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Sample records for contact hypersensitivity induced

  1. Paraben Contact Hypersensitivity

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    A K Bajaj

    1985-01-01

    Full Text Available One hundred patients suspected to be having contact hypersensitivity to topical medicaments were patch tested with methly and propyl parabens along with commercially available topical medicaments. Six patients showed positive reactions to parabens. Two patients each were positive to methyl paraben and propyl paraben and two showed positive reactions to both of these. Three patients each showed positive reactions to soframycin, econazole and nitrofurazone also.

  2. Oxazolone-induced contact hypersensitivity reduces lymphatic drainage but enhances the induction of adaptive immunity.

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    David Aebischer

    Full Text Available Contact hypersensitivity (CHS induced by topical application of haptens is a commonly used model to study dermal inflammatory responses in mice. Several recent studies have indicated that CHS-induced skin inflammation triggers lymphangiogenesis but may negatively impact the immune-function of lymphatic vessels, namely fluid drainage and dendritic cell (DC migration to draining lymph nodes (dLNs. On the other hand, haptens have been shown to exert immune-stimulatory activity by inducing DC maturation. In this study we investigated how the presence of pre-established CHS-induced skin inflammation affects the induction of adaptive immunity in dLNs. Using a mouse model of oxazolone-induced skin inflammation we observed that lymphatic drainage was reduced and DC migration from skin to dLNs was partially compromised. At the same time, a significantly stronger adaptive immune response towards ovalbumin (OVA was induced when immunization had occurred in CHS-inflamed skin as compared to uninflamed control skin. In fact, immunization with sterile OVA in CHS-inflamed skin evoked a delayed-type hypersensitivity (DTH response comparable to the one induced by conventional immunization with OVA and adjuvant in uninflamed skin. Striking phenotypic and functional differences were observed when comparing DCs from LNs draining uninflamed or CHS-inflamed skin. DCs from LNs draining CHS-inflamed skin expressed higher levels of co-stimulatory molecules and MHC molecules, produced higher levels of the interleukin-12/23 p40 subunit (IL-12/23-p40 and more potently induced T cell activation in vitro. Immunization experiments revealed that blockade of IL-12/23-p40 during the priming phase partially reverted the CHS-induced enhancement of the adaptive immune response. Collectively, our findings indicate that CHS-induced skin inflammation generates an overall immune-stimulatory milieu, which outweighs the potentially suppressive effect of reduced lymphatic vessel function.

  3. IL-10 controls dendritic cell-induced T-cell reactivation in the skin to limit contact hypersensitivity

    NARCIS (Netherlands)

    Girard-Madoux, Mathilde J. H.; Kel, Junda M.; Reizis, Boris; Clausen, Björn E.

    2012-01-01

    Background: IL-10 is a pleiotropic cytokine and potent negative regulator of both innate and adaptive immune responses. Consequently, IL-10-deficient (IL-10(-/-)) mice have enhanced contact hypersensitivity (CHS) to topical hapten. Objective: Although the importance of IL-10 production by

  4. 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.

  5. Sulphasalazine Induced Hypersensitivity Syndrome

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    Hatice Şanlı

    2013-05-01

    Full Text Available Drug-induced hypersensitivity syndrome (DIHS is one of the most dangerous drug reactions. Mortality and morbidity is increased by consequent systemic organ involvement. Maculopapular eruptions are the most common lesions accompanying DIHS, however, the morphology of skin lesions may vary. The most common cause of DIHS is the use of aromatic anticonvulsant drugs. However, one must not forget that other drugs may also cause DIHS. Early recognition of the condition is the most important step in the treatment. Herein, we present a case of DIHS triggered by sulphasalazine and associated with pustular eruption and maculopapular eruption.

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

    African Journals Online (AJOL)

    Annals of Medical and Health Sciences Research | Mar-Apr 2015 | Vol 5 | Issue 2 |. Amalgam Contact. Hypersensitivity. Lesion: An Unusual. Presentation‑Report of a. Rare Case ... 1Department of Medical Physics, School of Medicine,. 2Ionizing and Non‑ionizing Radiation Protection Research. Center, 3Student Research ...

  7. Regulatory B cells induced by ultraviolet B through toll-like receptor 4 signalling contribute to the suppression of contact hypersensitivity responses in mice.

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    Liu, Xiaoming; Huang, Haiyan; Gao, Hongbin; Wu, Xia; Zhang, Wei; Yu, Bo; Dou, Xia

    2017-12-05

    Ultraviolet (UV) B irradiation is known to suppress contact hypersensitivity (CHS) responses in mouse models by suppressing immune responses. However, the cellular mechanisms responsible for UVB-induced systemic suppression remain unclear. Regulatory B cells have been reported to play an inhibitory role during CHS. It is presently unknown whether regulatory B cells contribute to the effect of UVB phototherapy. To investigate the inductive effect of UVB on regulatory B cells and the underlying mechanisms by using a CHS mouse model. CHS was induced with oxazolone, and evaluated by histopathology, flow cytometry, and quantitative real-time polymerase chain reaction. We found that UVB irradiation induced regulatory B cell expansion and ameliorated CHS. UVB-induced regulatory B cells contribute to systemic immunosuppression by inhibiting the proliferation of T cells. Moreover, we determined that toll-like receptor (TLR) 4, the expression of which was upregulated in B cells after UVB exposure, played an essential role in the induction of regulatory B cells. Our data identified regulatory B cells as regulators of UVB-induced immunosuppression in CHS, and suggest the importance of the UVB-TLR4 axis in the generation of regulatory B cells. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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    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.

  9. Contact Hypersensitivity to Topical Antimicrobial and Antifungal Agents

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    A K Bajaj

    1982-01-01

    Full Text Available To find out the incidence of hypersensitivity to antimicrobial drugs patch tests with various commercially available antimicrobial agents were carried out in 112 patients suspected of contact sensitivity to these substances. Eighty eight patients showed positive reaction to one or more drugs. H incidence of contact sensitivity was observed with neomycin (48%, nitrofurazone (460/o and bromsalicyl chloranilide (45%, while gentian violet gentamicin and povidone iodine were found to be the least sensitizers (5%, 6% and 70/o - respectively. Multiple hypersensitivity (four or more drugs was observed in 25 patients and a large number of them had ulcers at the time of study or in the past.

  10. Immediate and delayed contact hypersensitivity to verbena plants

    DEFF Research Database (Denmark)

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

    1995-01-01

    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...

  11. Amalgam contact hypersensitivity lesion: an unusual presentation ...

    African Journals Online (AJOL)

    However, ACHL presenting primarily as a black pigmented lesion is extremely rare if not reported. The clinician should be aware of one such presentation of ACHL; we report a unique case of ACHL in a 30‑year‑old female with such a pigmented lesion in close contact with amalgam restorations. The lesion regressed ...

  12. A novel regulatory mechanism of naringenin through inhibition of T lymphocyte function in contact hypersensitivity suppression

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    Fang, Feng; Tang, Yijun; Gao, Zhe [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China)

    2010-06-25

    Naringenin, a flavonoid in grapefruits and citrus fruits, has been reported to exhibit anti-inflammatory and anti-oxidative activities. Contact hypersensitivity (CHS) is a T cell-mediated immune reaction, and the factors released from macrophages also contribute to this response. Previous studies showed that naringenin suppressed CHS by inhibiting activation and migration of macrophages. However, little is known about naringenin's effects on T lymphocytes. Our study indicated that naringenin potently suppressed picryl chloride (PCl)-induced contact hypersensitivity by inhibiting the proliferation and activation of T lymphocytes. In vitro, both of the activated hapten-specific T cells and the T cells stimulated with anti-CD3/anti-CD28 showed growth arrest after naringenin treatment. Furthermore, naringenin reduced CD69 (the protein level) and cytokines such as IL-2, TNF-{alpha}, and IFN-{gamma} (the mRNA level) expressions which highly expressed by activated T cells. Meanwhile, naringenin also induced T cell apoptosis by upregulation of Bax, Bad, PARP, cleaved-caspase 3 and downregulation of phosphorylated Akt, Bcl-2. These findings suggest that, besides its anti-inflammatory activities in macrophages, naringenin also showed inhibitory effects on the activation and proliferation of T cells to alleviate symptoms of contact hypersensitivity.

  13. Burning mouth syndrome: the role of contact hypersensitivity.

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    Marino, R; Capaccio, P; Pignataro, L; Spadari, F

    2009-05-01

    Burning mouth syndrome is a burning sensation or stinging disorder affecting the oral mucosa in the absence of any clinical signs or mucosal lesions. Some studies have suggested that burning mouth syndrome could be caused by the metals used in dental prostheses, as well as by acrylate monomers, additives and flavouring agents, although others have not found any aetiologic role for hypersensitivity to dental materials. To evaluate the extent and severity of adverse reactions to dental materials in a group of patients with burning mouth syndrome, and investigate the possible role of contact allergy in its pathogenesis. We prospectively studied 124 consecutive patients with burning mouth syndrome (108 males; mean age 57 years, range 41-83), all of whom underwent allergen patch testing between 2004 and 2007. Sixteen patients (13%) showed positive patch test reactions and were classified as having burning mouth syndrome type 3 or secondary burning mouth syndrome (Lamey's and Scala's classifications). Although we did not find any significant association between the patients and positive patch test reactions, it would be advisable to include hypersensitivity to dental components when evaluating patients experiencing intermittent oral burning without any clinical signs.

  14. 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....../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...

  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. Pathophysiology of stress-induced visceral hypersensitivity

    NARCIS (Netherlands)

    Stanisor, O.I.

