WorldWideScience

Sample records for contact hypersensitivity induced

  1. Hapten-Induced Contact Hypersensitivity, Autoimmune Reactions, and Tumor Regression: Plausibility of Mediating Antitumor Immunity

    Directory of Open Access Journals (Sweden)

    Dan A. Erkes

    2014-01-01

    Full Text Available Haptens are small molecule irritants that bind to proteins and elicit an immune response. Haptens have been commonly used to study allergic contact dermatitis (ACD using animal contact hypersensitivity (CHS models. However, extensive research into contact hypersensitivity has offered a confusing and intriguing mechanism of allergic reactions occurring in the skin. The abilities of haptens to induce such reactions have been frequently utilized to study the mechanisms of inflammatory bowel disease (IBD to induce autoimmune-like responses such as autoimmune hemolytic anemia and to elicit viral wart and tumor regression. Hapten-induced tumor regression has been studied since the mid-1900s and relies on four major concepts: (1 ex vivo haptenation, (2 in situ haptenation, (3 epifocal hapten application, and (4 antigen-hapten conjugate injection. Each of these approaches elicits unique responses in mice and humans. The present review attempts to provide a critical appraisal of the hapten-mediated tumor treatments and offers insights for future development of the field.

  2. Arsenic-induced alterations in the contact hypersensitivity response in Balb/c mice

    International Nuclear Information System (INIS)

    Patterson, Rachel; Vega, Libia; Trouba, Kevin; Bortner, Carl; Germolec, Dori

    2004-01-01

    Previous studies in our laboratory indicate that arsenic alters secretion of growth promoting and inflammatory cytokines in the skin that can regulate the migration and maturation of Langerhans cells (LC) during allergic contact dermatitis. Therefore, we hypothesized that arsenic may modulate hypersensitivity responses to cutaneous sensitizing agents by altering cytokine production, LC migration, and T-cell proliferation. To investigate this hypothesis, we examined the induction and elicitation phases of dermal sensitization. Mice exposed to 50 mg/l arsenic in the drinking water for 4 weeks demonstrated a reduction in lymph node cell (LNC) proliferation and ear swelling following sensitization with 2,4-dinitrofluorobenzene (DNFB), compared to control mice. LC and T-cell populations in the draining lymph nodes of DNFB-sensitized mice were evaluated by fluorescence-activated cell sorting; activated LC were reduced in cervical lymph nodes, suggesting that LC migration may be altered following arsenic exposure. Lymphocytes from arsenic-treated animals sensitized with fluorescein isothiocyanate (FITC) exhibited reduced proliferative responses following T-cell mitogen stimulation in vitro; however, lymphocyte proliferation from nonsensitized, arsenic-treated mice was comparable to controls. Arsenic exposure also reduced the number of thioglycollate-induced peritoneal macrophages and circulating neutrophils. These studies demonstrate that repeated, prolonged exposure to nontoxic concentrations of sodium arsenite alters immune cell populations and results in functional changes in immune responses, specifically attenuation of contact hypersensitivity

  3. A garlic extract protects from ultraviolet B (280-320 nm) radiation-induced suppression of contact hypersensitivity

    International Nuclear Information System (INIS)

    Reeve, V.E.; Bosnic, M.; Rozinova, E.; Boehm-Wilcox, C.

    1993-01-01

    Lyophilized aged garlic extract has been incorporated at concentrations of 0.1%, 1% and 4% by weight into semi purified powdered diets and fed to hairless mice. Under moderate UVB exposure conditions resulting in 58% suppression of the systemic contact hypersensitivity response in control-fed mice, a dose-responsive protection was observed in the garlic-fed mice; contact hypersensitivity in the UVB-exposed mice fed 4% garlic extract was suppressed by only 19%. If the UVB exposure was replaced by topical application of one of a series of lotions containing increasing concentrations of cis-urocanic acid, a dose-responsive suppression of contact hypersensitivity was demonstrated in control-fed mice (urocanic acid at 25, 50, 100 and 200 micrograms per mouse resulting in 22-46% suppression). Mice fed a diet containing 1% aged garlic extract were partially protected from cis-urocanic acid-induced suppression of contact hypersensitivity, with greater protection from the lower concentrations of urocanic acid. Mice fed a diet containing 4% aged garlic extract were protected from all concentrations of urocanic acid. The results indicate that aged garlic extract contains ingredient(s) that protect from UVB-induced suppression of contact hypersensitivity and suggest that the mechanism of protection is by antagonism of the cis-urocanic acid mediation of this form of immunosuppression

  4. Effect of gene-targeted mutation in TNF receptor (p55) on contact hypersensitivity and ultraviolet B-induced immunosuppression

    Energy Technology Data Exchange (ETDEWEB)

    Kondo, Seiji; Wang, Binghe; Fujisawa, Hiroshi [Univ. of Toronto, Ontario (Canada)] [and others

    1995-10-15

    Tumor necrosis factor {alpha} (TNF-{alpha}) is a pleiotropic proinflammatory cytokine. TNF-{alpha} has been implicated in the pathogenesis of delayed-type hypersensitivity reactions such as allergic contact hypersensitivity and has been suggested as a mediator of ultraviolet B (UVB)-induced immunosuppression. Conflicting reports, however, exist concerning the effects of TNF-{alpha} on contact hypersensitivity (CHS). To determine the role of TNF-{alpha} in the generation and regulation of CHS, gene-targeted mutant mice lacking TNF-receptor (p55) gene (TNF-R1(-) mice) were treated with dinitrofluorobenzene (DNFB) to induce CHS. TNF-R1(-) mice showed significant hyperresponsiveness in CHS (152.8 {+-} 20.9%, p < 0.025) compared with normal syngeneic mice (C57BL/6) assessed by ear swelling. To determine whether UVB can induce suppression in TNF-R1(-) mice, mice were irradiated on the shaved abdomen with 96 ml/cm{sup 2} UVB and 3 days later they were painted with 0.5% DNFB (sensitization dose), followed 5 days later with 0.2% DNFB to the left ear (challenge dose). Significant suppression of CHS was observed both locally (sensitization on irradiated site) and systemically (sensitization on unirradiated site) in UVB-irradiated TNF-R1(-) mice as well as in normal mice. To rule out possible signaling through p75 TNF-R, the mice were treated with anti-TNF-{alpha} Ab (V1q), which can neutralize any TNF effects through either receptor. V1q had no effect on these phenomena observed in TNF-R1(-) mice. These results suggest that TNF-{alpha} plays a regulatory role in CHS but is not required to induce UVB-mediated immunosuppression. 45 refs., 5 figs.

  5. Amalgam Contact Hypersensitivity Lesion: An Unusual Presentation ...

    African Journals Online (AJOL)

    Contact allergic reactions due to hypersensitivity to dental materials in professionals and ... Keywords: Amalgam, Amalgam contact hypersensitivity lesion, Lichenoid reaction, Oral mucosa ... was associated with mild burning sensation. The patient did ... OLLD in which oral and/or skin lesions appear in temporal association ...

  6. Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay.

    Science.gov (United States)

    Yao, Pan; Hongqian, Chu; Qinghe, Meng; Lanqin, Shang; Jianjun, Jiang; Xiaohua, Yang; Xuetao, Wei; Weidong, Hao

    2016-09-15

    Trichloroethylene (TCE) is a ubiquitous environmental contaminant. Occupational TCE exposure has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder. The development of CHS depends on innate and adaptive immune functions. Transforming growth factor-β activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis. We aimed to investigate the role of TAK1 activity in DC on TCE-induced CHS response. Control mice and DC-specific TAK1 deletion mice were treated with 80% (v/v) TCE using local lymph node assay (LLNA) to establish a TCE-induced CHS model. The draining lymph nodes (DLNs) were excised and the lymphocytes were measure for proliferation by BrdU-ELISA, T-cell phenotype analysis by flow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an inflammatory response in the ears, increased lymphocyte proliferation, elevated regulatory T-cell and activated T-cell percentages, and more IFN-γ producing CD8(+) T cells in DLNs. In contrast to control mice, DC-specific TAK1 deletion mice in the 80% TCE group showed an abolished CHS response and this was associated with defective T-cell expansion, activation and IFN-γ production. This effect may occur through Jnk and NF-κB signaling pathways. Overall, this study demonstrates a pivotal role of TAK1 in DCs in controlling TCE-induced CHS response and suggests that targeting TAK1 function in DCs may be a viable approach to preventing and treating TCE-related occupational health hazards. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Pan; Hongqian, Chu; Qinghe, Meng; Lanqin, Shang; Jianjun, Jiang; Xiaohua, Yang; Xuetao, Wei; Weidong, Hao, E-mail: whao@bjmu.edu.cn

    2016-09-15

    Trichloroethylene (TCE) is a ubiquitous environmental contaminant. Occupational TCE exposure has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder. The development of CHS depends on innate and adaptive immune functions. Transforming growth factor-β activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis. We aimed to investigate the role of TAK1 activity in DC on TCE-induced CHS response. Control mice and DC-specific TAK1 deletion mice were treated with 80% (v/v) TCE using local lymph node assay (LLNA) to establish a TCE-induced CHS model. The draining lymph nodes (DLNs) were excised and the lymphocytes were measure for proliferation by BrdU-ELISA, T-cell phenotype analysis by flow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an inflammatory response in the ears, increased lymphocyte proliferation, elevated regulatory T-cell and activated T-cell percentages, and more IFN-γ producing CD8{sup +} T cells in DLNs. In contrast to control mice, DC-specific TAK1 deletion mice in the 80% TCE group showed an abolished CHS response and this was associated with defective T-cell expansion, activation and IFN-γ production. This effect may occur through Jnk and NF-κB signaling pathways. Overall, this study demonstrates a pivotal role of TAK1 in DCs in controlling TCE-induced CHS response and suggests that targeting TAK1 function in DCs may be a viable approach to preventing and treating TCE-related occupational health hazards. - Highlights: • Lack of TAK1 in DC caused an abolished TCE-induced CHS response. • TAK1 in DCs was essential to maintain the homeostasis of T cells in TCE-induced CHS. • Intact TAK1 in DCs was critical to promote T-cell priming in TCE-induced CHS. • DC-specific TAK1 deficiency abolished the TCE-mediated phosphorylation of Jnk.

  8. Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay

    International Nuclear Information System (INIS)

    Yao, Pan; Hongqian, Chu; Qinghe, Meng; Lanqin, Shang; Jianjun, Jiang; Xiaohua, Yang; Xuetao, Wei; Weidong, Hao

    2016-01-01

    Trichloroethylene (TCE) is a ubiquitous environmental contaminant. Occupational TCE exposure has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder. The development of CHS depends on innate and adaptive immune functions. Transforming growth factor-β activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis. We aimed to investigate the role of TAK1 activity in DC on TCE-induced CHS response. Control mice and DC-specific TAK1 deletion mice were treated with 80% (v/v) TCE using local lymph node assay (LLNA) to establish a TCE-induced CHS model. The draining lymph nodes (DLNs) were excised and the lymphocytes were measure for proliferation by BrdU-ELISA, T-cell phenotype analysis by flow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an inflammatory response in the ears, increased lymphocyte proliferation, elevated regulatory T-cell and activated T-cell percentages, and more IFN-γ producing CD8 + T cells in DLNs. In contrast to control mice, DC-specific TAK1 deletion mice in the 80% TCE group showed an abolished CHS response and this was associated with defective T-cell expansion, activation and IFN-γ production. This effect may occur through Jnk and NF-κB signaling pathways. Overall, this study demonstrates a pivotal role of TAK1 in DCs in controlling TCE-induced CHS response and suggests that targeting TAK1 function in DCs may be a viable approach to preventing and treating TCE-related occupational health hazards. - Highlights: • Lack of TAK1 in DC caused an abolished TCE-induced CHS response. • TAK1 in DCs was essential to maintain the homeostasis of T cells in TCE-induced CHS. • Intact TAK1 in DCs was critical to promote T-cell priming in TCE-induced CHS. • DC-specific TAK1 deficiency abolished the TCE-mediated phosphorylation of Jnk.

  9. Chronic low-dose UVA irradiation induces local suppression of contact hypersensitivity, Langerhans cell depletion and suppressor cell activation in C3H/HeJ mice

    International Nuclear Information System (INIS)

    Bestak, Rosa; Halliday, G.M.

    1996-01-01

    It has previously been demonstrated that chronic low-dose solar-simulated UV radiation could induce both local and systemic immunosuppression as well as tolerance to a topically applied hapten. In this study, we have used a chronic low-dose UV-irradiation protocol to investigate the effects of UVA on the skin immune system of C3H/HeJ mice. Irradiation with UVA+B significantly suppressed the local and systemic primary contact hypersensitivity (CHS) response to the hapten 2,4,6-trinitrochlorobenzene. Furthermore, UVA+B reduced Langerhans cell (LC) and dendritic epidermal T cell (DETC) densities in chronically UV-irradiated mice. Ultraviolet A irradiation induced local, but not systemic, immunosuppression and reduced LC (32%) but not DETC from the epidermis compared to the shaved control animals. Treatment of mice with both UVA+B and UVA radiation also induced an impaired secondary CHS response, and this tolerance was transferable with spleen cells. (Author)

  10. Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

    International Nuclear Information System (INIS)

    Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta; Watanabe, Tatsuo; Imai, Yasuyuki

    2012-01-01

    Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

  11. Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Watanabe, Tatsuo [Laboratory of Food Chemistry, School of Food and Nutritional Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Imai, Yasuyuki, E-mail: imai@u-shizuoka-ken.ac.jp [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan)

    2012-11-01

    Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

  12. IL-1β-Dependent Activation of Dendritic Epidermal T Cells in Contact Hypersensitivity

    DEFF Research Database (Denmark)

    Nielsen, Morten M; Lovato, Paola; Macleod, Amanda S

    2014-01-01

    Substances that penetrate the skin surface can act as allergens and induce a T cell-mediated inflammatory skin disease called contact hypersensitivity (CHS). IL-17 is a key cytokine in CHS and was originally thought to be produced solely by CD4(+) T cells. However, it is now known that several cell...

  13. Protection against ultraviolet-B radiation-induced local and systemic suppression of contact hypersensitivity and edema responses in C3H/HeN mice by green tea polyphenols

    International Nuclear Information System (INIS)

    Katiyar, S.K.; Elmets, C.A.; Agarwal, Rajesh; Mukhtar, Hasan

    1995-01-01

    Exposure of skin to UV radiation can cause diverse biological effects, including induction of inflammation, alteration in cutaneous immune cells and impairment of contact hypersensitivity (CHS) responses. Our laboratory has demonstrated that oral feeding as well as topical application of a polyphenolic fraction isolated from green tea (GTP) affords protection against the carcinogenic effects of UVB (280-320 nm) radiation. In this study, we investigated whether GTP could protect against UVB-induced immunosuppression and cutaneous inflammatory responses in C3H mice. Immunosuppression was assessed by contact sensitization with 2,4-dinitrofluorobenzene applied to UVB-irradiated skin (local suppression) or to a distant site (systemic suppression), while double skin-fold swelling was used as the measure of UVB-induced inflammation. (author)

  14. Immediate and delayed contact hypersensitivity to verbena plants

    DEFF Research Database (Denmark)

    Potter, P C; Mather, S; Lockey, P

    1995-01-01

    Plants from the Verbenaceae family may cause contact dermatitis of unknown nature. This report describes 2 cases of allergic reactions to the Verbena species. A teenage boy developed an anaphylactic allergic response following contact with the leaves of Verbena hybrida. Characterization...... of the patient's specific IgE response to Verbena hybrida, using Western blots and autoradiography, identified the specific 62000 Dalton allergen present in the verbena leaves to which the patient reacted. This is the first report of an IgE-mediated immediate contact hypersensitivity reaction to Verbena hybrida......, a common perennial in South African gardens. The other case was a 23-year-old female gardener who developed immediate and delayed-type contact dermatitis from Verbena elegans 'Cleopatra' produced in a Danish nursery. Prick tests to plant material were considered positive and of an allergic nature....

  15. Copper hypersensitivity

    DEFF Research Database (Denmark)

    Fage, Simon W; Faurschou, Annesofie; Thyssen, Jacob P

    2014-01-01

    hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common...

  16. Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat.

    Science.gov (United States)

    Seluanov, Andrei; Hine, Christopher; Azpurua, Jorge; Feigenson, Marina; Bozzella, Michael; Mao, Zhiyong; Catania, Kenneth C; Gorbunova, Vera

    2009-11-17

    The naked mole-rat is the longest living rodent with a maximum lifespan exceeding 28 years. In addition to its longevity, naked mole-rats have an extraordinary resistance to cancer as tumors have never been observed in these rodents. Furthermore, we show that a combination of activated Ras and SV40 LT fails to induce robust anchorage-independent growth in naked mole-rat cells, while it readily transforms mouse fibroblasts. The mechanisms responsible for the cancer resistance of naked mole-rats were unknown. Here we show that naked mole-rat fibroblasts display hypersensitivity to contact inhibition, a phenomenon we termed "early contact inhibition." Contact inhibition is a key anticancer mechanism that arrests cell division when cells reach a high density. In cell culture, naked mole-rat fibroblasts arrest at a much lower density than those from a mouse. We demonstrate that early contact inhibition requires the activity of p53 and pRb tumor suppressor pathways. Inactivation of both p53 and pRb attenuates early contact inhibition. Contact inhibition in human and mouse is triggered by the induction of p27(Kip1). In contrast, early contact inhibition in naked mole-rat is associated with the induction of p16(Ink4a). Furthermore, we show that the roles of p16(Ink4a) and p27(Kip1) in the control of contact inhibition became temporally separated in this species: the early contact inhibition is controlled by p16(Ink4a), and regular contact inhibition is controlled by p27(Kip1). We propose that the additional layer of protection conferred by two-tiered contact inhibition contributes to the remarkable tumor resistance of the naked mole-rat.

  17. Lack of the purinergic receptor P2X7 results in resistance to contact hypersensitivity

    Science.gov (United States)

    Weber, Felix C.; Esser, Philipp R.; Müller, Tobias; Ganesan, Jayanthi; Pellegatti, Patrizia; Simon, Markus M.; Zeiser, Robert; Idzko, Marco; Jakob, Thilo

    2010-01-01

    Sensitization to contact allergens requires activation of the innate immune system by endogenous danger signals. However, the mechanisms through which contact allergens activate innate signaling pathways are incompletely understood. In this study, we demonstrate that mice lacking the adenosine triphosphate (ATP) receptor P2X7 are resistant to contact hypersensitivity (CHS). P2X7-deficient dendritic cells fail to induce sensitization to contact allergens and do not release IL-1β in response to lipopolysaccharide (LPS) and ATP. These defects are restored by pretreatment with LPS and alum in an NLRP3- and ASC-dependent manner. Whereas pretreatment of wild-type mice with P2X7 antagonists, the ATP-degrading enzyme apyrase or IL-1 receptor antagonist, prevents CHS, IL-1β injection restores CHS in P2X7-deficient mice. Thus, P2X7 is a crucial receptor for extracellular ATP released in skin in response to contact allergens. The lack of P2X7 triggering prevents IL-1β release, which is an essential step in the sensitization process. Interference with P2X7 signaling may be a promising strategy for the prevention of allergic contact dermatitis. PMID:21059855

  18. Cellular dynamics in the draining lymph nodes during sensitization and elicitation phases of contact hypersensitivity

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura; Geisler, Carsten; Nielsen, Martin Weiss

    2007-01-01

    BACKGROUND: The different role of various immunological effector cells in contact hypersensitivity (CHS) is receiving increased attention. During the past decade, the involvement of different cell types in CHS has been investigated by the use of antibody-induced depletion of specific subtypes...... of immunological cells and by studying knockout mice lacking one or more of these immunological cell populations. OBJECTIVES: To develop a method for studying the collective cellular dynamics of immune cells in the draining lymph nodes during CHS in intact animals. PATIENTS/METHODS: Mice were sensitized and....../or challenged with 2,4-dinitrofluorobenzene or oxazolone. Using multi-parameter flow cytometry we determined the proliferation, activation state, and absolute number of helper T cells, cytotoxic T cells, B cells, and natural killer cells in the draining lymph nodes. RESULTS: The presented method can be applied...

  19. Use of an ex vivo local lymph node assay to assess contact hypersensitivity potential.

    Science.gov (United States)

    Piccotti, Joseph R; Kawabata, Thomas T

    2008-07-01

    The local lymph node assay (LLNA) is used to assess the contact hypersensitivity potential of compounds. In the standard assay, mice are treated topically with test compound to the dorsum of both ears on Days 1-3. The induction of a hypersensitivity response is assessed on Day 6 by injecting [(3)H]-thymidine into a tail vein and measuring thymidine incorporation into DNA of lymph node cells draining the ears. The ex vivo LLNA is conducted similarly except lymphocyte proliferation is assessed after in vitro incubation of lymph node cells with [(3)H]-thymidine, which significantly reduces the amount of radioactive waste. The current study tested the use of this approach for hazard assessment of contact hypersensitivity and to estimate allergenic potency. Female BALB/c mice were treated on Days 1-3 with two nonsensitizers (4' -methoxyacetophenone, diethyl phthalate), three weak sensitizers (hydroxycitronellal, eugenol, citral), one weak-to-moderate sensitizer (hexylcinnamic aldehyde), two moderate sensitizers (isoeugenol, phenyl benzoate), and one strong sensitizer (dinitrochlorobenzene). On Day 6, isolated lymph node cells were incubated overnight with [(3)H]-thymidine and thymidine incorporation was measured by liquid scintillation spectrophotometry. The ex vivo LLNA accurately distinguished the contact sensitizers from the nonsensitizing chemicals, and correctly ranked the relative potency of the compounds tested. The EC3 values, i.e., the effective concentration of test substance needed to induce a stimulation index of 3, were as follows: 4' -methoxyacetophenone (> 50%), diethyl phthalate (> 50%), hydroxycitronellal (20.4%), eugenol (13.6%), citral (8.9%), isoeugenol (3.8%), hexylcinnamic aldehyde (2.7%), phenyl benzoate (2%), and dinitrochlorobenzene (0.02%). In addition, low inter-animal and inter-experiment variability was seen with 25% hexyl-cinnamic aldehyde (assay positive control). The results of the ex vivo LLNA in the current study were consistent with

  20. Gelofen Induced Hypersensitivity: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    M. Nikkhah Rankohie

    2016-07-01

    Full Text Available Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs are drugs commonly pre-scribed in dental practice for the management of pain and swelling. But, rarely hypersensitiv-ity reactions are reported. Case Report: A 28 year old woman underwent periodontal plastic surgery (gingival graft. Postoperative analgesics (400 mg Gelofen ,oral and antibiotics were administrated for the patient. Three hours after discharge of patient, she complained of redness, itching , rapid swelling of her eyes in 10 minutes, and watery eye discharge 1 hour after taking the drugs. She was treated with 8mg/2ml mg Dexamethasone IM at the dental department and with Hy-drocortisone 100mg/ml IM and antihistamine drugs at the hospital. Conclusion: There are no published protocols and sensitivity and specifity of skin pick testing and patch testing for Gelofen. So avoidance of re-exposure is the best management strategy. The use of Cox-2 specific medications would be a proper alternative for pain relief. (Sci J Hamadan Univ Med Sci 2016; 23 (2:179-183

  1. [Epidemiology of contact hypersensitivity to rubber components in manufacturers of automobile tires at the Stomil plant].

    Science.gov (United States)

    Rubisz-Brzezińska, J; Bogdanowski, T; Brzezińska-Wcisło, L; Mozdzanowska, K; Bajcar, S

    1990-01-01

    Dermatological examination and patch tests with 34 rubber components were carried out in 114 tire manufacturers, 78 women and 36 men aged 29 years on average, with a mean duration of work in the plant 7 years. For correct interpretation of the obtained results patch tests with the same components were done in two control groups that is in 120 healthy subjects and 120 patients with contact dermatitis. Patch tests with proper concentrations of the studied components were evaluated after 48, 72 and 96 hours. Positive patch tests were found most frequently with antioxidants--16.6% (including IPPD--8.6%), followed by vulcanization accelerators--10.6%, and other rubber components--11.4% in all. During about 3 years of follow-up in 4 manufacturers contact allergic eczema was noted and polyvalent hypersensitivity to antioxidants and vulcanization accelerators without clinical manifestations of this hypersensitivity was diagnosed in 3 other subjects.

  2. Nickel-induced hypersensitivity: etiology, immune reactions, prevention and therapy.

    Science.gov (United States)

    Hostýnek, Jurij J

    2002-08-01

    As a contact allergen causing type I and type IV hypersensitivity, mediated by reagins and allergen-specific T lymphocytes, expressed in a wide range of cutaneous eruptions following dermal or systemic exposure, nickel has acquired the distinction of being among the most frequent causes of hypersensitivity, occupationally as well as among the general population. In synoptic form the many effects that nickel has on the organism are presented, to provide a comprehensive picture of the aspects of that metal with many biologically noxious, but metallurgically indispensable characteristics. This paper reviews the epidemiology, the prognosis for occupational and non-occupational nickel allergic hypersensitivity (NAH), the many types of exposure and the resulting immune responses, immunotoxicity and rate of diffusion through the skin. Alternatives towards prevention and remediation, topical and systemic, for this pervasive and increasing form of morbidity resulting from multiple types of exposure are discussed. Merits and limitations of preventive measures in industry and private life are considered, as well as the effectiveness of topical and systemic therapy in treating NAH.

  3. MGL2 Dermal dendritic cells are sufficient to initiate contact hypersensitivity in vivo.

    Directory of Open Access Journals (Sweden)

    Yosuke Kumamoto

    Full Text Available Dendritic cells (DCs are the most potent antigen-presenting cells in the mammalian immune system. In the skin, epidermal Langerhans cells (LCs and dermal dendritic cells (DDCs survey for invasive pathogens and present antigens to T cells after migration to the cutaneous lymph nodes (LNs. So far, functional and phenotypic differences between these two DC subsets remain unclear due to lack of markers to identify DDCs.In the present report, we demonstrated that macrophage galactose-type C-type lectin (MGL 2 was exclusively expressed in the DDC subset in the skin-to-LN immune system. In the skin, MGL2 was expressed on the majority (about 88% of MHCII(+CD11c(+ cells in the dermis. In the cutaneous LN, MGL2 expression was restricted to B220(-CD8alpha(loCD11b(+CD11c(+MHCII(hi tissue-derived DC. MGL2(+DDC migrated from the dermis into the draining LNs within 24 h after skin sensitization with FITC. Distinct from LCs, MGL2(+DDCs localized near the high endothelial venules in the outer T cell cortex. In FITC-induced contact hypersensitivity (CHS, adoptive transfer of FITC(+MGL2(+DDCs, but not FITC(+MGL2(-DCs into naive mice resulted in the induction of FITC-specific ear swelling, indicating that DDCs played a key role in initiation of immune responses in the skin.These results demonstrated the availability of MGL2 as a novel marker for DDCs and suggested the contribution of MGL2(+ DDCs for initiating CHS.

  4. Brown coal derived humate inhibits contact hypersensitivity; An efficacy, toxicity and teratogenicity study in rats

    Energy Technology Data Exchange (ETDEWEB)

    Van Rensburg, C.E.J.; Snyman, J.R.; Mokoele, T.; Cromarty, A.D. [University of Pretoria, Pretoria (South Africa). Faculty of Health Science

    2007-10-15

    The effects of two humate products were compared to that of prednisolone on a contact hypersensitivity rat model. Rats, sensitized with dinitrofluorobenzene (DNFB), were placed on a daily oral treatment of 61 mg/kg BW of humate derived from either leonardite or bituminous coal or on prednisolone at one mg/kg BW and challenged 6 days later with a topical application of DNFB to the right ear. The inflamed ears were measured daily. In a toxicity study rats were exposed to daily oral treatment of leonardite humate at 1,000 mg/kg BW for 1 month. A teratogenicity study was done where pregnant rats were treated with 500 mg/kg BW on days 5 to 17 of pregnancy. Only the leonardite humate compared favourably with prednisolone in suppressing contact hypersensitivity. No signs of toxicity were observed and weight gain was normal during the 6-day and 1 month treatments and during the teratogenicity study with the leonardite humate. However, the rats on the other two products experienced slower weight gain. The identification of a naturally occurring nontoxic compound with anti-inflammatory activity is exciting and merits further evaluation in the treatment of patients suffering from inflammatory conditions.

  5. Drug-induced hypersensitivity syndrome with human herpesvirus-6 reactivation

    Directory of Open Access Journals (Sweden)

    Najeeba Riyaz

    2012-01-01

    Full Text Available A 45-year-old man, on carbamazepine for the past 3 months, was referred as a case of atypical measles. On examination, he had high-grade fever, generalized itchy rash, cough, vomiting and jaundice. A provisional diagnosis of drug hypersensitivity syndrome to carbamazepine was made with a differential diagnosis of viral exanthema with systemic complications. Laboratory investigations revealed leukocytosis with eosnophilia and elevated liver enzymes. Real-time multiplex polymerase chain reaction (PCR on throat swab and blood was suggestive of human herpesvirus-6 (HHV-6. Measles was ruled out by PCR and serology. The diagnosis of drug-induced hypersensitivity syndrome (DIHS was confirmed, which could explain all the features manifested by the patient. HHV-6 infects almost all humans by age 2 years. It infects and replicates in CD4 T lymphocytes and establishes latency in human peripheral blood monocytes or macrophages and early bone marrow progenitors. In DIHS, allergic reaction to the causative drug stimulates T cells, which leads to reactivation of the herpesvirus genome. DIHS is treated by withdrawal of the culprit drug and administration of systemic steroids. Our patient responded well to steroids and HHV-6 was negative on repeat real-time multiplex PCR at the end of treatment.

  6. Allopurinol-induced Severe Hypersensitivity with Acute Renal Failure

    Directory of Open Access Journals (Sweden)

    I-Hung Chen

    2005-05-01

    Full Text Available A 62-year-old male was sent to the emergency room due to a high fever and generalized skin rash after taking allopurinol for 9 days. Physical examination was normal except for the generalized skin rash presenting with erythematous macules. Complete blood count showed leukocytosis with eosinophilia. Blood biochemistry showed impaired renal and hepatic function. Pathologic examination concluded that the skin rash was erythema multiforme. These findings met the diagnostic criteria for allopurinol-induced hypersensitivity syndrome (AHS. Our patient not only had the most common skin lesion but soon developed acute renal failure that required intermittent hemodialysis, despite rapid discontinuation of allopurinol and adequate hydration and steroid therapy. No other causes of acute renal failure were found. Renal impairment was the worst part of the patient's condition and he never completely recovered. AHS should be considered in the differential diagnosis of acute renal and hepatic failure in patients with evidence of allergy and recent use of allopurinol.

  7. Jasmonic acid signaling modulates ozone-induced hypersensitive cell death.

    Science.gov (United States)

    Rao, M V; Lee, H; Creelman, R A; Mullet, J E; Davis, K R

    2000-09-01

    Recent studies suggest that cross-talk between salicylic acid (SA)-, jasmonic acid (JA)-, and ethylene-dependent signaling pathways regulates plant responses to both abiotic and biotic stress factors. Earlier studies demonstrated that ozone (O(3)) exposure activates a hypersensitive response (HR)-like cell death pathway in the Arabidopsis ecotype Cvi-0. We now have confirmed the role of SA and JA signaling in influencing O(3)-induced cell death. Expression of salicylate hydroxylase (NahG) in Cvi-0 reduced O(3)-induced cell death. Methyl jasmonate (Me-JA) pretreatment of Cvi-0 decreased O(3)-induced H(2)O(2) content and SA concentrations and completely abolished O(3)-induced cell death. Cvi-0 synthesized as much JA as did Col-0 in response to O(3) exposure but exhibited much less sensitivity to exogenous Me-JA. Analyses of the responses to O(3) of the JA-signaling mutants jar1 and fad3/7/8 also demonstrated an antagonistic relationship between JA- and SA-signaling pathways in controlling the magnitude of O(3)-induced HR-like cell death.

  8. Immunosuppressive Effect of Litsea cubeba L. Essential Oil on Dendritic Cell and Contact Hypersensitivity Responses

    Directory of Open Access Journals (Sweden)

    Hsin-Chun Chen

    2016-08-01

    Full Text Available Litsea cubeba L., also named as Makauy, is a traditional herb and has been used as cooking condiment or tea brewing to treat diseases for aborigines. The present study was undertaken to explore the chemical compositions of the fruit essential oil of L. cubeba (LCEO and the immunomodulatory effect of LCEO on dendritic cells and mice. The LCEO was analyzed using gas chromatography (GC and gas chromatography/mass spectrometry (GC/MS with direct injection (DI/GC or headspace-solid phase microextraction (HS-SPME/GC. In total, 56 components were identified, of which 48 were detected by DI/GC and 49 were detected by HS-SPME/GC. The principal compounds were citral (neral and geranial. An immunosuppressive activity of LCEO was investigated with bone marrow-derived dendritic cells (DCs which have a critical role to trigger the adaptive immunity. Additionally, the inhibitory effect of LCEO on immune response was elucidated by performing the contact hypersensitivity (CHS responses in mice. Our results clearly showed that LCEO decreases the production of TNF-α and cytokine IL-12 in a dose-dependent manner in lipopolysaccharide (LPS-stimulated DCs. CHS response and the infiltrative T cells were inhibited in the tested ears of the mice co-treated with LCEO. We demonstrate, for the first time, that the LCEO mainly containing citral exhibits an immunosuppressive effect on DCs and mice, indicating that LCEO can potentially be applied in the treatment of CHS, inflammatory diseases, and autoimmune diseases.

  9. Immunotoxicity of epicutaneously applied anticoagulant rodenticide warfarin: evaluation by contact hypersensitivity to DNCB in rats

    International Nuclear Information System (INIS)

    Kataranovski, Milena; Vlaski, Marija; Kataranovski, Dragan; Tosic, Natasa; Mandic-Radic, Slavka; Todorovic, Vera

    2003-01-01

    The immunotoxicity of epicutaneously administered anticoagulant rodenticide warfarin (WF) was examined in this work by using experimental contact hypersensitivity (CHS) reaction to hapten dinitrochlorobenzene (DNCB). WF (0.05 and 0.5 mg/kg) administration 24 h before the induction of CHS does not change expression of CHS evaluated by ear swelling assay. Regional draining lymph node response during sensitization phase was characterized by decreased cellularity but increased spontaneous and IL-2 stimulated proliferation of draining lymph node cells (DLC). No changes in IL-2 production and in numbers of CD25 + cells were noted and even decreased proliferative index (ratio of IL-2 stimulated to unstimulated DLC proliferation) was detected. Increase in granulocyte activity (MTT reduction and adhesion to plastic) was noted following application of WF solely with further increase following subsequent application of DNCB, when granulocyte activation (NBT reduction) was noted also. Access of WF into general circulation might be responsible for observed changes, what was supported by ex vivo changes in DLC and granulocyte functions assessed before initiation of sensitization and by in vitro effect of exogenous WF as well. Differential effects of WF on lymphocytes and granulocytes noted in this study highlight the need for simultaneous testing of both cell type activity what might constitute a more integrated approach in immunotoxicity studies

  10. Genetic and Imaging Approaches Reveal Pro-Inflammatory and Immunoregulatory Roles of Mast Cells in Contact Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Nicolas Gaudenzio

    2018-06-01

    Full Text Available Contact hypersensitivity (CHS is a common T cell-mediated skin disease induced by epicutaneous sensitization to haptens. Mast cells (MCs are widely deployed in the skin and can be activated during CHS responses to secrete diverse products, including some with pro-inflammatory and anti-inflammatory functions. Conflicting results have been obtained regarding pathogenic versus protective roles of MCs in CHS, and this has been attributed in part to the limitations of certain models for studying MC functions in vivo. This review discusses recent advances in the development and analysis of mouse models to investigate the roles of MCs and MC-associated products in vivo. Notably, fluorescent avidin-based two-photon imaging approaches enable in vivo selective labeling and simultaneous tracking of MC secretory granules (e.g., during MC degranulation and MC gene activation by real-time longitudinal intravital microscopy in living mice. The combination of such genetic and imaging tools has shed new light on the controversial role played by MCs in mouse models of CHS. On the one hand, they can amplify CHS responses of mild severity while, on the other hand, can limit the inflammation and tissue injury associated with more severe or chronic models, in part by representing an initial source of the anti-inflammatory cytokine IL-10.

  11. Agrobacterium -induced hypersensitive necrotic reaction in plant cells

    African Journals Online (AJOL)

    High necrosis and poor survival rate of target plant tissues are some of the major factors that affect the efficiency of Agrobacterium-mediated T-DNA transfer into plant cells. These factors may be the result of, or linked to, hypersensitive defense reaction in plants to Agrobacterium infection, which may involve the recognition ...

  12. Rice hypersensitive induced reaction protein 1 (OsHIR1) associates with plasma membrane and triggers hypersensitive cell death.

    Science.gov (United States)

    Zhou, Liang; Cheung, Ming-Yan; Li, Man-Wah; Fu, Yaping; Sun, Zongxiu; Sun, Sai-Ming; Lam, Hon-Ming

    2010-12-30

    In plants, HIR (Hypersensitive Induced Reaction) proteins, members of the PID (Proliferation, Ion and Death) superfamily, have been shown to play a part in the development of spontaneous hypersensitive response lesions in leaves, in reaction to pathogen attacks. The levels of HIR proteins were shown to correlate with localized host cell deaths and defense responses in maize and barley. However, not much was known about the HIR proteins in rice. Since rice is an important cereal crop consumed by more than 50% of the populations in Asia and Africa, it is crucial to understand the mechanisms of disease responses in this plant. We previously identified the rice HIR1 (OsHIR1) as an interacting partner of the OsLRR1 (rice Leucine-Rich Repeat protein 1). Here we show that OsHIR1 triggers hypersensitive cell death and its localization to the plasma membrane is enhanced by OsLRR1. Through electron microscopy studies using wild type rice plants, OsHIR1 was found to mainly localize to the plasma membrane, with a minor portion localized to the tonoplast. Moreover, the plasma membrane localization of OsHIR1 was enhanced in transgenic rice plants overexpressing its interacting protein partner, OsLRR1. Co-localization of OsHIR1 and OsLRR1 to the plasma membrane was confirmed by double-labeling electron microscopy. Pathogen inoculation studies using transgenic Arabidopsis thaliana expressing either OsHIR1 or OsLRR1 showed that both transgenic lines exhibited increased resistance toward the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. However, OsHIR1 transgenic plants produced more extensive spontaneous hypersensitive response lesions and contained lower titers of the invading pathogen, when compared to OsLRR1 transgenic plants. The OsHIR1 protein is mainly localized to the plasma membrane, and its subcellular localization in that compartment is enhanced by OsLRR1. The expression of OsHIR1 may sensitize the plant so that it is more prone to HR and hence can react more

  13. Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity.

    Science.gov (United States)

    Ding, Hao; Liu, Xiao-Chang; Mei, Qiao; Xu, Jian-Ming; Hu, Xiang-Yang; Hu, Jing

    2014-04-07

    Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption. However, previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever, rashes, colitis exacerbation and acute eosinophilic pneumonia. Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories. In light of symptom exacerbation of ulcerative colitis, increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration, and the Naranjo algorithm score of 10, the possibility of hypersensitivity reaction to mesalamine suppositories should be considered, warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories.

  14. Persistent Skin Reactions and Aluminium Hypersensitivity Induced by Childhood Vaccines

    DEFF Research Database (Denmark)

    Salik, Elaha; Løvik, Ida; Andersen, Klaus E

    2016-01-01

    There is increasing awareness of reactions to vaccination that include persistent skin reactions. We present here a retrospective investigation of long-lasting skin reactions and aluminium hypersensitivity in children, based on medical records and questionnaires sent to the parents. In the 10-year...... period 2003 to 2013 we identified 47 children with persistent skin reactions caused by childhood vaccinations. Most patients had a typical presentation of persisting pruritic subcutaneous nodules. Five children had a complex diagnostic process involving paediatricians, orthopaedics and plastic surgeons...... treated with potent topical corticosteroids and disappeared slowly. Although we advised families to continue vaccination of their children, one-third of parents omitted or postponed further vaccinations....

  15. Adrenergic β2-receptors mediates visceral hypersensitivity induced by heterotypic intermittent stress in rats.

    Directory of Open Access Journals (Sweden)

    Chunhua Zhang

    Full Text Available Chronic visceral pain in patients with irritable bowel syndrome (IBS has been difficult to treat effectively partially because its pathophysiology is not fully understood. Recent studies show that norepinephrine (NE plays an important role in the development of visceral hypersensitivity. In this study, we designed to investigate the role of adrenergic signaling in visceral hypersensitivity induced by heterotypical intermittent stress (HIS. Abdominal withdrawal reflex scores (AWRs used as visceral sensitivity were determined by measuring the visceromoter responses to colorectal distension. Colon-specific dorsal root ganglia neurons (DRGs were labeled by injection of DiI into the colon wall and were acutely dissociated for whole-cell patch-clamp recordings. Blood plasma level of NE was measured using radioimmunoassay kits. The expression of β2-adrenoceptors was measured by western blotting. We showed that HIS-induced visceral hypersensitivity was attenuated by systemic administration of a β-adrenoceptor antagonist propranolol, in a dose-dependent manner, but not by a α-adrenoceptor antagonist phentolamine. Using specific β-adrenoceptor antagonists, HIS-induced visceral hypersensitivity was alleviated by β2 adrenoceptor antagonist but not by β1- or β3-adrenoceptor antagonist. Administration of a selective β2-adrenoceptor antagonist also normalized hyperexcitability of colon-innervating DRG neurons of HIS rats. Furthermore, administration of β-adrenoceptor antagonist suppressed sustained potassium current density (IK without any alteration of fast-inactivating potassium current density (IA. Conversely, administration of NE enhanced the neuronal excitability and produced visceral hypersensitivity in healthy control rats, and blocked by β2-adrenoceptor antagonists. In addition, HIS significantly enhanced the NE concentration in the blood plasma but did not change the expression of β2-adrenoceptor in DRGs and the muscularis externa of the

  16. Persistent Skin Reactions and Aluminium Hypersensitivity Induced by Childhood Vaccines.

    Science.gov (United States)

    Salik, Elaha; Løvik, Ida; Andersen, Klaus E; Bygum, Anette

    2016-11-02

    There is increasing awareness of reactions to vaccination that include persistent skin reactions. We present here a retrospective investigation of long-lasting skin reactions and aluminium hypersensitivity in children, based on medical records and questionnaires sent to the parents. In the 10-year period 2003 to 2013 we identified 47 children with persistent skin reactions caused by childhood vaccinations. Most patients had a typical presentation of persisting pruritic subcutaneous nodules. Five children had a complex diagnostic process involving paediatricians, orthopaedics and plastic surgeons. Two patients had skin biopsies performed from their skin lesions, and 2 patients had the nodules surgically removed. Forty-two children had a patch-test performed with 2% aluminium chloride hexahydrate in petrolatum and 39 of them (92%) had a positive reaction. The persistent skin reactions were treated with potent topical corticosteroids and disappeared slowly. Although we advised families to continue vaccination of their children, one-third of parents omitted or postponed further vaccinations.

  17. Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions.

    LENUS (Irish Health Repository)

    McCormack, Mark

    2012-03-01

    An association between carbamazepine-induced hypersensitivity and HLA-A*3101 has been reported in populations of both European and Asian descent. We aimed to investigate HLA-A*3101 and other common variants across the genome as markers for cutaneous adverse drug reactions (cADRs) attributed to lamotrigine and phenytoin.

  18. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.

    LENUS (Irish Health Repository)

    McCormack, Mark

    2011-03-24

    Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B*1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) in the Han Chinese and other Asian populations but not in European populations.

  19. Drug-induced hypersensitivity syndrome associated with Epstein-Barr virus infection.

    Science.gov (United States)

    Descamps, V; Mahe, E; Houhou, N; Abramowitz, L; Rozenberg, F; Ranger-Rogez, S; Crickx, B

    2003-05-01

    Association of drug-induced hypersensitivity syndrome with viral infection is debated. Human herpesvirus 6 (HHV-6) reactivation has been the most frequently reported infection associated with this syndrome. However, a case of cytomegalovirus (CMV) infection was recently described associated with anticonvulsant-induced hypersensitivity syndrome. We report a case of severe allopurinol-induced hypersensitivity syndrome with pancreatitis associated with Epstein-Barr virus (EBV) infection. Active EBV infection was demonstrated in two consecutive serum samples by the presence of anti-EBV early antigen (EA) IgM antibodies and an increase in anti-EBV EA IgG antibodies, whereas no anti-EBV nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV-6 was suggested only by the presence of anti-HHV-6 IgM antibodies, but HHV-6 DNA was not detected by PCR in the serum. Other viral investigations showed previous infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination (hepatitis B virus), or absence of previous infection (hepatitis C virus, human immunodeficiency virus). We suggest that EBV infection may participate in some cases, as do the other herpesviruses HHV-6 or CMV, in the development of drug-induced hypersensitivity syndrome.

  20. Modulation of oxazolone-induced hypersensitivity in mice by selective PDE inhibitors

    Directory of Open Access Journals (Sweden)

    I. Moodley

    1995-01-01

    Full Text Available The effects of PDE inhibitors on oxazolone-induced contact hypersensitivity (CS were studied in mice. Rolipram, Ro 20-1724 and theophylline dose dependently inhibited CS but none caused >53% inhibition. ED30 values at 24 h before challenge for rolipram, Ro 20-1724 and theophylline were 2.1, 5.4 and 30.4 mg/kg, p.o., respectively. Milrinone and SKF 94836 at 30 mg/kg caused a small, but significant inhibition of 13% and 18%, respectively, although the inhibition (8% caused by zaprinast was not significant. Betamethasone (10 mg/kg, p.o. caused a marked inhibition (80% as did indomethacin (65% at 5 mg/kg, p.o.. Rolipram and Ro 20-1724 inhibited proliferation of mouse lymphoblasts with IC50 values of 0.08 μM and 0.83 μM, respectively. In contrast, zaprinast caused only a weak inhibition (IC50 = 119 μM of lymphocyte proliferation, whereas SKF 94836 and theophylline failed to cause any significant inhibition at 100 μM (26% and 2%, respectively. These findings suggest that PDE IV isozymes play a principal role in mediating CS by inhibiting lymphocyte activation.

  1. Pharmacological evaluation of NSAID-induced gastropathy as a "Translatable" model of referred visceral hypersensitivity.

    Science.gov (United States)

    Hummel, Michele; Knappenberger, Terri; Reilly, Meghan; Whiteside, Garth T

    2017-09-07

    To evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity. Gastric ulcer pain was induced by the oral administration of indomethacin to male, CD1 mice ( n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated. These mechanisms included: transient receptor potential (TRP), sodium and acid-sensing ion channels (ASICs) as well as opioid receptors and guanylate cyclase C (GC-C). Results showed that two opioids and a GC-C agonist, morphine, asimadoline and linaclotide, respectively, the TRP antagonists, AMG9810 and HC-030031 and the sodium channel blocker, carbamazepine, elicited a dose- and/or time-dependent attenuation of referred visceral hypersensitivity, while the ASIC blocker, amiloride, was ineffective at all doses tested. Together, these findings implicate opioid receptors, GC-C, and sodium and TRP channel activation as possible mechanisms associated with visceral hypersensitivity. More importantly, these findings also validate NSAID-induced gastropathy as a sensitive and clinically predictive mouse model suitable for assessing novel molecules with potential pain-attenuating properties.

  2. Activated platelets release sphingosine 1-phosphate and induce hypersensitivity to noxious heat stimuli in vivo

    Directory of Open Access Journals (Sweden)

    Daniela eWeth

    2015-04-01

    Full Text Available At the site of injury activated platelets release various mediators, one of which is sphingosine 1-phosphate (S1P. It was the aim of this study to explore whether activated human platelets had a pronociceptive effect in an in vivo mouse model and whether this effect was based on the release of S1P and subsequent activation of neuronal S1P receptors 1 or 3. Human platelets were prepared in different concentrations (105/µl, 106/µl, 107/µl and assessed in mice with different genetic backgrounds (WT, S1P1fl/fl, SNS-S1P1-/-, S1P3-/-. Intracutaneous injections of activated human platelets induced a significant, dose-dependent hypersensitivity to noxious thermal stimulation. The degree of heat hypersensitivity correlated with the platelet concentration as well as the platelet S1P content and the amount of S1P released upon platelet activation as measured with LC MS/MS. Despite the significant correlations between S1P and platelet count, no difference in paw withdrawal latency (PWL was observed in mice with a global null mutation of the S1P3 receptor or a conditional deletion of the S1P1 receptor in nociceptive primary afferents. Furthermore, neutralisation of S1P with a selective anti-S1P antibody did not abolish platelet induced heat hypersensitivity. Our results suggest that activated platelets release S1P and induce heat hypersensitivity in vivo. However, the platelet induced heat hypersensitivity was caused by mediators other than S1P.

  3. Presumed hydrochlorothiazide-associated immunologic-hypersensitivity-induced pericardial effusion

    Directory of Open Access Journals (Sweden)

    Michael J Chaskes

    2013-08-01

    Full Text Available A 50-year-old Caucasian female presented for a second opinion regarding a newly diagnosed pericardial effusion. Seven months previously, hydrochlorothiazide was introduced into her pharmacologic regimen to aid in the management of her hypertension. A routine echocardiogram indicated a large pericardial effusion with signs of early cardiac tamponade. The patient subsequently underwent successful pericardiocentesis with complete drainage of the pericardial effusion. The effusion was empirically attributed to a viral etiology. Repeat echocardiograms showed recurrence of the pericardial effusion. Prior to undergoing a second pericardiocentesis with pericardial biopsy, as her physicians recommended, the patient sought a second opinion. While obtaining the patient’s history, an allergy to sulfa was elicited. The possibility that the pericardial effusion may be secondary to an immunologic-hypersensitivity reaction was considered. It was recommended the patient discontinue the use of hydrochlorothiazide. Nine days following discontinuation of hydrochlorothiazide and without any other intervention, an echocardiogram was reported to show the size of the pericardial effusion had subsided substantially. Nine weeks following discontinuation, almost complete resolution of the pericardial effusion was reported. It is hypothesized that when treated with hydrochlorothiazide, the patient had an immune response leading to the pericardial effusion.

  4. Effect of Am-80, A Novel Retinoid Derivative, On Contact Hypersensitivity Caused by Repeated Applications of Hapten in Mice

    Directory of Open Access Journals (Sweden)

    Satoru Niwa

    2000-01-01

    Full Text Available Some retinoids show an anti-inflammatory action through regulation of transcription of various genes. In the present study, the inhibitory effect of 4-((5,6,7,8- tetrahydro-5,5,8,8-tetramethyl-2-naphthyl carbamoyl benzoic acid (Am-80, a synthetic retinoid, on mouse contact hypersensitivity provoked by repeated applications of 2,4-dinitrofluorobenzene (DNFB to the ear was investigated. Five-fold applications of DNFB on ears once per week elicited severe contact dermatitis with marked infiltration of inflammatory cells and elevation of anti-dinitrophenyl (DNP-IgE antibody in the serum. The Am-80 significantly inhibited ear swelling in a dose-dependent manner. In the histopathologic study, infiltration of inflammatory cells was clearly decreased by Am-80. However, Am-80 did not affect the production of DNP-specific IgE antibody both at the transcriptional and post-transcriptional levels. The effects of Am-80 on the transcriptional level of cytokines, interferon (IFN-γ, interleukin (IL-1 and IL-4 in cervical lymph nodes were investigated. Marked elevation of mRNA for all cytokines was observed and Am-80 potently inhibited the expression of IFN-γ mRNA, but not IL-1 and IL-4 mRNA. These findings indicated that Am-80 may inhibit the contact dermatitis at the post-sensitization phase by inhibiting IFN-γ production at the transcriptional level in mice.

  5. Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons

    Directory of Open Access Journals (Sweden)

    Langeslag Michiel

    2011-12-01

    Full Text Available Abstract Oncostatin M (OSM is a member of the interleukin-6 cytokine family and regulates eg. gene activation, cell survival, proliferation and differentiation. OSM binds to a receptor complex consisting of the ubiquitously expressed signal transducer gp130 and the ligand binding OSM receptor subunit, which is expressed on a specific subset of primary afferent neurons. In the present study, the effect of OSM on heat nociception was investigated in nociceptor-specific gp130 knock-out (SNS-gp130-/- and gp130 floxed (gp130fl/fl mice. Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of C57BL6J wild type mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to gp130fl/fl mice, OSM did not induce heat hypersensitivity in vivo in SNS-gp130-/- mice. OSM applied at the receptive fields of sensory neurons in in vitro skin-nerve preparations showed that OSM significantly increased the discharge rate during a standard ramp-shaped heat stimulus. The capsaicin- and heat-sensitive ion channel TRPV1, expressed on a subpopulation of nociceptive neurons, has been shown to play an important role in inflammation-induced heat hypersensitivity. Stimulation of cultured dorsal root ganglion neurons with OSM resulted in potentiation of capsaicin induced ionic currents. In line with these recordings, mice with a null mutation of the TRPV1 gene did not show any signs of OSM-induced heat hypersensitivity in vivo. The present data suggest that OSM induces thermal hypersensitivity by directly sensitizing nociceptors via OSMR-gp130 receptor mediated potentiation of TRPV1.

  6. Allergic contact dermatitis mimicking angioedema due to paraphenylendiamine hypersensitivity: a case report.

    Science.gov (United States)

    Tukenmez Demirci, Gulsen; Kivanc Altunay, Ilknur; Atis, Guldehan; Kucukunal, Asli

    2012-09-01

    Active sensitization to paraphenylendiamine (PPD) and related compounds from temporary black henna tattoos has become an epidemic in the recent years. Hair dyes also include PPD like black henna tatoos which cause allergic contact dermatitis. Skin lesions of allergic contact dermatitis from PPD are mostly seen as an exudative erythema, an erythema multiforme-like eruption or a bullous contact dermatitis. We, herein, report a 27 year-old woman with an angioedema-like reaction occurring after the first exposure to hair dye who was unaware of being previously sensitized to PPD from black henna tattoo.

  7. Expression of CD73 slows down migration of skin dendritic cells, affecting the sensitization phase of contact hypersensitivity reactions in mice.

    Science.gov (United States)

    Neuberger, A; Ring, S; Silva-Vilches, C; Schrader, J; Enk, A; Mahnke, K

    2017-09-01

    Application of haptens to the skin induces release of immune stimulatory ATP into the extracellular space. This "danger" signal can be converted to immunosuppressive adenosine (ADO) by the action of the ectonucleotidases CD39 and CD73, expressed by skin and immune cells. Thus, the expression and regulation of CD73 by skin derived cells may have crucial influence on the outcome of contact hypersensitivity (CHS) reactions. To investigate the role of CD73 expression during 2,4,6-trinitrochlorobenzene (TNCB) induced CHS reactions. Wild type (wt) and CD73 deficient mice were subjected to TNCB induced CHS. In the different mouse strains the resulting ear swelling reaction was recorded along with a detailed phenotypic analysis of the skin migrating subsets of dendritic cells (DC). In CD73 deficient animals the motility of DC was higher as compared to wt animals and in particular after sensitization we found increased migration of Langerin + DC from skin to draining lymph nodes (LN). In the TNCB model this led to a stronger sensitization as indicated by increased frequency of interferon-γ producing T cells in the LN and an increased ear thickness after challenge. CD73 derived ADO production slows down migration of Langerin + DC from skin to LN. This may be a crucial mechanism to avoid over boarding immune reactions against haptens. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  8. Ranitidine prevents postoperative transfusion-induced depression of delayed hypersensitivity

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hammer, J H; Moesgaard, F

    1989-01-01

    The influence of perioperative blood transfusion on postoperative depression of cell-mediated immunity (CMI) and the effect of ranitidine on transfusion-induced changes in postoperative CMI were investigated. CMI was assessed preoperatively and postoperatively by skin testing with seven common...

  9. Local suppression of contact hypersensitivity in mice by a new bifunctional psoralen, 4,4',5'-trimethylazapsoralen, and UVA radiation.

    Science.gov (United States)

    Aubin, F; Dall'Acqua, F; Kripke, M L

    1991-07-01

    Although psoralens plus UVA radiation (320-400 nm) have been widely used for the treatment of dermatologic diseases, the toxic effects of these agents have led investigators to develop new photochemotherapeutic compounds. One such compound is 4,4',5'-trimethylazapsoralen (TMAP), a new bifunctional molecule. The purpose of this study was to examine the immunologic side effects of repeated treatment of C3H mice with TMAP plus UVA radiation. During this treatment, the number of ATPase+, la+, and Thy-1+ dendritic epidermal cells greatly decreased in the treated site, despite the lack of phototoxicity. The reduction in the number of detectable cutaneous immune cells was accompanied by a decrease in the induction of contact hypersensitivity to dinitrofluorobenzene applied to the treated skin, an impairment in the antigen-presenting activity of draining lymph node cells, and the presence of suppressor lymphoid cells in the spleen of unresponsive mice. Treatment with UVA radiation alone also reduced the number of ATPase+, Ia+, and Thy-1+ cells in the skin, but did not cause any detectable alterations in immune function. This implies that morphologic alterations in these cells do not necessarily indicate loss of function. Thus, although TMAP in combination with UVA radiation is not overtly phototoxic, it is highly immunosuppressive in mice.

  10. Human telomeres are hypersensitive to UV-induced DNA Damage and refractory to repair.

    Directory of Open Access Journals (Sweden)

    Patrick J Rochette

    2010-04-01

    Full Text Available Telomeric repeats preserve genome integrity by stabilizing chromosomes, a function that appears to be important for both cancer and aging. In view of this critical role in genomic integrity, the telomere's own integrity should be of paramount importance to the cell. Ultraviolet light (UV, the preeminent risk factor in skin cancer development, induces mainly cyclobutane pyrimidine dimers (CPD which are both mutagenic and lethal. The human telomeric repeat unit (5'TTAGGG/CCCTAA3' is nearly optimal for acquiring UV-induced CPD, which form at dipyrimidine sites. We developed a ChIP-based technique, immunoprecipitation of DNA damage (IPoD, to simultaneously study DNA damage and repair in the telomere and in the coding regions of p53, 28S rDNA, and mitochondrial DNA. We find that human telomeres in vivo are 7-fold hypersensitive to UV-induced DNA damage. In double-stranded oligonucleotides, this hypersensitivity is a property of both telomeric and non-telomeric repeats; in a series of telomeric repeat oligonucleotides, a phase change conferring UV-sensitivity occurs above 4 repeats. Furthermore, CPD removal in the telomere is almost absent, matching the rate in mitochondria known to lack nucleotide excision repair. Cells containing persistent high levels of telomeric CPDs nevertheless proliferate, and chronic UV irradiation of cells does not accelerate telomere shortening. Telomeres are therefore unique in at least three respects: their biophysical UV sensitivity, their prevention of excision repair, and their tolerance of unrepaired lesions. Utilizing a lesion-tolerance strategy rather than repair would prevent double-strand breaks at closely-opposed excision repair sites on opposite strands of a damage-hypersensitive repeat.

  11. Loss of inducible photorepair in a frog cell line hypersensitive to solar UV light

    International Nuclear Information System (INIS)

    Chao, C.C.-K.

    1987-01-01

    The induction of enzymatic photorepair (EPR) in ICR 2A frog cells and a derived mutant cell line DRP36 hypersensitive to solar UV was studied. Using clonogenic assays, when induced wild-type cells demonstrated an 8-fold increase of EPR the mutant cells displayed a near-background level of inducible EPR. The constitutive EPR in mutant cells, however, was the same as in wild-type cells. A mixed culture of ICR 2A and DRP36 cells showed an intermediate inducible EPR depending upon the cell ratio. Inducible EPR was also detected at the DNA level in wild-type cells, but not in mutant cells. 29 refs.; 2 figs.; 2 tabs

  12. NKG2D-Dependent Activation of Dendritic Epidermal T cells in Contact Hypersensitivity

    DEFF Research Database (Denmark)

    Nielsen, Morten Milek; Dyring-Andersen, Beatrice; Schmidt, Jonas Damgård

    2015-01-01

    activated and produce IL-17 in an IL-1β-dependent manner during CHS. Various receptors on DETC, including NKG2D, are involved in DETC responses against tumors and during wound healing. The ligands for NKG2D (NKG2DL) are stress-induced proteins such as Mult-1, H60, Rae-1 in mice and MICA, MICB and ULBP...... in humans. Here, we show that allergens up-regulate expression of the NKG2DL Mult-1, H60 and Rae-1 in cultured mouse KC and of MICA in primary human KC. We demonstrate that Mult-1 is expressed in mouse skin exposed to allergen. Furthermore, we find that the vast majority of DETC in murine epidermis and skin...

  13. The preventive effect of resiniferatoxin on the development of cold hypersensitivity induced by spinal nerve ligation: involvement of TRPM8.

    Science.gov (United States)

    Koh, Won Uk; Choi, Seong-Soo; Kim, Ji Hyun; Yoon, Hye Joo; Ahn, Ho-Soo; Lee, Sun Kyung; Leem, Jeong Gil; Song, Jun Gol; Shin, Jin Woo

    2016-06-21

    Resiniferatoxin (RTX) is a potent analog of capsaicin and activates transient receptor potential (TRP) vanilloid type (TRPV) 1. In the current study, we investigated the preventive effect of perineural RTX on the development of cold hypersensitivity induced by spinal nerve ligation (SNL) in rats. Furthermore, we examined the association between the expression level of TRPV1, TRP ankyrin type (TRPA) 1 and TRP melastatin type (TRPM) 8 in the dorsal root ganglion (DRG) and cold hypersensitivity after SNL. RTX pretreatment prevented the development of SNL-induced hypersensitivity to mechanical, thermal, and cold stimuli. Western blot analysis 4 weeks after RTX pretreatment showed that RTX pretreatment decreased the protein expression level of SNL-induced TRPM8, but not TRPV1 or TRPA1, in the DRG of SNL rats. Immunofluorescent analysis revealed that up-regulated TRPM8-stained neurons after SNL co-localized with neurofilament 200-positive neurons located in the DRG. Pretreatment with perineural RTX significantly inhibits SNL-induced mechanical, thermal, and cold hypersensitivity. The antinociceptive effect of perineural RTX, especially on cold hypersensitivity, may be related to the suppression of TRPM8 expression in DRG.

  14. Effect of DA-9701 on colorectal distension-induced visceral hypersensitivity in a rat model.

    Science.gov (United States)

    Kim, Eun Ran; Min, Byung-Hoon; Lee, Tae Ho; Son, Miwon; Rhee, Poong-Lyul

    2014-07-01

    DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Co-rydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity.

  15. Metronidazole hypersensitivity.

    Science.gov (United States)

    Knowles, S; Choudhury, T; Shear, N H

    1994-03-01

    To report a case of a possible hypersensitivity reaction induced by metronidazole. An Asian woman with a history of recurrent vaginitis had previously developed localized erythema while on intravaginal metronidazole and nystatin. While receiving oral metronidazole for treatment of a current bacterial vaginosis, she developed chills, fever, generalized erythema, and a rash within 60 minutes of the first dose. Treatment with diphenhydramine was instituted. The following day while in the hospital, the patient's condition worsened; she experienced shortness of breath and increased edema of the extremities. Methylprednisolone was administered with diphenhydramine and her condition improved over the next 5 days. The patient's vaginitis was treated with gentian violet and she was discharged on a tapering dosage of prednisone. Metronidazole-induced cutaneous reactions and systemic hypersensitivity reactions are reviewed. Alternatives to metronidazole and other potential cross-reactive drugs are suggested for the treatment of recurrent vaginitis. Although the patient's initial reaction to metronidazole represented a rare event, written documentation and communication in the patient's native language may have prevented the subsequent severe hypersensitivity reaction.

  16. Immediate Hypersensitivity Reactions Induced by Triamcinolone in a Patient with Atopic Dermatitis.

    Science.gov (United States)

    Son, Jee Hee; Park, Sook Young; Cho, Yong Se; Chung, Bo Young; Kim, Hye One; Park, Chun Wook

    2018-03-19

    Corticosteroids are potent anti-inflammatory and anti-allergic agents used in the treatment of various inflammatory diseases, including allergic disease. They are frequently considered the therapy-of-choice for many skin diseases. However, allergic reactions caused by corticosteroids have been reported. Among these, delayed reactions to topical steroids are more common, whereas immediate reactions to systemic steroids are rare. Herein, we report the case of a 32-year-old woman with triamcinolone-induced immediate hypersensitivity reaction, in which the patient had a positive prick test result with triamcinolone. She has had atopic dermatitis (AD) for three years. She had used systemic steroid, cyclosporine, and antihistamine with topical steroids for AD. In clinic, approximately 10 minutes after intralesional injection of triamcinolone, she complained of erythematous patches with slight elevation and itching on the face, trunk, and both hands. After intravenous injection of dexamethasone, her symptoms got worse. After treatment with epinephrine, all symptoms resolved within two hours. We performed an open test and skin prick test. She had a positive result only from the prick test with triamcinolone; all other steroids showed negative results from the open tests. Dermatologists should be aware of the possibility of anaphylaxis or other allergic hypersensitivity in response to corticosteroids. © 2018 The Korean Academy of Medical Sciences.

  17. Allergic Contact Dermatitis Induced by Textile Necklace

    Directory of Open Access Journals (Sweden)

    Uffe Nygaard

    2013-11-01

    Full Text Available Allergic contact dermatitis to textile dyes is considered to be a rare phenomenon. A recent review reported a prevalence of contact allergy to disperse dyes between 0.4 and 6.7%. The relevance of positive patch testing was not reported in all studies. Textile dye allergy is easily overlooked and is furthermore challenging to investigate as textile dyes are not labelled on clothing. In this report, we present a case of allergic contact dermatitis to a textile necklace. The patch test showed strong reactions to the necklace and the azo dyes Disperse Orange 1 and Disperse Yellow 3. Despite the European legislation and the reduced use of disperse dyes in Third World countries, disperse azo dyes still induce new cases of allergic contact dermatitis.

  18. N-acetylcysteine attenuates hexavalent chromium-induced hypersensitivity through inhibition of cell death, ROS-related signaling and cytokine expression.

    Directory of Open Access Journals (Sweden)

    Yu-Hsuan Lee

    Full Text Available Chromium hypersensitivity (chromium-induced allergic contact dermatitis is an important issue in occupational skin disease. Hexavalent chromium (Cr (VI can activate the Akt, Nuclear factor κB (NF-κB, and Mitogen-activated protein kinase (MAPK pathways and induce cell death, via the effects of reactive oxygen species (ROS. Recently, cell death stimuli have been proposed to regulate the release of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α and interleukin-1 (IL-1. However, the exact effects of ROS on the signaling molecules and cytotoxicity involved in Cr(VI-induced hypersensitivity have not yet been fully demonstrated. N-acetylcysteine (NAC could increase glutathione levels in the skin and act as an antioxidant. In this study, we investigated the effects of NAC on attenuating the Cr(VI-triggered ROS signaling in both normal keratinocyte cells (HaCaT cells and a guinea pig (GP model. The results showed the induction of apoptosis, autophagy and ROS were observed after different concentrations of Cr(VI treatment. HaCaT cells pretreated with NAC exhibited a decrease in apoptosis and autophagy, which could affect cell viability. In addition, Cr (VI activated the Akt, NF-κB and MAPK pathways thereby increasing IL-1α and TNF-α production. However, all of these stimulation phenomena could be inhibited by NAC in both of in vitro and in vivo studies. These novel findings indicate that NAC may prevent the development of chromium hypersensitivity by inhibiting of ROS-induced cell death and cytokine expression.

  19. Pathogen-induced ERF68 regulates hypersensitive cell death in tomato.

    Science.gov (United States)

    Liu, An-Chi; Cheng, Chiu-Ping

    2017-10-01

    Ethylene response factors (ERFs) are a large plant-specific transcription factor family and play diverse important roles in various plant functions. However, most tomato ERFs have not been characterized. In this study, we showed that the expression of an uncharacterized member of the tomato ERF-IX subgroup, ERF68, was significantly induced by treatments with different bacterial pathogens, ethylene (ET) and salicylic acid (SA), but only slightly induced by bacterial mutants defective in the type III secretion system (T3SS) or non-host pathogens. The ERF68-green fluorescent protein (ERF68-GFP) fusion protein was localized in the nucleus. Transactivation and electrophoretic mobility shift assays (EMSAs) further showed that ERF68 was a functional transcriptional activator and was bound to the GCC-box. Moreover, transient overexpression of ERF68 led to spontaneous lesions in tomato and tobacco leaves and enhanced the expression of genes involved in ET, SA, jasmonic acid (JA) and hypersensitive response (HR) pathways, whereas silencing of ERF68 increased tomato susceptibility to two incompatible Xanthomonas spp. These results reveal the involvement of ERF68 in the effector-triggered immunity (ETI) pathway. To identify ERF68 target genes, chromatin immunoprecipitation combined with high-throughput sequencing (ChIP-seq) was performed. Amongst the confirmed target genes, a few genes involved in cell death or disease defence were differentially regulated by ERF68. Our study demonstrates the function of ERF68 in the positive regulation of hypersensitive cell death and disease defence by modulation of multiple signalling pathways, and provides important new information on the complex regulatory function of ERFs. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  20. Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice

    Science.gov (United States)

    Yan, Shengmin; Zhang, Hongxia; Zheng, Fei; Sheng, Nan; Guo, Xuejiang; Dai, Jiayin

    2015-06-01

    Perfluoroalkyl acids (PFAAs) are widely used in many applications due to their unique physical and chemical characteristics. Because of the increasing prevalence of metabolic syndromes, including obesity, dyslipidemia and insulin resistance, concern has arisen about the roles of environmental pollutants in such diseases. Earlier epidemiologic studies showed a potential association between perfluorooctanoic acid (PFOA) and glucose metabolism, but how PFOA influences glucose homeostasis is still unknown. Here, we report on the modulation of the phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT) signaling pathway in the livers of mice after 28 d of exposure to PFOA. Compared with normal mice, PFOA exposure significantly decreased the expression of the phosphatase and tensin homologue (PTEN) protein and affected the PI3K-AKT signaling pathway in the liver. Tolerance tests further indicated that PFOA exposure induced higher insulin sensitivity and glucose tolerance in mice. Biochemical analysis revealed that PFOA exposure reduced hepatic glycogen synthesis, which might be attributed to gluconeogenesis inhibition. The levels of several circulating proteins were altered after PFOA exposure, including proteins potentially related to diabetes and liver disease. Our results suggest that PFOA affected glucose metabolism and induced insulin hypersensitivity in mice.

  1. Electroacupuncture alleviates stress-induced visceral hypersensitivity through an opioid system in rats

    Science.gov (United States)

    Zhou, Yuan-Yuan; Wanner, Natalie J; Xiao, Ying; Shi, Xuan-Zheng; Jiang, Xing-Hong; Gu, Jian-Guo; Xu, Guang-Yin

    2012-01-01

    AIM: To investigate whether stress-induced visceral hypersensitivity could be alleviated by electroacupuncture (EA) and whether EA effect was mediated by endogenous opiates. METHODS: Six to nine week-old male Sprague-Dawley rats were used in this study. Visceral hypersensitivity was induced by a 9-d heterotypic intermittent stress (HIS) protocol composed of 3 randomly stressors, which included cold restraint stress at 4 °C for 45 min, water avoidance stress for 60 min, and forced swimming stress for 20 min, in adult male rats. The extent of visceral hypersensitivity was quantified by electromyography or by abdominal withdrawal reflex (AWR) scores of colorectal distension at different distention pressures (20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg). AWR scores either 0, 1, 2, 3 or 4 were obtained by a blinded observer. EA or sham EA was performed at classical acupoint ST-36 (Zu-San-Li) or BL-43 (Gao-Huang) in both hindlimbs of rats for 30 min. Naloxone (NLX) or NLX methiodide (m-NLX) was administered intraperitoneally to HIS rats in some experiments. RESULTS: HIS rats displayed an increased sensitivity to colorectal distention, which started from 6 h (the first measurement), maintained for 24 h, and AWR scores returned to basal levels at 48 h and 7 d after HIS compared to pre-HIS baseline at different distention pressures. The AWR scores before HIS were 0.6 ± 0.2, 1.3 ± 0.2, 1.9 ± 0.2 and 2.3 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. Six hours after termination of the last stressor, the AWR scores were 2.0 ± 0.1, 2.5 ± 0.1, 2.8 ± 0.2 and 3.5 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. EA given at classical acupoint ST-36 in both hindlimbs for 30 min significantly attenuated the hypersensitive responses to colorectal distention in HIS rats compared with sham EA treatment [AWRs at 20 mmHg: 2.0 ± 0.2 vs 0.7 ± 0.1, P = 4.23 711 E-4; AWRs at 40 mmHg: 2.6 ± 0.2 vs 1.5 ± 0.2, P

  2. IN VITRO MODELS TO EVALUATE DRUG-INDUCED HYPERSENSITIVITY: POTENTIAL TEST BASED ON ACTIVATION OF DENDRITIC CELLS

    Directory of Open Access Journals (Sweden)

    Valentina Galbiati

    2016-07-01

    Full Text Available Hypersensitivity drug reactions (HDRs are the adverse effect of pharmaceuticals that clinically resemble allergy. HDRs account for approximately 1/6 of drug-induced adverse effects, and include immune-mediated ('allergic' and non immune-mediated ('pseudo allergic' reactions. In recent years, the severe and unpredicted drug adverse events clearly indicate that the immune system can be a critical target of drugs. Enhanced prediction in preclinical safety evaluation is, therefore, crucial. Nowadays, there are no validated in vitro or in vivo methods to screen the sensitizing potential of drugs in the pre-clinical phase. The problem of non-predictability of immunologically-based hypersensitivity reactions is related to the lack of appropriate experimental models rather than to the lack of -understanding of the adverse phenomenon.We recently established experimental conditions and markers to correctly identify drug associated with in vivo hypersensitivity reactions using THP-1 cells and IL-8 production, CD86 and CD54 expression. The proposed in vitro method benefits from a rationalistic approach with the idea that allergenic drugs share with chemical allergens common mechanisms of cell activation. This assay can be easily incorporated into drug development for hazard identification of drugs, which may have the potential to cause in vivo hypersensitivity reactions. The purpose of this review is to assess the state of the art of in vitro models to assess the allergenic potential of drugs based on the activation of dendritic cells.

