night (dLAN) disrupts temporal organization of endogenous biological timing. Exposure to dLAN in adult mice is associated with elevated body mass and changes in metabolism putatively driven by voluntary changes in the time of food intake. We predicted that exposure of young mice to LAN could affect adult metabolic function. At 3 weeks (Experiment 1) or 5 weeks (Experiment 2) of age, mice were either mai...

  5. Mast cells and atopic dermatitis. Stereological quantification of mast cells in atopic dermatitis and normal human skin

    DEFF Research Database (Denmark)

    Damsgaard, T E; Olesen, A B; Sørensen, Flemming Brandt

    1997-01-01

    Stereological quantification of mast cell numbers was applied to sections of punch biopsies from lesional and nonlesional skin of atopic dermatitis patients and skin of healthy volunteers. We also investigated whether the method of staining and/or the fixative influenced the results...... of the determination of the mast cell profile numbers. The punch biopsies were taken from the same four locations in both atopic dermatitis patients and normal individuals. The locations were the scalp, neck and flexure of the elbow (lesional skin), and nates (nonlesional skin). Clinical scoring was carried out...... yielded the following results: (1) in atopic dermatitis lesional skin an increased number of mast cell profiles was found as compared with nonlesional skin, (2) comparing atopic dermatitis skin with normal skin, a significantly increased number of mast cell profiles per millimetre squared was found...

  6. A short-term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group

    NARCIS (Netherlands)

    Ruzicka, T.; Bieber, T.; Schöpf, E.; Rubins, A.; Dobozy, A.; Bos, J. D.; Jablonska, S.; Ahmed, I.; Thestrup-Pedersen, K.; Daniel, F.; Finzi, A.; Reitamo, S.

    1997-01-01

    Tacrolimus (FK 506) is an effective immunosuppressant drug for the prevention of rejection after organ transplantation, and preliminary studies suggest that topical application of tacrolimus is effective in the treatment of atopic dermatitis. We conducted a randomized, doubleblind, multicenter study

  7. Patterns of sensitization in infants and its relation to atopic dermatitis

    DEFF Research Database (Denmark)

    Jøhnke, Hanne; Norberg, Lene Annette; Vach, Werner

    2006-01-01

    Longitudinal studies in infant populations using validated diagnostic criteria of atopic dermatitis and sensitization are rarely reported, and disease definitions, testing procedures, age of study population and evaluation of objective markers vary between countries and studies. The objectives...... of this prospective birth cohort study were to investigate: (i) the prevalence, the cumulative incidence and the pattern of transient and persistent sensitization to common food- and aeroallergens in unselected infants, (ii) the association between sensitization and the development of atopic dermatitis (AD) and (iii......) the association between selected perinatal risk factors with respect to AD and post-natal sensitization. During a one-year period a cohort of 562 unselected newborns was established and followed up at the age of 3, 6, 9, 12 and 18 months of age. At all time points infants were examined clinically and by histamine...

  8. In vivo dendritic cell depletion reduces breeding efficiency, affecting implantation and early placental development in mice.

    Science.gov (United States)

    Krey, Gesa; Frank, Pierre; Shaikly, Valerie; Barrientos, Gabriela; Cordo-Russo, Rosalia; Ringel, Frauke; Moschansky, Petra; Chernukhin, Igor V; Metodiev, Metodi; Fernández, Nelson; Klapp, Burghard F; Arck, Petra C; Blois, Sandra M

    2008-09-01

    Implantation of mammalian embryos into their mother's uterus ensures optimal nourishment and protection throughout development. Complex molecular interactions characterize the implantation process, and an optimal synchronization of the components of this embryo-maternal dialogue is crucial for a successful reproductive outcome. In the present study, we investigated the role of dendritic cells (DC) during implantation process using a transgenic mouse system (DTRtg) that allows transient depletion of CD11c+ cells in vivo through administration of diphtheria toxin. We observed that DC depletion impairs the implantation process, resulting in a reduced breeding efficiency. Furthermore, the maturity of uterine natural killer cells at dendritic cell knockout (DCKO) implantation sites was affected as well; as demonstrated by decreased perforin expression and reduced numbers of periodic-acid-Schiff (PAS)-positive cells. This was accompanied by disarrangements in decidual vascular development. In the present study, we were also able to identify a novel DC-dependent protein, phosphatidylinositol transfer protein beta (PITPbeta), involved in implantation and trophoblast development using a proteomic approach. Indeed, DCKO mice exhibited substantial anomalies in placental development, including hypocellularity of the spongiotrophoblast and labyrinthine layers and reduced numbers of trophoblast giant cells. Giant cells also down-regulated their expression of two characteristic markers of trophoblast differentiation, placental lactogen 1 and proliferin. In view of these findings, dendritic cells emerge as possible modulators in the orchestration of events leading to the establishment and maintenance of pregnancy.

  9. Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice.

    Directory of Open Access Journals (Sweden)

    Kristie Lee

    Full Text Available Congenital hydrocephalus (CH is a life-threatening medical condition in which excessive accumulation of CSF leads to ventricular expansion and increased intracranial pressure. Stenosis (blockage of the Sylvian aqueduct (Aq; the narrow passageway that connects the third and fourth ventricles is a common form of CH in humans, although the genetic basis of this condition is unknown. Mouse models of CH indicate that Aq stenosis is associated with abnormal development of the subcommmissural organ (SCO a small secretory organ located at the dorsal midline of the caudal diencephalon. Glycoproteins secreted by the SCO generate Reissner's fibre (RF, a thread-like structure that descends into the Aq and is thought to maintain its patency. However, despite the importance of SCO function in CSF homeostasis, the genetic program that controls SCO development is poorly understood. Here, we show that the X-linked transcription factor SOX3 is expressed in the murine SCO throughout its development and in the mature organ. Importantly, overexpression of Sox3 in the dorsal diencephalic midline of transgenic mice induces CH via a dose-dependent mechanism. Histological, gene expression and cellular proliferation studies indicate that Sox3 overexpression disrupts the development of the SCO primordium through inhibition of diencephalic roof plate identity without inducing programmed cell death. This study provides further evidence that SCO function is essential for the prevention of hydrocephalus and indicates that overexpression of Sox3 in the dorsal midline alters progenitor cell differentiation in a dose-dependent manner.

  10. Heterozygous Lmna(delK32) mice develop dilated cardiomyopathy through a combined pathomechanism of haploinsufficiency and peptide toxicity

    DEFF Research Database (Denmark)

    Cattin, M. E.; Bertrand, A. T.; Schlossarek, S.

    2013-01-01

    itself has a clear deleterious effect on engineered heart tissues force of contraction, it also leads to the nuclear aggregation of viral-mediated expression of K32-lamin. In conclusion, Het mice are the first knock-in Lmna model with cardiac-specific phenotype at the heterozygous state. Altogether, our....... The pathomechanisms linking mutations to DCM remain to be elucidated. We investigated the phenotype and associated pathomechanisms of heterozygous Lmna(K32/) (Het) knock-in mice, which carry a human mutation. Het mice developed a cardiac-specific phenotype. Two phases, with two different pathomechanisms, could...... be observed that lead to the development of cardiac dysfunction, DCM and death between 35 and 70 weeks of age. In young Het hearts, there was a clear reduction in lamin A/C level, mainly due to the degradation of toxic K32-lamin. As a side effect, lamin A/C haploinsufficiency probably triggers the cardiac...

  11. Sulforaphane ameliorates the development of experimental autoimmune encephalomyelitis by antagonizing oxidative stress and Th17-related inflammation in mice.

    Science.gov (United States)

    Li, Bin; Cui, Wei; Liu, Jia; Li, Ru; Liu, Qian; Xie, Xiao-Hua; Ge, Xiao-Li; Zhang, Jing; Song, Xiu-Juan; Wang, Ying; Guo, Li

    2013-12-01

    Sulforaphane (SFN) is an organosulfur compound present in vegetables and has potent anti-oxidant and anti-inflammatory activities. This study was aimed at investigating the effect of treatment with SFN on inflammation and oxidative stress, and the potential mechanisms underlying the action of SFN in experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. Treatment with SFN significantly inhibited the development and severity of EAE in mice, accompanied by mitigating inflammatory infiltration and demyelination in the spinal cord of mice. The protective effect of SFN was associated with significantly improved distribution of claudin-5 and occludin, and decreased levels of MMP-9 expression, preserving the blood-brain barrier. Furthermore, the protection of SFN was also related to decreased levels of oxidative stress in the brains of mice by enhanced activation of the Nrf2/ARE pathway and increased levels of anti-oxidant HO-1 and NQO1 expression. In addition, treatment with SFN inhibited antigen-specific Th17 responses and enhanced IL-10 responses. Our data indicated that treatment with SFN inhibited EAE development and severity in mice by its anti-oxidant activity and antagonizing autoimmune inflammation. Our findings suggest that SFN and its analogues may be promising reagents for intervention of multiple sclerosis and other autoimmune diseases. © 2013.