    2014-01-01

    Visceral hypersensitivity is observed in the majority of patients with IBS and considered a pathophysiological mechanism. The aim of the work described in this thesis was to obtain a better understanding of the stress-related pathophysiology of visceral hypersensitivity. Investigations were carried

  17. Isotype-like suppression of T cell-mediated immunity in vivo. I. Delayed-type hypersensitivity specificity of T cell suppression induced by antigen-binding T cell factors that initiate contact sensitivity.

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    Ptak, W; Bereta, M; Ptak, M; Askenase, P W

    1986-03-01

    A new form of immunoregulation is described that is based on the recent suggestion that the effector phase of delayed-type hypersensitivity (DTH) responses consists of a cascade of steps that are dependent on the sequential action of two types of antigen-specific Ly-1+ effector cells. According to this formulation, which is based on analysis of contact sensitivity (CS) in mice, DTH consists of at least two T cell-dependent steps that must occur in sequence. The first of these steps occurs within 2 hr of challenge and depends on DTH-initiating, antigen-binding, antigen-specific T cell factors that sensitize the tissues for an obligatory initial vasoactive step, which allows the antigen/major histocompatibility complex (MHC)-restricted, Ly-1+ effector T cells of classic 24 to 48 hr DTH responses to enter the tissues and produce chemoattractant lymphokines. We have now found that nonspecific suppression of CS responses can be induced by i.v. injection of these antigen-binding, CS-initiating T cell factors. Injection of the antigen-binding T cell factor induces Ly-2+, I-J-, cyclophosphamide sensitive, seemingly nonspecific suppressor T cells to inhibit initiation of CS responses. These suppressor cells do not affect the late-acting lymphokine-producing T cells, but probably act by preventing production of antigen-specific factors of the type that are required to initiate DTH responses. Furthermore, injection of CS-initiating antigen-binding T cell factors also induces suppression of sheep red blood cell (SRBC)-specific DTH, but does not affect classic anti-SRBC B cell responses, which are dependent on antigen/MHC-restricted Ly-1+ helper T cells; skin allograft rejection responses are also not affected. Thus, the suppression is DTH-specific. In addition, suppression induced by antigen-binding T cell factors is Igh and not MHC/H-2 restricted. These findings and data in the companion manuscript showing that these suppressor T cells act by production of soluble suppressor

  18. Ceftriaxone Induced Hypersensitivity Reactions Following Intradermal Skin Test: Case Series

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    Sereen Rose Thomson

    2017-10-01

    Full Text Available The incidence of cephalosporin induced hypersensitivity reactions in non-penicillin allergic patients is about 1.7% and in penicillin allergic patients it is about 3-5%. Infact, cephalosporins are considered as the first choice in penicillin allergic patients who need antibiotic therapy intraoperatively. Prompt identification of patients with beta-lactam allergy would lead to an improved utilization of antibiotics and reduced occurrence of resistant strains. We hereby attempt to present a series of cases where ceftriaxone has been implicated in the manifestation of various hypersensitivity reactions. We have also tried to highlight some of the errors, risk factors and other drugs that precipitate a hypersensitivity reaction.

  19. Agrobacterium -induced hypersensitive necrotic reaction in plant ...

    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 ...

  20. [Hypersensitivity pneumonitis induced by Hypsizigus marumoreus].

    Science.gov (United States)

    Takaku, Yotaro; Takayanagi, Noboru; Minagawa, Shunsuke; Tsuchiya, Yutaka; Hijikata, Naoya; Hara, Kenichiro; Yamaji, Tomohisa; Tokunaga, Daido; Saito, Hiroo; Ubukata, Mikio; Kurashima, Kazuyoshi; Yanagisawa, Tsutomu; Sugita, Yutaka; Kawabata, Yoshinori

    2009-10-01

    We present the case of a 53-year-old woman who was employed at a mushroom (Pleurotus eryngii and Hypsizigus marumoreus) cultivation factory for 15 years. She was admitted to our hospital because of fever and dry cough. Chest radiography and CT scanning revealed diffuse ground glass opacity and centrilobular nodules in both lung fields. Serum KL-6 was elevated. In the bronchoalveolar lavage fluid, the CD4/CD8 ratio was reduced, and the lymphocyte fraction was very high. Transbronchial lung biopsy specimens showed lymphocyte alveolitis. After admission, the patient's symptoms improved rapidly without medication. Although these findings are compatible with hypersensitivity pneumonitis, it was difficult to identify a causative antigen. Serum antibody against Trichosporon was positive. A lymphocyte stimulation test of the peripheral blood was positive against extracts of P. eryngii and H. marumoreus. Furthermore, precipitins against the extracts of H. marumoreus were detected by a double immunodiffusion test. Therefore, we decided to conduct a challenge test using H. marumoreus. As an inhalation provocation test with H. marumoreus conducted in a sickroom caused the same clinical symptoms and signs as experienced in the workplace, we diagnosed hypersensitivity pneumonitis caused by H. marumoreus. A provocation test, in which antigen exposure is limited using a closed space, such as a sickroom, was simple, safe and effective for determining the antigen causing hypersensitivity pneumonitis.

  1. 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...... types, including γδ T cells, can produce IL-17. In this study, we determine the role of γδ T cells, especially dendritic epidermal T cells (DETCs), in CHS. Using a well-established model for CHS in which 2,4-dinitrofluorobenzene (DNFB) is used as allergen, we found that γδ T cells are important players...... in CHS. Thus, more IL-17-producing DETCs appear in the skin following exposure to DNFB in wild-type mice, and DNFB-induced ear swelling is reduced by ∼50% in TCRδ(-/-) mice compared with wild-type mice. In accordance, DNFB-induced ear swelling was reduced by ∼50% in IL-17(-/-) mice. We show that DNFB...

  2. Conditional deletion of TGF-βR1 using Langerin-Cre mice results in Langerhans cell deficiency and reduced contact hypersensitivity

    NARCIS (Netherlands)

    S.P. Zahner (Sonja P.); J.M. Kel (Junda); C.A.E. Martina (Cerithsa A.); I. Brouwers-Haspels (Inge); M.A. van Roon (Marian); B.E. Clausen (Bjorn)

    2011-01-01

    textabstractThe critical role of Langerhans cells (LC) in contact hypersensitivity (CHS) was recently questioned in studies using different LC-depletion mouse models. On one hand, inducible ablation of LC led to diminished ear swelling, suggesting functional redundancy between LC and (Langerin +)

  3. Conditional deletion of TGF-βR1 using Langerin-Cre mice results in Langerhans cell deficiency and reduced contact hypersensitivity

    NARCIS (Netherlands)

    Zahner, Sonja P.; Kel, Junda M.; Martina, Cerithsa A. E.; Brouwers-Haspels, Inge; van Roon, Marian A.; Clausen, Björn E.

    2011-01-01

    The critical role of Langerhans cells (LC) in contact hypersensitivity (CHS) was recently questioned in studies using different LC-depletion mouse models. On one hand, inducible ablation of LC led to diminished ear swelling, suggesting functional redundancy between LC and (Langerin(+)) dermal

  4. Hypersensitivity pneumonitis induced by Shiitake mushroom spores.

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    Ampere, Alexandre; Delhaes, Laurence; Soots, Jacques; Bart, Frederic; Wallaert, Benoit

    2012-08-01

    Hypersensitivity pneumonitis (HP) is a pulmonary granulomatosis involving an immunoallergic mechanism caused by chronic inhalation of antigens, most frequently organic substances, as well as chemicals. We report the first European case of hypersensitivity pneumonitis due to the inhalation of Shiitake mushroom spores. A 37-year-old French Caucasian man with a one-month history of persistent dry cough, shortness of breath and loss of weight was admitted to our hospital on December 2010. Anamnesis showed he was involved in mushroom production beginning in the summer of 2010. His temperature on admission was 36.6°C and he had a normal blood pressure (135/90 mmHg). Bilateral fine crackles were audible in the base of both lungs. Pulmonary function tests showed a mild restrictive pattern with decreased DLco and a PaO(2) of 65 mmHg, Chest CT scan revealed reticulo-nodular shadows, slight ground glass opacities, liner atelectasis, and subpleural opacities in both lung fields. Bronchoscopy was normal but cytological examination of BAL revealed a predominant lymphocytosis (55%). Serum precipitins to the Shiitake mushroom spores were positive (3 precipitins arcs with high intensity) and as a result we advised the patient to cease his mushroom production activities. The diagnosis of hypersensitivity pneumonitis due to inhalation of Shiitake mushroom spores was established as a result of the improvement of all of his clinical symptoms, i.e., cough, weight loss, bilateral fine crackles, mild restrictive pattern of pulmonary function, and reticulo-nodular shadows on chest CT, once exposure was eliminated. Recent interest in exotic mushrooms varieties, e.g., Shiitake, in developed countries because of their possible medicinal properties might increase the potential risk of HP among mushrooms workers. Therefore, healthcare professionals have to take this new potential respiratory disease into account.

  5. Lipstick Induced Contact Leucoderma

    Directory of Open Access Journals (Sweden)

    Gupta Lalit Kumar

    2001-01-01

    Full Text Available Lipstick is a commonly used cosmetic. Its use may sometimes lead to contact dermatitis. Contact leucoderma to lipsticks however, is not common. We report a patient developing contact leucoderma to lipstick in association with contact dermatitis.