  3. A single-arm Phase II validation study of preventing oxaliplatin-induced hypersensitivity reactions by dexamethasone: the AVOID trial

    Directory of Open Access Journals (Sweden)

    Yoshida Y

    2015-11-01

    Full Text Available Yoichiro Yoshida,1 Keiji Hirata,2 Hiroshi Matsuoka,3 Shigeyoshi Iwamoto,4 Masahito Kotaka,5 Hideto Fujita,6 Naoya Aisu,1 Seiichiro Hoshino,1 Takeo Kosaka,6 Kotaro Maeda,3 Fumiaki Kiyomi,7 Yuichi Yamashita1 1Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan; 2Department of Surgery, Fukuoka Sanno Hospital, Fukuoka, Japan; 3Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan; 4Department of Surgery, Kansai Medical University Hirakata Hospital, Osaka, Japan; 5Gastrointestinal Cancer Center, Sano Hospital, Kobe, Japan; 6Department of Surgical Oncology, Kanazawa Medical University, Uchinada, Japan; 7Academia, Industry and Government Collaborative Research Institute of Translational Medicine for Life Innovation, Fukuoka University, Fukuoka, Japan Background: Patients with colorectal cancer treated with oxaliplatin are at risk of hypersensitivity reactions, with the incidence estimated to be 12%–20%. Coinfusion of dexamethasone and oxaliplatin could potentially reduce the incidence of these reactions, but oxaliplatin is reported to be incompatible with alkaline compounds in solution. However, in a previous retrospective study we found that the pH of a solution of dexamethasone and oxaliplatin was less than 7.4, and that hypersensitivity to oxaliplatin could have been prevented by coinfusion of dexamethasone. We aimed to evaluate the effectiveness of coinfusion of dexamethasone and oxaliplatin to prevent oxaliplatin-induced hypersensitivity reactions.Patients and methods: The AVOID trial was a prospective, multicenter, open-label, single-arm Phase II trial conducted from January to September 2013. The study included 73 patients who received capecitabine plus oxaliplatin (XELOX or XELOX plus bevacizumab therapy for colorectal cancer. In all patients, oxaliplatin was administered in combination with dexamethasone. The primary outcome measure was the presence of

  4. Visceral hypersensitivity is provoked by 2,4,6-trinitrobenzene sulfonic acid-induced ileitis in rats

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Shah

    2016-07-01

    Full Text Available Background and Aims: Crohn’s Disease (CD, a chronic Inflammatory Bowel Disease, can occur in any part of the gastrointestinal tract, but most frequently in the ileum. Visceral hypersensitivity contributes for development of chronic abdominal pain in this disease. Currently, the understanding of the mechanism underlying hypersensitivity of Crohn’s ileitis has been hindered by a lack of specific animal model. The present study is undertaken to investigate the visceral hypersensitivity provoked by 2,4,6-trinitrobenzene sulfonic (TNBS-induced ileitis rats.Methods: Male Sprague-Dawley rats were anaesthetized and laparotomized for intraileal injection of TNBS (0.6 ml, 80 mg/kg body weight in 30% ethanol, n = 48, an equal volume of 30% Ethanol (n = 24 and Saline (n = 24, respectively. Visceral hypersensitivity was assessed by visceromotor responses (VMR to 20, 40, 60, 80 and 100 mmHg colorectal distension pressure (CRD at day 1, 3, 7, 14, 21 and 28. Immediately after CRD test, the rats were euthanized for collecting the terminal ileal segment for histopathological examinations and ELISA of myleoperoxidase and cytokines (TNF-α, IL-1β, IL-6, and dorsal root ganglia (T11 for determination of calcitonin gene-related peptide by immunohistochemistry, respectively. Results: Among all groups, TNBS-treatment showed transmural inflammation initially at 3 days, reached maximum at 7 days and persisted up to 21 days. The rats with ileitis exhibited (P < 0.05 VMR to CRD at day 7 to day 21. The calcitonin gene-related peptide-immunoreactive positive cells increased (P < 0.05 in dorsal root ganglia at day 7 to 21, which was persistently consistent with visceral hypersensitivity in TNBS-treated rats.Conclusions: TNBS injection into the ileum induced transmural ileitis including granuloma and visceral hypersensitivity. As this model mimics clinical manifestations of CD, it may provide a road map to probe the pathogenesis of gut inflammation and visceral

  5. Sex differences in stress-induced visceral hypersensitivity following early life adversity: a two hit model.

    Science.gov (United States)

    Prusator, D K; Greenwood-Van Meerveld, B

    2016-12-01

    Early life adversity (ELA) has been indicated as a risk factor for the development of stress axis dysfunction in adulthood, specifically in females. We previously showed that unpredictable ELA induces visceral hyperalgesia in adult female rats. It remains to be determined whether ELA alters visceral nociceptive responses to stress in adulthood. The current study tested the hypothesis that following ELA, exposure to an adulthood stressor, or second hit, serves as a risk factor for exaggerated stress-induced visceral hypersensitivity that is sex-specific. Following ELA, adult stress was induced via a single exposure (acute) or repetitive daily exposure, 1 h/day for 7 days (chronic), to water avoidance stress (WAS). Acute WAS increased pain behaviors in all adult female rats, however, females that experienced unpredictable ELA exhibited significantly more pain behaviors compared to those exposed to predictable ELA or controls. Following chronic WAS, all adult females exhibited increased pain responses, however, an exaggerated response was observed in rats exposed to unpredictable or predictable ELA compared to controls. Similarly, in adult male rats exposure to acute or chronic WAS increased pain behaviors, however, there were no differences in pain behaviors between ELA groups. This study highlights a novel consequence of ELA on stress-induced visceral nociception in adulthood that is sex-specific. More importantly, our study suggests that ELA not only serves as a risk factor for development of chronic pain in adulthood, but also serves as a predisposition for worsening of visceral pain following adult stress in female rats. © 2016 John Wiley & Sons Ltd.

  6. Short-term pre- and post-operative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception.

    Science.gov (United States)

    Cao, Jing; Wang, Po-Kai; Tiwari, Vinod; Liang, Lingli; Lutz, Brianna Marie; Shieh, Kun-Ruey; Zang, Wei-Dong; Kaufman, Andrew G; Bekker, Alex; Gao, Xiao-Qun; Tao, Yuan-Xiang

    2015-12-02

    Chronic stress has been reported to increase basal pain sensitivity and/or exacerbate existing persistent pain. However, most surgical patients have normal physiological and psychological health status such as normal pain perception before surgery although they do experience short-term stress during pre- and post-operative periods. Whether or not this short-term stress affects persistent postsurgical pain is unclear. In this study, we showed that pre- or post-surgical exposure to immobilization 6 h daily for three consecutive days did not change basal responses to mechanical, thermal, or cold stimuli or peak levels of incision-induced hypersensitivity to these stimuli; however, immobilization did prolong the duration of incision-induced hypersensitivity in both male and female rats. These phenomena were also observed in post-surgical exposure to forced swimming 25 min daily for 3 consecutive days. Short-term stress induced by immobilization was demonstrated by an elevation in the level of serum corticosterone, an increase in swim immobility, and a decrease in sucrose consumption. Blocking this short-term stress via intrathecal administration of a selective glucocorticoid receptor antagonist, RU38486, or bilateral adrenalectomy significantly attenuated the prolongation of incision-induced hypersensitivity to mechanical, thermal, and cold stimuli. Our results indicate that short-term stress during the pre- or post-operative period delays postoperative pain recovery although it does not affect basal pain perception. Prevention of short-term stress may facilitate patients' recovery from postoperative pain.

  7. Performance of genetic risk factors in prediction of trichloroethylene induced hypersensitivity syndrome.

    Science.gov (United States)

    Dai, Yufei; Chen, Ying; Huang, Hanlin; Zhou, Wei; Niu, Yong; Zhang, Mingrong; Bin, Ping; Dong, Haiyan; Jia, Qiang; Huang, Jianxun; Yi, Juan; Liao, Qijun; Li, Haishan; Teng, Yanxia; Zang, Dan; Zhai, Qingfeng; Duan, Huawei; Shen, Juan; He, Jiaxi; Meng, Tao; Sha, Yan; Shen, Meili; Ye, Meng; Jia, Xiaowei; Xiang, Yingping; Huang, Huiping; Wu, Qifeng; Shi, Mingming; Huang, Xianqing; Yang, Huanming; Luo, Longhai; Li, Sai; Li, Lin; Zhao, Jinyang; Li, Laiyu; Wang, Jun; Zheng, Yuxin

    2015-07-20

    Trichloroethylene induced hypersensitivity syndrome is dose-independent and potentially life threatening disease, which has become one of the serious occupational health issues and requires intensive treatment. To discover the genetic risk factors and evaluate the performance of risk prediction model for the disease, we conducted genomewide association study and replication study with total of 174 cases and 1761 trichloroethylene-tolerant controls. Fifty seven SNPs that exceeded the threshold for genome-wide significance (P < 5 × 10(-8)) were screened to relate with the disease, among which two independent SNPs were identified, that is rs2857281 at MICA (odds ratio, 11.92; P meta = 1.33 × 10(-37)) and rs2523557 between HLA-B and MICA (odds ratio, 7.33; P meta = 8.79 × 10(-35)). The genetic risk score with these two SNPs explains at least 20.9% of the disease variance and up to 32.5-fold variation in inter-individual risk. Combining of two SNPs as predictors for the disease would have accuracy of 80.73%, the area under receiver operator characteristic curves (AUC) scores was 0.82 with sensitivity of 74% and specificity of 85%, which was considered to have excellent discrimination for the disease, and could be considered for translational application for screening employees before exposure.

  8. Antibiotic-induced immediate type hypersensitivity is a risk factor for positive allergy skin tests for neuromuscular blocking agents.

    Science.gov (United States)

    Hagau, Natalia; Gherman, Nadia; Cocis, Mihaela; Petrisor, Cristina

    2016-01-01

    Skin tests for neuromuscular blocking agents (NMBAs) are not currently recommended for the general population undergoing general anaesthesia. In a previous study we have reported a high incidence of positive allergy tests for NMBAs in patients with a positive history of non-anaesthetic drug allergy, a larger prospective study being needed to confirm those preliminary results. The objective of this study was to compare the skin tests results for patients with a positive history of antibiotic-induced immediate type hypersensitivity reactions to those of controls without drug allergies. Ninety eight patients with previous antibiotic hypersensitivity and 72 controls were prospectively included. Skin tests were performed for atracurium, pancuronium, rocuronium, and suxamethonium. We found 65 positive skin tests from the 392 tests performed in patients with a positive history of antibiotic hypersensitivity (1 6.58%) and 23 positive skin tests from the 288 performed in controls (7.98%), the two incidences showing significant statistical difference (p = 0.0011). The relative risk for having a positive skin test for NMBAs for patients versus controls was 1.77 (1.15-2.76). For atracurium, skin tests were more often positive in patients with a positive history of antibiotic hypersensitivity versus controls (p = 0.02). For pancuronium, rocuronium and suxamethonium the statistical difference was not attained (p-values 0.08 for pancuronium, 0.23 for rocuronium, and 0.26 for suxamethonium). Patients with a positive history of antibiotic hypersensitivity seem to have a higher incidence of positive skin tests for NMBAs. They might represent a group at higher risk for developing intraoperative anaphylaxis compared to the general population. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  9. Acute cold hypersensitivity characteristically induced by oxaliplatin is caused by the enhanced responsiveness of TRPA1 in mice

    Directory of Open Access Journals (Sweden)

    Zhao Meng

    2012-07-01

    Full Text Available Abstract Background Oxaliplatin, a platinum-based chemotherapeutic agent, causes an unusual acute peripheral neuropathy. Oxaliplatin-induced acute peripheral neuropathy appears in almost all patients rapidly after infusion, and is triggered or exacerbated by cold, while its mechanisms are poorly understood. In this study, the involvement of thermosensitive transient receptor potential channels (TRPA1, TRPM8 and TRPV1 in oxaliplatin-induced acute hypersensitivity was investigated in mice. Results A single intraperitoneal administration of oxaliplatin (1–10 mg/kg induced cold but not mechanical hypersensitivity within 2 h in a dose-dependent manner. Infusion of the oxaliplatin metabolite, oxalate (1.7 mg/kg, also induced acute cold hypersensitivity, while another platinum-based chemotherapeutic agent, cisplatin (5 mg/kg, or the non-platinum-containing chemotherapeutic agent, paclitaxel (6 mg/kg failed to induce mechanical or cold hypersensitivity. The oxaliplatin-induced acute cold hypersensitivity was abolished by the TRPA1 antagonist HC-030031 (100 mg/kg and by TRPA1 deficiency. The nocifensive behaviors evoked by intraplantar injections of allyl-isothiocyanate (AITC; TRPA1 agonist were significantly enhanced in mice treated for 2 h with oxaliplatin (1–10 mg/kg in a dose-dependent manner, while capsaicin (TRPV1 agonist-evoked nocifensive behaviors were not affected. Menthol (TRPM8/TRPA1 agonist-evoked nocifensive-like behaviors were also enhanced by oxaliplatin pretreatment, which were inhibited by TRPA1 deficiency. Similarly, oxalate enhanced, but neither cisplatin nor paclitaxel affected AITC-evoked nocifensive behaviors. Pretreatment of cultured mouse dorsal root ganglia (DRG neurons with oxaliplatin (30–300 μM for 1, 2, or 4 h significantly increased the number of AITC-sensitive neurons in a concentration-dependent manner whereas there was no change in the number of menthol- or capsaicin-sensitive neurons

  10. Hypersensitivity vasculitis

    Science.gov (United States)

    Cutaneous small vessel vasculitis; Allergic vasculitis; Leukocytoclastic vasculitis ... Hypersensitivity vasculitis, or cutaneous small vessel vasculitis, is caused by: An allergic reaction to a drug or other foreign ...

  11. Transfection of normal human and Chinese hamster DNA corrects diepoxybutane-induced chromosomal hypersensitivity of Fanconi anemia fibroblasts

    International Nuclear Information System (INIS)

    Shaham, M.; Adler, B.; Ganguly, S.; Chaganti, R.S.K.

    1987-01-01

    Cultured cells from individuals affected with Fanconi anemia (FA) exhibit spontaneous chromosome breakage and hypersensitivity to the cell killing and clastogenic effects of the difunctional alkylating agent diepoxybutane (DEB). The authors report here the correction of both of these DEB-hypersensitivity phenotypes of FA cells achieved by cotransfection of normal placental of Chinese hamster lung cell DNA and the plasmid pSV2-neo-SVgpt. Transfectants were selected for clonogenic survival after treatment with DEB at a dose of 5 μgml. At this dose of DEB, the clonogenicity of normal fibroblasts was reduced to 50% and that of FA fibroblasts was reduced to zero. DEB-resistant (DEB/sup r/) colonies selected in this system exhibited a normal response to DEB-induced chromosome breakage and resistance to repeated DEB treatment. The neo and gpt sequences were detected by Southern blot analysis of DNA from one of four DEB/sup r/ colonies independently derived from transfection of human DNA and one of three DEB/sup r/ colonies independently derived from transfection of Chinese hamster DNA. The results demonstrate that DNA sequences that complement the two hallmark cellular phenotypes (cellular and chromosomal hypersensitivity to alkylating agents) of FA are present in human as well as Chinese hamster DNA. The cloning of these genes using transfection strategies can be expected to enable molecular characterization of FA

  12. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    International Nuclear Information System (INIS)

    Tamura, Akitoshi; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-01-01

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  13. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Akitoshi, E-mail: akitoshi-tamura@ds-pharma.co.jp; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  14. High cytokinin levels induce a hypersensitive-like response in tobacco

    Czech Academy of Sciences Publication Activity Database

    Novák, J.; Pavlů, J.; Novák, Ondřej; Nožková-Hlaváčková, V.; Špundová, M.; Hlavinka, J.; Koukalová, Š.; Skalák, J.; Černý, M.; Brzobohatý, B.

    2013-01-01

    Roč. 112, č. 1 (2013), s. 41-55 ISSN 0305-7364 R&D Projects: GA MŠk 1M06030; GA MŠk LK21306 Institutional support: RVO:61389030 Keywords : Cytokinin * hypersensitive response * hydrogen peroxide Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.295, year: 2013

  15. Gender and dose dependent ovalbumin induced hypersensitivity responses in murine model of food allergy

    Science.gov (United States)

    While federal regulations mandate the labeling of major food allergens, allowable food allergen thresholds have yet to be determined. Therefore the aim of this project was to identify the lowest egg allergen ovalbumin (OVA) dose causing hypersensitization using a validated murine model. Mice were or...

  16. Peripheral a-helical CRF (9-41) does not reverse stress-induced mast cell dependent visceral hypersensitivity in maternally separated rats

    NARCIS (Netherlands)

    van den Wijngaard, R. M.; Stanisor, O. I.; van Diest, S. A.; Welting, O.; Wouters, M. M.; de Jonge, W. J.; Boeckxstaens, G. E.

    2012-01-01

    Background Acute stress-induced hypersensitivity to colorectal distention was shown to depend on corticotropin releasing factor (CRF)-induced mast cell degranulation. At present it remains unclear whether CRF also induces chronic poststress activation of these cells. Accordingly, the objective of

  17. Cannabinoid 1 receptor knockout mice display cold allodynia, but enhanced recovery from spared-nerve injury-induced mechanical hypersensitivity.

    Science.gov (United States)

    Sideris, Alexandra; Piskoun, Boris; Russo, Lori; Norcini, Monica; Blanck, Thomas; Recio-Pinto, Esperanza

    2016-01-01

    significant recovery from spared-nerve injury-induced mechanical hypersensitivity are two novel phenotypes which characterize the global CB1R-/- mice. An increase in transient receptor potential channel of melastatin 8 channel function in DRG neurons may underlie the cold phenotype. Recovery of mechanical thresholds in the CB1R knockouts was independent of motor function. These results indicate that CB1R expression contributes to the development of persistent mechanical hypersensitivity, protects against the development of robust cold allodynia but is not involved in motor impairment following spared-nerve injury in mice. © The Author(s) 2016.

  18. Production of TNF-alpha by skin explants of dinitrochlorobenzene-challenged ears in rats: A model for the evaluation of contact hypersensitivity

    Directory of Open Access Journals (Sweden)

    Kataranovski Milena

    2002-01-01

    Full Text Available Background. Contact hypersensitivity (CHS is a local inflammatory response of the skin following challenge of hapten-sensitized animals. It is the consequence of cell infiltration of derm and the release of inflammation mediators, among which Tumor necrosis factor-alpha (TNF-α is one of the most important factors. The intensity of the inflammation could be quantified by ear swelling which is the classical manifestation of the reaction. This study was testing the working hypothesis that levels of TNF-α in skin organ culture medium should correlate with the intensity of CHS reaction measured in vivo by ear swelling assay, and with the density of dermal infiltrate in ear skin samples. In order to test the working hypothesis, the intensity of inflammatory reaction following challenge was evaluated by classical measurements of ear swelling, by the determination of TNF-α levels in culture fluids of ear skin following epicutaneous application of dinitrochlorobenzene (DNCB into the ears of sensitized animals. Methods. Animal model of CHS reaction to DNCB in Albino Oxford rats was used as described. Ear swelling was quantified in percentage terms as the difference in thickness between the challenged and nontreated ears of the same animal. Dermal infiltrate density in histopathologically analyzed samples of ear skin was evaluated by computer-assisted image analysis. Ear skin samples were cultured in standard medium for 24 h, and TNF-α concentration in the conditioned medium was subsequently determined with ELISA test. Results. Dose-dependent increase in the density of the dermal infiltrate and in TNF-α in CM were noted following the application of 0.65%, 1.3% and 2.6% of DNCB to the ears of previously sensitized rats. The correlation between ear swelling and the levels of TNF-α (r=0.933, p<0.001 in CM, and between ear swelling and dermal infiltrate density (r=0.916, p<0.001 was found. Correlation was also found between the density of the dermal

  19. The effect of chronic low-dose UVB radiation on Langerhans cells, sunburn cells, urocanic acid isomers, contact hypersensitivity and serum immunoglobulins in mice

    International Nuclear Information System (INIS)

    El-Ghorr, A.A.; Norval, M.; Lappin, M.B.

    1995-01-01

    C3H mice were irradiated three times a week for up to 6 weeks with either 500 J/m 2 or 1000 J/m 2 broadband UVB (270-350 nm) or 3000 J/m 2 narrowband UVB (311-312 nm; TL01 source). Each dose was suberythemal to the mouse strain used. The number of Langerhans cells (LC) in the epidermis was reduced by over 50% after 2 weeks of irradiation with the UVB source and by 20% following TL01 irradiation. Continued irradiation for up to 6 weeks resulted in no further decrease in LC numbers in the case of the UVB source but a steady decline to 40% in the case of the TL01 source. Sunburn cells were detected following irradiation with both sources but the numbers were very low in comparison with acute exposure. Ultraviolet-B exposure resulted in doubling of the thickness of the epidermis throughout the 6 weeks of irradiation while TL01 exposure did not alter epidermal thickness. Conversion of trans- to cis-urocanic acid (UCA) was observed with both UVB and TL01 sources. The percentage of cis-UCA started to return to normal after 4 weeks of TL01 exposure despite continued irradiation. As observed following a single exposure, the contact hypersensitivity (CH) response was significantly reduced following 6 weeks of UVB irradiation but was unaffected by TL01 exposure, indicating no correlation between cis-UCA levels and CH response. (author)

  20. Acute irritant threshold correlates with barrier function, skin hydration and contact hypersensitivity in atopic dermatitis and rosacea.

    Science.gov (United States)

    Darlenski, Razvigor; Kazandjieva, Jana; Tsankov, Nikolai; Fluhr, Joachim W

    2013-11-01

    The aim of the study was to disclose interactions between epidermal barrier, skin irritation and sensitization in healthy and diseased skin. Transepidermal water loss (TEWL) and stratum corneum hydration (SCH) were assessed in adult patients with atopic dermatitis (AD), rosacea and healthy controls. A 4-h patch test with seven concentrations of sodium lauryl sulphate was performed to determine the irritant threshold (IT). Contact sensitization pattern was revealed by patch testing with European baseline series. Subjects with a lower IT had higher TEWL values and lower SCH. Subjects with positive allergic reactions had significantly lower IT. In AD, epidermal barrier deterioration was detected on both volar forearm and nasolabial fold, while in rosacea, impeded skin physiology parameters were observed on the facial skin only, suggesting that barrier impediment is restricted to the face in rosacea, in contrast with AD where the abnormal skin physiology is generalized. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Soft-contact-lenses-induced complications

    Directory of Open Access Journals (Sweden)

    Suvajac Gordana

    2008-01-01

    Full Text Available Background/Aim. Soft contact lenses occupy significant place in ophthalmology, both in the correction of refraction anomalies and in the treatment of many eye diseases. The number of patients that wear soft contact lenses for the purpose of correcting ametropia is constantly increasing. Due to the increasing number of wearers, the percentage of complications that can lead to serious eye damage and serious vision loss is also increasing. The aim of this study was to point out the most common complications related to soft contact lens use. Methods. In the period from 1995−2004 this prospective study included 510 patients wearing soft contact lenses for correcting ametropia. None of the patients wore contact lenses before and none suffered from any system or local diseases that could affected the development of eventual complications. The study took seven years with the patients who wore conventional lenses and three years with those who wore replacement contact lenses. All the necessary ophthalmologic examinations were done (visual acuity, refractokeratometry, the quantity of tear film, biomicroscopic examination of anterior eye segment. All the complications were filmed by video camera. Results. Of all the patients, 19 had blepharitis, 73 suffered from “dry eye”, 57 had conjunctival hyperemia, 12 had conjunctivitis, 34 had gigantopapillary conjunctivitis (GPC, 93 had punctiform epitheliopathy, 20 had corneal infiltration, one patient had keratitis, 91 had corneal vascularisation, and 95 patients had corneal deposits. Conclusion. Both the type and frequency of complications related to soft contact lens use in our group of patients, proved to be significant. Some of this complications (keratitis can significantly damage vision and lead to loss of vision and sometimes can require operative treatment.

  2. Liver dysfunction induced by systemic hypersensitivity reaction to lamotrigine: case report

    Directory of Open Access Journals (Sweden)

    Sung Gyu Im

    2015-06-01

    Full Text Available Lamotrigine is an anticonvulsant drug used to treat partial and generalized seizure disorders. Hypersensitivity to lamotrigine usually causes mild symptoms such as fever, rash, and slight invasion of internal organs. However, a 33-year-old male patient who was admitted with Stevens-Johnson syndrome after taking lamotrigine for 15 days experienced hepatic failure and died 5 days after admission. This case demonstrates the importance of realizing that lamotrigine can lead to fatal hepatic failure, and that tests for the normal liver function should be performed when administering lamotrigine.

  3. Possible Immune Regulation of Natural Killer T Cells in a Murine Model of Metal Ion-Induced Allergic Contact Dermatitis

    Directory of Open Access Journals (Sweden)

    Kenichi Kumagai

    2016-01-01

    Full Text Available Metal often causes delayed-type hypersensitivity reactions, which are possibly mediated by accumulating T cells in the inflamed skin, called irritant or allergic contact dermatitis. However, accumulating T cells during development of a metal allergy are poorly characterized because a suitable animal model is unavailable. We have previously established novel murine models of metal allergy and found accumulation of both metal-specific T cells and natural killer (NK T cells in the inflamed skin. In our novel models of metal allergy, skin hypersensitivity responses were induced through repeated sensitizations by administration of metal chloride and lipopolysaccharide into the mouse groin followed by metal chloride challenge in the footpad. These models enabled us to investigate the precise mechanisms of the immune responses of metal allergy in the inflamed skin. In this review, we summarize the immune responses in several murine models of metal allergy and describe which antigen-specific responses occur in the inflamed skin during allergic contact dermatitis in terms of the T cell receptor. In addition, we consider the immune regulation of accumulated NK T cells in metal ion–induced allergic contact dermatitis.

  4. Increased 3H-spiperone binding sites in mesolimbic area related to methamphetamine-induced behavioral hypersensitivity

    International Nuclear Information System (INIS)

    Akiyama, K.; Sato, M.; Otsuki, S.

    1982-01-01

    The specific 3 H-spiperone binding to membrane homogenates of the striatum, mesolimbic area, and frontal cortex was examined in two groups of rats pretreated once daily with saline or 4 mg/kg of methamphetamine (MAP) for 14 days. At 7 days following cessation of chronic pretreatment, all rats received an injection of 4 mg/kg of MAP and were decapitated 1 hr after the injection. In the chronic saline-pretreatment group, the single administration of MAP induced significant changes in the number (Bmax) of specific 3 H-spiperone binding sites (a decrease in the striatum and an increase in the mesolimbic area and frontal cortex), but no significant changes in the affinity (KD) in any brain area. The chronic MAP pretreatment markedly augmented the changes in Bmax in the striatum and mesolimbic area. The increase in specific 3 H-spiperone binding sites in the mesolimbic area is discussed in relation to MAP-induced behavioral hypersensitivity

  5. Gram negative bacteria and contact lens induced acute red eye

    Directory of Open Access Journals (Sweden)

    Sankaridurg Padmaja

    1996-01-01

    Full Text Available Two patients using hydrogel contact lenses on a daily wear schedule slept overnight with the lenses and woke up with a Contact Lens Induced Acute Red Eye (CLARE. The contact lenses recovered aseptically at the time of the event grew significant colonies of Pseudomonas aeruginosa and Aeromonas hydrophila in patient A and Pseudomonas aeruginosa and Serratia liquefaciens from patient B. Similar organisams from the contact lenses were recovered from the lens case and lens care solutions of patient B. In both the patients the condition resolved on discontinuation of lens wear. Patient compliance as a requirement for successful contact lens wear is highlighted with the illustration of these cases.

  6. The excitatory amino acid receptor antagonist MK-801 prevents the hypersensitivity induced by spinal cord ischemia in the rat

    International Nuclear Information System (INIS)

    Hao, J.X.; Xu, X.J.; Aldskogius, H.; Seiger, A.; Wiesenfeld-Hallin, Z.

    1991-01-01

    Protection by the NMDA receptor antagonist MK-801 against transient spinal cord ischemia-induced hypersensitivity was studied in rats. The spinal ischemia was initiated by vascular occlusion resulting from the interaction between the photosensitizing dye Erythrosin B and an argon laser beam. The hypersensitivity, termed allodynia, where the animals reacted by vocalization to nonnoxious mechanical stimuli in the flank area, was consistently observed during several days after induction of the ischemia. Pretreatment with MK-801 (0.1-0.5 mg/kg, iv) 10 min before laser irradiation dose dependently prevented the occurrence of allodynia. The neuroprotective effect of MK-801 was not reduced by maintaining normal body temperature during and after irradiation. There was a significant negative correlation between the delay in the administration of MK-801 after irradiation and the protective effect of the drug. Histological examination revealed slight morphological damage in the spinal cord in 38% of control rats after 1 min of laser irradiation without pretreatment with MK-801. No morphological abnormalities were observed in rats after pretreatment with MK-801 (0.5 mg/kg). The present results provide further evidence for the involvement of excitatory amino acids, through activation of the NMDA receptor, in the development of dysfunction following ischemic trauma to the spinal cord

  7. Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity

    NARCIS (Netherlands)

    Bennett, Clare L.; van Rijn, Erwin; Jung, Steffen; Inaba, Kayo; Steinman, Ralph M.; Kapsenberg, Martien L.; Clausen, Björn E.

    2005-01-01

    Langerhans cells (LC) form a unique subset of dendritic cells ( DC) in the epidermis but so far their in vivo functions in skin immunity and tolerance could not be determined, in particular in relation to dermal DC ( dDC). Here, we exploit a novel diphtheria toxin (DT) receptor (DTR)/ DT- based

  8. Hydrodynamic instability induced liquid--solid contacts in film boiling

    International Nuclear Information System (INIS)

    Yao, S.; Henry, R.E.

    1976-01-01

    The film boiling liquid-solid contacts of saturated ethanol and water to horizontal flat gold plated copper are examined by using electric conductance probe. It is observed that the liquid-solid contacts occur over a wide temperature range, and generally, induced by hydrodynamic instabilities. The area of contact decreases exponentially with interface temperature and is liquid depth dependent. The averaged duration of contacts is strongly influenced by the dominant nucleation process, and thus, depends on the interface temperature and the wettability of the solid during the contact. The frequency of major contacts is about 1.5 times the bubble detaching frequency. It is found that the liquid-solid contacts may account for a large percentage of the film boiling heat transfer near the low temperature end of film boiling and decreases as the interface temperature increases

  9. Experimental Contact Lens to Prevent Glaucoma-Induced Blindness

    Science.gov (United States)

    ... An Experimental Contact Lens to Prevent Glaucoma-Induced Blindness By Sharon Reynolds Posted January 23, 2014 An ... group of conditions that can result in irreversible blindness. This vision loss can be reduced if glaucoma ...

  10. Bronchiolitis obliterans organising pneumonia associated with anticonvulsant hypersensitivity syndrome induced by lamotrigine.

    Science.gov (United States)

    Ghandourah, Hasan; Bhandal, Samarjeet; Brundler, Marie-Anne; Noseworthy, Mary

    2016-01-29

    A 14-year-old girl who was known to have a seizure disorder and on lamotrigine treatment was admitted to the hospital, with a history of rash, fever and cough. Her condition deteriorated with clinical features suggestive of anticonvulsant hypersensitivity syndrome (ACHS) complicated with bronchiolitis obliterans organising pneumonia (BOOP). Her chest CT showed multifocal parenchymal opacities and lung biopsy was typical for BOOP. Initially, the lamotrigine was discontinued since the onset of the rash, then she was treated for pneumonia with antibiotics, which may have delayed the diagnosis. Eventually, BOOP was considered and she was treated with a high dose of corticosteroid. She improved clinically and her repeated chest CT showed a marked resolution of the lesions. This case illustrates the possible occurrence of BOOP as a complication of ACHS secondary to lamotrigine treatment. 2016 BMJ Publishing Group Ltd.

  11. Models of Inflammation: Carrageenan- or Complete Freund's Adjuvant (CFA)-Induced Edema and Hypersensitivity in the Rat.

    Science.gov (United States)

    McCarson, Kenneth E

    2015-09-01

    Animal models of inflammation are used to assess the production of inflammatory mediators at sites of inflammation, the processing of pain sensation at CNS sites, the anti-inflammatory properties of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), and the efficacy of putative analgesic compounds in reversing cutaneous hypersensitivity. Detailed in this unit are methods to elicit and measure carrageenan- and complete Freund's adjuvant (CFA)-induced cutaneous inflammation. Due to possible differences between the dorsal root sensory system and the trigeminal sensory system, injections into either the footpad or vibrissal pad are described. In this manner, cutaneous inflammation can be assessed in tissue innervated by the lumbar dorsal root ganglion neurons (footpad) or by the trigeminal ganglion neurons (vibrissal pad). Copyright © 2015 John Wiley & Sons, Inc.

  12. Multiple cavities with halo sign in a case of invasive pulmonary aspergillosis during therapy for drug-induced hypersensitivity syndrome

    Directory of Open Access Journals (Sweden)

    Tomoo Ikari

    2017-01-01

    Full Text Available A 67-year-old female with rheumatoid arthritis and asthma-chronic obstructive pulmonary disease overlap syndrome was admitted for drug-induced hypersensitivity syndrome (DIHS caused by salazosulfapyridine. Human herpes virus 6 (HHV-6 variant B was strongly positive on peripheral blood. Multiple cavities with ground grass opacities rapidly emerged predominantly in the upper and middle lobes. She was diagnosed with invasive pulmonary aspergillosis (IPA, and was treated successfully with antifungal agents. Therapeutic systemic corticosteroids, emphysematous change in the lungs, and the worsening of the patient's general condition due to DIHS were considered major contributing factor leading to IPA. HHV-6 reactivation could have an effect on clinical course of IPA. Cavities with halo sign would provide an early clue to IPA in non-neutropenic and immunosuppressive patients.

  13. A Case of Sublingual Ranula That Responded Successfully to Localized Injection Treatment with OK-432 after Healing from Drug Induced Hypersensitivity Syndrome

    Directory of Open Access Journals (Sweden)

    Kunio Yoshizawa

    2016-01-01

    Full Text Available A ranula is a mucus retention cyst or pseudocyst caused by leakage of mucus from the sublingual gland and generally occurs in the oral floor. In addition, drug induced hypersensitivity syndrome (DIHS is a rare but well-recognized serious adverse effect characterized by fever, skin rashes, generalized lymphadenopathy, hepatitis, and hepatosplenomegaly and oral stomatitis. This paper presents the first case of successfully treated sublingual ranula with localized injection of OK-432 after healing from drug induced hypersensitivity syndrome, which has previously been unreported in the literature. We present the case of a 38-year-old Japanese woman with sublingual ranula that responded successfully to localized injection treatment with OK-432 after healing from drug induced hypersensitivity syndrome. She was affected with cutaneous myositis and interstitial lung disease when she was 26 years old. At the age 34 years, she received additional oral treatment of diaminodiphenyl-sulfone due to deterioration of the cutaneous myositis, which resulted in drug induced hypersensitivity syndrome (DIHS with severe oral stomatitis. Local injection of OK-432 to the ranula may be a very safe and useful treatment method even if the patient has a history of drug allergy and has connective tissue disease such as cutaneous myositis.

  14. Malaria-induced NLRP12/NLRP3-dependent caspase-1 activation mediates inflammation and hypersensitivity to bacterial superinfection.

    Directory of Open Access Journals (Sweden)

    Marco A Ataide

    2014-01-01

    Full Text Available Cyclic paroxysm and high fever are hallmarks of malaria and are associated with high levels of pyrogenic cytokines, including IL-1β. In this report, we describe a signature for the expression of inflammasome-related genes and caspase-1 activation in malaria. Indeed, when we infected mice, Plasmodium infection was sufficient to promote MyD88-mediated caspase-1 activation, dependent on IFN-γ-priming and the expression of inflammasome components ASC, P2X7R, NLRP3 and/or NLRP12. Pro-IL-1β expression required a second stimulation with LPS and was also dependent on IFN-γ-priming and functional TNFR1. As a consequence of Plasmodium-induced caspase-1 activation, mice produced extremely high levels of IL-1β upon a second microbial stimulus, and became hypersensitive to septic shock. Therapeutic intervention with IL-1 receptor antagonist prevented bacterial-induced lethality in rodents. Similar to mice, we observed a significantly increased frequency of circulating CD14(+CD16(-Caspase-1(+ and CD14(dimCD16(+Caspase-1(+ monocytes in peripheral blood mononuclear cells from febrile malaria patients. These cells readily produced large amounts of IL-1β after stimulation with LPS. Furthermore, we observed the presence of inflammasome complexes in monocytes from malaria patients containing either NLRP3 or NLRP12 pyroptosomes. We conclude that NLRP12/NLRP3-dependent activation of caspase-1 is likely to be a key event in mediating systemic production of IL-1β and hypersensitivity to secondary bacterial infection during malaria.

  15. Oral 2-hydroxyoleic acid inhibits reflex hypersensitivity and open-field-induced anxiety after spared nerve injury.

    Science.gov (United States)

    Avila-Martin, G; Galan-Arriero, I; Ferrer-Donato, A; Busquets, X; Gomez-Soriano, J; Escribá, P V; Taylor, J

    2015-01-01

    Recently, fatty acids have been shown to modulate sensory function in animal models of neuropathic pain. In this study, the antinociceptive effect of 2-hydroxyoleic acid (2-OHOA) was assessed following spared nerve injury (SNI) with reflex and cerebrally mediated behavioural responses. Initial antinociceptive behavioural screening of daily administration of 2-OHOA (400 mg/kg, p.o.) was assessed in Wistar rats by measuring hindlimb reflex hypersensitivity to von Frey and thermal plate stimulation up to 7 days after SNI, while its modulatory effect on lumbar spinal dorsal horn microglia reactivity was assessed with OX-42 immunohistochemistry. In vitro the effect of 2-OHOA (120 μM) on cyclooxygenase protein expression (COX-2/COX-1 ratio) in lipopolysaccharide-activated macrophage cells was tested with Western blot analysis. Finally, the effects of 2-OHOA treatment on the place escape aversion paradigm (PEAP) and the open-field-induced anxiety test were tested at 21 days following nerve injury compared with vehicle-treated sham and pregabalin-SNI (30 mg/kg, p.o.) control groups. Oral 2-OHOA significantly reduced ipsilateral mechanical and thermal hypersensitivity up to 7 days after SNI. Additionally 2-OHOA decreased the COX-2/COX-1 ratio in lipopolysaccharide-activated macrophage cells and OX-42 expression within the ipsilateral lumbar spinal dorsal horn 7 days after SNI. 2-OHOA significantly restored inner-zone exploration in the open-field test compared with the vehicle-treated sham group at 21 days after SNI. Oral administration of the modified omega 9 fatty acid, 2-OHOA, mediates antinociception and prevents open-field-induced anxiety in the SNI model in Wistar rats, which is mediated by an inhibition of spinal dorsal horn microglia activation. © 2014 European Pain Federation - EFIC®

  16. Paracetamol suppository induced allergic contact dermatitis

    Directory of Open Access Journals (Sweden)

    Rangaraj Murugaiyan

    2016-01-01

    Full Text Available Paracetamol, a para-aminophenol derivative given systemically can produce allergic reactions and has been reported so far, but allergic reaction due to suppositories is very rare. A 4 month old male child brought by his mother with complaints of raised dark coloured skin lesions over the perianal region for the past 3 days. The child had history of (H/o of fever for 4 days back for which paracetamol suppository was prescribed following which the child developed the lesion over the perianal region On examination a well defined hyperpigmented plaque of size 5*3 cms extending from anal verge posteriorly and anteriorly upto the beginning of scrotum with lateral extensions from the centre to the gluteals. In our case, the paracetamol suppository used caused an allergic reaction which made the child very irritable and the child developed an allergic contact dermatitis in the site where the suppository was kept and the surrounding area. We report this case because paracetamol suppository as such without preservative causing allergic contact dermatitis has not been reported so far and the treating doctor should keep in mind such type of reactions that might occur when used.

  17. Hypersensitive tourists

    DEFF Research Database (Denmark)

    Jensen, Martin Trandberg

    2016-01-01

    This research note sets forth a new agendum for sensuous tourism scholarship. It departs in the neglected study of the embodied life of hypersensitive tourists, and argues that the ambiguousness of the sensuous be better understood. To contextualise this argument the following suggests that aller......This research note sets forth a new agendum for sensuous tourism scholarship. It departs in the neglected study of the embodied life of hypersensitive tourists, and argues that the ambiguousness of the sensuous be better understood. To contextualise this argument the following suggests...... that allergic tourists make up a contemporary and increasingly relevant empirical field through which to illuminate the dark sides of the sensuous. Finally, the note develops four analytical dimensions that structure critical sensuous scholarship....

  18. Flexible textile-based strain sensor induced by contacts

    International Nuclear Information System (INIS)

    Zhang, Hui

    2015-01-01

    In this paper, the contact effects are used as the key sensing element to develop flexible textile-structured strain sensors. The structures of the contact are analyzed theoretically and the contact resistances are investigated experimentally. The electromechanical properties of the textiles are investigated to find the key factors which determine the sensitivity, repeatability, and linearity of the sensor. The sensing mechanism is based on the change of contact resistance induced by the change of the configuration of the textiles. In order to improve the performance of the textile strain sensor, the contact resistance is designed based on the electromechanical properties of the fabric. It can be seen from the results that the performance of the sensor is largely affected by the structure of the contacts, which are determined by the morphology of fiber surface and the structures of the yarn and fabric. (paper)

  19. The JAK2V617 mutation induces constitutive activation and agonist hypersensitivity in basophils from patients with polycythemia vera

    Science.gov (United States)

    Pieri, Lisa; Bogani, Costanza; Guglielmelli, Paola; Zingariello, Maria; Rana, Rosa Alba; Bartalucci, Niccolò; Bosi, Alberto; Vannucchi, Alessandro M.

    2009-01-01

    Background The JAK2V617F mutation has been associated with constitutive and enhanced activation of neutrophils, while no information is available concerning other leukocyte subtypes. Design and Methods We evaluated correlations between JAK2V617F mutation and the count of circulating basophils, the number of activated CD63+ basophils, their response in vitro to agonists as well as the effects of a JAK2 inhibitor. Results We found that basophil count was increased in patients with JAK2V617F -positive myeloproliferative neoplasms, particularly in those with polycythemia vera, and was correlated with the V617F burden. The burden of V617F allele was similar in neutrophils and basophils from patients with polycythemia vera, while total JAK2 mRNA content was remarkably greater in the basophils; however, the content of JAK2 protein in basophils was not increased. The number of CD63+ basophils was higher in patients with polycythemia vera than in healthy subjects or patients with essential thrombocythemia or primary myelofibrosis and was correlated with the V617F burden. Ultrastructurally, basophils from patients with polycythemia vera contained an increased number of granules, most of which were empty suggesting cell degranulation in vivo. Ex vivo experiments revealed that basophils from patients with polycythemia vera were hypersensitive to the priming effect of interleukin-3 and to f-MLP-induced activation; pre-treatment with a JAK2 inhibitor reduced polycythemia vera basophil activation. Finally, we found that the number of circulating CD63+ basophils was significantly greater in patients suffering from aquagenic pruritus, who also showed a higher V617F allele burden. Conclusions These data indicate that the number of constitutively activated and hypersensitive circulating basophils is increased in polycythemia vera, underscoring a role of JAK2V617F in these cells’ abnormal function and, putatively, in the pathogenesis of pruritus. PMID:19608683

  20. Transcriptome Analysis of Capsicum Chlorosis Virus-Induced Hypersensitive Resistance Response in Bell Capsicum.

    Science.gov (United States)

    Widana Gamage, Shirani M K; McGrath, Desmond J; Persley, Denis M; Dietzgen, Ralf G

    2016-01-01

    Capsicum chlorosis virus (CaCV) is an emerging pathogen of capsicum, tomato and peanut crops in Australia and South-East Asia. Commercial capsicum cultivars with CaCV resistance are not yet available, but CaCV resistance identified in Capsicum chinense is being introgressed into commercial Bell capsicum. However, our knowledge of the molecular mechanisms leading to the resistance response to CaCV infection is limited. Therefore, transcriptome and expression profiling data provide an important resource to better understand CaCV resistance mechanisms. We assembled capsicum transcriptomes and analysed gene expression using Illumina HiSeq platform combined with a tag-based digital gene expression system. Total RNA extracted from CaCV/mock inoculated CaCV resistant (R) and susceptible (S) capsicum at the time point when R line showed a strong hypersensitive response to CaCV infection was used in transcriptome assembly. Gene expression profiles of R and S capsicum in CaCV- and buffer-inoculated conditions were compared. None of the genes were differentially expressed (DE) between R and S cultivars when mock-inoculated, while 2484 genes were DE when inoculated with CaCV. Functional classification revealed that the most highly up-regulated DE genes in R capsicum included pathogenesis-related genes, cell death-associated genes, genes associated with hormone-mediated signalling pathways and genes encoding enzymes involved in synthesis of defense-related secondary metabolites. We selected 15 genes to confirm DE expression levels by real-time quantitative PCR. DE transcript profiling data provided comprehensive gene expression information to gain an understanding of the underlying CaCV resistance mechanisms. Further, we identified candidate CaCV resistance genes in the CaCV-resistant C. annuum x C. chinense breeding line. This knowledge will be useful in future for fine mapping of the CaCV resistance locus and potential genetic engineering of resistance into Ca

  1. Ion-Induced Surface Modification of Magnetically Operated Contacts

    Directory of Open Access Journals (Sweden)

    Karen Arushanov

    2012-02-01

    Full Text Available A study has been made of permalloy (iron-nickel contacts of reed switches before and after ion-induced surface modification using atomic force and optical microscopy, Auger electron and X-ray photoelectron spectroscopy. It has been found that the formation of surface nitride layers enhances corrosion and erosion resistance of contacts. We proposed to produce such layers directly into sealed reed switches by means of pulsing glow-discharge nitrogen plasma.

  2. An S-type anion channel SLAC1 is involved in cryptogein-induced ion fluxes and modulates hypersensitive responses in tobacco BY-2 cells.

    Science.gov (United States)

    Kurusu, Takamitsu; Saito, Katsunori; Horikoshi, Sonoko; Hanamata, Shigeru; Negi, Juntaro; Yagi, Chikako; Kitahata, Nobutaka; Iba, Koh; Kuchitsu, Kazuyuki

    2013-01-01

    Pharmacological evidence suggests that anion channel-mediated plasma membrane anion effluxes are crucial in early defense signaling to induce immune responses and hypersensitive cell death in plants. However, their molecular bases and regulation remain largely unknown. We overexpressed Arabidopsis SLAC1, an S-type anion channel involved in stomatal closure, in cultured tobacco BY-2 cells and analyzed the effect on cryptogein-induced defense responses including fluxes of Cl(-) and other ions, production of reactive oxygen species (ROS), gene expression and hypersensitive responses. The SLAC1-GFP fusion protein was localized at the plasma membrane in BY-2 cells. Overexpression of SLAC1 enhanced cryptogein-induced Cl(-) efflux and extracellular alkalinization as well as rapid/transient and slow/prolonged phases of NADPH oxidase-mediated ROS production, which was suppressed by an anion channel inhibitor, DIDS. The overexpressor also showed enhanced sensitivity to cryptogein to induce downstream immune responses, including the induction of defense marker genes and the hypersensitive cell death. These results suggest that SLAC1 expressed in BY-2 cells mediates cryptogein-induced plasma membrane Cl(-) efflux to positively modulate the elicitor-triggered activation of other ion fluxes, ROS as well as a wide range of defense signaling pathways. These findings shed light on the possible involvement of the SLAC/SLAH family anion channels in cryptogein signaling to trigger the plasma membrane ion channel cascade in the plant defense signal transduction network.

  3. Hair-dye induced erythema multiforme like allergic contact dermatitis

    Directory of Open Access Journals (Sweden)

    Mrinal Gupta

    2017-04-01

    Full Text Available Erythema multiforme (EM is an acute, self limited skin disease characterized by the sudden eruption of symmetrical lesions in typical targetoid fashion usually confined to face and extremities. The most commonly implicated factors include infections like herpes simplex, mycoplasma, drugs like antibiotics and anticonvulsants and vaccinations. Contact dermatitis induced EM is a rarely reported entity. Herein we present a case of a 40 year old female who presented with EM due to contact sensitivity to p-Paraphenylenediamine (PPD, a common coloring agent in hair-dyes and a potent sensitizer. Till date, there have been only a few case reports of PPD induced EM.

  4. Effect of mesenchymal stromal cells (MSC) on chronic visceral hypersensitivity in a radio-induced colonic ulceration model in the rat

    International Nuclear Information System (INIS)

    Durand, Christelle

    2014-01-01

    Patients who undergo pelvic radiotherapy may develop significant incidence of undesirable chronic gastrointestinal complications resulting from radiation-induced damages around the tumour. Chronic visceral pain is one of the radiation-induced side effects that greatly affects the quality of life of 'cancer survivors'. The lack of effective analgesic treatment highlights the importance of novel and effective therapeutic strategies. In our laboratory, mesenchymal stromal cell (MSC) based approach showed beneficial immunomodulatory and regenerative effects in a rat model of irreversible radiationinduced colonic ulcers. The goal of my work was to assess the relevance of this model to study radiation-induced visceral persistent hypersensitivity and its modulation by MSC treatment. We first demonstrated that this model is associated with long-lasting visceral hypersensitivity and central neuronal sensitization. In this context we showed then that mast cells (MC) are involved in the mechanism of peripheral sensitization. Moreover, we suggested the implication of the neuro-mediator NO . in the pathophysiology of persistent radiation-induced visceral hypersensitivity. We also suggested that MSC treatment reversed radiation-induced hypersensitivity by a mechanism that in part may involve the modulation of MC activation and/or the decrease in the number of MC and nerve fiber interactions. In addition, MSC treatment reduced the percentage of nitrinergic neurons, increased after irradiation, and restored colonic muscular contractibility. Such processes may promote the therapeutic benefit of MSC observed in our study. In conclusion, this work provided new insights on the therapeutic benefit of MSC in our study model and a new argument in favour of their use in a future clinical trial to cure abdomino-pelvic radiotherapy side effects. (author) [fr

  5. Fever as the only manifestation of hypersensitivity reactions associated with oxaliplatin in a patient with colorectal cancer Oxaliplatin-induced hypersensitivity reaction

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Hypersensitivity reactions (HSR) to oxaliplatin in patients with colorectal cancer include facial flushing, erythema,pruritis, fever, tachycardia, dyspnea, tongue swelling,rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. We report a patient with fever as the sole manifestation of initial HSR, review the literature and discuss the management of HSR. A 57-year-old female with T3N2M0 rectal adenocarcinoma received modified FOLFOX-6. She tolerated the first 8 cycles without any toxicities except grade 1 peripheral neuropathy and nausea. During 9th and 10th infusions,she developed fever to a maximum of 38.3℃ with stable hemodynamic status despite medications. During 11th infusion, she developed grade 3 HSR consisting of symptomatic bronchospasm, hypotension, nausea,vomiting, cough, and fever. On examination, she was pale, cyanotic, with a temperature of 38.8℃, BP dropped to 95/43 mm Hg, pulse of 116/min and O2 saturation of 88%-91%. She was hospitalized for management and recovered in 24 h. Fever alone is not a usual symptom of oxaliplatin HSR. It may be indicative that the patient may develop serious reactions subsequently, as did our patient who developed hypotension with the third challenge. Treatment and prevention consists of slowing the infusion rate, use of steroids and antagonists of Type 1 and 2 histamine receptor antagonists, whereas desensitization could help to provide the small number of patients who experience severe HSR with the ability to further receive an effective therapy for their colorectal cancer.

  6. Cytogenetic Effects of Low Dose Radiation in Mammalian Cells Analysis of the Phenomenon Hypersensitivity and Induced Radioresistence

    CERN Document Server

    Shmakova, N L; Nasonova, E A; Krasavin, E A; Rsjanina, A V

    2001-01-01

    The induction of cytogenetic damage after irradiation of chinese hamster cells and human melanoma cells within dose range 1-200 cGy was studied. The anaphase and metaphase analysis of chromosome damage and micronuclei test were applied. The hypersensitivity (HRS) at doses below 20 cGy and the increased radioresistence at higher doses (IR) were shown with all cytogenetic criteria for both cell lines. The phenomenon of HRS/IR was reproduced in synchronic as well as in asynchronic population of chinese hamster cells. This fact shows that HRS was caused by high radiosensitivity of all cells and can not be explained by any differential sensitivity of cells in different phases of the cell cycle. So it was supposed that the increasing radioresistence is determined by the inclusion of the inducible repair processes in all cells. This conclusion agress with the fact that there was no evidence of HRS on dose-effect curves and that some part of pre-existent damage was repaired after preliminary irradiation with low dose...

  7. Contact Lens-Induced Discomfort and Protein Changes in Tears.

    Science.gov (United States)

    Masoudi, Simin; Stapleton, Fiona Jane; Willcox, Mark Duncan Perry

    2016-08-01

    Ocular discomfort is among the main causes of contact lens wear discontinuation. This study investigated the association between subjective ocular comfort ratings and diurnal changes in tear protein concentrations with and without contact lens wear. The study was a prospective, open-label, single-group two-staged investigation. Basal tears were collected from 30 experienced contact lens wearers twice a day (morning and evening) using a noninvasive method without lens wear (stage 1) and during wear of Etafilcon A contact lenses (stage 2) for 7 to 10 days. Subjects rated their ocular comfort on a scale of 1 to 100 (with 100 as extremely comfortable) at each time of tear collection. Tears were analyzed using liquid quadrupole mass spectrometry in conjunction with selected reaction monitoring (SRM) method. End-of-day comfort was reduced when wearing lenses (87.8 ± 14.3 AM vs. 79.2 ± 16.6 PM) compared to no lens wear (88.3 ± 12.6 AM vs. 84.7 ± 13.3 PM) (AM vs. PM, p tears (p < 0.05, r = -0.29). Only the absolute concentration of prolactin-induced protein correlated with subjective comfort ratings. Taking into consideration that prolactin-induced protein can be associated with disruption in water transport in lacrimal glands, our findings may indicate that changes to aqueous secretion are associated with contact lens discomfort.

  8. Hypersensitivity Reactions from Excipients in Systemic Glucocorticoid Formulations

    DEFF Research Database (Denmark)

    Calogiuri, Gianfranco; Garvey, Lene H; Romita, Paolo

    2016-01-01

    Glucocorticoids are the most widely used drugs for the treatment of hypersensitivity, however these drugs themselves and the excipients contained in commercial corticosteroid formulations are able to induce severe immediate-type hypersensitivity reactions. Reactions involving excipients have been...

  9. Peripheral hyperpolarization-activated cyclic nucleotide-gated channels contribute to inflammation-induced hypersensitivity of the rat temporomandibular joint.

    Science.gov (United States)

    Hatch, R J; Jennings, E A; Ivanusic, J J

    2013-08-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels conduct an inward cation current (Ih ) that contributes to the maintenance of neuronal membrane potential and have been implicated in a number of animal models of neuropathic and inflammatory pain. In the current study, we investigated HCN channel involvement in inflammatory pain of the temporomandibular joint (TMJ). The contribution of HCN channels to inflammation (complete Freund's adjuvant; CFA)-induced mechanical hypersensitivity of the rat TMJ was tested with injections of the HCN channel blocker ZD7288. Retrograde labelling and immunohistochemistry was used to explore HCN channel expression in sensory neurons that innervate the TMJ. Injection of CFA into the TMJ (n = 7) resulted in a significantly increased mechanical sensitivity relative to vehicle injection (n = 7) (p blocked by co-injection of ZD7288 with the CFA (n = 7). Retrograde labelling and immunohistochemistry experiments revealed expression predominantly of HCN1 and HCN2 channel subunits in trigeminal ganglion neurons that innervate the TMJ (n = 3). No change in the proportion or intensity of HCN channel expression was found in inflamed (n = 6) versus control (n = 5) animals at the time point tested. Our findings suggest a role for peripheral HCN channels in inflammation-induced pain of the TMJ. Peripheral application of a HCN channel blocker could provide therapeutic benefit for inflammatory TMJ pain and avoid side effects associated with activation of HCN channels in the central nervous system. © 2012 European Federation of International Association for the Study of Pain Chapters.

  10. Correlation between hypersensitivity induced by esophageal acid infusion and the baseline impedance level in patients with suspected gastroesophageal reflux.

    Science.gov (United States)

    Seo, A Young; Shin, Cheol Min; Kim, Nayoung; Yoon, Hyuk; Park, Young Soo; Lee, Dong Ho

    2015-07-01

    To evaluate the relevance between the pH parameters and baseline impedance level or esophageal hypomotility in patients with suspected gastroesophageal reflux. The recordings of 51 patients with heartburn, acid regurgitation, globus or noncardiac chest pain were analyzed. Evaluation included a 24-h multichannel intraluminal impedance-pH test while on off-proton pump inhibitor therapy over 1 week, high-resolution manometry and Bernstein test. Mean baseline impedance level at the most distal portion of the impedance channel was assessed manually. Esophageal hypomotility was evaluated using transitional zone defect (TZD) and distal break (DB) length measurement. In the study subjects (n = 51), 6 had a DeMeester score of more than 14.7 and 14 had a positive symptom index. The Bernstein test was positive in ten patients. The baseline impedance level was inversely correlated with the acid exposure time % (r = -0.660, P reflux and weakly acid reflux time % measured by impedance monitoring showed a weak correlation with TZD + DB length (r = 0.327 and 0.324, P = 0.019 and 0.020, respectively). Although a positive Bernstein test has no relevance for the acid exposure time or acid-related symptoms as represented by the DeMeester score or symptom index, the baseline impedance level was significantly lower in patients with a positive Bernstein test than in those with a negative one (2,628.4 ± 862.7 vs. 1,752.2 ± 611.1 Ω, P = 0.004). A lower baseline impedance level is closely related to increased esophageal acid exposure. Hypersensitivity induced by esophageal acid infusion might be attributed to acid-induced mucosal changes of the esophagus.

  11. Allergic Contact Dermatitis (type IV hypersensitivity and type I hypersensitivity following aromatherapy with ayurvedic oils (Dhanwantharam thailam, Eladi coconut oil presenting as generalized erythema and pruritus with flexural eczema

    Directory of Open Access Journals (Sweden)

    Chembolli Lakshmi

    2014-01-01

    Full Text Available Herbal and Ayurvedic medications, believed to be "mild" and "natural" are usually sought as the first line of treatment before resorting to "stronger" allopathic medication. There are very few reports of adverse reactions to either topical and/or systemic Ayurvedic medications. Massage aromatherapy with ayurvedic oils plays an important role in alleviation of pain, but may cause allergic contact dermatitis. This is the second case report of allergic contact dermatitis to ayurvedic oil.

  12. Hypersensitivity Vasculitis

    Science.gov (United States)

    ... Our Board Our Team Anniversary Vasculitis Foundation Newsletters Annual Reports Press Page Literature Order Form Join Contact Us Awareness Donate Donate Support the VF Through the Amazon Smile Program United Way Giving Ways to Give ...

  13. Influence of contact conditions on vibration induced wear of metals

    International Nuclear Information System (INIS)

    Hofmann, P.J.; Schettler, T.; Wieling, N.; Steininger, D.A.

    1990-01-01

    Unfavourable design characteristics of nuclear power plant steam generators and heat exchangers in general may result in vibration induced tube wear. A systematic investigation was performed on the contact conditions which may appear between heat exchanger tubes and tube support structure and the influence of different parameters e.g., normal contact force, on the resulting steady state wear rates. It is concluded that not only are contact forces and sliding distances important in the wear process but also the type of relative motion has a decisive influence on the resulting wear rates. For a certain 'work rate', the wear rate caused by repeated impact motions between tube and tube support structure may be an order of magnitude higher than that caused by only sliding motion. This is the result of different operating wear mechanisms which are discussed in this paper. (orig.)

  14. Minocycline-induced hypersensitivity syndrome presenting with meningitis and brain edema: a case report

    Directory of Open Access Journals (Sweden)

    Lefebvre Nicolas

    2007-05-01

    Full Text Available Background Hypersentivity Syndrome (HS may be a life-threatening condition. It frequently presents with fever, rash, eosinophilia and systemic manifestations. Mortality can be as high as 10% and is primarily due to hepatic failure. We describe what we believe to be the first case of minocycline-induced HS with accompanying lymphocytic meningitis and cerebral edema reported in the literature. Case presentation A 31-year-old HIV-positive female of African origin presented with acute fever, lymphocytic meningitis, brain edema, rash, eosinophilia, and cytolytic hepatitis. She had been started on minocycline for inflammatory acne 21 days prior to the onset of symptoms. HS was diagnosed clinically and after exclusion of infectious causes. Minocycline was withdrawn and steroids were administered from the second day after presentation because of the severity of the symptoms. All signs resolved by the seventh day and steroids were tailed off over a period of 8 months. Conclusion Clinicians should maintain a high index of suspicion for serious adverse reactions to minocycline including lymphocytic meningitis and cerebral edema among HIV-positive patients, especially if they are of African origin. Safer alternatives should be considered for treatment of acne vulgaris. Early recognition of the symptoms and prompt withdrawal of the drug are important to improve the outcome.

  15. Disruption of δ-opioid receptor phosphorylation at threonine 161 attenuates morphine tolerance in rats with CFA-induced inflammatory hypersensitivity.

    Science.gov (United States)

    Chen, Hai-Jing; Xie, Wei-Yan; Hu, Fang; Zhang, Ying; Wang, Jun; Wang, Yun

    2012-04-01

    Our previous study identified Threonine 161 (Thr-161), located in the second intracellular loop of the δ-opioid receptor (DOR), as the only consensus phosphorylation site for cyclin-dependent kinase 5 (Cdk5). The aim of this study was to assess the function of DOR phosphorylation by Cdk5 in complete Freund's adjuvant (CFA)-induced inflammatory pain and morphine tolerance. Dorsal root ganglion (DRG) neurons of rats with CFA-induced inflammatory pain were acutely dissociated and the biotinylation method was used to explore the membrane localization of phosphorylated DOR at Thr-161 (pThr-161-DOR), and paw withdrawal latency was measured after intrathecal delivery of drugs or Tat-peptide, using a radiant heat stimulator in rats with CFA-induced inflammatory pain. Both the total amount and the surface localization of pThr-161-DOR were significantly enhanced in the ipsilateral DRG following CFA injection. Intrathecal delivery of the engineered Tat fusion-interefering peptide corresponding to the second intracellular loop of DOR (Tat-DOR-2L) increased inflammatory hypersensitivity, and inhibited DOR- but not µ-opioid receptor-mediated spinal analgesia in CFA-treated rats. However, intrathecal delivery of Tat-DOR-2L postponed morphine antinociceptive tolerance in rats with CFA-induced inflammatory pain. Phosphorylation of DOR at Thr-161 by Cdk5 attenuates hypersensitivity and potentiates morphine tolerance in rats with CFA-induced inflammatory pain, while disruption of the phosphorylation of DOR at Thr-161 attenuates morphine tolerance.

  16. Transfer and Contact-Induced Variation in Child Basque

    Directory of Open Access Journals (Sweden)

    Jennifer eAustin

    2015-01-01

    Full Text Available Young Basque-speaking children produce Differential Object Marking (DOM and pre-verbal complementizers in their speech, variants argued to stem from contact with Spanish (Austin, 2006, Rodríguez-Ordóñez, 2013. In this paper, I claim that despite their contact-induced origin, these forms reflect distinct developmental tendencies on the part of the child acquiring Basque. Children's use of pre-verbal complementizers in Basque seems to be a relief strategy that bilingual children employ until they have acquired the post-verbal complementizers in Basque, which are low-frequency morphemes. In contrast, the use of DOM is present in the adult input, although children use this construction to a greater extent than adults do. Finally, I discuss the implications of these findings for the part that child learners play in advancing language change.

  17. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart.

    Directory of Open Access Journals (Sweden)

    Boyd R Rorabaugh

    Full Text Available We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury.Adult male and female rats received daily injections of methamphetamine (5 mg/kg or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining.Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine.Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse.

  18. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart

    Science.gov (United States)

    Seeley, Sarah L.; Stoops, Thorne S.; D’Souza, Manoranjan S.

    2017-01-01

    Background We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Methods Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Results Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Conclusions Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse. PMID:28575091

  19. Cells Deficient in the Fanconi Anemia Protein FANCD2 are Hypersensitive to the Cytotoxicity and DNA Damage Induced by Coffee and Caffeic Acid.

    Science.gov (United States)

    Burgos-Morón, Estefanía; Calderón-Montaño, José Manuel; Orta, Manuel Luis; Guillén-Mancina, Emilio; Mateos, Santiago; López-Lázaro, Miguel

    2016-07-08

    Epidemiological studies have found a positive association between coffee consumption and a lower risk of cardiovascular disorders, some cancers, diabetes, Parkinson and Alzheimer disease. Coffee consumption, however, has also been linked to an increased risk of developing some types of cancer, including bladder cancer in adults and leukemia in children of mothers who drink coffee during pregnancy. Since cancer is driven by the accumulation of DNA alterations, the ability of the coffee constituent caffeic acid to induce DNA damage in cells may play a role in the carcinogenic potential of this beverage. This carcinogenic potential may be exacerbated in cells with DNA repair defects. People with the genetic disease Fanconi Anemia have DNA repair deficiencies and are predisposed to several cancers, particularly acute myeloid leukemia. Defects in the DNA repair protein Fanconi Anemia D2 (FANCD2) also play an important role in the development of a variety of cancers (e.g., bladder cancer) in people without this genetic disease. This communication shows that cells deficient in FANCD2 are hypersensitive to the cytotoxicity (clonogenic assay) and DNA damage (γ-H2AX and 53BP1 focus assay) induced by caffeic acid and by a commercial lyophilized coffee extract. These data suggest that people with Fanconi Anemia, or healthy people who develop sporadic mutations in FANCD2, may be hypersensitive to the carcinogenic activity of coffee.

  20. Localization of pellicle-induced open contacts using Charge-Induced Voltage Alteration

    Energy Technology Data Exchange (ETDEWEB)

    Cole, E.I. Jr.; Soden, J.M.

    1993-08-01

    The recently developed Charge-Induced Voltage Alteration (CIVA) technique for localizing open metal conductors was used successfully to identify transistors with electrically open metal-1 contacts to silicon. The transistors were in the I/O port circuitry of a failing microcontroller and were completely covered by a metal-2 power bus. The root cause of the open contacts was a subtle scratch in the pellicle over the contact reticle. The scratch prevented full exposure of the photoresist, resulting in incomplete removal of the interlevel oxide in several contact windows. In addition to this powerful new application of CIVA, a number of failure analysis techniques utilizing both the electrical and physical properties of the failing microcontrollers were employed to identify and confirm the open contacts. These techniques are reviewed and recommendations are given for improved pellicle/reticle inspection.

  1. Hypersensitivity reactions in patients receiving hemodialysis.

    Science.gov (United States)

    Butani, Lavjay; Calogiuri, Gianfranco

    2017-06-01

    To describe hypersensitivity reactions in patients receiving maintenance hemodialysis. PubMed search of articles published during the past 30 years with an emphasis on publications in the past decade. Case reports and review articles describing hypersensitivity reactions in the context of hemodialysis. Pharmacologic agents are the most common identifiable cause of hypersensitivity reactions in patients receiving hemodialysis. These include iron, erythropoietin, and heparin, which can cause anaphylactic or pseudoallergic reactions, and topical antibiotics and anesthetics, which lead to delayed-type hypersensitivity reactions. Many hypersensitivity reactions are triggered by complement activation and increased bradykinin resulting from contact system activation, especially in the context of angiotensin-converting enzyme inhibitor use. Several alternative pharmacologic preparations and dialyzer membranes are available, such that once an etiology for the reaction is established, recurrences can be prevented without affecting the quality of care provided to patients. Although hypersensitivity reactions are uncommon in patients receiving hemodialysis, they can be life-threatening. Moreover, considering the large prevalence of the end-stage renal disease population, the implications of such reactions are enormous. Most reactions are pseudoallergic and not mediated by immunoglobulin E. The multiplicity of potential exposures and the complexity of the environment to which patients on dialysis are exposed make it challenging to identify the precise cause of these reactions. Great diligence is needed to investigate hypersensitivity reactions to avoid recurrence in this high-risk population. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. Cement-Induced Chromate Occupational Allergic Contact Dermatitis.

    Science.gov (United States)

    Kridin, Khalaf; Bergman, Reuven; Khamaisi, Mogher; Zelber-Sagi, Shira; Weltfriend, Sara

    2016-01-01

    Hexavalent chromium in cement is a common cause of occupational allergic contact dermatitis (OACD). Analysis of patch test data during 1999 to 2013 was done. Patients with cement-induced chromate OACD filled the Dermatology Life Quality Index, graded 1 to 5. Of 4846 consecutive patients who were patch tested, 146 (3%) were chromate-sensitive. Of 46 (31.5%) who presented with chromate OACD, 27 (59%) had cement-induced chromate OACD. The proportion of chromate-sensitive patients with clinically relevant cement exposure increased from 7.7% in 2002 to 2004 to 28.7% in 2011 to 2013 (P = 0.04). The median age of presentation was younger than for other chromate-sensitive patients (32 vs 42 years). Hand eczema (88.9%) was the most frequent clinical presentation. Of the 27 with cement-induced chromate OACD, 21 (77.8%) had ongoing dermatitis at the time of the review. Although 14/27 (51.9%) changed their occupation to avoid exposure to cement, symptoms persisted in 9/14 (64.3%). Prolonged exposure to cement before development of symptoms was associated with chronicity. All the symptomatic patients experienced at least a moderate effect on their quality of life (grade 3 or higher on the Dermatology Life Quality Index). We recommend the adoption of the European legislation in Israel, to reduce the prevalence of chromate OACD from cement.

  3. CD1d knockout mice exhibit aggravated contact hypersensitivity responses due to reduced interleukin-10 production predominantly by regulatory B cells

    DEFF Research Database (Denmark)

    Fjelbye, Jonas; Antvorskov, Julie C; Buschard, Karsten

    2015-01-01

    .05) and peritoneal cavity (80.8% decrease; P challenge, which suggests an important regulatory and protective role of CD1d-dependent NKT cells in CHS in our model, at least in part via regulation of IL-10 producing B(regs) ....... knockout (CD1d KO) and wild-type (Wt) mice after contact allergen exposure. For induction of CHS, C57BL/6 CD1d KO mice (n = 6) and C57BL/6 Wt mice (n = 6) were sensitised with 1% (w/v) dinitrochlorobenzene (DNCB) or vehicle for three consecutive days and subsequently challenged with a single dose of 0...

  4. Pb induces superconductivity in Bi2Se3 analyzed by point contact spectroscopy

    OpenAIRE

    Arevalo-López, P.; López-Romero, R. E.; Escudero, R.

    2015-01-01

    Some topological insulators become superconducting when doped with Cu and Pd. Superconductivity in a non-superconductor may be induced by proximity effect: i.e. Contacting a non-superconductor with a superconductor. The superconducting macroscopic wave function will induce electronic pairing into the normal compound. In the simplest topological insulator, Bi$_2$Se$_3$, superconductivity may be induced with Pb. We studied with point contact junctions formed by contacting Bi$_2$Se$_3$ crystals ...