  12. Defects in the CAPN1 Gene Result in Alterations in Cerebellar Development and Cerebellar Ataxia in Mice and Humans

    Directory of Open Access Journals (Sweden)

    Yubin Wang

    2016-06-01

    Full Text Available A CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous or heterozygous CAPN1-null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knockout (KO mice also exhibit a mild form of ataxia due to abnormal cerebellar development, including enhanced neuronal apoptosis, decreased number of cerebellar granule cells, and altered synaptic transmission. Enhanced apoptosis is due to absence of calpain-1-mediated cleavage of PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1, which results in inhibition of the Akt pro-survival pathway in developing granule cells. Injection of neonatal mice with the indirect Akt activator, bisperoxovanadium, or crossing calpain-1 KO mice with PHLPP1 KO mice prevented increased postnatal cerebellar granule cell apoptosis and restored granule cell density and motor coordination in adult mice. Thus, mutations in CAPN1 are an additional cause of ataxia in mammals, including humans.

  13. Molecular Genetic of Atopic dermatitis: An Update

    Science.gov (United States)

    Al-Shobaili, Hani A.; Ahmed, Ahmed A.; Alnomair, Naief; Alobead, Zeiad Abdulaziz; Rasheed, Zafar

    2016-01-01

    Atopic dermatitis (AD) is a chronic multifactorial inflammatory skin disease. The pathogenesis of AD remains unclear, but the disease results from dysfunctions of skin barrier and immune response, where both genetic and environmental factors play a key role. Recent studies demonstrate the substantial evidences that show a strong genetic association with AD. As for example, AD patients have a positive family history and have a concordance rate in twins. Moreover, several candidate genes have now been suspected that play a central role in the genetic background of AD. In last decade advanced procedures similar to genome-wide association (GWA) and single nucleotide polymorphism (SNP) have been applied on different population and now it has been clarified that AD is significantly associated with genes of innate/adaptive immune systems, human leukocyte antigens (HLA), cytokines, chemokines, drug-metabolizing genes or various other genes. In this review, we will highlight the recent advancements in the molecular genetics of AD, especially on possible functional relevance of genetic variants discovered to date. PMID:27004062

  14. Management of Atopic Dermatitis in Japan.

    Science.gov (United States)

    Saeki, Hidehisa

    2017-01-01

    The guidelines for the treatment of atopic dermatitis (AD) issued by the Japanese Dermatological Association (JDA), which are basically designed for dermatologists, were first prepared in 2000 and revised in 2016. The guidelines for AD of the Japanese Society of Allergology (JSA), which are basically designed for allergologists, including internists, otorhinolaryngologists, ophthalmologists, and dermatologists, were first prepared in 2009 and revised in 2014. In this article, I review the definition, pathophysiology, etiology, epidemiology, diagnosis, severity classification, examination for diagnosis and severity assessment, and treatments for AD in Japan according to these two guidelines for AD (JDA and JSA). Based on the definition and diagnostic criteria for AD of the JDA, patients meeting three basic criteria, 1) pruritus, 2) typical morphology and distribution of the eczema, and 3) chronic or chronically relapsing course, are regarded as having AD. Treatment measures for AD basically consist of drug therapy, skin care, and elimination of exacerbating factors. Drugs that potently reduce AD-related inflammation in the skin are topical corticosteroids and tacrolimus. It is most important to promptly and accurately reduce inflammation related to AD by using these topical anti-inflammatory drugs. Proactive therapy refers to a treatment method in which, after inducing remission, a topical corticosteroid or tacrolimus ointment is intermittently applied to the skin in addition to skin care with moisturizers in order to maintain remission.

  15. Cytotoxic assessment of silver nanoparticles in embryonic development and kidney tissue in pregnant mice

    Directory of Open Access Journals (Sweden)

    Bagher seyedalipour

    2015-10-01

    Full Text Available Background and Aim: Regarding the widespread use of silver nanoparticles in medecine and lack of a detailed study of toxicity effects of these particles on fetus, this study was carried out to investigate histopathological changes of the kidneys and also embryonic development following exposure to silver nanoparticles. Materials and Methods: In this experimental study, thirty five female NMRI mice were randomly divided into five equal groups i.e. one control group and four experimental groups. The experimental groups intraperitoneally (IP received silver nanoparticles at concentrations of 50, 100, 200 and 400 mg/ kg . .every other day. On the 17th day  of pregnancy, the mice were dissected and  their kidneys and embryos tissues were separated and stained with hematoxylin and eosin for histopathological examinations. .Finally, the obtained data was fed into SPSS software (V:16 using statistical tests including Kolmogrof-Smearnof, one-way variance analysis, Dante, Mann-Whitney and Kruskal-Wallis and P<0.05 was taken as the significant level. Results: Histopathological assessment of kidney tissue following IP administration of silver nanoparticle indicated pathological changes including congestion, necrosis, inflammatory cell infiltration, vacuolar degeneration compared to the control group. Our findings showed that silver nanoparticles during the gestation period affects fetal organogenesis, evolution of neural structure, liver lobulation and fetal growth retardation. Mean number of somites in groups receiving doses of 200 and 400 mg kg, . significantly reduced compared to the control group (P<0.05. Conclusion: The obtained results suggest that  passing of silver nanoparticles through placenta is possible and damage caused by the particles  could lead to the deformity or developmental retardation of the fetus.

  16. Abnormal megakaryocyte development and platelet function in Nbeal2−/− mice

    Science.gov (United States)

    Lo, Richard W.; Li, Ling; Pluthero, Fred G.; Christensen, Hilary; Ni, Ran; Vaezzadeh, Nima; Hawkins, Cynthia E.; Weyrich, Andrew S.; Di Paola, Jorge; Landolt-Marticorena, Carolina; Gross, Peter L.

    2013-01-01

    Gray platelet syndrome (GPS) is an inherited bleeding disorder associated with macrothrombocytopenia and α-granule-deficient platelets. GPS has been linked to loss of function mutations in NEABL2 (neurobeachin-like 2), and we describe here a murine GPS model, the Nbeal2−/− mouse. As in GPS, Nbeal2−/− mice exhibit splenomegaly, macrothrombocytopenia, and a deficiency of platelet α-granules and their cargo, including von Willebrand factor (VWF), thrombospondin-1, and platelet factor 4. The platelet α-granule membrane protein P-selectin is expressed at 48% of wild-type levels and externalized upon platelet activation. The presence of P-selectin and normal levels of VPS33B and VPS16B in Nbeal2−/− platelets suggests that NBEAL2 acts independently of VPS33B/VPS16B at a later stage of α-granule biogenesis. Impaired Nbeal2−/− platelet function was shown by flow cytometry, platelet aggregometry, bleeding assays, and intravital imaging of laser-induced arterial thrombus formation. Microscopic analysis detected marked abnormalities in Nbeal2−/− bone marrow megakaryocytes, which when cultured showed delayed maturation, decreased survival, decreased ploidy, and developmental abnormalities, including abnormal extracellular distribution of VWF. Our results confirm that α-granule secretion plays a significant role in platelet function, and they also indicate that abnormal α-granule formation in Nbeal2−/− mice has deleterious effects on megakaryocyte survival, development, and platelet production. PMID:23861251

  17. R6/2 Huntington's disease mice develop early and progressive abnormal brain metabolism and seizures.

    Science.gov (United States)

    Cepeda-Prado, Efrain; Popp, Susanna; Khan, Usman; Stefanov, Dimitre; Rodríguez, Jorge; Menalled, Liliana B; Dow-Edwards, Diana; Small, Scott A; Moreno, Herman

    2012-05-09

    A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several Huntington's disease (HD) mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated using in vivo functional MRI (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6/2 at early and advanced stages of disease. Significantly higher fMRI signals [relative cerebral blood volumes (rCBVs)] and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions, thus identifying a mechanism accounting for the abnormal fMRI findings. [(14)C] 2-deoxyglucose maps to investigate patterns of glucose utilization were also generated. An interesting mismatch between increases in rCBV and decreases in glucose uptake was observed. Finally, we evaluated the sensitivity of this mouse line to audiogenic seizures early in the disease course. We found that R6/2 mice had an increased susceptibility to develop seizures. Together, these findings identified seizure activity in R6/2 mice and show that neuroimaging measures sensitive to oxygen metabolism can be used as in vivo biomarkers, preceding the onset of an overt behavioral phenotype. Since fMRI-rCBV can also be obtained in patients, we propose that it may serve as a translational tool to evaluate therapeutic responses in humans and HD mouse models.