  6. Lipstick Induced Contact Leucoderma

    OpenAIRE

    Gupta Lalit Kumar; Jain Suresh Kumar; Khare Ashok Kumar

    2001-01-01

    Lipstick is a commonly used cosmetic. Its use may sometimes lead to contact dermatitis. Contact leucoderma to lipsticks however, is not common. We report a patient developing contact leucoderma to lipstick in association with contact dermatitis.

  7. Live Imaging of the Skin Immune Responses: Visualization of the Contact Hypersensitivity Response.

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    Egawa, Gyohei; Honda, Tetsuya; Kabashima, Kenji

    2018-01-01

    A variety of immune cells are involved in cutaneous immune responses. Over the last decade, intravital imaging has become an important technique used to capture the dynamic behavior of immune cells in the physiological context. In this chapter, we describe essential techniques for visualizing immune cells in the skin, focusing on the contact hypersensitivity response. Using fluorescent dyes and transgenic reporter animals, many kinds of immune cells and skin components can be visualized in three dimensions and in a noninvasive manner.

  8. Ceftriaxone Induced Hypersensitivity Reactions Following Intradermal Skin Test: Case Series

    OpenAIRE

    Sereen Rose Thomson; Balaji Ommurugan; Navin Patil

    2017-01-01

    The incidence of cephalosporin induced hypersensitivity reactions in non-penicillin allergic patients is about 1.7% and in penicillin allergic patients it is about 3-5%. Infact, cephalosporins are considered as the first choice in penicillin allergic patients who need antibiotic therapy intraoperatively. Prompt identification of patients with beta-lactam allergy would lead to an improved utilization of antibiotics and reduced occurrence of resistant strains. We hereby attempt to present a ser...

  9. 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.

  10. CD8+ T cell migration to the skin requires CD4+ help in a murine model of contact hypersensitivity.

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    Nanna Fyhrquist

    Full Text Available The relative roles of CD4+ and CD8+ T cells in contact hypersensitivity responses have not been fully solved, and remain an important question. Using an adoptive transfer model, we investigated the role of the respective T cell subset. Magnetic bead separated CD4+ and CD8+ T cells from oxazolone sensitized C57BL/6 mice were transferred into RAG-/- mice, followed by hapten challenge and analysis of inflammatory parameters at 24 hours post exposure. The CD4+ T cell recipient mice developed partial contact hypersensitivity responses to oxazolone. CD8+ T cells caused significant amplification of the response in recipients of both CD4+ and CD8+ T cells including ear swelling, type 1 inflammatory mediators, and cell killing. Unexpectedly, CD8+ T cells were not sufficient to mediate contact hypersensitivity, although abundantly present in the lymph nodes in the CD8+ T cell reconstituted mice. There were no signs of inflammation at the site of hapten exposure, indicating impaired recruitment of CD8+ T cells in the absence of CD4+ T cells. These data show that CD4+ T cells mediate contact hypersensitivity to oxazolone, but CD8+ T cells contribute with the most potent effector mechanisms. Moreover, our results suggest that CD4+ T cell function is required for the mobilization of CD8+ effector T cells to the site of hapten exposure. The results shed new light on the relative importance of CD4+ and CD8+ T cells during the effector phase of contact hypersensitivity.

  11. Dynamical optical imaging monocytes/macrophages migration and activation in contact hypersensitivity (Conference Presentation)

    Science.gov (United States)

    Zhang, Zhihong

    2017-02-01

    Inflammatory monocytes/macrophages (Mon/Mφ) play an important role in cutaneous allergic inflammation. However, their migration and activation in dermatitis and how they accelerate the inflammatory reaction are largely unknown. Optical molecular imaging is the most promising tool for investigating the function and motility of immune cells in vivo. We have developed a multi-scale optical imaging approach to evaluate the spatio-temporal dynamic behavior and properties of immune cells from the whole field of organs to the cellular level at the inflammatory site in delayed type hypersensitivity reaction. Here, we developed some multi-color labeling mouse models based on the endogenous labeling with fluorescent proteins and the exogenous labeling with fluorescent dyes. We investigated the cell movement, cell interaction and function of immunocytes (e.g. Mon/Mφ, DC, T cells and neutrophils) in the skin allergy inflammation (e.g., contact hypersensitivity) by using intravital microscopy. The long-term imaging data showed that after inflammatory Mon/Mφ transendothelial migration in dermis, they migrating in interstitial space of dermis. Depletion of blood monocyte with clodronate liposome extremely reduced the inflammatory reaction. Our finding provided further insight into inflammatory Mon/Mφ mediating the inflammatory cascade through functional migration in allergic contact dermatitis.

  12. Burning mouth syndrome: a possible etiologic role for local contact hypersensitivity.

    Science.gov (United States)

    Dutrée-Meulenberg, R O; Kozel, M M; van Joost, T

    1992-06-01

    The pathogenesis of the burning mouth syndrome (BMS) is not yet understood. Apart from psychologic factors, several etiologic "somatic" factors have been reported. In 22 patients (19 women, 3 men, mean age 56 years) classified with BMS, clinical and laboratory investigations were performed, with particular emphasis on the role of contact hypersensitivity. Twenty of the 22 patients wore a complete or partial denture. Besides clinical and laboratory investigations patch testing was performed with a standard routine series and a standardized denture-dental (acrylate and metal) series. Folate, iron, pyridoxine deficiency, and Candida infections were found, but correction of the deficiency or treatment of the infection was of no benefit. Contact allergy to allergens used in the production of acrylate-based dentures was observed in six (27%) of the cases (all wore a denture); positive reactions were seen to N,N,-dimethyl-4-toluidine (3 cases), to 4-tolyldiethanolamine (2 cases), to benzoylperoxide (2 cases), and to oligotriacrylate (1 case). In six cases (27%) a possible relevant sensitization was seen to dental metals and in particular to gold chloride (four cases). The possible role of local hypersensitivity reactions to denture or dental components as etiologic factors in BMS must be considered.

  13. TU-572, a potent and selective CD45 inhibitor, suppresses IgE-mediated anaphylaxis and murine contact hypersensitivity reactions.

    Science.gov (United States)

    Hamaguchi, T; Takahashi, A; Manaka, A; Sato, M; Osada, H

    2001-12-01

    CD45, receptor-type protein tyrosine phosphatases (PTPases) are essential components of signaling through both the T cell receptor and the B cell antigen receptor. However, the functional significance of CD45 in the signaling pathway through the high-affinity immunoglobulin (Ig) E receptor has not yet been established. In this study, we demonstrate that the potent CD45 inhibitor negatively regulates IgE-dependent anaphylaxis and contact hypersensitivity reactions. We have previously found that TU-572, 2-[(4-methylthiopyridin-2-yl)methylsulfinyl]-5-isopropoxybenzimidazole, had a potent and selective inhibitory effect against PTPase activity of CD45. Using a CD45 inhibitor, we examined in vitro and in vivo IgE-mediated responses. TU-572 potently inhibited histamine release from rat peritoneal mast cells and mouse systemic anaphylaxis reaction using monoclonal anti-dinitrophenyl (DNP) IgE and DNP-BSA. TU-572 also suppressed the immediate-type hypersensitivity response induced by repeated epicutaneous application of trinitrochlorobenzene in BALB/c mice. These findings revealed that the PTPase activity of CD45 played a critical role in signal transduction of IgE-mediated anaphylaxis in vitro and in vivo. PTPase inhibitors such as TU-572 are useful in the treatment of allergic diseases. Copyright 2002 S. Karger AG, Basel

  14. Anisakis simplex: from obscure infectious worm to inducer of immune hypersensitivity.

    Science.gov (United States)

    Audicana, M Teresa; Kennedy, Malcolm W

    2008-04-01

    Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites ("gastroallergic anisakiasis"), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive.

  15. Role of lipid in the induction of hapten-specific delayed hypersensitivity and contact sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Dailey, M.O.; Hunter, R.L.

    1974-04-01

    Guinea pigs immunized with bovine serum albumin conjugated with dinitrophenol (BSA-DNP), in Freund's complete adjuvant, produce antibody to the DNP and delayed-type hypersensitivity (DTH) to the BSA. We report that immunization with BSA-DNP doubly conjugated with medium chain fatty acids (L-BSA-DNP) stimulates the production of DTH specific for the hapten DNP with minimal antibody to DNP and no detectable immune response to the carrier BSA. The production of hapten-specific DTH reactions was assessed by two methods. First, animals immunized with L-BSA-DNP produced typical contact sensitivity reactions to epidermal challenge with dinitrofluorobenzene. Second, they produced grossly and microscopically typical delayed hypersensitivity reactions to the intradermal injection of DNP conjugated either to BSA or to a non-cross-reacting carrier, hen egg albumin. In further experiments, DNP-specific DTH was produced by animals immunized with BSA-DNP to which lipid groups had been attached by electrostatic rather than covalent bonds. Evidence is discussed which indicates that the production of DTH to haptens and proteins is largely a function of the lipophilic nature of the entire immunogen and is not dependent upon properties of individual antigenic determinants. Autoradiographic studies with /sup 125/I-labeled material demonstrated that the lipid-rich antigens are localized in the paracortical area of lymph nodes, in close proximity to the thymus-derived cells which are stimulated in the induction of DTH.

  16. 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.