  5. The sesquiterpene botrydial produced by Botrytis cinerea induces the hypersensitive response on plant tissues and its action is modulated by salicylic acid and jasmonic acid signaling.

    Science.gov (United States)

    Rossi, Franco Rubén; Gárriz, Andrés; Marina, María; Romero, Fernando Matías; Gonzalez, María Elisa; Collado, Isidro González; Pieckenstain, Fernando Luis

    2011-08-01

    Botrytis cinerea, as a necrotrophic fungus, kills host tissues and feeds on the remains. This fungus is able to induce the hypersensitive response (HR) on its hosts, thus taking advantage on the host's defense machinery for generating necrotic tissues. However, the identity of HR effectors produced by B. cinerea is not clear. The aim of this work was to determine whether botrydial, a phytotoxic sesquiterpene produced by B. cinerea, is able to induce the HR on plant hosts, using Arabidopsis thaliana as a model. Botrydial induced the expression of the HR marker HSR3, callose deposition, and the accumulation of reactive oxygen species and phenolic compounds. Botrydial also induced the expression of PR1 and PDF1.2, two pathogenesis-related proteins involved in defense responses regulated by salicylic acid (SA) and jasmonic acid (JA), respectively. A. thaliana and tobacco plants defective in SA signaling were more resistant to botrydial than wild-type plants, as opposed to A. thaliana plants defective in JA signaling, which were more sensitive. It can be concluded that botrydial induces the HR on its hosts and its effects are modulated by host signaling pathways mediated by SA and JA.

  6. Is the drug-induced hypersensitivity syndrome (DIHS due to human herpesvirus 6 infection or to allergy-mediated viral reactivation? Report of a case and literature review

    Directory of Open Access Journals (Sweden)

    Borgia Guglielmo

    2010-03-01

    Full Text Available Abstract Background Drug-Induced Hypersensitivity Syndrome (DIHS is a severe and rare systemic reaction triggered by a drug (usually an antiepileptic drug. We present a case of DISH and we review studies on the clinical features and treatment of DIHS, and on its pathogenesis in which two elements (Herpesvirus infection and the drug interact with the immune system to trigger such a syndrome that can lead to death in about 20% of cases. Case presentation We report the case of a 26-year old woman with fever, systemic maculopapular rash, lymphadenopathy, hepatitis and eosinophilic leukocytosis. She had been treated with antibiotics that gave no benefit. She was taking escitalopram and lamotrigine for a bipolar disease 30 days before fever onset. Because the patient's general condition deteriorated, betamethasone and acyclovir were started. This treatment resulted in a mild improvement of symptoms. Steroids were rapidly tapered and this was followed with a relapse of fever and a worsening of laboratory parameters. Human herpesvirus 6 (HHV-6 DNA was positive as shown by PCR. Drug-Induced Hypersensitivity Syndrome (DIHS was diagnosed. Symptoms regressed on prednisone (at a dose of 50 mg/die that was tapered very slowly. The patient recovered completely. Conclusions The search for rare causes of fever led to complete resolution of a very difficult case. As DIHS is a rare disease the most relevant issue is to suspect and include it in differential diagnosis of fevers of unknown origin. Once diagnosed, the therapy is easy (steroidal administration and often successful. However our case strongly confirms that attention should be paid on the steroidal tapering that should be very slow to avoid a relapse.

  7. Investigation of Seminal Plasma Hypersensitivity Reactions

    Science.gov (United States)

    1998-10-01

    diseases, chronic vaginal candidiasis ); 3) establish the prevalence of BSS and localized/systemic seminal plasma protein hypersensitivity among the GW...of further investigation as our population grows. Subsequent pharmacologic treatment of this female for chronic vaginal candidiasis with an...partner.2Ř Subsequently, women experiencing localized vaginal inflammation, characterized by burning and pain and occurring immediately after contact

  8. Demethylation regulation of BDNF gene expression in dorsal root ganglion neurons is implicated in opioid-induced pain hypersensitivity in rats.

    Science.gov (United States)

    Chao, Yu-Chieh; Xie, Fang; Li, Xueyang; Guo, Ruijuan; Yang, Ning; Zhang, Chen; Shi, Rong; Guan, Yun; Yue, Yun; Wang, Yun

    2016-07-01

    Repeated administration of morphine may result in opioid-induced hypersensitivity (OIH), which involves altered expression of numerous genes, including brain-derived neurotrophic factor (BDNF) in dorsal root ganglion (DRG) neurons. Yet, it remains unclear how BDNF expression is increased in DRG neurons after repeated morphine treatment. DNA methylation is an important mechanism of epigenetic control of gene expression. In the current study, we hypothesized that the demethylation regulation of certain BDNF gene promoters in DRG neurons may contribute to the development of OIH. Real-time RT-PCR was used to assess changes in the mRNA transcription levels of major BDNF exons including exon I, II, IV, VI, as well as total BDNF mRNA in DRGs from rats after repeated morphine administration. The levels of exon IV and total BDNF mRNA were significantly upregulated by repeated morphine administration, as compared to that in saline control group. Further, ELISA array and immunocytochemistry study revealed a robust upregulation of BDNF protein expression in DRG neurons after repeated morphine exposure. Correspondingly, the methylation levels of BDNF exon IV promoter showed a significant downregulation by morphine treatment. Importantly, intrathecal administration of a BDNF antibody, but not control IgG, significantly inhibited mechanical hypersensitivity that developed in rats after repeated morphine treatment. Conversely, intrathecal administration of an inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (5-aza-dC) markedly upregulated the BDNF protein expression in DRG neurons and enhanced the mechanical allodynia after repeated morphine exposure. Together, our findings suggest that demethylation regulation of BDNF gene promoter may be implicated in the development of OIH through epigenetic control of BDNF expression in DRG neurons. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Tuberculin-induced delayed-type hypersensitivity reaction in a model of hu-PBMC-SCID mice grafted with autologous skin.

    Science.gov (United States)

    Tsicopoulos, A.; Pestel, J.; Fahy, O.; Vorng, H.; Vandenbusche, F.; Porte, H.; Eraldi, L.; Wurtz, A.; Akoum, H.; Hamid, Q.; Wallaert, B.; Tonnel, A. B.

    1998-01-01

    We have developed an animal model to study human delayed-type hypersensitivity reactions. Previous studies in humans have shown after tuberculin injection the presence of a mononuclear cell infiltration, with almost no eosinophils, associated with a preferential Th-1-type cytokine profile. Human skin graft obtained from tuberculin-reactive donors was grafted onto the back of severe combined immunodeficient mice. After healing, mice were reconstituted intraperitoneally with peripheral mononuclear cells. Tuberculin and diluent were injected intradermally, and skin biopsies were performed 72 hours later. Skin grafts were divided into two parts, one for immunohistochemistry and one for in situ hybridization studies. Immunohistochemistry was performed on cryostat sections using the alkaline phosphatase anti-alkaline phosphatase technique. In the tuberculin-injected sites as compared with the diluent-injected sites, there were significant increases in the number of CD45+ pan leukocytes and CD4+, CD8+, CD45RO+ T cells but not in CD68+ monocytes/macrophages and EG2 or MBP+ eosinophils. The activation markers CD25 and HLA-DR were up-regulated in the tuberculin-injected sites. In situ hybridization was performed using 35S-labeled riboprobes for interleukin (IL)-2, interferon (IFN)-gamma, IL-4, and IL-5. After tuberculin injection, a preferential Th-1-type cytokine profile was observed with significant increases in the numbers of IL-2 and IFN-gamma mRNA-expressing cells. These results are similar to those reported after tuberculin-induced delayed-type hypersensitivity in humans, suggesting that this model might be useful to study cutaneous inflammatory reaction. Images Figure 4 PMID:9626072

  10. The combined predictive capacity of rat models of algogen-induced and neuropathic hypersensitivity to clinically used analgesics varies with nociceptive endpoint and consideration of locomotor function

    DEFF Research Database (Denmark)

    Munro, Gordon; Storm, Ann; Hansen, Merete K.

    2012-01-01

    deficits developed quickly and persisted for at least 3 weeks post-injury. In contrast, evoked cold hypersensitivity, or movement-associated behavioural deficits (rotarod, beam-walking) were less manifested or dissipated rapidly post-injury. Mechanical hypersensitivity was dose-dependently reversed...

  11. Gosha-jinki-gan reduced oxaliplatin-induced hypersensitivity to cold sensation and its effect would be related to suppression of the expression of TRPM8 and TRPA1 in rats.

    Science.gov (United States)

    Kato, Yoshinori; Tateai, Yoshikazu; Ohkubo, Misao; Saito, Yuka; Amagai, Syun-ya; Kimura, Yu-Suke; Iimura, Naohumi; Okada, Megumi; Matsumoto, Akiko; Mano, Yasunari; Hirosawa, Iori; Ohuchi, Kaori; Tajima, Masataka; Asahi, Mariko; Kotaki, Hajime; Yamada, Harumi

    2014-01-01

    Peripheral neuropathy is a common side effect of the chemotherapeutic agent oxaliplatin (Oxp), and is associated with hypersensitivity to cold sensation in the acute stage. Recently, gosha-jinki-gan (GJG), a Japanese herbal medicine, was reported to improve Oxp-induced cold hypersensitivity. However, the mechanism for this effect was not elucidated. We hypothesized that the effect of GJG on Oxp-induced cold hypersensitivity may be associated with the expression of the transient receptor potential melastatin 8 (TRPM8) and transient receptor potential ankyrin 1 (TRPA1) channels, which are cold-gated ion channels. To assess this hypothesis, we examined alteration of the withdrawal response to cold stimulation following coadministration of GJG and Oxp in rats, and the relationship between this altered withdrawal response and the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG). Assessment of cold hypersensitivity was performed at 4 and 10°C using a cold plate. Compared with Oxp administration alone, coadministration of GJG (oral dose: 1 g/kg/day for 12 days) and Oxp (intraperitoneal dose: 4 mg/kg twice a week) significantly reduced the withdrawal response to cold stimulation. On the 12th day of drug administration, the L4-L6 DRG were removed and the expression of TRPM8 and TRPA1 mRNA was determined using RT-PCR. The expression of TRPM8 and TRPA1 in the DRG of rats that were coadministered GJG and Oxp decreased significantly compared with that in the rats administered Oxp alone. These results suggest that coadministration of GJG may improve Oxp-induced cold hypersensitivity by suppressing the overexpression of TRPM8 and TRPA1 mRNA.

  12. Classification and pathophysiology of radiocontrast media hypersensitivity.

    Science.gov (United States)

    Brockow, Knut; Ring, Johannes

    2010-01-01

    Hypersensitivity reactions to radiocontrast media (RCM) are unpredictable and are a concern for radiologists and cardiologists. Immediate hypersensitivity reactions manifest as anaphylaxis, and an allergic IgE-mediated mechanism has been continuously discussed for decades. Non-immediate reactions clinically are exanthemas resembling other drug-induced non-immediate hypersensitivities. During the past years, evidence is increasing that some of these reactions may be immunological. Repeated reactions after re-exposure, positive skin tests, and presence of specific IgE antibodies as well as positive basophil activation tests in some cases, and positive lymphocyte transformation or lymphocyte activation tests in others, indicate that a subgroup of both immediate and non-immediate reactions are of an allergic origin, although many questions remain unanswered. Recently reported cases highlight that pharmacological premedication is not safe to prevent RCM hypersensitivity in patients with previous severe reactions. These insights may have important consequences. A large multicenter study on the value of skin tests in RCM hypersensitivity concluded that skin testing is a useful tool for diagnosis of RCM allergy. It may have a role for the selection of a safe product in previous reactors, although confirmatory validation data is still scarce. In vitro tests to search for RCM-specific cell activation still are in development. In conclusion, recent data indicate that RCM hypersensitivity may have an allergic mechanism and that allergological testing is useful and may indicate tolerability. Copyright 2010 S. Karger AG, Basel.

  13. Intra-articular nerve growth factor regulates development, but not maintenance, of injury-induced facet joint pain & spinal neuronal hypersensitivity.

    Science.gov (United States)

    Kras, J V; Kartha, S; Winkelstein, B A

    2015-11-01

    The objective of the current study is to define whether intra-articular nerve growth factor (NGF), an inflammatory mediator that contributes to osteoarthritic pain, is necessary and sufficient for the development or maintenance of injury-induced facet joint pain and its concomitant spinal neuronal hyperexcitability. Male Holtzman rats underwent painful cervical facet joint distraction (FJD) or sham procedures. Mechanical hyperalgesia was assessed in the forepaws, and NGF expression was quantified in the C6/C7 facet joint. An anti-NGF antibody was administered intra-articularly in additional rats immediately or 1 day following facet distraction or sham procedures to block intra-articular NGF and test its contribution to initiation and/or maintenance of facet joint pain and spinal neuronal hyperexcitability. NGF was injected into the bilateral C6/C7 facet joints in separate rats to determine if NGF alone is sufficient to induce these behavioral and neuronal responses. NGF expression increases in the cervical facet joint in association with behavioral sensitivity after that joint's mechanical injury. Intra-articular application of anti-NGF immediately after a joint distraction prevents the development of both injury-induced pain and hyperexcitability of spinal neurons. Yet, intra-articular anti-NGF applied after pain has developed does not attenuate either behavioral or neuronal hyperexcitability. Intra-articular NGF administered to the facet in naïve rats also induces behavioral hypersensitivity and spinal neuronal hyperexcitability. Findings demonstrate that NGF in the facet joint contributes to the development of injury-induced joint pain. Localized blocking of NGF signaling in the joint may provide potential treatment for joint pain. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  14. Formalin-induced behavioural hypersensitivity and neuronal hyperexcitability are mediated by rapid protein synthesis at the spinal level

    Science.gov (United States)

    Asante, Curtis O; Wallace, Victoria C; Dickenson, Anthony H

    2009-01-01

    Background The mammalian target of rapamycin (mTOR) is a key regulator of mRNA translation whose action can be inhibited by the drug rapamycin. Forms of long-term plasticity require protein synthesis and evidence indicates that mRNA in dendrites, axon terminals and cell bodies is essential for long-term synaptic plasticity. Specific to pain, shifts in pain thresholds and responsiveness are an expression of neuronal plasticity and this likely contributes to persistent pain. We investigated this by inhibiting the activity of mTOR with rapamycin at the spinal level, of rats that were subjected to the formalin test, using both behavioural and electrophysiological techniques. Results For in vivo electrophysiology, Sprague Dawley rats were fully anaesthetised and single-unit extracellular recordings were obtained from lamina V wide dynamic range (WDR) dorsal horn spinal neurones at the region where input is received from the hind paw. Neuronal responses from naive rats showed that rapamycin-sensitive pathways were important in nociceptive-specific C-fibre mediated transmission onto WDR neurones as well mechanically-evoked responses since rapamycin was effective in attenuating these measures. Formalin solution was injected into the hind paw prior to which, rapamycin or vehicle was applied directly onto the exposed spinal cord. When rapamycin was applied to the spinal cord prior to hind paw formalin injection, there was a significant attenuation of the prolonged second phase of the formalin test, which comprises continuing afferent input to the spinal cord, neuronal hyperexcitability and an activated descending facilitatory drive from the brainstem acting on spinal neurones. In accordance with electrophysiological data, behavioural studies showed that rapamycin attenuated behavioural hypersensitivity elicited by formalin injection into the hind paw. Conclusion We conclude that mTOR has a role in maintaining persistent pain states via mRNA translation and thus protein

  15. Formalin-induced behavioural hypersensitivity and neuronal hyperexcitability are mediated by rapid protein synthesis at the spinal level

    Directory of Open Access Journals (Sweden)

    Wallace Victoria C

    2009-06-01

    Full Text Available Abstract Background The mammalian target of rapamycin (mTOR is a key regulator of mRNA translation whose action can be inhibited by the drug rapamycin. Forms of long-term plasticity require protein synthesis and evidence indicates that mRNA in dendrites, axon terminals and cell bodies is essential for long-term synaptic plasticity. Specific to pain, shifts in pain thresholds and responsiveness are an expression of neuronal plasticity and this likely contributes to persistent pain. We investigated this by inhibiting the activity of mTOR with rapamycin at the spinal level, of rats that were subjected to the formalin test, using both behavioural and electrophysiological techniques. Results For in vivo electrophysiology, Sprague Dawley rats were fully anaesthetised and single-unit extracellular recordings were obtained from lamina V wide dynamic range (WDR dorsal horn spinal neurones at the region where input is received from the hind paw. Neuronal responses from naive rats showed that rapamycin-sensitive pathways were important in nociceptive-specific C-fibre mediated transmission onto WDR neurones as well mechanically-evoked responses since rapamycin was effective in attenuating these measures. Formalin solution was injected into the hind paw prior to which, rapamycin or vehicle was applied directly onto the exposed spinal cord. When rapamycin was applied to the spinal cord prior to hind paw formalin injection, there was a significant attenuation of the prolonged second phase of the formalin test, which comprises continuing afferent input to the spinal cord, neuronal hyperexcitability and an activated descending facilitatory drive from the brainstem acting on spinal neurones. In accordance with electrophysiological data, behavioural studies showed that rapamycin attenuated behavioural hypersensitivity elicited by formalin injection into the hind paw. Conclusion We conclude that mTOR has a role in maintaining persistent pain states via m

  16. Amalgam Contact Hypersensitivity Lesion: An Unusual Presentation ...

    African Journals Online (AJOL)

    of electromagnetic fields (e.g. Wi‑Fi, mobile phones and mobile base stations) in intensifying the release of mercury from dental amalgam restorations. Over the past years, our laboratory has focused on studying the health effects of exposure to some common and/or occupational sources of electromagnetic fields such as ...

  17. RXLR and CRN Effectors from the Sunflower Downy Mildew Pathogen Plasmopara halstedii Induce Hypersensitive-Like Responses in Resistant Sunflower Lines

    Science.gov (United States)

    Gascuel, Quentin; Buendia, Luis; Pecrix, Yann; Blanchet, Nicolas; Muños, Stéphane; Vear, Felicity; Godiard, Laurence

    2016-01-01

    Plasmopara halstedii is an obligate biotrophic oomycete causing downy mildew disease on sunflower, Helianthus annuus, an economically important oil crop. Severe symptoms of the disease (e.g., plant dwarfism, leaf bleaching, sporulation and production of infertile flower) strongly impair seed yield. Pl resistance genes conferring resistance to specific P. halstedii pathotypes were located on sunflower genetic map but yet not cloned. They are present in cultivated lines to protect them against downy mildew disease. Among the 16 different P. halstedii pathotypes recorded in France, pathotype 710 is frequently found, and therefore continuously controlled in sunflower by different Pl genes. High-throughput sequencing of cDNA from P. halstedii led us to identify potential effectors with the characteristic RXLR or CRN motifs described in other oomycetes. Expression of six P. halstedii putative effectors, five RXLR and one CRN, was analyzed by qRT-PCR in pathogen spores and in the pathogen infecting sunflower leaves and selected for functional analyses. We developed a new method for transient expression in sunflower plant leaves and showed for the first time subcellular localization of P. halstedii effectors fused to a fluorescent protein in sunflower leaf cells. Overexpression of the CRN and of 3 RXLR effectors induced hypersensitive-like cell death reactions in some sunflower near-isogenic lines resistant to pathotype 710 and not in susceptible corresponding lines, suggesting they could be involved in Pl loci-mediated resistances. PMID:28066456

  18. RXLR and CRN effectors from the sunflower downy mildew pathogen Plasmopara halstedii induce hypersensitive-like responses in resistant sunflower lines

    Directory of Open Access Journals (Sweden)

    Quentin Gascuel

    2016-12-01

    Full Text Available Plasmopara halstedii is an obligate biotrophic oomycete causing downy mildew disease on sunflower, Helianthus annuus, an economically important oil crop. Severe symptoms of the disease (e.g. plant dwarfism, leaf bleaching, sporulation and production of infertile flower strongly impair seed yield. Pl resistance genes conferring resistance to specific P. halstedii pathotypes were located on sunflower genetic map but yet not cloned. They are present in cultivated lines to protect them against downy mildew disease. Among the 16 different P. halstedii pathotypes recorded in France, pathotype 710 is frequently found, and therefore continuously controlled in sunflower by different Pl genes. High-throughput sequencing of cDNA from P. halstedii led us to identify potential effectors with the characteristic RXLR or CRN motifs described in other oomycetes. Expression of six P. halstedii putative effectors, five RXLR and one CRN, was analysed by qRT-PCR in pathogen spores and in the pathogen infecting sunflower leaves and these six effectors were selected for functional analyses. We developed a new method for transient expression in sunflower plant leaves and showed for the first time subcellular localization of P. halstedii effectors fused to a fluorescent protein in sunflower leaf cells. Overexpression of the CRN and of 3 RXLR effectors induced hypersensitive-like cell death reactions in some sunflower near-isogenic lines resistant to pathotype 710 and not in susceptible corresponding lines, suggesting they could be involved in Pl loci-mediated resistances.

  19. Variation in plant defense against invasive herbivores: evidence for a hypersensitive response in eastern hemlocks (Tsuga canadensis).

    Science.gov (United States)

    Radville, Laura; Chaves, Arielle; Preisser, Evan L

    2011-06-01

    Herbivores can trigger a wide array of morphological and chemical changes in their host plants. Feeding by some insects induces a defensive hypersensitive response, a defense mechanism consisting of elevated H(2)O(2) levels and tissue death at the site of herbivore feeding. The invasive hemlock woolly adelgid Adelges tsugae ('HWA') and elongate hemlock scale Fiorinia externa ('EHS') feed on eastern hemlocks; although both are sessile sap feeders, HWA causes more damage than EHS. The rapid rate of tree death following HWA infestation has led to the suggestion that feeding induces a hypersensitive response in hemlock trees. We assessed the potential for an herbivore-induced hypersensitive response in eastern hemlocks by measuring H(2)O(2) levels in foliage from HWA-infested, EHS-infested, and uninfested trees. Needles with settled HWA or EHS had higher H(2)O(2) levels than control needles, suggesting a localized hypersensitive plant response. Needles with no direct contact to settled HWA also had high H(2)O(2) levels, suggesting that HWA infestation may induce a systemic defense response in eastern hemlocks. There was no similar systemic defensive response in the EHS treatment. Our results showed that two herbivores in the same feeding guild had dramatically different outcomes on the health of their shared host.

  20. Positive allosteric modulation of GABA-A receptors reduces capsaicin-induced primary and secondary hypersensitivity in rats

    DEFF Research Database (Denmark)

    Hansen, Rikke Rie; Erichsen, Helle K; Brown, David T

    2012-01-01

    GABA-A receptor positive allosteric modulators (PAMs) mediate robust analgesia in animal models of pathological pain, in part via enhancing injury-induced loss of GABA-A-α2 and -α3 receptor function within the spinal cord. As yet, a lack of clinically suitable tool compounds has prevented this co...

  1. Toxin- and cadmium-induced cell death events in tomato suspension cells resemble features of hypersensitive response

    NARCIS (Netherlands)

    Iakimova, E.T.; Woltering, E.J.; Yordanova, Z.P.

    2007-01-01

    Elicitors of different origin (fumonisin B1, fungal toxin), camptothecin (alkaloid from Camptotheca acuminata), mastoparan (wasp venom) and the heavy metal (cadmium) were tested for their ability to induce programmed cell death (PCD) in a model system of tomato cell culture, line MsK8. By employing

  2. Comparative evaluation of Type 1 latex hypersensitivity in patients with chronic urticaria, rubber factory workers and healthy control subjects

    NARCIS (Netherlands)

    Piskin, Gamze; Akyol, Aynur; Uzar, Hatice; Tulek, Necla; Boyvat, Ayse; Gurgey, Erbak

    2003-01-01

    Latex hypersensitivity manifests itself most commonly with contact urticaria. In this study, we investigated the frequency of latex hypersensitivity as a possible aetiological factor in patients with chronic urticaria (CU) and compared latex hypersensitivity of CU patients (n = 50) with that of

  3. Current-induced dynamics in carbon atomic contacts

    DEFF Research Database (Denmark)

    Lu, Jing Tao; Gunst, Tue; Brandbyge, Mads

    2011-01-01

    voltage, which can be used to explore current-induced vibrational instabilities due the NC/BP forces. Furthermore, using tight-binding and the Brenner potential we illustrate how Langevin-type molecular-dynamics calculations including the Joule heating effect for the carbon-chain systems can be performed...... be used to explore current-induced dynamics and instabilities. We find instabilities at experimentally relevant bias and gate voltages for the carbon-chain system. © 2011 Lü et al....... carbon chain connecting electrically gated graphene electrodes. This illustrates how the device stability can be predicted solely from the modes obtained from the Langevin equation, including the current-induced forces. We point out that the gate offers control of the current, independent of the bias...

  4. Development of novel immunogens on the hypersensitivity induced proteins by the combination of radiation technology and biotechnology

    International Nuclear Information System (INIS)

    Lee, Ju Woon; Byun, Myung Woo; Kim, Jae Hun; Seo, Ji Hyun

    2006-01-01

    The irradiated house dust mite allergen showed the conformational change with disappearance of major allergen and aggregation to higher molecular weights. The irradiated house dust mite allergens showed the change of epitope from results of the reduction of binding ability of house dust mite-allergic patients' serum (IgE) and polyclonal rabbit IgG against the irradiated allergens. In assessment of immunogenicity and allergenicity, irradiated house dust mite allergen showed the reduction of allergenicity with decrease of concentration for IL-4 and IL-5, the cytokine inducing allergy. For the assessment of the possibility as therapeutic immunogen of irradiated house dust mite allergen, allergic induced-mouse model were established. Irradiated allergen showed the maintainment of immunogenicity and the reduction of allergenicity from the result of maintain of IgG and reduction of IgE. Blue spots against irradiated allergen decreased raising with radiation dose in passive cutaneous anaphylaxis. The therapeutic effect was measured by reduction of house dust mite-specific IgE, IL-4 and IL-5. Induction of allergy after immunization of irradiated house dust mite allergen decreased by the reduction of house dust mite-specific IgE and IL-4 release. Therefore, house dust mite allergen modified by irradiation could be used as an effective immunogens for the prevention and treatment of allergy

  5. Development of novel immunogens on the hypersensitivity induced proteins by the combination of radiation technology and biotechnology

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ju Woon; Byun, Myung Woo; Kim, Jae Hun; Seo, Ji Hyun

    2006-01-15

    The irradiated house dust mite allergen showed the conformational change with disappearance of major allergen and aggregation to higher molecular weights. The irradiated house dust mite allergens showed the change of epitope from results of the reduction of binding ability of house dust mite-allergic patients' serum (IgE) and polyclonal rabbit IgG against the irradiated allergens. In assessment of immunogenicity and allergenicity, irradiated house dust mite allergen showed the reduction of allergenicity with decrease of concentration for IL-4 and IL-5, the cytokine inducing allergy. For the assessment of the possibility as therapeutic immunogen of irradiated house dust mite allergen, allergic induced-mouse model were established. Irradiated allergen showed the maintainment of immunogenicity and the reduction of allergenicity from the result of maintain of IgG and reduction of IgE. Blue spots against irradiated allergen decreased raising with radiation dose in passive cutaneous anaphylaxis. The therapeutic effect was measured by reduction of house dust mite-specific IgE, IL-4 and IL-5. Induction of allergy after immunization of irradiated house dust mite allergen decreased by the reduction of house dust mite-specific IgE and IL-4 release. Therefore, house dust mite allergen modified by irradiation could be used as an effective immunogens for the prevention and treatment of allergy.

  6. Stevens-Johnson syndrome and toxic epidermal necrolysis due to anticonvulsants share certain clinical and laboratory features with drug-induced hypersensitivity syndrome, despite differences in cutaneous presentations.

    Science.gov (United States)

    Teraki, Y; Shibuya, M; Izaki, S

    2010-10-01

    Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is characterized by late disease onset, fever, rash, hepatic dysfunction, haematological abnormalities, lymphadenopathy and often, human herpesvirus (HHV) reactivation. The diagnosis of DIHS is based on the combined presence of these findings. Anticonvulsants are a major cause of DIHS and may also cause Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We examined whether SJS/TEN due to anticonvulsants display similar clinical and laboratory features seen in DIHS. Patients diagnosed with SJS or TEN due to anticonvulsants (n = 8) were examined and their clinical features and laboratory findings were compared with patients with anticonvulsant-related DIHS (n = 6). Seven of the eight patients with SJS/TEN developed symptoms > 3 weeks after starting anticonvulsants. Hepatic dysfunction was present in six patients with SJS/TEN and five patients with DIHS. Leucocytosis and/or eosinophilia was noted in seven patients with SJS/TEN and four patients with DIHS. Only one patient in the SJS/TEN group had atypical lymphocytosis; this was present in four patients with DIHS. Reactivation of HHV-6 was detected in one of the four patients tested in the SJS/TEN group, although it was seen in five of the six patients with DIHS. TSJS/TEN due to anticonvulsants may exhibit some clinical and laboratory features of DIHS. The nature of the cutaneous involvement should be emphasized in the diagnosis of DIHS. © 2009 The Author(s). Journal compilation © 2009 British Association of Dermatologists.

  7. Immunotherapy of allergic contact dermatitis.

    Science.gov (United States)

    Spiewak, Radoslaw

    2011-08-01

    The term 'immunotherapy' refers to treating diseases by inducing, enhancing or suppressing immune responses. As allergy is an excessive, detrimental immune reaction to otherwise harmless environmental substances, immunotherapy of allergic disease is aimed at the induction of tolerance toward sensitizing antigens. This article focuses on the historical developments, present state and future outlook for immunotherapy with haptens as a therapeutic modality for allergic contact dermatitis. Inspired by the effectiveness of immunotherapy in respiratory allergies, attempts were undertaken at curing allergic contact dermatitis by means of controlled administration of the sensitizing haptens. Animal and human experiments confirmed that tolerance to haptens can be induced most effectively when the induction of tolerance precedes attempted sensitization. In real life, however, therapy is sought by people who are already sensitized and an effective reversal of hypersensitivity seems more difficult to achieve. Decades of research on Rhus hypersensitivity led to a conclusion that immunotherapy can suppress Rhus dermatitis, however, only to a limited degree, for a short period of time, and at a high risk of side effects, which makes this method therapeutically unprofitable. Methodological problems with most available studies of immunotherapy of contact allergy to nickel make any definite conclusions impossible at this stage.

  8. Plant innate immunity induced by flagellin suppresses the hypersensitive response in non-host plants elicited by Pseudomonas syringae pv. averrhoi.

    Directory of Open Access Journals (Sweden)

    Chia-Fong Wei

    Full Text Available A new pathogen, Pseudomonas syringae pv. averrhoi (Pav, which causes bacterial spot disease on carambola was identified in Taiwan in 1997. Many strains of this pathovar have been isolated from different locations and several varieties of hosts. Some of these strains, such as HL1, are nonmotile and elicit a strong hypersensitive response (HR in nonhost tobacco leaves, while other strains, such as PA5, are motile and elicit a weak HR. Based on the image from a transmission electron microscope, the results showed that HL1 is flagellum-deficient and PA5 has normal flagella. Here we cloned and analyzed the fliC gene and glycosylation island from Pav HL1 and PA5. The amino acid sequences of FliC from HL1 and PA5 are identical to P. s. pvs. tabaci (Pta, glycinea and phaseolicola and share very high similarity with other pathovars of P. syringae. In contrast to the flagellin mutant PtaΔfliC, PA5ΔfliC grows as well as wild type in the host plant, but it elicits stronger HR than wild type does in non-host plants. Furthermore, the purified Pav flagellin, but not the divergent flagellin from Agrobacterium tumefaciens, is able to impair the HR induced by PA5ΔfliC. PA5Δfgt1 possessing nonglycosylated flagella behaved as its wild type in both bacterial growth in host and HR elicitation. Flagellin was infiltrated into tobacco leaves either simultaneously with flagellum-deficient HL1 or prior to the inoculation of wild type HL1, and both treatments impaired the HR induced by HL1. Moreover, the HR elicited by PA5 and PA5ΔfliC was enhanced by the addition of cycloheximide, suggesting that the flagellin is one of the PAMPs (pathogen-associated molecular patterns contributed to induce the PAMP-triggered immunity (PTI. Taken together, the results shown in this study reveal that flagellin in Pav is capable of suppressing HR via PTI induction during an incompatible interaction.

  9. Plant Innate Immunity Induced by Flagellin Suppresses the Hypersensitive Response in Non-Host Plants Elicited by Pseudomonas syringae pv. averrhoi

    Science.gov (United States)

    Wei, Chia-Fong; Hsu, Shih-Tien; Deng, Wen-Ling; Wen, Yu-Der; Huang, Hsiou-Chen

    2012-01-01

    A new pathogen, Pseudomonas syringae pv. averrhoi (Pav), which causes bacterial spot disease on carambola was identified in Taiwan in 1997. Many strains of this pathovar have been isolated from different locations and several varieties of hosts. Some of these strains, such as HL1, are nonmotile and elicit a strong hypersensitive response (HR) in nonhost tobacco leaves, while other strains, such as PA5, are motile and elicit a weak HR. Based on the image from a transmission electron microscope, the results showed that HL1 is flagellum-deficient and PA5 has normal flagella. Here we cloned and analyzed the fliC gene and glycosylation island from Pav HL1 and PA5. The amino acid sequences of FliC from HL1 and PA5 are identical to P. s. pvs. tabaci (Pta), glycinea and phaseolicola and share very high similarity with other pathovars of P. syringae. In contrast to the flagellin mutant PtaΔfliC, PA5ΔfliC grows as well as wild type in the host plant, but it elicits stronger HR than wild type does in non-host plants. Furthermore, the purified Pav flagellin, but not the divergent flagellin from Agrobacterium tumefaciens, is able to impair the HR induced by PA5ΔfliC. PA5Δfgt1 possessing nonglycosylated flagella behaved as its wild type in both bacterial growth in host and HR elicitation. Flagellin was infiltrated into tobacco leaves either simultaneously with flagellum-deficient HL1 or prior to the inoculation of wild type HL1, and both treatments impaired the HR induced by HL1. Moreover, the HR elicited by PA5 and PA5ΔfliC was enhanced by the addition of cycloheximide, suggesting that the flagellin is one of the PAMPs (pathogen-associated molecular patterns) contributed to induce the PAMP-triggered immunity (PTI). Taken together, the results shown in this study reveal that flagellin in Pav is capable of suppressing HR via PTI induction during an incompatible interaction. PMID:22911741

  10. Cytokines Expression and Nitric Oxide Production under Induced Infection to Typhimurium in Chicken Lines Divergently Selected for Cutaneous Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Rani Singh

    2012-07-01

    Full Text Available In the present study, the impact of Salmonella Typhimurium on cell-mediated immunity (CMI was investigated in 5 week-old immuno divergent broiler lines selected for the high and low response to phytohemagglutinin-P. The immune response was assessed in peripheral-blood mononuclear cells (PBMCs induced with Salmonella Typhimurium at different time intervals (0 h, 0.5 h, 2 h, 4 h, 6 h, 12 h and 24 h. The differential mRNA expression patterns of IFN-γ, IL-2 and iNOS were evaluated by quantitative real time PCR. In-vitro production of nitric oxide (NO was also estimated in the culture supernatant and correlated with iNOS mRNA expression. Present study showed higher production of NO in the high cell-mediated line (HCMI as compared to the low cell-mediated line (LCMI upon stimulation with Salmonella Typhimurium. Correspondingly, higher mRNA expression of iNOS and IFN-γ were observed in high response birds (HCMI; but IL-2 was down regulated in this line compared to the low response birds (LCMI. Significantly (p<0.05 higher expression of iNOS, IFN-γ and higher production of NO in high line indicated that the selection for PHA-P response might be employed for increasing the immune competence against Salmonella Typhimurium in chicken flocks.

  11. Pharmacological activation/inhibition of the cannabinoid system affects alcohol withdrawal-induced neuronal hypersensitivity to excitotoxic insults.

    Directory of Open Access Journals (Sweden)

    Marina Rubio

    Full Text Available Cessation of chronic ethanol consumption can increase the sensitivity of the brain to excitotoxic damages. Cannabinoids have been proposed as neuroprotectants in different models of neuronal injury, but their effect have never been investigated in a context of excitotoxicity after alcohol cessation. Here we examined the effects of the pharmacological activation/inhibition of the endocannabinoid system in an in vitro model of chronic ethanol exposure and withdrawal followed by an excitotoxic challenge. Ethanol withdrawal increased N-methyl-D-aspartate (NMDA-evoked neuronal death, probably by altering the ratio between GluN2A and GluN2B NMDA receptor subunits. The stimulation of the endocannabinoid system with the cannabinoid agonist HU-210 decreased NMDA-induced neuronal death exclusively in ethanol-withdrawn neurons. This neuroprotection could be explained by a decrease in NMDA-stimulated calcium influx after the administration of HU-210, found exclusively in ethanol-withdrawn neurons. By contrast, the inhibition of the cannabinoid system with the CB1 receptor antagonist rimonabant (SR141716 during ethanol withdrawal increased death of ethanol-withdrawn neurons without any modification of NMDA-stimulated calcium influx. Moreover, chronic administration of rimonabant increased NMDA-stimulated toxicity not only in withdrawn neurons, but also in control neurons. In summary, we show for the first time that the stimulation of the endocannabinoid system is protective against the hyperexcitability developed during alcohol withdrawal. By contrast, the blockade of the endocannabinoid system is highly counterproductive during alcohol withdrawal.

  12. Mast Cells Limit the Exacerbation of Chronic Allergic Contact Dermatitis in Response to Repeated Allergen Exposure.

    Science.gov (United States)

    Gimenez-Rivera, Vladimir-Andrey; Siebenhaar, Frank; Zimmermann, Carolin; Siiskonen, Hanna; Metz, Martin; Maurer, Marcus

    2016-12-01

    Allergic contact dermatitis is a chronic T cell-driven inflammatory skin disease that is caused by repeated exposure to contact allergens. Based on murine studies of acute contact hypersensitivity, mast cells (MCs) are believed to play a role in its pathogenesis. The role of MCs in chronic allergic contact dermatitis has not been investigated, in part because of the lack of murine models for chronic contact hypersensitivity. We developed and used a chronic contact hypersensitivity model in wild-type and MC-deficient mice and assessed skin inflammatory responses to identify and characterize the role of MCs in chronic allergic contact dermatitis. Ear swelling chronic contact hypersensitivity responses increased markedly, up to 4-fold, in MC-deficient Kit W-sh/W-sh (Sash) and MCPT5-Cre + iDTR + mice compared with wild-type mice. Local engraftment with MCs protected Sash mice from exacerbated ear swelling after repeated oxazolone challenge. Chronic contact hypersensitivity skin of Sash mice exhibited elevated levels of IFN-γ, IL-17α, and IL-23, as well as increased accumulation of Ag-specific IFN-γ-producing CD8 + tissue-resident memory T (T RM ) cells. The CD8 + T cell mitogen IL-15, which was increased in oxazolone-challenged skin of Sash mice during the accumulation of cutaneous T RM cells, was efficiently degraded by MCs in vitro. MCs protect from the exacerbated allergic skin inflammation induced by repeated allergen challenge, at least in part, via effects on CD8 + T RM cells. MCs may notably influence the course of chronic allergic contact dermatitis. A better understanding of their role and the underlying mechanisms may lead to better approaches for the treatment of this common, disabling, and costly condition. Copyright © 2016 by The American Association of Immunologists, Inc.

  13. Enkephalin and dynorphin neuropeptides are differently correlated with locomotor hypersensitivity and levodopa-induced dyskinesia in parkinsonian rats.

    Science.gov (United States)

    Sgroi, Stefania; Capper-Loup, Christine; Paganetti, Paolo; Kaelin-Lang, Alain

    2016-06-01

    The opioidergic neuropeptides dynorphin (DYN) and enkephalin (ENK) and the D1 and D2 dopaminergic receptors (D1R, D2R) are involved in the striatal control of motor and behavioral function. In Parkinson's disease, motor disturbances such as "on-off" motor fluctuations and involuntary movements (dyskinesia) are severe complications that often arise after chronic l-dihydroxyphenylalanine (l-DOPA) treatment. Changes in the striatal expression of preproENK (PPENK), proDYN (PDYN), D1R, and D2R mRNA have been observed in parkinsonian animals treated with l-DOPA. Enhanced opioidergic transmission has been found in association with l-DOPA-induced dyskinesia, but the connection of PPENK, PDYN, D1R, and D2R mRNA expression with locomotor activity remains unclear. In this study, we measured PPENK, PDYN, D1R and D2R mRNA levels by in situ hybridization in the striatum of 6-OHDA hemi-parkinsonian rats treated with l-DOPA (PD+l-DOPA group), along with two control groups (PD+saline and naive+l-DOPA). We found different levels of expression of PPENK, PDYN, D1R and D2R mRNA across the experimental groups and correlated the changes in mRNA expression with dyskinesia and locomotor variables assessed by open field test during several phases of l-DOPA treatment. Both PDYN and PPENK mRNA levels were correlated with the severity of dyskinesia, while PPENK mRNA levels were also correlated with the frequency of contralateral rotational movements and with locomotor variables. Moreover, a strong correlation was found between D1R mRNA expression and D2R mRNA expression in the PD+l-DOPA group. These findings suggest that, in parkinsonian animals treated with l-DOPA, high levels of PPENK are a prerequisite for a locomotor sensitization to l-DOPA treatment, while PDYN overexpression is responsible only for the development of dyskinesia. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Probing wavenumbers of current-induced excitations in point-contact experiments

    Directory of Open Access Journals (Sweden)

    Z Wei

    2010-06-01

    Full Text Available Z Wei, M TsoiDepartment of Physics, Center for Nano and Molecular Science and Technology, and Texas Materials Institute, The University of Texas at Austin, Austin, TX, USAAbstract: We demonstrate how a mechanical point-contact technique can provide information on the wavenumber of spin waves excited by high-density electrical current in magnetic multilayers. By varying the size of point-contacts, we have been able to control the size of the excitation volume and therefore the wavelength of current-induced spin waves. This leads to a technique with in situ sensitivity to wavenumbers of current-induced excitations. Our detailed size-dependent measurements support the prediction that the excited wavelength is determined by the contact size.Keywords: spin transfer torque, giant magnetoresistance, spin waves, point contact

  15. Direct contact condensation induced transition from stratified to slug flow

    International Nuclear Information System (INIS)

    Strubelj, Luka; Ezsoel, Gyoergy; Tiselj, Iztok

    2010-01-01

    Selected condensation-induced water hammer experiments performed on PMK-2 device were numerically modelled with three-dimensional two-fluid models of computer codes NEPTUNE C FD and CFX. Experimental setup consists of the horizontal pipe filled with the hot steam that is being slowly flooded with cold water. In most of the experimental cases, slow flooding of the pipe was abruptly interrupted by a strong slugging and water hammer, while in the selected experimental runs performed at higher initial pressures and temperatures that are analysed in the present work, the transition from the stratified into the slug flow was not accompanied by the water hammer pressure peak. That makes these cases more suitable tests for evaluation of the various condensation models in the horizontally stratified flows and puts them in the range of the available CFD (Computational Fluid Dynamics) codes. The key models for successful simulation appear to be the condensation model of the hot vapour on the cold liquid and the interfacial momentum transfer model. The surface renewal types of condensation correlations, developed for condensation in the stratified flows, were used in the simulations and were applied also in the regions of the slug flow. The 'large interface' model for inter-phase momentum transfer model was compared to the bubble drag model. The CFD simulations quantitatively captured the main phenomena of the experiments, while the stochastic nature of the particular condensation-induced water hammer experiments did not allow detailed prediction of the time and position of the slug formation in the pipe. We have clearly shown that even the selected experiments without water hammer present a tough test for the applied CFD codes, while modelling of the water hammer pressure peaks in two-phase flow, being a strongly compressible flow phenomena, is beyond the capability of the current CFD codes.

  16. Dilemma in the Diagnosis of Povidone-Iodine Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Patil N

    2016-01-01

    Full Text Available Povidone-iodine is a commonly used antiseptic solution in surgical practice. Almost every patient who needs a minor or a major surgical procedure (sometimes, a medical procedure too gets exposed to this antiseptic. Even though the use of this antiseptic is widespread, the number of cases reporting hypersensitivity to it is meagre. This case report highlights a case of povidone-iodine – induced hypersensitivity, which presented a great difficulty in diagnosis, due to the usage of other drugs that could have been more likely causes for this hypersensitivity.

  17. Chronic hypersensitivity pneumonitis.

    Science.gov (United States)

    Pereira, Carlos Ac; Gimenez, Andréa; Kuranishi, Lilian; Storrer, Karin

    2016-01-01

    Hypersensitivity pneumonitis (HSP) is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary.

  18. 7th drug hypersensitivity meeting: part one

    OpenAIRE

    Carr, Daniel F.; Chung, Wen-Hung; Jenkiins, Rosalind E.; Chaponda, Mas; Nwikue, Gospel; Cornejo Castro, Elena M.; Antoine, Daniel J.; Pirmohamed, Munir; Wuillemin, Natascha; Dina, Dolores; Eriksson, Klara K.; Yerly, Daniel; Pavlos, Rebecca; Mckinnin, Elizabeth; Ostrov, David

    2016-01-01

    Table of contents Oral Abstracts O1 Functionally distinct HMGB1 isoforms correlate with physiological processes in drug-induced SJS/TEN Daniel F. Carr, Wen-Hung Chung, Rosalind E. Jenkiins, Mas Chaponda, Gospel Nwikue, Elena M. Cornejo Castro, Daniel J. Antoine, Munir Pirmohamed O2 Hypersensitivity reactions to beta-lactams, does the t cell recognition pattern influence the clinical picture? Natascha Wuillemin, Dolores Dina, Klara K. Eriksson, Daniel Yerly O3 Specific binding characteristics ...

  19. Drug hypersensitivity syndrome

    Directory of Open Access Journals (Sweden)

    Rashmi Kumari

    2011-01-01

    Full Text Available Drug hypersensitivity syndrome (DHS is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs, viz., phenytoin (PHT, carbamazepine (CBZ, phenobarbital (PB, lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.

  20. Allergic contact dermatitis induced by zinc pyrithione in shampoo: a case report

    Directory of Open Access Journals (Sweden)

    Chih-Wei Hsieh

    2010-12-01

    Full Text Available Shampoo-induced allergic contact dermatitis is difficult to diagnose clinically because it can involve multiple and variable areas where the shampoo flows. Zinc pyrithione is a common active agent in medicated shampoo that is known to have good anti-dandruff and antifungal effects. Despite its low risk of sensitization, cases of allergic contact dermatitis still occur because of the popularity of such products. We report a 33-year-old man who developed pruritic rash on his scalp, face, neck, and hands after using a new shampoo containing zinc pyrithione. A patch test revealed a positive reaction to zinc pyrithione and personal shampoo containing zinc pyrithione.

  1. Food hypersensitivity by inhalation

    Directory of Open Access Journals (Sweden)

    Bahna Sami L

    2009-02-01

    Full Text Available Abstract Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization.

  2. Chronic hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    Pereira CA

    2016-09-01

    Full Text Available Carlos AC Pereira,1 Andréa Gimenez,2 Lilian Kuranishi,2 Karin Storrer 2 1Interstitial Lung Diseases Program, 2Pulmonology Postgraduate, Federal University of São Paulo, São Paulo, Brazil Abstract: Hypersensitivity pneumonitis (HSP is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary. Keywords: interstitial lung diseases, extrinsic allergic alveolitis, diffuse lung disease, lung immune response, HRCT, farmers lung

  3. Cutaneous and systemic hypersensitivity reactions to metallic implants

    DEFF Research Database (Denmark)

    Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C

    2011-01-01

    Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous....... However, other metal ions as well as bone cement components can cause such hypersensitivity reactions. To complicate things, patients may also develop delayed-type hypersensitivity reactions to metals (ie, in-stent restenosis, prosthesis loosening, inflammation, pain, or allergic contact dermatitis...

  4. An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Chun-Bing Chen

    2018-01-01

    Full Text Available Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS/drug-induced hypersensitivity syndrome (DIHS, or Stevens–Johnson syndrome (SJS/toxic epidermal necrolysis (TEN. Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs. The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity.

  5. An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity

    Science.gov (United States)

    Abe, Riichiro; Pan, Ren-You; Wang, Chuang-Wei

    2018-01-01

    Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria) to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), or Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR) molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity. PMID:29651444

  6. Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera.

    Science.gov (United States)

    Patel, Ryan; Brice, Nicola L; Lewis, Richard J; Dickenson, Anthony H

    2015-12-01

    Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity. © 2015 The Authors. European Journal of Neuroscience published by Federation of

  7. Metal Hypersensitivity in Orthodontic Patients

    Directory of Open Access Journals (Sweden)

    Sandhya Maheshwari Sanjeev K

    2015-06-01

    Full Text Available Orthodontic treatment of individuals with metal hypersensitivity is a matter of concern for the orthodontist. Orthodontic appliances contain metals like Nickel, Cobalt and Chromium etc. Metals may cause allergic reactions and are known as allergens. Reaction to these metals is due to biodegradation of metals in the oral cavity. This may lead to the formation of corrosion products and their exposure to the patient. Nickel is the most common metal to cause hypersensitivity reaction. Chromium ranks second among the metals, known to trigger allergic reactions. The adverse biological reactions to these metals may include hypersensitivity, dermatitis and asthma. In addition, a significant carcinogenic and mutagenic potential has been demonstrated. The orthodontist must be familiar with the best possible alternative treatment modalities to provide the safest, most effective care possible in these cases. The present article focuses on the issue of metal hypersensitivity and its management in orthodontic

  8. Contact dermatitis following sustained exposure to pecans (Carya illinoensis): a case report.

    Science.gov (United States)

    Joyce, Kathleen M; Boyd, Jason; Viernes, Jay L

    2006-04-01

    Type I hypersensitivity reactions following ingestion of peanuts and tree nuts are well characterized. Cutaneous hypersensitivity reactions are less well characterized, yet they remain the second most common reaction pattern to contact with or ingestion of such nuts. We present a case of a patient who experienced an acute vesicular cutaneous reaction after prolonged contact with pecans. This case illustrates the salient features of contact dermatitis and serves as a reminder that contact with allergenic foods can lead to hypersensitivity reactions.

  9. Occupational protein contact dermatitis.

    Science.gov (United States)

    Barbaud, Annick; Poreaux, Claire; Penven, Emmanuelle; Waton, Julie

    2015-01-01

    Occupational contact dermatitis is generally caused by haptens but can also be induced by proteins causing mainly immunological contact urticaria (ICU); chronic hand eczema in the context of protein contact dermatitis (PCD). In a monocentric retrospective study, from our database, only 31 (0.41%) of patients with contact dermatitis had positive skin tests with proteins: 22 had occupational PCD, 3 had non-occupational PCD, 5 occupational ICU and 1 cook had a neutrophilic fixed food eruption (NFFE) due to fish. From these results and analysis of literature, the characteristics of PCD can be summarized as follows. It is a chronic eczematous dermatitis, possibly exacerbated by work, suggestive if associated with inflammatory perionyxix and immediate erythema with pruritis, to be investigated when the patient resumes work after a period of interruption. Prick tests with the suspected protein-containing material are essential, as patch tests have negative results. In case of multisensitisation revealed by prick tests, it is advisable to analyse IgE against recombinant allergens. A history of atopy, found in 56 to 68% of the patients, has to be checked for. Most of the cases are observed among food-handlers but PCD can also be due to non-edible plants, latex, hydrolysed proteins or animal proteins. Occupational exposure to proteins can thus lead to the development of ICU. Reflecting hypersensitivity to very low concentrations of allergens, investigating ICU therefore requires caution and prick tests should be performed with a diluted form of the causative protein-containing product. Causes are food, especially fruit peel, non-edible plants, cosmetic products, latex, animals.

  10. Contact induced spin relaxation in graphene spin valves with Al2O3 and MgO tunnel barriers

    Directory of Open Access Journals (Sweden)

    Walid Amamou

    2016-03-01

    Full Text Available We investigate spin relaxation in graphene by systematically comparing the roles of spin absorption, other contact-induced effects (e.g., fringe fields, and bulk spin relaxation for graphene spin valves with MgO barriers, Al2O3 barriers, and transparent contacts. We obtain effective spin lifetimes by fitting the Hanle spin precession data with two models that include or exclude the effect of spin absorption. Results indicate that additional contact-induced spin relaxation other than spin absorption dominates the contact effect. For tunneling contacts, we find reasonable agreement between the two models with median discrepancy of ∼20% for MgO and ∼10% for Al2O3.

  11. Upregulation of Ih expressed in IB4-negative Aδ nociceptive DRG neurons contributes to mechanical hypersensitivity associated with cervical radiculopathic pain

    OpenAIRE

    Da-Lu Liu; Na Lu; Wen-Juan Han; Rong-Gui Chen; Rui Cong; Rou-Gang Xie; Yu-Fei Zhang; Wei-Wei Kong; San-Jue Hu; Ceng Luo

    2015-01-01

    Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron?s ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensit...

  12. Experimental photoallergic contact dermatitis (photo-ACD) and persistent light reactivity (PLR) induced by bisphenol-A

    International Nuclear Information System (INIS)

    Maguire, H.C. Jr.

    1986-01-01

    Bisphenol-A, a compound widely used in the plastics industry, clinically has been reported to induce photo-ACD and PLR. In mice, the authors find that Bisphenol-A (Bis-A) is a substantial photosensitizer and can serve as a model compound for the study of the cutaneous disorder, PLR. Mice were photosensitized by 2 daily applications of 1% Bis-A followed by irradiation of the skin site with UVB (280-320nm) and UVA (320-400nm). Sometimes, intradermal C.parvum (30 μ g) and/or pretreatment with cyclophosphamide (Cy; 50mg/kg) was used for nonspecific immunopotentiation. Photochallenge of an ear with chemical followed by UVA is usually done on Day 6. The reaction is consistent with that of delayed type hypersensitivity. Positive photochallenge sites react to UVA alone, thereby mimicking the clinical condition of the persistent light reactor

  13. Respiratory hypersensitivity reactions to NSAIDs in Europe

    DEFF Research Database (Denmark)

    Makowska, J S; Burney, P; Jarvis, D

    2016-01-01

    BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper...... and lower respiratory tract disorders. METHODS: The GA(2) LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled...... prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants...

  14. Association of HLA genotypes with phenobarbital hypersensitivity in children.

    Science.gov (United States)

    Manuyakorn, Wiparat; Mahasirimongkol, Surakameth; Likkasittipan, Plernpit; Kamchaisatian, Wasu; Wattanapokayakit, Sukanya; Inunchot, Wimala; Visudtibhan, Anannit; Wichukchinda, Nuanjun; Benjaponpitak, Suwat

    2016-10-01

    Phenobarbital hypersensitivity is one of the common drug hypersensitivity syndromes in children. Clinical symptoms of phenobarbital hypersensitivity vary from maculopapular rashes (MPs) to severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Drug hypersensitivity has been demonstrated to be associated with variations in the HLA genotypes. This study was to investigate the association between the variations of HLA genotypes and phenobarbital hypersensitivity in Thai children. The cases were Thai children, between 0 and 18 years of age, who were diagnosed with phenobarbital hypersensitivity, which included SCARs and MPs. The control patients were Thai children of a corresponding age who had taken phenobarbital for at least 12 weeks without any hypersensitivity reaction. Blood samples were collected for HLA genotyping by using a reverse-sequence-specific oligonucleotide (SSO) probes method. The carrier rates of HLA alleles were compared between 47 cases (27 SCARs and 20 MPs) and 54 controls. The carrier rates of HLA-A*01:01 and HLA-B*13:01 were significantly higher in the phenobarbital-induced SCARs than in the tolerant controls (18.5% vs. 1.85%, p = 0.01, odds ratio [OR] 11.66, 95% confidence interval [CI] 1.21-578.19; 37.04% vs. 11.11%, p = 0.009, OR 4.60, 95%CI 1.29-17.98). There was a trend of a higher carrier rate of HLA-C*06:02 in the phenobarbital-induced SCARs when compared with those in the tolerant controls (29.63% vs. 11.11%, p = 0.059, OR 3.31, 95% CI 0.88-13.31). In contrast to the phenobarbital-induced SCARs, only the HLA-A*01:01 carrier rate in the phenobarbital-induced MPs was significantly higher than those in the tolerant controls (20% vs. 1.85%, p = 0.017, OR 12.69, 95% CI 1.15-661.62). An association between phenobarbital hypersensitivity and HLA-A*01:01 and HLA-B*13:01 has been demonstrated in Thai children

  15. Carboplatin hypersensitivity: evaluation and successful desensitization protocol.

    Science.gov (United States)

    Bruchim, Ilan; Goldberg, Arnon; Fishman, Ami; Confino-Cohen, Ronit

    2014-01-01

    Carboplatin-induced immediate hypersensitivity reactions are relatively common among patients with gynecological malignancies. Once this occurs, the patient might be at risk for future carboplatin-induced reactions. This study evaluated the efficacy of allergic consultation, carboplatin skin testing and desensitization as a single intervention strategy in this population. Patients with a well-documented immediate reaction to carboplatin were offered allergy consultation, carboplatin skin testing and a desensitization plan in a single visit between scheduled chemotherapy sessions. Fifty-five patients with an immediate reaction were evaluated. After allergist assessment, 44 (89%) of 49 patients skin tested had a positive result. A total of 207 carboplatin desensitization cycles were administered to 49 women. Among them, 10 patients had a mild immediate hypersensitivity reaction during desensitization. Five patients subsequently tolerated carboplatin administered in the prolonged desensitization protocol. In the data presented, we propose a strategy that is both cost effective and very convenient for the patient. The diagnostic procedure, including allergist consultation and skin test, can be completed in less than 2 h. In most cases where carboplatin is indispensable, desensitization can be administered without overnight hospitalization.

  16. AcrA suppressor alterations reverse the drug hypersensitivity phenotype of a TolC mutant by inducing TolC aperture opening

    Science.gov (United States)

    Weeks, Jon W.; Celaya-Kolb, Teresa; Pecora, Sara; Misra, Rajeev

    2010-01-01

    Summary In Escherichia coli, the TolC–AcrAB complex forms a major antibiotic efflux system with broad substrate specificity. During the complex assembly, the periplasmic helices and bottom turns of TolC are thought to interact with a hairpin helix of AcrA and hairpin loops of AcrB respectively. In the present study we show that a four-residue substitution in TolC’s turn 1, which connects outer helices 3 and 4 proximal to TolC’s periplasmic aperture, confers antibiotic hypersensitivity without affecting TolC-mediated phage or colicin infection. However, despite the null-like drug sensitivity phenotype, chemical cross-linking analysis revealed no apparent defects in the ability of the mutant TolC protein to physically interact with AcrA and AcrB. A role for TolC turn 1 residues in the functional assembly of the tripartite efflux pump complex was uncovered through isolating suppressor mutations of the mutant TolC protein that mapped within acrA and by utilizing a labile AcrA protein. The data showed that AcrA-mediated suppression of antibiotic sensitivity was achieved by dilating the TolC aperture/channel in an AcrB-dependent manner. The results underscore the importance of the periplasmic turn 1 of TolC in the functional assembly of the tripartite efflux complex and AcrA in transitioning TolC from its closed to open state. PMID:20132445

  17. 355-nm hypersensitization of optical fibers

    NARCIS (Netherlands)

    Canagasabey, A.; Canning, J.; Groothoff, N.

    2003-01-01

    A study is presented on 355-nm hypersensitization of optical fibers. It is found that the intrinsic 244-nm photosensitivity of boron-codoped germanosilicate optical fibers is enhanced by 355-nm hypersensitization. Hypersensitization through standard polymer coating is also demonstrated.

  18. Tunnel Oxides Formed by Field-Induced Anodisation for Passivated Contacts of Silicon Solar Cells

    Directory of Open Access Journals (Sweden)

    Jingnan Tong

    2018-02-01

    Full Text Available Tunnel silicon oxides form a critical component for passivated contacts for silicon solar cells. They need to be sufficiently thin to allow carriers to tunnel through and to be uniform both in thickness and stoichiometry across the silicon wafer surface, to ensure uniform and low recombination velocities if high conversion efficiencies are to be achieved. This paper reports on the formation of ultra-thin silicon oxide layers by field-induced anodisation (FIA, a process that ensures uniform oxide thickness by passing the anodisation current perpendicularly through the wafer to the silicon surface that is anodised. Spectroscopical analyses show that the FIA oxides contain a lower fraction of Si-rich sub-oxides compared to wet-chemical oxides, resulting in lower recombination velocities at the silicon and oxide interface. This property along with its low temperature formation highlights the potential for FIA to be used to form low-cost tunnel oxide layers for passivated contacts of silicon solar cells.

  19. Extract of Rhus verniciflua Bark Suppresses 2,4-Dinitrofluorobenzene-Induced Allergic Contact Dermatitis

    Directory of Open Access Journals (Sweden)

    Dong Ki Park

    2013-01-01

    Full Text Available Rhus verniciflua Stokes (RV has traditionally been used as a food supplement and a traditional herbal medicine for centuries in Korea. Recent studies suggest that RV has potent antioxidative, antitumor, and anti-inflammatory properties. In this study, the anti-inflammatory effects of RV from mice sensitized with 2,4-dinitrofluorobenzene (DNFB and activated macrophages were investigated. The results showed that RV reduced ear swelling and hyperplasia of ear tissue as well as an increase in vascular permeability, which are characteristics of allergic contact dermatitis (ACD with evident histomorphological changes in epidermis and dermis. Decreased numbers of infiltrated mast cells were seen in RV extract treated group, using toluidine blue staining. RV extract significantly regulates the expression of inducible nitric oxide synthase (iNOS at the translational level in activated macrophages. Furthermore, RV extract and its active compound, fisetin, attenuated the level of tumor necrosis factor-α (TNF-α and interleukin 6 (IL-6 mRNA in LPS-stimulated macrophages. Anti-ACD effect of RV extract may be due to the suppression of iNOS and proinflammatory cytokines which might be mediated via the NFκB signaling pathways. Collectively, RV extract has potential for alleviating ACD-like symptoms induced by DNFB in the mouse.

  20. Effect of Lithospermi Radix on Contact Dermatitis Induced by Dinitrofluorobenzene in Mice

    Directory of Open Access Journals (Sweden)

    Kim Han-Na

    2012-06-01

    Full Text Available Objectives: The root of Lithospermum erythrorhizon Sieb. et Zucc. (Lithospermi Radix, LR is a kind of heat clearing and blood cooling medicinal herbs. It can clear away heat and cool the blood, reduce toxins and disperse maculae. LR has long been used as efficacious therapy for inflammation, burns, frostbite and skin diseases such as eczema and psoriasis. Methods: In the present study, we investigate anti-allergic and anti-inflammatory effects of LR by using the 1-fluoro-2, 4- dinitrofluorobenzene (DNFB-induced contact dermatitis mouse model. Results: Topical application of 10 mg/mL of LR effectively inhibited skin lesions induced by repeated paintings with DNFB. Topical application of LR also inhibited hyperplasia, edema, spongiosis and infiltrations of mononuclear cells. In addition, production levels of total immunoglobulin and IgG1 in serum were decreased by using LR in vivo. Conclusions: These data suggest that LR acts as an antiinflammatory agent, improving skin lesions in CD mice.

  1. [Anticonvulsant hypersensitivity syndrome and lamotrigine-associated anticonvulsant hypersensitivity syndrome].

    Science.gov (United States)

    Taillia, H; Alla, P; Fournier, B; Bounolleau, P; Ouologem, M; Ricard, D; Sallansonnet-Froment, M; de Greslan, T; Renard, J-L

    2009-10-01

    Anticonvulsant hypersensitivity syndrome (AHS) is defined by the association of high fever, cutaneous rash and multiorgan-system abnormalities (incidence, one in 1000 to one in 10,000 exposures). Fatal complications are described in 10%. This reaction usually develops 1 to 12 weeks after initiation of an aromatic anticonvulsant. Drug rash with eosinophilia and systemic symptoms (DRESS) can be discussed as differential diagnosis. Several hypotheses have been put forward to explain the pathogenesis of AHS. These include accumulation of toxic metabolites, antibody production and viral infection. The one based on toxic metabolites has found the greatest acceptance due to the fact that it can be proven by an in vitro test, the lymphocyte toxicity assay. In vivo, skin biopsies show characteristic findings of erythema multiform or typical leucocytoclastic angitis. The patch-test is positive in 80% of the cases. Lamotrigine-associated anticonvulsant hypersensitivity syndrome (LASH) is rare and was described in 1998. We report two new cases demonstrating the two particular configurations of apparition of LASH found in the 14 cases from the review of literature (Pubmed: anticonvulsant hypersensitivity syndrome - lamotrigine): high doses of lamotrigine (or lamotrigine in very young or old patients), and lamotrigine associated with another anti-epileptic (phenobarbital or sodium valproate). We discuss the links between DRESS after lamotrigine and LASH as illustrated in a new case.

  2. Intestinal Fungal Dysbiosis Is Associated With Visceral Hypersensitivity in Patients With Irritable Bowel Syndrome and Rats.

    Science.gov (United States)

    Botschuijver, Sara; Roeselers, Guus; Levin, Evgeni; Jonkers, Daisy M; Welting, Olaf; Heinsbroek, Sigrid E M; de Weerd, Heleen H; Boekhout, Teun; Fornai, Matteo; Masclee, Ad A; Schuren, Frank H J; de Jonge, Wouter J; Seppen, Jurgen; van den Wijngaard, René M

    2017-10-01

    Visceral hypersensitivity is one feature of irritable bowel syndrome (IBS). Bacterial dysbiosis might be involved in the activation of nociceptive sensory pathways, but there have been few studies of the role of the mycobiome (the fungal microbiome) in the development of IBS. We analyzed intestinal mycobiomes of patients with IBS and a rat model of visceral hypersensitivity. We used internal transcribed spacer 1-based metabarcoding to compare fecal mycobiomes of 18 healthy volunteers with those of 39 patients with IBS (with visceral hypersensitivity or normal levels of sensitivity). We also compared the mycobiomes of Long-Evans rats separated from their mothers (hypersensitive) with non-handled (normally sensitive) rats. We investigated whether fungi can cause visceral hypersensitivity using rats exposed to fungicide (fluconazole and nystatin). The functional relevance of the gut mycobiome was confirmed in fecal transplantation experiments: adult maternally separated rats were subjected to water avoidance stress (to induce visceral hypersensitivity), then given fungicide and donor cecum content via oral gavage. Other rats subjected to water avoidance stress were given soluble β-glucans, which antagonize C-type lectin domain family 7 member A (CLEC7A or DECTIN1) signaling via spleen-associated tyrosine kinase (SYK), a SYK inhibitor to reduce visceral hypersensitivity, or vehicle (control). The sensitivity of mast cells to fungi was tested with mesenteric windows (ex vivo) and the human mast cell line HMC-1. α diversity (Shannon index) and mycobiome signature (stability selection) of both groups of IBS patients differed from healthy volunteers, and the mycobiome signature of hypersensitive patients differed from that of normally sensitive patients. We observed mycobiome dysbiosis in rats that had been separated from their mothers compared with non-handled rats. Administration of fungicide to hypersensitive rats reduced their visceral hypersensitivity to normal

  3. Titanium contacts to graphene: process-induced variability in electronic and thermal transport

    Science.gov (United States)

    Freedy, Keren M.; Giri, Ashutosh; Foley, Brian M.; Barone, Matthew R.; Hopkins, Patrick E.; McDonnell, Stephen

    2018-04-01

    Contact resistance (R C) is a major limiting factor in the performance of graphene devices. R C is sensitive to the quality of the interface and the composition of the contact, which are affected by the graphene transfer process and contact deposition conditions. In this work, a linear correlation is observed between the composition of Ti contacts, characterized by x-ray photoelectron spectroscopy, and the Ti/graphene contact resistance measured by the transfer length method. We find that contact composition is tunable via deposition rate and base pressure. Reactor base pressure is found to effect the resultant contact resistance. The effect of contact deposition conditions on thermal transport measured by time-domain thermoreflectance is also reported. Interfaces with higher oxide composition appear to result in a lower thermal boundary conductance. Possible origins of this thermal boundary conductance change with oxide composition are discussed.

  4. Electromagnetic hypersensitivity: Fact or fiction?

    International Nuclear Information System (INIS)

    Genuis, Stephen J.; Lipp, Christopher T.

    2012-01-01

    As the prevalence of wireless telecommunication escalates throughout the world, health professionals are faced with the challenge of patients who report symptoms they claim are connected with exposure to some frequencies of electromagnetic radiation (EMR). Some scientists and clinicians acknowledge the phenomenon of hypersensitivity to EMR resulting from common exposures such as wireless systems and electrical devices in the home or workplace; others suggest that electromagnetic hypersensitivity (EHS) is psychosomatic or fictitious. Various organizations including the World Health Organization as well as some nation states are carefully exploring this clinical phenomenon in order to better explain the rising prevalence of non-specific, multi-system, often debilitating symptoms associated with non-ionizing EMR exposure. As well as an assortment of physiological complaints, patients diagnosed with EHS also report profound social and personal challenges, impairing their ability to function normally in society. This paper offers a review of the sparse literature on this perplexing condition and a discussion of the controversy surrounding the legitimacy of the EHS diagnosis. Recommendations are provided to assist health professionals in caring for individuals complaining of EHS. - Highlights: ► Many people report symptoms when near devices emanating electromagnetic fields(EMF). ► Electromagnetic hypersensitivity (EHS) research has generated conflicting outcomes. ► Recent evidence suggests pathophysiological change in some individuals with EHS. ► EHS patients consistently report profound social and personal challenges. ► Clinicians need to be apprised of the EHS condition and potential interventions.

  5. Climate hypersensitivity to solar forcing?

    Directory of Open Access Journals (Sweden)

    W. Soon

    2000-05-01

    Full Text Available We compare the equilibrium climate responses of a quasi-dynamical energy balance model to radiative forcing by equivalent changes in CO2, solar total irradiance (Stot and solar UV (SUV. The response is largest in the SUV case, in which the imposed UV radiative forcing is preferentially absorbed in the layer above 250 mb, in contrast to the weak response from global-columnar radiative loading by increases in CO2 or Stot. The hypersensitive response of the climate system to solar UV forcing is caused by strongly coupled feedback involving vertical static stability, tropical thick cirrus ice clouds and stratospheric ozone. This mechanism offers a plausible explanation of the apparent hypersensitivity of climate to solar forcing, as suggested by analyses of recent climatic records. The model hypersensitivity strongly depends on climate parameters, especially cloud radiative properties, but is effective for arguably realistic values of these parameters. The proposed solar forcing mechanism should be further confirmed using other models (e.g., general circulation models that may better capture radiative and dynamical couplings of the troposphere and stratosphere.Key words: Meteorology and atmospheric dynamics (climatology · general or miscellaneous · Solar physics · astrophysics · and astronomy (ultraviolet emissions

  6. The Role of III-V Substrate Roughness and Deoxidation Induced by Digital Etch in Achieving Low Resistance Metal Contacts

    Directory of Open Access Journals (Sweden)

    Florent Ravaux

    2017-06-01

    Full Text Available To achieve low contact resistance between metal and III-V material, transmission-line-model (TLM structures of molybdenum (Mo were fabricated on indium phosphide (InP substrate on the top of an indium gallium arsenide (InGaAs layer grown by molecular beam epitaxy. The contact layer was prepared using a digital etch procedure before metal deposition. The contact resistivity was found to decrease significantly with the cleaning process. High Resolution Transmission & Scanning Electron Microscopy (HRTEM & HRSTEM investigations revealed that the surface roughness of treated samples was increased. Further analysis of the metal-semiconductor interface using Energy Electron Loss Spectroscopy (EELS showed that the amount of oxides (InxOy, GaxOy or AsxOy was significantly decreased for the etched samples. These results suggest that the low contact resistance obtained after digital etching is attributed to the combined effects of the induced surface roughness and oxides removal during the digital etch process.

  7. Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS: 11 years retrospective study in Thailand

    Directory of Open Access Journals (Sweden)

    Akarin Hiransuthikul

    2016-10-01

    Conclusions: DRESS is associated with severe morbidity and mortality. Phenytoin, nevirapine, allopurinol, and cotrimoxazole were the major causes. Allopurinol-induced DRESS had the longest onset time, and was associated with higher eosinophilia and incidence of renal involvement. Raising awareness among both health care providers and public for early detection and withdrawal of the causative agent is critical to save life and reduce morbidity.