  18. Analysis of epidermal lipids in normal and atopic dogs, before and after administration of an oral omega-6/omega-3 fatty acid feed supplement. A pilot study.

    Science.gov (United States)

    Popa, Iuliana; Pin, Didier; Remoué, Noëlle; Remoué, Nathalie; Osta, Bilal; Callejon, Sylvie; Videmont, Emilie; Gatto, Hugues; Portoukalian, Jacques; Haftek, Marek

    2011-12-01

    Alterations of the lipid expression in the skin of human and canine atopic subjects may be one of the key factors in the disease development. We have analyzed the ultrastructure of the clinically uninvolved skin of atopic dogs and compared it with the lipid composition of their tape-stripped stratum corneum (SC). The effect of a 2 month treatment of atopic dogs by food supplementation with a mixture of essential fatty acids was evaluated on skin samples taken before and after the treatment period. Electron microscopy revealed that the non-lesional skin of atopic dogs exhibited an abnormal and largely incomplete structure of the lamellar lipids with little cohesion between the corneocyte strata. The SC of atopic dogs was characterized by a significant decrease in the lipid content when compared to the healthy controls. Following oral supplementation with the mixture of essential fatty acids, the overall lipid content of the SC markedly increased. This feature was observed both with the free and, most importantly, with the protein-bound lipids (cholesterol, fatty acids and ceramides), the latter constituting the corneocyte-bound scaffold for ordinate organisation of the extracellular lipid bi-layers. Indeed, the semi-quantitative electron microscopy study revealed that the treatment resulted in a significantly improved organization of the lamellar lipids in the lower SC, comparable to that of the healthy dogs. Our results indicate the potential interest of long-term alimentary supplementation with omega-6 and omega-3 essential fatty acids in canine atopic dermatitis.

  19. Barhl1 is directly regulated by thyroid hormone in the developing cerebellum of mice

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Hongyan, E-mail: hongyan_dong@hc-sc.gc.ca [Hazard Identification Division, Environmental Health Science and Research Bureau, Health Canada, 50 Columbine Driveway, Ottawa, Ontario, Canada K1A 0K9 (Canada); Yauk, Carole L. [Mechanistic Studies Division, Environmental Health Science and Research Bureau, Health Canada, 50 Columbine Driveway, Ottawa, Ontario, Canada K1A 0K9 (Canada); Wade, Michael G. [Hazard Identification Division, Environmental Health Science and Research Bureau, Health Canada, 50 Columbine Driveway, Ottawa, Ontario, Canada K1A 0K9 (Canada)

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer Thyroid hormone receptor binds to the promoter region of Barhl1. Black-Right-Pointing-Pointer Barhl1 expression in cerebellum is negatively regulated by thyroid hormone. Black-Right-Pointing-Pointer Negative regulation of Barhl1 by thyroid hormone was confirmed in vitro. Black-Right-Pointing-Pointer Thyroid hormone may play a role in normal brain development through transcriptional control of Barhl1. -- Abstract: Thyroid hormones (THs) are essential for the brain development. Despite considerable effort, few genes directly regulated by THs have been identified. In this study, we investigate the effects of THs on the regulation of Barhl1, a transcription factor that regulates sensorineural development. Using DNA microarray combined with chromatin immunoprecipitation (ChIP-chip), we identified a TR{beta} binding site in the promoter of Barhl1. The binding was further confirmed by ChIP-PCR. The site is located approximately 755 bp upstream of the transcription start site. Reporter vectors containing the binding site or mutated fragments were transfected into GH3 cells. T3 treatment decreased the transcriptional activity of the wild fragment but not the mutant. Two 28 bp oligonucleotides containing sequences that resemble known TH response elements (TREs) were derived from this binding site and DNA-protein interaction was performed using electrophoretic mobility shift assays (EMSA). Binding analysis in a nuclear extract containing TR{beta} revealed that one of these fragments bound TR{beta}. This complex was shifted with the addition of anti-TR{beta} antibody. We investigated Barhl1 expression in animal models and TH-treated cultured cells. Both long term treatment with 6-propyl-2-thiouracil and short-term treatment with 0.05% methimazole/1% sodium perchlorate (both treatments render mice hypothyroid) resulted in up-regulation of Barhl1. TH supplementation of hypothyroid mice caused a decrease in the expression of Barhl1

  20. Investigating the effects of nanoparticles on reproduction and development in Drosophila melanogaster and CD-1 mice

    Science.gov (United States)

    Philbrook, Nicola Anne

    Manufactured nanoparticles (NPs) are a class of small (≤ 100 nm) materials that are being used for a variety of purposes, including industrial lubricants, food additives, antibacterial agents, as well as delivery systems for drug and gene therapies. Their unique characteristics due to their small size as well as their parent materials allow them to be exploited in convenience applications; however, some of these properties also allow them to interact with and invade biological systems. Few studies have been performed to determine the potential harm that NPs can inflict on reproductive and developmental processes in organisms. In this study, Drosophila melanogaster and CD-1 mice were orally exposed to varying doses of titanium dioxide (TiO 2) NPs, silver (Ag) NPs, or hydroxyl-functionalized carbon nanotubes (fCNTs) and Drosophila were also exposed to microparticles (MPs) as a control for particle size. The subsequent effect of these materials on reproduction and development were evaluated. Strikingly, each type of NP studied negatively affected either reproduction or development in one or both of the two model systems. TiO2 NPs significantly negative effected both CD-1 mouse development (100 mg/kg or 1000 mg/kg) as well as Drosophila female fecundity (0.005%-0.5% w/v). Ag NPs significantly reduced mouse fetus viability after prenatal exposure to10 mg/kg. Ag NPs also significantly decreased the developmental success of Drosophila when they were directly exposed to these NPs (0.05% - 0.5% w/v) compared to both the vehicle and MP controls. fCNTs significantly increased the presence of morphological defects, resorptions and skeletal abnormalities in CD-1 mice, but had little effect on Drosophila. We speculate that the differences seen in the effects of NP types may be partially due to differences in reproductive physiology as well as each organism's ability to internalize these NPs. Whereas the differing response of each organism to a NP type was likely due in part to

  1. Barhl1 is directly regulated by thyroid hormone in the developing cerebellum of mice

    International Nuclear Information System (INIS)

    Dong, Hongyan; Yauk, Carole L.; Wade, Michael G.

    2011-01-01

    Highlights: ► Thyroid hormone receptor binds to the promoter region of Barhl1. ► Barhl1 expression in cerebellum is negatively regulated by thyroid hormone. ► Negative regulation of Barhl1 by thyroid hormone was confirmed in vitro. ► Thyroid hormone may play a role in normal brain development through transcriptional control of Barhl1. -- Abstract: Thyroid hormones (THs) are essential for the brain development. Despite considerable effort, few genes directly regulated by THs have been identified. In this study, we investigate the effects of THs on the regulation of Barhl1, a transcription factor that regulates sensorineural development. Using DNA microarray combined with chromatin immunoprecipitation (ChIP-chip), we identified a TRβ binding site in the promoter of Barhl1. The binding was further confirmed by ChIP-PCR. The site is located approximately 755 bp upstream of the transcription start site. Reporter vectors containing the binding site or mutated fragments were transfected into GH3 cells. T3 treatment decreased the transcriptional activity of the wild fragment but not the mutant. Two 28 bp oligonucleotides containing sequences that resemble known TH response elements (TREs) were derived from this binding site and DNA–protein interaction was performed using electrophoretic mobility shift assays (EMSA). Binding analysis in a nuclear extract containing TRβ revealed that one of these fragments bound TRβ. This complex was shifted with the addition of anti-TRβ antibody. We investigated Barhl1 expression in animal models and TH-treated cultured cells. Both long term treatment with 6-propyl-2-thiouracil and short-term treatment with 0.05% methimazole/1% sodium perchlorate (both treatments render mice hypothyroid) resulted in up-regulation of Barhl1. TH supplementation of hypothyroid mice caused a decrease in the expression of Barhl1 compared to control animals. Similarly, the expression of Barhl1 in cultured GH3 decreased with the addition of T3. Given