  17. Identification of MHC Haplotypes Associated with Drug-induced Hypersensitivity Reactions in Cynomolgus Monkeys.

    Science.gov (United States)

    Wu, Hong; Whritenour, Jessica; Sanford, Jonathan C; Houle, Christopher; Adkins, Karissa K

    2017-01-01

    Drug-induced hypersensitivity reactions can significantly impact drug development and use. Studies to understand risk factors for drug-induced hypersensitivity reactions have identified genetic association with specific human leukocyte antigen (HLA) alleles. Interestingly, drug-induced hypersensitivity reactions can occur in nonhuman primates; however, association between drug-induced hypersensitivity reactions and major histocompatibility complex (MHC) alleles has not been described. In this study, tissue samples were collected from 62 cynomolgus monkeys from preclinical studies in which 9 animals had evidence of drug-induced hypersensitivity reactions. Microsatellite analysis was used to determine MHC haplotypes for each animal. A total of 7 haplotypes and recombinant MHC haplotypes were observed, with distribution frequency comparable to known MHC I allele frequency in cynomolgus monkeys. Genetic association analysis identified alleles from the M3 haplotype of the MHC I B region (B*011:01, B*075:01, B*079:01, B*070:02, B*098:05, and B*165:01) to be significantly associated (χ2 test for trend, p reactions. Sequence similarity from alignment of alleles in the M3 haplotype B region and HLA alleles associated with drug-induced hypersensitivity reactions in humans was 86% to 93%. These data demonstrate that MHC alleles in cynomolgus monkeys are associated with drug-induced hypersensitivity reactions, similar to HLA alleles in humans.

  18. [Epicutaneous patch testing in delayed drug hypersensitivity reactions induced by antiepileptic drugs].

    Science.gov (United States)

    Ben Mahmoud, Lobna; Bahloul, Najla; Ghozzi, Hanen; Kammoun, Brahim; Hakim, Ahmed; Sahnoun, Zouheir; Kammoun, Sami; Zeghal, Khaled

    2017-10-01

    Antiepileptic drugs are widely used and are associated with numerous side effects including skin eruptions. Epicutaneous tests have been used with variable success in skin drug reactions. The purpose of this study was to evaluate the profitability of epicutaneous tests in delayed hypersensitivity reactions induced by antiepileptic drugs. We analyzed all cases of allergic skin reactions to antiepileptic drugs notified in regional pharmacovigilance center of Sfax (Tunisia) between June 1, 2014 and April 30, 2016. The imputation score, determined using the French imputation method, should be at least doubtful. Patch-tests were performed in accordance with the general Europen network on Drug Allergy/European Academy of Allergy and Clinical Immunology (ENDA/EAACI) guidelines. Patch-tests were read according to the generally accepted criteria of the International contact dermatitis research group (ICDRG). In our study, 20 patients were included, among which 23 events were observed. The drug involved in delayed hypersensitivity reactions was carbamazepine in 11 cases, phenobarbital in 10 cases and valproic acid in 4 cases. The clinical reactions caused by the drug were classified as maculopapular exanthema (11 cases), DRESS syndrome (6 cases), Stevens-Johnson syndrome (2 cases), fixed drug eruption (2 cases) and erythroderma (2 cases). Patch-tests were positive in 19 patients (95 %). Cross-reactivity between antiepileptic drugs was observed in 4 cases: between valproic acid and carbamazepine in 2 cases between valproic acid and phenobarbital in 1 case and between phenobarbital and carbamazepine in 1 case. In this study, patch testing was a safe and useful method in confirming the culprit drug in delayed hypersensitivity reactions induced by antiepileptic drugs. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  19. Peripheral neuropathy induces cutaneous hypersensitivity in chronically spinalized rats.

    Science.gov (United States)

    Pitcher, Graham M; Ritchie, Jennifer; Henry, James L

    2013-07-01

    The present study was aimed at the issue of whether peripheral nerve injury-induced chronic pain is maintained by supraspinal structures governing descending facilitation to the spinal dorsal horn, or whether altered peripheral nociceptive mechanisms sustain central hyperexcitability and, in turn, neuropathic pain. We examined this question by determining the contribution of peripheral/spinal mechanisms, isolated from supraspinal influence(s), in cutaneous hypersensitivity in an animal model of peripheral neuropathy. Adult rats were spinalized at T8-T9; 8 days later, peripheral neuropathy was induced by implanting a 2-mm polyethylene cuff around the left sciatic nerve. Hind paw withdrawal responses to mechanical or thermal plantar stimulation were evaluated using von Frey filaments or a heat lamp, respectively. Spinalized rats without cuff implantation exhibited a moderate decrease in mechanical withdrawal threshold on ~day 10 (P day 18 (P day 4; P day 10; P neuropathy may have a pathologically relevant role in both inducing and sustaining neuropathic pain. Wiley Periodicals, Inc.

  20. Functions of Exosomes and Microbial Extracellular Vesicles in Allergy and Contact and Delayed-Type Hypersensitivity.

    Science.gov (United States)

    Nazimek, Katarzyna; Bryniarski, Krzysztof; Askenase, Philip W

    2016-01-01

    Extracellular vesicles, such as exosomes, are newly recognized intercellular conveyors of functional molecular mechanisms. Notably, they transfer RNAs and proteins between different cells that can then participate in the complex pathogenesis of allergic and related hypersensitivity responses and disease mechanisms, as described herein. This review highlights this important new appreciation of the in vivo participation of such extracellular vesicles in the interactions between allergy-mediating cells. We take into account paracrine epigenetic exchanges mediated by surrounding stromal cells and the endocrine receipt of exosomes from distant cells via the circulation. Exosomes are natural ancient nanoparticles of life. They are made by all cells and in some form by all species down to fungi and bacteria, and are present in all fluids. Besides a new focus on their role in the transmission of genetic regulation, exosome transfer of allergens was recently shown to induce allergic inflammation. Importantly, regulatory and tolerogenic exosomes can potently inhibit allergy and hypersensitivity responses, usually acting nonspecifically, but can also proceed in an antigen-specific manner due to the coating of the exosome surface with antibodies. Deep analysis of processes mediated by exosomes should result in the development of early diagnostic biomarkers, as well as allergen-specific, preventive and therapeutic strategies. These will likely significantly diminish the risks of current allergen-specific parenteral desensitization procedures, and of the use of systemic immunosuppressive drugs. Since extracellular vesicles are physiological, they can be fashioned for the specific delivery of therapeutic molecular instructions through easily tolerated, noninvasive routes, such as oral ingestion, nasal administration, and perhaps even inhalation. © 2016 S. Karger AG, Basel.

  1. Functions of Exosomes and Microbial Extracellular Vesicles in Allergy and Contact and Delayed-Type Hypersensitivity

    Science.gov (United States)

    Nazimek, Katarzyna; Bryniarski, Krzysztof; Askenase, Philip W.

    2016-01-01

    Extracellular vesicles, such as exosomes, are newly recognized intercellular conveyors of functional molecular mechanisms. Notably, they transfer RNAs and proteins between cells in general, that then can participate, as described herein, in the complex pathogenesis of allergic and related hypersensitivity responses and disease mechanisms. This review highlights this important new appreciation of the in vivo participation of such extracellular vesicles in the interactions between allergy-mediating cells, taking into account paracrine epigenetic exchanges mediated by surrounding stromal cells and the endocrine receipt of exosomes from distant cells via the circulation. Exosomes are natural ancient nanoparticles of life. They are made by all cells and in some form by all species down to fungi and bacteria, and are present in all fluids. Besides a new focus on their role in the transmission of genetic regulation, exosome transfer of allergens was recently shown to induce allergic inflammation. Importantly, regulatory and tolerogenic exosomes can potently inhibit allergy and hypersensitivity responses, usually acting non-specifically, but also can proceed in an antigen-specific manner due to coating of the exosome surface with antibodies. Deep analysis of processes mediated by exosomes should result in development of early diagnostic biomarkers, as well as allergen-specific, preventive and therapeutic strategies. These likely will significantly diminish the risks of current allergen specific parenteral desensitization procedures, and of the use of systemic immunosuppressive drugs. Since extracellular vesicles are physiological, they can be fashioned for specific delivery of therapeutic molecular instructions through easily tolerated, non-invasive routes, such as oral ingestion, nasal administration, and perhaps even inhalation. PMID:27820941

  2. 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.

  3. Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity

    Science.gov (United States)

    Audicana, M. Teresa; Kennedy, Malcolm W.

    2008-01-01

    Summary: Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites (“gastroallergic anisakiasis”), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive. PMID:18400801

  4. Hypersensitivity pneumonitis induced by spores of Lyophyllum aggregatum.

    Science.gov (United States)

    Tsushima, K; Fujimoto, K; Yamazaki, Y; Takamizawa, A; Amari, T; Koizumi, T; Kubo, K

    2001-10-01

    Lyophyllum aggregatum (LA) is called Shimeji in Japanese and is eaten commonly as a mushroom. Shimeji mushrooms are cultivated in an indoor environment all year round. This study aimed to clarify the clinical features of hypersensitivity pneumonitis (HP) induced by LA. Ten patients showed mild respiratory symptoms including dry cough, sputum, and low-grade fever. We tried to characterize the clinical features and the findings using chest high-resolution CT (HRCT), pulmonary function tests (PFTs), and BAL fluid (BALF) tests in patients with HP induced by LA. HP was diagnosed from clinical features, HRCT findings, BALF findings, lung histology, and lymphocyte stimulation tests (LSTs) for LA. Laboratory findings showed mean (+/- SD) elevated levels of C-reactive protein (0.78 +/- 1.3 mg/dL), erythrocyte sedimentation rate (48 +/- 23 mm/h), and gamma-globulin (26.9 +/- 7.6%). PFTs revealed a slight decrease in the percentage diffusing capacity of the lung for carbon monoxide, possibly due to the presence of epithelial granulomas in the alveoli. Although 4 of 10 patients showed normal findings on the chest radiograph (CXR), chest HRCT findings of all patients showed centrilobular small nodules and diffuse ground-glass opacities. The BALF testing revealed an increase in total cell counts, showing predominantly activated T lymphocytes. The CD4/CD8 cell ratio was significantly decreased (0.5 +/- 0.3). The results of the LSTs were positive in seven of seven cases. Since patients with HP induced by LA typically have mild respiratory symptoms and sometimes normal CXR findings, their conditions might remain undiagnosed. However, the chest HRCT images showed the typical subacute phase of HP.