  8. Mechanism of action and efficacy of RX-111, a thieno[2,3-c]pyridine derivative and small molecule inhibitor of protein interaction with glycosaminoglycans (SMIGs), in delayed-type hypersensitivity, TNBS-induced colitis and experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Harris, Nicholas; Koppel, Juraj; Zsila, Ferenc; Juhas, Stefan; Il'kova, Gabriela; Kogan, Faina Yurgenzon; Lahmy, Orly; Wildbaum, Gizi; Karin, Nathan; Zhuk, Regina; Gregor, Paul

    2016-04-01

    Elucidate the mechanism of action of the small molecule inhibitor of protein binding to glycosaminoglycans, RX-111 and assay its anti-inflammatory activity in animal models of inflammatory disease. The glycosaminoglycan, heparin, was used in the mechanism of action study of RX-111. Human T lymphocytes and umbilical vein endothelial cells were used to assay the in vitro activity of RX-111. Mouse and rat models of disease were used to assay the anti-inflammatory activity of RX-111 in vivo. Circular dichroism and UV/Vis absorption spectroscopy were used to study the binding of RX-111 to the glycosaminoglycan, heparin. T lymphocyte rolling on endothelial cells under shear flow was used to assay RX-111 activity in vitro. Delayed-type hypersensitivity (DTH) and tri-nitrobenzene sulfonic acid (TNBS)-induced colitis in mice and experimental autoimmune encephalomyelitis (EAE) in rats were used to assay anti-inflammatory activity of RX-111 in vivo. RX-111 was shown to bind directly to heparin. It inhibited leukocyte rolling on endothelial cells under shear flow and reduced inflammation in the mouse model of DTH. RX-111 was efficacious in the mouse model of inflammatory bowel disease, TNBS-induced colitis and the rat model of multiple sclerosis, EAE. RX-111 exercises its broad spectrum anti-inflammatory activity by a singular mechanism of action, inhibition of protein binding to the cell surface GAG, heparan sulfate. RX-111 and related thieno[2,3-c]pyridine derivatives are potential therapeutics for the treatment of inflammatory and autoimmune diseases.

  9. Upregulation of the sodium channel NaVβ4 subunit and its contributions to mechanical hypersensitivity and neuronal hyperexcitability in a rat model of radicular pain induced by local DRG inflammation

    Science.gov (United States)

    Xie, Wenrui; Tan, Zhi-Yong; Barbosa, Cindy; Strong, Judith A.; Cummins, Theodore R.; Zhang, Jun-Ming

    2016-01-01

    High frequency spontaneous firing in myelinated sensory neurons plays a key role in initiating pain behaviors in several different models, including the radicular pain model in which the rat lumbar dorsal root ganglia (DRG) are locally inflamed. The sodium channel isoform NaV1.6 contributes to pain behaviors and spontaneous activity in this model. Among all the isoforms in adult DRG, NaV1.6 is the main carrier of TTX-sensitive resurgent Na currents that allow high-frequency firing. Resurgent currents flow after a depolarization or action potential, as a blocking particle exits the pore. In most neurons the regulatory β4 subunit is potentially the endogenous blocker. We used in vivo siRNA mediated knockdown of NaVβ4 to examine its role in the DRG inflammation model. NaVβ4 but not control siRNA almost completely blocked mechanical hypersensitivity induced by DRG inflammation. Microelectrode recordings in isolated whole DRGs showed that NaVβ4 siRNA blocked the inflammation-induced increase in spontaneous activity of Aβ neurons, and reduced repetitive firing and other measures of excitability. NaVβ4 was preferentially expressed in larger diameter cells; DRG inflammation increased its expression and this was reversed by NaVβ4 siRNA, based on immunohistochemistry and Western blotting. NaVβ4 siRNA also reduced immunohistochemical NaV1.6 expression. Patch clamp recordings of TTX-sensitive Na currents in acutely cultured medium diameter DRG neurons showed that DRG inflammation increased transient and especially resurgent current; effects blocked by NaVβ4 siRNA. NaVβ4 may represent a more specific target for pain conditions that depend on myelinated neurons expressing NaV1.6. PMID:26785322

  10. Hypersensitivity to pain in congenital blindness

    DEFF Research Database (Denmark)

    Slimani, Hocine; Danti, Sabrina; Ricciardi, Emiliano

    2013-01-01

    Vision is important for avoiding encounters with objects in the environment that may imperil physical integrity. We tested whether, in the absence of vision, a lower pain threshold would arise from an adaptive shift to other sensory channels. We therefore measured heat and cold pain thresholds an...... that blind subjects are more attentive to signals of external threats. These findings indicate that the absence of vision from birth induces a hypersensitivity to painful stimuli, lending new support to a model of sensory integration of vision and pain processing......., congenitally blind subjects have lower heat pain thresholds, rate suprathreshold heat pain stimuli as more painful, and have increased sensitivity for cold pain stimuli. Thresholds for nonpainful thermal stimulation did not differ between groups. The results of the pain questionnaires further indicated...

  11. Cloning and expression of candidate allergens from Culicoides obsoletus for diagnosis of insect bite hypersensitivity in horses

    NARCIS (Netherlands)

    Meide, van der N.M.A.; Roders, N.; Sloet van Oldruitenborgh-Oosterbaan, M.M.; Schaap, P.J.; Oers, van M.M.; Leibold, W.; Savelkoul, H.F.J.; Tijhaar, E.

    2013-01-01

    Insect bite hypersensitivity (IBH) is an IgE-mediated (Type I) hypersensitivity reaction induced by allergens from biting midges of the Culicoides spp. The aim of the present study was to identify, clone and express recombinant allergens from C. obsoletus, the main species found feeding on horses in

  12. Realistic-contact-induced enhancement of rectifying in carbon-nanotube/graphene-nanoribbon junctions

    International Nuclear Information System (INIS)

    Zhang, Xiang-Hua; Li, Xiao-Fei; Wang, Ling-Ling; Xu, Liang; Luo, Kai-Wu

    2014-01-01

    Carbon-nanotube/graphene-nanoribbon junctions were recently fabricated by the controllable etching of single-walled carbon-nanotubes [Wei et al., Nat. Commun. 4, 1374 (2013)] and their electronic transport properties were studied here. First principles results reveal that the transmission function of the junctions show a heavy dependence on the shape of contacts, but rectifying is an inherent property which is insensitive to the details of contacts. Interestingly, the rectifying ratio is largely enhanced in the junction with a realistic contact and the enhancement is insensitive to the details of contact structures. The stability of rectifying suggests a significant feasibility to manufacture realistic all-carbon rectifiers in nanoelectronics

  13. Women with dysmenorrhoea are hypersensitive to experimentally induced forearm ischaemia during painful menstruation and during the pain-free follicular phase.

    Science.gov (United States)

    Iacovides, S; Avidon, I; Baker, F C

    2015-07-01

    Monthly primary dysmenorrhoeic pain is associated with increased sensitivity to painful stimuli, particularly in deep tissue. We investigated whether women with dysmenorrhoea, compared with controls, have increased sensitivity to experimentally induced deep-tissue muscle ischaemia in a body area distant from that of referred menstrual pain. The sub-maximal effort tourniquet test was used to induce forearm ischaemia in 11 women with severe dysmenorrhoea and in nine control women both during menstruation and in the follicular phase of the menstrual cycle. Von Frey hair assessments confirmed the presence of experimental ischaemia. Women rated the intensity of menstrual and ischaemic pain on a 100-mm visual analogue scale. Women with dysmenorrhoea [mean (SD): 68 (20) mm] reported significantly greater menstrual pain compared with controls [mean (SD): 2 (6) mm; p = 0.0001] during the menstruation phase. They also rated their forearm ischaemic pain as significantly greater than the controls during the menstruation [dysmenorrhoeics vs. controls mean (SD): 58 (19) mm vs. 31 (21) mm, p menstruation phase and pain-free follicular phase. These findings suggest the presence of long-lasting changes in muscle pain sensitivity in women with dysmenorrhoea. Our findings that dysmenorrhoeic women are hyperalgesic to a clinically relevant, deep-muscle ischaemic pain in areas outside of referred menstrual pain confirm other studies showing long-lasting changes in pain sensitivity outside of the painful period during menstruation. © 2014 European Pain Federation - EFIC®

  14. Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions.

    Science.gov (United States)

    Böhm, Ruwen; Cascorbi, Ingolf

    2016-01-01

    Adverse drug reactions adverse drug reaction (ADR) occur in approximately 17% of patients. Avoiding ADR is thus mandatory from both an ethical and an economic point of view. Whereas, pharmacogenetics changes of the pharmacokinetics may contribute to the explanation of some type A reactions, strong relationships of genetic markers has also been shown for drug hypersensitivity belonging to type B reactions. We present the classifications of ADR, discuss genetic influences and focus on delayed-onset hypersensitivity reactions, i.e., drug-induced liver injury, drug-induced agranulocytosis, and severe cutaneous ADR. A guidance how to read and interpret the contingency table is provided as well as an algorithm whether and how a test for a pharmacogenetic biomarker should be conducted.

  15. Improved reactive nanoparticles to treat dentin hypersensitivity.

    Science.gov (United States)

    Toledano-Osorio, Manuel; Osorio, Estrella; Aguilera, Fátima S; Luis Medina-Castillo, Antonio; Toledano, Manuel; Osorio, Raquel

    2018-05-01

    The aim of this study was to evaluate the effectiveness of different nanoparticles-based solutions for dentin permeability reduction and to determine the viscoelastic performance of cervical dentin after their application. Four experimental nanoparticle solutions based on zinc, calcium or doxycycline-loaded polymeric nanoparticles (NPs) were applied on citric acid etched dentin, to facilitate the occlusion and the reduction of the fluid flow at the dentinal tubules. After 24 h and 7 d of storage, cervical dentin was evaluated for fluid filtration. Field emission scanning electron microscopy, energy dispersive analysis, AFM and Nano-DMA analysis were also performed. Complex, storage, loss modulus and tan delta (δ) were assessed. Doxycycline-loaded NPs impaired tubule occlusion and fluid flow reduction trough dentin. Tubules were 100% occluded in dentin treated with calcium-loaded NPs or zinc-loaded NPs, analyzed at 7 d. Dentin treated with both zinc-NPs and calcium-NPs attained the highest reduction of dentinal fluid flow. Moreover, when treating dentin with zinc-NPs, complex modulus values attained at intertubular and peritubular dentin were higher than those obtained after applying calcium-NPs. Zinc-NPs are then supposed to fasten active dentin remodeling, with increased maturity and high mechanical properties. Zinc-based nanoparticles are then proposed for effective dentin remineralization and tubular occlusion. Further research to finally prove for clinical benefits in patients with dentin hypersensitivity using Zn-doped nanoparticles is encouraged. Erosion from acids provokes dentin hypersensitivity (DH) which presents with intense pain of short duration. Open dentinal tubules and demineralization favor DH. Nanogels based on Ca-nanoparticles and Zn-nanoparticles produced an efficient reduction of fluid flow. Dentinal tubules were filled by precipitation of induced calcium-phosphate deposits. When treating dentin with Zn-nanoparticles, complex modulus

  16. Electromagnetic hypersensitivity: Fact or fiction?

    Energy Technology Data Exchange (ETDEWEB)

    Genuis, Stephen J., E-mail: sgenuis@ualberta.ca [University of Alberta (Canada); Lipp, Christopher T. [Faculty of Medicine at the University of Calgary (Canada)

    2012-01-01

    As the prevalence of wireless telecommunication escalates throughout the world, health professionals are faced with the challenge of patients who report symptoms they claim are connected with exposure to some frequencies of electromagnetic radiation (EMR). Some scientists and clinicians acknowledge the phenomenon of hypersensitivity to EMR resulting from common exposures such as wireless systems and electrical devices in the home or workplace; others suggest that electromagnetic hypersensitivity (EHS) is psychosomatic or fictitious. Various organizations including the World Health Organization as well as some nation states are carefully exploring this clinical phenomenon in order to better explain the rising prevalence of non-specific, multi-system, often debilitating symptoms associated with non-ionizing EMR exposure. As well as an assortment of physiological complaints, patients diagnosed with EHS also report profound social and personal challenges, impairing their ability to function normally in society. This paper offers a review of the sparse literature on this perplexing condition and a discussion of the controversy surrounding the legitimacy of the EHS diagnosis. Recommendations are provided to assist health professionals in caring for individuals complaining of EHS. - Highlights: Black-Right-Pointing-Pointer Many people report symptoms when near devices emanating electromagnetic fields(EMF). Black-Right-Pointing-Pointer Electromagnetic hypersensitivity (EHS) research has generated conflicting outcomes. Black-Right-Pointing-Pointer Recent evidence suggests pathophysiological change in some individuals with EHS. Black-Right-Pointing-Pointer EHS patients consistently report profound social and personal challenges. Black-Right-Pointing-Pointer Clinicians need to be apprised of the EHS condition and potential interventions.

  17. The effect of radiosensitizers on the survival response of hypoxic mammalian cells: The low X-ray dose region, hypersensitivity and induced radioresistance

    International Nuclear Information System (INIS)

    Skov, K.A.; MacPhail, H.S.; Marples, B.

    1994-01-01

    It has been shown previously that the extent of chemical modification of the hypoxic radiation response is dependent on dose. Some types of sensitizer are more effective at low doses (to 4 Gy) than at higher doses. Since such drugs are possible adjuvants to radiotherapy, the mechanisms responsible for the variable response at clinical doses are summarized, and the effects of cisplatin and buthionine sulfoximine on the purported induced response to radiation in hypoxic cells are presented. Cisplatin at a low, nontoxic concentration (1 μM) appears to abolish the increased radioresistant portion of the survival response. A role for high-mobility-group protein binding by platinum drugs is hypothesized to explain their interaction with radiation, and conversely, it is suggested that the heretofore unexplained different behavior of certain hypoxic sensitizers at low doses could be, at least in part, an effect on the induction of resistance. 36 refs., 2 figs

  18. Spermatozoa from the maned wolf (Chrysocyon brachyurus) display typical canid hyper-sensitivity to osmotic and freezing-induced injury, but respond favorably to dimethyl sulfoxide.

    Science.gov (United States)

    Johnson, Amy E M; Freeman, Elizabeth W; Wildt, David E; Songsasen, Nucharin

    2014-06-01

    We assessed the influences of medium osmolality, cryoprotectant and cooling and warming rate on maned wolf (Chrysocyon brachyurus) spermatozoa. Ejaculates were exposed to Ham's F10 medium (isotonic control) or to this medium plus NaCl (350-1000mOsm), sucrose (369 and 479mOsm), 1M glycerol (1086mOsm) or dimethyl sulfoxide (Me2SO, 1151mOsm) for 10 min. Each sample then was diluted back into Ham's medium and assessed for sperm motility and plasma membrane integrity. Although glycerol and Me2SO had no influence (P>0.05), NaCl and sucrose solutions affected sperm motility (P0.05) to the control. As osmolality of the NaCl solution increased, motility decreased to maned wolf spermatozoa are similar to domestic dog sperm in their sensitivity to osmotic-induced motility damage, the plasma membranes tolerate dehydration, and the cells respond favorably to Me2SO as a cryoprotectant. Published by Elsevier Inc.

  19. Air pressure-induced iridocornea contact in a patient with primary angle closure observed with a dynamic Scheimpflug analyzer.

    Science.gov (United States)

    Kawashima, Rumi; Matsushita, Kenji; Fujimoto, Hisataka; Maeda, Naoyuki; Nishida, Kohji

    2015-01-01

    To report air pressure-induced corneal deformation and iridocornea contact in eyes with primary angle closure (PAC) during intraocular pressure (IOP) measurement performed using a novel noncontact tonometer. A single case report. We report a patient with bilateral angle closure. One eye had acute PAC and the other had PAC. The latter was evaluated by the movements of the cornea and iris during IOP measurement using a noncontact tonometer. During the examination, the corneal endothelium and the iris came into contact at the mid-peripheral pupillary area in the left eye with PAC during the corneal reaction to an air puff. In contrast, the corneal endothelium in the pupillary area did not come into contact with the iris. Although we observed only 1 case and there could be limitations in its interpretation, IOP measurements using a noncontact tonometer may create mechanical stress on the corneal endothelium in eyes with PAC with a very shallow anterior chamber.

  20. Detection of local inflammation induced by repeated exposure to contact allergens by use of IVIS SpectrumCT analyses

    DEFF Research Database (Denmark)

    Nielsen, Morten M.; Schmidt, Jonas D.; Christensen, Jan P.

    2017-01-01

    Background: Contact allergy is characterized by local skin inflammation that, in some cases, can result in systemic immune activation. Objectives: To investigate whether IVIS SpectrumCT analyses can be used to detect the immune response induced by contact allergens. Methods: Mice were repeatedly...... exposed to vehicle or allergens on the ears. The local and systemic responses were analysed at different times with the ProSense 750 FAST probe in IVIS SpectrumCT measurements. In addition, changes in ear thickness, cytokine profile in the skin and immunological phenotype in the draining lymph nodes...... and spleen were determined. Results: Local inflammation was detected by ProSense 750 FAST and correlated with changes in ear thickness, cytokine profile and immunological phenotype following exposure to the strong contact allergen 2,4-dinitrofluorobenzene. Analysis of the systemic response with ProSense 750...

  1. Dendritic cells' death induced by contact sensitizers is controlled by Nrf2 and depends on glutathione levels

    Energy Technology Data Exchange (ETDEWEB)

    El Ali, Zeina [UMR996 - Inflammation, Chemokines and Immunopathology-, INSERM, Univ Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry (France); Deloménie, Claudine [IFR141 IPSIT, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry (France); Botton, Jérémie [INSERM, UMR1153 Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Team (France); Pallardy, Marc [UMR996 - Inflammation, Chemokines and Immunopathology-, INSERM, Univ Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry (France); Kerdine-Römer, Saadia, E-mail: saadia.kerdine-romer@u-psud.fr [UMR996 - Inflammation, Chemokines and Immunopathology-, INSERM, Univ Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry (France)

    2017-05-01

    Dendritic cells (DC) are known to play a major role during contact allergy induced by contact sensitizers (CS). Our previous studies showed that Nrf2 was induced in DC and controlled allergic skin inflammation in mice in response to chemicals. In this work, we raised the question of the role of Nrf2 in response to a stress provoked by chemical sensitizers in DC. We used two well-described chemical sensitizers, dinitrochlorobenzene (DNCB) and cinnamaldehyde (CinA), known to have different chemical reactivity and mechanism of action. First, we performed a RT-qPCR array showing that CinA was a higher inducer of immune and detoxification genes compared to DNCB. Interestingly, in the absence of Nrf2, gene expression was dramatically affected in response to DNCB but was slightly affected in response to CinA. These observations prompted us to study DC's cell death in response to both chemicals. DNCB and CinA increased apoptotic cells and decreased living cells in the absence of Nrf2. The characterization of DC apoptosis induced by both CS involved the mitochondrial-dependent caspase pathway and was regulated via Nrf2 in response to both chemicals. Oxidative stress induced by DNCB, and leading to cell death, was regulated by Nrf2. Unlike CinA, DNCB treatment provoked a significant reduction of intracellular GSH levels and up-regulated bcl-2 gene expression, under the control of Nrf2. This work underlies that chemical reactivity may control Nrf2-dependent gene expression leading to different cytoprotective mechanisms in DC. - Highlights: • Nrf2 controls cell death induced by contact sensitizers in dendritic cells. • DNCB reduced GSH levels and up-regulated bcl-2 gene expression unlike CinA. • Chemical reactivity controls Nrf2-dependent genes having protective effect in DC.

  2. Direct contact with endoderm-like cells efficiently induces cardiac progenitors from mouse and human pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Hideki Uosaki

    Full Text Available RATIONALE: Pluripotent stem cell-derived cardiac progenitor cells (CPCs have emerged as a powerful tool to study cardiogenesis in vitro and a potential cell source for cardiac regenerative medicine. However, available methods to induce CPCs are not efficient or require high-cost cytokines with extensive optimization due to cell line variations. OBJECTIVE: Based on our in-vivo observation that early endodermal cells maintain contact with nascent pre-cardiac mesoderm, we hypothesized that direct physical contact with endoderm promotes induction of CPCs from pluripotent cells. METHOD AND RESULT: To test the hypothesis, we cocultured mouse embryonic stem (ES cells with the endodermal cell line End2 by co-aggregation or End2-conditioned medium. Co-aggregation resulted in strong induction of Flk1(+ PDGFRa(+ CPCs in a dose-dependent manner, but the conditioned medium did not, indicating that direct contact is necessary for this process. To determine if direct contact with End2 cells also promotes the induction of committed cardiac progenitors, we utilized several mouse ES and induced pluripotent (iPS cell lines expressing fluorescent proteins under regulation of the CPC lineage markers Nkx2.5 or Isl1. In agreement with earlier data, co-aggregation with End2 cells potently induces both Nkx2.5(+ and Isl1(+ CPCs, leading to a sheet of beating cardiomyocytes. Furthermore, co-aggregation with End2 cells greatly promotes the induction of KDR(+ PDGFRa(+ CPCs from human ES cells. CONCLUSIONS: Our co-aggregation method provides an efficient, simple and cost-effective way to induce CPCs from mouse and human pluripotent cells.

  3. The radiation hypersensitivity of cells at mitosis.

    Science.gov (United States)

    Stobbe, C C; Park, S J; Chapman, J D

    2002-12-01

    Mitotic cells are hypersensitive to ionizing radiation, exhibiting single-hit inactivation coefficients near to those of repair deficient cell lines and lymphocytes. To elucidate possible mechanisms for this hypersensitivity, the kinetics of oxygen radiosensitization, the proportion of indirect effect by OH radicals and the kinetics of radiation-induced DNA strand breakage in the chromatin of mitotic cells were investigated. Synchronized populations of >90% mitotic HT-29 cells were obtained by the mitotic shake-off method. Cells were irradiated at indirect effect of OH radicals was investigated with the radical scavenger, DMSO. DNA strand breakage was measured by the comet assay. Mitotic HT-29 cell inactivation is well described by a single-hit inactivation coefficient (alpha) of 1.14 +/- 0.06 Gy(-1). The oxygen enhancement ratio of mitotic cells (at 10% survival) was found to be approximately 2.0, significantly lower than the value of 2.8 measured for interphase (asynchronous) cells. More than 60% of mitotic cell killing was eliminated when the media contained 2 M DMSO, indicating that indirect effect is as important in the killing of mitotic cells as it is for interphase cells. The chromatin in mitotic cells was found to be ~2.8 times more sensitive to radiation-induced DNA single-strand breakage than the chromatin of interphase cells. The alpha-inactivation coefficient of mitotic HT-29 cells was ~30 times larger than that of interphase cells. Mitotic cell chromatin appears to contain intrinsic DNA breaks that are not lethal. In addition, chromatin in mitotic cells was found to be more susceptible to radiation-induced DNA strand-breakage than the dispersed chromatin of interphase cells. How the enhanced production of these simple DNA lesions (that are usually reparable) translates into the lethal (non-reparable) events associated with alpha-inactivation is not known. The compaction/dispersion status of DNA throughout the cell cycle appears to be an important

  4. Health-related quality of life in food hypersensitive schoolchildren and their families: parents' perceptions

    Directory of Open Access Journals (Sweden)

    Marklund Birgitta

    2006-08-01

    Full Text Available Abstract Background About 20% of schoolchildren and adolescents in Sweden suffer from perceived food hypersensitivity (e.g. allergy or intolerance. Our knowledge of how child food hypersensitivity affects parents HRQL and what aspects of the hypersensitivity condition relate to HRQL deterioration in the family is limited. Thus the aim of this study was to investigate the parent-reported HRQL in families with a schoolchild considered to be food hypersensitive. The allergy-associated parameters we operated with were number of offending food items, adverse food reactions, additional hypersensitivity, allergic diseases and additional family members with food hypersensitivity. These parameters, along with age and gender were assessed in relation to child, parent and family HRQL. Methods In May 2004, a postal questionnaire was distributed to parents of 220 schoolchildren with parent-reported food hypersensitivity (response rate 74%. Two questionnaires were used: CHQ-PF28 and a study-specific questionnaire including questions on allergy-associated parameters. In order to find factors that predict impact on HRQL, stepwise multiple linear regression analyses were carried out. Results An important predictor of low HRQL was allergic disease (i.e. asthma, eczema, rhino conjunctivitis in addition to food hypersensitivity. The higher the number of allergic diseases, the lower the physical HRQL for the child, the lower the parental HRQL and the more disruption in family activities. Male gender predicted lower physical HRQL than female gender. If the child had sibling(s with food hypersensitivity this predicted lower psychosocial HRQL for the child and lower parental HRQL. Food-induced gastro-intestinal symptoms predicted lower parental HRQL while food-induced breathing difficulties predicted higher psychosocial HRQL for the child and enhanced HRQL with regards to the family's ability to get along. Conclusion The variance in the child's physical HRQL was to a

  5. ATM status of the clinically radio-hypersensitive

    International Nuclear Information System (INIS)

    Clarke, R. A.; Hasnain, H.; Goozee, G.; Alvandi, R.; Miller, A.; Kearsley, J.H.; Farrell, A.; Bittell, G.; Chen, P.; Lavin, M.

    1996-01-01

    The aim of this study was to characterise the response to ionising radiation of normal tissues from patients that display early and acute hypersensitivity to radiotherapy. Methods include cell proliferation assay using MTT, induced chromosomal aberration testing, cell cycle response to radiation via FACs, mutation analysis of Ataxia Telangiectasia (AT) gene, p53 and AT Western analysis. It is now well appreciated that standard clinical doses (1.8-2 Gy per fraction per day) produce predictable acute and late toxicity in most patients. Occasionally, however, the standard clinical dose produces acute and late toxicity which can exceed the norm both in their extent and timing. The study confirmed the innate cellular radiosensitivity of the clinically radio-hypersensitive patients. No indication of AT gene mutations was found

  6. Hypersensitivity to mosquito bite manifested as Skeeter syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Pérez-Vanzzini

    2015-02-01

    Full Text Available The reactions to mosquito bites are immunological reactions with involvement of IgE, IgG and T cells mediated hypersensitivity. These reactions are common and range from small local reactions, large local reactions to systemic allergic reactions. Skeeter syndrome is defined as a large local induced inflammatory reaction to mosquito bite and sometimes accompanied by systemic symptoms such as fever and vomiting. Diagnosis is based on clinical history and physical examination, supported by the identification of specific IgE by skin testing. Treatment includes prevention, antihistamines and steroids in some cases. Specific immunotherapy still requires further study. This paper reports two cases of patients with hypersensitivity reactions to mosquito bites, which were evaluated in our center presenting positive skin tests.

  7. Allergic Contact Dermatitis

    Directory of Open Access Journals (Sweden)

    Meltem Önder

    2009-03-01

    Full Text Available Allergic contact dermatitis is the delayed type hypersensitivity reaction to exogenous agents. Allergic contact dermatitis may clinically present acutely after allergen exposure and initial sensitization in a previously sensitized individual. Acute phase is characterized by erythematous, scaly plaques. In severe cases vesiculation and bullae in exposed areas are very characteristic. Repeated or continuous exposure of sensitized individual with allergen result in chronic dermatitis. Lichenification, erythematous plaques, hyperkeratosis and fissuring may develop in chronic patients. Allergic contact dermatitis is very common dermatologic problem in dermatology daily practice. A diagnosis of contact dermatitis requires the careful consideration of patient history, physical examination and patch testing. The knowledge of the clinical features of the skin reactions to various contactans is important to make a correct diagnosis of contact dermatitis. It can be seen in every age, in children textile product, accessories and touch products are common allergens, while in adults allergic contact dermatitis may be related with topical medicaments. The contact pattern of contact dermatitis depends on fashion and local traditions as well. The localization of allergic reaction should be evaluated and patients’ occupation and hobbies should be asked. The purpose of this review is to introduce to our collaques up dated allergic contact dermatitis literatures both in Turkey and in the World.

  8. Hypersensitivity pneumonitis: an immunopathology review.

    Science.gov (United States)

    Woda, Bruce A

    2008-02-01

    Hypersensitivity pneumonitis (HSP) is an immunologically mediated alveolar and interstitial lung disease caused by repeated inhalation of organic dusts and some occupational agents. The pathogenesis of HSP is uncertain. A number of unexplained features of HSP remain, namely (1) why do so few exposed individuals develop clinical HSP, (2) what triggers an acute episode after prolonged periods of previous sensitization, and (3) what leads to disease progression. This article considers these issues and aims to discuss and clarify current concepts in pathogenesis. Pertinent literature review in conjunction with the author's personal interpretive opinion. Current data suggest that individuals with a T(H)1 dominant response are likely to develop clinical disease. There is also some evidence that genetic factors such as polymorphisms in the major histocompatibility complex, tumor necrosis factor alpha, and tissue inhibitor of metalloproteinase 3 are associated with the development of or resistance to the disease.

  9. Evaporation-induced flow in an inviscid liquid line at any contact angle

    Science.gov (United States)

    Petsi, A. J.; Burganos, V. N.

    2006-04-01

    The problem of potential flow inside an evaporating liquid line, shaped as an infinitely long cylindrical segment lying on a flat surface, is considered and an analytical solution is obtained for any contact angle in (0,π) . In this way, microflow details inside linear liquid bodies evaporating on hydrophilic, hydrophobic, and strongly hydrophobic substrates can now be obtained. The mathematical formulation employs the velocity potential and stream function formulations in bipolar coordinates and the solution is obtained using the technique of Fourier transform. Both pinned and depinned contact lines are considered. The solution is applicable to any evaporation mechanism but for illustration purposes numerical results are presented here for the particular case of kinetically controlled evaporation. For hydrophilic substrates, the flow inside the evaporating liquid line is directed towards the edges for pinned contact lines, thus, promoting a coffee stain effect. The opposite flow direction is observed for depinned contact lines. However, for strongly hydrophobic substrates, flow is directed outwards for both pinned and depinned contact lines, but owing to its low magnitude compared to that on hydrophilic substrates, a craterlike colloidal deposit should be expected rather than a ringlike deposit, in agreement with experimental observations.

  10. Hypersensitivity to contrast media and dyes.

    Science.gov (United States)

    Brockow, Knut; Sánchez-Borges, Mario

    2014-08-01

    This article updates current knowledge on hypersensitivity reactions to diagnostic contrast media and dyes. After application of a single iodinated radiocontrast medium (RCM), gadolinium-based contrast medium, fluorescein, or a blue dye, a hypersensitivity reaction is not a common finding; however, because of the high and still increasing frequency of those procedures, patients who have experienced severe reactions are nevertheless frequently encountered in allergy departments. Evidence on allergologic testing and management is best for iodinated RCM, limited for blue dyes, and insufficient for fluorescein. Skin tests can be helpful in the diagnosis of patients with hypersensitivity reactions to these compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Cutaneous drug hypersensitivity : Immunological and genetic perspective

    Directory of Open Access Journals (Sweden)

    Kisalay Ghosh

    2011-01-01

    Full Text Available Drug hypersensitivity is an unpredictable, immunologically mediated adverse reaction, clustered in a genetically predisposed individual. The role of "hapten concept" in immune sensitization has recently been contested by the "pharmacological interaction" hypothesis. After completion of the "human genome project" and with the availability of high-resolution genotyping, genetic susceptibility to hypersensitivity for certain drugs has been proved beyond doubt though the trend is ethnicity and phenotype dependent. Application of this newly acquired knowledge may reduce or abolish the morbidity and mortality associated with cutaneous drug hypersensitivity.

  12. Reaction induced nucleation and growth v. grain coarsening in contact metamorphic, impure carbonates

    DEFF Research Database (Denmark)

    Berger, Alfons; Brodhag, Sabine; Herwegh, Marco

    2010-01-01

    aureole of the Adamello pluton (N-Italy). As a function of increasing distance from the pluton contact, the investigated samples have peak metamorphic temperatures ranging from the stability field of diopside/tremolite down to diagenetic conditions. All samples consist of calcite as the dominant matrix...

  13. An adhesive contact mechanics formulation based on atomistically induced surface traction

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Houfu [Department of Civil and Environmental Engineering, University of California, Berkeley, CA 94720 (United States); Ren, Bo [Livermore Software Technology Corporation, 7374 Las Positas Road, Livermore, CA 94551 (United States); Li, Shaofan, E-mail: shaofan@berkeley.edu [Department of Civil and Environmental Engineering, University of California, Berkeley, CA 94720 (United States)

    2015-12-01

    In this work, we have developed a novel multiscale computational contact formulation based on the generalized Derjuguin approximation for continua that are characterized by atomistically enriched constitutive relations in order to study macroscopic interaction between arbitrarily shaped deformable continua. The proposed adhesive contact formulation makes use of the microscopic interaction forces between individual particles in the interacting bodies. In particular, the double-layer volume integral describing the contact interaction (energy, force vector, matrix) is converted into a double-layer surface integral through a mathematically consistent approach that employs the divergence theorem and a special partitioning technique. The proposed contact model is formulated in the nonlinear continuum mechanics framework and implemented using the standard finite element method. With no large penalty constant, the stiffness matrix of the system will in general be well-conditioned, which is of great significance for quasi-static analysis. Three numerical examples are presented to illustrate the capability of the proposed method. Results indicate that with the same mesh configuration, the finite element computation based on the surface integral approach is faster and more accurate than the volume integral based approach. In addition, the proposed approach is energy preserving even in a very long dynamic simulation.

  14. Friction-induced vibrations and self-organization mechanics and non-equilibrium thermodynamics of sliding contact

    CERN Document Server

    Nosonovsky, Michael

    2013-01-01

    Many scientists and engineers do not realize that, under certain conditions, friction can lead to the formation of new structures at the interface, including in situ tribofilms and various patterns. In turn, these structures-usually formed by destabilization of the stationary sliding regime-can lead to the reduction of friction and wear. Friction-Induced Vibrations and Self-Organization: Mechanics and Non-Equilibrium Thermodynamics of Sliding Contact combines the mechanical and thermodynamic methods in tribology, thus extending the field of mechanical friction-induced vibrations to non-mechanical instabilities and self-organization processes at the frictional interface. The book also relates friction-induced self-organization to novel biomimetic materials, such as self-lubricating, self-cleaning, and self-healing materials. Explore Friction from a Different Angle-as a Fundamental Force of Nature The book begins with an exploration of friction as a fundamental force of nature throughout the history of science....

  15. Blockage of High-Affinity Choline Transporter Increases Visceral Hypersensitivity in Rats with Chronic Stress

    Directory of Open Access Journals (Sweden)

    Chen Zhao

    2018-01-01

    Full Text Available Background. Visceral hypersensitivity is a common feature of irritable bowel syndrome. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1 is of crucial importance in choline uptake system. However, involvement of CHT1 in visceral hypersensitivity remains unknown. The research aimed to study the CHT1 expression in dorsal root ganglions (DRGs and the role of CHT1 in visceral hypersensitivity. Methods. Repetitive water avoidance stress (WAS was used to induce visceral hypersensitivity in rats. Colorectal distension (CRD was determined, and the abdominal withdrawal reflex (AWR and threshold intensity data were recorded to measure the visceral sensitivity. After intraperitoneal injection of hemicholinium-3 (HC-3, the specific inhibitor of CHT1, CRD data were also recorded. The CHT1 expression of DRGs was investigated by Western blotting, immunohistochemistry, and quantitative RT-PCR. Acetylcholine levels in the DRGs were detected by the assay kit. Results. Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats. After the administration of HC-3, the AWR score in WAS group was significantly increased at higher distension pressure while the threshold intensity was significantly reduced compared to the normal saline group. Acetylcholine concentration was significantly lower than the normal saline rats. Conclusion. Our research firstly reports that CHT1 is overexpressed in noninflammatory visceral hypersensitivity, and blockage of CHT1 can enhance the visceral hypersensitivity. CHT1 may play an inhibitory role in visceral hypersensitivity.

  16. Blockage of High-Affinity Choline Transporter Increases Visceral Hypersensitivity in Rats with Chronic Stress

    Science.gov (United States)

    2018-01-01

    Background Visceral hypersensitivity is a common feature of irritable bowel syndrome. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1) is of crucial importance in choline uptake system. However, involvement of CHT1 in visceral hypersensitivity remains unknown. The research aimed to study the CHT1 expression in dorsal root ganglions (DRGs) and the role of CHT1 in visceral hypersensitivity. Methods Repetitive water avoidance stress (WAS) was used to induce visceral hypersensitivity in rats. Colorectal distension (CRD) was determined, and the abdominal withdrawal reflex (AWR) and threshold intensity data were recorded to measure the visceral sensitivity. After intraperitoneal injection of hemicholinium-3 (HC-3), the specific inhibitor of CHT1, CRD data were also recorded. The CHT1 expression of DRGs was investigated by Western blotting, immunohistochemistry, and quantitative RT-PCR. Acetylcholine levels in the DRGs were detected by the assay kit. Results Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats. After the administration of HC-3, the AWR score in WAS group was significantly increased at higher distension pressure while the threshold intensity was significantly reduced compared to the normal saline group. Acetylcholine concentration was significantly lower than the normal saline rats. Conclusion Our research firstly reports that CHT1 is overexpressed in noninflammatory visceral hypersensitivity, and blockage of CHT1 can enhance the visceral hypersensitivity. CHT1 may play an inhibitory role in visceral hypersensitivity. PMID:29849603

  17. Immediate-type hypersensitivity to polyethylene glycols

    DEFF Research Database (Denmark)

    Wenande, E; Garvey, L H

    2016-01-01

    Polyethylene glycols (PEGs) or macrogols are polyether compounds widely used in medical and household products. Although generally considered biologically inert, cases of mild to life-threatening immediate-type PEG hypersensitivity are reported with increasing frequency. Nevertheless, awareness...

  18. Genetic evidence for an essential role of neuronally expressed IL-6 signal transducer gp130 in the induction and maintenance of experimentally induced mechanical hypersensitivity in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Constantin Cristina E

    2011-09-01

    Full Text Available Abstract Tenderness and mechanical allodynia are key symptoms of malignant tumor, inflammation and neuropathy. The proinflammatory cytokine interleukin-6 (IL-6 is causally involved in all three pathologies. IL-6 not only regulates innate immunity and inflammation but also causes nociceptor sensitization and hyperalgesia. In general and in most cell types including immune cells and sensory neurons, IL-6 binds soluble μ receptor subunits which heteromerizes with membrane bound IL-6 signal transducer gp130. In the present study, we used a conditional knock-out strategy to investigate the importance of signal transducer gp130 expressed in C nociceptors for the generation and maintenance of mechanical hypersensitivity. Nociceptors were sensitized to mechanical stimuli by experimental tumor and this nociceptor sensitization was preserved at later stages of the pathology in control mice. However, in mice with a conditional deletion of gp130 in Nav1.8 expressing nociceptors mechanical hypersensitivity by experimental tumor, nerve injury or inflammation recovery was not preserved in the maintenance phase and nociceptors exhibited normal mechanical thresholds comparable to untreated mice. Together, the results argue for IL-6 signal transducer gp130 as an essential prerequisite in nociceptors for long-term mechanical hypersensitivity associated with cancer, inflammation and nerve injury.

  19. Resident Rounds: Part III - Case Report: Betel Quid Induced Irritant Contact Dermatitis of the Hand.

    Science.gov (United States)

    Mathieu, Regine J; Cheraghi, Nikoo; Russo, Marian A

    2016-06-01

    Betel quid is a drug used in Far East Asia, India, and the South Pacific. The habit of betel quid chewing is widely reported to cause oral cancer and tooth and gum disease. However, skin disease due to betel quid use is underreported. We report a case of irritant contact dermatitis to betel quid components in a 35-year-old male betel quid user who presented for evaluation of a persistent rash on his fingertips.

  20. Sociolinguistic and Contact-induced Variation in Hungarian Language Use in Subcarpathia, Ukraine

    Directory of Open Access Journals (Sweden)

    István Csernicskó

    2012-01-01

    Full Text Available In addition to showing regional and social variation, the language use of the minority Hungarians of Subcarpathia, Ukraine, also presents a reflection of the region’s complex linguistic history and its effects from contact with Russian and Ukrainian. On the basis of quantitative empirical findings, this study shows Subcarpathian Hungarians to be a sociolinguistically stratified group of speakers whose Hungarian language use varies in a systematic manner according to sex, age, level of education, and place of residence. The paper also outlines some of the main differences in the language use of Hungarians in Subcarpathia and Hungary which are manifested in statistically significant ways.

  1. Oral lichenoid contact lesions induced by areca nut and betel quid chewing: a mini review.

    Science.gov (United States)

    Reichart, Peter A; Warnakulasuriya, Saman

    2012-08-01

    Betel quid (BQ) and areca nut chewing is widely prevalent in many parts of Asia and Asian-migrant communities throughout the world. Global reports estimate 600 million users. Sufficient evidence of carcinogenicity has been found for BQ and its main ingredient, areca nut. BQ areca nut users have an increased risk of potentially malignant disorders. Among chewers, BQ remains in contact with the oral mucosa for prolonged periods. This review examines the clinical and pathological aspects of lichenoid lesions caused by areca nut and BQ, a condition that has received little attention in the published literature. © 2012 Blackwell Publishing Asia Pty Ltd.

  2. Incidence of hypersensitivity and anaphylaxis with sugammadex.

    Science.gov (United States)

    Min, K Chris; Woo, Tiffany; Assaid, Christopher; McCrea, Jacqueline; Gurner, Deborah M; Sisk, Christine McCrary; Adkinson, Franklin; Herring, W Joseph

    2018-06-01

    To evaluate the incidence of hypersensitivity and anaphylaxis after administration of sugammadex. Retrospective analysis. Sugammadex clinical development program and post-marketing experience. Surgical patients and healthy volunteers who received sugammadex or placebo/comparator with anesthesia and/or neuromuscular blockade (NMB). Sugammadex administered as 2.0 mg/kg at reappearance of the second twitch, 4.0 mg/kg at 1-2 post-tetanic count, or 16.0 mg/kg at 3 min after rocuronium 1.2 mg/kg. Three analytical methods were used: 1) automated MedDRA queries; 2) searches of adverse events (AEs) consistent with treatment-related hypersensitivity reactions as diagnosed by the investigator; and 3) a retrospective adjudication of AEs suggestive of hypersensitivity by a blinded, independent adjudication committee (AC). In addition, a search of all post-marketing reports of events of hypersensitivity was performed, and events were retrospectively adjudicated by an independent AC. Anaphylaxis was determined according to Sampson Criterion 1. The pooled dataset included 3519 unique subjects who received sugammadex and 544 who received placebo. The automated MedDRA query method showed no apparent increase in hypersensitivity or anaphylaxis with sugammadex as compared to placebo or neostigmine. Similarly, there was a low overall incidence of AEs of treatment-related hypersensitivity (sugammadex and placebo or neostigmine. Finally, the retrospective adjudication of AEs suggestive of hypersensitivity showed a low incidence of hypersensitivity (0.56% and 0.21% for sugammadex 2 mg/kg and 4 mg/kg, respectively), with an incidence similar to subjects who received placebo (0.55%). There were no confirmed cases of anaphylaxis in the pooled studies. During post-marketing use, spontaneous reports of anaphylaxis occurred with approximately 0.01% of sugammadex doses. Subjects who received sugammadex with general anesthesia and/or NMB had a low overall incidence of

  3. Contact spectroscopy on S/TI/N devices: Induced pairing on the surface of a topological insulator

    Science.gov (United States)

    Stehno, Martin P.; Ngabonziza, Prosper; Snelder, Marieke; Myoren, Hiroaki; Pan, Yu; de Visser, Anne; Huang, Y.; Golden, Mark S.; Brinkman, Alexander

    Translating concepts of topological quantum computation into applications requires fine-tuning of parameters in the model Hamiltonians of candidate systems. Such level of control has proven difficult to achieve in devices where superconductors are used to induce pairing in topological insulator (TI) materials. While local probe experiments have indicated features of p-wave superconducting correlations in TIs (as suggested by theory), results on extended devices often remain ambiguous. We present contact spectroscopy data on superconductor/topological insulator/normal metal devices with bulk-insulating TI material and compare these with bulk conducting samples. We discuss the magnitude of the induced gap and unusual features in the conductance traces of the bulk-insulating samples that may suggest the presence of p-wave type correlations in the TI. This work is financially supported by the Dutch Foundation for Fundamental Research on Matter (FOM), the Netherlands Organization for Scientific Research (NWO), and by the European Research Council (ERC).

  4. Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy.

    Science.gov (United States)

    Chen, Jiahuan; Ganguly, Anutosh; Mucsi, Ashley D; Meng, Junchen; Yan, Jiacong; Detampel, Pascal; Munro, Fay; Zhang, Zongde; Wu, Mei; Hari, Aswin; Stenner, Melanie D; Zheng, Wencheng; Kubes, Paul; Xia, Tie; Amrein, Matthias W; Qi, Hai; Shi, Yan

    2017-02-01

    Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell-DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1-dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin-cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1-dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell-mediated DC suppression in a contact-dependent manner. © 2017 Chen et al.

  5. Contact-induced apical asymmetry drives the thigmotropic responses of Candida albicans hyphae.

    Science.gov (United States)

    Thomson, Darren D; Wehmeier, Silvia; Byfield, FitzRoy J; Janmey, Paul A; Caballero-Lima, David; Crossley, Alison; Brand, Alexandra C

    2015-03-01

    Filamentous hyphae of the human pathogen, Candida albicans, invade mucosal layers and medical silicones. In vitro, hyphal tips reorient thigmotropically on contact with small obstacles. It is not known how surface topography is sensed but hyphae lacking the cortical marker, Rsr1/Bud1, are unresponsive. We show that, on surfaces, the morphology of hyphal tips and the position of internal polarity protein complexes are asymmetrically skewed towards the substratum and biased towards the softer of two surfaces. In nano-fabricated chambers, the Spitzenkörper (Spk) responded to touch by translocating across the apex towards the point of contact, where its stable maintenance correlated with contour-following growth. In the rsr1Δ mutant, the position of the Spk meandered and these responses were attenuated. Perpendicular collision caused lateral Spk oscillation within the tip until after establishment of a new growth axis, suggesting Spk position does not predict the direction of growth in C. albicans. Acute tip reorientation occurred only in cells where forward growth was countered by hyphal friction sufficient to generate a tip force of ∼ 8.7 μN (1.2 MPa), more than that required to penetrate host cell membranes. These findings suggest mechanisms through which the organization of hyphal tip growth in C. albicans facilitates the probing, penetration and invasion of host tissue. © 2014 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.

  6. Role of insular cortex in visceral hypersensitivity model in rats subjected to chronic stress.

    Science.gov (United States)

    Yi, LiSha; Sun, HuiHui; Ge, Chao; Chen, Ying; Peng, HaiXia; Jiang, YuanXi; Wu, Ping; Tang, YinHan; Meng, QingWei; Xu, ShuChang

    2014-12-30

    Abnormal processing of visceral sensation at the level of the central nervous system has been proven to be important in the pathophysiologic mechanisms of stress related functional gastrointestinal disorders. However, the specific mechanism is still not clear. The insular cortex (IC) was considered as one important visceral sensory area. Moreover, the IC has been shown to be involved in various neuropsychiatric diseases such as panic disorders and post-traumatic stress disorder. However, whether the IC is important in psychological stress related visceral hypersensitivity has not been studied yet. In our study, through destruction of the bilateral IC, we explored whether the IC played a critical role in the formation of visceral hypersensitivity induced by chronic stress on rats. Chronic partial restraint stress was used to establish viscerally hypersensitive rat model. Bilateral IC lesions were generated by N-methyl-D-day (door) aspartate. After a recovery period of 7 days, 14-day consecutive restraint stress was performed. The visceromotor response to colorectal distension was monitored by recording electromyogram to measure rats׳ visceral sensitivity. We found that bilateral insular cortex lesion could markedly inhibit the formation of visceral hypersensitivity induced by chronic stress. The insular cortex plays a critical role in the pathophysiology of stress-related visceral hypersensitivity.

  7. Lateral-electric-field-induced spin polarization in a suspended GaAs quantum point contact

    Science.gov (United States)

    Pokhabov, D. A.; Pogosov, A. G.; Zhdanov, E. Yu.; Shevyrin, A. A.; Bakarov, A. K.; Shklyaev, A. A.

    2018-02-01

    The conductance of a GaAs-based suspended quantum point contact (QPC) equipped with lateral side gates has been experimentally studied in the absence of the external magnetic field. The half-integer conductance plateau ( 0.5 ×2 e2/h ) has been observed when an asymmetric voltage between the side gates is applied. The appearance of this plateau has been attributed to the spin degeneracy lifting caused by the spin-orbit coupling associated with the lateral electric field in the asymmetrically biased QPC. We have experimentally demonstrated that, despite the relatively small g-factor in GaAs, the observation of the spin polarization in the GaAs-based QPC became possible after the suspension due to the enhancement of the electron-electron interaction and the effect of the electric field guiding. These features are caused by a partial confinement of the electric field lines within a suspended semiconductor layer with a high dielectric constant.

  8. Contact Lens-Induced Discomfort and Inflammatory Mediator Changes in Tears.

    Science.gov (United States)

    Masoudi, Simin; Zhao, Zhenjun; Stapleton, Fiona; Willcox, Mark

    2017-01-01

    Studies indicate that contact lens (CL) discontinuation mostly occurs because of dryness and discomfort symptoms. This study aimed to investigate relationships between changes in the concentration of tear inflammatory mediators with subjective comfort ratings with CL wear and no contact lens wear between morning and evening. Forty-five subjects collected tears twice daily in the morning and in the evening with or without lenses. Comfort was rated subjectively on a scale from 1 to 100 (where 100 was extremely comfortable) just before each tear collection. Tear samples were assayed for complement components (C3 and C3a), leukotriene B4 (LTB4), secretory phospholipase A2 (sPLA2), secretory immunoglobulin A (sIgA), and bradykinin using commercially available immuno-based assay kits. Comfort ratings showed a statistically significant decline from morning to evening both with CL (89.0±10.1 AM vs. 76.7±15.2 PM; P0.05). Leukotriene B4 levels were slightly higher in CL (CL 43.4±12.6 pg/ml vs. No CL 39.4±13.4 pg/mL; P=0.034), whereas the concentration of LTB4, C3, C3a, and sIgA dropped by the end of the day in the presence or absence of lens wear (Ptear levels were not correlated with comfort ratings in any of the conditions. Leukotriene B4 had a higher concentration in the evening, and when measured as a ratio to sIgA, there was a trend for increased concentration of this mediator during CL wear. Although specific mediators showed changes from morning to evening with and without lens wear, most of these were not correlated with subjective comfort ratings in lens wear. The only mediator that showed an increase in concentration during the day and during lens wear was LTB4, and further studies on this mediator are warranted.

  9. Minocycline Prevents Muscular Pain Hypersensitivity and Cutaneous Allodynia Produced by Repeated Intramuscular Injections of Hypertonic Saline in Healthy Human Participants.

    Science.gov (United States)

    Samour, Mohamad Samir; Nagi, Saad Saulat; Shortland, Peter John; Mahns, David Anthony

    2017-08-01

    Minocycline, a glial suppressor, prevents behavioral hypersensitivities in animal models of peripheral nerve injury. However, clinical trials of minocycline in human studies have produced mixed results. This study addressed 2 questions: can repeated injections of hypertonic saline (HS) in humans induce persistent hypersensitivity? Can pretreatment with minocycline, a tetracycline antibiotic with microglial inhibitory effects, prevent the onset of hypersensitivity? Twenty-seven healthy participants took part in this double-blind, placebo-controlled study, consisting of 6 test sessions across 2 weeks. At the beginning of every session, pressure-pain thresholds of the anterior muscle compartment of both legs were measured to determine the region distribution and intensity of muscle soreness. To measure changes in thermal sensitivity in the skin overlying the anterior muscle compartment of both legs, quantitative sensory testing was used to measure the cutaneous thermal thresholds (cold sensation, cold pain, warm sensation, and heat pain) and a mild cooling stimulus was applied to assess the presence of cold allodynia. To induce ongoing hypersensitivity, repeated injections of HS were administered into the right tibialis anterior muscle at 48-hour intervals. In the final 2 sessions (days 9 and 14), only sensory assessments were done to plot the recovery after cessation of HS administrations and drug washout. By day 9, nontreated participants experienced a significant bilateral increase in muscle soreness (P minocycline-treated participants experienced a bilateral 70% alleviation in muscle soreness (P minocycline-treated participants showed cold allodynia. This study showed that repeated injections of HS can induce a hypersensitivity that outlasts the acute response, and the development of this hypersensitivity can be reliably attenuated with minocycline pretreatment. Four repeated injections of HS at 48-hour intervals induce a state of persistent hypersensitivity in

  10. Cutaneous and systemic hypersensitivity reactions to metallic implants.

    Science.gov (United States)

    Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C

    2011-01-01

    Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous, and vasculitic eruptions may occur. Also, more complex immune reactions may develop around the implants, resulting in pain, inflammation, and loosening. Nickel, cobalt, and chromium are the three most common metals that elicit both cutaneous and extracutaneous allergic reactions from chronic internal exposure. However, other metal ions as well as bone cement components can cause such hypersensitivity reactions. To complicate things, patients may also develop delayed-type hypersensitivity reactions to metals (ie, in-stent restenosis, prosthesis loosening, inflammation, pain, or allergic contact dermatitis) following the insertion of intravascular stents, dental implants, cardiac pacemakers, or implanted gynecologic devices. Despite repeated attempts by researchers and clinicians to further understand this difficult area of medicine, the association between metal sensitivity and cutaneous allergic reactions remains to be fully understood. This review provides an update of the current knowledge in this field and should be valuable to health care providers who manage patients with conditions related to this field.

  11. Spin current induced by a charged tip in a quantum point contact

    Energy Technology Data Exchange (ETDEWEB)

    Shchamkhalova, B.S., E-mail: s.bagun@gmail.com

    2017-03-15

    We show that the charged tip of the probe microscope, which is widely used in studying the electron transport in low-dimensional systems, induces a spin current. The effect is caused by the spin–orbit interaction arising due to an electric field produced by the charged tip. The tip acts as a spin-flip scatterer giving rise to the spin polarization of the net current and the occurrence of a spin density in the system.

  12. Diclofenac hypersensitivity: antibody responses to the parent drug and relevant metabolites.

    Directory of Open Access Journals (Sweden)

    Andrea Harrer

    2010-10-01

    Full Text Available Hypersensitivity reactions against nonsteroidal antiinflammatory drugs (NSAIDs like diclofenac (DF can manifest as Type I-like allergic reactions including systemic anaphylaxis. However, except for isolated case studies experimental evidence for an IgE-mediated pathomechanism of DF hypersensitivity is lacking. In this study we aimed to investigate the possible involvement of drug- and/or metabolite-specific antibodies in selective DF hypersensitivity.DF, an organochemically synthesized linkage variant, and five major Phase I metabolites were covalently coupled to carrier proteins. Drug conjugates were analyzed for coupling degree and capacity to crosslink receptor-bound IgE antibodies from drug-sensitized mice. With these conjugates, the presence of hapten-specific IgE antibodies was investigated in patients' samples by ELISA, mediator release assay, and basophil activation test. Production of sulfidoleukotrienes by drug conjugates was determined in PBMCs from DF-hypersensitive patients. All conjugates were shown to carry more than two haptens per carrier molecule. Immunization of mice with drug conjugates induced drug-specific IgE antibodies capable of triggering mediator release. Therefore, the conjugates are suitable tools for detection of drug-specific antibodies and for determination of their anaphylactic activity. Fifty-nine patients were enrolled and categorized as hypersensitive either selectively to DF or to multiple NSAIDs. In none of the patients' samples evidence for drug/metabolite-specific IgE in serum or bound to allergic effector cells was found. In contrast, a small group of patients (8/59, 14% displayed drug/metabolite-specific IgG.We found no evidence for an IgE-mediated effector mechanism based on haptenation of protein carriers in DF-hypersensitive patients. Furthermore, a potential involvement of the most relevant metabolites in DF hypersensitivity reactions could be excluded.

  13. Effect of cup inclination on predicted contact stress-induced volumetric wear in total hip replacement.

    Science.gov (United States)

    Rijavec, B; Košak, R; Daniel, M; Kralj-Iglič, V; Dolinar, D

    2015-01-01

    In order to increase the lifetime of the total hip endoprosthesis, it is necessary to understand mechanisms leading to its failure. In this work, we address volumetric wear of the artificial cup, in particular the effect of its inclination with respect to the vertical. Volumetric wear was calculated by using mathematical models for resultant hip force, contact stress and penetration of the prosthesis head into the cup. Relevance of the dependence of volumetric wear on inclination of the cup (its abduction angle ϑA) was assessed by the results of 95 hips with implanted endoprosthesis. Geometrical parameters obtained from standard antero-posterior radiographs were taken as input data. Volumetric wear decreases with increasing cup abduction angle ϑA. The correlation within the population of 95 hips was statistically significant (P = 0.006). Large cup abduction angle minimises predicted volumetric wear but may increase the risk for dislocation of the artificial head from the cup in the one-legged stance. Cup abduction angle and direction of the resultant hip force may compensate each other to achieve optimal position of the cup with respect to wear and dislocation in the one-legged stance for a particular patient.

  14. Laser-induced nanostructures on a polymer irradiated through a contact mask

    Energy Technology Data Exchange (ETDEWEB)

    Neděla, O. [Department of Solid State Engineering, Institute of Chemical Technology, 166 28 Prague (Czech Republic); Slepička, P., E-mail: petr.slepicka@vscht.cz [Department of Solid State Engineering, Institute of Chemical Technology, 166 28 Prague (Czech Republic); Malý, J.; Štofík, M. [Department of Biology, Faculty of Science, J.E. Purkyně University, 400 96 Usti nad Labem (Czech Republic); Švorčík, V. [Department of Solid State Engineering, Institute of Chemical Technology, 166 28 Prague (Czech Republic)

    2014-12-01

    Highlights: • The unique nanopatterning method of PEN was proposed. • Laser treatment through micrometer slit was utilized. • Dimensions of nanostructures can be precisely controlled. • Laser treatment changes the PEN surface chemistry and morphology (sensor applications). - Abstract: The nanopatterning method applied through micrometer slit for polyethylene naphthalate (PEN) substrate was proposed in this paper. Surface roughness, formation of nanoscale ripple-like structures and the dependence of their dimensions on the value of laser fluence was determined by atomic force and laser confocal microscopy, and compared with values obtained from samples irradiated directly (without a contact mask) under similar conditions. The morphology of the unirradiated surface of the substrate in between the slits is also studied, as well as the morphology of the transitional area between the irradiated and unirradiated surface. Thin layer of gold was deposited on selected samples. Chemical composition of the surface was determined from XPS spectra. The potential application of this research can be found predominantly in the field of selective sensor applications, where the designated area for the consecutive grafting procedures is of great importance.

  15. Hypersensitivity myocarditis associated with ephedra use.

    Science.gov (United States)

    Zaacks, S M; Klein, L; Tan, C D; Rodriguez, E R; Leikin, J B

    1999-01-01

    Ephedrine has previously been described as a causative factor of vasculitis but myocarditis has not yet been associated with either ephedrine or its plant derivative ephedra. A 39-year-old African American male with hypertension presented to Rush Presbyterian St. Luke's Medical Center with a 1-month history of progressive dyspnea on exertion, orthopnea, and dependent edema. He was taking Ma Huang (Herbalife) 1-3 tablets twice daily for 3 months along with other vitamin supplements, pravastatin, and furosemide. Physical examination revealed a male in mild respiratory distress. The lung fields had rales at both bases without audible wheezes. Internal jugular venous pulsations were 5 cm above the sternal notch. Medical therapy with intravenous furosemide and oral enalapril was initiated upon admission. Cardiac catheterization with coronary angiography revealed normal coronary arteries, a dilated left ventricle, moderate pulmonary hypertension, and a pulmonary capillary wedge pressure of 34 mm Hg. The patient had right ventricular biopsy performed demonstrating mild myocyte hypertrophy and an infiltrate consisting predominantly of lymphocytes with eosinophils present in significantly increased numbers. Treatment for myocarditis was initiated with azothioprine 200 mg daily and prednisone 60 mg per day with a tapering course over 6 months. Anticoagulation with warfarin and diuretics was initiated and angiotensin-converting enzyme inhibition was continued. Hydralazine was added later. One month into therapy, an echocardiogram demonstrated improved left ventricular function with only mild global hypokinesis. A repeat right ventricular biopsy 2 months after the first admission showed no evidence of myocarditis. At 6 months, left ventricular ejection fraction was normal (EFN 50%) and the patient asymptomatic. Ephedra (Ma Huang) is the suspected cause of hypersensitivity myocarditis in this patient due to the temporal course of disease and its propensity to induce vasculitis.

  16. Occupational contact urticaria and protein contact dermatitis.

    Science.gov (United States)

    Doutre, Marie-Sylvie

    2005-01-01

    Irritant dermatitis and eczema are the most prevalent occupational skin diseases. Less common are immediate contact reactions such as contact urticaria and protein contact dermatitis. Occupational contact urticaria can be subdivided into two categories, immunological and non immunological. However, some agents can induce these two types of reactions. Contact urticaria to natural rubber latex is particularly frequent among health care personnel, but contact urticaria to a wide variety of other substances occurs in many other occupations. Among those at risk are cooks, bakers, butchers, restaurant personnel, veterinarians, hairdressers, florists, gardeners, and forestry workers. Protein contact dermatitis in some of these occupations is caused principally by proteins of animal or plant origin, especially among individuals with a history of atopic dermatitis. Diagnosis requires careful interrogation, clinical examination and skin tests (open tests and prick tests with immediate lecture) to identify a particular contact allergen.

  17. Entomologic evaluation of insect hypersensitivity in horses.

    Science.gov (United States)

    Greiner, E C

    1995-04-01

    Potential methods of incriminating insects as the cause of insect hypersensitivity are presented. A listing of the biting midges known to attack horses in North America is presented also. An example of how species may be determined to be the cause of the hypersensitivity is given using data from a recent study in Florida. Light trap collections indicated the temporal and geographic distribution of potential contributing species and collections made by vacuuming horses further delineated species by proving they feed on horses and the correct locations on the horses to match lesion distribution. Culicoides hypersensitivity in horses in Florida seems to be caused by a series of species active and feeding on the horses at different times of the year.

  18. Drug hypersensitivity in clonal mast cell disorders

    DEFF Research Database (Denmark)

    Bonadonna, P; Pagani, M; Aberer, W

    2015-01-01

    and severity of immediate hypersensitivity reactions. Mastocytosis in adults is associated with a history of anaphylaxis in 22-49%. Fatal anaphylaxis has been described particularly following hymenoptera stings, but also occasionally after the intake of drugs such as nonsteroidal anti-inflammatory drugs......, opioids and drugs in the perioperative setting. However, data on the frequency of drug hypersensitivity in mastocytosis and vice versa are scarce and evidence for an association appears to be limited. Nevertheless, clonal MC disorders should be ruled out in cases of severe anaphylaxis: basal serum...... tryptase determination, physical examination for cutaneous mastocytosis lesions, and clinical characteristics of anaphylactic reaction might be useful for differential diagnosis. In this position paper, the ENDA group performed a literature search on immediate drug hypersensitivity reactions in clonal MC...

  19. Mesenchymal Stem Cells Induce Epithelial to Mesenchymal Transition in Colon Cancer Cells through Direct Cell-to-Cell Contact

    Directory of Open Access Journals (Sweden)

    Hidehiko Takigawa

    2017-05-01

    Full Text Available We previously reported that in an orthotopic nude mouse model of human colon cancer, bone marrow–derived mesenchymal stem cells (MSCs migrated to the tumor stroma and promoted tumor growth and metastasis. Here, we evaluated the proliferation and migration ability of cancer cells cocultured with MSCs to elucidate the mechanism of interaction between cancer cells and MSCs. Proliferation and migration of cancer cells increased following direct coculture with MSCs but not following indirect coculture. Thus, we hypothesized that direct contact between cancer cells and MSCs was important. We performed a microarray analysis of gene expression in KM12SM colon cancer cells directly cocultured with MSCs. Expression of epithelial-mesenchymal transition (EMT–related genes such as fibronectin (FN, SPARC, and galectin 1 was increased by direct coculture with MSCs. We also confirmed the upregulation of these genes with real-time polymerase chain reaction. Gene expression was not elevated in cancer cells indirectly cocultured with MSCs. Among the EMT-related genes upregulated by direct coculture with MSCs, we examined the immune localization of FN, a well-known EMT marker. In coculture assay in chamber slides, expression of FN was seen only at the edges of cancer clusters where cancer cells directly contacted MSCs. FN expression in cancer cells increased at the tumor periphery and invasive edge in orthotopic nude mouse tumors and human colon cancer tissues. These results suggest that MSCs induce EMT in colon cancer cells via direct cell-to-cell contact and may play an important role in colon cancer metastasis.

  20. Prevention of experimentally induced irritant contact dermatitis by extracts of Isatis tinctoria compared to pure tryptanthrin and its impact on UVB-induced erythema.

    Science.gov (United States)

    Heinemann, Christian; Schliemann-Willers, Sibylle; Oberthür, Christine; Hamburger, Matthias; Elsner, Peter

    2004-05-01

    Lipophilic extracts of Isatis tinctoria L. exhibit significant activity against several clinically relevant targets of inflammation. The alkaloid tryptanthrin was identified as one of the active principles in woad and characterised as a potent dual inhibitor of COX-2 and 5-LOX. Here, the anti-inflammatory efficacy of topical application of three different Isatis extracts and tryptanthrin was investigated in human volunteers. Two different models were used, namely the sodium lauryl sulphate (SLS)-induced irritant contact dermatitis (ICD) and UVB-induced erythema. Twenty healthy volunteers without any skin disease participated in the study. Cumulative irritant contact dermatitis was induced on test fields on the volunteers' backs by twice daily application of 0.5 % sodium lauryl sulphate over a period of four days. Half of the test fields were treated with the test substances during the eliciting phase, while the remaining test fields were treated over a period of 4 days after induction of dermatitis. In the second model, a UVB erythema on the volunteers' lower backs was induced using the double minimal erythema dose (MED). Twenty-four hours after irradiation the test fields were treated with the test substances over a period of 3 days. All reactions were assessed visually and by non-invasive bioengineering methods (evaporimetry and chromametry). Treatment with extracts during the ICD eliciting phase led to a significantly smaller increase of visual scores and transepidermal water loss compared to the untreated test field. For tryptanthrin this benefit was also observed, but the improvement was not statistically significant. When treatment was performed after completing the eliciting phase, accelerated resolution of the irritant reaction could not be observed. In the UVB erythema model anti-inflammatory effects of the test substances were not observed.

  1. Cornea stress test--evaluation of corneal endothelial function in vivo by contact lens induced stress

    Directory of Open Access Journals (Sweden)

    Saini Jagjit

    1997-01-01

    Full Text Available Reliable and valid assessment of corneal endothelial function is a critical input for diagnosing, prognosticating and monitoring progression of disorders affecting corneal endothelium. In 123 eyes, corneal endothelial function was assessed employing data from the corneal hydration recovery dynamics. Serial pachometric readings were recorded on Haag-Striet pachometer with Mishima-Hedbys modification before and after two hours of thick soft contact lens wear. Percentage Recovery Per Hour (PRPH was derived from raw data as an index of endothelial function. Assessed PRPH in pseudophakic corneal oedema and Fuchs′ endothelial dystrophy eyes (35.9 +/- 9.8% was significantly lower than normal controls (61.9 +/- 10.5%. On employing receiver operation characteristics curve analysis the tested results demonstrated high sensitivity (87% and specificity (92% for detection of low endothelial function at PRPH cut off of 47.5%. Using this PRPH cut off, 80% of Fuchs′ endothelial dystrophy and 93.3% of pseudophakic corneal oedema eyes could be demonstrated to have low endothelial function. A total of 66.7% of diabetic eyes also demonstrated PRPH of lower than 47.5%. Clear corneal grafts demonstrated PRPH values of 24.6% to 73.0%. Of 6 corneal grafts that demonstrated initial PRPH of lower than 47.5%, 4 failed within 4 to 6 months. Our data demonstrated high sensitivity and specificity of this corneal stress test. PRPH index was useful in quantifying endothelial function in clinical disorders including diabetes mellitus. The index PRPH was demonstrated to be useful in monitoring and prognosticating outcome of corneal grafts.

  2. On the possibility of contact-induced spin polarization in interfaces of armchair nanotubes with transition metal substrates

    Energy Technology Data Exchange (ETDEWEB)

    Kuzubov, Alexander A. [Siberian Federal University, 79 Svobodny Prospect, 660041 Krasnoyarsk (Russian Federation); Kirensky Institute of Physics, 50 Akademgorodok, 660036 Krasnoyarsk (Russian Federation); Kovaleva, Evgenia A., E-mail: kovaleva.evgeniya1991@mail.ru [Siberian Federal University, 79 Svobodny Prospect, 660041 Krasnoyarsk (Russian Federation); Kirensky Institute of Physics, 50 Akademgorodok, 660036 Krasnoyarsk (Russian Federation); Tomilin, Felix N.; Mikhaleva, Natalya S.; Kuklin, Artem V. [Siberian Federal University, 79 Svobodny Prospect, 660041 Krasnoyarsk (Russian Federation); Kirensky Institute of Physics, 50 Akademgorodok, 660036 Krasnoyarsk (Russian Federation)

    2015-12-15

    The interaction between armchair carbon and boron nitride nanotubes (NT) with ferromagnetic transition metal (TM) surfaces, namely, Ni(111) and Co(0001), was studied by means of density functional theory. Different configurations of composite compartments mutual arrangement were considered. Partial densities of states and spin density spatial distribution of optimized structures were investigated. Influence of ferromagnetic substrate on nanotubes’ electronic properties was discussed. The values of spin polarization magnitude at the Fermi level are also presented and confirm the patterns of spin density spatial distribution. - Highlights: • Interaction of armchair nanotubes with ferromagnetic metal surfaces was investigated. • Different configurations of nanotube's location were considered. • For all nanotubes the energy difference between configurations is negligible. • Nanotubes were found to be more or less spin-polarized regarding to the configuration. • BN nanotubes demonstrate vanishing of the band gap and contact-induced conductivity.

  3. Isolation of uvh1, an Arabidopsis mutant hypersensitive to ultraviolet light and ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Harlow, G. R.; Jenkins, M. E.; Pittalwala, T. S.; Mount, D. W.

    1994-02-15

    A genetic screen for mutants of Arabidopsis that are hypersensitive to UV light was developed and used to isolate a new mutant designated uvh1. UV hypersensitivity in uvh1 was due to a single recessive trait that is probably located on chromosome 3. Although isolated as hypersensitive to an acute exposure to UV-C light, uvh1 was also hypersensitive to UV-B wavelengths, which are present in sunlight that reaches the earth's surface. UV-B damage to both wild-type and uvh1 plants could be significantly reduced by subsequent exposure of UV-irradiated plants to photoreactivating light, showing that photoreactivation of UV-B damage is important for plant viability and that uvh1 plants are not defective in photoreactivation. A new assay for DNA damage, the Dral assay, was developed and used to show that exposure of wild-type and uvh1 plants to a given dose of UV light induces the same amount of damage in chloroplast and nuclear DNA. Thus, uvh1 is not defective in a UV protective mechanism. uvh1 plants were also found to be hypersensitive to ionizing radiation. These results suggest that uvh1 is defective in a repair or tolerance mechanism that normally provides plants with resistance to several types of DNA damage.

  4. Isolation of uvh1, an Arabidopsis mutant hypersensitive to ultraviolet light and ionizing radiation

    International Nuclear Information System (INIS)

    Harlow, G.R.; Jenkins, M.E.; Pittalwala, T.S.; Mount, D.W.

    1994-01-01

    A genetic screen for mutants of Arabidopsis that are hypersensitive to UV light was developed and used to isolate a new mutant designated uvh1. UV hypersensitivity in uvh1 was due to a single recessive trait that is probably located on chromosome 3. Although isolated as hypersensitive to an acute exposure to UV-C light, uvh1 was also hypersensitive to UV-B wavelengths, which are present in sunlight that reaches the earth's surface. UV-B damage to both wild-type and uvh1 plants could be significantly reduced by subsequent exposure of UV-irradiated plants to photoreactivating light, showing that photoreactivation of UV-B damage is important for plant viability and that uvh1 plants are not defective in photoreactivation. A new assay for DNA damage, the Dral assay, was developed and used to show that exposure of wild-type and uvh1 plants to a given dose of UV light induces the same amount of damage in chloroplast and nuclear DNA. Thus, uvh1 is not defective in a UV protective mechanism. uvh1 plants were also found to be hypersensitive to ionizing radiation. These results suggest that uvh1 is defective in a repair or tolerance mechanism that normally provides plants with resistance to several types of DNA damage

  5. Hypersensitivity reaction studies of a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation.

    Science.gov (United States)

    Wang, Hongbo; Cheng, Guang; Du, Yuan; Ye, Liang; Chen, Wenzhong; Zhang, Leiming; Wang, Tian; Tian, Jingwei; Fu, Fenghua

    2013-03-01

    The commercial drug paclitaxel (Taxol) may introduce hypersensitivity reactions associated with the polyethoxylated castor oil-ethanol solvent. To overcome these problems, we developed a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation, known as Lipusu. In this study, we performed in vitro and in vivo experiments to compare the safety profiles of Lipusu and Taxol, with special regard to hypersensitivity reactions. First, Swiss mice were used to determine the lethal dosages, and then to evaluate hypersensitivity reactions, followed by histopathological examination and enzyme-linked immunosorbent assays (ELISAs) of serum SC5b-9 and lung histamine. Additionally, healthy human serum was used to analyze in vitro complement activation. Finally, an MTT assay was used to determine the in vitro anti-proliferation activity. Our data clearly showed that Lipusu displayed a much higher safety margin and did not induce hypersensitivity or hypersensitivity-related lung lesions, which may be associated with the fact that Lipusu did not activate complement or increase histamine release in vivo. Moreover, Lipusu did not promote complement activation in healthy human serum in vitro, and demonstrated anti-proliferative activity against human cancer cells, similar to that of Taxol. Therefore, the improved formulation of paclitaxel, which exhibited a much better safety profile and comparable cytotoxic activity to Taxol, may bring a number of benefits to cancer patients.