  2. Development of High-Field Permanent Magnetic Circuits for NMRI/MRI and Imaging on Mice

    Directory of Open Access Journals (Sweden)

    Guangxin Wang

    2016-01-01

    Full Text Available The high-field permanent magnetic circuits of 1.2 T and 1.5 T with novel magnetic focusing and curved-surface correction are developed. The permanent magnetic circuit comprises a magnetic yoke, main magnetic steel, nonspherical curved-surface magnetic poles, plugging magnetic steel, and side magnetic steel. In this work, a novel shimming method is proposed for the effective correction of base magnetic field (B0 inhomogeneities, which is based on passive shimming on the telescope aspheric cutting, grinding, and fine processing technology of the nonspherical curved-surface magnetic poles and active shimming adding higher-order gradient coils. Meanwhile, the magnetic resonance imaging dedicated alloy with high-saturation magnetic field induction intensity and high electrical resistivity is developed, and nonspherical curved-surface magnetic poles which are made of the dedicated alloy have very good anti-eddy-current effect. In addition, the large temperature coefficient problem of permanent magnet can be effectively controlled by using a high quality temperature controller and deuterium external locking technique. Combining our patents such as gradient coil, RF coil, and integration computer software, two kinds of small animal Micro-MRI instruments are developed, by which the high quality MRI images of mice were obtained.

  3. Deletion of Menin in craniofacial osteogenic cells in mice elicits development of mandibular ossifying fibroma.

    Science.gov (United States)

    Lee, S; Liu, P; Teinturier, R; Jakob, J; Tschaffon, M; Tasdogan, A; Wittig, R; Hoeller, S; Baumhoer, D; Frappart, L; Vettorazzi, S; Bertolino, P; Zhang, C; Tuckermann, J

    2018-02-01

    Ossifying fibroma (OF) is a rare benign tumor of the craniofacial bones that can reach considerable and disfiguring dimensions if left untreated. Although the clinicopathological characteristics of OF are well established, the underlying etiology has remained largely unknown. Our work indicates that Men1-a tumor suppressor gene responsible of Multiple endocrine neoplasia type 1-is critical for OF formation and shows that mice with targeted disruption of Men1 in osteoblasts (Men1 Runx2Cre ) develop multifocal OF in the mandible with a 100% penetrance. Using lineage-tracing analysis, we demonstrate that loss of Men1 arrests stromal osteoprogenitors in OF at the osterix-positive pre-osteoblastic differentiation stage. Analysis of Men1-lacking stromal spindle cells isolated from OF (OF-derived MSCs (OFMSCs)) revealed a downregulation of the cyclin-dependent kinase (CDK) inhibitor Cdkn1a, consistent with an increased proliferation rate. Intriguingly, the re-expression of Men1 in Men1-deficient OFMSCs restored Cdkn1a expression and abrogated cellular proliferation supporting the tumor-suppressive role of Men1 in OF. Although our work presents the first evidence of Men1 in OF development, it further provides the first genetic mouse model of OF that can be used to better understand the molecular pathogenesis of these benign tumors and to potentially develop novel treatment strategies.

  4. Allergen-Specific Immunotherapy with Monomeric Allergoid in a Mouse Model of Atopic Dermatitis

    Science.gov (United States)

    Babakhin, Alexander; Andreev, Sergey; Nikonova, Alexandra; Shilovsky, Igor; Buzuk, Andrey; Elisyutina, Olga; Fedenko, Elena; Khaitov, Musa

    2015-01-01

    Atopic dermatitis (AD) is a widespread and difficult to treat allergic skin disease and is a tough challenge for healthcare. In this study, we investigated whether allergen-specific immunotherapy (ASIT) with a monomeric allergoid obtained by succinylation of ovalbumin (sOVA) is effective in a mouse model of atopic dermatitis. An experimental model of AD was reproduced by epicutaneous sensitization with ovalbumin (OVA). ASIT was performed with subcutaneous (SC) administration of increasing doses of OVA or sOVA. The levels of anti-OVA antibodies, as well as cytokines, were detected by ELISA. Skin samples from patch areas were taken for histologic examination. ASIT with either OVA or sOVA resulted in a reduction of both the anti-OVA IgE level and the IgG1/IgG2a ratio. Moreover, ASIT with sOVA increased the IFN-γ level in supernatants after splenocyte stimulation with OVA. Histologic analysis of skin samples from the sites of allergen application showed that ASIT improved the histologic picture by decreasing allergic inflammation in comparison with untreated mice. These data suggest that ASIT with a succinylated allergen represents promising approach for the treatment of AD. PMID:26275152

  5. Gene-Targeted Mice with the Human Troponin T R141W Mutation Develop Dilated Cardiomyopathy with Calcium Desensitization.

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    Mohun Ramratnam

    Full Text Available Most studies of the mechanisms leading to hereditary dilated cardiomyopathy (DCM have been performed in reconstituted in vitro systems. Genetically engineered murine models offer the opportunity to dissect these mechanisms in vivo. We generated a gene-targeted knock-in murine model of the autosomal dominant Arg141Trp (R141W mutation in Tnnt2, which was first described in a human family with DCM. Mice heterozygous for the mutation (Tnnt2R141W/+ recapitulated the human phenotype, developing left ventricular dilation and reduced contractility. There was a gene dosage effect, so that the phenotype in Tnnt2R141W/+mice was attenuated by transgenic overexpression of wildtype Tnnt2 mRNA transcript. Male mice exhibited poorer survival than females. Biomechanical studies on skinned fibers from Tnnt2R141W/+ hearts showed a significant decrease in pCa50 (-log[Ca2+] required for generation of 50% of maximal force relative to wildtype hearts, indicating Ca2+ desensitization. Optical mapping studies of Langendorff-perfused Tnnt2R141W/+ hearts showed marked increases in diastolic and peak systolic intracellular Ca2+ ([Ca2+]i, and prolonged systolic rise and diastolic fall of [Ca2+]i. Perfused Tnnt2R141W/+ hearts had slower intrinsic rates in sinus rhythm and reduced peak heart rates in response to isoproterenol. Tnnt2R141W/+ hearts exhibited a reduction in phosphorylated phospholamban relative to wildtype mice. However, crossing Tnnt2R141W/+ mice with phospholamban knockout (Pln-/- mice, which exhibit increased Ca2+ transients and contractility, had no effect on the DCM phenotype. We conclude that the Tnnt2 R141W mutation causes a Ca2+ desensitization and mice adapt by increasing Ca2+-transient amplitudes, which impairs Ca2+ handling dynamics, metabolism and responses to β-adrenergic activation.

  6. Involvement of host stroma cells and tissue fibrosis in pancreatic tumor development in transgenic mice.

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    Itai Spector

    Full Text Available INTRODUCTION: Stroma cells and extracellular matrix (ECM components provide the pivotal microenvironment for tumor development. The study aimed to evaluate the importance of the pancreatic stroma for tumor development. METHODS: Pancreatic tumor cells were implanted subcutaneously into green fluorescent protein transgenic mice, and stroma cells invading the tumors were identified through immunohistochemistry. Inhibition of tumor invasion by stroma cells was achieved with halofuginone, an inhibitor of TGFβ/Smad3 signaling, alone or in combination with chemotherapy. The origin of tumor ECM was evaluated with species-specific collagen I antibodies and in situ hybridization of collagen α1(I gene. Pancreatic fibrosis was induced by cerulean injection and tumors by spleen injection of pancreatic tumor cells. RESULTS: Inhibition of stroma cell infiltration and reduction of tumor ECM levels by halofuginone inhibited development of tumors derived from mouse and human pancreatic cancer cells. Halofuginone reduced the number only of stroma myofibroblasts expressing both contractile and collagen biosynthesis markers. Both stroma myofibroblasts and tumor cells generated ECM that contributes to tumor growth. Combination of treatments that inhibit stroma cell infiltration, cause apoptosis of myofibroblasts and inhibit Smad3 phosphorylation, with chemotherapy that increases tumor-cell apoptosis without affecting Smad3 phosphorylation was more efficacious than either treatment alone. More tumors developed in fibrotic than in normal pancreas, and prevention of tissue fibrosis greatly reduced tumor development. CONCLUSIONS: The utmost importance of tissue fibrosis and of stroma cells for tumor development presents potential new therapy targets, suggesting combination therapy against stroma and neoplastic cells as a treatment of choice.