  5. Role of TRPV1 in inflammation-induced airway hypersensitivity

    OpenAIRE

    Lee, Lu-Yuan; Gu, Qihai

    2009-01-01

    Airway hypersensitivity is a common pathophysiological feature in various airway inflammatory diseases. Increasing evidence suggests that activation of the transient receptor potential vanilloid type 1 receptor (TRPV1) plays an important part in the manifestation of various symptoms of airway hypersensitivity. This mini-review focuses on recent studies that have revealed several potential contributing factors to the increase in TRPV1 sensitivity in pulmonary sensory neurons during airway infl...

  6. Potential role of blood dendritic cells in elicitation phase of contact hypersensitivity response – preliminary study

    Directory of Open Access Journals (Sweden)

    Aleksandra Lesiak

    2016-06-01

    Full Text Available Introduction . In contrast to our broad knowledge about the role of dendritic cells in the sensitization phase of the contact hypersensitivity response (CHS, very little is known about their function in the effector phase. The pathophysiological mechanism of blood dendritic cells’ participation in the inflammatory response in CHS is an emerging subject of study and needs to be scrutinized. Objective . To assess the presence and type of human blood dendritic cells (BDC – plasmacytoid DC (pDC and myeloid DC (mDC – at the elicitation site of CHS. Material and methods. The study group consisted of 25 healthy volunteers with a mean age of 22.3 ±6.1. Each patient before the trial was sensitized with DPCP, and after 3 weeks skin biopsies were taken from the elicitation site and were immunohistochemically stained with monoclonal mouse IgG1 antibodies against blood dendritic cell antigens (BDCA. Results . Skin biopsies were divided into two groups: group 1 where the CHS score was assessed as 0 (no reaction; n = 7 and group 2 where the CHS score was assessed as 1 (any response noted; n = 18. Compared to group 1, group 2 had a significantly lower percentage of pDC (60% vs. 15% respectively in the inflammatory infiltrate site. We also observed that the percentage of mDC was higher in group 2 compared to group 1, although this result was not statistically significant. Conclusions . Our findings provide some data on composition of inflammatory infiltrate in the elicitation phase of CHS. We suggest that the imbalance between pDC and mDC may be a key to understanding the effector phase of CHS.

  7. Prevention of ultraviolet radiation-induced immunosuppression by sunscreen in Candida albicans-induced delayed-type hypersensitivity

    OpenAIRE

    Chen, Quan; LI, RUNXIANG; Zhao, Xiaoxia; LIANG, BIHUA; MA, SHAOYIN; Li, Zhenjie; ZHU, HUILAN

    2016-01-01

    Ultraviolet (UV) radiation-induced immunosuppression leading to skin cancer has received increased attention in previous years. The present study aimed to investigate the immunoprotection offered by Anthelios sunscreen in a mouse model of Candida albicans-induced delayed-type hypersensitivity. Anthelios sunscreen was applied to the skin on the dorsal skin of BALB/c mice treated with a sub-erythema dose of solar-simulated radiation. Delayed-type hypersensitivity was induced by immunization wit...

  8. Contribution of afferent pathways to nerve injury-induced spontaneous pain and evoked hypersensitivity.

    Science.gov (United States)

    King, Tamara; Qu, Chaoling; Okun, Alec; Mercado, Ramon; Ren, Jiyang; Brion, Triza; Lai, Josephine; Porreca, Frank

    2011-09-01

    A predominant complaint in patients with neuropathic pain is spontaneous pain, often described as burning. Recent studies have demonstrated that negative reinforcement can be used to unmask spontaneous neuropathic pain, allowing for mechanistic investigations. Here, ascending pathways that might contribute to evoked and spontaneous components of an experimental neuropathic pain model were explored. Desensitization of TRPV1-positive fibers with systemic resiniferatoxin (RTX) abolished spinal nerve ligation (SNL) injury-induced thermal hypersensitivity and spontaneous pain, but had no effect on tactile hypersensitivity. Ablation of spinal NK-1 receptor-expressing neurons blocked SNL-induced thermal and tactile hypersensitivity as well as spontaneous pain. After nerve injury, upregulation of neuropeptide Y (NPY) is observed almost exclusively in large-diameter fibers, and inactivation of the brainstem target of these fibers in the nucleus gracilis prevents tactile but not thermal hypersensitivity. Blockade of NPY signaling within the nucleus gracilis failed to block SNL-induced spontaneous pain or thermal hyperalgesia while fully reversing tactile hypersensitivity. Moreover, microinjection of NPY into nucleus gracilis produced robust tactile hypersensitivity, but failed to induce conditioned place aversion. These data suggest that spontaneous neuropathic pain and thermal hyperalgesia are mediated by TRPV1-positive fibers and spinal NK-1-positive ascending projections. In contrast, the large-diameter dorsal column projection can mediate nerve injury-induced tactile hypersensitivity, but does not contribute to spontaneous pain. Because inhibition of tactile hypersensitivity can be achieved either by spinal manipulations or by inactivation of signaling within the nucleus gracilis, the enhanced paw withdrawal response evoked by tactile stimulation does not necessarily reflect allodynia. Copyright © 2011 International Association for the Study of Pain. Published by

  9. Rice Hypersensitive Induced Reaction Protein 1 (OsHIR1 associates with plasma membrane and triggers hypersensitive cell death

    Directory of Open Access Journals (Sweden)

    Sun Sai-Ming

    2010-12-01

    Full Text Available Abstract Background 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. Result 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. Conclusion 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

  10. HLA-A★3101 and Carbamazepine-Induced Hypersensitivity Reactions in Europeans

    Science.gov (United States)

    McCormack, Mark; Alfirevic, Ana; Bourgeois, Stephane; Farrell, John J.; Kasperavičiūtė, Dalia; Carrington, Mary; Sills, Graeme J.; Marson, Tony; Jia, Xiaoming; de Bakker, Paul I.W.; Chinthapalli, Krishna; Molokhia, Mariam; Johnson, Michael R.; O’Connor, Gerard D.; Chaila, Elijah; Alhusaini, Saud; Shianna, Kevin V.; Radtke, Rodney A.; Heinzen, Erin L.; Walley, Nicole; Pandolfo, Massimo; Pichler, Werner; Park, B. Kevin; Depondt, Chantal; Sisodiya, Sanjay M.; Goldstein, David B.; Deloukas, Panos; Delanty, Norman; Cavalleri, Gianpiero L.; Pirmohamed, Munir

    2011-01-01

    BACKGROUND 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. METHODS We performed a genomewide association study of samples obtained from 22 subjects with carbamazepine-induced hypersensitivity syndrome, 43 subjects with carbamazepine-induced maculopapular exanthema, and 3987 control subjects, all of European descent. We tested for an association between disease and HLA alleles through proxy single-nucleotide polymorphisms and imputation, confirming associations by high-resolution sequence-based HLA typing. We replicated the associations in samples from 145 subjects with carbamazepine-induced hypersensitivity reactions. RESULTS The HLA-A★3101 allele, which has a prevalence of 2 to 5% in Northern European populations, was significantly associated with the hypersensitivity syndrome (P = 3.5×10−8). An independent genomewide association study of samples from subjects with maculopapular exanthema also showed an association with the HLA-A★3101 allele (P = 1.1×10−6). Follow-up genotyping confirmed the variant as a risk factor for the hypersensitivity syndrome (odds ratio, 12.41; 95% confidence interval [CI], 1.27 to 121.03), maculopapular exanthema (odds ratio, 8.33; 95% CI, 3.59 to 19.36), and SJS–TEN (odds ratio, 25.93; 95% CI, 4.93 to 116.18). CONCLUSIONS The presence of the HLA-A★3101 allele was associated with carbamazepine-induced hypersensitivity reactions among subjects of Northern European ancestry. The presence of the allele increased the risk from 5.0% to 26.0%, whereas its absence reduced the risk from 5.0% to 3.8%. (Funded by the U.K. Department of Health and others.) PMID:21428769

  11. 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....

  12. 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.

  13. 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.