  6. Effect of Green Tea Extract on T cell Mediated Hypersensitivity Reaction in BALB/c Mice Exposed to Gamma Irradiation

    International Nuclear Information System (INIS)

    Hashim, A.M.; Ismail Al-kadey, M.M.I.; Shabon, M.H.; Hussien, S.M.

    2010-01-01

    Gamma radiation is widely used in the treatment of malignant neoplasms. However, it deprives the host immune function which may retard tumor rejection by the immune response. The main purpose of the present study is to test the ability of green tea dry extract to restore the T cell hypersensitivity reaction in gamma irradiated BALB/c mice. It aims also to elucidate the possible mechanism of action of ionizing radiation and green tea dry extract in the immune function. Four groups of BALB/c mice, each of ten, have been used in each experiment. The first group served as a control, the second group received green tea dry extract and the third group was exposed to 2 Gy gamma irradiation, while the fourth group received green tea dry extract before and after gamma irradiation. The following parameters were determined, the contact sensitivity reaction by the mouse ear swelling response, local dendritic cell migration, local lymph node weight, lymphocyte proliferation, spleen and thymus weight with their lymphocyte count. The effect of gamma irradiation and green tea dry extract on the elicitation phase of contact sensitivity was also determined. Data from the present study showed that gamma irradiation caused a significant decrease of the mouse ear swelling response and retarded dendritic cell migration. They also showed a significant decline in the lymphocytes proliferation in lymph node draining the contact sensitizer application. Total body exposure to 2 Gy gamma irradiation induced marked decline of thymus weight and thymocyte count, while it reduced spleen weight and spleenocyte count to a lesser extent. Exposure to gamma irradiation enhanced the elicitation phase of contact sensitivity. Administration of green tea dry extract partially preserved the contact sensitivity response to oxazolone in gamma irradiated BALB/c mice. It markedly minimized the enhancement of the elicitation phase of ear swelling. In conclusion, the present study heralds a beneficial role of

  7. Dentine hypersensitivity: real or imagined | Gbadebo | Nigerian ...

    African Journals Online (AJOL)

    Background: Dentine hypersensitivity is a common presentation of cause of pain and or discomfort with mastication which has been shown to affect the quality of life of the affected individual. It is also a common cause of presentation at the dental clinics. However, the cause, diagnosis and possible management to give relief ...

  8. Tuberculous Lymphadenitis: Skin Delayed-Type Hypersensitivity ...

    African Journals Online (AJOL)

    Tuberculous Lymphadenitis: Skin Delayed-Type Hypersensitivity Reaction and Cellular Immune Responses. ... The tuberculin skin test (TST) and peripheral blood mono-nuclear cells (PBMCs) culture were conducted using PPD. The cytokines were measured using commercial kits. Results: The mean TST was 24.6 ±8.0 ...

  9. Severe Hyperacusis, Photophobia, and Skin Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Alessandra Barbara Fioretti

    2016-01-01

    Full Text Available We report a case of a patient with severe hyperacusis, photophobia, and skin hypersensitivity. The patient was initially treated with sound therapy and medical therapy for 4 months and successfully with a selective serotonin reuptake inhibitor (SSRI and cognitive behavioral therapy which improved her mood and the tolerance for sounds and light.

  10. Hypersensitivity reactions due to black henna tattoos and their components: are the clinical pictures related to the immune pathomechanism?

    Science.gov (United States)

    Calogiuri, Gianfranco; Di Leo, Elisabetta; Butani, Lavjay; Pizzimenti, Stefano; Incorvaia, Cristoforo; Macchia, Luigi; Nettis, Eustachio

    2017-01-01

    Hypersensitivity to para-phenylenediamine (PPD) and related compounds induced by temporary black henna tattoos has become a serious health problem worldwide. Different patterns of sensitization with various clinical aspects are described in literature due to PPD associated to henna tattoo and these manifestations are likely correlated with the immunological and dermatological pathomechanisms involved. Henna is the Persian name of the plant Lawsonia inermis, Fam. Lythraceae . It is a woody shrub that grow in regions of North Africa, South Asia, India and Sri Lanka. Nowadays it is rather frequent to see temporary "tattoos" performed with henna. To make tattoos darker and long-lasting PPD has been associated to henna in tattoo drawings mixtures, so obtaining " black henna ". In these years there has been a rise of contact sensitization to PPD and in medical literature an increased number of cases have been reported on temporary henna tattoo application. Here we review the various clinical patterns related to PPD and henna tattoo, to investigate the possible link between clinic-morphological pictures and the immunological response to PPD and henna. The literature underlines that different clinical manifestations are related to black henna containing PPD, and its derivative products may cause delayed-type as well as immediate-type reactions. Further studies are needed to investigate the relationship between clinical and morphological aspects of PPD contact dermatitis and the T cell subsets predominance.

  11. A class I (Senofilcon A) soft contact lens prevents UVB-induced ocular effects, including cataract, in the rabbit in vivo.

    Science.gov (United States)

    Giblin, Frank J; Lin, Li-Ren; Leverenz, Victor R; Dang, Loan

    2011-06-01

    UVB radiation from sunlight is known to be a risk factor for human cataract. The purpose in this study was to investigate the ability of a class I UV-blocking soft contact lens to protect against UVB-induced effects on the ocular tissues of the rabbit in vivo. Eyes of rabbits were exposed to UVB light for 30 minutes (270-360 nm, peak at 310 nm, 1.7 mW/cm(2) on the cornea). Eyes were irradiated in the presence of either a UV-blocking senofilcon A contact lens, a minimally UV-blocking lotrafilcon A contact lens, or no contact lens at all. Effects on the cornea and lens were evaluated at various times after exposure. Eyes irradiated with no contact lens protection showed corneal epithelial cell loss plus lens epithelial cell swelling, vacuole formation, and DNA single-strand breaks, as well as lens anterior subcapsular opacification. The senofilcon A lens protected nearly completely against the UVB-induced effects, whereas the lotrafilcon A lens showed no protection. The results indicate that use of a senofilcon A contact lens is beneficial in protecting ocular tissues of the rabbit against the harmful effects of UVB light, including photokeratitis and cataract.

  12. Contact dermatitis due to xanthium strumarium

    Directory of Open Access Journals (Sweden)

    J S Pasricha

    1990-01-01

    Full Text Available A 50-year-old mining engineer at Dhanbad was having air bome contact Dermatitis suspected to be caused by Xanthium strumarium. Patch tests with a 15% aqueous extract of air dried leaves showed a severe positive reaction, but the patient also had positive patch tests with Parthenium hysterphorus and a few other weeds and trees known to cause air-borne contact dermatitis. The titre of contact hypersensitivity with the extract of Xanthium struma′rium was more than 1:100,000 and for Parthenium hysterophrous it was 1:10 indicating a high degree of hypersensitivity to Xanthium strumarium. Further tests in 14 other patients revealed a high prevalence of cross sensitivity between these two plants both of which belong to the compositae family.

  13. A Pseudomonas aeruginosa strain isolated from a contact lens-induced acute red eye (CLARE) is protease-deficient.

    Science.gov (United States)

    Estrellas, P S; Alionte, L G; Hobden, J A

    2000-03-01

    Pseudomonas aeruginosa proteases are thought to be important virulence factors in the pathogenesis of corneal disease. This study examined protease production from two strains of P. aeruginosa responsible for two very distinct clinical diseases: strain Paer1, isolated from a Contact Lens-induced Acute Red Eye (CLARE), and strain KEI 1025, isolated from a corneal ulcer. Strains were compared to a laboratory strain (ATCC 19660) known to produce severe keratitis in experimentally infected mice for protease production and for ocular virulence. Protease production was examined with colorimetric assays, gelatin zymography and western blots. Elastase A activity was quantitated with a staphylolytic assay. Ocular virulence was examined using a mouse scratch model of keratitis. In contrast to strains KEI 1025 or ATCC 19660, Paer1 was unable to produce enzymatically active elastase A, elastase, and protease IV. All three strains produced active alkaline protease. Strains KEI 1025 and ATCC 19660 produced a fulminant keratitis in mice whereas Paer1 produced a mild transient infection. Restoration of elastase activity in Paer1 via genetic complementation did not result in a virulent phenotype. Co-infection of mouse eyes with strains Paer1 and ATCC 19660 resulted in the eventual loss of Paer1 from corneal tissue. These studies suggest that P. aeruginosa elastase A and/or protease IV, but not alkaline protease or elastase, contribute to the ocular virulence of this organism.

  14. Case of immediate hypersensitivity to beer.

    Science.gov (United States)

    Inoue, Tomoko; Yagami, Akiko; Shimojo, Naoshi; Hara, Kazuhiro; Nakamura, Masashi; Matsunaga, Kayoko

    2016-06-01

    We report here a case of immediate hypersensitivity to beer, in which a female patient developed angioedema of the eyelids shortly after consuming beer. In skin prick tests, the patient showed positive reactions to the base ingredients of beer, particularly malt and barley. The specific serum immunoglobulin E antibodies against barley and malt displayed weakly positive reactivity. To identify the immunoreactive antigens, malt and barley proteins were separated by 2-D polyacrylamide gel electrophoresis and immunoreacted with the patient's serum. The results of mass spectrometric analysis revealed that the main antigen was a protein with similarity to protein z-type serpin. Notably, the identified antigen had a molecular weight of 20-25 kDa, which is markedly smaller than that previously reported for protein Z4 (44 kDa). Taken together, these analyses indicate that a possible new antigen which belongs to the protein Z family elicits immediate hypersensitivity to beer. © 2015 Japanese Dermatological Association.

  15. Language Contact.

    Science.gov (United States)

    Nelde, Peter Hans

    1995-01-01

    Examines the phenomenon of language contact and recent trends in linguistic contact research, which focuses on language use, language users, and language spheres. Also discusses the role of linguistic and cultural conflicts in language contact situations. (13 references) (MDM)

  16. Patch testers' opinions regarding diagnostic criteria for metal hypersensitivity reactions to metallic implants.

    Science.gov (United States)

    Schalock, Peter C; Thyssen, Jacob P

    2013-01-01

    Metal hypersensitivity reactions to implanted devices remain a challenging and controversial topic. Diagnostic criteria and methods are not well delineated. Diagnostic criteria for hypersensitivity reactions after metallic device implantation are evaluated in this study by a multinational group of patch testers using Thyssen's previously published criteria. A total of 119 dermatologists at the 2012 European Contact Dermatitis Society and 2013 American Contact Dermatitis Society meetings answered a survey regarding their opinions on topics relating to metal hypersensitivity. Four major and 5 minor diagnostic criteria emerged. Approximately 80% of respondents found the following criteria useful (major criteria): chronic dermatitis beginning weeks to months after metallic implantation, eruption overlying the metal implant, positive patch test to a metal component of the implant, and complete clearing after removal of the potentially allergenic implant. Minor criteria (metals (eg, lymphocyte transformation test). In the challenging situation such as a symptomatic or failing orthopedic device, applying these 4 major criteria and the 5 supportive minor criteria may be useful for guiding decision making.

  17. Dentin Hypersensitivity: Recent Concepts in Management

    Directory of Open Access Journals (Sweden)

    Vijay Mantri

    2011-01-01

    Full Text Available Tooth sensitivity is a very common clinical presentation which can cause considerable concern for patients. Dentin hypersensitivity (DH is characterized by short sharp pain arising from exposed dentin in response to stimuli. The most widely accepted theory of how the pain occurs is Brannstrom′s hydrodynamic theory, fluid movement within the dentinal tubules. The condition generally involves the facial surfaces of teeth near the cervical aspect and is very common in premolars and canines. This condition is frequently encountered by dentists, periodontists, hygienists and dental therapists. Some dental professionals lack confidence in treating DH. The management of this condition requires a good understanding of the complexity of the problem, as well as the variety of treatments available. This review considers the etiopathogenesis, incidence, diagnosis, prevention and management of dentinal hypersensitivity. DH is diagnosed after elimination of other possible causes of the pain. Any treatment plan for DH should include identifying and eliminating predisposing etiologic factors. Professionals should appreciate the role causative factors play in localizing and initiating hypersensitive lesions. It is important to identify these factors so that prevention can be included in the treatment plan. Treatments can be self-administered by the patient at home or be applied by a dental professional in the dental office. At-home methods tend to be simple and inexpensive and can treat simultaneously generalized DH affecting many teeth Desensitizing treatment should be delivered systematically, beginning with prevention and at-home treatments. The latter may be supplemented with in-office modalities.

  18. Effect of Schizonepeta tenuifolia extract on mast cell-mediated immediate-type hypersensitivity in rats.

    Science.gov (United States)

    Shin, T Y; Jeong, H J; Jun, S M; Chae, H J; Kim, H R; Baek, S H; Kim, H M

    1999-11-01

    We investigated the effect of an aqueous extract of Schizonepeta tenuifolia (STAE) on mast cell-mediated immediate-type hypersensitivity. STAE inhibited systemic allergic reaction induced by compound 48/80 in rats dose-dependently. STAE also inhibited plasma histamine levels induced by compound 48/80. STAE inhibited local allergic reaction activated by anti-dinitrophenyl (DNP) IgE. In addition, STAE does-dependently inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. However, STAE had a significant enhancing effect on anti-DNP IgE-induced tumor necrosis factor-alpha (TNF-alpha) production from RPMC. These results indicate that STAE inhibits immediate-type hypersensitivity and suggest that STAE can selectively activate the TNF-alpha production from RPMC.

  19. Prevention of diabetes in NOD mice by repeated exposures to a contact allergen inducing a sub-clinical dermatitis

    DEFF Research Database (Denmark)

    Engkilde, Kaare; Buschard, Karsten; Hansen, Axel Jacob Kornerup

    2010-01-01

    Type 1 diabetes is an autoimmune disease, while allergic contact dermatitis although immune mediated, is considered an exposure driven disease that develops due to epicutaneous contact with reactive low-molecular chemicals. The objective of the present study was to experimentally study the effect...... of contact allergens on the development of diabetes in NOD mice. As the link between contact allergy and diabetes is yet unexplained we also examined the effect of provocation with allergens on Natural Killer T (NKT) cells, since involvement of NKT cells could suggest an innate connection between the two...

  20. Upregulation of Ih expressed in IB4-negative Aδ nociceptive DRG neurons contributes to mechanical hypersensitivity associated with cervical radiculopathic pain

    Science.gov (United States)

    Liu, Da-Lu; Lu, Na; Han, Wen-Juan; Chen, Rong-Gui; Cong, Rui; Xie, Rou-Gang; Zhang, Yu-Fei; Kong, Wei-Wei; Hu, San-Jue; Luo, Ceng

    2015-01-01

    Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron’s ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensitivity. Amongst nociceptive DRG neurons, a mechanically sensitive neuron, isolectin B4 negative Aδ-type (IB4− Aδ) DRG neuron displays spontaneous activity with hyperexcitability after chronic compression of cervical DRGs. Focal mechanical stimulation on somata of IB4- Aδ neuron induces abnormal hypersensitivity. Upregulated HCN1 and HCN3 channels and increased Ih current on this subset of primary nociceptors underlies the spontaneous activity together with neuronal mechanical hypersensitivity, which further contributes to the behavioral mechanical hypersensitivity associated with CRP. This study sheds new light on the functional plasticity of a specific subset of nociceptive DRG neurons to mechanical stimulation and reveals a novel mechanism that could underlie the mechanical hypersensitivity associated with cervical radiculopathy. PMID:26577374

  1. Adrenergic receptors are a fallible index of adrenergic denervation hypersensitivity

    DEFF Research Database (Denmark)

    Dejgaard, Anders; Liggett, S B; Christensen, N J

    1991-01-01

    In view of evidence that neither interindividual nor induced intra-individual variations of adrenergic receptor status are related to metabolic or haemodynamic sensitivity to adrenaline in vivo, we took an alternative approach to assessment of the relevance of adrenergic receptor measurement...... by measuring these in a group of subjects with well-documented adrenergic denervation hypersensitivity, patients with diabetic autonomic neuropathy. Mononuclear leukocyte beta 2-adrenergic receptor densities (and binding affinities), measured with 125I-labelled pindolol, and isoproterenol-stimulated cyclic AMP...... accumulation, in samples from patients with insulin-dependent diabetes mellitus (IDDM) with diabetic autonomic neuropathy (n = 8), were no different from those in samples from patients with IDDM without neuropathy (n = 8), or from non-diabetic subjects (n = 8). In addition, platelet alpha 2-adrenergic receptor...

  2. Autophagic components contribute to hypersensitive cell death in Arabidopsis

    DEFF Research Database (Denmark)

    Hofius, Daniel; Schultz-Larsen, Torsten; Joensen, Jan

    2009-01-01

    Autophagy has been implicated as a prosurvival mechanism to restrict programmed cell death (PCD) associated with the pathogen-triggered hypersensitive response (HR) during plant innate immunity. This model is based on the observation that HR lesions spread in plants with reduced autophagy gene...... expression. Here, we examined receptor-mediated HR PCD responses in autophagy-deficient Arabidopsis knockout mutants (atg), and show that infection-induced lesions are contained in atg mutants. We also provide evidence that HR cell death initiated via Toll/Interleukin-1 (TIR)-type immune receptors through...... the defense regulator EDS1 is suppressed in atg mutants. Furthermore, we demonstrate that PCD triggered by coiled-coil (CC)-type immune receptors via NDR1 is either autophagy-independent or engages autophagic components with cathepsins and other unidentified cell death mediators. Thus, autophagic cell death...

  3. Leukotriene B₄-leukotriene B₄ receptor axis promotes oxazolone-induced contact dermatitis by directing skin homing of neutrophils and CD8⁺ T cells.

    Science.gov (United States)

    Lv, Jiaoyan; Zou, Linlin; Zhao, Lina; Yang, Wei; Xiong, Yingluo; Li, Bingji; He, Rui

    2015-09-01

    Leukotriene B4 (LTB4 ) is a lipid mediator that is rapidly generated in inflammatory sites, and its functional receptor, BLT1, is mostly expressed on immune cells. Contact dermatitis is a common inflammatory skin disease characterized by skin oedema and abundant inflammatory infiltrates, primarily including neutrophils and CD8(+) T cells. The role of the LTB4 -BLT1 axis in contact dermatitis remains largely unknown. In this study, we found up-regulated gene expression of 5-lipoxygenase and leukotriene A4 hydrolase, two critical enzymes for LTB4 synthesis, BLT1 and elevated LTB4 levels in skin lesions of oxazolone (OXA)-induced contact dermatitis. BLT1 deficiency or blockade of LTB4 and BLT1 by the antagonists, bestatin and U-75302, respectively, in the elicitation phase caused significant decreases in ear swelling and skin-infiltrating neutrophils and CD8(+) T cells, which was accompanied by significantly reduced skin expression of CXCL1, CXCL2, interferon-γ and interleukin-1β. Furthermore, neutrophil depletion during the elicitation phase of OXA-induced contact dermatitis also caused significant decreases in ear swelling and CD8(+) T-cell infiltration accompanied by significantly decreased LTB4 synthesis and gene expression of CXCL2, interferon-γ and interleukin-1β. Importantly, subcutaneous injection of exogenous LTB4 restored the skin infiltration of CD8(+) T cells in neutrophil-depleted mice following OXA challenge. Collectively, our results demonstrate that the LTB4 -BLT1 axis contributes to OXA-induced contact dermatitis by mediating skin recruitment of neutrophils, which are a major source of LTB4 that sequentially direct CD8(+) T-cell homing to OXA-challenged skin. Hence, LTB4 and BLT1 could be potential therapeutic targets for the treatment of contact dermatitis. © 2015 John Wiley & Sons Ltd.

  4. Leukotriene B4—leukotriene B4 receptor axis promotes oxazolone-induced contact dermatitis by directing skin homing of neutrophils and CD8+ T cells

    Science.gov (United States)

    Lv, Jiaoyan; Zou, Linlin; Zhao, Lina; Yang, Wei; Xiong, Yingluo; Li, Bingji; He, Rui

    2015-01-01

    Leukotriene B4 (LTB4) is a lipid mediator that is rapidly generated in inflammatory sites, and its functional receptor, BLT1, is mostly expressed on immune cells. Contact dermatitis is a common inflammatory skin disease characterized by skin oedema and abundant inflammatory infiltrates, primarily including neutrophils and CD8+ T cells. The role of the LTB4–BLT1 axis in contact dermatitis remains largely unknown. In this study, we found up-regulated gene expression of 5-lipoxygenase and leukotriene A4 hydrolase, two critical enzymes for LTB4 synthesis, BLT1 and elevated LTB4 levels in skin lesions of oxazolone (OXA)-induced contact dermatitis. BLT1 deficiency or blockade of LTB4 and BLT1 by the antagonists, bestatin and U-75302, respectively, in the elicitation phase caused significant decreases in ear swelling and skin-infiltrating neutrophils and CD8+ T cells, which was accompanied by significantly reduced skin expression of CXCL1, CXCL2, interferon-γ and interleukin-1β. Furthermore, neutrophil depletion during the elicitation phase of OXA-induced contact dermatitis also caused significant decreases in ear swelling and CD8+ T-cell infiltration accompanied by significantly decreased LTB4 synthesis and gene expression of CXCL2, interferon-γ and interleukin-1β. Importantly, subcutaneous injection of exogenous LTB4 restored the skin infiltration of CD8+ T cells in neutrophil-depleted mice following OXA challenge. Collectively, our results demonstrate that the LTB4–BLT1 axis contributes to OXA-induced contact dermatitis by mediating skin recruitment of neutrophils, which are a major source of LTB4 that sequentially direct CD8+ T-cell homing to OXA-challenged skin. Hence, LTB4 and BLT1 could be potential therapeutic targets for the treatment of contact dermatitis. PMID:25959240

  5. Fasting mitigates immediate hypersensitivity: a pivotal role of endogenous D-beta-hydroxybutyrate.

    Science.gov (United States)

    Nakamura, Shigeru; Hisamura, Ryuji; Shimoda, Sachiko; Shibuya, Izumi; Tsubota, Kazuo

    2014-01-01

    Fasting is a rigorous type of dietary restriction that is associate with a number of health benefits. During fasting, ketone bodies significantly increase in blood and become major body fuels, thereby sparing glucose. In the present study, we investigated effects of fasting on hypersensitivity. In addition, we also investigated the possible role of D-beta-hydroxybutyrate provoked by fasting in the attenuation of immediate hypersensitivity by fasting. Effects of fasting on systemic anaphylaxis were examined using rat model of toluene 2, 4-diisocyanate induced nasal allergy. In addition to food restriction, a ketogenic high-fat and low-carbohydrate diet that accelerates fatty acid oxidation and systemic instillation of D-beta-hydroxybutyrate were employed to elevate internal D-beta-hydroxybutyrate concentration. We assessed relationship between degranulation of rat peritoneal mast cells and internal D-beta-hydroxybutyrate concentration in each treatment. Changes in [Ca(2+)]i responses to compound 48/80 were analyzed in fura 2-loaded rat peritoneal mast cells derived from the ketogenic diet and fasting. Immediate hypersensitivity reaction was significantly suppressed by fasting. A significant reduction in mast cells degranulation, induced by mast cell activator compound 48/80, was observed in rat peritoneal mast cells delivered from the 24 hours fasting treatment. In addition, mast cells delivered from a ketogenic diet and D-beta-hydroxybutyrate infusion treatment also had reduced mast cell degranulation and systemic D-beta-hydroxybutyrate concentrations were elevated to similar extent as the fasting state. The peak increase in [Ca(2+)]i was significantly lower in the ketogenic diet and fasting group than that in the control diet group. The results of the present study demonstrates that fasting suppress hypersensitivity reaction, and indicate that increased level of D-beta-hydroxybutyrate by fasting plays an important role, via the stabilization of mast cells, in

  6. Is dermatitis palmaris sicca an irritant contact dermatitis?

    Science.gov (United States)

    Chen, Fu-Juan; Liu, Zhen; Zhou, Ying; Chen, Yong-Hua; Fan, Yi-Ming

    2013-01-01

    Dermatitis palmaris sicca (DPS) is a common dry-fissured palmar dermatitis in Asian women. It may be an irritant contact dermatitis, but the immunophenotype of the cells in its infiltrate is unknown. The aim of this study was to evaluate the role of inflammatory cells in the pathogenesis of DPS. Patch testing was done in 68 patients with DPS, 87 subjects with hand eczema, and 31 healthy subjects. Immunophenotyping of cutaneous inflammatory cells was performed in 8 patients with DPS, 10 subjects with hand eczema, and 8 healthy individuals. Positive patch rates were higher in patients with DPS and those with hand eczema compared with healthy controls, but strong positive (++ or +++) reactions in DPS were fewer compared with hand eczema. Density of CD3, CD4, CD8, and CD68 cells in skin lesions of DPS and hand eczema was significantly higher than that in normal skin. Sparse CD20 cells were present only in hand eczema. Compared with hand eczema, the number of CD3, CD8, CD68, and dermal CD1a cells decreased, but epidermal CD1a cells and CD4/CD8 ratio increased in DPS. The absolute lack of CD20 cells and relative scarcity of dermal CD8 and CD1a cells in skin lesions might be insufficient to induce contact hypersensitivity, so DPS may be an irritant but not allergic contact dermatitis.

  7. Contact Dermatitis for the Practicing Allergist.

    Science.gov (United States)

    Bernstein, David I

    2015-01-01

    This article provides an overview of important practice recommendations from the recently updated Contact Dermatitis Practice Parameter. This updated parameter provides essential recommendations pertaining to clinical history, physical examination, and patch testing evaluation of patients suspected of allergic contact dermatitis. In addition to providing guidance for performing and interpreting closed patch testing, the updated parameter provides concrete recommendations for assessing metal hypersensitivity in patients receiving prosthetic devices, for evaluating workers with occupational contact dermatitis, and also for addressing allergic contact dermatitis in children. Finally, the document provides practical recommendations useful for educating patients regarding avoidance of exposure to known contact sensitizers in the home and at work. The Contact Dermatitis Parameter is designed as a practical, evidence-based clinical tool to be used by allergists and dermatologists who routinely are called upon to evaluate patients with skin disorders. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. Povidone-iodine induced post-surgical irritant contact dermatitis localized outside of the surgical incision area. Report of 27 cases and a literature review.

    Science.gov (United States)

    Borrego, Leopoldo; Hernández, Noelia; Hernández, Zaida; Peñate, Yeray

    2016-05-01

    Povidone-iodine solution is an antiseptic that is used worldwide as surgical paint and is considered to have a low irritant potential. Post-surgical severe irritant dermatitis has been described after the misuse of this antiseptic in the surgical setting. Between January 2011 and June 2013, 27 consecutive patients with post-surgical contact dermatitis localized outside of the surgical incision area were evaluated. Thirteen patients were also available for patch testing. All patients developed dermatitis the day after the surgical procedure. Povidone-iodine solution was the only liquid in contact with the skin of our patients. Most typical lesions were distributed in a double lumbar parallel pattern, but they were also found in a random pattern or in areas where a protective pad or an occlusive medical device was glued to the skin. The patch test results with povidone-iodine were negative. Povidone-iodine-induced post-surgical dermatitis may be a severe complication after prolonged surgical procedures. As stated in the literature and based on the observation that povidone-iodine-induced contact irritant dermatitis occurred in areas of pooling or occlusion, we speculate that povidone-iodine together with occlusion were the causes of the dermatitis epidemic that occurred in our surgical setting. Povidone-iodine dermatitis is a problem that is easily preventable through the implementation of minimal routine changes to adequately dry the solution in contact with the skin. © 2015 The International Society of Dermatology.

  9. Piezo2: A Candidate Biomarker for Visceral Hypersensitivity in Irritable Bowel Syndrome?

    OpenAIRE

    Bai, Tao; Li, Ying; Xia, Jing; Jiang, Yudong; Zhang, Lei; Wang, Huan; Qian, Wei; Song, Jun; Hou, Xiaohua

    2017-01-01

    Background/Aims Currently, there exists no biomarker for visceral hypersensitivity in irritable bowel syndrome (IBS). Piezo proteins have been proven to play an important role in the mechanical stimulation to induce visceral pain in other tissues and may also be a biomarker candidate. The aim of this study was to test the expressions of Piezo1 and Piezo2 proteins in the intestinal epithelial cells from different intestinal segments and to explore the correlation between Piezo proteins express...

  10. Drug desensitization in the management of hypersensitivity reactions to monoclonal antibodies and chemotherapy.

    Science.gov (United States)

    Mezzano, Veronica; Giavina-Bianchi, Pedro; Picard, Matthieu; Caiado, Joana; Castells, Mariana

    2014-04-01

    Hypersensitivity reactions to monoclonal antibodies and chemotherapy, which may vary in severity from mild to life-threatening, can lead to their discontinuation and replacement by alternative agents that are often less effective, more toxic, and/or more expensive. Drug desensitization has emerged as the best treatment modality capable of allowing re-introduction of the hypersensitivity reaction-inducing medication in highly sensitized patients in need of first line therapies. In recent years, the availability of new anti-neoplastic drugs and therapeutic monoclonal antibodies has increased, as has the potential for hypersensitivity reactions. Development of desensitization protocols for these new medications requires a careful assessment of the potential risks and benefits. The purposes of this review are to provide an overview of the presentation of hypersensitivity reactions amenable to desensitization and to increase awareness of the indications for and outcomes of desensitization protocols. Rapid drug desensitization has proven to be a safe and effective way of administering first line therapy to patients with hypersensitivity reactions, providing an extremely powerful treatment modality for patients for whom alternative drugs are deemed unacceptable. Rapid drug desensitization protocols should be administered only by highly trained allergists and nurses who have experience in determining which reactions are amenable to desensitization, and can identify high risk patients and provide them with appropriate care. Efforts should be made to increase awareness of the remarkable safety and efficacy of rapid drug desensitization among non-allergists, especially in the fields of oncology and rheumatology, so as to favor its universal application. Development of desensitization units to provide state-of-the-art care is possible only through coordinated teamwork.

  11. Quantitative Risk Assessment of Contact Sensitization

    DEFF Research Database (Denmark)

    Api, Anne Marie; Belsito, Donald; Bickers, David

    2010-01-01

    Background: Contact hypersensitivity quantitative risk assessment (QRA) for fragrance ingredients is being used to establish new international standards for all fragrance ingredients that are potential skin sensitizers. Objective: The objective was to evaluate the retrospective clinical data...... as potential sensitizers. Methods: This article reviews clinical data for three fragrance ingredients cinnamic aldehyde, citral, and isoeugenol to assess the utility of the QRA approach for fragrance ingredients. Results: This assessment suggests that had the QRA approach been available at the time standards...

  12. The Link between Hypersensitivity Syndrome Reaction Development and Human Herpes Virus-6 Reactivation

    Directory of Open Access Journals (Sweden)

    Joshua C. Pritchett

    2012-01-01

    Data Sources and Extraction. Drugs identified as causes of (i idiosyncratic reactions, (ii drug-induced hypersensitivity, drug-induced hepatotoxicity, acute liver failure, and Stevens-Johnson syndrome, and (iii human herpes virus reactivation in PubMed since 1997 have been collected and discussed. Results. Data presented in this paper show that HHV-6 reactivation is associated with more severe organ involvement and a prolonged course of disease. Conclusion. This analysis of HHV-6 reactivation associated with drug-induced severe cutaneous reactions and hepatotoxicity will aid in causality assessment and clinical diagnosis of possible life-threatening events and will provide a basis for further patient characterization and therapy.

  13. Recombinant culicoides obsoletus complex allergens stimulate antigen-specific T cells on insect bite hypersensitive Shetland ponies in vitro

    NARCIS (Netherlands)

    Meulenbroeks, C.; Meide, van der N.M.A.; Willemse, T.; Rutten, V.; Tijhaar, E.J.

    2015-01-01

    Background Ponies may suffer from Insect bite hypersensitivity (IBH), an allergic IgE-mediated pruritic skin disorder, induced by allergens from biting midges of the Culicoides spp. Hypothesis/Objectives To determine whether recombinant Culicoides obsoletus allergens are able to activate T cells of

  14. An unusual oral habit presenting as Dentin Hypersensitivity | Afolabi ...

    African Journals Online (AJOL)

    We present the case of a 30-year-old man with an unusual oral habit- office pin chewing and filing of the front tooth which resulted in dentine hypersensitivity. Clinical relevance: The role of daily oral habits and techniques of cessation were suggested in the management of dentine hypersensitivity. Keywords: Unusual oral ...

  15. Teenagers' experiences of living with food hypersensitivity: a qualitative study.

    Science.gov (United States)

    MacKenzie, Heather; Roberts, Graham; van Laar, Darren; Dean, Taraneh

    2010-06-01

    Teenagers are a high-risk group for food-hypersensitivity fatalities, engage in risk-taking behaviours and may experience impaired quality of life. Understanding their experience is important to inform their care. This study aimed to describe the lived experiences of teenagers with food hypersensitivity. Individual semi-structured interviews were conducted with 21 teenagers (13-18 yr) with food hypersensitivity to a variety of foods and analysed using a phenomenological approach. Teenagers described living with (or coming to know) food hypersensitivity (FHS) as a way of life but still found living with food hypersensitivity to be burdensome. A necessary part of living with food hypersensitivity was coping with associated burden; a variety of coping strategies were employed to this effect. Teenagers described ways in which the burden of living with food hypersensitivity was alleviated or exacerbated by others. Management of food hypersensitivity was based on an assessment of acceptable risk resulting in varying levels of precaution taking. Teenagers' understanding of their FHS and ability to cope with it needs to be regularly assessed. Educational support may be required to ensure they take an appropriate level of precautions to minimize the chance of future reactions while not over compromising their quality of life. Psychological support may be required to help them to utilize healthy adaptive strategies to cope with the stresses of living with FHS. This approach is also likely to facilitate the smooth handover of responsibility from parent to teenager.

  16. Association between Severity of Tooth Wear and Dentinal Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Ashok Ayer

    2016-11-01

    Full Text Available Background & Objectives: Tooth wear (attrition, abrasion, erosion, and abfraction is perceived globally as ever increasing problem. Several outcome of the tooth wear are hypersensitivity, esthetic problems, functional impairment, annoyance to the patient, and fracture of the tooth. Among these, the measurable and more commonly reported outcome is hypersensitivity to stimuli. Although dentin hypersensitivity is a common clinical condition and is generally reported by the patient after experiencing a sharp, short pain caused by one of the several different external stimuli, it is often inadequately understood. None of the scientific literature available till date attempted to establish the relationship between tooth wear and dentin hypersensitivity which could be a key factor in monitoring those patients.  The aim of the study was to estimate the association between severity of teeth wear and sensitivity in the patients with reported dentinal hypersensitivity.Materials & Methods: Fifty patients with dentin hypersensitivity were investigated for tooth wear. Tooth wear measured using exact tooth wear index and level of sensitivity to stimuli was recorded using a numerical rating scale. Results: Enamel wear at cervical region of teeth showed a positive correlation (p=.010, similarly, dentin wear at cervical region of teeth showed positive correlation and significant association (p<.001 with dentinal hypersensitivity.Conclusion: The observation supports a significant association between severities of tooth surface wear and dentinal hypersensitivity.

  17. Cytokine overproduction and crosslinker hypersensitivity are unlinked in Fanconi anemia macrophages.

    Science.gov (United States)

    Garbati, Michael R; Hays, Laura E; Rathbun, R Keaney; Jillette, Nathaniel; Chin, Kathy; Al-Dhalimy, Muhsen; Agarwal, Anupriya; Newell, Amy E Hanlon; Olson, Susan B; Bagby, Grover C

    2016-03-01

    The Fanconi anemia proteins participate in a canonical pathway that repairs cross-linking agent-induced DNA damage. Cells with inactivated Fanconi anemia genes are universally hypersensitive to such agents. Fanconi anemia-deficient hematopoietic stem cells are also hypersensitive to inflammatory cytokines, and, as importantly, Fanconi anemia macrophages overproduce such cytokines in response to TLR4 and TLR7/8 agonists. We questioned whether TLR-induced DNA damage is the primary cause of aberrantly regulated cytokine production in Fanconi anemia macrophages by quantifying TLR agonist-induced TNF-α production, DNA strand breaks, crosslinker-induced chromosomal breakage, and Fanconi anemia core complex function in Fanconi anemia complementation group C-deficient human and murine macrophages. Although both M1 and M2 polarized Fanconi anemia cells were predictably hypersensitive to mitomycin C, only M1 macrophages overproduced TNF-α in response to TLR-activating signals. DNA damaging agents alone did not induce TNF-α production in the absence of TLR agonists in wild-type or Fanconi anemia macrophages, and mitomycin C did not enhance TLR responses in either normal or Fanconi anemia cells. TLR4 and TLR7/8 activation induced cytokine overproduction in Fanconi anemia macrophages. Also, although TLR4 activation was associated with induced double strand breaks, TLR7/8 activation was not. That DNA strand breaks and chromosome breaks are neither necessary nor sufficient to account for the overproduction of inflammatory cytokines by Fanconi anemia cells suggests that noncanonical anti-inflammatory functions of Fanconi anemia complementation group C contribute to the aberrant macrophage phenotype and suggests that suppression of macrophage/TLR hyperreactivity might prevent cytokine-induced stem cell attrition in Fanconi anemia. © Society for Leukocyte Biology.

  18. A Class I UV-Blocking (senofilcon A) Soft Contact Lens Prevents UVA-induced Yellow Fluorescence and NADH loss in the Rabbit Lens Nucleus in vivo

    Science.gov (United States)

    Giblin, Frank J.; Lin, Li-Ren; Simpanya, Mukoma F.; Leverenz, Victor R.; Fick, Catherine E.

    2012-01-01

    It is known that fluorescence, much of it caused by UVA light excitation, increases in the aging human lens, resulting in loss of sharp vision. This study used an in vivo animal model to investigate UVA-excited fluorescence in the rabbit lens, which contains a high level of the UVA chromophore NADH, existing both free and bound to λ-crystallin. Also, the ability of a Class I (senofilcon A) soft contact lens to protect against UVA-induced effects on the rabbit lens was tested. Rabbit eyes were irradiated with UVA light in vivo (100 mW/cm2 on the cornea) for 1 hour using monochromatic 365 nm light. Irradiation was conducted in the presence of either a senofilcon A contact lens, a minimally UV-absorbing lotrafilcon A contact lens, or no contact lens at all. Eyes irradiated without a contact lens showed blue 365 nm-excited fluorescence initially, but this changed to intense yellow fluorescence after 1 hour. Isolated, previously irradiated lenses exhibited yellow fluorescence originating from the lens nucleus when viewed under 365 nm light, but showed normal blue fluorescence arising from the cortex. Previously irradiated lenses also exhibited a faint yellow color when observed under visible light. The senofilcon A contact lens protected completely against the UVA-induced effects on fluorescence and lens yellowing, whereas the lotrafilcon A lens showed no protection. The UVA-exposure also produced a 53% loss of total NADH (free plus bound) in the lens nucleus, with only a 13% drop in the anterior cortex. NADH loss in the nucleus was completely prevented with use of a senofilcon A contact lens, but no significant protection was observed with a lotrafilcon A lens. Overall, the senofilcon A lens provided an average of 67% protection against UVA-induced loss of four pyridine nucleotides in four different regions of the lens. HPLC analysis with fluorescence detection indicated a nearly six-fold increase in 365 nm-excited yellow fluorescence arising from lens nuclear

  19. Clinical efficacy of toothpaste containing potassium citrate in treating dentin hypersensitivity

    Directory of Open Access Journals (Sweden)

    Shih-Ya Shen

    2009-12-01

    Conclusion: The prevalence of dentin hypersensitivity in this study was 38%. The use of desensitizing toothpaste containing potassium citrate with oral hygiene instruction can effectively reduce dentin hypersensitivity.

  20. Non-contact test of coating by means of laser-induced ultrasonic excitation and holographic sound representation

    International Nuclear Information System (INIS)

    Crostack, H.A.; Pohl, K.Y.; Radtke, U.

    1991-01-01

    In order to circumvent the problems of introducing and picking off sound, which occur in conventional ultrasonic testing, a completely non-contact test process was developed. The ultrasonic surface wave required for the test is generated without contact by absorption of laser beams. The recording of the ultrasound also occurs by a non-contact holographic interferometry technique, which permits a large scale representation of the sound. Using the example of MCrAlY and ZrO 2 layers, the suitability of the process for testing thermally sprayed coatings on metal substrates is identified. The possibilities and limits of the process for the detection and description of delamination and cracks are shown. (orig.) [de

  1. Changes in homologous and heterologous gap junction contacts during maturation-inducing hormone-dependent meiotic resumption in ovarian follicles of Atlantic croaker

    Science.gov (United States)

    Bolamba, D.; Patino, R.; Yoshizaki, G.; Thomas, P.

    2003-01-01

    Homologous (granulosa cell-granulosa cell) gap junction (GJ) contacts increase in ovarian follicles of Atlantic croaker (Micropogonias undulatus) during the early (first) stage of maturation, but their profile during the second stage [i.e., during maturation-inducing hormone (MIH)-mediated meiotic resumption] is unknown. The profile of homologous GJ contacts during the second stage of maturation in croaker follicles was examined in this study and compared to that of heterologous (granulosa cell-oocyte) GJ, for which changes have been previously documented. Follicles were incubated with human chorionic gonadotropin to induce maturational competence (first stage), and then with MIH to induce meiotic resumption. The follicles were collected for examination immediately before and after different durations of MIH exposure until the oocyte had reached the stage of germinal vesicle breakdown (GVBD; index of meiotic resumption). Ultrathin sections were observed by transmission electron microscopy, and homologous and heterologous GJ contacts were quantified along a 100-??m segment of granulosa cell-zona radiata complex per follicle (three follicles/time/fish, n=3 fish). Relatively high numbers of both types of GJ were observed before and after the first few hours of MIH exposure (up to the stage of oil droplet coalescence). GJ numbers declined during partial yolk globule coalescence (at or near GVBD) and were just under 50% of starting values after the completion of GVBD (P<0.05). These results confirm earlier observations that GVBD temporally correlates with declining heterologous GJ contacts, and for the first time in teleosts show that there is a parallel decline in homologous GJ. The significance of the changes in homologous and heterologous GJ is uncertain and deserves further study. ?? 2003 Elsevier Science (USA). All rights reserved.

  2. Development of a novel non-contact inspection technique to detect micro cracks under the surface of a glass substrate by thermal stress-induced light scattering method

    Science.gov (United States)

    Sakata, Yoshitaro; Terasaki, Nao; Nonaka, Kazuhiro

    2017-05-01

    Fine polishing techniques, such as a chemical mechanical polishing treatment, are important techniques in glass substrate manufacturing. However, these techniques may cause micro cracks under the surface of glass substrates because they used mechanical friction. A stress-induced light scattering method (SILSM), which was combined with light scattering method and mechanical stress effects, was proposed for inspecting surfaces to detect polishing-induced micro cracks. However, in the conventional SILSM, samples need to be loaded with physical contact, and the loading point is invisible in transparent materials. Here, we introduced a novel non-contact SILSM using a heating device. A glass substrate was heated first, and then the light scattering intensity of micro cracks was detected by a cooled charge-couple device camera during the natural cooling process. Results clearly showed during the decreasing surface temperature of a glass substrate, appropriate thermal stress is generated for detecting micro cracks by using the SILSM and light scattering intensity from micro cracks changes. We confirmed that non-contact thermal SILSM (T-SILSM) can detect micro cracks under the surface of transparent materials.

  3. (001) 3C SiC/Ni contact interface: In situ XPS observation of annealing induced Ni2Si formation and the resulting barrier height changes

    Science.gov (United States)

    Tengeler, Sven; Kaiser, Bernhard; Chaussende, Didier; Jaegermann, Wolfram

    2017-04-01

    The electronic states of the (001) 3C SiC/Ni interface prior and post annealing are investigated via an in situ XPS interface experiment, allowing direct observation of the induced band bending and the transformation from Schottky to ohmic behaviour for the first time. A single domain (001) 3C SiC sample was prepared via wet chemical etching. Nickel was deposited on the sample in multiple in situ deposition steps via RF sputtering, allowing observation of the 3C SiC/Ni interface formation. Over the course of the experiments, an upward band bending of 0.35 eV was observed, along with defect induced Fermi level pinning. This indicates a Schottky type contact behaviour with a barrier height of 0.41 eV. The subsequent annealing at 850 °C for 5 min resulted in the formation of a Ni2Si layer and a reversal of the band bending to 0.06 eV downward. Thus explaining the ohmic contact behaviour frequently reported for annealed n-type 3C SiC/Ni contacts.

  4. Current induced multi-mode propagating spin waves in a spin transfer torque nano-contact with strong perpendicular magnetic anisotropy

    Science.gov (United States)

    Mohseni, S. Morteza; Yazdi, H. F.; Hamdi, M.; Brächer, T.; Mohseni, S. Majid

    2018-03-01

    Current induced spin wave excitations in spin transfer torque nano-contacts are known as a promising way to generate exchange-dominated spin waves at the nano-scale. It has been shown that when these systems are magnetized in the film plane, broken spatial symmetry of the field around the nano-contact induced by the Oersted field opens the possibility for spin wave mode co-existence including a non-linear self-localized spin-wave bullet and a propagating mode. By means of micromagnetic simulations, here we show that in systems with strong perpendicular magnetic anisotropy (PMA) in the free layer, two propagating spin wave modes with different frequency and spatial distribution can be excited simultaneously. Our results indicate that in-plane magnetized spin transfer nano-contacts in PMA materials do not host a solitonic self-localized spin-wave bullet, which is different from previous studies for systems with in plane magnetic anisotropy. This feature renders them interesting for nano-scale magnonic waveguides and crystals since magnon transport can be configured by tuning the applied current.

  5. (001) 3C SiC/Ni contact interface: In situ XPS observation of annealing induced Ni{sub 2}Si formation and the resulting barrier height changes

    Energy Technology Data Exchange (ETDEWEB)

    Tengeler, Sven, E-mail: stengeler@surface.tu-darmstadt.de [Institute of Material Science, Technische Universität Darmstadt, 64287 Darmstadt (Germany); Univ. Grenoble Alpes, CNRS, LMGP, F-38000 Grenoble (France); Kaiser, Bernhard [Institute of Material Science, Technische Universität Darmstadt, 64287 Darmstadt (Germany); Chaussende, Didier [Univ. Grenoble Alpes, CNRS, LMGP, F-38000 Grenoble (France); Jaegermann, Wolfram [Institute of Material Science, Technische Universität Darmstadt, 64287 Darmstadt (Germany)

    2017-04-01

    Highlights: • Schottky behavior (Φ{sub B} = 0.41 eV) and Fermi level pining were found pre annealing. • Ni{sub 2}Si formation was confirmed for 5 min at 850 °C. • 3C/Ni{sub 2}Si Fermi level alignment is responsible for ohmic contact behavior. • Wet chemical etching (Si–OH/C–H termination) does not impair Ni{sub 2}Si formation. - Abstract: The electronic states of the (001) 3C SiC/Ni interface prior and post annealing are investigated via an in situ XPS interface experiment, allowing direct observation of the induced band bending and the transformation from Schottky to ohmic behaviour for the first time. A single domain (001) 3C SiC sample was prepared via wet chemical etching. Nickel was deposited on the sample in multiple in situ deposition steps via RF sputtering, allowing observation of the 3C SiC/Ni interface formation. Over the course of the experiments, an upward band bending of 0.35 eV was observed, along with defect induced Fermi level pinning. This indicates a Schottky type contact behaviour with a barrier height of 0.41 eV. The subsequent annealing at 850 °C for 5 min resulted in the formation of a Ni{sub 2}Si layer and a reversal of the band bending to 0.06 eV downward. Thus explaining the ohmic contact behaviour frequently reported for annealed n-type 3C SiC/Ni contacts.

  6. (001) 3C SiC/Ni contact interface: In situ XPS observation of annealing induced Ni_2Si formation and the resulting barrier height changes

    International Nuclear Information System (INIS)

    Tengeler, Sven; Kaiser, Bernhard; Chaussende, Didier; Jaegermann, Wolfram

    2017-01-01

    Highlights: • Schottky behavior (Φ_B = 0.41 eV) and Fermi level pining were found pre annealing. • Ni_2Si formation was confirmed for 5 min at 850 °C. • 3C/Ni_2Si Fermi level alignment is responsible for ohmic contact behavior. • Wet chemical etching (Si–OH/C–H termination) does not impair Ni_2Si formation. - Abstract: The electronic states of the (001) 3C SiC/Ni interface prior and post annealing are investigated via an in situ XPS interface experiment, allowing direct observation of the induced band bending and the transformation from Schottky to ohmic behaviour for the first time. A single domain (001) 3C SiC sample was prepared via wet chemical etching. Nickel was deposited on the sample in multiple in situ deposition steps via RF sputtering, allowing observation of the 3C SiC/Ni interface formation. Over the course of the experiments, an upward band bending of 0.35 eV was observed, along with defect induced Fermi level pinning. This indicates a Schottky type contact behaviour with a barrier height of 0.41 eV. The subsequent annealing at 850 °C for 5 min resulted in the formation of a Ni_2Si layer and a reversal of the band bending to 0.06 eV downward. Thus explaining the ohmic contact behaviour frequently reported for annealed n-type 3C SiC/Ni contacts.

  7. Allergic contact dermatitis to propolis in a violin maker.

    Science.gov (United States)

    Lieberman, Heather D; Fogelman, Joshua P; Ramsay, David L; Cohen, David E

    2002-02-01

    Allergy to colophony is well noted in the literature, however, there have been few case reports of allergic contact dermatitis to propolis in musicians and instrument makers. We report a case of a stringed instrument craftsman who developed allergic contact dermatitis to propolis, a component of Italian varnish. A review of the components, applications, and the clinical manifestations of hypersensitivity reactions to propolis are presented.

  8. Tumor endothelial marker 5 expression in endothelial cells during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Vallon, Mario, E-mail: m.vallon@arcor.de [Nuklearmedizinische Klinik und Poliklinik, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Munich (Germany); Rohde, Franziska; Janssen, Klaus-Peter [Chirurgische Klinik und Poliklinik, Technische Universitaet Muenchen, Munich (Germany); Essler, Markus [Nuklearmedizinische Klinik und Poliklinik, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Munich (Germany)

    2010-02-01

    Tumor endothelial marker (TEM) 5 is an adhesion G-protein-coupled receptor upregulated in endothelial cells during tumor and physiologic angiogenesis. So far, the mechanisms leading to upregulation of TEM5 and its function during angiogenesis have not been identified. Here, we report that TEM5 expression in endothelial cells is induced during capillary-like network formation on Matrigel, during capillary morphogenesis in a three-dimensional collagen I matrix, and upon confluence on a two-dimensional matrix. TEM5 expression was not induced by a variety of soluble angiogenic factors, including VEGF and bFGF, in subconfluent endothelial cells. TEM5 upregulation was blocked by toxin B from Clostridium difficile, an inhibitor of the small GTPases Rho, Rac, and Cdc42. The Rho inhibitor C3 transferase from Clostridium botulinum did not affect TEM5 expression, whereas the Rac inhibitor NSC23766 suppressed TEM5 upregulation. An excess of the soluble TEM5 extracellular domain or an inhibitory monoclonal TEM5 antibody blocked contact inhibition of endothelial cell proliferation resulting in multilayered islands within the endothelial monolayer and increased vessel density during capillary formation. Based on our results we conclude that TEM5 expression during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of proliferation in endothelial cells.

  9. Outpatient desensitization in selected patients with platinum hypersensitivity reactions.

    Science.gov (United States)

    O'Malley, David M; Vetter, Monica Hagan; Cohn, David E; Khan, Ambar; Hays, John L

    2017-06-01

    Platinum-based chemotherapies are a standard treatment for both initial and recurrent gynecologic cancers. Given this widespread use, it is important to be aware of the features of platinum hypersensitivity reactions and the subsequent treatment of these reactions. There is also increasing interest in the development of desensitization protocols to allow patients with a history of platinum hypersensitivity to receive further platinum based therapy. In this review, we describe the management of platinum hypersensitivity reactions and the desensitization protocols utilized at our institution. We also describe the clinical categorizations utilized to triage patients to appropriate desensitization protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Diode laser-induced tissue effects: in vitro tissue model study and in vivo evaluation of wound healing following non-contact application.

    Science.gov (United States)

    Havel, Miriam; Betz, Christian S; Leunig, Andreas; Sroka, Ronald

    2014-08-01

    The basic difference between the various common medical laser systems is the wavelength of the emitted light, leading to altered light-tissue interactions due to the optical parameters of the tissue. This study examines laser induced tissue effects in an in vitro tissue model using 1,470 nm diode laser compared to our standard practice for endonasal applications (940 nm diode laser) under standardised and reproducible conditions. Additionally, in vivo induced tissue effects following non-contact application with focus on mucosal healing were investigated in a controlled intra-individual design in patients treated for hypertrophy of nasal turbinate. A certified diode laser system emitting the light of λ = 1470 nm was evaluated with regards to its tissue effects (ablation, coagulation) in an in vitro setup on porcine liver and turkey muscle tissue model. To achieve comparable macroscopic tissue effects the laser fibres (600 µm core diameter) were fixed to a computer controlled stepper motor and the laser light was applied in a reproducible procedure under constant conditions. For the in vivo evaluation, 20 patients with nasal obstruction due to hyperplasia of inferior nasal turbinates were included in this prospective randomised double-blinded comparative trial. The endoscopic controlled endonasal application of λ = 1470 nm on the one and λ = 940 nm on the other side, both in 'non-contact' mode, was carried out as an outpatient procedure under local anaesthesia. The postoperative wound healing process (mucosal swelling, scab formation, bleeding, infection) was endoscopically documented and assessed by an independent physician. In the experimental setup, the 1,470 nm laser diode system proved to be efficient in inducing tissue effects in non-contact mode with a reduced energy factor of 5-10 for highly perfused liver tissue to 10-20 for muscle tissue as compared to the 940 nm diode laser system. In the in vivo evaluation scab formation

  11. European Society of Contact Dermatitis guideline for diagnostic patch testing -- recommendations on best practice

    DEFF Research Database (Denmark)

    Johansen, Jeanne D; Aalto-Korte, Kristiina; Agner, Tove

    2015-01-01

    The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions an...

  12. Plasticity in intact A delta- and C-fibers contributes to cold hypersensitivity in neuropathic rats.

    Science.gov (United States)

    Ji, G; Zhou, S; Kochukov, M Y; Westlund, K N; Carlton, S M

    2007-11-30

    Cold hypersensitivity is a common sensory abnormality accompanying peripheral neuropathies and is difficult to treat. Progress has been made in understanding peripheral mechanisms underlying neuropathic pain but little is known concerning peripheral mechanisms of cold hypersensitivity. The aim of this study was to analyze the contribution of uninjured primary afferents to the cold hypersensitivity that develops in neuropathic rats. Rats with a lumbar 5 (L5) and L6 spinal nerve ligation (SNL, Chung model) but not sham, developed mechanical allodynia, evidenced by decreased paw withdrawal thresholds and increased magnitude of response to von Frey stimulation. Cold hypersensitivity also developed in SNL but not sham rats, evidenced by enhanced nociceptive behaviors induced by placement on a cold plate (6 degrees C) or application of icilin (a transient receptor potential M8 (TRPM8)/transient receptor potential A1 (TRPA1) receptor agonist) to nerve-injured hind paws. Single fiber recordings demonstrated that the mean conduction velocities of intact L4 cutaneous A delta- and C-fibers were not different between naive and SNL rats; however, mechanical thresholds of the A delta- but not the C-fibers were significantly decreased in SNL compared with naive. There was a higher prevalence of C-mechanoheat-cold (CMHC) fibers in SNL compared with naive, but the overall percentage of cold-sensitive C-fibers was not significantly increased compared with naive. This was in contrast to the numerous changes in A delta-fibers: the percentage of L4 cold sensitive A delta-, but not C-fibers, was significantly increased, the percentage of L4 icilin-sensitive A delta-, but not C-fibers, was significantly increased, the icilin-induced activity of L4 A delta-, but not C-fibers, was significantly increased. Icilin-induced activity was blocked by the TRPA1 antagonist Ruthenium Red. The results indicate plasticity in both A delta- and C-uninjured fibers, but A delta fibers appear to provide a

  13. Tumor Necrosis Factor Alpha Signaling in Trigeminal Ganglion Contributes to Mechanical Hypersensitivity in Masseter Muscle During Temporomandibular Joint Inflammation.

    Science.gov (United States)

    Ito, Reio; Shinoda, Masamichi; Honda, Kuniya; Urata, Kentaro; Lee, Jun; Maruno, Mitsuru; Soma, Kumi; Okada, Shinji; Gionhaku, Nobuhito; Iwata, Koichi

    To determine the involvement of tumor necrosis factor alpha (TNFα) signaling in the trigeminal ganglion (TG) in the mechanical hypersensitivity of the masseter muscle during temporomandibular joint (TMJ) inflammation. A total of 55 male Sprague-Dawley rats were used. Following injection of Complete Freund's Adjuvant into the TMJ, the mechanical sensitivities of the masseter muscle and the overlying facial skin were measured. Satellite glial cell (SGC) activation and TNFα expression in the TG were investigated immunohistochemically, and the effects of their inhibition on the mechanical hypersensitivity of the masseter muscle were also examined. Student t test or two-way repeated-measures analysis of variance followed by Bonferroni multiple comparisons test were used for statistical analyses. P < .05 was considered to reflect statistical significance. Mechanical allodynia in the masseter muscle was induced without any inflammatory cell infiltration in the muscle after TMJ inflammation. SGC activation and an increased number of TNFα-immunoreactive cells were induced in the TG following TMJ inflammation. Intra-TG administration of an inhibitor of SGC activity or of TNFα-neutralizing antibody depressed both the increased number of TG cells encircled by activated SGCs and the mechanical hypersensitivity of the masseter following TMJ inflammation. These findings suggest that persistent masseter hypersensitivity associated with TMJ inflammation was mediated by SGC-TG neuron interactions via TNFα signaling in the TG.

  14. Repeated exposure to hair dye induces regulatory T cells in mice

    DEFF Research Database (Denmark)

    Rubin, I M C; Dabelsteen, S; Nielsen, M M

    2010-01-01

    We have recently shown that commercial p-phenylenediamine (PPD)-containing hair dyes are potent immune activators that lead to severe contact hypersensitivity in an animal model. However, only a minority of people exposed to permanent hair dyes develops symptomatic contact hypersensitivity...

  15. Tc1-mediated contact sensitivity reaction, its mechanism and regulation

    Directory of Open Access Journals (Sweden)

    Magdalena Zemelka-Wiącek

    2014-07-01

    Full Text Available The contact hypersensitivity reaction (CHS to haptens is a classic example of cell-mediated immune response. In the effector phase, two stages can be distinguished: an early component, that appears only 2 hours after subsequent contact with the hapten, and the late component that develops approximately 24 hours later which is mediated by TCRαβ+ cells. The effector lymphocytes may be CD4+ T helper 1 (Th1 cells or CD8+ T cytotoxic 1 (Tc1 cells, which depends on the employed hapten and/or mice strain. NKT lymphocytes play the crucial role in the CHS initiation, by supporting B1 cells in the antigen-specific IgM antibodies production. The development of an early component is essential for the recruitment of T effector (Teff cells to the side of hapten deposition and for the complete expansion of inflammatory reaction. The CHS reaction is under T regulatory (Treg cells control, both in the induction phase as well as in the effector phase. A new view of a negative regulation of the Tc1 mediated CHS response is based on the suppression induced by epicutaneous (EC application of protein antigen. The DNP-BSA skin application, on a gauze patch, leads to a state of immunosuppression. This maneuver results in rising the population of Treg cells with TCRαβ+CD4+CD25+Foxp3+ phenotype. The mechanism of suppression requires direct contact between Treg cells and Teff cells and the participation of CTLA-4 molecule is also necessary. The described method of evoking immune tolerance via EC immunization may contribute to elaborate a new method of allergic contact dermatitis therapy. This is because of its effectiveness, ease of induction and non-invasive protein antigen application.

  16. Changes in gnathosonic and tooth contact characteristics induced by experimental occlusal interferences created using a full-cast double crown.

    Science.gov (United States)

    Asazuma, Y; Isogai, Y; Watanabe, K; Hara, K

    1995-03-01

    Occlusal sounds, contact timings and time moments were measured and analysed on 10 subjects onto whom an occlusal interference was created experimentally. A full-cast double crown was unilaterally set on the upper first molar of each subject, then gradually elevated for 0.06, 0.10, 0.20 and 0.30 mm by inserting a pre-calibrated metal folio. Occlusal sound was measured with an analyser designed for the purpose. Timings and time moments were analysed with a T-scan system. All measurements were performed at least 10 times per subject. The results showed that prolonged occlusal sound duration, changes in acoustic signal waveform and increased shift of the centre of effort were observed concomitantly with crown elevation. Differences in these values at 0.06 mm as compared with those at baseline were not statistically significant. This could be explained through a physiological compensation by the periodontal ligament. The differences with baseline were statistically significant from 0.10 mm ongoing. The distribution of occlusal conacts was determined by the use of a newly developed parameter. Referred to as 'Tap Score', the parameter consists of converting contact timings occurring in seven ranges into least-square-based weighted scores. Analysis of the tap score disclosed evident imbalance between the crowned and the non-crowned side starting from 0.10 mm elevation, whereby a forward shift of the major contact point was observed on the non-crowned side. Our study demonstrated that evident changes in gnathosonic and T-scan parameters are likely to occur at a crown elevation within a 0.06-0.10 mm range.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Is Tadpole Pupil in an Adolescent Girl Caused by Denervation Hypersensitivity?

    Science.gov (United States)

    Hansen, Jonas Kjeldbjerg; Møller, Hans Ulrik

    2017-06-01

    Tadpole pupil is a rarely encountered phenomenon caused by episodic, segmental iris dilator muscle spasm of short duration (2-15 minutes), occurring in clusters without a known precipitating factor. It has most commonly been described in women aged 28 to 48 years. A few hypotheses on pathogenesis have been discussed but none has been proved. Here, we present an adolescent girl with bilateral tadpole pupil that appeared during physical exercise. This is the first pediatric case of tadpole pupil, not caused by preceding surgery, to be published. Based on (1) this case in which tadpole pupil developed when the norepinephrine level rose during exercise, (2) the high ratio of patients with tadpole pupil who concurrently have or later develop Horner syndrome, in which denervation hypersensitivity is well described, (3) a previous report of a patient with both tadpole pupil and Horner syndrome who had denervation hypersensitivity on pharmacological testing, (4) a 29-year-old man with unilateral tadpole pupil induced by exercise, and (5) a 19-year-old man with bilateral tadpole pupil and possible autonomic neuropathy, we suggest denervation hypersensitivity as a probable pathogenic mechanism causing tadpole pupil. In addition, a suggestion for investigations to be performed in future pediatric cases is provided. Georg Thieme Verlag KG Stuttgart · New York.

  18. Progressive anticonvulsant hypersensitivity syndrome associated with change of drug product

    DEFF Research Database (Denmark)

    Sabroe, T.P.; Sabers, A.

    2008-01-01

    This report describes the laboratory and physical manifestations of lamotrigine-like toxicity in a young man with refractory epilepsy receiving lamotrigine presenting as anticonvulsant hypersensitivity syndrome (AHS) associated with an abrupt change of drug product Udgivelsesdato: 2008/6...

  19. Occupational trichloroethylene hypersensitivity syndrome: human herpesvirus 6 reactivation and rash phenotypes.

    Science.gov (United States)

    Kamijima, Michihiro; Wang, Hailan; Yamanoshita, Osamu; Ito, Yuki; Xia, Lihua; Yanagiba, Yukie; Chen, Cishan; Okamura, Ai; Huang, Zhenlie; Qiu, Xinxiang; Song, Xiangrong; Cai, Tingfeng; Liu, Lili; Ge, Yichen; Deng, Yingyu; Naito, Hisao; Yoshikawa, Tetsushi; Tohyama, Mikiko; Li, Laiyu; Huang, Hanlin; Nakajima, Tamie

    2013-12-01

    Trichloroethylene (TCE) is an industrial solvent which can cause severe generalized dermatitis, i.e., occupational TCE hypersensitivity syndrome. Reactivation of latent human herpesvirus 6 (HHV6) can occur in such patients, which has made TCE known as a causative chemical of drug-induced hypersensitivity syndrome (DIHS). This study aimed to clarify HHV6 status, cytokine profiles and their association with rash phenotypes in patients with TCE hypersensitivity syndrome. HHV6 DNA copy numbers, anti-HHV6 antibody titers, and cytokines were measured in blood prospectively sampled 5-7 times from 28 hospitalized patients with the disease. The patients (19 had exfoliative dermatitis (ED) and 9 had non-ED type rash) generally met the diagnostic criteria for DIHS. Viral reactivation defined as increases in either HHV6 DNA (≥100 genomic copies/10(6) peripheral blood mononuclear cells) or antibody titers was identified in 24 (89%) patients. HHV6 DNA, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-5, IL-6 and IL-10 concentrations were remarkably higher in the patients than in the healthy workers (p<0.01). Positive correlations between HHV6 DNA, TNF-α, IFN-γ, IL-6 and IL-10 were significant (p<0.05) except for that between HHV6 DNA and IFN-γ. An increase in HHV6 DNA was positively associated with an increase in TNF-α on admission (p<0.01). HHV6 DNA, the antibody titers, TNF-α and IL-10 concentrations were significantly higher in ED than in the non-ED type (p<0.05). Reactivated HHV6 and the increased cytokines could be biomarkers of TCE hypersensitivity syndrome. The higher-level reactivation and stronger humoral responses were associated with ED-type rash. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  20. Desensitization to ceftaroline in a patient with multiple medication hypersensitivity reactions.

    Science.gov (United States)

    Jones, Justin M; Richter, Lisa M; Alonto, Augusto; Leedahl, David D

    2015-02-01

    The case of a patient with multiple medication hypersensitivity reactions and a methicillin-resistant Staphylococcus aureus (MRSA) infection who underwent desensitization to ceftaroline is reported. A 32-year-old Caucasian woman with asthma, gastroesophageal reflux disease, heart murmur, and major depression was admitted for MRSA cellulitis with a subcutaneous abscess along the left sternomanubrial joint and clavicular osteomyelitis secondary to port placement after gastric bypass surgery. The patient had an extensive history of hypersensitivity reactions. Pertinent documented allergies were as follows: penicillin (anaphylaxis), daptomycin (anaphylaxis), vancomycin (hives), linezolid (hives), ertapenem (rash), ciprofloxacin (rash), and tigecycline (rash). The patient also reported previous reactions to aztreonam (unknown) and gentamicin (hives). The pharmacy was consulted to develop a desensitization protocol for ceftaroline. The desensitization protocol used three serial dilutions of ceftaroline to make 14 sequential infusions with escalating doses. Intramuscular epinephrine, i.v. diphenhydramine, and i.v. methylprednisolone were ordered as needed for the development of immediate hypersensitivity reactions during or after administration of ceftaroline. The cumulative dose (574.94 mg) was administered intravenously over 225 minutes with no breakthrough symptoms reported during or after the desensitization protocol. Ceftaroline fosamil 600 mg i.v. every 12 hours was continued for six weeks. Desensitization to ceftaroline was conducted for a patient with extensive history of hypersensitivity reactions to other drugs, including penicillin-induced anaphylaxis. Desensitization and subsequent treatment with full doses of ceftaroline were accomplished without apparent adverse effects. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  1. Bulk-Like Electrical Properties Induced by Contact-Limited Charge Transport in Organic Diodes: Revised Space Charge Limited Current

    KAUST Repository

    Xu, Guangwei

    2018-02-22

    Charge transport governs the operation and performance of organic diodes. Illuminating the charge-transfer/transport processes across the interfaces and the bulk organic semiconductors is at the focus of intensive investigations. Traditionally, the charge transport properties of organic diodes are usually characterized by probing the current–voltage (I–V) curves of the devices. However, to unveil the landscape of the underlying potential/charge distribution, which essentially determines the I–V characteristics, still represents a major challenge. Here, the electrical potential distribution in planar organic diodes is investigated by using the scanning Kelvin probe force microscopy technique, a method that can clearly separate the contact and bulk regimes of charge transport. Interestingly, by applying to devices based on novel, high mobility organic materials, the space-charge-limited-current-like I–V curves, which are previously believed to be a result of the bulk transport, are surprisingly but unambiguously demonstrated to be caused by contact-limited conduction. A model accounting is developed for the transport properties of both the two metal/organic interfaces and the bulk. The results indicate that pure interface-dominated transport can indeed give rise to I–V curves similar to those caused by bulk transport. These findings provide a new insight into the charge injection and transport processes in organic diodes.

  2. A Rare Diabetic Autonomic Neuropathy: Carotid Sinus Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Ahmet Kaya

    2016-03-01

    Full Text Available Carotid sinus hypersensitivity is a common cause of fainting and falls in the elderly, and can be diagnosed by carotid sinus massage. We present a 67-year-old diabetic man who was admitted with hyperglycemia. During thyroid examination, clouding of consciousness occurred with unilateral palpation. Asystole was documented for 4.8 seconds and suspected for 7 seconds upon carotid sinus massage. A cardioverter defibrillator was implanted. Carotid sinus hypersensitivity should be kept in mind when examining diabetic patients.

  3. Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs: An Update

    OpenAIRE

    Sánchez-Borges, Mario; Caballero-Fonseca, Fernan; Capriles-Hulett, Arnaldo; González-Aveledo, Luis

    2010-01-01

    After beta lactam antibiotics, hypersensitivity reactions to nonsteroidal antiinflammatory drugs are the second cause of hypersensitivity to drugs. Acute manifestations affect the respiratory tract (aspirin exacerbated respiratory disease), the skin (urticaria and angioedema), or are generalized (anaphylaxis). Correct diagnosis and treatment in order to prevent unnecessary morbidity and the potential risk of death from these severe reactions, and to provide proper medical advice on future dru...

  4. The role for decorin in delayed-type hypersensitivity

    Science.gov (United States)

    Seidler, Daniela G.; Mohamed, Negia A.; Bocian, Carla; Stadtmann, Anika; Hermann, Sven; Schäfers, Klaus; Schäfers, Michael; Iozzo, Renato V.; Zarbock, Alexander; Götte, Martin

    2016-01-01

    Decorin, a small leucine-rich proteoglycan, regulates extracellular matrix organization, growth factor-mediated signaling and cell growth. As decorin may directly modulate immune responses, we investigated its role in a mouse model of contact allergy (oxazolone-mediated delayed-type hypersensitivity, DTH) in decorin-deficient (Dcn−/−) and wild-type mice. Dcn−/− mice showed a reduced ear swelling 24 hours after oxazolone treatment with a concurrent attenuation of leukocyte infiltration. These findings were corroborated by reduced glucose metabolism as determined by 18FDG uptake in positron emission tomography scans. Unexpectedly, polymorphonuclear leukocyte numbers in Dcn−/− blood vessels were significantly increased, accompanied by large numbers of flattened leukocytes adherent to the endothelium. Intravital microscopy, flow chamber and static adhesion assays confirmed increased adhesion and reduced transmigration of Dcn−/− leukocytes. Circulating blood neutrophil numbers were significantly increased in Dcn−/− mice 24 hours after DTH elicitation, but only moderately increased in wild-type mice. Expression of the pro-inflammatory cytokine TNF-α was reduced, while syndecan-1 and ICAM-1 were overexpressed in inflamed ears of Dcn−/− mice, indicating that these adhesion molecules could be responsible for increased leukocyte adhesion. Decorin treatment of endothelial cells increased tyrosine phosphorylation and reduced syndecan-1 expression. Notably, absence of syndecan-1 in a genetic background lacking decorin rescued the attenuated DTH phenotype of Dcn−/− mice. Collectively, these results implicate a role for decorin in mediating DTH responses by influencing polymorphonuclear leukocyte attachment to the endothelium. This occurs via two non-mutually exclusive mechanisms that involve a direct anti-adhesive effect on polymorphonuclear leukocytes and a negative regulation of ICAM-1 and syndecan-1 expression. PMID:22043007

  5. Desensitization for Drug Hypersensitivity to Chemotherapy and Monoclonal Antibodies.

    Science.gov (United States)

    Bonamichi-Santos, Rafael; Castells, Mariana

    2016-01-01

    Chemotherapies drugs and monoclonal antibodies are key components of the treatment of cancer patients and patients with chronic inflammatory conditions to provide increase in life expectancy and quality of life. Their increased use has lead to an increase in drugs hypersensitivity reactions (DHR) worldwide. DHR to those agents prevented their use and promoted the use of second line therapies to protect patients' hypersensitive reactions and anaphylaxis. Second line medications may not fully address the patients' medical condition and it is desirable to keep patients on first line therapy. Drug hypersensitivity symptoms can range from mild cutaneous reactions to life-threatening anaphylaxis. Rapid drug desensitization (RDD) is a novel approach to the management of drug hypersensitivity reactions which are IgE and non-IgE mediated. Through the diferent desensitization protocols patients can receive the full dose of the medications that they have presented a hypersensitive reaction and been protected against anaphylaxis. This review looks at the current literature on hypersensitivity reactions (HSR) to chemotherapy drugs and monoclonal antibodies and the potential use of RDD for their management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Nonimmediate hypersensitivity reactions to iodinated contrast media.