  7. Adiponectin haploinsufficiency promotes mammary tumor development in MMTV-PyVT mice by modulation of phosphatase and tensin homolog activities.

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    Janice B B Lam

    Full Text Available Adiponectin is an adipokine possessing beneficial effects on obesity-related medical complications. A negative association of adiponectin levels with breast cancer development has been demonstrated. However, the precise role of adiponectin deficiency in mammary carcinogenesis remains elusive.In the present study, MMTV-polyomavirus middle T antigen (MMTV-PyVT transgenic mice with reduced adiponectin expressions were established and the stromal effects of adiponectin haploinsufficiency on mammary tumor development evaluated. In mice from both FVB/N and C57BL/6J backgrounds, insufficient adiponectin production promoted mammary tumor onset and development. A distinctive basal-like subtype of tumors, with a more aggressive phenotype, was derived from adiponectin haplodeficient MMTV-PyVT mice. Comparing with those from control MMTV-PyVT mice, the isolated mammary tumor cells showed enhanced tumor progression in re-implanted nude mice, accelerated proliferation in primary cultures, and hyperactivated phosphatidylinositol-3-kinase (PI3K/Akt/beta-catenin signaling, which at least partly attributed to the decreased phosphatase and tensin homolog (PTEN activities. Further analysis revealed that PTEN was inactivated by a redox-regulated mechanism. Increased association of PTEN-thioredoxin complexes was detected in tumors derived from mice with reduced adiponectin levels. The activities of thioredoxin (Trx1 and thioredoxin reductase (TrxR1 were significantly elevated, whereas treatment with either curcumin, an irreversible inhibitor of TrxR1, or adiponectin largely attenuated their activities and resulted in the re-activation of PTEN in these tumor cells. Moreover, adiponectin could inhibit TrxR1 promoter-mediated transcription and restore the mRNA expressions of TrxR1.Adiponectin haploinsufficiency facilitated mammary tumorigenesis by down-regulation of PTEN activity and activation of PI3K/Akt signalling pathway through a mechanism involving Trx1/TrxR1

  8. Purified blueberry anthocyanins and blueberry juice alter development of obesity in mice fed an obesogenic high-fat diet.

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    Prior, Ronald L; E Wilkes, Samuel; R Rogers, Theodore; Khanal, Ramesh C; Wu, Xianli; Howard, Luke R

    2010-04-14

    Male C57BL/6J mice (25 days of age) were fed either a low-fat diet (10% kcal from fat) (LF) or a high-fat diet (45% kcal from fat) (HF45) for a period of 72 days. Blueberry juice or purified blueberry anthocyanins (0.2 or 1.0 mg/mL) in the drinking water were included in LF or HF45 treatments. Sucrose was added to the drinking water of one treatment to test if the sugars in blueberry juice would affect development of obesity. Total body weights (g) and body fat (%) were higher and body lean tissue (%) was lower in the HF45 fed mice compared to the LF fed mice after 72 days, but in mice fed HF45 diet plus blueberry juice or blueberry anthocyanins (0.2 mg/mL), body fat (%) was not different from those mice fed the LF diet. Anthocyanins (ACNs) decreased retroperitoneal and epididymal adipose tissue weights. Fasting serum glucose concentrations were higher in mice fed the HF45 diet. However, it was reduced to LF levels in mice fed the HF45 diet plus 0.2 mg of ACNs/mL in the drinking water, but not with blueberry juice. beta cell function (HOMA-BCF) score was lowered with HF45 feeding but returned to normal levels in mice fed the HF45 diet plus purified ACNs (0.2 mg/mL). Serum leptin was elevated in mice fed HF45 diet, and feeding either blueberry juice or purified ACNs (0.2 mg/mL) decreased serum leptin levels relative to HF45 control. Sucrose in drinking water, when consumption was restricted to the volume of juice consumed, produced lower serum leptin and insulin levels, leptin/fat, and retroperitoneal and total fat (% BW). Blueberry juice was not as effective as the low dose of anthocyanins in the drinking water in preventing obesity. Additional studies are needed to determine factors responsible for the differing responses of blueberry juice and whole blueberry in preventing the development of obesity.

  9. Eczema, Atopic Dermatitis, or Atopic Eczema: Analysis of Global Search Engine Trends.

    Science.gov (United States)

    Xu, Shuai; Thyssen, Jacob P; Paller, Amy S; Silverberg, Jonathan I

    The lack of standardized nomenclature for atopic dermatitis (AD) creates challenges for scientific communication, patient education, and advocacy. We sought to determine the relative popularity of the terms eczema, AD, and atopic eczema (AE) using global search engine volumes. A retrospective analysis of average monthly search volumes from 2014 to 2016 of Google, Bing/Yahoo, and Baidu was performed for eczema, AD, and AE in English and 37 other languages. Google Trends was used to determine the relative search popularity of each term from 2006 to 2016 in English and the top foreign languages, German, Turkish, Russian, and Japanese. Overall, eczema accounted for 1.5 million monthly searches (84%) compared with 247 000 searches for AD (14%) and 44 000 searches for AE (2%). For English language, eczema accounted for 93% of searches compared with 6% for AD and 1% for AE. Search popularity for eczema increased from 2006 to 2016 but remained stable for AD and AE. Given the ambiguity of the term eczema, we recommend the universal use of the next most popular term, AD.

  10. Diet Quality throughout Early Life in Relation to Allergic Sensitization and Atopic Diseases in Childhood

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    Anh N. Nguyen

    2017-08-01

    Full Text Available Early-life nutrition is an important modifiable determinant in the development of a child’s immune system, and may thereby influence the risk of allergic sensitization and atopic diseases. However, associations between overall dietary patterns and atopic diseases in childhood remain unclear. We examined associations of diet quality in early life with allergic sensitization, self-reported physician-diagnosed inhalant and food allergies, eczema, and asthma among 5225 children participating in a population-based cohort in the Netherlands. Diet was assessed during pregnancy, infancy, and childhood using validated food-frequency questionnaires. We calculated food-based diet quality scores (0–10 or 0–15, reflecting adherence to dietary guidelines. At age 10 years, allergic sensitization was assessed with skin prick tests. Information on physician-diagnosed inhalant and food allergies, eczema, and asthma was obtained with questionnaires. We observed no associations between diet quality during pregnancy and allergic sensitization (odds ratio (OR = 1.05 per point in the diet score, 95% confidence interval (CI: 0.99, 1.13, allergies (0.96, 95% CI: 0.88, 1.04, eczema (0.99, 95% CI: 0.93, 1.06, or asthma (0.93, 95% CI: 0.85, 1.03 in childhood. Also, diet quality in infancy or childhood were not associated with atopic outcomes in childhood. Our findings do not support our hypothesis that a healthy dietary pattern in early life is associated with a lower risk of allergic sensitization or atopic diseases in childhood.

  11. [Written personalized action plan for atopic dermatitis: a patient education tool].

    Science.gov (United States)

    Gabeff, R; Assathiany, R; Barbarot, S; Salinier, C; Stalder, J-F

    2014-07-01

    Atopic dermatitis (AD) is the most frequent children's chronic skin disease. Management of AD can be difficult because local treatments must be adapted to the skin's condition. Between consultations, sudden changes in the state of the disease can make it difficult to manage local treatment. Parents and children need information that will help them adapt their treatment to the course of their disease. Aiming to enable parents to better treat their atopic child by themselves, we have developed a personalized action plan in order to simplify, personalize, and adapt the medical prescription to the state of the disease. The Personalized Written Action Plan for Atopics (PA2P) is based on the model used in the treatment of asthma, with integrated specificities for AD in children. The aim of this study was to assess the feasibility and pertinence of the PA2P for pediatricians to use in private practice. A total of 479 pediatricians answered a questionnaire sent by e-mail. The vast majority of the respondents gave positive reviews of the tool: 99% of the pediatricians declared the tool to be pertinent, qualifying it as clear and logical. The PA2P appeared to be appropriate for the atopic patient because it improves the families' involvement in the application of local treatment by offering personalized care and by simplifying the doctor's prescription. Finally, 72% of doctors responding to the questionnaire were willing to take part in future studies involving parents. More than a gadget, the PA2P could become a useful tool for therapeutic patient education. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Adherence to recommendations for primary prevention of atopic disease in neonatology clinical practice.