  14. Toll-Like Receptor 4 in Paraventricular Nucleus Mediates Visceral Hypersensitivity Induced by Maternal Separation

    Directory of Open Access Journals (Sweden)

    Hui-Li Tang

    2017-05-01

    Full Text Available Neonatal maternal separation (MS is a major early life stress that increases the risk of emotional disorders, visceral pain perception and other brain dysfunction. Elevation of toll-like receptor 4 (TLR4 signaling in the paraventricular nucleus (PVN precipitates early life colorectal distension (CRD-induced visceral hypersensitivity and pain in adulthood. The present study aimed to investigate the role of TLR4 signaling in the pathogenesis of postnatal MS-induced visceral hypersensitivity and pain during adulthood. The TLR4 gene was selectively knocked out in C57BL/10ScSn mice (Tlr4-/-. MS was developed by housing the offspring alone for 6 h daily from postnatal day 2 to day 15. Visceral hypersensitivity and pain were assessed in adulthood. Tlr4+/+, but not Tlr4-/-, mice that had experienced neonatal MS showed chronic visceral hypersensitivity and pain. TLR4 immunoreactivity was observed predominately in microglia in the PVN, and MS was associated with an increase in the expression of protein and/or mRNA levels of TLR4, corticotropin-releasing factor (CRF, CRF receptor 1 (CRFR1, tumor necrosis factor-α, and interleukin-1β in Tlr4+/+ mice. These alterations were not observed in Tlr4-/- mice. Local administration of lipopolysaccharide, a TLR4 agonist, into the lateral cerebral ventricle elicited visceral hypersensitivity and TLR4 mRNA expression in the PVN, which could be prevented by NBI-35965, an antagonist to CRFR1. The present results indicate that neonatal MS induces a sensitization and upregulation of microglial TLR4 signaling activity, which facilitates the neighboring CRF neuronal activity and, eventually, precipitates visceral hypersensitivity in adulthood.Highlights(1Neonatal MS does not induce chronic visceral hypersensitivity and pain in Tlr4-/- mice.(2Neonatal MS increases the expression of TLR4 mRNA, CRF protein and mRNA, CRFR1 protein, TNF-α protein, and IL-1β protein in Tlr4+/+ mice.(3TLR4 agonist LPS (i.c.v. elicits visceral

  15. 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.

  16. [Hypersensitivity pneumonitis induced by Aspergillus niger--a case report].

    Science.gov (United States)

    Miyazaki, Hiroo; Gemma, Hitoshi; Uemura, Keiichi; Ono, Takahisa; Masuda, Masafumi; Sano, Takehisa; Sato, Masaki; Koshimizu, Naoki; Suda, Takafumi; Chida, Kingo

    2004-07-01

    A 52-year-old woman was hospitalized because of severe cough in August 1994. She had engaged in culturing roses in greenhouses since 1968, and had developed a cough during the summer of 1990. Chest radiography showed diffuse ground-glass opacity in both lung fields, and she suffered from hypoxemia (PaO2 = 45.6 torr) while breathing room air. The lymphocyte count in the bronchoalveolar lavage fluid was increased, and transbronchial lung biopsy specimens showed lymphocyte alveolitis in the alveolar spaces. After admission, the patient's symptoms improved rapidly without medication. However, on her return to work, the cough and hypoxemia reappeared. In her rose culture, she had used Rockwool, and Aspergillus niger was detected predominantly in the Rockwool. Precipitins against the extracts of Aspergillus niger were detected with the double immunodiffusion test and the inhalation provocation test yielded clinical symptoms. Our diagnosis was hypersensitivity pneumonitis caused by Aspergillus niger.

  17. Therapeutic effects for hypersensitivity pneumonitis induced by Japanese mushroom (Bunashimeji).

    Science.gov (United States)

    Tsushima, Kenji; Furuya, Shino; Yoshikawa, Sumiko; Yasuo, Masanori; Yamazaki, Yoshitaka; Koizumi, Tomonobu; Fujimoto, Keisaku; Kubo, Keishi

    2006-10-01

    Bunashimeji-related hypersensitivity pneumonitis is found among workers who cultivate the mushroom in indoor facilities. An evaluation of protective measures was initiated using the outcomes of clinical, immunological, and radiological findings. Twenty-two patients presented with symptoms of HP; all were employed cultivating Bunashimeji mushrooms in indoor facilities. After hospitalization, 6 of 22 patients quit their job to avoid exposure to spores (Avoidance group). Sixteen patients continued to work used a mask for 3 months, and were then divided into two subgroups: Mask alone (seven patients) and mask plus oral prednisolone (Mask + PSL) (nine patients). The erythrocyte sedimentation rate (ESR), serum Krebs von der Lungen-6 (KL-6), surfactant protein-D (SP-D), lymphocyte stimulation test (LST), ground-glass scores in chest high-resolution computed tomography (HRCT), and bronchoalveolar lavage (BAL) were assessed before and after treatment. Complete avoidance resulted in a significant decrease in LST. There was a significant decrease after PSL treatment in serum KL-6, SP-D, and total cell counts in the BAL fluid in the Mask + PSL group. In the Mask alone group, serum KL-6, SP-D, ground-glass scores in chest HRCT and total cell counts in BAL fluid showed high levels compared with the other two groups. Complete cessation was the best treatment for hypersensitivity pneumonitis. The use of a mask was ineffective for patients with a high serum KL-6 and SP-D concentration and severe ground-glass opacity on chest HRCT. Initial treatment with PSL is recommended for these patients with high levels of total cell counts in BAL fluid.

  18. Influence of chemical structure on hypersensitivity reactions induced by antiepileptic drugs: the role of the aromatic ring.

    NARCIS (Netherlands)

    Handoko, K.B.; Puijenbroek, E.P. van; Bijl, A.H.; Hermens, W.A.; Rijkom, JE Zwart-van; Hekster, Y.A.; Egberts, T.C.G.

    2008-01-01

    OBJECTIVE: Antiepileptic drugs (AEDs) can cause various 'idiosyncratic' hypersensitivity reactions, i.e. the mechanism by which AEDs induce hypersensitivity is unknown. The aim of this study was to assess whether the presence of an aromatic ring as a commonality in chemical structures of AEDs can

  19. Influence of chemical structure on hypersensitivity reactions induced by antiepileptic drugs : the role of the aromatic ring

    NARCIS (Netherlands)

    Handoko, Kim B; van Puijenbroek, Eugène P; Bijl, Annemarie H; Hermens, Walter A J J; Zwart-van Rijkom, Jeannette E F; Hekster, Yechiel A; Egberts, Toine C G

    2008-01-01

    OBJECTIVE: Antiepileptic drugs (AEDs) can cause various 'idiosyncratic' hypersensitivity reactions, i.e. the mechanism by which AEDs induce hypersensitivity is unknown. The aim of this study was to assess whether the presence of an aromatic ring as a commonality in chemical structures of AEDs can

  20. Methanosphaera stadtmanae induces a type IV hypersensitivity response in a mouse model of airway inflammation.

    Science.gov (United States)

    Bernatchez, Emilie; Gold, Matthew J; Langlois, Anick; Blais-Lecours, Pascale; Boucher, Magali; Duchaine, Caroline; Marsolais, David; McNagny, Kelly M; Blanchet, Marie-Renée

    2017-04-01

    Despite improved awareness of work-related diseases and preventive measures, many workers are still at high risk of developing occupational hypersensitivity airway diseases. This stems from a lack of knowledge of bioaerosol composition and their potential effects on human health. Recently, archaea species were identified in bioaerosols, raising the possibility that they play a major role in exposure-related pathology. Specifically, Methanosphaera stadtmanae (MSS) and Methanobrevibacter smithii (MBS) are found in high concentrations in agricultural environments and respiratory exposure to crude extract demonstrates immunomodulatory activity in mice. Nevertheless, our knowledge of the specific impact of methanogens exposure on airway immunity and their potential to induce airway hypersensitivity responses in workers remains scant. Analysis of the lung mucosal response to methanogen crude extracts in mice demonstrated that MSS and MBS predominantly induced TH17 airway inflammation, typical of a type IV hypersensitivity response. Furthermore, the response to MSS was associated with antigen-specific IgG1 and IgG2a production. However, despite the presence of eosinophils after MSS exposure, only a weak TH2 response and no airway hyperresponsiveness were observed. Finally, using eosinophil and mast cell-deficient mice, we confirmed that these cells are dispensable for the TH17 response to MSS, although eosinophils likely contribute to the exacerbation of inflammatory processes induced by MSS crude extract exposure. We conclude that, as MSS induces a clear type IV hypersensitivity lung response, it has the potential to be harmful to workers frequently exposed to this methanogen, and that preventive measures should be taken to avoid chronic hypersensitivity disease development in workers. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  1. 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.

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

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    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.

  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

    Conflicting observations have been reported concerning the role of CD1d-dependent natural killer T (NKT) cells in contact hypersensitivity (CHS), supporting either a disease-promoting or downregulatory function. We studied the role of NKT cells in CHS by comparing the immune response in CD1d...

  4. 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.

  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. Prevention of ultraviolet radiation‑induced immunosuppression by sunscreen in Candida albicans‑induced delayed‑type hypersensitivity.

    Science.gov (United States)

    Chen, Quan; Li, Runxiang; Zhao, Xiaoxia; Liang, Bihua; Ma, Shaoyin; Li, Zhenjie; Zhu, Huilan

    2016-07-01

    Ultraviolet (UV) radiation-induced immunosuppression leading to skin cancer has received increased attention in previous years. The present study aimed to investigate the immunoprotection offered by Anthelios sunscreen in a mouse model of Candida albicans‑induced delayed‑type hypersensitivity. Anthelios sunscreen was applied to the skin on the dorsal skin of BALB/c mice treated with a sub‑erythema dose of solar‑simulated radiation. Delayed‑type hypersensitivity was induced by immunization with Candida albicans. Changes in the skin thickness of the foot pads were measured, and immunosuppression rates were also evaluated. The expression levels of CD207, CD80 and CD86 in the Langerhans cells were semi‑quantitatively detected using Western blotting and immunohistochemical assays. The delayed‑type hypersensitivity mouse model was successfully established. The minimal erythema doses of UVA and UVB exposure to the mice were 2,000 and 145 mJ/cm2, respectively. The immunosuppression rates in the sunscreen group and non‑sunscreen group were 24.39 and 65.85%, respectively (Psunscreen group, compared with those in the non‑sunscreen group. UV exposure reduced Candida albicans antigen‑induced delayed‑type hypersensitivity. Anthelios sunscreen was found to protect the skin from immunosuppression through the activation of epidermal Langerhans cells.