    Science.gov (United States)

    Gómez, Enrique; Ariza, Adriana; Blanca-López, Natalia; Torres, Maria J

    2013-08-01

    To provide a detailed analysis of the latest findings on the mechanisms underlying the nonimmediate reactions to iodinated contrast media and comment on the recent advances in diagnosis, focusing on the roles of the skin test, drug provocation test (DPT), and lymphocyte transformation test (LTT). Several studies have reported new findings supporting an important role for T-lymphocytes in the nonimmediate reactions to iodinated contrast media. The LTT has been used as an in-vitro tool for diagnosis, but with variable results. However, the inclusion of autologous monocyte-derived dendritic cells as professional antigen-presenting cells has improved the sensitivity of this test. Regarding in-vivo diagnosis, although skin testing has been routine, it has now been shown that its sensitivity and negative predictive value are low. Recent studies have demonstrated that the DPT is a well tolerated and useful procedure that is necessary to confirm the diagnosis of nonimmediate hypersensitivity reactions to iodinated contrast media. Nonimmediate reactions to contrast media are usually T-cell mediated. Diagnosis is based on skin testing, although its sensitivity and negative predictive value are not optimal. Consequently, drug provocation testing is often needed to confirm the diagnosis and also to seek alternative contrast media that can be tolerated.

  7. Severe dapsone hypersensitivity syndrome in a child

    Directory of Open Access Journals (Sweden)

    So Yoon Choi

    2013-06-01

    Full Text Available Dapsone (4,4'-diaminodiphenylsulfone, DDS, a potent anti-inflammatory agent, is widely used in the treatment of leprosy and several chronic inflammatory skin diseases. Dapsone therapy rarely results in development of dapsone hypersensitivity syndrome, which is characterized by fever, hepatitis, generalized exfoliative dermatitis, and lymphadenopathy. Here, we describe the case of an 11-year-old Korean boy who initially presented with high fever, a morbilliform skin rash, generalized lymphadenopathy, hepatosplenomegaly, and leukopenia after 6 weeks of dapsone intake. Subsequently, he exhibited cholecystitis, gingivitis, colitis, sepsis, aseptic meningitis, disseminated intravascular coagulation, syndrome of inappropriate antidiuretic hormone secretion, pneumonia, pleural effusions, peritonitis, bronchiectatic changes, exfoliative dermatitis, and acute renal failure. After 2 months of supportive therapy, and prednisolone and antibiotic administration, most of the systemic symptoms resolved, with the exception of exfoliative dermatitis and erythema, which ameliorated over the following 4 months. Agranulocytosis, atypical lymphocytosis, aseptic meningitis, and bronchiectatic changes along with prolonged systemic symptoms with exfoliative dermatitis were the most peculiar features of the present case.

  8. Hazards of the 'hard cash': hypersensitivity pneumonitis.

    Science.gov (United States)

    Kupeli, Elif; Karnak, Demet; Sak, Serpil Dizbay; Kayacan, Oya

    2010-01-01

    Hypersensitivity pneumonitis (HP) is a nonimmunoglobulin E-related immune-mediated parenchymal lung disease. A 45-year-old woman who was a lifelong nonsmoker with a six-month history of frequent episodes of cough and dyspnea was admitted to hospital. She had been working as a money counter for 20 years at a central bank. Bibasilar crackles on lung auscultation, ground-glass opacities and a mosaic pattern on high-resolution computed tomography, restrictive abnormality on pulmonary function tests and mild hypoxemia were the prominent findings. Bronchoalveolar lavage fluid analysis revealed a predominance of CD4-positive T cells, and she tested positive on her natural challenge test. She was diagnosed with subacute HP based on established criteria. She was advised to discontinue counting fresh banknotes. Prednisolone was commenced, then tapered to discontinue in the ensuing six months. Clinical and radiological improvement was achieved within two months. To the authors' knowledge, the present report is the first to describe 'hard cash HP', possibly caused by chipping dust or printing dye.

  9. Visceral pain hypersensitivity in functional gastrointestinal disorders.

    Science.gov (United States)

    Farmer, A D; Aziz, Q

    2009-01-01

    Functional gastrointestinal disorders (FGIDs) are a highly prevalent group of heterogeneous disorders whose diagnostic criteria are symptom based in the absence of a demonstrable structural or biochemical abnormality. Chronic abdominal pain or discomfort is a defining characteristic of these disorders and a proportion of patients may display heightened pain sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity (VPH). We examined the most recent literature in order to concisely review the evidence for some of the most important recent advances in the putative mechanisms concerned in the pathophysiology of VPH. VPH may occur due to anomalies at any level of the visceral nociceptive neuraxis. Important peripheral and central mechanisms of sensitization that have been postulated include a wide range of ion channels, neurotransmitter receptors and trophic factors. Data from functional brain imaging studies have also provided evidence for aberrant central pain processing in cortical and subcortical regions. In addition, descending modulation of visceral nociceptive pathways by the autonomic nervous system, hypothalamo-pituitary-adrenal axis and psychological factors have all been implicated in the generation of VPH. Particular areas of controversy have included the development of efficacious treatment of VPH. Therapies have been slow to emerge, mainly due to concerns regarding safety. The burgeoning field of genome wide association studies may provide further evidence for the pleiotropic genetic basis of VPH development. Tangible progress will only be made in the treatment of VPH when we begin to individually characterize patients with FGIDs based on their clinical phenotype, genetics and visceral nociceptive physiology.

  10. Tolerance and immunity in mice infected with herpes simplex virus: simultaneous induction of protective immunity and tolerance to delayed-type hypersensitivity.

    Science.gov (United States)

    Nash, A A; Gell, P G; Wildy, P

    1981-05-01

    Unresponsiveness to delayed type hypersensitivity was induced in mice following an intravenous injection of herpes simplex virus. The principal tolerogens used were thymidine kinase-deficient virus mutants which grow poorly in vivo; u.v.-inactivated and to a lesser extent formalin-inactivated virus were also tolerogenic. The tolerance induced was specific for the virus type. Despite the tolerance to delayed hypersensitivity, anti-viral immunity is present as determined by the rapid inactivation of infectious virus. The mechanism of tolerance to herpes virus and the importance of these observations for the pathogenesis of viral disease is discussed.

  11. Carbamazepine-hypersensitivity: assessment of clinical and in vitro chemical cross-reactivity with phenytoin and oxcarbazepine.

    Science.gov (United States)

    Pirmohamed, M; Graham, A; Roberts, P; Smith, D; Chadwick, D; Breckenridge, A M; Park, B K

    1991-01-01

    1. Seven patients clinically diagnosed as being hypersensitive to carbamazepine and one patient hypersensitive to both carbamazepine and oxcarbazepine have been identified. They have been compared with a control group (hereafter referred to as 'control subjects') comprising five patients on chronic carbamazepine therapy without adverse effects and 12 healthy volunteers who have never been exposed to anticonvulsants. 2. An in vitro cytotoxicity assay employing mononuclear leucocytes as target cells has been used first, to determine the ability of 10 different human livers to bioactivate carbamazepine to a cytotoxic metabolite, and secondly, to compare the cell defences of carbamazepine-hypersensitive patients and control subjects to oxidative drug metabolites generated by a murine microsomal system, using a blinded protocol. 3. With human liver microsomes, the metabolism-dependent cytotoxicity of carbamazepine increased with increasing microsomal protein concentration. At a protein concentration of 2 mg per incubation, the cytotoxicity of carbamazepine with human liver microsomes (n = 10 livers) increased from 7.2 +/- 0.8% (baseline) to 16.4 +/- 2.1% (with NADPH; P = 0.002). 4. In the presence of phenobarbitone-induced mouse microsomes and NADPH, the mean increase in cytotoxicity above the baseline with carbamazepine was significantly greater (P less than 0.001) for the cells from the carbamazepine-hypersensitive patients (7.9 +/- 0.8%) than from control subjects (2.6 +/- 0.3%). 5. In the presence of phenobarbitone-induced mouse microsomes and NADPH, there was no significant difference in cytotoxicity between the cells from carbamazepine hypersensitive patients and from control subjects in the presence of either phenytoin or oxcarbazepine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1768568

  12. Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma.

    Science.gov (United States)

    Engberg, Anna E; Nilsson, Per H; Huang, Shan; Fromell, Karin; Hamad, Osama A; Mollnes, Tom Eirik; Rosengren-Holmberg, Jenny P; Sandholm, Kerstin; Teramura, Yuji; Nicholls, Ian A; Nilsson, Bo; Ekdahl, Kristina N

    2015-01-01

    Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-γ, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Effects of Acupuncture on 1-chloro-2,4-dinitrochlorobenzene-induced Allergic Contact Dermatitis in Mice

    Directory of Open Access Journals (Sweden)

    Cuicui Chen

    2017-08-01

    Full Text Available Allergic contact dermatitis (ACD is a chronic inflammatory skin disease. Topical corticosteroids are the first-line therapy for ACD despite their significant adverse effects. Acupuncture has been widely used in the treatment of various skin diseases, but its underlying mechanism remains unrevealed. In this study, we investigated the characteristics of acupuncture treatment based on effectiveness and mechanism. BALB/c mice received 1-chloro-2,4-dinitrobenzene (DNCB application to build AD-like model. Results showed that acupuncture was an effective treatment method in inhibiting inflammatory conditions, serum IgE levels, and expression of proinflammatory cytokine Th2 (IL-4, IL-6, and Th2 (IL-1β, TNF-α mRNA compared with DNCB treatment. Acupuncture treatment also inhibited nuclear factor-κB p65, phosphorylation of IκBα, and phosphorylation of occludin proteins expression. Furthermore, it could improve the expression of epidermal growth factor in both mRNA and protein levels. These results suggest that acupuncture, as an alternative therapy treatment for its no significant side effects, was effective in alleviating ACD by reducing proinflammatory cytokines and changing proteins' expression.

  14. Effects of Acupuncture on 1-chloro-2,4-dinitrochlorobenzene-induced Allergic Contact Dermatitis in Mice.

    Science.gov (United States)

    Chen, Cuicui; Liu, Xiaozhu; Li, Yinfeng; Liang, Huankun; Li, Kangyan; Li, Jiali; Cheng, Chengwu; Liu, Xianpan; Zhong, Shuhai; Li, Laiqing; Wang, Yan

    2017-08-01

    Allergic contact dermatitis (ACD) is a chronic inflammatory skin disease. Topical corticosteroids are the first-line therapy for ACD despite their significant adverse effects. Acupuncture has been widely used in the treatment of various skin diseases, but its underlying mechanism remains unrevealed. In this study, we investigated the characteristics of acupuncture treatment based on effectiveness and mechanism. BALB/c mice received 1-chloro-2,4-dinitrobenzene (DNCB) application to build AD-like model. Results showed that acupuncture was an effective treatment method in inhibiting inflammatory conditions, serum IgE levels, and expression of proinflammatory cytokine Th2 (IL-4, IL-6), and Th2 (IL-1β, TNF-α) mRNA compared with DNCB treatment. Acupuncture treatment also inhibited nuclear factor-κB p65, phosphorylation of IκBα, and phosphorylation of occludin proteins expression. Furthermore, it could improve the expression of epidermal growth factor in both mRNA and protein levels. These results suggest that acupuncture, as an alternative therapy treatment for its no significant side effects, was effective in alleviating ACD by reducing proinflammatory cytokines and changing proteins' expression. Copyright © 2017. Published by Elsevier B.V.

  15. Hypersensitivity pneumonitis: a complex lung disease.

    Science.gov (United States)

    Riario Sforza, Gian Galeazzo; Marinou, Androula

    2017-01-01

    Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, is a respiratory syndrome involving the lung parenchyma and specifically the alveoli, terminal bronchioli, and alveolar interstitium, due to a delayed allergic reaction. Such reaction is secondary to a repeated and prolonged inhalation of different types of organic dusts or other substances to which the patient is sensitized and hyper responsive, primarily consisting of organic dusts of animal or vegetable origin, more rarely from chemicals. The prevalence of HP is difficult to evaluate because of uncertainties in detection and misdiagnosis and lacking of widely accepted diagnostic criteria, and varies considerably depending on disease definition, diagnostic methods, exposure modalities, geographical conditions, agricultural and industrial practices, and host risk factors. HP can be caused by multiple agents that are present in work places and in the home, such as microbes, animal and plant proteins, organic and inorganic chemicals. The number of environment, settings and causative agents is increasing over time. From the clinical point of view HP can be divided in acute/subacute and chronic, depending on the intensity and frequency of exposure to causative antigens. The mainstay in managing HP is the avoidance of the causative antigen, though the complete removal is not always possible due to the difficulties to identify the agent or because its avoidance may lead to major changes in life style or occupational settings. HP is a complex syndrome that needs urgently for more stringent and selective diagnostic criteria and validation, including wider panels of IgG, and a closer collaboration with occupational physicians, as part of a multidisciplinary expertise.

  16. Constructing a classification of hypersensitivity/allergic diseases for ICD-11 by crowdsourcing the allergist community.

    Science.gov (United States)

    Tanno, L K; Calderon, M A; Goldberg, B J; Gayraud, J; Bircher, A J; Casale, T; Li, J; Sanchez-Borges, M; Rosenwasser, L J; Pawankar, R; Papadopoulos, N G; Demoly, P

    2015-06-01

    The global allergy community strongly believes that the 11th revision of the International Classification of Diseases (ICD-11) offers a unique opportunity to improve the classification and coding of hypersensitivity/allergic diseases via inclusion of a specific chapter dedicated to this disease area to facilitate epidemiological studies, as well as to evaluate the true size of the allergy epidemic. In this context, an international collaboration has decided to revise the classification of hypersensitivity/allergic diseases and to validate it for ICD-11 by crowdsourcing the allergist community. After careful comparison between ICD-10 and 11 beta phase linearization codes, we identified gaps and trade-offs allowing us to construct a classification proposal, which was sent to the European Academy of Allergy and Clinical Immunology (EAACI) sections, interest groups, executive committee as well as the World Allergy Organization (WAO), and American Academy of Allergy Asthma and Immunology (AAAAI) leaderships. The crowdsourcing process produced comments from 50 of 171 members contacted by e-mail. The classification proposal has also been discussed at face-to-face meetings with experts of EAACI sections and interest groups and presented in a number of business meetings during the 2014 EAACI annual congress in Copenhagen. As a result, a high-level complex structure of classification for hypersensitivity/allergic diseases has been constructed. The model proposed has been presented to the WHO groups in charge of the ICD revision. The international collaboration of allergy experts appreciates bilateral discussion and aims to get endorsement of their proposals for the final ICD-11. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Effect of ranitidine on postoperative suppression of natural killer cell activity and delayed hypersensitivity

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Pedersen, B K; Moesgaard, F

    1989-01-01

    hypersensitivity (DTH) antigens, and blood drawn immediately before and 24 hours after skin incision was analyzed for spontaneous and in vitro stimulated (IL-2, IFN-alpha or indomethacin) natural killer (NK) cell activity and PHA and PPD-stimulated lymphocyte proliferation. Lymphocyte subsets (helper......-cell activity (p less than 0.02). Postoperative decrease in helper/inducer-T cell numbers was not significantly lessened (p = 0.07), and ranitidine did not influence the levels of suppressor-T cells. PHA and PPD responses in peripheral blood mononuclear cells were unaltered. The results may suggest potential...

  18. Trends in incidence of occupational asthma, contact dermatitis, noise-induced hearing loss, carpal tunnel syndrome and upper limb musculoskeletal disorders in European countries from 2000 to 2012.

    Science.gov (United States)

    Stocks, S Jill; McNamee, Roseanne; van der Molen, Henk F; Paris, Christophe; Urban, Pavel; Campo, Giuseppe; Sauni, Riitta; Martínez Jarreta, Begoña; Valenty, Madeleine; Godderis, Lode; Miedinger, David; Jacquetin, Pascal; Gravseth, Hans M; Bonneterre, Vincent; Telle-Lamberton, Maylis; Bensefa-Colas, Lynda; Faye, Serge; Mylle, Godewina; Wannag, Axel; Samant, Yogindra; Pal, Teake; Scholz-Odermatt, Stefan; Papale, Adriano; Schouteden, Martijn; Colosio, Claudio; Mattioli, Stefano; Agius, Raymond

    2015-04-01

    The European Union (EU) strategy for health and safety at work underlines the need to reduce the incidence of occupational diseases (OD), but European statistics to evaluate this common goal are scarce. We aim to estimate and compare changes in incidence over time for occupational asthma, contact dermatitis, noise-induced hearing loss (NIHL), carpal tunnel syndrome (CTS) and upper limb musculoskeletal disorders across 10 European countries. OD surveillance systems that potentially reflected nationally representative trends in incidence within Belgium, the Czech Republic, Finland, France, Italy, the Netherlands, Norway, Spain, Switzerland and the UK provided data. Case counts were analysed using a negative binomial regression model with year as the main covariate. Many systems collected data from networks of 'centres', requiring the use of a multilevel negative binomial model. Some models made allowance for changes in compensation or reporting rules. Reports of contact dermatitis and asthma, conditions with shorter time between exposure to causal substances and OD, were consistently declining with only a few exceptions. For OD with physical causal exposures there was more variation between countries. Reported NIHL was increasing in Belgium, Spain, Switzerland and the Netherlands and decreasing elsewhere. Trends in CTS and upper limb musculoskeletal disorders varied widely within and between countries. This is the first direct comparison of trends in OD within Europe and is consistent with a positive impact of European initiatives addressing exposures relevant to asthma and contact dermatitis. Taking a more flexible approach allowed comparisons of surveillance data between and within countries without harmonisation of data collection methods. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. Efficacy of the saponin component of Impatiens capensis Meerb.in preventing urushiol-induced contact dermatitis.

    Science.gov (United States)

    Motz, Vicki A; Bowers, Christopher P; Kneubehl, Alexander R; Lendrum, Elizabeth C; Young, Linda M; Kinder, David H

    2015-03-13

    Many different tribes of American Indians used jewelweed, Impatiens capensis Meerb, as a plant mash to reduce development of poison ivy dermatitis. Saponins are a natural soapy constituent found within plants. A 2012 study suggested that saponins may be present in jewelweed which could be responsible for its efficacy in preventing rash development following contact with Toxicodendron radicans (L.) Kuntze (poison ivy). This study validated this hypothesis and demonstrated additional biological activity of the jewelweed saponin containing extract. Fresh I. capensis leaves were extracted with methanol and further partitioned between ethyl acetate and water, with a final separation between water and n-butanol, to obtain a saponin containing extract. The presence of saponins in the extract was demonstrated by the observation of foaming and using a vanillin colorimetric assay for total saponins. Efficacy of the saponin containing extracts in rash reduction was tested by brushing poison ivy (PI) onto the forearms of volunteers (N=23) in six locations and treating these PI exposed areas with distilled water (control), saponin containing extracts, fresh plant mashes, and soaps made with and without plant extracts. Saponin containing extracts were further tested for biological activity against both gram negative and gram positive bacteria and against cancer cell lines A-375, HT-29, and MCF-7. Additionally, because saponins have been shown to have a stimulatory effect in cardiac muscle 2 µl saponin extract was applied superficially to black worms, Lumbriculus variegatus (N=5). Both saponin containing extracts and all soaps tested were effective in reducing poison ivy dermatitis; thus, saponin content correlates with PI rash prevention. No apparent antibiosis was observed against any bacteria tested; however, dose response cytotoxicity was documented against MCF-7 breast cancer cells and cytostatic activity was seen against the HT-29 colon cancer cell lines. Lumbriculus

  20. Estradiol-induced alopecia in five dogs after contact with a transdermal gel used for the treatment of postmenopausal symptoms in women.

    Science.gov (United States)

    Wiener, Dominique J; Rüfenacht, Silvia; Koch, Hans J; Mauldin, Elizabeth A; Mayer, Ursula; Welle, Monika M

    2015-10-01

    Noninflammatory alopecia is a frequent problem in dogs. Estrogen-induced alopecia is well described in dogs, with estrogen producing testicular tumors and canine female hyperestrogenism. To increase awareness that extensive alopecia in dogs can be caused by exposure to estradiol gel used by owners to treat their postmenopausal symptoms. Skin biopsies from five dogs with extensive alopecia were examined. Owners were asked for a thorough case history, including possible exposure to an estradiol gel. Complete blood work and serum chemistry panel analysis were performed to investigate possible underlying causes. Formalin-fixed skin biopsy samples were obtained from lesional skin and histopathology was performed. All owners confirmed the use of a transdermal estradiol gel and close contact with the affected dogs before development of alopecia. Histopathologic examination showed a similar picture in all five dogs. Most hair follicles were predominantly either in kenogen or telogen and hair follicle infundibula showed mild to moderate dilation. Hair regrowth was present in all five dogs after the exposure to the estradiol gel was stopped or minimized. Blood work and serum chemistry panel were within normal limits in all cases. One dog had elevated estradiol concentrations, whereas in another dog estradiol concentrations were within normal limits. Alopecia can occur after contact with a transdermal gel used as treatment for postmenopausal symptoms in women. Estradiol gel used by female owners therefore represents a possible cause for noninflammatory alopecia in dogs. Estradiol concentrations are not necessarily elevated in affected dogs. © 2015 ESVD and ACVD.

  1. Hypersensitivity Reaction Associated with Abacavir Therapy in an Indian HIV Patient - A Case Report.

    Science.gov (United States)

    Janardhanan, Manju; Amberkar V, Mohan Babu; Vidyasagar, Sudha; Kumari K, Meena; Holla, Sadhana N

    2014-09-01

    The most important and unique adverse effect of abacavir (ABC) is fatal hypersensitivity reaction (HSR). The objective of this report is to describe a case of ABC induced HSR that occurred in an Indian HIV patient during treatment. Although this adverse effect is not uncommon, it is perhaps underreported or has never been reported so far in an Indian case scenario. A 44-year-old known case of HIV-1 was admitted in view of his worsening condition and very low CD4 cell counts 3 cells/μL. He was on anti-retroviral therapy since three years but not regular. On the basis of treatment failure, non-compliance and progressive low CD4 counts, the anti HIV regime was switched over to abacavir 600 mg+ atazanavir/ ritonavir 300mg/100mg Two weeks after ABC therapy he presented with maculopapular rash, headache and signs of hepatic damage (serum AST, ALP and ALT increased to 3-4 fold) suggestive of hypersensitivity reaction. As we know discontinuation of the drug is the ultimate litmus test to confirm diagnosis of drug induced adverse reaction. We did confirm ABC induced HSR by de-challenge wherein, rash disappeared within 2-3 days and LFT came back to normal within 5 days. However, no rechallenge was done. HSR was more in favour of ABC because atazanavir failed to produce any similar reaction after re-challenge.

  2. LANL Contacts

    Science.gov (United States)

    : (505) 665-3664 ethics@lanl.gov Journalist queries Communications Office (505) 667-7000 Media contacts programs and employee resources. General Employee directory Emergency communication Communications Office (505) 667-7000 Ethics & Audits Internal Audit: (505) 665-3104 Ethics Office: (505) 667-7506 Fax

  3. Hypersensitivity to thrombin of platelets from hypercholesterolemic rats

    International Nuclear Information System (INIS)

    Winocour, P.D.; Rand, M.L.; Kinlough-Rathbone, R.L.; Mustard, J.F.

    1986-01-01

    Hypersensitivity of platelets to thrombin has been associated with hypercholesterolemia. The authors have examined the mechanisms involved in this hypersensitivity. Rats were given diets rich in milk fat and containing added cholesterol and taurocholate to produce hypercholesterolemia (HC) (262 +/- 25 mg%) or added sitosterol as a normocholesterolemic control (NC) (89 +/- 6 mg%). Washed platelets were prelabelled with 14 C-serotonin. In the presence of acetylsalicyclic acid (ASA) (to inhibit thromboxane A 2 (TXA 2 ) formation) and creatine phosphate/creatine phosphokinase (CP/CPK) (to remove released ADP), HC platelets aggregated more (26 +/- 1%) and released more 14 C (9.1 +/- 2.0%) than NC platelets (aggregation: 0%, p 14 C release: 1.5 +/- 0.5%, p 2 formation is involved in the hypersensitivity of HC platelets to thrombin. Total binding of 125 I-thrombin to HC platelets was less than that to NC platelets but HC platelets were smaller and had less protein than NC platelets; the thrombin binding per mg platelet protein was the same for HC and NC platelets, indicating that hypersensitivity to thrombin of HC platelets does not result from increased thrombin binding. Thus, hypersensitivity of HC platelets to thrombin is not due to TXA 2 formation, the action of released ADP or increased thrombin binding

  4. Association of anticonvulsant hypersensitivity syndrome with Herpesvirus 6, 7.

    Science.gov (United States)

    Oskay, Tuğba; Karademir, Asli; Ertürk, Ozcan I

    2006-07-01

    Anticonvulsant hypersensitivity syndrome (AHS) is one of the most severe forms of drug eruption with potentially lethal, and multiorgan involvement. Recently, it has been suggested that Human Herpesvirus (HHV) infection has been involved in this syndrome, although the pathogenesis of this syndrome remains still unclear. The objective of this study was to determine the clinical characteristics of AHS and the possible role of viral infection as a co-factor. We prospectively analyzed clinical, laboratory and virological findings for 23 cases of AHS. A viral study including viral serology and a polymerase chain reaction (PCR) was performed. The most common anticonvulsant was carbamazepine (12) followed by phenytoin (6), phenobarbital (4) and gabapentin (1). All patients met fulfill the clinical criteria of AHS. Even though internal organ involvement such as liver (52%), kidney (34%), and lung (13%) has been observed, involvement of heart, lung, thyroid, muscle, pancreas, spleen, and brain was less frequent. We also noted two patients who died due to multiorgan failure. No association with viral infection including HSV, VZV, HHV-8, CMV, EBV, measles, rubella and parvovirus B19 was detected in the current series. Increased serum anti-HHV-6 IgG and HHV-7 titers and presence of HHV-6 and -7 DNA in serum, revealed by PCR analysis, suggested reactivation of HHV-6. In contrast to the control groups, DNA for HHV-6 was detected in serum in 5 out of the 23 patients while HHV-7 was seen in two patients. We found an evidence to link reactivation of HHV-6 or HHV-7 in the development of only carbamazepine-induced AHS. We propose that some cases of AHS are accompanied by reactivation of not only HHV-6 but also HHV-7. HHV infection may contribute to the severity, prolongation, or relapse of AHS and may possibly have fatal consequences in some susceptible individuals receiving the anticonvulsants.

  5. Asthma and chemical hypersensitivity: prevalence, etiology, and age of onset.

    Science.gov (United States)

    Caress, S M; Steinemann, A C

    2009-02-01

    This study investigates asthma's national prevalence and potential overlap with chemical hypersensitivity. It also examines asthma's etiology, age of onset, and demographic characteristics. Data were collected from a geographically weighted random sample of the continental U.S. (1058 cases), in four seasonal cohorts (2005-2006). The study found that 12.9% of the sample report asthma, 11.6% report chemical hypersensitivity, and 31.4% of those with asthma report chemical hypersensitivity. Among asthmatics, 38% report irritation from scented products, 37.2% report health problems from air fresheners, and 13.6% report their asthma was caused by toxic exposure. Asthma cases affected each racial/ethic group in roughly the same proportion, with nearly 50% classified as childhood onset.

  6. Multinational experience with hypersensitivity drug reactions in Latin America.

    Science.gov (United States)

    Jares, Edgardo José; Sánchez-Borges, Mario; Cardona-Villa, Ricardo; Ensina, Luis Felipe; Arias-Cruz, Alfredo; Gómez, Maximiliano; Barayazarra, Susana; Bernstein, Jonathan A; Serrano, Carlos D; Cuello, Mabel Noemi; Morfin-Maciel, Blanca María; De Falco, Alicia; Cherrez-Ojeda, Iván

    2014-09-01

    Epidemiologic drug allergy data from Latin America are scarce, and there are no studies on specific procedures focusing on this topic in Latin America. To assess the clinical characteristics and management of hypersensitivity drug reactions in different Latin American countries. An European Network of Drug Allergy questionnaire survey was implemented in 22 allergy units in 11 Latin American countries to report on consecutive patients who presented with a suspected hypersensitivity drug reaction. Each unit used its own protocols to investigate patients. Included were 868 hypersensitivity drug reactions in 862 patients (71% of adults and elderly patients were women and 51% of children were girls, P = .0001). Children presented with less severe reactions than adults and elderly patients (P Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. FOOD HYPERSENSITIVITY AND PRODUCTS OF ANIMAL ORIGIN RESOURCES

    Directory of Open Access Journals (Sweden)

    A. B. Lisitsyn

    2017-01-01

    Full Text Available The number of people with food hypersensitivity, namely food intolerance and food allergies, grows every year. Food intolerance is classified into following types: enzymopathy; leaky gut syndrome; psychogenic food intolerance; detoxification insufficiency and true food intolerance. Food allergens mainly are glycoproteins, haptensor polypeptides. Most cases of food allergy are IgE-mediated allergic reactions. Recent discoveries in medicine, detailing and classification of food hypersensitivity require further researches to develop modern techniques and product recipes with specified propertiesfor consumers with food hypersensitivity. Existing technologies are based on the elimination and or reduction of the content of the allergenic substance in food. The article provides an overview of causes of food intolerance and food allergy, legislative background, a list of food allergens and methods of control, market profile of hypoallergenic produce and scientific approaches to creating hypoallergenic food products based on raw materials of animal origin.

  8. [Adaptive desensitization for acetylsalicylic acid hypersensitivity: A success story?].

    Science.gov (United States)

    Mühlmeier, G; Hausch, R; Maier, H

    2015-10-01

    Adaptive desensitization still remains the only causative therapy for acetylsalicylic acid (ASA) hypersensitivity and is carried out nearly worldwide. To date there are hardly any data available on disease development under current desensitization therapy and longitudinal data in particular are missing. Out of a large collective of patients with proven hypersensitivity to ASA, 194 patients with initiated desensitization treatment were observed for periods up to 5 years (average 32 months). Patients with immediate reactions to systemic challenge tests revealed a response rate of 77% after 12 months of therapy. In this period 12% reached complete remission, 38% showed a clear reduction in symptoms, 32% reached partial remission, 13% remained unchanged and 5% suffered from disease progression. Adaptive desensitization therapy for hypersensitivity to ASA has been shown to be an effective causative therapy and chronic hyperplastic sinusitis as well as bronchial asthma could be improved. For the determination of maintenance dosages and required time periods more data are needed.

  9. Metal hypersensitivity after knee arthroplasty: fact or fiction?

    Science.gov (United States)

    Innocenti, Massimo; Vieri, Berti; Melani, Tommaso; Paoli, Tommaso; Carulli, Christian

    2017-06-07

    Hypersensitivity to metals in the general population has an incidence of about 15%, and in rising also for the higher number of joint replacements in the last decades. Total Knee Arthroplasty (TKA) represents the most performed orthopaedic procedure during last years, and it seems to be particularly associated with sensitization after surgery. On the other hand, there is a rising amount of patients with painful but well implanted and functioning TKAs: in certain cases, after the exclusion of the most frequent causes of failure, a condition of hypersensitivity may be found, and a revision with anallergic implants is mandatory. The present study is a review of the potential problems related to hypersensitivity in TKA, its possible diagnostic procedures, and the surgical options to date available. Medical history, patch testing, and other specific laboratory assays are useful to assess a status of metals hypersensitivity before surgery in subjects undergoing a knee replacement, or even after TKA in patients complaining pain in otherwise well implanted and aligned prostheses. However, few groups worlwide deal with such condition, and all proposed diagnostic protocols may be considered still today conjectural. On the other hand, these represent the most updated knowledge of this condition, and may be useful for both the patient and the orthopaedic surgeon. Once assessed a possible or ascertained allergy to metals, several options are available for primary andr revision knee surgery, in order to avoid the risk of hypersensitivity. A review of the recent publications on this topic and an overview of the related aspects has been made to understand a condition to date considered negligible. Hypersensitivity to metals has not to be nowadays considered a "fiction", but rather a possible preoperative risk or a postoperative cause of failure of TKA. Crucial is the information of patients and the medical history, associated in suspect cases to laboratory testings. Today in the

  10. Efficacy of two commercially available dentifrices in reducing dentinal hypersensitivity

    Directory of Open Access Journals (Sweden)

    Prasad KVV

    2010-01-01

    Full Text Available Objective: A parallel design clinical study evaluated reduction in hypersensitivity after brushing for 12 weeks with Anchor toothpaste (containing potassium citrate, zinc citrate, triclosan and sodium monofluorophosphate (test and Colgate Total (sodium fluoride, silica, triclosan and copolymer (control dentifrices. Materials and Methods: Sixty adults with sensitivity to hot and cold stimulus in at least two tooth surfaces were stratified at the baseline examination by tactile, hot and cold stimuli scores in two balanced groups. Subjects were randomly allocated the test and control dentifrices and evaluated after 6 and 12 weeks of dentifrice use for hypersensitivity. Results: The two teeth that were selected in each patient were designated as two different sets. The 12 th -week scores as compared to baseline scores for tactile, heat and cold tests in the test group showed a reduction in tooth hypersensitivity by 36.67% (P < 0.01, 20.35% (P < 0.01 and 53.64 % (P < 0.01, respectively, in the first set of teeth and 43.75% (P < 0.01, 24.48% (P < 0.01 and 59.78% (P < 0.01, respectively, in the second set of teeth. The 12 th -week scores as compared to baseline scores for tactile, heat and cold tests in the control group showed a reduction in tooth hypersensitivity by 42.86% (P < 0.01, 13.02% (P < 0.01 and 45.14% (P < 0.01, respectively, in the first set of teeth and 40% (P < 0.01, 16.59% (P < 0.01 and 44.16% (P < 0.01, respectively, in the second set of teeth. Conclusions: Both the products reduced dentinal hypersensitivity in the study subjects at the end of the 12-week period. However, there was no statistically significant difference in reduction in hypersensitivity between the two products.

  11. Corticosteroid hypersensitivity studies in a skin allergy clinic.

    Science.gov (United States)

    Berbegal, L; DeLeon, F J; Silvestre, J F

    2015-12-01

    Corticosteroids can cause hypersensitivity reactions, particularly delayed-type allergic reactions. A new classification system for testing hypersensitivity to corticosteroids distributes the drugs into 3 groups according to molecular structure; patients are classified according to whether they are allergic to agents in 1 or more of the groups. We aimed to describe the clinical characteristics of corticosteroid-allergic patients treated at our clinic and apply the new classification system to them; we also compared these patients' characteristics to those of others treated at our clinic. Retrospective study of cases of delayed-type corticosteroid hypersensitivity treated in the skin allergy clinic of a tertiary level hospital over an 11-year period. We reviewed the records of 2857 patients, finding 33 with at least one positive patch test result showing corticosteroid hypersensitivity. Atopic dermatitis and hand involvement were less common in our corticosteroid-allergic patients. All were allergic to a group 1 corticosteroid (most often, budesonide, the culprit in 87.9%). Testing with a specific corticosteroid series revealed that 14 (42.4%) were also allergic to corticosteroids in group 2 and/or group 3. None were allergic exclusively to group 2 or group 3 agents. Twenty-one patients were exposed to a corticosteroid cream from a group their patch test results indicated allergy to; 13 of them (61.9%) did not develop a hypersensitivity reaction. The Spanish standard series only contains group 1 corticosteroids. In the interest of improving allergy management, we recommend testing with a specific corticosteroid series and a patient's own creams whenever patch testing with a standard series reveals a hypersensitivity reaction to corticosteroids. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  12. Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs)

    DEFF Research Database (Denmark)

    Nissen, Christoffer V; Bindslev-Jensen, Carsten; Mørtz, Charlotte G

    2015-01-01

    BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are reported to be the second most common cause of drug hypersensitivity. In 2011, experts from the EAACI/ENDA group and GA(2)LEN proposed a new classification system for NSAID hypersensitivity. The aim of this study was to classify...... responders reacted to non-pyrazolone drugs. Only one patient could not be classified according to the EAACI/ENDA system. An overlap between respiratory and cutaneous symptoms was found in 15/39 (38%) of patients. CONCLUSIONS: All but one of our patients could be classified according to the EAACI...

  13. Functional dyspepsia: The role of visceral hypersensitivity in its pathogenesis

    Institute of Scientific and Technical Information of China (English)

    John Keohane; Eamonn M M Quigley

    2006-01-01

    Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists.It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process.The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review,we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.

  14. Functional dyspepsia: the role of visceral hypersensitivity in its pathogenesis.

    LENUS (Irish Health Repository)

    Keohane, John

    2012-02-03

    Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.

  15. Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands

    NARCIS (Netherlands)

    Schurink, A.; Wolc, A.; Ducro, B.J.; Frankena, K.; Garrick, D.J.; Dekkers, J.C.M.; Arendonk, van J.A.M.

    2012-01-01

    Background: Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite

  16. HLA-A*31:01 and HLA-B*15:02 as genetic markers for carbamazepine hypersensitivity in children

    Science.gov (United States)

    Amstutz, Ursula; Ross, Colin J.D.; Castro-Pastrana, Lucila I.; Rieder, Michael J.; Shear, Neil H.; Hayden, Michael R.; Carleton, Bruce C.

    2013-01-01

    The occurrence of hypersensitivity reactions including rare but life-threatening Stevens-Johnson syndrome (SJS) and drug-induced hypersensitivity syndrome (HSS) limits the use of the anticonvulsant carbamazepine (CBZ). HLA-B*15:02 and HLA-A*31:01 have been identified as predictive genetic markers for CBZ hypersensitivity in Asian and European patients. To replicate these genetic associations in pediatric patients from North America with a diverse ethnic background, we investigated HLA-A*31:01 and HLA-B*15:02 in 42 children with CBZ hypersensitivity, and 91 CBZ-tolerant children from across Canada. HLA-A*31:01 was significantly associated with CBZ-HSS (odds ratio (OR): 26.4, p=0.0025) and maculopapular exanthems (OR: 8.6, p=0.0037), but not with CBZ-SJS. Conversely, HLA-B*15:02 was associated with CBZ-SJS (OR: 38.6, p=0.002), but not HSS and maculopapular exanthems. This study is the first to demonstrate the association of HLA-A*31:01 with CBZ hypersensitivity in children, providing important replication of this association and highlighting the importance of HLA-A*31:01 as a predictive biomarker across various ancestries. PMID:23588310

  17. Gastroesophageal reflux symptoms not responding to proton pump inhibitor: GERD, NERD, NARD, esophageal hypersensitivity or dyspepsia?

    Science.gov (United States)

    Bashashati, Mohammad; Hejazi, Reza A; Andrews, Christopher N; Storr, Martin A

    2014-01-01

    Gastroesophageal reflux (GER) is a common gastrointestinal process that can generate symptoms of heartburn and chest pain. Proton pump inhibitors (PPIs) are the gold standard for the treatment of GER; however, a substantial group of GER patients fail to respond to PPIs. In the past, it was believed that acid reflux into the esophagus causes all, or at least the majority, of symptoms attributed to GER, with both erosive esophagitis and nonerosive outcomes. However, with modern testing techniques it has been shown that, in addition to acid reflux, the reflux of nonacid gastric and duodenal contents into the esophagus may also induce GER symptoms. It remains unknown how weakly acidic or alkaline refluxate with a pH similar to a normal diet induces GER symptoms. Esophageal hypersensitivity or functional dyspepsia with superimposed heartburn may be other mechanisms of symptom generation, often completely unrelated to GER. Detailed studies investigating the pathophysiology of esophageal hypersensitivity are not conclusive, and definitions of the various disease states may overlap and are often confusing. The authors aim to clarify the pathophysiology, definition, diagnostic techniques and medical treatment of patients with heartburn symptoms who fail PPI therapy. PMID:24719900

  18. Fexofenadine Suppresses Delayed-Type Hypersensitivity in the Murine Model of Palladium Allergy

    Directory of Open Access Journals (Sweden)

    Ryota Matsubara

    2017-06-01

    Full Text Available Palladium is frequently used in dental materials, and sometimes causes metal allergy. It has been suggested that the immune response by palladium-specific T cells may be responsible for the pathogenesis of delayed-type hypersensitivity in study of palladium allergic model mice. In the clinical setting, glucocorticoids and antihistamine drugs are commonly used for treatment of contact dermatitis. However, the precise mechanism of immune suppression in palladium allergy remains unknown. We investigated inhibition of the immune response in palladium allergic mice by administration of prednisolone as a glucocorticoid and fexofenadine hydrochloride as an antihistamine. Compared with glucocorticoids, fexofenadine hydrochloride significantly suppressed the number of T cells by interfering with the development of antigen-presenting cells from the sensitization phase. Our results suggest that antihistamine has a beneficial effect on the treatment of palladium allergy compared to glucocorticoids.

  19. Delayed-Type Hypersensitivity to Metals of Environmental Burden in Patients with Takotsubo Syndrome - Is There a Clinical Relevance?

    Directory of Open Access Journals (Sweden)

    Jan Manousek

    Full Text Available Takotsubo syndrome (TS is a heart condition characterised by a sudden transient left ventricular dysfunction; its pathophysiology is probably associated with elevated levels of catecholamines but the exact mechanism is not known as yet. Literature and clinical experience suggest that TS affects persons with various comorbidities. This pilot work aims to evaluate the frequency of comorbidities with potential pathological immune reactivity, and to evaluate the potential association between TS and hypersensitivity to metals assessed by LTT-MELISA®.A total of 24 patients (23 women, 1 man with a history of TS attack and 27 healthy controls were evaluated. Hypersensitivity was evaluated by a lymphocyte transformation test (LTT-MELISA®; a questionnaire of environmental burden was used to select evaluated metals. A total of 19 patients (79% had at least one condition that might potentially be associated with pathological immune reactivity (autoimmune thyroid disease, drug allergy, bronchial asthma, cancer, contact dermatitis, rheumatoid arthritis. Hypersensitivity to metals was identified significantly more frequently in TS patients than in healthy controls (positive reaction to at least one metal was identified in 95.8% of TS patients and in 59.3% of controls; p = 0.003; the difference was statistically significant for mercury (45.8% and 14.8%, respectively; p = 0.029.Our work shows that conditions with pathological immune reactivity occur frequently in TS patients, and our data suggest a possible association between TS and hypersensitivity to metals (mercury in particular evaluated by LTT-MELISA®. We also suggest that apart from the triggering stress factor, potential existence of other serious conditions should be considered when taking medical history of TS patients.

  20. Delayed-Type Hypersensitivity to Metals of Environmental Burden in Patients with Takotsubo Syndrome – Is There a Clinical Relevance?

    Science.gov (United States)

    Manousek, Jan; Stejskal, Vera; Kubena, Petr; Jarkovsky, Jiri; Nemec, Petr; Lokaj, Petr; Dostalova, Ludmila; Zadakova, Andrea; Pavlusova, Marie; Benesova, Klara; Kala, Petr; Miklik, Roman; Spinar, Jindrich; Parenica, Jiri

    2016-01-01

    Objective Takotsubo syndrome (TS) is a heart condition characterised by a sudden transient left ventricular dysfunction; its pathophysiology is probably associated with elevated levels of catecholamines but the exact mechanism is not known as yet. Literature and clinical experience suggest that TS affects persons with various comorbidities. This pilot work aims to evaluate the frequency of comorbidities with potential pathological immune reactivity, and to evaluate the potential association between TS and hypersensitivity to metals assessed by LTT-MELISA®. Methodology, Results A total of 24 patients (23 women, 1 man) with a history of TS attack and 27 healthy controls were evaluated. Hypersensitivity was evaluated by a lymphocyte transformation test (LTT-MELISA®); a questionnaire of environmental burden was used to select evaluated metals. A total of 19 patients (79%) had at least one condition that might potentially be associated with pathological immune reactivity (autoimmune thyroid disease, drug allergy, bronchial asthma, cancer, contact dermatitis, rheumatoid arthritis). Hypersensitivity to metals was identified significantly more frequently in TS patients than in healthy controls (positive reaction to at least one metal was identified in 95.8% of TS patients and in 59.3% of controls; p = 0.003); the difference was statistically significant for mercury (45.8% and 14.8%, respectively; p = 0.029). Conclusion Our work shows that conditions with pathological immune reactivity occur frequently in TS patients, and our data suggest a possible association between TS and hypersensitivity to metals (mercury in particular) evaluated by LTT-MELISA®. We also suggest that apart from the triggering stress factor, potential existence of other serious conditions should be considered when taking medical history of TS patients. PMID:27824862

  1. Management of Insect Sting Hypersensitivity: An Update

    OpenAIRE

    Pesek, Robert D.; Lockey, Richard F.

    2013-01-01

    Reactions to Hymenoptera insect stings are common. While most are self-limited, some induce systemic allergic reactions or anaphylaxis. Prompt recognition, diagnosis, and treatment of these reactions are important for improving quality-of-life and reducing the risk of future sting reactions. This review summarizes the current recommendations to diagnose and treat Hymenoptera sting induced allergic reactions and highlights considerations for various populations throughout the world.

  2. Sleep fragmentation exacerbates mechanical hypersensitivity and alters subsequent sleep-wake behavior in a mouse model of musculoskeletal sensitization.

    Science.gov (United States)

    Sutton, Blair C; Opp, Mark R

    2014-03-01

    Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on subsequent sleep of mice as demonstrated by increased

  3. Contact activation: a revision.

    Science.gov (United States)

    Schmaier, A H

    1997-07-01

    In conclusion, a revised view of the contact system has been presented. This system has little to do with the initiation of hemostasis. Like lupus anticoagulants, deficiencies of contact proteins give prolonged APTTs but may be risk factors for thrombosis. BK from kininogens is a potent modulator of vascular biology inducing vasodilation, tissue plasminogen activator release, and prostacyclin liberation. Kininogens, themselves, are selective inhibitors of alpha-thrombin-induced platelet activation preventing alpha-thrombin from cleaving the cloned thrombin receptor after arginine41. Kininogens' alpha-thrombin inhibitory activity exists in intact kininogens, BK, and all of BK's breakdown products. HK also is the pivotal protein for contact protein assembly on endothelium. It is the receptor for prekallikrein which when bound to HK becomes activated to kallikrein by an endothelial cell enzyme system independent of activated forms of plasma factor XII. Prekallikrein activation on endothelial cells results in kinetically favorable single chain urokinase and plasminogen activation. Thus the "physiologic, negatively charged surface" for contact system activation is really the assembly of these proteins on cell membranes and activation by membrane-associated enzymes.

  4. Hypersensitivity reactions to penicillins: studies in a group of patients with negative benzylpenicillin G skin test.

    Science.gov (United States)

    Qiao, H-L; Li, Z; Yang, J; Tian, X; Gao, N; Jia, L-J

    2009-06-01

    Although skin tests are usually employed to evaluate current penicillin allergy status, a negative result does not exclude hypersensitivity. There is a need for accurate in vitro tests to exclude hypersensitivity. A radioallergosorbent test (RAST) is a potentially good supplementary approach, but there is little information on the suitability of this method to diagnose penicillin hypersensitivity in subjects with a negative skin test to benzylpenicillin. A total of 133 patients with a negative skin test to benzylpenicillin G (PG) and all of whom developed allergic reactions to PG were studied. RAST was used to detect eight kinds of specific IgE antibodies to penicillins in serum, which included four kinds of major and minor antigenic determinants to four penicillin drugs. The combination sites for the specific IgE antibodies were studied by RAST inhibition test. The rate of positive reactions for the specific IgE antibodies was 59.40% (79/133). Of the eight kinds of antigenic determinants, the positive rates for specific IgE against the major and minor determinants were 39.10% (52) and 42.86% (57) respectively. Of the four drugs, positive cases only to PG were 10 (7.5%), were significantly fewer than the cross-reacting positive cases (36) to PG (P penicillins could induce specific responses with a variable degree of cross-reactivity among the different penicillins. Radioallergosorbent test is a good complementary test in persons who are skin-test negative with PG, and the sensitivity of RAST increases with increasing specificity of IgE antibodies to be detected. 6-APA and the groups, making part of the different side-chains on penicillins, all contributed to the cross-reactivity.

  5. Annealing-induced interfacial reactions and the effects on the electrical properties of Ga doped ZnO/CuxS contacts to p-GaN

    International Nuclear Information System (INIS)

    Gu, Wen; Wu, Xingyang; Song, Peng; Zhang, Jianhua

    2015-01-01

    Highlights: • The electrical properties of GZO/CuS x contacts to p-GaN annealed at different temperatures in air have been studied. • Ohmic contacts were formed by annealing the contacts at 500 and 600 °C in air. • The oxygen in air was found to be essential for the formation of ohmic contact. • The possible formation mechanism of the ohmic contacts was illustrated. - Abstract: Ga-doped ZnO (GZO) contacts to p-GaN were investigated by using Cu x S interlayers under different annealing temperatures. It is shown that the GZO/Cu x S contacts annealed at 300 and 400 °C for 3 min in air exhibited non-ohmic characteristics. However, annealing the contacts at 500 and 600 °C in air resulted in linear current–voltage characteristics. The lowest specific contact resistivity of 1.66 × 10 −2 Ω cm 2 was obtained for the contact annealed at 500 °C. To account for the formation mechanism of the ohmic contact, AES and XPS were used to analyze the interfacial properties of the GZO/Cu x S/p-GaN and Cu x S/p-GaN interfaces, respectively. The possible reasons were discussed in detail, suggesting that the interfacial reactions and atomic diffusions are thought to be responsible for forming such a low contact resistance

  6. Acupuncture Alleviates Colorectal Hypersensitivity and Correlates with the Regulatory Mechanism of TrpV1 and p-ERK

    Directory of Open Access Journals (Sweden)

    Shao-Jun Wang

    2012-01-01

    Full Text Available Here we used a mouse model of zymosan-induced colorectal hypersensitivity, a similar model of IBS in our previous work, to evaluate the effectiveness of the different number of times of acupuncture and elucidate its potential mechanism of EA treatment. Colorectal distension (CRD tests show that intracolonic zymosan injection does, while saline injection does not, induce a typical colorectal hypersensitivity. EA treatment at classical acupoints Zusanli (ST36 and Shangjuxu (ST37 in both hind limbs for 15 min slightly attenuated and significantly blunted the hypersensitive responses after first and fifth acupunctures, respectively, to colorectal distention in zymosan treatment mice, but not in saline treatment mice. Western blot results indicated that ion channel and TrpV1 expression in colorectum as well as ERK1/2 MAPK pathway activation in peripheral and central nerve system might be involved in this process. Hence, we conclude that EA is a potential therapeutic tool in the treatment and alleviation of chronic abdominal pain, and the effectiveness of acupuncture analgesia is accumulative with increased number of times of acupuncture when compared to that of a single time of acupuncture.

  7. A preconditioning nerve lesion inhibits mechanical pain hypersensitivity following subsequent neuropathic injury

    Directory of Open Access Journals (Sweden)

    Wu Ann

    2011-01-01

    Full Text Available Abstract Background A preconditioning stimulus can trigger a neuroprotective phenotype in the nervous system - a preconditioning nerve lesion causes a significant increase in axonal regeneration, and cerebral preconditioning protects against subsequent ischemia. We hypothesized that a preconditioning nerve lesion induces gene/protein modifications, neuronal changes, and immune activation that may affect pain sensation following subsequent nerve injury. We examined whether a preconditioning lesion affects neuropathic pain and neuroinflammation after peripheral nerve injury. Results We found that a preconditioning crush injury to a terminal branch of the sciatic nerve seven days before partial ligation of the sciatic nerve (PSNL; a model of neuropathic pain induced a significant attenuation of pain hypersensitivity, particularly mechanical allodynia. A preconditioning lesion of the tibial nerve induced a long-term significant increase in paw-withdrawal threshold to mechanical stimuli and paw-withdrawal latency to thermal stimuli, after PSNL. A preconditioning lesion of the common peroneal induced a smaller but significant short-term increase in paw-withdrawal threshold to mechanical stimuli, after PSNL. There was no difference between preconditioned and unconditioned animals in neuronal damage and macrophage and T-cell infiltration into the dorsal root ganglia (DRGs or in astrocyte and microglia activation in the spinal dorsal and ventral horns. Conclusions These results suggest that prior exposure to a mild nerve lesion protects against adverse effects of subsequent neuropathic injury, and that this conditioning-induced inhibition of pain hypersensitivity is not dependent on neuroinflammation in DRGs and spinal cord. Identifying the underlying mechanisms may have important implications for the understanding of neuropathic pain due to nerve injury.

  8. Incidence of abacavir hypersensitivity reactions in euroSIDA

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Friis-Møller, Nina; Mocroft, Amanda

    2008-01-01

    BACKGROUND: The aim of the study was to investigate the incidence of abacavir-related hypersensitivity reaction (HSR) and associated deaths in EuroSIDA HIV-1-infected patients. METHODS: Poisson regression models were developed to compare incidence of abacavir discontinuation according to the line...

  9. Auditory Hypersensitivity in Children with Autism Spectrum Disorders

    Science.gov (United States)

    Lucker, Jay R.

    2013-01-01

    A review of records was completed to determine whether children with auditory hypersensitivities have difficulty tolerating loud sounds due to auditory-system factors or some other factors not directly involving the auditory system. Records of 150 children identified as not meeting autism spectrum disorders (ASD) criteria and another 50 meeting…

  10. Culicoides species attracted to horses with and without insect hypersensitivity

    NARCIS (Netherlands)

    Rijt, van der R.; Boom, van den R.; Jongema, Y.; Sloet van Oldruitenborgh-Oosterbaan, M.M.

    2008-01-01

    The aims of this study were to determine (1) which species of Culicoides is most commonly attracted to horses, (2) whether horses suffering insect hypersensitivity attract more Culicoides spp. than unaffected horses, and (3) the times when Culicoides spp. are most active. Horses affected by insect

  11. Trichloroethylene hypersensitivity syndrome: a disease of fatal outcome.

    Science.gov (United States)

    Jung, Hyun Gul; Kim, Hyung Hun; Song, Bong Gun; Kim, Eun Jin

    2012-01-01

    Trichloroethylene is commonly used as an industrial solvent and degreasing agent. The clinical features of acute and chronic intoxication with trichloroethylene are well-known and have been described in many reports, but hypersensitivity syndrome caused by trichloroethylene is rarely encountered. For managing patients with trichloroethylene hypersensitivity syndrome, avoiding trichloroethylene and initiating glucocorticoid have been generally accepted. Generally, glucocorticoid had been tapered as trichloroethylene hypersensitivity syndrome had ameliorated. However, we encountered a typical case of trichloroethylene hypersensitivity syndrome refractory to high dose glucocorticoid treatment. A 54-year-old Korean man developed jaundice, fever, red sore eyes, and generalized erythematous maculopapular rashes. A detailed history revealed occupational exposure to trichloroethylene. After starting intravenous methylprednisolone, his clinical condition improved remarkably, but we could not reduce prednisolone because his liver enzyme and total bilirubin began to rise within 2 days after reducing prednisolone under 60 mg/day. We recommended an extended admission for complete recovery, but the patient decided to leave the hospital against medical advice. The patient visited the emergency department due to pneumonia and developed asystole, which did not respond to resuscitation.

  12. Cyproterone acetate in the treatment of oestrogen hypersensitivity vulvovaginitis.

    Science.gov (United States)

    Nguyen, Yvonne; Bradford, Jennifer; Fischer, Gayle

    2018-02-01

    Oestrogen hypersensitivity vulvovaginitis is a rare chronic cyclical vulvovaginitis responsive to oestrogen suppression or antagonism. We present a case series of 16 patients with refractory cyclical vulvovaginitis, all of whom responded to oestrogen suppression with cyproterone acetate. © 2017 The Australasian College of Dermatologists.

  13. Prioritized Contact Transport Stream

    Science.gov (United States)

    Hunt, Walter Lee, Jr. (Inventor)

    2015-01-01

    A detection process, contact recognition process, classification process, and identification process are applied to raw sensor data to produce an identified contact record set containing one or more identified contact records. A prioritization process is applied to the identified contact record set to assign a contact priority to each contact record in the identified contact record set. Data are removed from the contact records in the identified contact record set based on the contact priorities assigned to those contact records. A first contact stream is produced from the resulting contact records. The first contact stream is streamed in a contact transport stream. The contact transport stream may include and stream additional contact streams. The contact transport stream may be varied dynamically over time based on parameters such as available bandwidth, contact priority, presence/absence of contacts, system state, and configuration parameters.

  14. Ultraviolet-irradiated urocanic acid suppresses delayed-type hypersensitivity to herpes simplex virus in mice

    International Nuclear Information System (INIS)

    Ross, J.A.; Howie, S.E.; Norval, M.; Maingay, J.; Simpson, T.J.

    1986-01-01

    Ultraviolet radiation is known to induce a transient defect in epidermal antigen presentation which leads to the generation of antigen-specific suppression of the delayed-type hypersensitivity (DTH) response. The putative receptor in skin for the primary event in UV-suppression is urocanic acid (UCA) which may then interact locally, or systemically, with antigen presenting cells or initiate a cascade of events resulting in suppression. We present the first direct evidence that UCA, when irradiated with a dose (96 mJ/cm2) of UVB radiation known to suppress the DTH response to herpes simplex virus, type 1 (HSV-1) in mice, can induce suppression following epidermal application or s.c. injection of the irradiated substance. This suppression is transferable with nylon wool-passed spleen cells

  15. Impact-Induced Muscle Damage and Contact-Sport: Aetiology, Effects on Neuromuscular Function and Recovery, and the Modulating Effects of Adaptation and Recovery Strategies.

    Science.gov (United States)

    Naughton, Mitchell; Miller, Joanna; Slater, Gary J

    2017-11-28

    Athletes involved in contact-sports are habitually exposed to skeletal muscle damage as part of their training and performance environments. This often leads to exercise-induced muscle damage (EIMD) resulting from repeated eccentric and/or high-intensity exercise, and impact-induced muscle damage (IIMD) resulting from collisions with opponents and the playing surface. Whilst EIMD has been an area of extensive investigation, IIMD has received comparatively little research, with the magnitude and timeframe of alterations following IIMD not presently well understood. It is currently thought that EIMD occurs through an overload of mechanical stress causing ultrastructural damage to the cellular membrane constituents. Damage leads to compromised ability to produce force which manifest immediately and persist for up to 14 days following exercise exposure. IIMD has been implicated in attenuated neuromuscular performance and recovery with inflammatory process implicated, although the underlying time course remains unclear. Exposure to EIMD leads to an adaptation to subsequent exposures, a phenomenon known as the repeated-bout effect. An analogous adaptation has been suggested to occur following IIMD, however, to date this contention remains equivocal. Whilst a considerable body of research has explored the efficacy of recovery strategies following EIMD, strategies promoting recovery from IIMD are limited to investigations using animal contusion models. Strategies such as cryotherapy and antioxidant supplementation, which focus on attenuating the secondary inflammatory response may provide additional benefit in IIMD and are explored herein. Further research is required to firstly establish a model of generating IIMD and then explore broader areas around IIMD in athletic populations.

  16. Protective effects of different marigold (Calendula officinalis L.) and rosemary cream preparations against sodium-lauryl-sulfate-induced irritant contact dermatitis.

    Science.gov (United States)

    Fuchs, S M; Schliemann-Willers, S; Fischer, T W; Elsner, P

    2005-01-01

    In the present study, we evaluated the protective action of cream preparations containing seven different types of marigold and rosemary extracts in vivo in healthy volunteers with experimentally induced irritant contact dermatitis (ICD). Marigold and rosemary extracts in base cream DAC (Deutscher Arzneimittel-Codex = German Pharmaceutical Codex) were tested in a 4-day repetitive irritation test using sodium lauryl sulfate. The effect was evaluated visually and quantified by noninvasive bioengineering methods, namely chromametry and tewametry. When the test products were applied parallel to the induction period of ICD, a statistically significant protective effect of all cream preparations was observed by all methods. This effect, although not statistically significant, was superior to control by undyed marigold und faradiol ester-enriched extracts in chromametry and by dyed and undyed rosemary extracts in tewametry. The sequential treatment (postirritation) once a day for 5 days was without any effect. Thus, a protective effect of some marigold and rosemary extracts against ICD could be shown in the elicitation phase. Copyright (c) 2005 S. Karger AG, Basel.

  17. Easter egg hunt dermatitis: systemic allergic contact dermatitis associated with chocolate ingestion.

    Science.gov (United States)

    Jacob, Sharon E; Hamann, Dathan; Goldenberg, Alina; Connelly, Elizabeth A

    2015-01-01

    Pediatric systemic allergic contact dermatitis to nickel has previously been reported in association with cocoa. We present four clinical cases of hypersensitivity temporally associated with chocolate consumption at Easter. Clinicians should be aware of the potential for foods high in nickel to provoke patients with known nickel sensitivity and systemic dermatitis. © 2014 Wiley Periodicals, Inc.

  18. The Edible Brown Seaweed Ecklonia cava Reduces Hypersensitivity in Postoperative and Neuropathic Pain Models in Rats

    Directory of Open Access Journals (Sweden)

    Jae Goo Kim

    2014-06-01

    Full Text Available The current study was designed to investigate whether edible brown seaweed Ecklonia cava extracts exhibits analgesic effects in plantar incision and spared nerve injury (SNI rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT and thermal hypersensitivity tests measured by von Frey filaments and a hot/cold plate analgesia meter. Pain-related behavior was also determined through analysis of ultrasonic vocalization. The results of experiments showed MWT values of the group that was treated with E. cava extracts by 300 mg/kg significantly increased; on the contrary, number of ultrasonic distress vocalization of the treated group was reduced at 6 h and 24 h after plantar incision operation (62.8%, p < 0.05. Moreover, E. cava 300 mg/kg treated group increased the paw withdrawal latency in hot-and cold-plate tests in the plantar incision rats. After 15 days of continuous treatment with E. cava extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity response by MWT compared with the control group. In conclusion, these results suggest that E. cava extracts have potential analgesic effects in the case of postoperative pain and neuropathic pain in rats.

  19. A comparative behavioural study of mechanical hypersensitivity in 2 pain models in rats and humans.

    Science.gov (United States)

    Reitz, Marie-Céline; Hrncic, Dragan; Treede, Rolf-Detlef; Caspani, Ombretta

    2016-06-01

    The assessment of pain sensitivity in humans has been standardized using quantitative sensory testing, whereas in animals mostly paw withdrawal thresholds to diverse stimuli are measured. This study directly compares tests used in quantitative sensory testing (pinpricks, pressure algometer) with tests used in animal studies (electronic von Frey test: evF), which we applied to the dorsal hind limbs of humans after high frequency stimulation and rats after tibial nerve transection. Both experimental models induce profound mechanical hypersensitivity. At baseline, humans and rats showed a similar sensitivity to evF with 0.2 mm diameter tips, but significant differences for other test stimuli (all P pain models (P pain sensitivity, but probe size and shape should be standardized. Hypersensitivity to blunt pressure-the leading positive sensory sign after peripheral nerve injury in humans-is a novel finding in the tibial nerve transection model. By testing outside the primary zone of nerve damage (rat) or activation (humans), our methods likely involve effects of central sensitization in both species.

  20. Hypersensitivity reactions to food colours with special reference to the natural colour annatto extract (butter colour).

    Science.gov (United States)

    Mikkelsen, H; Larsen, J C; Tarding, F

    1978-01-01

    It is well known that synthetic food colours especially some azo dyes can provoke hypersensitivity reactions such as urticaria, angioneurotic oedema, and astma (Michaëlsson and Juhlin, 1973, Granholt and Thune, 1975). Natural food colours are scarcely investigated with respect to potential allergic properties. Annatto extract, a commonly used food colour in edible fats e.g. butter, has been tested in patients. Among 61 consecutive patients suffereing from chornic urticaria and/or angioneurotic oedema 56 patients were orally provoked by annatto extract during elimination diet. Challenge was performed with a dose equivalent to the amount used in 25 grammes of butter. Twentysix per cent of the patients reacted to this colour 4 hours (SD: 2,6) after intake. Similar challenges with synthetic dyes showed the following results: Tartrazine 11%, Sunset Yellow FCF 17%, Food Red 17 16%, Amaranth 9%, Ponceau 4 R 15%, Erythrosine 12% and Brillant Blue FCF 14%. The present study indicates that natural food colours may induce hypersensitivity reactions as frequent as synthetic dyes.

  1. A Comparative Study of the Expression of Cytotoxic Proteins in Allergic Contact Dermatitis and Psoriasis : Spongiotic Skin Lesions in Allergic Contact Dermatitis Are Highly Infiltrated by T Cells Expressing Perforin and Granzyme B

    OpenAIRE

    Yawalkar, Nikhil; Hunger, Robert E.; Buri, Caroline; Schmid, Simone; Egli, Fabienne; Brand, Christoph U.; Mueller, Christoph; Pichler, Werner J.; Braathen, Lasse R.

    2001-01-01

    Recent reports indicate that cytotoxic T cells are critically involved in contact hypersensitivity reactions in animals. In this study we sought to investigate the in vivo expression of cytotoxic granule proteins in the elicitation phase of allergic contact dermatitis in humans. Skin biopsy specimens were obtained from patients with allergic contact dermatitis (n = 8) and psoriasis (n = 6) and from controls with normal skin (n = 6). Expression of perforin and granzyme B was investigated by in...

  2. p38 MAPK inhibition suppresses the TLR-hypersensitive phenotype in FANCC- and FANCA-deficient mononuclear phagocytes

    Science.gov (United States)

    Anur, Praveen; Yates, Jane; Garbati, Michael R.; Vanderwerf, Scott; Keeble, Winifred; Rathbun, Keaney; Hays, Laura E.; Tyner, Jeffrey W.; Svahn, Johanna; Cappelli, Enrico; Dufour, Carlo

    2012-01-01

    Fanconi anemia, complementation group C (FANCC)–deficient hematopoietic stem and progenitor cells are hypersensitive to a variety of inhibitory cytokines, one of which, TNFα, can induce BM failure and clonal evolution in Fancc-deficient mice. FANCC-deficient macrophages are also hypersensitive to TLR activation and produce TNFα in an unrestrained fashion. Reasoning that suppression of inhibitory cytokine production might enhance hematopoiesis, we screened small molecules using TLR agonist–stimulated FANCC- and Fanconi anemia, complementation group A (FANCA)–deficient macrophages containing an NF-κB/AP-1–responsive reporter gene (SEAP). Of the 75 small molecules screened, the p38 MAPK inhibitor BIRB 796 and dasatinib potently suppressed TLR8-dependent expression of the reporter gene. Fanconi anemia (FA) macrophages were hypersensitive to the TLR7/8 activator R848, overproducing SEAP and TNFα in response to all doses of the agonist. Low doses (50nM) of both agents inhibited p38 MAPK–dependent activation of MAPKAPK2 (MK2) and suppressed MK2-dependent TNFα production without substantially influencing TNFα gene transcription. Overproduction of TNFα by primary FA cells was likewise suppressed by these agents and involved inhibition of MK2 activation. Because MK2 is also known to influence production and/or sensitivity to 2 other suppressive factors (MIP-1α and IFNγ) to which FA hematopoietic progenitor cells are uniquely vulnerable, targeting of p38 MAPK in FA hematopoietic cells is a rational objective for preclinical evaluation. PMID:22234699

  3. p38 MAPK inhibition suppresses the TLR-hypersensitive phenotype in FANCC- and FANCA-deficient mononuclear phagocytes.

    Science.gov (United States)

    Anur, Praveen; Yates, Jane; Garbati, Michael R; Vanderwerf, Scott; Keeble, Winifred; Rathbun, Keaney; Hays, Laura E; Tyner, Jeffrey W; Svahn, Johanna; Cappelli, Enrico; Dufour, Carlo; Bagby, Grover C

    2012-03-01

    Fanconi anemia, complementation group C (FANCC)-deficient hematopoietic stem and progenitor cells are hypersensitive to a variety of inhibitory cytokines, one of which, TNFα, can induce BM failure and clonal evolution in Fancc-deficient mice. FANCC-deficient macrophages are also hypersensitive to TLR activation and produce TNFα in an unrestrained fashion. Reasoning that suppression of inhibitory cytokine production might enhance hematopoiesis, we screened small molecules using TLR agonist-stimulated FANCC- and Fanconi anemia, complementation group A (FANCA)-deficient macrophages containing an NF-κB/AP-1-responsive reporter gene (SEAP). Of the 75 small molecules screened, the p38 MAPK inhibitor BIRB 796 and dasatinib potently suppressed TLR8-dependent expression of the reporter gene. Fanconi anemia (FA) macrophages were hypersensitive to the TLR7/8 activator R848, overproducing SEAP and TNFα in response to all doses of the agonist. Low doses (50nM) of both agents inhibited p38 MAPK-dependent activation of MAPKAPK2 (MK2) and suppressed MK2-dependent TNFα production without substantially influencing TNFα gene transcription. Overproduction of TNFα by primary FA cells was likewise suppressed by these agents and involved inhibition of MK2 activation. Because MK2 is also known to influence production and/or sensitivity to 2 other suppressive factors (MIP-1α and IFNγ) to which FA hematopoietic progenitor cells are uniquely vulnerable, targeting of p38 MAPK in FA hematopoietic cells is a rational objective for preclinical evaluation.

  4. The Possible Role of Contact Sensitization to Fragrances and Preservatives in Poikiloderma of Civatte

    OpenAIRE

    Khunkhet S; Wattanakrai P

    2014-01-01

    Numerous mechanisms have been postulated to play an important role in the pathogenesis of poikiloderma of Civatte, including chronic exposure to ultraviolet radiation, menopause-related hormonal changes, contact hypersensitivity and genetic predisposition. Herein, we report a case of contact sensitization to fragrances and commonly used preservatives, methylchloroisothiazolinone and methylisothiazolinone, also widely known as Kathon CG, in a post-menopausal woman with poikiloderma of Civatte,...

  5. The Possible Role of Contact Sensitization to Fragrances and Preservatives in Poikiloderma of Civatte

    OpenAIRE

    Khunkhet, Saranya; Wattanakrai, Penpun

    2014-01-01

    Numerous mechanisms have been postulated to play an important role in the pathogenesis of poikiloderma of Civatte (PC), including chronic exposure to ultraviolet radiation, menopause-related hormonal changes, contact hypersensitivity and genetic predisposition. Herein, we report a case of contact sensitization to fragrances and commonly used preservatives, methylchloroisothiazolinone and methylisothiazolinone, also widely known as Kathon CG, in a post-menopausal woman with PC, who denied exce...

  6. Cow's milk protein allergy and other food hypersensitivities in infants.

    Science.gov (United States)

    Venter, Carina

    2009-01-01

    Food hypersensitivity (FHS) is the umbrella term used to describe both food allergy, which involves the immune system, and food intolerances, which do not. It is therefore important that the diagnosis is made by a specialist health care professional such as a paediatrician or allergist. Some experienced dietitians and health visitors may be able to assist in making a diagnosis. The diagnostic work-up includes a medical history and blood tests/skin tests (where applicable). A food and symptom diary followed by a special test diet to identify the foods causing the infant's symptoms may also be needed. Once a diagnosis is made, dietary advice should be given to eliminate or reduce the intake of the offending foods. For cow's milk hypersensitivity in infants, this will include choosing the most appropriate specialised infant formula.

  7. The Role of Esophageal Hypersensitivity in Functional Esophageal Disorders.

    Science.gov (United States)

    Farmer, Adam D; Ruffle, James K; Aziz, Qasim

    2017-02-01

    The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.