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    Passariello, Annalisa; Terrin, Gianluca; Baldassarre, Maria E; Bisceglia, Massimo; Ruotolo, Serena; Berni Canani, Roberto

    2010-08-01

    The prevalence and severity of atopic manifestations in children are increasing in western countries in the last decades. Specific nutritional intervention may prevent or delay the onset of atopic diseases in infants at high risk of developing allergy. These nutritional interventions should be applied early in the perinatal period to have a chance of success. Thus, we assessed adherence to the dietary management recommendations of the Committee on Nutrition and Section on Allergy and Immunology of the American Academy of Pediatrics (AAP) for the prevention of atopic diseases in neonatal age through an audit study. Questionnaire was administered to the chiefs of 30 maternity units (MU) with more than 1500 live births/yr to report the policy applied in their MU. Twenty-two MU returned the questionnaire. Identification of high-risk newborns was routinely performed only in 7/22 MU (31.8%). High-risk newborns were identified by the presence of at least two or one first-degree relative (parent or sibling) with documented allergic disease by 18.2% and 45.5% of MU, respectively. Specific maternal dietary restrictions during lactation were adopted in 7/22 MU (31.8%). Extensively or partially hydrolyzed formula was prescribed for bottle-fed high-risk infants in 22.7% of MU. Only 2/22 MU have a policy in complete agreement with the nutritional intervention proposed by the AAP. Our study suggest a poor adherence to dietary recommendations for primary prevention of atopic disease in neonatology clinical practice. Further efforts should be planned to improve the knowledge and the application of these preventive strategies.

  13. Ozone-Induced Nasal Type 2 Immunity in Mice Is Dependent on Innate Lymphoid Cells.

    Science.gov (United States)

    Kumagai, Kazuyoshi; Lewandowski, Ryan; Jackson-Humbles, Daven N; Li, Ning; Van Dyken, Steven J; Wagner, James G; Harkema, Jack R

    2016-06-01

    Epidemiological studies suggest that elevated ambient concentrations of ozone are associated with activation of eosinophils in the nasal airways of atopic and nonatopic children. Mice repeatedly exposed to ozone develop eosinophilic rhinitis and type 2 immune responses. In this study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced eosinophilic rhinitis by using lymphoid-sufficient C57BL/6 mice, Rag2(-/-) mice that are devoid of T cells and B cells, and Rag2(-/-)Il2rg(-/-) mice that are depleted of all lymphoid cells including ILCs. The animals were exposed to 0 or 0.8 ppm ozone for 9 consecutive weekdays (4 h/d). Mice were killed 24 hours after exposure, and nasal tissues were selected for histopathology and gene expression analysis. ILC-sufficient C57BL/6 and Rag2(-/-) mice exposed to ozone developed marked eosinophilic rhinitis and epithelial remodeling (e.g., epithelial hyperplasia and mucous cell metaplasia). Chitinase-like proteins and alarmins (IL-33, IL-25, and thymic stromal lymphopoietin) were also increased morphometrically in the nasal epithelium of ozone-exposed C57BL/6 and Rag2(-/-) mice. Ozone exposure elicited increased expression of Il4, Il5, Il13, St2, eotaxin, MCP-2, Gob5, Arg1, Fizz1, and Ym2 mRNA in C57BL/6 and Rag2(-/-) mice. In contrast, ozone-exposed ILC-deficient Rag2(-/-)Il2rg(-/-) mice had no nasal lesions or overexpression of Th2- or ILC2-related transcripts. These results indicate that ozone-induced eosinophilic rhinitis, nasal epithelial remodeling, and type 2 immune activation are dependent on ILCs. To the best of our knowledge, this is the first study to demonstrate that ILCs play an important role in the nasal pathology induced by repeated ozone exposure.

  14. Current Views on the Pathogenesis and Principles of External Treatment of Atopic Dermatitis in Children

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    Nikolay N. Murashkin

    2016-01-01

    Full Text Available The article analyzes the current data on the pathogenesis of atopic dermatitis. It discusses the role of the damaged dermal barrier structure in the development of food allergies and presents the results confirming the theory of transdermal sensibilisation to allergens in addition to hereditary and exogenous factors. Current local treatment of atopic dermatitis using topical glucocorticosteroids (tGCs aimed at reducing the severity of symptoms is often associated with the risk of complications. The data on the effective use of topical calcineurin inhibitors (TCI to eliminate the side effects of tGCs are presented. The results of the possible use of pimecrolimus in the form of 1% cream for gradual withdrawal of tGCs in the long-term use are shown. The data of reviews and meta-analyses for the last decade are given showing that there is no evidence that the use of TIC is associated with an increased risk of lymphoma. The authors conclude that pimecrolimus in the form of 1% cream is the best medication for topical therapy in children with mild and moderate form of the disease. It is also considered the best preparation for the proactive treatment of atopic dermatitis in the long period of time in order to prevent recurrences.

  15. Signal transduction around thymic stromal lymphopoietin (TSLP in atopic asthma

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    Kuepper Michael

    2008-08-01

    Full Text Available Abstract Thymic stromal lymphopoietin (TSLP, a novel interleukin-7-like cytokine, triggers dendritic cell-mediated inflammatory responses ultimately executed by T helper cells of the Th2 subtype. TSLP emerged as a central player in the development of allergic symptoms, especially in the airways, and is a prime regulatory cytokine at the interface of virus- or antigen-exposed epithelial cells and dendritic cells (DCs. DCs activated by epithelium-derived TSLP can promote naïve CD4+ T cells to adopt a Th2 phenotype, which in turn recruite eosinophilic and basophilic granulocytes as well as mast cells into the airway mucosa. These different cells secrete inflammatory cytokines and chemokines operative in inducing an allergic inflammation and atopic asthma. TSLP is, thus, involved in the control of both an innate and an adaptive immune response. Since TSLP links contact of allergen with the airway epithelium to the onset and maintainance of the asthmatic syndrome, defining the signal transduction underlying TSLP expression and function is of profound interest for a better understandimg of the disease and for the development of new therapeutics.

  16. Genetic pharmacotherapy as an early CNS drug development strategy: testing glutaminase inhibition for schizophrenia treatment in adult mice

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    Susana eMingote

    2016-01-01

    Full Text Available Genetic pharmacotherapy is an early drug development strategy for the identification of novel CNS targets in mouse models prior to the development of specific ligands. Here for the first time, we have implemented this strategy to address the potential therapeutic value of a glutamate-based pharmacotherapy for schizophrenia involving inhibition of the glutamate recycling enzyme phosphate-activated glutaminase. Mice constitutively heterozygous for GLS1, the gene encoding glutaminase, manifest a schizophrenia resilience phenotype, a key dimension of which is an attenuated locomotor response to propsychotic amphetamine challenge. If resilience is due to glutaminase deficiency in adulthood, then glutaminase inhibitors should have therapeutic potential. However, this has been difficult to test given the dearth of neuroactive glutaminase inhibitors. So, we used genetic pharmacotherapy to test the therapeutic potential of glutaminase inhibition. We specifically asked whether adult induction of GLS1 heterozygosity would attenuate amphetamine responsiveness. We generated conditional floxGLS1 mice and crossed them with global CAG ERT2 cre/+ mice to produce GLS1 iHET mice, susceptible to tamoxifen induction of GLS1 heterozygosity. One month after tamoxifen treatment of adult GLS1 iHET mice, we found a 50% reduction in GLS1 allelic abundance and glutaminase mRNA levels in the brain. While GLS1 iHET mice showed some recombination prior to tamoxifen, there was no impact on mRNA levels. We then asked whether induction of GLS heterozygosity would attenuate the locomotor response to propsychotic amphetamine challenge. Before tamoxifen, control and GLS1 iHET mice did not differ in their response to amphetamine. One month after tamoxifen treatment, amphetamine-induced hyperlocomotion was blocked in GLS1 iHET mice. The block was largely maintained after 5 months. Thus, a genetically induced glutaminase reduction — mimicking pharmacological inhibition — strongly