  7. EXPRESS: Histone hyperacetylation modulates spinal type II metabotropic glutamate receptor alleviating stress-induced visceral hypersensitivity in female rats.

    Science.gov (United States)

    Cao, Dong-Yuan; Bai, Guang; Ji, Yaping; Karpowicz, Jane M; Traub, Richard J

    2016-01-01

    Stress is often a trigger to exacerbate chronic pain including visceral hypersensitivity associated with irritable bowel syndrome, a female predominant functional bowel disorder. Epigenetic mechanisms that mediate stress responses are a potential target to interfere with visceral pain. The purpose of this study was to examine the effect of a histone deacetylase inhibitor, suberoylanilide hydroxamic acid, on visceral hypersensitivity induced by a subchronic stressor in female rats and to investigate the involvement of spinal glutamate receptors. Three daily sessions of forced swim induced visceral hypersensitivity. Intrathecal suberoylanilide hydroxamic acid prevented or reversed the stress-induced visceral hypersensitivity, increased spinal histone 3 acetylation and increased mGluR2 and mGluR3 expression. Chromatin immunoprecipitation (ChIP) analysis revealed enrichment of H3K9Ac and H3K18Ac at several promoter Grm2 and Grm3 regions. The mGluR2/3 antagonist LY341495 reversed the inhibitory effect of suberoylanilide hydroxamic acid on the stress-induced visceral hypersensitivity. In surprising contrast, stress and/or suberoylanilide hydroxamic acid had no effect on spinal NMDA receptor expression or function. These data reveal histone modification modulates mGluR2/3 expression in the spinal cord to attenuate stressinduced visceral hypersensitivity. HDAC inhibitors may provide a potential approach to relieve visceral hypersensitivity associated with irritable bowel syndrome.

  8. Primary irritant and delayed-contact hypersensitivity reactions to the freshwater cyanobacterium Cylindrospermopsis raciborskii and its associated toxin cylindrospermopsin

    Directory of Open Access Journals (Sweden)

    Seawright Alan A

    2006-03-01

    Full Text Available Abstract Background Freshwater cyanobacteria are common inhabitants of recreational waterbodies throughout the world; some cyanobacteria can dominate the phytoplankton and form blooms, many of which are toxic. Numerous reports in the literature describe pruritic skin rashes after recreational or occupational exposure to cyanobacteria, but there has been little research conducted on the cutaneous effects of cyanobacteria. Using the mouse ear swelling test (MEST, we sought to determine whether three toxin-producing cyanobacteria isolates and the purified cyanotoxin cylindrospermopsin produced delayed-contact hypersensitivity reactions. Methods Between 8 and 10 female Balb/c mice in each experiment had test material applied to depilated abdominal skin during the induction phase and 10 or 11 control mice had vehicle only applied to abdominal skin. For challenge (day 10 and rechallenge (day 17, test material was applied to a randomly-allocated test ear; vehicle was applied to the other ear as a control. Ear thickness in anaesthetised mice was measured with a micrometer gauge at 24 and 48 hours after challenge and rechallenge. Ear swelling greater than 20% in one or more test mice is considered a positive response. Histopathology examination of ear tissues was conducted by independent examiners. Results Purified cylindrospermopsin (2 of 9 test mice vs. 0 of 5 control mice; p = 0.51 and the cylindrospermopsin-producing cyanobacterium C. raciborskii (8 of 10 test mice vs. 0 of 10 control mice; p = 0.001 were both shown to produce hypersensitivity reactions. Irritant reactions were seen on abdominal skin at induction. Two other toxic cyanobacteria (Microcystis aeruginosa and Anabaena circinalis did not generate any responses using this model. Histopathology examinations to determine positive and negative reactions in ear tissues showed excellent agreement beyond chance between both examiners (κ = 0.83. Conclusion The irritant properties and cutaneous

  9. [Chronic hypersensitivity pneumonitis induced by Shiitake mushroom cultivation: case report and review of literature].

    Science.gov (United States)

    Kai, Naoko; Ishii, Hiroshi; Iwata, Atsuko; Umeki, Kenji; Shirai, Ryo; Morinaga, Ryotaro; Kishi, Kenji; Tokimatsu, Issei; Hiramatsu, Kazufumi; Yamagata, Eiji; Kadota, Jun-Ichi

    2008-05-01

    A 72-year-old man, a Shiitake mushroom grower over fifty years, was admitted to our hospital because of bilateral chest interstitial shadow with chronic cough and breathlessness. Chest computed tomography showed traction bronchiectasis, subpleural micro-cystic changes and partial ground-glass opacities in both lungs, and mild mediastinal lymphadenopathy. A diagnosis of chronic hypersensitivity pneumonitis induced by Shiitake mushrooms was comprehensively confirmed by occupational history, radiological findings, and positive findings of an incidental environmental provocation test and lymphocyte stimulation test for Shiitake mushroom extracts. We reviewed the clinical features in five patients with chronic hypersensitivity pneumonitis induced by Shiitake mushrooms reported in Japan. There was a tendency toward increasing lymphocytes and high CD4/CD8 ratio in bronchoalveolar lavage fluids. Treatment with steroids seems to have a limited effect, while avoidance of the antigen is important.

  10. Contact Hypersensitivity to Mikenia Scandens- A Recently Introduced Wild Creeper of Assam and Meghalaya

    Directory of Open Access Journals (Sweden)

    J S Pasricha

    1987-01-01

    Full Text Available A wild creeper Mikenia scandens was observed to grow profusely over the plantations throughout the states of Assam and Meghalaya. To evaluate the potential of this weed for causing contact dermatitis patch tests were performed with the leaves of this plant on patients having contact dermatitis dus to various causes′. Out of 31 patients tested at Guwahati, 2 patients showed (+ + reactions and another 2 showed (+ reactions. These patients had dermatitis on their hands (2 cases, face (1 and legs (1 respectively. Out of 100 patients tested at Delhi who had never been exposed to this plants, 2 patients showed (+ + reactions. 1 patient showed (+ reaction while another 8 patients showed ( + reactions. These reactions are likely to be instances of cross sensitivity to an as yet unidentified chemical. It seems important to monitor the development of further cases of contact dermatitis due to this plants.

  11. Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin.

    Science.gov (United States)

    Correa da Rosa, Joel; Malajian, Dana; Shemer, Avner; Rozenblit, Mariya; Dhingra, Nikhil; Czarnowicki, Tali; Khattri, Saakshi; Ungar, Benjamin; Finney, Robert; Xu, Hui; Zheng, Xiuzhong; Estrada, Yeriel D; Peng, Xiangyu; Suárez-Fariñas, Mayte; Krueger, James G; Guttman-Yassky, Emma

    2015-03-01

    Atopic dermatitis (AD) is the most common inflammatory disease. The prevalence of allergic contact dermatitis to allergens (eg, fragrance) is higher in patients with AD, despite a trend toward weaker clinical allergic contact dermatitis reactions. The role of the AD skin phenotype in modulating allergic sensitization to common sensitizers has not been evaluated. We sought to investigate whether patients with AD have altered tissue immune responses on allergen challenge. Gene expression and immunohistochemistry studies were performed on biopsy specimens from 10 patients with AD and 14 patients without AD patch tested with common contact allergens (nickel, fragrance, and rubber). Although 1085 differentially expressed genes (DEGs) were commonly modulated in patch-tested skin from patients with AD and patients without AD versus control skin, 1185 DEGs were uniquely altered in skin from patients without AD, and only 246 DEGs were altered in skin from patients with AD. Although many inflammatory products (ie, matrix metalloproteinase 12/matrix metalloproteinase 1/S100A9) were upregulated in both groups, higher-magnitude changes and upregulation of interferon responses were evident only in the non-AD group. Stratification by allergen showed decreased expression of immune, TH1-subset, and TH2-subset genes in nickel-related AD responses, with increased TH17/IL-23 skewing. Rubber/fragrance showed similar trends of lesser magnitude. Negative regulators showed higher expression in patients with AD. Through contact sensitization, our study offers new insights into AD. Allergic immune reactions were globally attenuated and differentially polarized in patients with AD, with significant decreases in levels of TH1 products, some increases in levels of TH17 products, and inconsistent upregulation in levels of TH2 products. The overall hyporesponsiveness in skin from patients with background AD might be explained by baseline immune abnormalities, such as increased TH2, TH17, and

  12. 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...

  13. 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...... ranitidine therapy, and whole blood transfusion was given to 24 of these patients. Postoperative skin test response was more reduced in transfused vs nontransfused patients (-57% vs -38%, p less than 0.0001). Fourteen of the 24 patients receiving blood transfusion could be exactly matched to 14 patients...