  8. The Prevalence of food hypersensitivity in young adults

    DEFF Research Database (Denmark)

    Østerballe, Morten; Mørtz, Charlotte G; Hansen, Tine Kjær

    2009-01-01

    by questionnaire, skin prick test (SPT) and histamin release (HR) followed by oral challenge to the most common allergenic foods. FHS was divided into primary and secondary FHS. Primary FHS was defined as being independent of pollen sensitization, whereas secondary FHS was defined as reactions to pollen related......Osterballe M, Mortz CG, Hansen TK, Andersen KE, Bindslev-Jensen C. The Prevalence of food hypersensitivity in young adults. Pediatr Allergy Immunol 2009. (c) 2009 The Authors Journal compilation (c) 2009 John Wiley & Sons A/SA rising prevalence of food hypersensitivity (FHS) and severe allergic...... reactions to foods have been reported in the last decade. However, little is known on the prevalence in young adults. This study estimated the prevalence of FHS to the most common allergenic foods in an unselected population of young adults. We investigated a cohort of 1272 young adults 22 years of age...

  9. Old, new and hidden causes of perioperative hypersensitivity

    DEFF Research Database (Denmark)

    Garvey, Lene Heise

    2016-01-01

    intravenously such as neuromuscular blocking agents (NMBA), induction agents and antibiotics have traditionally been reported to be implicated most commonly. It has recently become apparent that there are geographical differences in sensitization patterns related to variation in exposures, referral patterns...... and performance and interpretation of investigations. Differences in sensitization to NMBAs are partly explained by cross sensitization to pholcodine, an ingredient in cough-medicines available in some countries. While NMBAs are the most common causes of perioperative hypersensitivity in some countries, this may...... in causes of perioperative hypersensitivity emerging over time and to increase awareness about the “hidden allergens” in the perioperative setting. Some practical advice on how to approach the patient testing negative on all initial investigations is also included....

  10. [Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab].

    Science.gov (United States)

    Boin, C; Lambert, S; Thomann, P; Aujoulat, O; Kieffer, P

    2016-06-01

    Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  11. Investigation into the effects of using two or four acupuncture needles with bidirectional rotation on experimentally-induced contact heat pain in healthy subjects.

    Science.gov (United States)

    Paley, Carole A; Johnson, Mark I

    2015-02-01

    There is growing evidence from experimental studies that the acupuncture dose or technique influences the speed of onset of hypoalgesia. The aim of this study was to investigate the effects of acupuncture using two or four needles on experimental contact thermal pain in healthy volunteers. Forty two participants were randomised into three groups: four-needle group (LI4, LI11, LI10, TE5), two-needle group (verum at LI4, LI11 and mock at LI10, TE5) and mock acupuncture group (LI4, LI11, LI10, TE5). Each participant rated pain intensity (visual analogue scale, VAS) to a series of noxious stimuli administered to the forearm 2°C above the heat pain threshold during needling and immediately after removal of the needles. Experimentally-induced heat pain intensity (VAS) during and after the intervention was lower than pre-intervention but there were no statistically significant differences in this change between groups. There were no statistically significant differences between groups in the time taken for pain intensity to decrease by 33% from pre-intervention. However, a 33% decrease in pain intensity within 3 min of needle insertion was observed for 13 participants (92.9%) in the four-needle group compared with 66.7% of participants in the two-needle group and 57.1% in the mock acupuncture group. There was less variance in VAS in the four-needle group, suggesting more consistency in hypoalgesic response when using more needles. There is tentative evidence that four needles may be superior to two needles in generating rapid onset hypoalgesia. The findings suggest that further investigation is warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. IgE-mediated hypersensitivity reactions to cannabis in laboratory personnel.

    Science.gov (United States)

    Herzinger, T; Schöpf, P; Przybilla, B; Ruëff, F

    2011-01-01

    There have been sporadic reports of hypersensitivity reactions to plants of the Cannabinaceae family (hemp and hops), but it has remained unclear whether these reactions are immunologic or nonimmunologic in nature. We examined the IgE-binding and histamine-releasing properties of hashish and marijuana extracts by CAP-FEIA and a basophil histamine release test. Two workers at a forensic laboratory suffered from nasal congestion, rhinitis, sneezing and asthmatic symptoms upon occupational contact with hashish or marijuana, which they had handled frequently for 25 and 16 years, respectively. Neither patient had a history of atopic disease. Serum was analyzed for specific IgE antibodies to hashish or marijuana extract by research prototype ImmunoCAP, and histamine release from basophils upon exposure to hashish or marijuana extracts was assessed. Results were matched to those of 4 nonatopic and 10 atopic control subjects with no known history of recreational or occupational exposure to marijuana or hashish. Patient 1 had specific IgE to both hashish and marijuana (CAP class 2), and patient 2 to marijuana only (CAP class 2). Controls proved negative for specific IgE except for 2 atopic individuals with CAP class 1 to marijuana and 1 other atopic individual with CAP class 1 to hashish. Stimulation of basophils with hashish or marijuana extracts elicited histamine release from basophils of both patients and 4 atopic control subjects. Our results suggest an IgE-related pathomechanism for hypersensitivity reactions to marijuana or hashish. Copyright © 2011 S. Karger AG, Basel.

  13. A haemodynamic study of pulmonary hypertension in chronic hypersensitivity pneumonitis.

    Science.gov (United States)

    Oliveira, Rudolf K F; Pereira, Carlos A C; Ramos, Roberta P; Ferreira, Eloara V M; Messina, Carolina M S; Kuranishi, Lilian T; Gimenez, Andrea; Campos, Orlando; Silva, Célia M C; Ota-Arakaki, Jaquelina S

    2014-08-01

    Chronic hypersensitivity pneumonitis is a common fibrotic interstitial lung disease. The prevalence of pulmonary hypertension diagnosed by right heart catheterisation and its cardiopulmonary function findings in patients with chronic hypersensitivity pneumonitis are unknown. Consecutive symptomatic patients with chronic hypersensitivity pneumonitis were prospectively evaluated. All patients were submitted to right heart catheterisation, pulmonary function testing, a 6-min walk test, echocardiography, blood gas determination and N-terminal pro-brain natriuretic peptide analyses. Nonhypoxaemic patients also underwent incremental cardiopulmonary exercise testing. 50 patients underwent right heart catheterisation; 25 (50%) of these had pulmonary hypertension and 22 (44%) had a pre-capillary haemodynamic pattern. The patients with pre-capillary pulmonary hypertension had lower forced vital capacity (mean ± sd 50 ± 17% versus 69 ± 22% predicted, p<0.01), carbon monoxide diffusing capacity (37 ± 12% versus 47 ± 14% predicted, p<0.01), arterial oxygen tension (median (interquartile range) 59.0 (47.8-69.3) versus 73.0 (62.2-78.5) mmHg, p<0.01) and saturation after the 6-min walk test (78 ± 8% versus 86 ± 7%, p<0.01). In pre-capillary pulmonary hypertension, oxygen uptake was also lower at the anaerobic threshold (41 ± 11% versus 50 ± 8% predicted, p=0.04) and at peak exercise (12.8 ± 1.6 versus 15.0 ± 2.5 mL · kg(-1) · min(-1), p=0.02). Pre-capillary pulmonary hypertension is common in symptomatic chronic hypersensitivity pneumonitis and is related to interstitial lung disease severity. Additionally, pulmonary hypertension is more prevalent in hypoxaemic patients with impaired lung function and exercise capacity. ©ERS 2014.

  14. Induction of Hypozincemia and Hepatic Metallothionein Synthesis in Hypersensitivity Reactions.

    Science.gov (United States)

    1978-06-19

    cells to produce endogenous pyrogen (EP), the mediator of febrile response. Controversial evidence exists, however , concerning the differentiation of LEM...hypersensitivity reactions, Kampschmid t and Pulliam (1) proposed that leukocytic endogenous mediator (LEN) is released from phagocytic cells after... endogenous mediator(s) such as LEN, no conclusive evidence is available to indicate a mRNA requirement for the production of potential mediator(s

  15. Contact Lens Care

    Science.gov (United States)

    ... Consumers Consumer Information by Audience For Women Contact Lens Care Share Tweet Linkedin Pin it More sharing ... www.fda.gov/medwatch Learn More about Contact Lens Care Other Tips on Contact Lenses Decorative Contact ...

  16. Cracking the egg: An insight into egg hypersensitivity.

    Science.gov (United States)

    Dhanapala, Pathum; De Silva, Chamika; Doran, Tim; Suphioglu, Cenk

    2015-08-01

    Hypersensitivity to the chicken egg is a widespread disorder mainly affecting 1-2% of children worldwide. It is the second most common food allergy in children, next to cow's milk allergy. Egg allergy is mainly caused by hypersensitivity to four allergens found in the egg white; ovomucoid, ovalbumin, ovotransferrin and lysozyme. However, some research suggests the involvement of allergens exclusively found in the egg yolk such as chicken serum albumin and YGP42, which may play a crucial role in the overall reaction. In egg allergic individuals, these allergens cause conditions such as itching, atopic dermatitis, bronchial asthma, vomiting, rhinitis, conjunctivitis, laryngeal oedema and chronic urticaria, and anaphylaxis. Currently there is no permanent cure for egg allergy. Upon positive diagnosis for egg allergy, strict dietary avoidance of eggs and products containing traces of eggs is the most effective way of avoiding future hypersensitivity reactions. However, it is difficult to fully avoid eggs since they are found in a range of processed food products. An understanding of the mechanisms of allergic reactions, egg allergens and their prevalence, egg allergy diagnosis and current treatment strategies are important for future studies. This review addresses these topics and discusses both egg white and egg yolk allergy as a whole. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Suspected zonisamide-related anticonvulsant hypersensitivity syndrome in a cat.

    Science.gov (United States)

    Collinet, Audrey; Sammut, Veronique

    2017-12-15

    CASE DESCRIPTION A 2-year-old neutered male domestic shorthair cat was evaluated for sudden onset of cluster seizures. CLINICAL FINDINGS At an emergency clinic, the cat had hyperimmunoglobulinemia and thrombocytopenia. On referral, treatment with levetiracetam, zonisamide, and phenobarbital initially provided good control of cluster seizure activity (attributable to epilepsy of unknow origin). Two weeks later, assessments revealed that serum phenobarbital concentration was within the ideal range but serum zonisamide concentration exceeded the recommended therapeutic range. The dosage of zonisamide was therefore decreased. Four days after dosage reduction, the cat developed generalized lymphadenopathy. Cytologic analysis of lymph node aspirate samples revealed a heterogeneous population of well-differentiated lymphocytes, interpreted as marked reactivity. Although neoplasia could not be ruled out, hypersensitivity to phenobarbital was suspected, and this treatment was discontinued. TREATMENT AND OUTCOME Despite cessation of phenobarbital administration, generalized peripheral lymphadenopathy progressed and hyperglobulinemia and cytopenias developed. These abnormalities resolved after discontinuation of zonisamide administration. The cat remained seizure free with no recurrence of the aforementioned concerns after reinstitution of phenobarbital treatment. CLINICAL RELEVANCE To the authors' knowledge, this is the first reported case of zonisamide-related lymphadenopathy, hyperglobulinemia, and cytopenias in a cat. Anticonvulsant hypersensitivity syndrome is well documented in human medicine, but little information has been published in the veterinary medical literature. Although the effects of anticonvulsant hypersensitivity syndrome in this cat were serious, these effects were reversible with treatment discontinuation.

  18. Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Preschool Children

    Directory of Open Access Journals (Sweden)

    Kidon Mona

    2007-12-01

    Full Text Available Although extensively studied in adults, nonsteroidal anti-inflammatory drug (NSAID hypersensitivity in children, especially in young children, remains poorly defined. Pediatricians, prescribing antipyretics for children, rarely encounter significant problems, but the few epidemiologic studies performed show conflicting results. Although it is clear that some patients with acetylsalicylic acid (ASA-sensitive asthma have their clinical onset of disease in childhood and bronchoconstriction after ASA challenge is seen in 0 to 22% of asthmatic children so challenged, ibuprofen at antipyretic doses may cause acute respiratory problems only in a very small number of mild to moderate asthmatics. The recently elucidated mechanism of action of acetaminophen may explain some occurrences of adverse reactions in patients with cross-reactive NSAID hypersensitivity on the basis of its inhibitory activity on the newly described enzyme, cyclooxygenase (COX-3. This nonspecific sensitivity to inhibition of COX is most likely genetically determined and shows a remarkable association with atopic disease even in the very young age group and possibly an increased predilection in specific ethnic groups. This review summarizes state-of-the-art published data on NSAID hypersensitivity in preschool children.

  19. Linezolid desensitization for a patient with multiple medication hypersensitivity reactions.

    Science.gov (United States)

    Bagwell, Autumn D; Stollings, Joanna L; White, Katie D; Fadugba, Olajumoke O; Choi, Jane J

    2013-01-01

    To describe a case in which a linezolid desensitization protocol was successfully used for a polymicrobial surgical wound infection in a patient with multiple drug hypersensitivity reactions. A 24-year-old woman with vocal cord dysfunction requiring tracheostomy was admitted for a surgical wound infection following a tracheostomy fistula closure procedure. The patient reported multiple antibiotic allergies including penicillins (rash), sulfonamides (rash), vancomycin (anaphylaxis), azithromycin (rash), cephalosporins (anaphylaxis), levofloxacin (unspecified), clindamycin (unspecified), and carbapenems (unspecified). Gram stain of the purulent wound drainage demonstrated mixed gram-negative and gram-positive flora, and bacterial cultures were overgrown with Proteus mirabilis, which precluded identification of other pathogens. Following failed test doses of linezolid, tigecycline, and daptomycin, all of which resulted in hypersensitivity reactions, a 16-step linezolid desensitization protocol was developed and successfully implemented without adverse reactions. The patient completed a 2-week course of antibiotic therapy that included linezolid upon finishing the desensitization protocol. Linezolid is useful in treating complicated and uncomplicated skin and soft tissue infections caused by gram-positive bacteria. With precautions, including premedication, a monitored nursing unit, and immediate availability of an emergency anaphylaxis kit, drug desensitization allows patients the ability to safely use medications to which they may have an immediate hypersensitivity reaction. Minimal data exist on linezolid desensitization protocols. Linezolid desensitization can be a viable option in patients requiring antimicrobial therapy for complicated gram-positive skin infections.

  20. The value of family history in the diagnosis of hypersensitivity pneumonitis in children

    Directory of Open Access Journals (Sweden)

    Joana Cardoso

    2014-04-01

    Full Text Available Hypersensitivity pneumonitis (HP, or extrinsic allergic alveolitis, is an immunologically mediated disease resulting from the inhalation of organic substances that trigger an inflammatory response in the alveolar wall, bronchioles, and interstitium in susceptible individuals. Although HP is predominantly an occupational disease, seen in adulthood, cases in children have been described. The diagnosis of HP requires a high degree of suspicion. The treatment consists in avoiding contact with the antigen, and, in some cases, systemic corticosteroids might be necessary in order to prevent its progression to pulmonary fibrosis. We report the clinical cases of three children with a history of contact with birds and a family history of HP. All three patients presented with cough and dyspnea on exertion. The disease was diagnosed on the basis of the clinical history and ancillary diagnostic test results consistent with the diagnosis, including a predominance of lymphocytes (> 60%, CD8+ T lymphocytes in particular in bronchoalveolar lavage fluid and a ground-glass pattern seen on HRCT of the chest. Early diagnosis is crucial in order to prevent HP from progressing to pulmonary fibrosis. Hereditary factors seem to influence the onset of the disease.

  1. Evaluation of the irritancy and hypersensitivity potential following topical application of didecyldimethylammonium chloride

    Science.gov (United States)

    Anderson, Stacey E.; Shane, Hillary; Long, Carrie; Lukomska, Ewa; Meade, B. Jean; Marshall, Nikki B.

    2016-01-01

    Didecyldimethylammonium chloride (DDAC) is a dialkyl-quaternary ammonium compound that is used in numerous products for its bactericidal, virucidal and fungicidal properties. There have been clinical reports of immediate and delayed hypersensitivity reactions in exposed individuals; however, the sensitization potential of DDAC has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAC following dermal exposure in a murine model. DDAC induced significant irritancy (0.5 and 1%), evaluated by ear swelling in female Balb/c mice. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.0625–1%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.17%. Dermal exposure to DDAC did not induce increased production of IgE as evaluated by phenotypic analysis of draining lymph node B-cells (IgE+B220+) and measurement of total serum IgE levels. Additional phenotypic analyses revealed significant and dose-responsive increases in the absolute number of B-cells, CD4+ T-cells, CD8+ T-cells and dendritic cells in the draining lymph nodes, along with significant increases in the percentage of B-cells (0.25% and 1% DDAC) at Day 10 following 4 days of dermal exposure. There was also a significant and dose-responsive increase in the number of activated CD44 + CD4 + and CD8+ T-cells and CD86+ B-cells and dendritic cells following exposure to all concentrations of DDAC. These results demonstrate the potential for development of irritation and hypersensitivity responses to DDAC following dermal exposure and raise concerns about the use of this chemical and other quaternary ammonium compounds that may elicit similar effects. PMID:27216637

  2. Family and twin studies on methacholine hypersensitivity

    Directory of Open Access Journals (Sweden)

    Robert G Townley

    1998-01-01

    Full Text Available Essentially all asthmatics demonstrate a marked sensitivity to inhaled methacholine and histamine, termed non-specific bronchial (airway hyperresponsiveness (BHR. Airway hyperresponsiveness is a characteristic not only of asthmatics, but can be found in many persons with allergic rhinitis as well as in members of asthmatics' families. The presence of BHR usually precedes the development of clinically identifiable asthma. In recent years there has been an emphasis on inflammation, inducing hyperresponsiveness. However, these factors increase airway hyperresponsiveness by a magnitude of only three-fold compared with normal subjects. The important question is not why asthmatics respond, but why normal subjects do not. The normal subjects are quite able to maintain normal airway function in the presence of high concentrations of methacholine or histamine in vivo but not in vitro, suggesting the presence of protective mechanisms in vivo that are either lacking in, or are less effective in, the asthmatic subjects. There is a strong correlation between the degree of airway hyperresponsiveness and the severity of asthma. In order to determine whether methacholine sensitivity could be used as a potential genetic marker, we studied 750 subjects from 53 asthma families and 26 control families. The best sensitivity and specificity is at 200 breath units. Only 6% of the allergic rhinitis subjects showed a high positive response, but 30% overlapped with asthmatics in that they reacted with 200 breath units or less. There was a group of non-atopic subjects from asthma families who responded by 200 breath units, but there was a significantly lower percentage from normal families. Being from an asthma family is a risk factor in terms of subsequent development of asthma and increased airway reactivity. The parent data suggest that airway reactivity is transmitted to succeeding generations. Studies of twins have revealed that the concordance of asthma is higher in

  3. Anti-inflammatory and anti-hypersensitive effects of the crude extract, fractions and triterpenes obtained from Chrysophyllum cainito leaves in mice.

    Science.gov (United States)

    Meira, Nicole Anzanelo; Klein, Luiz Carlos; Rocha, Lilian W; Quintal, Zhelmy Martin; Monache, Franco Delle; Cechinel Filho, Valdir; Quintão, Nara Lins Meira

    2014-02-03

    Chrysophyllum cainito, popularly known as "star apple", caimito, "abiu-roxo" or "abiu-do-Pará", is a tree of about 25m in height. Besides its culinary use, it is also used in folk medicine for the treatment of diabetes mellitus and several inflammatory diseases. The crude methanolic extract (CME) was submitted to phytochemical studies for obtaining fractions and isolated compounds. They were monitored by thin-layer-chromatography (TLC). The biological activity was evaluated in mice using the carrageenan-induced mechanical hypersensitivity and paw oedema. Biochemical assays, such as myeloperoxidase (MPO) and activity and cytokines levels quantification, were carried out to analyse the involvement of neutrophil migration and IL-1β and TNFα production. Some adverse effects were investigated using the open-field and rota-rod tests, and it was also measured the rectal temperature. This study demonstrates, for the first time, the anti-hypersensitivity and anti-inflammatory effects of CME, fractions and two isolated triterpenes obtained from the leaves of Chrysophyllum cainito on carrageenan-induced hypersensitivity and paw-oedema. The mice treated with CME or chloroform fraction (CHCl3) presented reduction in mechanical hypersensitivity. The effect of the CME seemed to be partially related to the anti-inflammatory activity, as the paw-oedema and MPO activity were also significantly inhibited. The isolated compound Lup-20(29)-en-3β-O-hexanoate demonstrated more reduction of the hypersensitivity than 3β-Lup-20(29)-en-3-yl acetate, suggesting that this molecule might be partially responsible for the biological effects obtained with CME and CHCl3 fractions. Finally, animals treated with CME and CHCl3 did not present changes in locomotor activity, motor performance or body temperature. Our data demonstrates, for the first time, that the crude extract, fractions and pure compounds obtained from the Chrysophyllum cainito leaves possess important anti-hypersensitive

  4. Systemic contact dermatitis due to nickel

    Directory of Open Access Journals (Sweden)

    Taruli Olivia

    2015-08-01

    Full Text Available Introduction: Systemic contact dermatitis (SCD is a systemic reactivation of a previous allergic contact dermatitis. The initial exposure may usually be topical, followed by oral, intravenous or inhalation exposure leading to a systemic hypersensitivity reaction. A case of a 27 year-old male with SCD due to nickel is reported Case Report: A 27 year-old male presented with recurrent pruritic eruption consist of deep seated vesicles on both palmar and left plantar since 6 months before admission. This complaint began after patient consumed excessive amounts of chocolate, canned food, and beans. The patient worked as a technician in a food factory. History of allergy due to nickel was acknowledged since childhood. The clinical presentation was diffuse deep seated vesicles, and multiple erythematous macules to plaques, with collarette scale. Patch test using the European standard showed a +3 result to nickel. The patient was diagnosed as systemic contact dermatitis due to nickel. The treatments were topical corticosteroid and patient education of avoidance of both contact and systemic exposure to nickel. The patient showed clinical improvement after 2 weeks. Discussion: SCD was diagnosed due to the history of massive consumption of food containing nickel in a patient who had initial sensitization to nickel, with clinical features and the patch test result. Advice to be aware of nickel and its avoidance is important in SCD management.

  5. The prevalence of dentin hypersensitivity in general dental practices in the northwest United States.

    Science.gov (United States)

    Cunha-Cruz, Joana; Wataha, John C; Heaton, Lisa J; Rothen, Marilynn; Sobieraj, Martin; Scott, JoAnna; Berg, Joel

    2013-03-01

    The prevalence of dentin hypersensitivity is uncertain, yet appropriate diagnosis and treatment of dentin hypersensitivity require accurate knowledge regarding its prevalence. The authors conducted a study to estimate the prevalence of dentin hypersensitivity in general dental practices and to investigate associated risk factors. The authors conducted a cross-sectional survey of 787 adult patients from 37 general dental practices within Northwest Practice-based Research Collaborative in Evidence-based DENTistry (PRECEDENT). Dentin hypersensitivity was diagnosed by means of participants' responses to a question regarding pain in their teeth and gingivae, and practitioner-investigators conducted a clinical examination to rule out alternative causes of pain. Participants recorded their pain level on a visual analog scale and the Seattle Scales in response to a one-second air blast. The authors used generalized estimating equation log-linear models to estimate the prevalence and the prevalence ratios. The prevalence of dentin hypersensitivity was 12.3 percent; patients with hypersensitivity had, on average, 3.5 hypersensitive teeth. The prevalence of dentin hypersensitivity was higher among 18- to 44-year olds than among participants 65 years or older; it also was higher in women than in men, in participants with gingival recession than in those without gingival recession and in participants who underwent at-home tooth whitening than in those who did not. Hypersensitivity was not associated with obvious occlusal trauma, noncarious cervical lesions or aggressive toothbrushing habits. One in eight participants from general practices had dentin hypersensitivity, which was a chronic condition causing intermittent, low-level pain. Patients with hypersensitivity were more likely to be younger, to be female and to have a high prevalence of gingival recession and at-home tooth whitening. Given dentin hypersensitivity's prevalence, clinicians should diagnose it only after

  6. Prime and boost aerosol exposure via fog machine or shisha smoke followed by cinnamon hypersensitivity and anaphylaxis to spiced food.

    Science.gov (United States)

    Jensen-Jarolim, Erika; Roth-Walter, Franziska; Leitner, Erich; Buchleitner, Stefan; Vogelsang, Harald; Kinaciyan, Tamar

    2016-01-01

    Cinnamon aldehyde (alias cinnamaldehyde) is widely used in food, textile or cosmetic industry. It is mostly associated with contact allergy, but immediate type allergies have been reported. The present study was triggered by a case of anaphylactic events to cinnamon in food and upon skin prick test. We investigated a possible correlation of exposure to a disco fog machine and/or shisha consumption with immediate type hypersensitivity to cinnamon aldehyde in the patient and healthy volunteers. In both fog machines and shisha pipes heating of glycerol-based fluids before evaporation renders chemical transversion to malodorous acrolein. Therefore, both methods are frequently operated with aroma additives. Cinnamon aldehyde and derivatives could be detected by gas chromatography in sampled fog flavored with cola fragrance. The patient as well as healthy (mostly female) volunteers were skin prick tested using cinnamon aldehyde diluted in 0.9 % NaCl, Vaseline® or fog fluid. Persons with a history of exposure to disco fog or shisha (n = 10, mean 32.8 years) reacted with a significantly larger wheal and flare reaction in the skin test (p = 0.0115, p = 0.0146, or p = 0.098) than the non-exposed (n = 8, mean 37.3 years). Both groups were gender matched, but differed in the mean age by 4.5 years. This reaction was specific as compared to skin reactivity to cinnamon alcohol, with only a trend to higher reactivity in exposed persons (ns). From our data we conclude that hapten fragrances such as cinnamon aldehyde may during heating in glycerol fluids associate to complete antigens and via inspiration lead to specific immediate type hypersensitivity. In some cases the hypersensitivity may be unmasked by spiced food containing cinnamon aldehyde or related chemicals, and lead to severe adverse reactions.

  7. α-lipoic acid suppresses neuronal excitability and attenuates colonic hypersensitivity to colorectal distention in diabetic rats

    Directory of Open Access Journals (Sweden)

    Sun Y

    2017-07-01

    Full Text Available Yan Sun,1,* Pan-Pan Yang,1,* Zhen-Yuan Song,2 Yu Feng,1 Duan-Min Hu,1 Ji Hu,1 Guang-Yin Xu,3 Hong-Hong Zhang1,3 1Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Endocrinology, The East District of Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 3Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, People’s Republic of China *These authors contributed equally to this work Aim: Patients with long-standing diabetes often demonstrate intestinal dysfunction, characterized as constipation or colonic hypersensitivity. Our previous studies have demonstrated the roles of voltage-gated sodium channels NaV1.7 and NaV1.8 in dorsal root ganglion (DRG in colonic hypersensitivity of rats with diabetes. This study was designed to determine roles of antioxidant α-lipoic acid (ALA on sodium channel activities and colonic hypersensitivity of rats with diabetes. Methods: Streptozotocin was used to induce diabetes in adult female rats. Colonic sensitivity was measured by behavioral responses to colorectal distention in rats. The excitability and sodium channel currents of colon projection DRG neurons labeled with DiI were measured by whole-cell patch-clamp recordings. The expressions of NaV1.7 and NaV1.8 of colon DRGs were measured by western blot analysis. Results: ALA treatment significantly increased distention threshold in responding to colorectal distension in diabetic rats compared with normal saline treatment. ALA treatment also hyperpolarized the resting membrane potentials, depolarized action potential threshold, increased rheobase, and decreased frequency of action potentials evoked by ramp current stimulation. Furthermore, ALA treatment also reduced neuronal sodium current densities of DRG neurons innervating the colon from rats with diabetes. In addition, ALA

  8. Carboplatin hypersensitivity in children with glial tumors: a report of two cases

    Directory of Open Access Journals (Sweden)

    Tugce Kazgan

    2016-12-01

    Full Text Available Carboplatin, commonly used chemotherapeutic agent in treatment of pediatric cancers, can cause life-threatening hypersensitivty reactions. Carboplatin hypersensitivity is protocol-specific and associated with repeated doses and prolonged use of the drug. Vincristin and carboplatin combination is used efficiently in treatment of pediatric low-grade gliomas. However, hypersensitivity reactions are frequently observed during usage of this protocol. Desensitization strategies with variable success rates were reported. Failure of these strategies may lead to cessation of carboplatin Here, we report two cases with carboplatin hypersensitivity treated with epinephrine administration, in whom carboplatin was discontinued after hypersensitivity reaction. [Cukurova Med J 2016; 41(4.000: 796-798

  9. The possible role of contact sensitization to fragrances and preservatives in poikiloderma of civatte.

    Science.gov (United States)

    Khunkhet, Saranya; Wattanakrai, Penpun

    2014-09-01

    Numerous mechanisms have been postulated to play an important role in the pathogenesis of poikiloderma of Civatte (PC), including chronic exposure to ultraviolet radiation, menopause-related hormonal changes, contact hypersensitivity and genetic predisposition. Herein, we report a case of contact sensitization to fragrances and commonly used preservatives, methylchloroisothiazolinone and methylisothiazolinone, also widely known as Kathon CG, in a post-menopausal woman with PC, who denied excessive sun exposure and a family history. After abstaining from the use of her personal care products containing the documented allergens, not only the itching and burning symptoms, but also the cutaneous changes appeared to improve partially. This report underlines the possible influence of contact hypersensitivity in the pathogenesis of PC.

  10. The Possible Role of Contact Sensitization to Fragrances and Preservatives in Poikiloderma of Civatte

    Directory of Open Access Journals (Sweden)

    Saranya Khunkhet

    2014-11-01

    Full Text Available Numerous mechanisms have been postulated to play an important role in the pathogenesis of poikiloderma of Civatte (PC, including chronic exposure to ultraviolet radiation, menopause-related hormonal changes, contact hypersensitivity and genetic predisposition. Herein, we report a case of contact sensitization to fragrances and commonly used preservatives, methylchloroisothiazolinone and methylisothiazolinone, also widely known as Kathon CG, in a post-menopausal woman with PC, who denied excessive sun exposure and a family history. After abstaining from the use of her personal care products containing the documented allergens, not only the itching and burning symptoms, but also the cutaneous changes appeared to improve partially. This report underlines the possible influence of contact hypersensitivity in the pathogenesis of PC.

  11. Evaluation of basophil activation test in suspected food hypersensitivity.

    Science.gov (United States)

    Pignatti, Patrizia; Yacoub, Mona-Rita; Testoni, Claudia; Pala, Gianni; Corsetti, Maura; Colombo, Giselda; Meriggi, Antonio; Moscato, Gianna

    2017-07-01

    Food hypersensitivity is characterized by a wide range of symptoms. The relationship between symptoms and food is more frequently suspected than objectively proven. Basophil activation test (BAT) is based on the evaluation of activation markers on blood basophils in vitro stimulated with drugs or allergens. The aim of the study was to evaluate the usefulness of BAT when introduced in the routine work-up of suspected food hypersensitivity. BAT was requested in subjects with food adverse reactions when a discrepancy existed among history and skin prick test (SPT) and/or specific IgE. Data from 150 subjects were analysed using CD63 as basophil activation marker. Thirty controls were evaluated for cut-offs. Immunoblots was performed with the sera of representative subjects positive for BAT and negative for SPT and sIgE. 1,024 BAT were carried out, the agreement (positive/positive and negative/negative) was 78.5% for BAT vs. SPT and 78.3% for BAT vs. IgE. Atopic patients, but not atopic controls, more frequently had a positive BAT than non-atopic patients (P tested food) and both negative sIgE and SPT. Immunoblots revealed the presence of sIgE for the tested foods in representative patients with positive BAT, negative SPT and sIgE. Introduction of BAT in routine of food hypersensitivity, limited to subjects with a discrepancy between history and traditional tests, might be useful particularly when total IgE are low. © 2015 International Clinical Cytometry Society. © 2015 International Clinical Cytometry Society.

  12. A Class I UV-blocking (senofilcon A) soft contact lens prevents UVA-induced yellow fluorescence and NADH loss in the rabbit lens nucleus in vivo.

    Science.gov (United States)

    Giblin, Frank J; Lin, Li-Ren; Simpanya, Mukoma F; Leverenz, Victor R; Fick, Catherine E

    2012-09-01

    It is known that fluorescence, much of it caused by UVA light excitation, increases in the aging human lens, resulting in loss of sharp vision. This study used an in vivo animal model to investigate UVA-excited fluorescence in the rabbit lens, which contains a high level of the UVA chromophore NADH, existing both free and bound to λ-crystallin. Also, the ability of a Class I (senofilcon A) soft contact lens to protect against UVA-induced effects on the rabbit lens was tested. Rabbit eyes were irradiated with UVA light in vivo (100 mW/cm(2) on the cornea) for 1 h using monochromatic 365 nm light. Irradiation was conducted in the presence of either a senofilcon A contact lens, a minimally UV-absorbing lotrafilcon A contact lens, or no contact lens at all. Eyes irradiated without a contact lens showed blue 365 nm-excited fluorescence initially, but this changed to intense yellow fluorescence after 1 h. Isolated, previously irradiated lenses exhibited yellow fluorescence originating from the lens nucleus when viewed under 365 nm light, but showed normal blue fluorescence arising from the cortex. Previously irradiated lenses also exhibited a faint yellow color when observed under visible light. The senofilcon A contact lens protected completely against the UVA-induced effects on fluorescence and lens yellowing, whereas the lotrafilcon A lens showed no protection. The UVA-exposure also produced a 53% loss of total NADH (free plus bound) in the lens nucleus, with only a 13% drop in the anterior cortex. NADH loss in the nucleus was completely prevented with use of a senofilcon A contact lens, but no significant protection was observed with a lotrafilcon A lens. Overall, the senofilcon A lens provided an average of 67% protection against UVA-induced loss of four pyridine nucleotides in four different regions of the lens. HPLC analysis with fluorescence detection indicated a nearly six-fold increase in 365 nm-excited yellow fluorescence arising from lens nuclear

  13. Considerations on the electromagnetic hypersensitivity and idiopathic environmental intolerances

    International Nuclear Information System (INIS)

    Perrin, Anne

    2017-01-01

    After having noticed that environmental and health concerns are an important matter of concern in our society, and that always more pathologies are blamed on the environment, the author more particularly addresses electromagnetic hypersensitivity (EHS) which is considered by the WHO as a part of idiopathic environmental intolerances (IEI). He more particularly discusses the various conditions of emergence of these syndromes as they have been noticed, analysed and identified in different countries and in different studies. He discusses the possible definition to be given to these syndromes and their possible meaning

  14. Hypersensitive transition spectrum of f-element and coordination structure

    International Nuclear Information System (INIS)

    Cao Xuan; Song Chongli; Zhu Youngjun

    1992-10-01

    Some f-f transitions of Ln(An) metallic ions have particular super-sensitivity to the change of coordination environments. This is called super-sensitive transitions. Based on the irreducible tensor operator method, a computation model and corresponding computer program for calculating the hypersensitive transition spectrum of f-element were developed. By comparing the theoretical spectra of all possible coordination structures with experimental one, the possible coordination structures of complex can be determined. The coordination structures of Nd 3+ , Er 3 + hydrate and their extraction complex with H(DEHP) were successfully determined by this method, and the experimental spectra were also assigned

  15. Electromagnetic hypersensitivity: The opinion of an observer neurologist

    Science.gov (United States)

    Marc-Vergnes, Jean-Pierre

    2010-11-01

    Electromagnetic hypersensitivity (EHS) is a recent, uncertain and somehow confusing concept. It is now widely agreed that people claiming to be EHS really experience symptoms. However, no evidence for a causal link between the symptoms and electromagnetic fields (EMF) has been reported. Thus, we have to wonder whether EHS constitutes truly a relevant entity. Most of the previous studies suffer from methodological flaws. Owing to the quantification of symptoms, the interdisciplinary assessment of patients, and the use of personal exposimeters, the recent studies are of better quality. A set of convergent associated signs suggests that individual neuropsychic factors take a prominent, but maybe not unique, part in this condition.

  16. Non-contact test of coating by means of laser-induced ultrasonic excitation and holographic sound representation. Beruehrungslose Pruefung von Beschichtungen mittels laserinduzierter Ultraschallanregung und holographischer Schallabbildung

    Energy Technology Data Exchange (ETDEWEB)

    Crostack, H A; Pohl, K Y [QZ-DO Qualitaetszentrum Dortmund GmbH und Co. KG (Germany); Radtke, U [Dortmund Univ. (Germany). Fachgebiet Qualitaetskontrolle

    1991-01-01

    In order to circumvent the problems of introducing and picking off sound, which occur in conventional ultrasonic testing, a completely non-contact test process was developed. The ultrasonic surface wave required for the test is generated without contact by absorption of laser beams. The recording of the ultrasound also occurs by a non-contact holographic interferometry technique, which permits a large scale representation of the sound. Using the example of MCrAlY and ZrO[sub 2] layers, the suitability of the process for testing thermally sprayed coatings on metal substrates is identified. The possibilities and limits of the process for the detection and description of delamination and cracks are shown. (orig.).

  17. The effect of prophylaxis with chloroquine and proguanil on delayed-type hypersensitivity and antibody production following vaccination with diphtheria, tetanus, polio, and pneumococcal vaccines

    DEFF Research Database (Denmark)

    Gyhrs, A; Pedersen, B K; Bygbjerg, I

    1991-01-01

    (1,000 mg/week), or 4) proguanil hydrochloride (200 mg/day) for six weeks. Skin testing was performed on days 0 and 28. Vaccinations with diphtheria, tetanus, polio, and pneumococcal polysaccharide antigen vaccines were performed on day 28, and the presence of specific antibodies was determined...... dosages, does not induce any detectable suppression of delayed-type hypersensitivity or vaccination responses to diphtheria, tetanus, polio, or pneumococcal polysaccharide antigens....

  18. Unique microRNAs appear at different times during the course of a delayed-type hypersensitivity reaction in human skin

    DEFF Research Database (Denmark)

    Gulati, Nicholas; Løvendorf, Marianne B; Zibert, John R

    2015-01-01

    Diphencyprone (DPCP) is a hapten that induces delayed-type hypersensitivity (DTH) reactions. MicroRNAs (miRNAs) are short non-coding RNAs that negatively regulate gene expression and have been implicated in various inflammatory skin diseases, but their role in DTH reactions is not well understood......, and therefore, may inform on the paradoxical ability of DPCP to treat both autoimmune conditions (alopecia areata) and conditions of ineffective immunity (melanoma)....

  19. Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.

    Science.gov (United States)

    Schappacher, Katie A; Styczynski, Lauren; Baccei, Mark L

    2017-09-01

    Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Low doses of VNC (15 or 30 μg/kg) failed to alter nociceptive withdrawal reflexes at any age examined compared with vehicle-injected littermate controls. Meanwhile, high dose VNC (60 μg/kg) evoked mechanical hypersensitivity in both sexes beginning at P26 that persisted until adulthood and included both static and dynamic mechanical allodynia. Hind paw withdrawal latencies to noxious heat and cold were unaffected by high doses of VNC, suggesting a selective effect of neonatal VNC on mechanical pain sensitivity. Gross and fine motor function appeared normal after VNC treatment, although a small decrease in weight gain was observed. The VNC regimen also produced a significant decrease in intraepidermal nerve fiber density in the hind paw skin by P33. Overall, the present results demonstrate that high-dose administration of VNC during the early postnatal period selectively evokes a mechanical hypersensitivity that is slow to emerge during adolescence, providing further evidence that aberrant sensory input during early life can have prolonged consequences for pain processing.

  20. Interleukin-17A and Neutrophils in a Murine Model of Bird-Related Hypersensitivity Pneumonitis.

    Directory of Open Access Journals (Sweden)

    Masahiro Ishizuka

    Full Text Available Hypersensitivity pneumonitis (HP is an immune mediated lung disease induced by the repeated inhalation of a wide variety of antigens. Bird-related hypersensitivity pneumonitis (BRHP is one of the most common forms of HP in human and results from the inhalation of avian antigens. The findings of a recent clinical analysis suggest that in addition to Th1 factors, the levels of interleukin(IL-17 and IL-17-associated transcripts are increased in the setting of HP, and that both IL-17A and neutrophils are crucial for the development of pulmonary inflammation in murine models of HP. Our objectives were to investigate the roles of IL-17A and neutrophils in granuloma-forming inflammation in an acute HP model. We developed a mouse model of acute BRHP using pigeon dropping extract. We evaluated the process of granuloma formation and the roles of both IL-17A and neutrophils in a model. We found that the neutralization of IL-17A by the antibody attenuated granuloma formation and the recruitment of neutrophils, and also decreased the expression level of chemokine(C-X-C motif ligand 5 (CXCL5 in the acute HP model. We confirmed that most of the neutrophils in the acute HP model exhibited immunoreactivity to the anti-IL-17 antibody. We have identified the central roles of both IL-17A and neutrophils in the pathogenesis of granuloma formation in acute HP. We have also assumed that neutrophils are an important source of IL-17A in an acute HP model, and that the IL-17A-CXCL5 pathway may be responsible for the recruitment of neutrophils.

  1. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... One Use Facts About Colored Contacts and Halloween Safety Colored Contact Lens Facts Over-the-Counter Costume ... Costume Contact Lenses Can Ruin Vision Eye Makeup Safety In fact, it is illegal to sell colored ...

  2. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... One Use Facts About Colored Contacts and Halloween Safety Colored Contact Lens Facts Over-the-Counter Costume ... use of colored contact lenses , from the U.S. Food and Drug Administration (FDA). Are the colored lenses ...

  3. Trends in incidence of occupational asthma, contact dermatitis, noise-induced hearing loss, carpal tunnel syndrome and upper limb musculoskeletal disorders in European countries from 2000 to 2012

    NARCIS (Netherlands)

    Stocks, S. Jill; McNamee, Roseanne; van der Molen, Henk F.; Paris, Christophe; Urban, Pavel; Campo, Giuseppe; Sauni, Riitta; Martínez Jarreta, Begoña; Valenty, Madeleine; Godderis, Lode; Miedinger, David; Jacquetin, Pascal; Gravseth, Hans M.; Bonneterre, Vincent; Telle-Lamberton, Maylis; Bensefa-Colas, Lynda; Faye, Serge; Mylle, Godewina; Wannag, Axel; Samant, Yogindra; Pal, Teake; Scholz-Odermatt, Stefan; Papale, Adriano; Schouteden, Martijn; Colosio, Claudio; Mattioli, Stefano; Agius, Raymond

    2015-01-01

    The European Union (EU) strategy for health and safety at work underlines the need to reduce the incidence of occupational diseases (OD), but European statistics to evaluate this common goal are scarce. We aim to estimate and compare changes in incidence over time for occupational asthma, contact

  4. A quick and robust method for quantification of the hypersensitive response in plants

    Directory of Open Access Journals (Sweden)

    Oskar N. Johansson

    2015-12-01

    Full Text Available One of the most studied defense reactions of plants against microbial pathogens is the hypersensitive response (HR. The HR is a complex multicellular process that involves programmed cell death at the site of infection. A standard method to quantify plant defense and the HR is to measure the release of cellular electrolytes into water after infiltration with pathogenic bacteria. In this type of experiment, the bacteria are typically delivered into the plant tissue through syringe infiltration. Here we report the development of a vacuum infiltration protocol that allows multiple plant lines to be infiltrated simultaneously and assayed for defense responses. Vacuum infiltration did not induce more wounding response in Arabidopsis leaf tissue than syringe inoculation, whereas throughput and reproducibility were improved. The method was used to study HR-induced electrolyte loss after treatment with the bacterium Pseudomonas syringae pv. tomato DC3000 harboring the effector AvrRpm1, AvrRpt2 or AvrRps4. Specifically, the influence of bacterial titer on AvrRpm1-induced HR was investigated. Not only the amplitude, but also the timing of the maximum rate of the HR reaction was found to be dose-dependent. Finally, using vacuum infiltration, we were able quantify induction of phospholipase D activity after AvrRpm1 recognition in leaves labeled with 33PO4.

  5. CT findings associated with survival in chronic hypersensitivity pneumonitis

    International Nuclear Information System (INIS)

    Chung, Jonathan H.; Montner, Steven M.; Adegunsoye, Ayodeji; Vij, Rekha; Noth, Imre; Strek, Mary E.; Oldham, Justin M.; Husain, Aliya N.

    2017-01-01

    To identify CT findings in chronic hypersensitivity pneumonitis (cHP) associated with survival. Two thoracic radiologists assessed CT scans for specific imaging findings and patterns in 132 subjects with cHP. Survival analyses were performed. The majority of subjects had an inconsistent with usual interstitial pneumonitis pattern on CT (55.3%,73/132). Hypersensitivity pneumonitis (HP) diagnosis on CT was less common in those with fibrosis (66.1%, 74/112) than those without fibrosis (85%,17/20). Smoking was associated with a lower prevalence of HP on CT (p=0.04). CT features of pulmonary fibrosis, especially traction bronchiectasis (HR 8.34, 95% CI 1.98-35.21) and increased pulmonary artery (PA)/aorta ratio (HR 2.49, 95% CI 1.27-4.89) were associated with worse survival, while ground-glass opacity (HR 0.31, 95% CI 0.12-0.79) was associated with improved survival. Survival association with imaging was less pronounced after adjustment for gender, age and physiology score. A substantial proportion of cHP cases have a non-HP-like appearance. Ground-glass opacity, pulmonary fibrosis features and elevated PA/aorta ratio on CT likely reflect varying degrees of disease severity in cHP and may inform future clinical prediction models. (orig.)

  6. The Role of Esophageal Hypersensitivity in Functional Heartburn.

    Science.gov (United States)

    Kondo, Takashi; Miwa, Hiroto

    2017-08-01

    Functional heartburn (FH) is defined as a functional esophageal disorder characterized by symptoms of chronic heartburn with no apparent correlation to acid or nonacid reflux. In addition, its symptoms persist despite the lack of organic abnormalities or inflammation, esophageal motility disorders, or metabolic disorders. Although conditions presenting with esophageal symptoms without endoscopic abnormalities were previously categorized as nonerosive reflux disease, such conditions are now classified into 3 categories under Rome IV criteria: nonerosive reflux disease, reflux hypersensitivity, and FH. Although many aspects of FH remain unclear, its onset mechanism is considered to be strongly associated with peripheral or central sensitization, given the fact that its symptoms seem to be unrelated to gastroesophageal reflux. In addition, the cause of such hypersensitivity is an interesting topic in itself, and psychological factors, such as stress followed by increasing esophageal permeability are gaining attention as factors that can potentially influence this condition. There is a great unmet clinical need for therapeutic drugs that can be used to treat FH, and the development of novel drugs, diagnostic tests and biomarkers is eagerly awaited.

  7. CT findings associated with survival in chronic hypersensitivity pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Jonathan H.; Montner, Steven M. [University of Chicago Medical Center, Department of Radiology, Chicago, IL (United States); Adegunsoye, Ayodeji; Vij, Rekha; Noth, Imre; Strek, Mary E. [University of Chicago Medical Center, Section of Pulmonary/Critical Care, Department of Medicine, Chicago, IL (United States); Oldham, Justin M. [University of California at Davis, Section of Pulmonary/Critical Care, Department of Medicine, Sacramento, CA (United States); Husain, Aliya N. [University of Chicago Medical Center, Department of Pathology, Chicago, IL (United States)

    2017-12-15

    To identify CT findings in chronic hypersensitivity pneumonitis (cHP) associated with survival. Two thoracic radiologists assessed CT scans for specific imaging findings and patterns in 132 subjects with cHP. Survival analyses were performed. The majority of subjects had an inconsistent with usual interstitial pneumonitis pattern on CT (55.3%,73/132). Hypersensitivity pneumonitis (HP) diagnosis on CT was less common in those with fibrosis (66.1%, 74/112) than those without fibrosis (85%,17/20). Smoking was associated with a lower prevalence of HP on CT (p=0.04). CT features of pulmonary fibrosis, especially traction bronchiectasis (HR 8.34, 95% CI 1.98-35.21) and increased pulmonary artery (PA)/aorta ratio (HR 2.49, 95% CI 1.27-4.89) were associated with worse survival, while ground-glass opacity (HR 0.31, 95% CI 0.12-0.79) was associated with improved survival. Survival association with imaging was less pronounced after adjustment for gender, age and physiology score. A substantial proportion of cHP cases have a non-HP-like appearance. Ground-glass opacity, pulmonary fibrosis features and elevated PA/aorta ratio on CT likely reflect varying degrees of disease severity in cHP and may inform future clinical prediction models. (orig.)

  8. Metalworking fluid-associated hypersensitivity pneumonitis: a workshop summary.

    Science.gov (United States)

    Kreiss, K; Cox-Ganser, J

    1997-10-01

    A workshop discussing eight clusters of hypersensitivity pneumonitis in the automotive industry among metalworking fluid-exposed workers concluded that a risk exists for this granulomatous lung disease where water-based fluids are used and unusual microbial contaminants predominate. Strong candidates for microbial etiology are nontuberculous mycobacteria and fungi. Cases of hypersensitivity pneumonitis occur among cases with other work-related respiratory symptoms and chest diseases. Reversibility of disease has occurred in many cases with exposure cessation, allowing return to work to jobs without metalworking fluid exposures or, in some situations, to jobs without the same metalworking fluid exposures. Cases have been recognized with metalworking fluid exposures generally less than 0.5 mg/m3. The workshop participants identified knowledge gaps regarding risk factors, exposure-response relationships, intervention efficacy, and natural history, as well as surveillance needs to define the extent of the problem in this industry. In the absence of answers to these questions, guidance for prevention is necessarily limited.

  9. [Drug-induced oral ulcerations].

    Science.gov (United States)

    Madinier, I; Berry, N; Chichmanian, R M

    2000-06-01

    Different side effects of drugs have been described in the oral cavity, including oral ulcerations. Direct contact between drugs and oral mucosa may induce chemical burn or local hypersensitivity. Less frequently, these drug-induced oral ulcerations are part of a complex reaction with cutaneous or systemic manifestations. Sometimes, one or more oral ulcerations appear as the main side-effect of a drug, or exceptionally as solitary lesions. Solitary oral ulcerations usually appear after few weeks of treatment. In most of cases, these lesions resist to conventional treatments, with a rapid healing following the suppression of the responsible drug. This diagnosis is usually difficult, particularly with patients receiving multiple drug therapy. Besides, special attention must be paid to new drugs. Oral ulcerations following symptoms of burning mouth, metallic taste, dysgueusia or agueusia are strongly suggestive of a pharmacological origin. Most of the molecules able to induce solitary oral ulcerations are commonly prescribed in a) rheumatology: NSAI (diclofenac, flurbiprofen, indomethacin, naproxen), long-term rheumatoid arthritis therapy (azathioprine, methotrexate, penicillamine, gold compounds, tiopronin); b) cardiology: angiotensin-converting-enzyme inhibitors (captopril, enalapril), angiotensin 2-receptor antagonist (losartan), anti-angorous (nicorandil), c) psychiatry: antidepressants (fluoxetine, lithium), d) AIDS therapy (foscarnet, zalcitabine).

  10. Patch testers' opinions regarding diagnostic criteria for metal hypersensitivity reactions to metallic implants

    DEFF Research Database (Denmark)

    Schalock, Peter C; Thyssen, Jacob P

    2013-01-01

    Metal hypersensitivity reactions to implanted devices remain a challenging and controversial topic. Diagnostic criteria and methods are not well delineated.......Metal hypersensitivity reactions to implanted devices remain a challenging and controversial topic. Diagnostic criteria and methods are not well delineated....

  11. Genome-wide association study of insect bite hypersensitivity in swedish-born icelandic horses

    NARCIS (Netherlands)

    Shrestha, M.; Eriksson, S.; Schurink, A.; Andersson, L.S.; Sundquist, M.; Frey, R.; Brostrom, H.; Bergstrom, T.; Ducro, B.J.; lindgren, G.

    2015-01-01

    Insect bite hypersensitivity (IBH) is the most common allergic skin disease in horses and is caused by biting midges, mainly of the genus Culicoides. The disease predominantly comprises a type I hypersensitivity reaction, causing severe itching and discomfort that reduce the welfare and commercial

  12. Baroreflex Sensitivity And Autonomic Nervous System Function In Carotid Sinus Hypersensitivity

    DEFF Research Database (Denmark)

    Brinth, Louise Schouborg; Pors, Kirsten; Theibel, Ann Cathrine

    2015-01-01

    hypersensitivity ranging from reduced to increased sensitivity compared to controls. We wanted to establish whether measures of baroreflex sensitivity and autonomic function differed between patients diagnosed with carotid sinus hypersensitivity and age matched controls. We included 36 patients (12 women; 74 +/-10...... sensitivity may not follow the same neuronal pathways as those responding to the crude external pressures applied during carotid sinus massage...

  13. Successful desensitization protocol for hypersensitivity reaction probably caused by dabrafenib in a patient with metastatic melanoma.

    Science.gov (United States)

    Bar-Sela, Gil; Abu-Amna, Mahmoud; Hadad, Salim; Haim, Nissim; Shahar, Eduardo

    2015-09-01

    Vemurafenib and dabrafenib are both orally bioavailable small molecule agents that block mitogen activated protein kinase signalling in patients with melanoma and BRAF(V600E) mutation. Generalized hypersensitivity reactions to vemurafenib or dabrafenib have not been described. Continuing vemurafenib or dabrafenib therapy despite hypersensitivity reaction is especially important in patients with melanoma and BRAF(V600E) mutation, in whom this mutation plays a critical role in tumour growth. Desensitization protocols to overcome hypersensitivity reactions by gradual reintroduction of small amounts of the offending drug up to full therapeutic doses are available for many anti-cancer agents, including vemurafenib but, to the best of our knowledge, have not been reported for dabrafenib. We describe a patient with metastatic melanoma who developed Type I hypersensitivity reaction to vemurafenib and to subsequent treatment with dabrafenib, and who was successfully treated by drug desensitization which allowed safe prolonged continuation of dabrafenib. The development of hypersensitivity reactions for both dabrafenib and vemurafinib in the current case could be because these drugs have a similar chemical structure and cause a cross-reactivity. However, hypersensitivity reaction to a non-medicinal ingredient shared by the two drugs is also possible. Oral desensitization appears to be an option for patients with hypersensitivity Type I to dabrafenib. This approach may permit clinicians to safely administer dabrafenib to patients who experience hypersensitivity reactions to this life-prolonging medication. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Hypersensitive cell death in plants : its mechanisms and role in plant defense against pathogens

    NARCIS (Netherlands)

    Iakimova, E.T.; Michalczuk, L.; Woltering, E.J.

    2005-01-01

    This review is a recent update in the understanding of the hypersensitive response (HR) of plants with special consideration to the physiological and biochemical determinants in different model systems. Hypersensitive response is reviewed as a form of programmed cell death (PCD) representing one of

  15. Detective quantum efficiency gains compared with speed gains for hypersensitized astronomical plates

    International Nuclear Information System (INIS)

    Kaye, A.L.

    1977-01-01

    It is reasonable to assume that gains in detective quantum efficiency (DQE) are far better criteria for assessing the performance of hypersensitizing techniques than gains in speed. It is shown here that gains in speed can be misleading, for some methods of hypersensitization give plates of increased speed but reduced detective quantum efficiency. (author)

  16. Prevalence of parent-reported immediate hypersensitivity food allergy in Chilean school-aged children.

    Science.gov (United States)

    Hoyos-Bachiloglu, R; Ivanovic-Zuvic, D; Álvarez, J; Linn, K; Thöne, N; de los Ángeles Paul, M; Borzutzky, A

    2014-01-01

    Food allergies (FAs) affect 2-4% of school-aged children in developed countries and strongly impact their quality of life. The prevalence of FA in Chile remains unknown. Cross-sectional survey study of 488 parents of school-aged children from Santiago who were asked to complete a FA screening questionnaire. Parents who reported symptoms suggestive of FA were contacted to answer a second in-depth questionnaire to determine immediate hypersensitivity FA prevalence and clinical characteristics of school-aged Chilean children. A total of 455 parents answered the screening questionnaire: 13% reported recurrent symptoms to a particular food and 6% reported FA. Forty-three screening questionnaires (9%) were found to be suggestive of FA. Parents of 40 children answered the second questionnaire; 25 were considered by authors to have FA. FA rate was 5.5% (95% CI: 3.6-7.9). Foods reported to frequently cause FA included walnut, peanut, egg, chocolate, avocado, and banana. Children with FA had more asthma (20% vs. 7%, Phistory compatible with anaphylaxis. Of 13 children who sought medical attention, 70% were diagnosed with FA; none were advised to acquire an epinephrine autoinjector. Up to 5.5% of school-aged Chilean children may suffer from FA, most frequently to walnut and peanut. It is critical to raise awareness in Chile regarding FA and recognition of anaphylaxis, and promote epinephrine autoinjectors in affected children. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

  17. Sub-acute occupational hypersensitivity pneumonitis due to low-level exposure to diisocyanates in a secretary.

    Science.gov (United States)

    Schreiber, J; Knolle, J; Sennekamp, J; Schulz, K T; Hahn, J U; Hering, K G; Raulf-Heimsoth, M; Merget, R

    2008-09-01

    There is virtually no information in the literature about the exposure levels needed to induce hypersensitivity pneumonitis (HP) by diisocyanates. The present study reports a case of occupational HP due to diisocyanates after low-level exposure. A 53-yr-old female never-smoker developed progressive shortness of breath on exertion, cough, fatigue and flu-like symptoms shortly after she began work as a secretary of a car body repair shop. A diagnosis of HP was made 2 yrs later, based on a restrictive ventilatory defect, a reticulonodular and discrete ground-glass pattern on high-resolution computed tomography, lymphocytosis in bronchoalveolar lavage and specific immunoglobulin G antibodies to diisocyanate human serum albumin conjugates in the patient's serum. The diagnosis was confirmed by recovery after exposure cessation and deterioration after re-exposure. Ambient monitoring revealed air concentrations of different diisocyanate monomers below the detection limit in both the patient's work station and in front of the paint spray booths, with the exception of one measurement that showed 4,4-methylenediphenyl diisocyanate concentrations of 3 microg x m(-3) in front of one booth (corresponding to a total reactive isocyanate group concentration of 1 microg x m(-3)). The present authors conclude that concentrations of diisocyanates far below current exposure limits may induce hypersensitivity pneumonitis in susceptible subjects.

  18. National prevalence of asthma and chemical hypersensitivity: an examination of potential overlap.

    Science.gov (United States)

    Caress, Stanley M; Steinemann, Anne C

    2005-05-01

    The objective of this study was to investigate the linkage between asthma and chemical hypersensitivity. The authors conducted a population study with a random sample of 1057 geographically weighted cases to determine the prevalence of both asthma and chemical hypersensitivity in the American population and to explore their co-occurrence. A total of 14.1% of the respondents reported being diagnosed with asthma and 11.2% reported a hypersensitivity to chemicals. Of those with asthma, 27.2% also reported being hypersensitive to chemicals and 7.4% reported also being diagnosed with multiple chemical sensitivities (MCS). Of those diagnosed with MCS, 42% reported also being diagnosed with asthma. Additionally, 29.7% of those with asthma said air fresheners caused breathing difficulties, and 37.2% found scented products irritating. The results indicate that there is significant overlap between some forms of asthma and chemical hypersensitivity.

  19. Linking Anxiety and Insistence on Sameness in Autistic Children: The Role of Sensory Hypersensitivity.

    Science.gov (United States)

    Black, Karen R; Stevenson, Ryan A; Segers, Magali; Ncube, Busiswe L; Sun, Sol Z; Philipp-Muller, Aviva; Bebko, James M; Barense, Morgan D; Ferber, Susanne

    2017-08-01

    Sensory hypersensitivity and insistence on sameness (I/S) are common, co-occurring features of autism, yet the relationship between them is poorly understood. This study assessed the impact of sensory hypersensitivity on the clinical symptoms of specific phobia, separation anxiety, social anxiety and I/S for autistic and typically developing (TD) children. Parents of 79 children completed questionnaires on their child's difficulties related to sensory processing, I/S, and anxiety. Results demonstrated that sensory hypersensitivity mediated 67% of the relationship between symptoms of specific phobia and I/S and 57% of the relationship between separation anxiety and I/S. No relationship was observed between sensory hypersensitivity and social anxiety. These mediation effects of sensory hypersensitivity were found only in autistic children, not in TD children.

  20. NR2B Expression in Rat DRG Is Differentially Regulated Following Peripheral Nerve Injuries That Lead to Transient or Sustained Stimuli-Evoked Hypersensitivity.

    Science.gov (United States)

    Norcini, Monica; Sideris, Alexandra; Adler, Samantha M; Hernandez, Lourdes A M; Zhang, Jin; Blanck, Thomas J J; Recio-Pinto, Esperanza

    2016-01-01

    Following injury, primary sensory neurons undergo changes that drive central sensitization and contribute to the maintenance of persistent hypersensitivity. NR2B expression in the dorsal root ganglia (DRG) has not been previously examined in neuropathic pain models. Here, we investigated if changes in NR2B expression within the DRG are associated with hypersensitivities that result from peripheral nerve injuries. This was done by comparing the NR2B expression in the DRG derived from two modalities of the spared nerve injury (SNI) model, since each variant produces different neuropathic pain phenotypes. Using the electronic von Frey to stimulate the spared and non-spared regions of the hindpaws, we demonstrated that sural-SNI animals develop sustained neuropathic pain in both regions while the tibial-SNI animals recover. NR2B expression was measured at Day 23 and Day 86 post-injury. At Day 23 and 86 post-injury, sural-SNI animals display strong hypersensitivity, whereas tibial-SNI animals display 50 and 100% recovery from post-injury-induced hypersensitivity, respectively. In tibial-SNI at Day 86, but not at Day 23 the perinuclear region of the neuronal somata displayed an increase in NR2B protein. This retention of NR2B protein within the perinuclear region, which will render them non-functional, correlates with the recovery observed in tibial-SNI. In sural-SNI at Day 86, DRG displayed an increase in NR2B mRNA which correlates with the development of sustained hypersensitivity in this model. The increase in NR2B mRNA was not associated with an increase in NR2B protein within the neuronal somata. The latter may result from a decrease in kinesin Kif17, since Kif17 mediates NR2B transport to the soma's plasma membrane. In both SNIs, microglia/macrophages showed a transient increase in NR2B protein detected at Day 23 but not at Day 86, which correlates with the initial post-injury induced hypersensitivity in both SNIs. In tibial-SNI at Day 86, but not at Day 23

  1. Tyre noise predictions from computed road surface texture induced contact pressure; Romen no outotsu ni kiinsuru sesshoku atsuryoku ni yoru tire soon no suitei

    Energy Technology Data Exchange (ETDEWEB)

    Mikami, T. [Japan Automobile Research Institute Inc., Tsukuba (Japan)

    1999-07-01

    A method for tire/road noise prediction is studied based on the result of road surface profile measurement (horizontal direction measurement interval 3mm, horizontal direction measurement accuracy 8{mu}m, distance measured 1655m, using a laser-aided profile meter). The obtained road surface profile is used for the calculation of contact pressure that occurs between the tire tread and road surface (using the 2-dimensional calculation model of Clapp et al.). For the examination of the relationship between the contact pressure and generated noise, tire noise is measured using a microphone array provided near the tire circumference. The frequency spectral ratio between the generated noise and contact pressure is determined as a transmission function. It may be said that the transmission function is unique to the tire, not dependent on the road surface profile. The road surface profile is determined by use of the transmission function, and this enables the prediction of the noise from the tire. Noises were measured on several kinds of road surfaces different in coarseness for a passenger car and truck, and the values from these actual measurements are compared with the predicted values, and then it is found that the prediction model is valid. (NEDO)

  2. Contact Dermatitis in Pediatrics.

    Science.gov (United States)

    Pelletier, Janice L; Perez, Caroline; Jacob, Sharon E

    2016-08-01

    Contact dermatitis is an umbrella term that describes the skin's reaction to contacted noxious or allergenic substances. The two main categories of contact dermatitis are irritant type and allergic type. This review discusses the signs, symptoms, causes, and complications of contact dermatitis. It addresses the testing, treatment, and prevention of contact dermatitis. Proper management of contact dermatitis includes avoidance measures for susceptible children. Implementation of a nickel directive (regulating the use of nickel in jewelry and other products that come into contact with the skin) could further reduce exposure to the most common allergens in the pediatric population. [Pediatr Ann. 2016;45(8):e287-e292.]. Copyright 2016, SLACK Incorporated.

  3. Spreading depression analysis of contact behaviour of rats.

    Science.gov (United States)

    Tikal, K

    1977-08-01

    Social contact behaviour induced by spreading cortical depression was studied in rats. The controls looked for and remained in contact, whereas between the rats with spreading cortical depression and their other partners there was no contact. This phenomenon is due mainly to the absence of an active urge for contact. The contact behaviour of rats is evidently controlled by the cerebral cortex or by subcortical areas of the brain which are inhibited after the elicitation of spreading depression. The experiments show that the contact behaviour of rats has at least two components - an active urge for contact and passive tolerance of contact.

  4. Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain

    Directory of Open Access Journals (Sweden)

    Rachel D. Moloney

    2015-01-01

    Full Text Available Glutamate, the main excitatory neurotransmitter in the central nervous system, exerts its effect through ionotropic and metabotropic receptors. Of these, group III mGlu receptors (mGlu 4, 6, 7, 8 are among the least studied due to a lack of pharmacological tools. mGlu7 receptors, the most highly conserved isoform, are abundantly distributed in the brain, especially in regions, such as the amygdala, known to be crucial for the emotional processing of painful stimuli. Visceral hypersensitivity is a poorly understood phenomenon manifesting as an increased sensitivity to visceral stimuli. Glutamate has long been associated with somatic pain processing leading us to postulate that crossover may exist between these two modalities. Moreover, stress has been shown to exacerbate visceral pain. ADX71743 is a novel, centrally penetrant, negative allosteric modulator of mGlu7 receptors. Thus, we used this tool to explore the possible involvement of this receptor in the mediation of visceral pain in a stress-sensitive model of visceral hypersensitivity, namely the Wistar Kyoto (WKY rat. ADX71743 reduced visceral hypersensitivity in the WKY rat as exhibited by increased visceral sensitivity threshold with concomitant reductions in total number of pain behaviours. Moreover, AD71743 increased total distance and distance travelled in the inner zone of the open field. These findings show, for what is to our knowledge, the first time, that mGlu7 receptor signalling plays a role in visceral pain processing. Thus, negative modulation of the mGlu7 receptor may be a plausible target for the amelioration of stress-induced visceral pain where there is a large unmet medical need.

  5. Kiss-induced severe anaphylactic reactions

    Directory of Open Access Journals (Sweden)

    Atanasković-Marković Marina

    2010-01-01

    Full Text Available Introduction. Ingestion is the principal route for food allergens to trigger allergic reaction in atopic persons. However, in some highly sensitive patients severe symptoms may develop upon skin contact and by inhalation. The clinical spectrum ranges from mild facial urticaria and angioedema to life-threatening anaphylactic reactions. Outline of Cases. We describe cases of severe anaphylactic reactions by skin contact, induced by kissing in five children with prior history of severe anaphylaxis caused by food ingestion. These cases were found to have the medical history of IgE mediated food allergy, a very high total and specific serum IgE level and very strong family history of allergy. Conclusion. The presence of tiny particles of food on the kisser's lips was sufficient to trigger an anaphylactic reaction in sensitized children with prior history of severe allergic reaction caused by ingestion of food. Allergic reaction provoked with food allergens by skin contact can be a risk factor for generalized reactions. Therefore, extreme care has to be taken in avoiding kissing allergic children after eating foods to which they are highly allergic. Considering that kissing can be a cause of severe danger for the food allergic patient, such persons should inform their partners about the risk factor for causing their food hypersensitivity.

  6. Irritant Contact Dermatitis : Diagnosis and Risk Factors

    NARCIS (Netherlands)

    Schuttelaar, Maria; Johansen, Jeanne Duus; Lepoittevin, Jean-Pierre; Thyssen, Jacob P.

    2016-01-01

    Irritant contact dermatitis is frequent and is induced by direct and repeated contact with skin irritants such as detergents, abrasives, solvents and physical factors such as dry air and occlusion (by wearing gloves) but also water. When dermatitis has developed, even a minimal skin irritation, like

  7. Spinal Microgliosis Due to Resident Microglial Proliferation Is Required for Pain Hypersensitivity after Peripheral Nerve Injury

    Directory of Open Access Journals (Sweden)

    Nan Gu

    2016-07-01

    Full Text Available Peripheral nerve injury causes neuropathic pain accompanied by remarkable microgliosis in the spinal cord dorsal horn. However, it is still debated whether infiltrated monocytes contribute to injury-induced expansion of the microglial population. Here, we found that spinal microgliosis predominantly results from local proliferation of resident microglia but not from infiltrating monocytes after spinal nerve transection (SNT by using two genetic mouse models (CCR2RFP/+:CX3CR1GFP/+ and CX3CR1creER/+:R26tdTomato/+ mice as well as specific staining of microglia and macrophages. Pharmacological inhibition of SNT-induced microglial proliferation correlated with attenuated neuropathic pain hypersensitivities. Microglial proliferation is partially controlled by purinergic and fractalkine signaling, as CX3CR1−/− and P2Y12−/− mice show reduced spinal microglial proliferation and neuropathic pain. These results suggest that local microglial proliferation is the sole source of spinal microgliosis, which represents a potential therapeutic target for neuropathic pain management.

  8. Cell division in Escherichia coli BS-12 is hypersensitive to deoxyribonucleic acid damage by ultraviolet light

    International Nuclear Information System (INIS)

    Bridges, B.A.; Mottershead, R.P.; Green, M.H.

    1977-01-01

    Escherichia coli BS-12 uvrA lon is hypersensitive to ultraviolet light. On minimal agar plates at densities in excess of about 10(7) bacteria per plate, as few as one or two photoreversible pyrimidine dimers in the entire genome are sufficient to cause inhibition of cell division. Most of the resulting filaments are unable to divide or form a viable colony. Inhibition of cell division appears to be a rapid consequence of replication of deoxyribonucleic acid containing a pyrimidine dimer. Photoreversibility of the inhibition of cell division persists indefinitely, indicating that the continued presence of the pyrimidine dimers (or the continued generation of daughter strand gaps) is necessary to maintain the division-inhibited state. In view of the kinetics for the production of filamentation by ultraviolet light and the extremely low average inducing fluence (0.03 J/m2), it is concluded that the initiating signal is not the same as that causing other inducible phenomena such as prophage induction or Weigle reactivation

  9. Participation of the phosphoinositide metabolism in the hypersensitive response of Citrus limon against Alternaria alternata

    Directory of Open Access Journals (Sweden)

    XIMENA ORTEGA

    2001-01-01

    Full Text Available Lemon seedlings inoculated with Alternaria alternata develop a hypersensitive response (HR that includes the induction of Phenylalanine ammonia-lyase (PAL, E. C. 4.3.1.5 and the synthesis of scoparone. The signal transduction pathway involved in the development of this response is unknown. We used several inhibitors of the Phosphoinositide (PI animal system to study a possible role of Inositol-1,4,5-triphosphate (IP3 in the transduction of the fungal conidia signal in Citrus limon. The HR was only partially inhibited by EGTA, suggesting that not only external but internal calcium as well are necessary for a complete development of the HR. In this plant system, Alternaria alternata induced an early accumulation of the second messenger IP3. When lemon seedlings were watered long term with LiCl, an inhibitor of the phosphoinositide cycle, the IP3 production was reduced, and the LiCl-watered plants could neither induce PAL nor synthesize scoparone in response to fungal conidia. Furthermore, neomycin, a Phospholipase C (PLC, E. C. 3.1.4.3 inhibitor, also inhibited PAL induction and scoparone synthesis in response to A. alternata. These results suggest that IP3 could be involved in the signal transduction pathway for the development of the HR of Citrus limon against A. alternata

  10. Childhood hypersensitivity pneumonitis associated with fungal contamination of indoor hydroponics.

    Science.gov (United States)

    Engelhart, Steffen; Rietschel, Ernst; Exner, Martin; Lange, Lars

    2009-01-01

    Childhood hypersensitivity pneumonitis (HP) is often associated with exposure to antigens in the home environment. We describe a case of HP associated with indoor hydroponics in a 14-year-old girl. Water samples from hydroponics revealed Aureobasidium pullulans as the dominant fungal micro-organism (10(4)CFU/ml). The diagnosis is supported by the existence of serum precipitating antibodies against A. pullulans, lymphocytic alveolitis on bronchoalveolar lavage (BAL) fluid, a corresponding reaction on a lung biopsy, and the sustained absence of clinical symptoms following the removal of hydroponics from the home. We conclude that hydroponics should be considered as potential sources of fungal contaminants when checking for indoor health complaints.