  17. Toll-like receptor 2 signaling protects mice from tumor development in a mouse model of colitis-induced cancer.

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    Emily L Lowe

    2010-09-01

    Full Text Available Inflammatory bowel disease (IBD is a disorder of chronic inflammation with increased susceptibility to colorectal cancer. The etiology of IBD is unclear but thought to result from a dysregulated adaptive and innate immune response to microbial products in a genetically susceptible host. Toll-like receptor (TLR signaling induced by intestinal commensal bacteria plays a crucial role in maintaining intestinal homeostasis, innate immunity and the enhancement of intestinal epithelial cell (IEC integrity. However, the role of TLR2 in the development of colorectal cancer has not been studied. We utilized the AOM-DSS model for colitis-associated colorectal cancer (CAC in wild type (WT and TLR2(-/- mice. Colons harvested from WT and TLR2(-/- mice were used for histopathology, immunohistochemistry, immunofluorescence and cytokine analysis. Mice deficient in TLR2 developed significantly more and larger colorectal tumors than their WT controls. We provide evidence that colonic epithelium of TLR2(-/- mice have altered immune responses and dysregulated proliferation under steady-state conditions and during colitis, which lead to inflammatory growth signals and predisposition to accelerated neoplastic growth. At the earliest time-points assessed, TLR2(-/- colons exhibited a significant increase in aberrant crypt foci (ACF, resulting in tumors that developed earlier and grew larger. In addition, the intestinal microenvironment revealed significantly higher levels of IL-6 and IL-17A concomitant with increased phospho-STAT3 within ACF. These observations indicate that in colitis, TLR2 plays a protective role against the development of CAC.

  18. Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice

    NARCIS (Netherlands)

    Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even; Hao, Qin; Hugenholtz, Floor; Sonne, Si Brask; Derrien, Muriel; Pedersen, Lone Møller; Petersen, Rasmus Koefoed; Mortensen, Alicja; Licht, Tine Rask; Rømer, Maria Unni; Vogel, Ulla Birgitte; Waagbø, Linn Jeanette; Giallourou, Natasa; Feng, Qiang; Xiao, Liang; Liu, Chuan; Liaset, Bjørn; Kleerebezem, Michiel; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

    2016-01-01

    Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low

  19. Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice

    NARCIS (Netherlands)

    Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even; Hao, Qin; Hugenholtz, Floor; Sonne, Si Brask; Derrien, Muriel; Pedersen, Lone Møller; Petersen, Rasmus Koefoed; Mortensen, Alicja; Licht, Tine Rask; Rømer, Maria Unni; Vogel, Ulla Birgitte; Waagbø, Linn Jeanette; Giallourou, Natasa; Feng, Qiang; Xiao, Liang; Liu, Chuan; Liaset, Bjørn; Kleerebezem, Michiel; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

    2016-01-01

    Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose

  20. Muscle-directed gene therapy for phenylketonuria (PKU): Development of transgenic mice with muscle-specific phenylalanine hydroxylase expression

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    Harding, C.O.; Messing, A.; Wolff, J.A. [Univ. of Wisconsin, Madison, WI (United States)

    1994-09-01

    Phenylketonuria (PKU) is an attractive target for gene therapy because of shortcomings in current therapy including lifelong commitment to a difficult and expensive diet, persistent mild cognitive deficits in some children despite adequate dietary therapy, and maternal PKU syndrome. Phenylalanine hydroxylase (PAH) is normally expressed only in liver, but we propose to treat PKU by introducing the gene for PAH into muscle. In order to evaluate both the safety and efficacy of this approach, we have a developed a trangenic mouse which expresses PAH in both cardiac and skeletal muscle. The transgene includes promoter and enhancer sequences from the mouse muscle creatine kinase (MCK) gene fused to the mouse liver PAH cDNA. Mice which have inherited the transgene are healthy, active, and do not exhibit any signs of muscle weakness or wasting. Ectopic PAH expression in muscle is not detrimental to the health, neurologic function, or reproduction of the mice. Pah{sup enu2} hyperphenylalaninemic mice, a model of human PAH deficiency, bred to carry the transgene have substantial PAH expression in cardiac and skeletal muscle but none in liver. Muscle PAH expression alone does not complement the hyperphenylalaninemic phenotype of Pah{sup enu2} mice. However, administration of reduced tetrahydrobiopterin to transgenic Pah{sup enu2} mice is associated with a 25% mean decrease in serum phenylalanine levels. We predict that ectopic expression of PAH in muscle along with adequate muscle supplies of reduced biopterin cofactor will decrease hyperphenylalaninemia in PKU.

  1. Development of donor-derived thymic lymphomas after allogeneic bone marrow transplantation in AKR/J mice

    International Nuclear Information System (INIS)

    Yasumizu, R.; Hiai, H.; Sugiura, K.

    1988-01-01

    The transplantation of bone marrow cells from BALB/c (but not C57BL/6 and C3H/HeN) mice was observed to lead to the development of thymic lymphomas (leukemias) in AKR/J mice. Two leukemic cell lines, CAK1.3 and CAK4.4, were established from the primary culture of two thymic lymphoma, and surface phenotypes of these cell lines found to be H-2d and Thy-1.2+, indicating that these lymphoma cells are derived from BALB/c donor bone marrow cells. Further analyses of surface markers revealed that CAK1.3 is L3T4+ Lyt2+ IL2R-, whereas CAK4.4 is L3T4- Lyt2- IL2R+. Both CAK1.3 and CAK4.4 were transplantable into BALB/c but not AKR/J mice, further indicating that these cells are of BALB/c bone marrow donor origin. The cells were found to produce XC+-ecotropic viruses, but xenotropic and mink cell focus-forming viruses were undetectable. Inasmuch as thymic lymphomas are derived from bone marrow cells of leukemia-resistant BALB/c strain of mice under the allogeneic environment of leukemia-prone AKR/J mice, this animal model may serve as a useful tool not only for the analysis of leukemic relapse after bone marrow transplantation but also for elucidation of the mechanism of leukemogenesis

  2. An update on the treatment of canine atopic dermatitis

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    Marsella R

    2012-08-01

    Full Text Available Rosanna MarsellaDepartment of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida Gainesville, FL, USAAbstract: Remarkable progress has been made in recent years concerning our understanding of the pathogenesis of canine atopic dermatitis (AD. As our understanding improves, the therapeutic approach evolves. Of utmost importance is the documentation of skin barrier impairment in canine AD: ceramides deficiency leads to increased permeability and increased allergen penetration and sensitization. It is currently unknown whether this dysfunction is primary and genetically inherited or secondary to inflammation but it is accepted that skin barrier deficiency plays an important role in either starting or minimally exacerbating canine AD. Thus, the therapeutic approach has changed from focusing on the control of the inflammation to a combined approach that includes therapies aimed at skin barrier repair. The issue of skin barrier repair has been addressed both with oral administration of essential fatty acids and the topical application of products containing a combination of ceramides and fatty acids. These strategies are most helpful as adjunctive treatments and would be best used in young patients that have not developed chronic skin changes. Importantly, treatment for canine AD is multimodal and tailored to the individual patient, the age, and the duration of the disease. Client education plays an important role in explaining the importance of a long-term approach to minimize flare-ups and, in this context, topical therapy to correct skin barrier can be of great benefit. This is an area still in infancy and much work is needed to identify the best formulation. In human medicine, long-term use of moisturizers can have a profound effect on skin barrier and gene expression of proteins involved in skin barrier. This effect is variable depending on the formulation used. It is reasonable to speculate that the same may be

  3. Sox9-dependent expression of Gstm6 in Sertoli cells during testis development in mice.

    Science.gov (United States)

    Beverdam, Annemiek; Svingen, Terje; Bagheri-Fam, Stefan; Bernard, Pascal; McClive, Peter; Robson, Mathew; Khojasteh, Mahdi Banan; Salehi, Mahboubeh; Sinclair, Andrew H; Harley, Vincent R; Koopman, Peter

    2009-03-01

    Glutathione S-transferases (GSTs) are an important family of multifunctional enzymes that play a role in the protection of tissues by the detoxification of hazardous and carcinogenic compounds. We found previously that Gstm6 is upregulated in the somatic cells of male mouse fetal gonads relative to female gonads. In this study, we describe the spatial and temporal expression pattern of Gstm6 during mouse development. We show that Gstm6 is predominantly expressed in the reproductive system, at significantly higher levels in XY gonads compared with XX gonads from 11.5 dpc onwards, and remains expressed in the testes in adult mice. Its expression is associated with the Sertoli cell lineage, and is dependent on the expression of the male sex-determining gene Sox9. Our data suggest that Gstm6 plays a male-specific role in gonad development or function, possibly by modulating the exposure of somatic tissue and/or germ cells to endogenous or exogenous toxicants.