  11. Desensitization of delayed-type hypersensitivity in mice: suppressive environment

    Directory of Open Access Journals (Sweden)

    Takashi Katsura

    1993-01-01

    Full Text Available The systemic injection of high doses of antigen into a preimmunized animal results in transient unresponsiveness of cell-mediated immune responses. This phenomenon is known as desensitization. Serum interleukin 2 (IL-2 activity was found transiently in desensitized mice at 3 h after the antigen challenge. These mice could not reveal antigen nonspecific delayed-type hypersensitivity (DTH 1 d after the challenge. Specific suppression of DTH was observed at later stages. Sera from 3 h desensitized mice showed suppressive effects on DTH in preo immunized mice. Administration of recombinant IL-2 into preimmunized mice led to the failure of development of DTH to antigens. These observations suggest that IL-2 plays an important role in the suppressive environment.

  12. The potent, indirect adenosine monophosphate-activated protein kinase activator R419 attenuates mitogen-activated protein kinase signaling, inhibits nociceptor excitability, and reduces pain hypersensitivity in mice

    Directory of Open Access Journals (Sweden)

    Galo L. Mejia

    2016-07-01

    Full Text Available Abstract. There is a great need for new therapeutics for the treatment of pain. A possible avenue to development of such therapeutics is to interfere with signaling pathways engaged in peripheral nociceptors that cause these neurons to become hyperexcitable. There is strong evidence that mitogen-activated protein kinases and phosphoinositide 3-kinase (PI3K/mechanistic target of rapamycin signaling pathways are key modulators of nociceptor excitability in vitro and in vivo. Activation of adenosine monophosphate-activated protein kinase (AMPK can inhibit signaling in both of these pathways, and AMPK activators have been shown to inhibit nociceptor excitability and pain hypersensitivity in rodents. R419 is one of, if not the most potent AMPK activator described to date. We tested whether R419 activates AMPK in dorsal root ganglion (DRG neurons and if this leads to decreased pain hypersensitivity in mice. We find that R419 activates AMPK in DRG neurons resulting in decreased mitogen-activated protein kinase signaling, decreased nascent protein synthesis, and enhanced P body formation. R419 attenuates nerve growth factor (NGF-induced changes in excitability in DRG neurons and blocks NGF-induced mechanical pain amplification in vivo. Moreover, locally applied R419 attenuates pain hypersensitivity in a model of postsurgical pain and blocks the development of hyperalgesic priming in response to both NGF and incision. We conclude that R419 is a promising lead candidate compound for the development of potent and specific AMPK activation to inhibit pain hypersensitivity as a result of injury.

  13. On the phenomenon of electromagnetic hypersensitivity; Das Phaenomen der Elektrosensibilitaet

    Energy Technology Data Exchange (ETDEWEB)

    David, E.; Reissenweber, J.; Wojtysiak, A.; Pfotenhauer, M. [Witten-Herdecke Univ., Witten (Germany). Inst. fuer Normale und Pathologische Physiologie; Witten-Herdecke Univ., Witten (Germany). Zentrum fuer Elektropathologie

    2002-07-01

    For more than fifteen years electromagnetic fields (EMFs) are intensively discussed in connection with health hazards in mass media as well as questions of standard setting by the authorities. The present elaboration gives an extended overview over the actual situation of the special electromagnetic hypersensitivity issue in relation to electromagnetic field research in the international scientific community. There are parallels and analogies between the symptoms of electromagnetic hypersensitivity and those of the Multiple-Chemical-Sensitivity-Syndrome and other environmental diseases. The first part deals with the biophysical fundamental knowledge of interactions between electromagnetic fields and biological systems such as man or animal including threshold values and threshold philosophy. Then hypothetical mechanisms of action of EMF are demonstrated, with a special focus on the melatonin hypothesis, which has not been proved in all its parts up to now. Additionally, in the context of our biomedical research into disorders of well-being we conducted an analysis of written and telephone questions about the EMF issue which are sent to our center. The results are of scientific and political interest and are demonstrated in detail. (orig.) [German] Das Phaenomen der Elektrosensibilitaet gewinnt zunehmend an Bedeutung innerhalb der Diskussion um die medizinisch-biologischen Wirkungen elektromagnetischer Felder. Es konnte bisher nicht nachgewiesen werden, dass die Elektrosensibilitaet/Magnetosensibilitaet als eigenstaendige Krankheitseinheit (Krankheitsentitaet) existiert. Es handelt sich dabei um ein Phaenomen, das vor etwa 15 Jahren benannt und zunaechst nicht ernst genommen wurde. Im Rahmen des relativ jungen medizinisch-biologischen Fachgebietes Elektropathologie scheinen weitere Untersuchungen erforderlich, um die teilweise auch widerspruechlichen Befunde aufzuklaeren und zu erfahren, ob Felder Befindlichkeitsstoerungen ausloesen koennen, die in aehnlicher Form

  14. Contact Stress Design Parameters for Titanium Bearings, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Air-Lock's Phase I effort tested the effects of ball induced contact stresses on Titanium bearing races. The contact stress design limit that would achieve a...

  15. Contact mechanics: contact area and interfacial separation from small contact to full contact

    International Nuclear Information System (INIS)

    Yang, C; Persson, B N J

    2008-01-01

    We present a molecular dynamics study of the contact between a rigid solid with a randomly rough surface and an elastic block with a flat surface. The numerical calculations mainly focus on the contact area and the interfacial separation from small contact (low load) to full contact (high load). For a small load the contact area varies linearly with the load and the interfacial separation depends logarithmically on the load. For a high load the contact area approaches the nominal contact area (i.e. complete contact), and the interfacial separation approaches zero. The numerical results have been compared with analytical theory and experimental results. They are in good agreement with each other. The present findings may be very important for soft solids, e.g. rubber, or for very smooth surfaces, where complete contact can be reached at moderately high loads without plastic deformation of the solids

  16. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM).

    Science.gov (United States)

    Brockow, Knut; Przybilla, Bernhard; Aberer, Werner; Bircher, Andreas J; Brehler, Randolf; Dickel, Heinrich; Fuchs, Thomas; Jakob, Thilo; Lange, Lars; Pfützner, Wolfgang; Mockenhaupt, Maja; Ott, Hagen; Pfaar, Oliver; Ring, Johannes; Sachs, Bernhardt; Sitter, Helmut; Trautmann, Axel; Treudler, Regina; Wedi, Bettina; Worm, Margitta; Wurpts, Gerda; Zuberbier, Torsten; Merk, Hans F

    Drug hypersensitivity reactions are unpredictable adverse drug reactions. They manifest either within 1-6 h following drug intake (immediate reactions) with mild to life-threatening symptoms of anaphylaxis, or several hours to days later (delayed reactions), primarily as exanthematous eruptions. It is not always possible to detect involvement of the immune system (allergy). Waiving diagnostic tests can result in severe reactions on renewed exposure on the one hand, and to unjustified treatment restrictions on the other. With this guideline, experts from various specialist societies and institutions have formulated recommendations and an algorithm for the diagnosis of allergies. The key principles of diagnosing allergic/hypersensitivity drug reactions are presented. Where possible, the objective is to perform allergy diagnostics within 4 weeks-6 months following the reaction. A clinical classification of symptoms based on the morphology and time course of the reaction is required in order to plan a diagnostic work-up. In the case of typical symptoms of a drug hypersensitivity reaction and unequivocal findings from validated skin and/or laboratory tests, a reaction can be attributed to a trigger with sufficient confidence. However, skin and laboratory tests are often negative or insufficiently reliable. In such cases, controlled provocation testing is required to clarify drug reactions. This method is reliable and safe when attention is paid to indications and contraindications and performed under appropriate medical supervision. The results of the overall assessment are discussed with the patient and documented in an "allergy passport" in order to ensure targeted avoidance in the future and allow the use of alternative drugs where possible.

  17. Cross-sensitivity of X-ray-hypersensitive cells derived from LEC strain rats to DNA-damaging agents

    International Nuclear Information System (INIS)

    Okui, T.; Endoh, D.; Arai, S.; Isogai, E.; Hayashi, M.

    1996-01-01

    The cross-sensitivity of X-ray-hypersensitive lung fibroblasts from LEC strain (LEC) rats to other DNA-damaging agents was examined. The LEC cells were 2- to 3-fold more sensitive to bleomycin (BLM) that induces DNA double-strand breaks, and to a cross-linking agent, mitomycin C, than the cells from WKAH strain (WKAH) rats, while they were slightly sensitive to alkylating agents, ethyl nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine, but not to UV-irradiation. Although no difference was observed in the initial yields of DNA double-strand breaks induced by BLM between LEC and WKAH cells, the repair process of DNA double-strand breaks was significantly slower in LEC cells than in WKAH cells

  18. The scientific rationale and development of an optimized dentifrice for the treatment of dentin hypersensitivity.

    Science.gov (United States)

    Tavss, Edward A; Fisher, Steven W; Campbell, Shannon; Bonta, Yolanda; Darcy-Siegel, Joann; Blackwell, Bernie L; Volpe, Anthony R; Miller, Steven E

    2004-02-01

    To describe the development of a new dentin hypersensitivity treatment, Colgate Sensitive Maximum Strength dentifrice, containing 5% potassium nitrate as the anti-hypersensitivity active agent. The objective was to develop a home-use hypersensitivity dentifrice that would be superior to the market leader, improving on what is available, which also contains 5% potassium nitrate as the anti-hypersensitivity active agent. In vivo (clinicals, taste evaluation and rat caries), in vitro (potassium flux) and analytical (rheology, dispensed volume, scanning electron microscopy, electron scanning chemical analysis and radioactive dentin abrasion) methods were performed. The objective was accomplished with the development of a new activated silica technology that resulted in enhanced potassium ion activity. In vitro documentation, supported by clinical studies, demonstrated that the resulting formula is more effective than the market leader for relief of hypersensitivity pain. Fast pain relief in less than 2 weeks and long-lasting protection against pain with regular use have also been clinically documented. Furthermore, FDA-required in vivo and in vitro studies indicate that this formula, which contains 0.45% stannous fluoride (1100 ppm fluoride) as the anti-caries active agent, is effective against caries. Good taste, acceptable rheology, acceptable abrasivity, and cosmetic and chemical stability have all been engineered into this unique dentin hypersensitivity treatment. In summary, a highly efficacious consumer friendly treatment for dentin hypersensitivity has been developed.

  19. Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies.

    Science.gov (United States)

    Tai, Yu-Hsiao; Tai, Yi-Jou; Hsu, Heng-Cheng; Lee, Shu-Ping; Chen, Yun-Yuan; Chiang, Ying-Cheng; Chen, Yu-Li; Chen, Chi-An; Cheng, Wen-Fang

    2017-01-01

    We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease ( P Kruskal-Wallis test), serous and mixed histological types ( P = 0.003, Kruskal-Wallis test), malignant ascites ( P = 0.009, chi-square test), and history of other drug allergy ( P test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P test) and dose (6,816 vs. 3,844 mg, P test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications.

  20. Cervical dentin hypersensitivity: a cross-sectional investigation in Athens, Greece.

    Science.gov (United States)

    Rahiotis, C; Polychronopoulou, A; Tsiklakis, K; Kakaboura, A

    2013-12-01

    The purpose of this study was to identify the prevalence of cervical dentin hypersensitivity in a cross-sectional investigation of Greek adults. Seven hundred and sixty-seven subjects were examined. Participants were patients processed for first examination in the Clinic of Oral Diagnosis and Radiology at the Faculty of Dentistry, University of Athens. The evaluation of hypersensitivity was performed using two methods: for each tooth, the response to a) tactile stimulus and b) air-blast stimulus was measured. Additional factors such as smoking habits, oral health behaviour, consumption of acidic foods, type of toothbrush, daily use of fluoride solution and of desensitising toothpaste, gingival recession and non-carious cervical lesions were recorded and evaluated as causative factors. Descriptive statistics on the demographics of the study sample, of oral health behaviour characteristics and of oral examination findings were performed. Comparisons of these characteristics in the presence or absence of hypersensitivity were conducted with the chi-square test. Data were further analysed using multiple logistic regression modelling. Among study participants, 21·3% had at least one cervical dentin hypersensitivity reaction to the tactile stimulus, and 38·6%, to the air-blast stimulus. Multivariate analysis detected association of the hypersensitivity in tactile or air-blast stimulus with the non-carious lesions and with the gingival recessions. Additionally, a relation between hypersensitivity and air-blast stimulus with gender (female) was found. There was no association between the hypersensitivity in both of the stimuli and the level of education, smoking, consumption of acidic foods, type of toothbrush and daily use of fluoride solution or desensitising toothpaste. The overall prevalence of cervical dentin hypersensitivity in the adult population in Athens ranged from 21·3% to 38·6% depending on the type of stimuli. Cervical non-carious lesions and gingival

  1. Insights into the mechanism of Piper betle leaf-induced contact leukomelanosis using C57BL/6 mice as the animal model and tyrosinase assays.

    Science.gov (United States)

    Liu, Han-Nan; Liu, Tsung-Yun; Chen, Chih-Chiang; Lee, Ding-Dar; Chang, Yun-Ting

    2011-08-01

    Steamed piper betle leaves (PBL) were once used by many Taiwanese women to treat pigment disorders on the face. Most women claimed a quick, favourable response at first, only to be overcome with facial leukomelanosis later. C57BL/6 mice were randomly assigned to different groups to study if PBL could cause the following effects: contact dermatitis, leukomelanosis, or hair bleaching. Intracellular melanin content was measured by tyrosinase assays. Most steamed PBL-treated mice developed contact dermatitis and postinflammatory hyperpigmentation (PIH) on their shaved backs. About half developed bleached hair to varying extents. The steamed PBL did not only bleach the hairs, but also, unexpectedly, stimulated melanocyte replication, indicated by the fact that the number of functional melanocytes in the tail epidermis increased significantly after treatment (P = 0.007). Using tyrosinase assays PBL extract at the undiluted concentration showed limited inhibition of melanogenesis, probably via melanocytotoxicity. The leukomelanosis observed in patients might be the consequence of PIH combined with a mixed reaction (hyper- and hypopigmentation), probably due to the different volatile chemicals that surface after steaming the PBL. This conflicting mixed reaction suggests that counteractive ingredients might exist in PBL. PBL, if purified, might be a promising source of a novel bleaching agent. © 2011 The Authors; Australasian Journal of Dermatology © 2011 The Australasian College of Dermatologists.

  2. Pregabalin Suppresses Spinal Neuronal Hyperexcitability and Visceral Hypersensitivity in the Absence of Peripheral Pathophysiology

    Science.gov (United States)

    Bannister, Kirsty; Sikandar, Shafaq; Bauer, Claudia S.; Dolphin, Annette C.; Porreca, Frank; Dickenson, Anthony H.

    2011-01-01

    Background Opioid induced hyperalgesia is recognised in the laboratory and the clinic, generating central hyperexcitability in the absence of peripheral pathology. We investigated pregabalin, indicated for neuropathic pain, and ondansetron, a drug that disrupts descending serotonergic processing in the central nervous system, on spinal neuronal hyperexcitability and visceral hypersensitivity in a rat model of opioid induced hyperalgesia. Methods Sprague-Dawley rats (180-200 g) were implanted with morphine (90μg · μl−1 · hr−1) or saline (0.9% w/v) filled osmotic mini-pumps. On days 7-10 in isoflurane anaesthetized animals we evaluated the effects of (a) systemic pregabalin on spinal neuronal and visceromotor responses and (b) spinal ondansetron on dorsal horn neuronal responses. The messenger RNA levels of α2δ-1, 5HT3A and mu-opioid receptor in the dorsal root ganglia of all animals were analysed. Results In morphine-treated animals the evoked spinal neuronal responses were enhanced to a sub-set of thermal and mechanical stimuli. This activity was attenuated by pregabalin (by at least 71%) and ondansetron (37%), and the visceromotor response to a sub-set of colorectal distension pressures was attenuated by pregabalin (52.8%) (n = 8 for all measures, P < 0.05). Messenger RNA levels were unchanged. Conclusions The inhibitory action of pregabalin in opioid induced hyperalgesia animals is not neuropathy-dependent nor reliant on up-regulation of the α2δ-1 subunit of voltage gated calcium channels, mechanisms proposed essential for pregabalin’s efficacy in neuropathy. In opioid induced hyperalgesia, which extends to colonic distension, a serotonergic facilitatory system may be upregulated creating an environment that’s permissive for pregabalin-mediated analgesia without peripheral pathology. PMID:21602662

  3. Hypersensitivity pneumonitis in nonhuman primates: studies on the relationship of immunoregulation and disease activity

    International Nuclear Information System (INIS)

    Keller, R.H.; Calvanico, N.J.; Stevens, J.O.

    1982-01-01

    We investigated the relationship of immunoregulation to disease activity in a nonhuman primate model of pigeon breeder's disease. Two Macaca arctoides monkeys developed classical symptoms of hypersensitivity pneumonitis after sensitization and prolonged bronchial challenge, whereas 2 other monkeys remained asymptomatic after in vivo challenge. There were no differences in the percentages of T cells, B cells, monocytes, or FCγ-bearing T cells between symptomatic and asymptomatic animals. Nonetheless, we found a population of concanavalin A-induced, pigeon serum- (PS) induced, and spontaneous T cells that functioned as suppressor cells in autologous in vitro co-cultures in asymptomatic animals that were missing or nonfunctional in symptomatic animals. Monocyte suppressors functioned in both groups. We used low-dose total body irradiation (TBI) to inactivate T suppressor cells. Fifteen radiation units of TBI caused no change in the physical activity, routine chemistries, or blood counts of the 4 animals. After TBI, however, the previously asymptomatic animals developed fever, tachypnea, and signs of pulmonary congestion after in vivo challenge with PS. There was no change in the response to challenge in the symptomatic group. This altered response to in vivo challenge in the previously asymptomatic group persisted for 2 wk after TBI. During this period the difference in in vitro immunoregulatory activity between Con A-induced, PS-induced, and spontaneous T cells in symptomatic and asymptomatic animals disappeared. Monocyte suppressors, however, continued to function in both groups after TBI. these data suggest that the monkey is an appropriate model for studies of human HP and that T cell immunoregulation may be an important element in the pathogenesis and disease activity of HP

  4. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... Cleveland. "This is far from the truth." Real People, Real Problems with Colored Contact Lenses Julian: Teenager ... about the members of the eye-care team . Consumer warning about the improper use of colored contact ...

  5. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... One Use Facts About Colored Contacts and Halloween Safety Colored Contact Lens Facts Over-the-Counter Costume ... new application of artificial intelligence shows whether a patient’s eyes point to high blood pressure or risk ...

  6. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... Costume Contacts May Contain Chemicals Harmful to Eyes Four Ways Over-the-Counter Costume Contact Lenses Can ... was in severe pain and on medication for four weeks, and couldn't see well enough to ...

  7. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... sell contacts without a prescription are breaking the law, and may be fined $11,000 per violation. " ... wear any kind of contact lens. In Butler's case, the lenses caused an infection and left her ...

  8. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... Hazard: The Hidden Dangers of Buying Decorative Contact Lenses Without a Prescription Leer en Español: Peligros asociados ... truth." Real People, Real Problems with Colored Contact Lenses Julian: Teenager Blinded In One Eye By Non- ...

  9. Colored Contact Lens Dangers

    Science.gov (United States)

    ... Hazard: The Hidden Dangers of Buying Decorative Contact Lenses Without a Prescription Leer en Español: Peligros asociados ... truth." Real People, Real Problems with Colored Contact Lenses Julian: Teenager Blinded In One Eye By Non- ...

  10. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... Cleveland. "This is far from the truth." Real People, Real Problems with Colored Contact Lenses Julian: Teenager ... the lenses. Never share contact lenses with another person. Get follow up exams with your eye care ...

  11. Contact Angle Goniometer

    Data.gov (United States)

    Federal Laboratory Consortium — Description:The FTA32 goniometer provides video-based contact angle and surface tension measurement. Contact angles are measured by fitting a mathematical expression...

  12. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... like a suction cup." Halloween is a popular time for people to use colored contact lenses to ... wear costume contact lenses for Halloween or any time of year, follow these guidelines: Get an eye ...

  13. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... glow-in-the-dark lizard lenses, costume contacts can certainly add a spooky, eye-popping touch. But ... consideration as a standard contact lens because they can be purchased over-the-counter or on the ...

  14. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... contact lenses , from the U.S. Food and Drug Administration (FDA). Are the colored lenses you are considering ... Follow The Academy Professionals: Education Guidelines News Multimedia Public & Patients: Contact Us About the Academy Jobs at ...

  15. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... not require the same level of care or consideration as a standard contact lens because they can ... sell contacts without a prescription are breaking the law, and may be fined $11,000 per violation. " ...

  16. Dermatitis, contact (image)

    Science.gov (United States)

    This picture shows a skin inflammation (dermatitis) caused by contact with a material that causes an allergic reaction in this person. Contact dermatitis is a relatively common condition, and can be caused ...

  17. Contact materials for nanoelectronics

    KAUST Repository

    Alshareef, Husam N.; Quevedo-Ló pez, Manuel Angel Quevedo; Majhi, Prashant

    2011-01-01

    In this article, we review current research activities in contact material development for electronic and nanoelectronic devices. A fundamental issue in contact materials research is to understand and control interfacial reactions and phenomena

  18. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... the United States. All contact lenses are medical devices that require a prescription and proper fitting by an eye-care professional. Retailers that sell contacts without a ...

  19. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... prescription. Follow the contact lens care directions for cleaning, disinfecting, and wearing the lenses. Never share contact ... with Industry Medical Disclaimer Privacy Policy Terms of Service For Advertisers For Media Ophthalmology Job Center © American ...

  20. Human Tear Fluid Reduces Culturability of Contact Lens Associated Pseudomonas aeruginosa Biofilms but Induces Expression of the Virulence Associated Type III Secretion System

    Science.gov (United States)

    Wu, Yvonne T.; Tam, Connie; Zhu, Lucia S.; Evans, David J.; Fleiszig, Suzanne M. J.

    2017-01-01

    Purpose The type III secretion system (T3SS) is a significant virulence determinant for Pseudomonas aeruginosa. Using a rodent model, we found that contact lens (CL)-related corneal infections were associated with lens surface biofilms. Here, we studied the impact of human tear fluid on CL-associated biofilm growth and T3SS expression. Methods P. aeruginosa biofilms were formed on contact lenses for up to 7 days with or without human tear fluid, then exposed to tear fluid for 5 or 24 h. Biofilms were imaged using confocal microscopy. Bacterial culturability was quantified by viable counts, and T3SS gene expression measured by RT-qPCR. Controls included trypticase soy broth, PBS and planktonic bacteria. Results With or without tear fluid, biofilms grew to ~108 cfu viable bacteria by 24 h. Exposing biofilms to tear fluid after they had formed without it on lenses reduced bacterial culturability ~180-fold (pbacteria [5.46 ± 0.24-fold for T3SS transcriptional activitor exsA (p=.02), and 3.76 ± 0.36-fold for T3SS effector toxin exoS (p=.01)]. Tear fluid further enhanced exsA and exoS expression in CL-grown biofilms, but not planktonic bacteria, by 2.09 ± 0.38-fold (p = 0.04) and 1.89 ± 0.26-fold (p<.001), respectively. Conclusions Considering the pivitol role of the T3SS in P. aeruginosa infections, its induction in CL-grown P. aeruginosa biofilms by tear fluid might contribute to the pathogenesis of CL-related P. aeruginosa keratitis. PMID:27670247

  1. Nickel, palladium and rhodium induced IFN-gamma and IL-10 production as assessed by in vitro ELISpot-analysis in contact dermatitis patients

    Directory of Open Access Journals (Sweden)

    Ensoli Fabrizio

    2008-05-01

    Full Text Available Abstract Background Recent attempts to diminish nickel use in most industrial products have led to an increasing utilization of alternative metal compounds for destinations such as the alloys used in orthopaedics, jewellery and dentistry. The present study was undertaken with the aim to evaluate the potential for an allergic response to nickel, palladium and rhodium on the basis of antigen-specific induction of inflammatory/regulatory cytokines, and to characterize, according to the cytokine profiles, the nature of simultaneous positive patch tests elicited in vivo. Peripheral blood mononuclear cells (PBMC from 40 patients with different patch test results were kept in short term cultures in the presence of optimized concentrations of NiSO4 × 6H2O, PdCl2 and Rh(CH3COO2. The production of IFN-γ and IL-10 elicited by metal compounds were analyzed by the ELISpot assay. Results We found a specific IFN-γ response by PBMC upon in vitro stimulation with nickel or palladium in well recognized allergic individuals. All controls with a negative patch test to a metal salt showed an in vitro IL-10 response and not IFN-γ production when challenged with the same compound. Interestingly, all subjects with positive patch test to both nickel and palladium (group 3 showed an in vitro response characterized by the release of IFN-γ after nickel stimulation and production of IL-10 in response to palladium. Conclusion These results strongly suggest that the different cytokine profiles elicited in vitro reflect different immune responses which may lead to the control of the allergic responses or to symptomatic allergic contact dermatitis. The development of sensitive and specific in vitro assays based on the determination of the cytokine profiles in response to contact allergens may have important diagnostic and prognostic implications and may prove extremely useful in complementing the diagnostic limits of traditional patch testing.

  2. Nickel, palladium and rhodium induced IFN-gamma and IL-10 production as assessed by in vitro ELISpot-analysis in contact dermatitis patients

    Science.gov (United States)

    Bordignon, Valentina; Palamara, Francesca; Cordiali-Fei, Paola; Vento, Antonella; Aiello, Arianna; Picardo, Mauro; Ensoli, Fabrizio; Cristaudo, Antonio

    2008-01-01

    Background Recent attempts to diminish nickel use in most industrial products have led to an increasing utilization of alternative metal compounds for destinations such as the alloys used in orthopaedics, jewellery and dentistry. The present study was undertaken with the aim to evaluate the potential for an allergic response to nickel, palladium and rhodium on the basis of antigen-specific induction of inflammatory/regulatory cytokines, and to characterize, according to the cytokine profiles, the nature of simultaneous positive patch tests elicited in vivo. Peripheral blood mononuclear cells (PBMC) from 40 patients with different patch test results were kept in short term cultures in the presence of optimized concentrations of NiSO4 × 6H2O, PdCl2 and Rh(CH3COO)2. The production of IFN-γ and IL-10 elicited by metal compounds were analyzed by the ELISpot assay. Results We found a specific IFN-γ response by PBMC upon in vitro stimulation with nickel or palladium in well recognized allergic individuals. All controls with a negative patch test to a metal salt showed an in vitro IL-10 response and not IFN-γ production when challenged with the same compound. Interestingly, all subjects with positive patch test to both nickel and palladium (group 3) showed an in vitro response characterized by the release of IFN-γ after nickel stimulation and production of IL-10 in response to palladium. Conclusion These results strongly suggest that the different cytokine profiles elicited in vitro reflect different immune responses which may lead to the control of the allergic responses or to symptomatic allergic contact dermatitis. The development of sensitive and specific in vitro assays based on the determination of the cytokine profiles in response to contact allergens may have important diagnostic and prognostic implications and may prove extremely useful in complementing the diagnostic limits of traditional patch testing. PMID:18482439

  3. Contact Lens Risks

    Science.gov (United States)

    ... There is a risk of eye infection from bacteria in swimming pool water, hot tubs, lakes and the ocean Replace your contact lens storage case every 3 months or as directed by your eye care professional. Other Risks of Contact Lenses Other risks of contact lenses include pink eye ( ...

  4. Hydrogenation of passivated contacts

    Energy Technology Data Exchange (ETDEWEB)

    Nemeth, William; Yuan, Hao-Chih; LaSalvia, Vincenzo; Stradins, Pauls; Page, Matthew R.

    2018-03-06

    Methods of hydrogenation of passivated contacts using materials having hydrogen impurities are provided. An example method includes applying, to a passivated contact, a layer of a material, the material containing hydrogen impurities. The method further includes subsequently annealing the material and subsequently removing the material from the passivated contact.

  5. Mixed Lubricated Line Contacts

    NARCIS (Netherlands)

    Faraon, I.C.

    2005-01-01

    The present work deals with friction in mixed lubricated line contacts. Components in systems are becoming smaller and due to, for instance power transmitted, partial contact may occur. In industrial applications, friction between the moving contacting surfaces cannot be avoided, therefore it is

  6. New Cosmetic Contact Allergens

    Directory of Open Access Journals (Sweden)

    An Goossens

    2015-02-01

    Full Text Available Allergic and photo-allergic contact dermatitis, and immunologic contact urticaria are potential immune-mediated adverse effects from cosmetics. Fragrance components and preservatives are certainly the most frequently observed allergens; however, all ingredients must be considered when investigating for contact allergy.

  7. electro-hypersensitivity: survey among general practitioners, occupational physicians and hygienist from the Netherlands

    International Nuclear Information System (INIS)

    Bonnet-Belfais, Monique; Salines, Georges

    2017-01-01

    From October 2013 through January 2014, Dutch and Swiss researchers conducted a survey in the Netherlands on electro-hypersensitive (EHS) people among the health care providers likely to be consulted for primary care and prevention. (author)

  8. Hypersensitivity reactions to metallic implants-diagnostic algorithm and suggested patch test series for clinical use

    DEFF Research Database (Denmark)

    Schalock, Peter C; Menné, Torkil; Johansen, Jeanne D

    2011-01-01

    Cutaneous and systemic hypersensitivity reactions to implanted metals are challenging to evaluate and treat. Although they are uncommon, they do exist, and require appropriate and complete evaluation. This review summarizes the evidence regarding evaluation tools, especially patch and lymphocyte...... transformation tests, for hypersensitivity reactions to implanted metal devices. Patch test evaluation is the gold standard for metal hypersensitivity, although the results may be subjective. Regarding pre-implant testing, those patients with a reported history of metal dermatitis should be evaluated by patch...... testing. Those without a history of dermatitis should not be tested unless considerable concern exists. Regarding post-implant testing, a subset of patients with metal hypersensitivity may develop cutaneous or systemic reactions to implanted metals following implant. For symptomatic patients, a diagnostic...

  9. Nickel in nails, hair and plasma from nickel-hypersensitive women

    DEFF Research Database (Denmark)

    Gammelgaard, Bente; Veien, Niels

    1990-01-01

    The concentrations of nickel in finger-nails, toe-nails, hair and plasma from 71 nickel-hypersensitive women and 20 non-hypersensitive women were determined. Nickel concentrations in finger-nails were significantly higher than in toe-nails in both the nickel-hypersensitive group and the control...... group. Nickel-sensitive women had significantly higher levels of nickel in toe-nails, hair and plasma than had control subjects, whereas there was no significant difference in nickel concentration in finger-nails between the two groups. No correlation could be demonstrated between nickel levels in any...... combination of nails, hair and plasma in the nickel-hypersensitive or in the control group....

  10. Calcitonin gene-related peptide regulates type IV hypersensitivity through dendritic cell functions.

    Directory of Open Access Journals (Sweden)

    Norihisa Mikami

    Full Text Available Dendritic cells (DCs play essential roles in both innate and adaptive immune responses. In addition, mutual regulation of the nervous system and immune system is well studied. One of neuropeptides, calcitonin gene-related peptide (CGRP, is a potent regulator in immune responses; in particular, it has anti-inflammatory effects in innate immunity. For instance, a deficiency of the CGRP receptor component RAMP 1 (receptor activity-modifying protein 1 results in higher cytokine production in response to LPS (lipopolysaccharide. On the other hand, how CGRP affects DCs in adaptive immunity is largely unknown. In this study, we show that CGRP suppressed Th1 cell differentiation via inhibition of IL-12 production in DCs using an in vitro co-culture system and an in vivo ovalbumin-induced delayed-type hypersensitivity (DTH model. CGRP also down-regulated the expressions of chemokine receptor CCR2 and its ligands CCL2 and CCL12 in DCs. Intriguingly, the frequency of migrating CCR2(+ DCs in draining lymph nodes of RAMP1-deficient mice was higher after DTH immunization. Moreover, these CCR2(+ DCs highly expressed IL-12 and CD80, resulting in more effective induction of Th1 differentiation compared with CCR2(- DCs. These results indicate that CGRP regulates Th1 type reactions by regulating expression of cytokines, chemokines, and chemokine receptors in DCs.

  11. Comparison of Esophageal Function Tests in Chinese Patients with Functional Heartburn and Reflux Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Feng Gao

    2017-01-01

    Full Text Available Objective. To investigate the differences in the results of esophageal function tests for functional heartburn (FH and reflux hypersensitivity (RH. Methods. Patients with FH and RH and healthy volunteers (HVs from the Department of Gastroenterology, Beijing Anzhen Hospital and Beijing Chao-Yang hospital, who underwent high-resolution manometry and impedance (HRIM, and 24-hour multichannel intraluminal impedance and pH recording (MII/pH between 2014 and 2016, were enrolled in this study. Results. 36 HV, 147 FH patients, and 91 RH patients were enrolled. The postreflux swallow-induced peristaltic wave index (PSPW index and mean nocturnal baseline impedance (MNBI values were significantly lower in RH than in FH and HV. The ineffective esophageal motility (IEM, fragmented peristalsis rates, total bolus exposure, proximal total reflux events, and distal total reflux events were significantly greater in RH than in FH and HV. Conclusions. Compared to HV and FH patients, RH patients exhibited greater IEM and fragmented peristalsis rates, a greater total bolus exposure, more proximal total and distal total reflux events, and reduced chemical clearance and mucosal integrity. By using the above described parameters, HRIM and MII/pH assays could be used to correctly classify RH and FH and hence allow physicians to provide adequate relief from associated symptoms.

  12. The re-establishment of hypersensitive cells in the crypts of irradiated mouse intestine

    International Nuclear Information System (INIS)

    Ijiri, K.; Potten, C.S.

    1984-01-01

    Two doses of γ-radiation separated by various time intervals have been used to investigate when after irradiation the cell population susceptible to acute cell death is re-established. Dead cells were scored 3 or 6 h after the second dose. Within 1-2 days of small doses (0.5 Gy) the sensitive cells, recognized histologically as apoptotic cells, are re-established at the base of the crypt (around cell position 6). After higher doses (9.0 Gy) they are not re-established until about the fourth day after irradiation. Even in the enlarged regenerating crypts the sensitive cells are found at the same position at the crypt base. It has been estimated that the crypt contains five or six cells that are susceptible to low doses (0.5 Gy) (hypersensitive cells) and up to a total of only seven or eight susceptible cells that can be induced by any dose to enter the sequence of changes implicit in apoptosis. Between 4 and 10 days after an intitial irradiation of 9.0 Gy the total number of susceptible cells increased from seven to eight to about 10 to 13 per crypt. (author)

  13. Identification of 4 ataxia telangiectasia cell lines hypersensitive to. gamma. -irradiation but not to hydrogen peroxide

    Energy Technology Data Exchange (ETDEWEB)

    Cantoni, O.; Sestili, P.; Santoro, M.P.; Tannoia, M.C.; Cattabeni, F. (Universita degli Studi di Urbino (Italy). Istituto di Farmacologia e Farmacognosia and Centro di Farmacologia Oncologia Sperimentale); Novelli, G.; Dallapiccola, B. (Universit degli Studi di Urbino (Italy). Cattedra di Genetica); Fiorilli, M. (Universita di Roma ' La Sapienze' (Italy). Cattedra di Allergologia e Immunologia Clinica)

    1989-09-01

    The effct of hydrogen peroxide on the rate of semi-conservative DNA synthesis in ataxia telangiectasia (AT) and normal human lymphoblastoid cells was investigated. The rate of DNA synthesis in AT cells was not depressed to a lesser extent than in normal cells, as might have been expected since H{sub 2O2} is a radiomimetic agent. On the contrary, 4 AT cell lines displayed a higher sensitivity to the inhibitory effect of H{sub 2O2} on DNA synthesis than 2 normal cell lines. Comparable levels of cytotoxicity were detected in cell vaibility studies. Furthermore, neither the level of DNA breakage produced by H{sub 2O2}, nor the rate of repair of these lesions was signigicantly different in normal and AT cells. Together, these results indicate that the AT cell lines utilized in this study are not hypersensitive to the oxidant. It is suggested that H-2-O-2 may not induce lethality via the direct ation of the hydroxyl radical (OH). (Author). 20 refs.; 3 figs.; 1 tab.

  14. [Assessment of hypersensitivity to honey-bee venom in beekeepers by skin tests].

    Science.gov (United States)

    Becerril-Ángeles, Martín; Núñez-Velázquez, Marco; Marín-Martínez, Javier

    2013-01-01

    Beekeepers are exposed to frequent honey-bee stings, and have the risk to develop hypersensitivity to bee venom, but long-term exposure can induce immune tolerance in them. Up to 30% of beekeepers show positive skin tests with honey-bee venom. The prevalence of systemic reactions to bee stings in beekeepers is from 14% to 42%. To know the prevalence of hypersensitivity to honeybee venom in Mexican beekeepers and non-beekeepers by the use of skin tests. A group of 139 beekeepers and a group of 60 non-beekeeper volunteers had a history and physical related to age, sex, family and personal atopic history and time of exposure to bee stings. Both groups received intradermal skin tests with honey-bee venom, 0.1 mcg/mL and 1 mcg/mL, and histamine sulphate 0.1 mg/mL and Evans solution as controls. The skin tests results of both groups were compared by chi-squared test. Of the group of beekeepers, 116 were men (83%) and 23 women, average age was 39.3 years, had atopic family history 28% and personal atopy 13%, average time of exposure to bee stings was 10.9 years, skin tests with honey-bee venom were positive in 16.5% and 11% at 1 mcg/mL and 0.1 mcg/mL, respectively. In the non-beekeepers group venom skin tests were positive in 13.3% and 6.7% at 1 mcg/mL and 0.1 mcg/mL. We did not find significant differences between the two venom concentrations tested in both groups, neither in the number of positive skin tests between the two groups. We found hypersensivity to honey-bee venom slightly higher in the beekeepers than in the group apparently not exposed. Both honey-bee venom concentrations used did not show difference in the results of the skin tests. The similarity of skin tests positivity between both groups could be explained by immune tolerance due to continued exposure of beekeepers.

  15. Effects of long-term vasodilator therapy in patients with carotid sinus hypersensitivity.

    Science.gov (United States)

    Brignole, M; Menozzi, C; Gaggioli, G; Musso, G; Foglia-Manzillo, G; Mascioli, G; Fradella, G; Bottoni, N; Mureddu, R

    1998-08-01

    In patients affected by carotid sinus hypersensitivity, long-term vasodilator therapy might increase the risk of syncopal episodes by reducing systolic blood pressure and venous return to the heart. Thirty-two patients (mean age 73 +/- 9 years; 20 men) who met all the following criteria were included: (1) one or more episodes of syncope occurring during long-term (>6 months) treatment with angiotensin-converting enzyme inhibitors, long-acting nitrates, calcium antagonists, or a combination of these; (2) a positive response to carotid sinus massage, defined as the reproduction of spontaneous syncope in the presence of ventricular asystole > or =3 seconds or a fall in systolic blood pressure > or =50 mm Hg; (3) negative workup for other causes of syncope. The patients were randomly assigned to continue or to discontinue use of vasodilators; carotid sinus massage was repeated 2 weeks after randomization. By the end of the study period, the baseline values of systolic blood pressure were significantly different between the 2 groups of patients both in supine (P=.01) and upright (P=.03) positions. Syncope had been induced by carotid sinus massage in 81% of patients in the "on-vasodilator" group and in 62% of patients in the "off-vasodilator" group (P=.21). The cardioinhibitory reflex was of similar magnitude in the 2 groups, being found in 50% of the patients in each group, with a maximum ventricular pause of 7.1 +/- 2.7 and 6.7 +/- 1.8 seconds, respectively. The percentage decrease of blood pressure did not differ between the 2 groups, even if, in absolute values, the baseline difference of blood pressure roughly persisted for the duration of the test. In consequence of that, the rise of blood pressure to similar values was delayed approximately 30 seconds in the "on-vasodilator" group and took more than 2 minutes to return to baseline values. In patients affected by carotid sinus hypersensitivity, chronic vasodilator therapy does not have a direct effect on carotid

  16. Delayed-type hypersensitivity to fragrance materials in a select North American population.

    Science.gov (United States)

    Belsito, Donald V; Fowler, Joseph F; Sasseville, Denis; Marks, James G; De Leo, Vincent A; Storrs, Frances J

    2006-03-01

    In published reports from Europe, 3- and 4-(4-hydroxy-4-methylpentyl)cyclohexene-1-carboxaldehyde (HMPCC) (Lyral) has been described as a common cause of allergic contact dermatitis (ACD). In Europe, the rates of reaction to HMPCC among patients undergoing patch testing for suspected ACD have varied from 1.2 to 17.0%, depending on the country. Data on the incidence of sensitivity to HMPCC among North Americans with suspected ACD have not been reported. The goals of this study were (1) to assess the incidence of delayed-type hypersensitivity reactions to HMPCC among patients undergoing patch testing for evaluation of eczematous dermatitis at six centers throughout North America; (2) to determine the most appropriate concentration of HMPCC to use in performing patch tests; and (3) to compare and contrast the incidence rates for HMPCC hypersensitivity to those for other fragrance materials screened with the North American Contact Dermatitis Group (NACDG) screening tray, which includes fragrance mix, Myroxilon pereirae (balsam of Peru), cinnamic aldehyde, ylang ylang oil, jasmine absolute, and tea tree oil. This report represents the prospective multicenter data on patients tested with the fragrance-related allergens on the NACDG standard screening tray and with HMPCC at 5%, 1.5%, and 0.5% concentrations in petrolatum. Statistical analyses were performed with Student's t-test (two tailed) and the chi-square test. Data from 1,603 patients evaluated at five US sites and one Canadian site were analyzed. Most patients (87.8%) were Caucasian. The majority (67%) were women, and 26.2% had a history consistent with atopic dermatitis. The patients ranged in age from 1 to 88 years, and the mean +/- standard deviation was 46.3 +/- 16.5 years. Myroxilon pereirae (balsam of Peru) and fragrance mix were the most frequent patch-test-positive fragrance allergens (6.6% and 5.9%, respectively). Cinnamic aldehyde (1.7%), ylang ylang oil (0.6%), jasmine absolute (0.4%), HMPCC (0.4% for 5

  17. Electrophilic nitro-fatty acids suppress allergic contact dermatitis in mice.

    Science.gov (United States)

    Mathers, A R; Carey, C D; Killeen, M E; Diaz-Perez, J A; Salvatore, S R; Schopfer, F J; Freeman, B A; Falo, L D

    2017-04-01

    Reactions between nitric oxide (NO), nitrite (NO2-), and unsaturated fatty acids give rise to electrophilic nitro-fatty acids (NO 2 -FAs), such as nitro oleic acid (OA-NO 2 ) and nitro linoleic acid (LNO 2 ). Endogenous electrophilic fatty acids (EFAs) mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction reactions. Hence, there is considerable interest in employing NO 2 -FAs and other EFAs for the prevention and treatment of inflammatory disorders. Thus, we sought to determine whether OA-NO 2 , an exemplary nitro-fatty acid, has the capacity to inhibit cutaneous inflammation. We evaluated the effect of OA-NO 2 on allergic contact dermatitis (ACD) using an established model of contact hypersensitivity in C57Bl/6 mice utilizing 2,4-dinitrofluorobenzene as the hapten. We found that subcutaneous (SC) OA-NO 2 injections administered 18 h prior to sensitization and elicitation suppresses ACD in both preventative and therapeutic models. In vivo SC OA-NO 2 significantly inhibits pathways that lead to inflammatory cell infiltration and the production of inflammatory cytokines in the skin. Moreover, OA-NO 2 is capable of enhancing regulatory T-cell activity. Thus, OA-NO 2 treatment results in anti-inflammatory effects capable of inhibiting ACD by inducing immunosuppressive responses. Overall, these results support the development of OA-NO 2 as a promising therapeutic for ACD and provides new insights into the role of electrophilic fatty acids in the control of cutaneous immune responses potentially relevant to a broad range of allergic and inflammatory skin diseases. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Long-term sensitization of mechanosensitive and -insensitive afferents in mice with persistent colorectal hypersensitivity

    OpenAIRE

    Feng, Bin; La, Jun-ho; Schwartz, Erica S.; Tanaka, Takahiro; McMurray, Timothy P.; Gebhart, G. F.

    2012-01-01

    Afferent input contributes significantly to the pain and colorectal hypersensitivity that characterize irritable bowel syndrome. In the present study, we investigated the contributions of mechanically sensitive and mechanically insensitive afferents (MIAs; or silent afferents) to colorectal hypersensitivity. The visceromotor response to colorectal distension (CRD; 15–60 mmHg) was recorded in mice before and for weeks after intracolonic treatment with zymosan or saline. After CRD tests, the di...

  19. Expression of antibacterial resistance at the site of a delayed hypersensitivity reaction.

    OpenAIRE

    Patel, P J

    1980-01-01

    The site of a delayed hypersensitivity reaction to tuberculin or bovine serum ablumin was shown to contain mechanisms that expressed increased antibacterial activity, as evidenced by restricted growth of a local inoculum of Listeria monocytogenes. As was the case with a delayed hypersensitivity reaction, the local generation of antibacterial activity was antigen specific and T-cell dependent. Antibacterial resistance was always expressed at the site of injection of specific antigen in sensiti...

  20. Defining conservation units in a stocking-induced genetic melting pot: unraveling native and multiple exotic genetic imprints of recent and historical secondary contact in Adriatic grayling.

    Science.gov (United States)

    Meraner, Andreas; Cornetti, Luca; Gandolfi, Andrea

    2014-04-01

    The definition of conservation units is crucial for the sustainable management of endangered species, though particularly challenging when recent and past anthropogenic and natural gene flow might have played a role. The conservation of the European grayling, Thymallus thymallus, is particularly complex in its southern distribution area, where the Adriatic evolutionary lineage is endangered by a long history of anthropogenic disturbance, intensive stocking and potentially widespread genetic introgression. We provide mtDNA sequence and microsatellite data of 683 grayling from 30 sites of Adriatic as well as Danubian and Atlantic origin. We apply Bayesian clustering and Approximate Bayesian Computation (ABC) to detect microgeographic population structure and to infer the demographic history of the Adriatic populations, to define appropriate conservation units. Varying frequencies of indigenous genetic signatures of the Adriatic grayling were revealed, spanning from marginal genetic introgression to the collapse of native gene pools. Genetic introgression involved multiple exotic source populations of Danubian and Atlantic origin, thus evidencing the negative impact of few decades of stocking. Within the Adige River system, a contact zone of western Adriatic and eastern Danubian populations was detected, with ABC analyses suggesting a historical anthropogenic origin of eastern Adige populations, most likely founded by medieval translocations. Substantial river-specific population substructure within the Adriatic grayling Evolutionary Significant Unit points to the definition of different conservation units. We finally propose a catalog of management measures, including the legal prohibition of stocking exotic grayling and the use of molecular markers in supportive- and captive-breeding programs.

  1. Direct Cell-Cell Contact between Mesenchymal Stem Cells and Endothelial Progenitor Cells Induces a Pericyte-Like Phenotype In Vitro

    Directory of Open Access Journals (Sweden)

    Markus Loibl

    2014-01-01

    Full Text Available Tissue engineering techniques for the regeneration of large bone defects require sufficient vascularisation of the applied constructs to ensure a sufficient supply of oxygen and nutrients. In our previous work, prevascularised 3D scaffolds have been successfully established by coculture of bone marrow derived stem cells (MSCs and endothelial progenitor cells (EPCs. We identified stabilising pericytes (PCs as part of newly formed capillary-like structures. In the present study, we report preliminary data on the interactions between MSCs and EPCs, leading to the differentiation of pericyte-like cells. MSCs and EPCs were seeded in transwell cultures, direct cocultures, and single cultures. Cells were cultured for 10 days in IMDM 10% FCS or IMDM 5% FCS 5% platelet lysate medium. Gene expression of PC markers, CD146, NG2, αSMA, and PDGFR-β, was analysed using RT-PCR at days 0, 3, 7, and 10. The upregulation of CD146, NG2, and αSMA in MSCs in direct coculture with EPCs advocates the MSCs’ differentiation towards a pericyte-like phenotype in vitro. These results suggest that pericyte-like cells derive from MSCs and that cell-cell contact with EPCs is an important factor for this differentiation process. These findings emphasise the concept of coculture strategies to promote angiogenesis for cell-based tissue engineered bone grafts.

  2. Food hypersensitivity in patients over 14 years of age suffering from atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Jarmila Čelakovská

    2014-01-01

    Full Text Available Background: Patients suffering from atopic dermatitis often describe food hypersensitivity. Rising prevalence of food hypersensitivity and severe allergic reactions to foods have been reported, but the data are scarce. Aims and Objectives: Evaluation of food hypersensitivity reactions in patients suffering from atopic dermatitis. Materials and Methods: The dermatological examination was performed in patients of age 14 years and above and the detailed history was taken concerning the food hypersensitivity. Results: A total of 228 patients were examined-72 men, 156 women, average age 26.2 (SD 9.5 years. The food hypersensitivity reactions were recorded in 196 patients from 228 (86%, no reactions were recorded in 32 patients (24%. Foods with the most often recorded reactions are: Nuts (in 35% of patients, tomatoes (in 20%, and kiwi (in 17, 5%, apples and spices (in 16%, tangerines and oranges (in 15%, capsicum (in 13%, fishes (in 12%, celery (in 9%, and chocolate (in 7%. Conclusion: Food hypersensitivity reactions are recorded in 86% of patients suffering from atopic dermatitis. Nuts, tomatoes, and pollen-associated foods play a role in the majority of patients suffering from atopic dermatitis.

  3. Food hypersensitivity in patients over 14 years of age suffering from atopic dermatitis.

    Science.gov (United States)

    Celakovská, Jarmila; Ettler, K; Ettlerová, K; Vaněčková, J

    2014-05-01

    Patients suffering from atopic dermatitis often describe food hypersensitivity. Rising prevalence of food hypersensitivity and severe allergic reactions to foods have been reported, but the data are scarce. Evaluation of food hypersensitivity reactions in patients suffering from atopic dermatitis. The dermatological examination was performed in patients of age 14 years and above and the detailed history was taken concerning the food hypersensitivity. A total of 228 patients were examined-72 men, 156 women, average age 26.2 (SD 9.5) years. The food hypersensitivity reactions were recorded in 196 patients from 228 (86%), no reactions were recorded in 32 patients (24%). Foods with the most often recorded reactions are: Nuts (in 35% of patients), tomatoes (in 20%), and kiwi (in 17, 5%), apples and spices (in 16%), tangerines and oranges (in 15%), capsicum (in 13%), fishes (in 12%), celery (in 9%), and chocolate (in 7%). Food hypersensitivity reactions are recorded in 86% of patients suffering from atopic dermatitis. Nuts, tomatoes, and pollen-associated foods play a role in the majority of patients suffering from atopic dermatitis.

  4. Desensitization in delayed drug hypersensitivity reactions -- an EAACI position paper of the Drug Allergy Interest Group.

    Science.gov (United States)

    Scherer, K; Brockow, K; Aberer, W; Gooi, J H C; Demoly, P; Romano, A; Schnyder, B; Whitaker, P; Cernadas, J S R; Bircher, A J

    2013-07-01

    Drug hypersensitivity may deprive patients of drug therapy, and occasionally no effective alternative treatment is available. Successful desensitization has been well documented in delayed drug hypersensitivity reactions. In certain situations, such as sulfonamide hypersensitivity in HIV-positive patients or hypersensitivity to antibiotics in patients with cystic fibrosis, published success rates reach 80%, and this procedure appears helpful for the patient management. A state of clinical tolerance may be achieved by the administration of increasing doses of the previously offending drug. However, in most cases, a pre-existent sensitization has not been proven by positive skin tests. Successful re-administration may have occurred in nonsensitized patients. A better understanding of the underlying mechanisms of desensitization is needed. Currently, desensitization in delayed hypersensitivity reactions is restricted to mild, uncomplicated exanthems and fixed drug eruptions. The published success rates vary depending on clinical manifestations, drugs, and applied protocols. Slower protocols tend to be more effective than rush protocols; however, underreporting of unsuccessful procedures is very probable. The decision to desensitize a patient must always be made on an individual basis, balancing risks and benefits. This paper reviews the literature and presents the expert experience of the Drug Hypersensitivity Interest Group of the European Academy of Allergy and Clinical Immunology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. [Contact glass tonometer].

    Science.gov (United States)

    Dekker, P W; Kanngiesser, H; Robert, Y C

    1996-05-01

    This paper presents a tonometer built into a contactlens, which allows to measure the eye-pressure and to perform ophthalmoscopy at the same time. Artificially induced changes of the eye-pressure and their influence on the visible fundus can now be checked simultaneously. The contactlens-tonometer (CGT) also is able to record continuously the pulse-curve, which can indicate any circulatory problem. So, the device is expected to give us additional diagnostic criteria of early glaucoma. Each ophthalmologyst in the field will be able to perform with this device a oculodynamometry in an easy way. By this it is possible to estimate the pressure-tolerance of the optic disk from glaucoma-patients. There have been taken some measurements on enucleated human eyes, comparing our device with a Statham-transducer in the vitreous. We found a good correlation. In a second step, we made measurements (65) on healthy volunteers, comparing the device with Perkins-Tonometry. We found a correlation (R = 0.58). The error of the measurements was about +/- 3 mm Hg. Considering both, the deviation of the Perkins-Tonometer with which our results were compared, and the fact of a good correlation (R = 0.999) in the study with the enucleated human eyes, we found that the contact-lens-tonometer measures the intraocular pressure exactly. In future studies, we want to analyze the dynamic component of the measurements.

  6. The Relationship between Grandiose and Vulnerable (Hypersensitive Narcissism

    Directory of Open Access Journals (Sweden)

    Emanuel Jauk

    2017-09-01

    Full Text Available Narcissistic grandiosity is characterized by overt expressions of feelings of superiority and entitlement, while narcissistic vulnerability reflects hypersensitivity and introversive self-absorbedness. Clinical evidence suggests that grandiosity is accompanied by vulnerable aspects, pointing to a common foundation. Subclinical personality research, however, views grandiose and vulnerable narcissism as independent traits. Grandiose narcissism displays substantial correlation with extraversion, while vulnerable narcissism correlates highly with introversion. We investigated if (1 controlling for intro-/extraversion might reveal a “common core” of grandiose and vulnerable narcissism, and if (2 the correlation between both aspects might be higher at higher levels of narcissism. Latent variable structural equation modeling and segmented regression analysis confirmed these hypotheses in a large non-clinical sample (N = 1,006. Interindividual differences in intro-/extraversion mask the common core of grandiose and vulnerable narcissism. The association between both aspects increases at high levels (upper 10% of grandiose narcissism, which suggests a possible transition to clinically relevant (pathological narcissism.

  7. The Relationship between Grandiose and Vulnerable (Hypersensitive) Narcissism

    Science.gov (United States)

    Jauk, Emanuel; Weigle, Elena; Lehmann, Konrad; Benedek, Mathias; Neubauer, Aljoscha C.

    2017-01-01

    Narcissistic grandiosity is characterized by overt expressions of feelings of superiority and entitlement, while narcissistic vulnerability reflects hypersensitivity and introversive self-absorbedness. Clinical evidence suggests that grandiosity is accompanied by vulnerable aspects, pointing to a common foundation. Subclinical personality research, however, views grandiose and vulnerable narcissism as independent traits. Grandiose narcissism displays substantial correlation with extraversion, while vulnerable narcissism correlates highly with introversion. We investigated if (1) controlling for intro-/extraversion might reveal a “common core” of grandiose and vulnerable narcissism, and if (2) the correlation between both aspects might be higher at higher levels of narcissism. Latent variable structural equation modeling and segmented regression analysis confirmed these hypotheses in a large non-clinical sample (N = 1,006). Interindividual differences in intro-/extraversion mask the common core of grandiose and vulnerable narcissism. The association between both aspects increases at high levels (upper 10%) of grandiose narcissism, which suggests a possible transition to clinically relevant (pathological) narcissism. PMID:28955288

  8. Exploring Some Aspects Associated with Dentine Hypersensitivity in Children

    Directory of Open Access Journals (Sweden)

    Caleb Shitsuka

    2015-01-01

    Full Text Available Background. The etiology of dentine hypersensitivity (DH is still inconclusive and there are few studies concerning it in children. Aim. To evaluate clinical, dietary, and salivary variables in children with DH complaints. Design. Forty-eight children were asked about DH. Data regarding dietary habits were collected from the children’s parents and an examination was performed to determine dental erosion. Dental biofilm was estimated by oral hygiene status, according to Greene and Vermillion’s Simplified Oral Hygiene Index (OHI-S. Whole saliva was collected under mechanical stimulation and evaluated salivary flow rate, initial pH, buffer capacity, and calcium and phosphate concentrations. The temperature of soft drinks, drinking method, sense of bitter taste, and other variables were also determined. Possible factors associated with DH were analyzed by univariate and multiple Poisson regression analyses. The prevalence ratio (PR values and 95% confidence intervals (95% CI were calculated. Results. DH was associated with the presence of dental erosion (PR; 95% CI = 2.23; 1.05 to 4.71 and salivary flow rate (2.49; 1.05 to 5.91. When the presence of erosion was not included, other variables were retained as follows: bitter taste (2.36; 1.38 to 4.03, OHI-S (0.47; 0.23 to 0.97. Conclusion. DH in children is associated with factors related to dental erosion.

  9. A Case of Immediate Hypersensitivity Reaction to Maltitol

    Directory of Open Access Journals (Sweden)

    Ana Rodríguez Trabado

    2017-01-01

    Full Text Available Background. Maltitol is a sugar alcohol that is frequently used as a noncaloric sweetener, although it is also used as an excipient, a plasticizer in gelatin capsules, and an emollient. It has not been previously described as an agent involved in immediate hypersensitivity reactions. Methods. We report on an anaphylactoid reaction with pharyngeal occlusion suffered by a 60-year-old man after ingestion of a candy containing maltitol syrup. A prick-to-prick test was performed with the candy and maltitol powder. Other allergens were excluded as causative agents of the adverse reaction, although the patient refused to undergo an oral challenge test with the candy. A basophil activation test (BAT was performed with maltitol powder, and a dose-response curve was generated. The test was also performed in 3 healthy controls. Results. Both prick-to-prick tests were negative. The result of the BAT was positive at all the concentrations tested in the patient’s blood and negative in all the controls. Conclusions. The BAT can help to clarify the agents implicated in an adverse reaction and can reduce the risk involved in diagnosis. The BAT can also prove useful in the study of reactions caused by low-molecular-weight antigens, for which routine diagnostic tests are not feasible.

  10. Hypersensitivity pneumonitis with Mycobacterium avium complex among spa workers.

    Science.gov (United States)

    Moraga-McHaley, Stephanie Ann; Landen, Michael; Krapfl, Heidi; Sewell, C Mack

    2013-01-01

    The New Mexico Department of Health (NMDOH) investigated the cause of two cases of hypersensitivity pneumonitis (HP) in spa maintenance workers with laboratory confirmed Mycobacterium avium complex (MAC). The investigation occurred in tandem with worker protection and swimming pool regulatory investigations by the New Mexico Environment Department at the spa where the workers were employed. The investigation was conducted in order to identify unreported cases, exposure source(s), and to prevent further worker exposure. NMDOH surveyed 57 spa employees about symptoms and exposures, categorized jobs according to self-reported exposure to water, and computed odds ratios for symptom reporting by exposure category. Environmental isolates from spa water and filter swabs were cultured and compared to patient isolates by the Environmental and Applied Microbiology Team, Centers for Disease Control and Prevention (CDC). Workers with the highest exposure reported more HP-like symptoms (OR = 9.6), as did intermediate exposure workers (OR = 6.5), compared to workers with no aerosolized water exposure. Two of 13 environmental isolates were closely related to one of the patient isolates. Workers were likely exposed during spray cleaning of cartridge filters in a poorly ventilated work space. Recommendations include inhibiting organism growth in spa systems, assuring the use of respiratory protection, and adequately ventilating work spaces where filters and equipment are cleaned.

  11. Treatment of Dentine Hypersensitivity by Diode Laser: A Clinical Study

    Directory of Open Access Journals (Sweden)

    Romeo Umberto

    2012-01-01

    Full Text Available Introduction. Dentine hypersensitivity (DH is characterized by pain after stimuli that usually provoke no symptoms. This study compared the effectiveness of GaAlAs diode laser alone and with topical sodium fluoride gel (NaF. Materials and Methods. The study was conducted on 10 patients (8 F/2 M, age 25–60 and 115 teeth with DH assessed by air and tactile stimuli measured by Numeric Rating Scale (NRS. Teeth were randomly divided into G1 (34 teeth treated by 1.25% NaF; G2 (33 teeth lased at 0.5 W PW (T on 100 m and T off 100 ms, fluence 62.2 J/cm2 in defocused mode with a 320 μ fiber. Each tooth received three 1′ applications; G3 (48 teeth received NaF gel plus laser at same G2 parameters. NRS was checked at each control. Results. Significant pain reduction was showed. The NRS reduction percentages were calculated, and there was a concrete decrease of DH above all in G3 than G2 and G1. Conclusion. Diode laser is a useful device for DH treatment if used alone and mainly if used with NaF gel.

  12. Evaluation of the hypersensitivity potential of alternative butter flavorings

    Science.gov (United States)

    Anderson, Stacey E.; Franko, Jennifer; Wells, J.R.; Lukomska, Ewa; Meade, B. Jean

    2015-01-01

    Concern has been raised over the association of diacetyl with lung disease clinically resembling bronchiolitis obliterans in food manufacturing workers. This has resulted in the need for identification of alternative chemicals to be used in the manufacturing process. Structurally similar chemicals, 2,3-pentanedione, 2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione, used as constituents of synthetic flavoring agents have been suggested as potential alternatives for diacetyl, however, immunotoxicity data on these chemicals are limited. The present study evaluated the dermal irritation and sensitization potential of diacetyl alternatives using a murine model. None of the chemicals were identified as dermal irritants when tested at concentrations up to 50%. Similar to diacetyl (EC3 = 17.9%), concentration-dependent increases in lymphocyte proliferation were observed following exposure to all four chemicals, with calculated EC3 values of 15.4% (2,3-pentanedione), 18.2% (2,3-hexanedione), 15.5% (3,4-hexanedione) and 14.1% (2,3-heptanedione). No biologically significant elevations in local or total serum IgE were identified after exposure to 25–50% concentrations of these chemicals. These results demonstrate the potential for development of hypersensitivity responses to these proposed alternative butter flavorings and raise concern about the use of structurally similar replacement chemicals. Additionally, a contaminant with strong sensitization potential was found in varying concentrations in diacetyl obtained from different producers. PMID:24007741

  13. Hazards of the ‘Hard Cash’: Hypersensitivity Pneumonitis

    Directory of Open Access Journals (Sweden)

    Elif Kupeli

    2010-01-01

    Full Text Available Hypersensitivity pneumonitis (HP is a nonimmunoglobulin E-related immune-mediated parenchymal lung disease. A 45-year-old woman who was a lifelong nonsmoker with a six-month history of frequent episodes of cough and dyspnea was admitted to hospital. She had been working as a money counter for 20 years at a central bank. Bibasilar crackles on lung auscultation, ground-glass opacities and a mosaic pattern on high-resolution computed tomography, restrictive abnormality on pulmonary function tests and mild hypoxemia were the prominent findings. Bronchoalveolar lavage fluid analysis revealed a predominance of CD4-positive T cells, and she tested positive on her natural challenge test. She was diagnosed with subacute HP based on established criteria. She was advised to discontinue counting fresh banknotes. Prednisolone was commenced, then tapered to discontinue in the ensuing six months. Clinical and radiological improvement was achieved within two months. To the authors’ knowledge, the present report is the first to describe ‘hard cash HP’, possibly caused by chipping dust or printing dye.

  14. Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    Ayodeji Adegunsoye

    2017-08-01

    Full Text Available In chronic hypersensitivity pneumonitis (CHP, lack of improvement or declining lung function may prompt use of immunosuppressive therapy. We hypothesised that use of azathioprine or mycophenolate mofetil with prednisone reduces adverse events and lung function decline, and improves transplant-free survival. Patients with CHP were identified. Demographic features, pulmonary function tests, incidence of treatment-emergent adverse events (TEAEs and transplant-free survival were characterised, compared and analysed between patients stratified by immunosuppressive therapy. A multicentre comparison was performed across four independent tertiary medical centres. Among 131 CHP patients at the University of Chicago medical centre (Chicago, IL, USA, 93 (71% received immunosuppressive therapy, and had worse baseline forced vital capacity (FVC and diffusing capacity, and increased mortality compared with those who did not. Compared to patients treated with prednisone alone, TEAEs were 54% less frequent with azathioprine therapy (p=0.04 and 66% less frequent with mycophenolate mofetil (p=0.002. FVC decline and survival were similar between treatment groups. Analyses of datasets from four external tertiary medical centres confirmed these findings. CHP patients who did not receive immunosuppressive therapy had better survival than those who did. Use of mycophenolate mofetil or azathioprine was associated with a decreased incidence of TEAEs, and no difference in lung function decline or survival when compared with prednisone alone. Early transition to mycophenolate mofetil or azathioprine may be an appropriate therapeutic approach in CHP, but more studies are needed.

  15. Change in FVC and survival in chronic fibrotic hypersensitivity pneumonitis.

    Science.gov (United States)

    Gimenez, Andrea; Storrer, Karin; Kuranishi, Lilian; Soares, Maria Raquel; Ferreira, Rimarcs Gomes; Pereira, Carlos A C

    2018-04-01

    The predictive value of the decline in FVC by ≥10% on survival in patients with fibrotic hypersensitivity pneumonitis is unknown. Of 112 patients included, 66 (59%) had surgical lung biopsies. Patients with ≥10% decline in predicted FVC after 6-12 months had a significantly increased risk of all-cause mortality (median survival 53 months, 95% CI 37 to 69 vs 139 months, 95% CI 66 to 212 months, p=0.007). On multivariate analysis remained associated with increasing mortality: decline in FVC by ≥10% (HR 4.13, 95% CI 1.96 to 8.70, p=0.005), lower FVC% (HR 1.03, 95% CI 1.01 to 1.05, p=0.003) and with decreasing mortality improvement with antigen avoidance (HR 0.18, 95% CI 0.04 to 0.77, p=0.021). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Hypersensitive Reaction to Tattoos: A Growing Menace in Rural India.

    Science.gov (United States)

    Shashikumar, B M; Harish, M R; Shwetha, B; Kavya, M; Deepadarshan, K; Phani, H N

    2017-01-01

    Increased enthusiasm toward newer fashion trends among rural India along with the lack of government regulation has led to increased tattoo reactions. The objective of this study is to describe various clinical manifestations of hypersensitive reactions to tattoo ink reported at a tertiary care hospital in Mandya district. An observational study was carried out over a period of 1 year from June 2014 to May 2015 at Mandya Institute of Medical Sciences, Mandya. All the patients reporting with allergic reaction due to tattooing were included in the present study after obtaining informed consent. Transient acute inflammatory reaction, infections, and skin diseases localized on tattooed area were excluded from this study. A detailed history regarding the onset, duration and color used for tattooing were collected. Cutaneous examination and biopsy was to done to know the type of reaction. Fifty cutaneous allergic reactions were diagnosed among 39 patients. Mean age of subjects was 22 years and mean duration before the appearance of lesion was 7 months. Common colors associated with reactions were red (53.9%), black (33.3%), green (5.1%), and multicolor (7.7%). Itching was the predominant symptom. Skin lesions mainly consisted of lichenoid papules and plaques, eczematous lesions, and verrucous lesions. Lichenoid histopathology reaction was the most common tissue allergic reaction. Increasing popularity of tattooing among young people has predisposed to parallel increase in adverse reactions. Red pigment is most common cause of allergic reaction in the present study, and lichenoid reaction is the most common reaction.

  17. CONTACT RESISTANCE MODELING

    Directory of Open Access Journals (Sweden)

    S. V. LOSKUTOV

    2018-05-01

    Full Text Available Purpose. To determine the contribution of the real contact spots distribution in the total conductivity of the conductors contact. Methodology. The electrical contact resistance research was carried out on models. The experimental part of this work was done on paper with a graphite layer with membranes (the first type and conductive liquids with discrete partitions (the second type. Findings. It is shown that the contact electrical resistance is mainly determined by the real area of metal contact. The experimental dependence of the electrical resistance of the second type model on the distance between the electrodes and the potential distribution along the sample surface for the first type model were obtained. The theoretical model based on the principle of electric field superposition was considered. The dependences obtained experimentally and calculated by using the theoretical model are in good agreement. Originality. The regularity of the electrical contact resistance formation on a large number of membranes was researched for the first time. A new model of discrete electrical contact based on the liquid as the conducting environment with nuclear membrane partitions was developed. The conclusions of the additivity of contact and bulk electrical resistance were done. Practical value. Based on these researches, a new experimental method of kinetic macroidentation that as a parameter of the metal surface layer deformation uses the real contact area was developed. This method allows to determine the value of average contact stresses, yield point, change of the stress on the depth of deformation depending on the surface treatment.

  18. UVB-induced systemic immunosuppression: role of mast cells and histamine

    International Nuclear Information System (INIS)

    Hart, P.H.; Grimbaldeston, M.A.; Finlay-Jones, J.J.

    1999-01-01

    Full text: UVB radiation (290-320 nm) is immunosuppressive by multiple mechanisms allowing the outgrowth of UV-induced tumours in both mouse and man. Furthermore, patients with non-melanoma skin cancers have a higher risk of death from other cancers which could be explained by UV-induced immunomodulation. The mechanism(s) of suppression by UVB depend on whether the sensitising antigen is applied to the irradiated site ('local') or to non-irradiated sites ('systemic'). In the former, the activity of UV-induced TNFα is important as it affects the migration of Langerhans cells to draining lymph nodes. In contrast, histamine from dermal mast cells is critical to the early events by which UVB can suppress systemic immune responses. The prevalence of dermal mast cells in 7 strains and substrains of mice correlates directly with their susceptibility to UVB-induced systemic immunosuppression. Furthermore, mast cell depleted mice (Wf/Wf) are resistant to UVB-induced systemic immunomodulation. However, they become susceptible after reconstitution of the site to be irradiated with bone marrow derived mast cell precursors. The mice also gain susceptibility to cis-urocanic acid-induced systemic immunomodulation. There is considerable evidence that histamine is the mast cell product critical to downstream immunosuppressive events. Firstly, physiological concentrations of histamine suppress contact hypersensitivity responses. Secondly, histamine receptor antagonists halve UVB-induced systemic immunosuppression. Thirdly, mice with different UVB-susceptibilities are equally susceptible to histamine-induced immunosuppression, and finally, histamine can suppress contact hypersensitivity responses in Wf/Wf mice. We suggest that histamine may be immunomodulatory by multiple pathways. Histamine can induce the production of immunosuppressive prostanoids from keratinocytes. A lymphocyte-derived, histamine-induced suppressor factor was reported in the 1970's. More recently histamine has

  19. Effect of ultraviolet B irradiation on delayed-type hypersensitivity, cytotoxic T lymphocyte activity, and skin graft rejection

    International Nuclear Information System (INIS)

    Tamaki, K.; Iijima, M.

    1989-01-01

    The influence of ultraviolet B irradiation on the induction of delayed-type hypersensitivity reactions to alloantigens by epidermal cells (EC), on the generation of cytotoxic T lymphocyte activity to alloantigens, and on skin graft rejection was studied. After the skin was irradiated with UVB in vitro, EC were obtained. The EC were injected subcutaneously, and the DTH reaction was compared with that induced by non-UVB-irradiated EC. A reduction in the DTH reaction was observed (from 62% to 99.1%). CTL activity in these mice was assessed after in vitro stimulation. CTL activity in mice sensitized with UVB-irradiated EC was significantly reduced. Furthermore, mice sensitized with UVB-irradiated EC did not reject a subsequent skin allograft in an accelerated fashion, whereas mice sensitized with non-UVB-irradiated EC did. The mechanism(s) of these reactions and the clinical application of the UVB irradiation prior to grafting are discussed

  20. The problem of dizziness and syncope in old age: transient ischemic attacks versus hypersensitive carotid sinus reflex.

    Science.gov (United States)

    Uesu, C T; Eisenman, J I; Stemmer, E A

    1976-03-01

    In the elderly, a transient ischemic attack (TIA) and a hypersensitive carotid sinus reflex (HCSR) often co-exist and can pose a diagnostic challenge. Seven cases are presented. HCSR is a relative condition; besides increased irritability of the receptor or target organs, susceptibility of the nerve center to ischemia probably is induced by a slow heart rate or low blood pressure in any patient with pre-existing occlusive cerebrovascular disease. Dizziness and syncope of this type represent hemodynamic TIA in contrast to thromboembolic TIA. The carotid sinus massage test is recommended for differentiating the two types of TIA; the treatments differ. At present there is no uniform management that can be applied to either TIA or HCSR routinely. Therefore, treatment should be approached on an individual basis, keeping in mind the different pathophysiologic factors operating in the specific patient.