  4. Effects of chronic carbon monoxide exposure on fetal growth and development in mice

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    Venditti Carolina C

    2011-12-01

    Full Text Available Abstract Background Carbon monoxide (CO is produced endogenously, and can also be acquired from many exogenous sources: ie. cigarette smoking, automobile exhaust. Although toxic at high levels, low level production or exposure lends to normal physiologic functions: smooth muscle cell relaxation, control of vascular tone, platelet aggregation, anti- inflammatory and anti-apoptotic events. In pregnancy, it is unclear at what level maternal CO exposure becomes toxic to the fetus. In this study, we hypothesized that CO would be embryotoxic, and we sought to determine at what level of chronic CO exposure in pregnancy embryo/fetotoxic effects are observed. Methods Pregnant CD1 mice were exposed to continuous levels of CO (0 to 400 ppm from conception to gestation day 17. The effect on fetal/placental growth and development, and fetal/maternal CO concentrations were determined. Results Maternal and fetal CO blood concentrations ranged from 1.12- 15.6 percent carboxyhemoglobin (%COHb and 1.0- 28.6%COHb, respectively. No significant difference was observed in placental histological morphology or in placental mass with any CO exposure. At 400 ppm CO vs. control, decreased litter size and fetal mass (p Conclusions Exposure to levels at or below 300 ppm CO throughout pregnancy has little demonstrable effect on fetal growth and development in the mouse.

  5. Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer's disease transgenic mice.

    Science.gov (United States)

    Cheng, David; Spiro, Adena S; Jenner, Andrew M; Garner, Brett; Karl, Tim

    2014-01-01

    Impairments in cognitive ability and widespread pathophysiological changes caused by neurotoxicity, neuroinflammation, oxidative damage, and altered cholesterol homeostasis are associated with Alzheimer's disease (AD). Cannabidiol (CBD) has been shown to reverse cognitive deficits of AD transgenic mice and to exert neuroprotective, anti-oxidative, and anti-inflammatory properties in vitro and in vivo. Here we evaluate the preventative properties of long-term CBD treatment in male AβPPSwe/PS1ΔE9 (AβPP × PS1) mice, a transgenic model of AD. Control and AD transgenic mice were treated orally from 2.5 months of age with CBD (20 mg/kg) daily for 8 months. Mice were then assessed in the social preference test, elevated plus maze, and fear conditioning paradigms, before cortical and hippocampal tissues were analyzed for amyloid load, oxidative damage, cholesterol, phytosterols, and inflammation. We found that AβPP × PS1 mice developed a social recognition deficit, which was prevented by CBD treatment. CBD had no impact on anxiety or associative learning. The prevention of the social recognition deficit was not associated with any changes in amyloid load or oxidative damage. However, the study revealed a subtle impact of CBD on neuroinflammation, cholesterol, and dietary phytosterol retention, which deserves further investigation. This study is the first to demonstrate CBD's ability to prevent the development of a social recognition deficit in AD transgenic mice. Our findings provide the first evidence that CBD may have potential as a preventative treatment for AD with a particular relevance for symptoms of social withdrawal and facial recognition.

  6. Gender-specific effects of endogenous testosterone: female alpha-estrogen receptor-deficient C57Bl/6J mice develop glomerulosclerosis.

    Science.gov (United States)

    Elliot, S J; Berho, M; Korach, K; Doublier, S; Lupia, E; Striker, G E; Karl, M

    2007-08-01

    Young female mice on a C57Bl/6J (B6) background are considered glomerulosclerosis (GS)-resistant but aging B6 mice develop mild GS. Estrogen deficiency accelerates while estrogen replacement retards GS in young sclerosis-prone oligosyndactyly mutant mice on an ROP background. To explore the effects of sex hormones on glomerular structure and function in the context of gender and genetic background, we studied mice in which the estrogen-receptor (ER) genes alpha- or -beta were deleted (alpha- or betaER knockout (KO)) and crossed into the B6 background. We also studied ovariectomized (Ovx) B6 mice given testosterone. Male and female betaERKO and male alphaERKO mice had no glomerular dysfunction at 9 months of age; however, alphaERKO female mice displayed albuminuria and GS. Ovx prevented glomerular dysfunction in alphaERKO female mice by eliminating endogenous testosterone production while exogenous testosterone induced GS in Ovx B6 mice. Androgen receptor (AR) expression and function was found in microdissected glomeruli and cultured mesangial cells. Testosterone compared to placebo increased both AR expression and TGF-beta1 mRNA levels in glomeruli isolated from female B6 mice. Estrogen deficiency had no deleterious effects on the glomeruli in B6 mice. Our study shows that genetic traits strongly influence the GS-promoting effects of estrogen deficiency while testosterone induces GS in a gender-specific manner.

  7. Role of subchondral bone properties and changes in development of load-induced osteoarthritis in mice.

    Science.gov (United States)

    Adebayo, O O; Ko, F C; Wan, P T; Goldring, S R; Goldring, M B; Wright, T M; van der Meulen, M C H

    2017-12-01

    Animal models recapitulating post-traumatic osteoarthritis (OA) suggest that subchondral bone (SCB) properties and remodeling may play major roles in disease initiation and progression. Thus, we investigated the role of SCB properties and its effects on load-induced OA progression by applying a tibial loading model on two distinct mouse strains treated with alendronate (ALN). Cyclic compression was applied to the left tibia of 26-week-old male C57Bl/6 (B6, low bone mass) and FVB (high bone mass) mice. Mice were treated with ALN (26 μg/kg/day) or vehicle (VEH) for loading durations of 1, 2, or 6 weeks. Changes in articular cartilage and subchondral and epiphyseal cancellous bone were analyzed using histology and microcomputed tomography. FVB mice exhibited thicker cartilage, a thicker SCB plate, and higher epiphyseal cancellous bone mass and tissue mineral density than B6 mice. Loading induced cartilage pathology, osteophyte formation, and SCB changes; however, lower initial SCB mass and stiffness in B6 mice did not attenuate load-induced OA severity compared to FVB mice. By contrast, FVB mice exhibited less cartilage damage, and slower-growing and less mature osteophytes. In B6 mice, inhibiting bone remodeling via ALN treatment exacerbated cartilage pathology after 6 weeks of loading, while in FVB mice, inhibiting bone remodeling protected limbs from load-induced cartilage loss. Intrinsically lower SCB properties were not associated with attenuated load-induced cartilage loss. However, inhibiting bone remodeling produced differential patterns of OA pathology in animals with low compared to high SCB properties, indicating that these factors do influence load-induced OA progression. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  8. Adam8 Limits the Development of Allergic Airway Inflammation in Mice

    Science.gov (United States)

    Knolle, Martin D.; Nakajima, Takahiro; Hergrueter, Anja; Gupta, Kushagra; Polverino, Francesca; Craig, Vanessa J.; Fyfe, Susanne E.; Zahid, Muhammad; Permaul, Perdita; Cernadas, Manuela; Montano, Gilbert; Tesfaigzi, Yohannes; Sholl, Lynette; Kobzik, Lester; Israel, Elliot; Owen, Caroline A.

    2013-01-01

    To determine whether a disintegrin and a metalloproteinase-8 (Adam8) regulates allergic airway inflammation (AAI) and airway hyper-responsiveness (AHR), we compared AAI and AHR in wild type (WT) versus Adam8−/− mice in different genetic backgrounds sensitized and challenged with ovalbumin (OVA) or house dust mite protein extract (HDM). OVA- and HDM-treated Adam8−/− mice had higher lung leukocyte counts, more airway mucus metaplasia, greater lung levels of some TH2 cytokines, and higher methacholine-induced increases in central airway resistance than allergen-treated WT mice. Studies of OVA-treated Adam8 bone marrow chimeric mice confirmed that leukocyte-derived Adam8 predominantly mediated Adam8’s anti-inflammatory activities in murine airways. Airway eosinophils and macrophages both expressed Adam8 in WT mice with AAI. Adam8