  14. Increased DC trafficking to lymph nodes and contact hypersensitivity in junctional adhesion molecule-A–deficient mice

    Science.gov (United States)

    Cera, Maria Rosaria; Del Prete, Annalisa; Vecchi, Annunciata; Corada, Monica; Martin-Padura, Ines; Motoike, Toshiyuki; Tonetti, Paolo; Bazzoni, Gianfranco; Vermi, William; Gentili, Francesca; Bernasconi, Sergio; Sato, Thomas N.; Mantovani, Alberto; Dejana, Elisabetta

    2004-01-01

    Junctional adhesion molecule-A (JAM-A) is a transmembrane adhesive protein expressed at endothelial junctions and in leukocytes. In the present work, we found that DCs also express JAM-A. To evaluate the biological relevance of this observation, Jam-A–/– mice were generated and the functional behavior of DCs in vitro and in vivo was studied. In vitro, Jam-A–/– DCs showed a selective increase in random motility and in the capacity to transmigrate across lymphatic endothelial cells. In vivo, Jam-A–/– mice showed enhanced DC migration to lymph nodes, which was not observed in mice with endothelium-restricted deficiency of the protein. Furthermore, increased DC migration to lymph nodes was associated with enhanced contact hypersensitivity (CHS). Adoptive transfer experiments showed that JAM-A–deficient DCs elicited increased CHS in Jam-A+/+ mice, further supporting the concept of a DC-specific effect. Thus, we identified here a novel, non-redundant role of JAM-A in controlling DC motility, trafficking to lymph nodes, and activation of specific immunity. PMID:15343392

  15. 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.

  16. 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...

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

    Science.gov (United States)

    Novák, Jan; Pavlů, Jaroslav; Novák, Ondřej; Nožková-Hlaváčková, Vladimíra; Špundová, Martina; Hlavinka, Jan; Koukalová, Šárka; Skalák, Jan; Černý, Martin; Brzobohatý, Břetislav

    2013-07-01

    Cytokinins are positive regulators of shoot development. However, it has previously been demonstrated that efficient activation of the cytokinin biosynthesis gene ipt can cause necrotic lesions and wilting in tobacco leaves. Some plant pathogens reportedly use their ability to produce cytokinins in disease development. In response to pathogen attacks, plants can trigger a hypersensitive response that rapidly kills cells near the infection site, depriving the pathogen of nutrients and preventing its spread. In this study, a diverse set of processes that link ipt activation to necrotic lesion formation were investigated in order to evaluate the potential of cytokinins as signals and/or mediators in plant defence against pathogens. The binary pOp-ipt/LhGR system for dexamethasone-inducible ipt expression was used to increase endogenous cytokinin levels in transgenic tobacco. Changes in the levels of cytokinins and the stress hormones salicylic, jasmonic and abscisic acid following ipt activation were determined by ultra-performance liquid chromatography-electrospray tandem mass spectrometry (UPLC-MS/MS). Trends in hydrogen peroxide content and lipid peroxidation were monitored using the potassium iodide and malondialdehyde assays. The subcellular distribution of hydrogen peroxide was investigated using 3,3'-diaminobenzidine staining. The dynamics of transcripts related to photosynthesis and pathogen response were analysed by reverse transcription followed by quantitative PCR. The effects of cytokinins on photosynthesis were deciphered by analysing changes in chlorophyll fluorescence and leaf gas exchange. Plants can produce sufficiently high levels of cytokinins to trigger fast cell death without any intervening chlorosis - a hallmark of the hypersensitive response. The results suggest that chloroplastic hydrogen peroxide orchestrates the molecular responses underpinning the hypersensitive-like response, including the inhibition of photosynthesis, elevated levels of

  18. CLINICAL MANIFESTATIONS OF INTRAORAL CONTACT HYPERSENSITIVITY AMONG DENTAL PATIENTS WITH METHACRYLATE ALLERGY

    Directory of Open Access Journals (Sweden)

    Atanas Chonin

    2016-12-01

    Full Text Available After acrylic resins have been developed they found a broad area of application. Today they have totally replaced the amalgam and are used in the manufacturing of dental prosthesis, restorative materials, root canal filling materials, bonding materials and glass ionomers. As a consequence, the number of allergic reactions to these materials is increasing. Purpose: The aim of this study was to evaluate the most common intraoral clinical manifestations of allergic reactions to plastic materials used in dentistry. Materials and methods: The study population consisted of 200 interviewed participants divided into two groups: dental patients with methacrylic restorations and occupationally exposed to methacrylates manicurists and dental technicians. All of them had dental treatments with acrylic materials. 154 of them were patch tested with 24 methacrylate allergens compiled from (MethAcrylate Series Adhesives, Dental & Other, (MethAcrylate Series - Nails Artificial Series (MN- 1000 (Chemotechnique Diagnostics Vellinge, Sweden. 30 patients (19.48% showed positive reactions to tested substances. Results: Erythema was observed in 8 (26.66 % patients, edematous changes in oral tissues in 4 (13.33% patients. In 60% of patients with positive reactions, there were no intraoral findings. Aphthous or lichenoid eruptions which are specific for contact allergy to dental materials were not registered during intraoral inspections. Conclusions: According to results of this study we cannot confirm that there are specific intra or extra oral changes pathognomonic for methacrylate allergy in dental patients.

  19. [Contact hypersensitivity to Kathon CG. Apropos of 35 cases among 977 tested subjects].

    Science.gov (United States)

    Ledieu, G; Martin, P; Thomas, P

    1991-01-01

    Kathon CG (Rohm and Haas) is a mixture of two isothiazolinones: chloromethylisothiazolinone and methylisothiazolinone. It is widely used in aqueous solution as antimicrobial agent in cosmetics (CG means cosmetic grade) instead of parabens. Routine testing is effected with Kathon CG in aqueous solution at 100 ppm (Trolab) in finn chamber tests on scanpor (ICDRG directives). Between September 1987 and September 1989, 977 patients (538 women, 439 men) referred for suspected contact allergy were tested. Thirty-five patients (77 p. 100 of whom were young women) with a history of allergy to cosmetics were found to be positive. Face, hands or both were involved in 15, 7 and 9 cases respectively, and a lupus-like reaction was observed in one patient. Our results (frequency: 3.6 p. 100) were compared with previously published results ranging from 0.67 p. 100 to 16.1 p. 100 (tables IV and V). Such wide variations can be explained by different selections of patients, different uses of cosmetics and lack of standardization in testing. Patch tests were strongly positive (quoted + +) in all cases. None of the irritant effects previously reported (3, 8, 28) was detected. In a control study carried out two months later, diluted patch tests (100, 50, 25, 15 and 7.5 ppm) were performed in 15 patients and were positive in 11 of them: 5 at 25 ppm, 1 at 15 ppm and 5 only at 100 ppm. Contrary to previous suggestions (7, 28, 36), there was no correlation between allergenic potential and minimal concentration, so that the "no response concentration" concept could not be confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Nadroparin carries a potentially high risk of inducing cutaneous delayed-type hypersensitivity responses.

    Science.gov (United States)

    Schindewolf, Marc; Recke, Andreas; Zillikens, Detlef; Lindhoff-Last, Edelgard; Ludwig, Ralf J

    2017-07-01

    Heparins are widely used for the prophylaxis/treatment of thromboembolic events. As adverse effects, heparin-induced skin lesions occur frequently (in 7.5-39% of patients). Skin lesions may be the only clinical manifestation of life-threatening immune-mediated heparin-induced thrombocytopenia, but are commonly caused by a delayed-type hypersensitivity response [heparin-induced delayed-type hypersensitivity (HIHS)]. Risk factors have not been prospectively identified. To identify possible risk factors for heparin-induced skin lesions from three independent clinical trials in a combined analysis. A pooled analysis from prospective studies was performed, and possible risk factors were included in a multiple logistic regression analysis. Obesity (body mass index of > 25), prolonged anticoagulant therapy, prior heparin exposure and younger age (< 55 years) were confirmed as independent risk factors for HIHS. The choice of anticoagulant preparation had the greatest influence. On comparison of dalteparin, enoxaparin, fondaparinux, unfractionated heparin, and nadroparin, the latter was associated with the highest risk of eliciting HIHS (odds ratio of 30.2, 95%CI: 11.7-77.9). The high risk associated with nadroparin has been validated in controlled trials, and this emphasizes the singularity of each heparin preparation in terms of allergenicity and that individualized anticoagulation is required. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. 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.

  2. Physical Association of Arabidopsis Hypersensitive Induced Reaction Proteins (HIRs) with the Immune Receptor RPS2*

    OpenAIRE

    Qi, Yiping; Tsuda, Kenichi; Nguyen, Le V.; Wang, Xia; Lin, Jinshan; Murphy, Angus S.; Glazebrook, Jane; Thordal-Christensen, Hans; Katagiri, Fumiaki

    2011-01-01

    Arabidopsis RPS2 is a typical nucleotide-binding leucine-rich repeat resistance protein, which indirectly recognizes the bacterial effector protein AvrRpt2 and thereby activates effector-triggered immunity (ETI). Previously, we identified two hypersensitive induced reaction (AtHIR) proteins, AtHIR1 (At1g09840) and AtHIR2 (At3g01290), as potential RPS2 complex components. AtHIR proteins contain the stomatin/prohibitin/flotillin/HflK/C domain (also known as the prohibitin domain or band 7 domai...

  3. Polymorphism in glutamate cysteine ligase catalytic subunit (GCLC) is associated with sulfamethoxazole-induced hypersensitivity in HIV/AIDS patients.

    Science.gov (United States)

    Wang, Danxin; Curtis, Amanda; Papp, Audrey C; Koletar, Susan L; Para, Michael F

    2012-07-23

    Sulfamethoxazole (SMX) is a commonly used antibiotic for prevention of infectious diseases associated with HIV/AIDS and immune-compromised states. SMX-induced hypersensitivity is an idiosyncratic cutaneous drug reaction with genetic components. Here, we tested association of candidate genes involved in SMX bioactivation and antioxidant defense with SMX-induced hypersensitivity. Seventy seven single nucleotide polymorphisms (SNPs) from 14 candidate genes were genotyped and assessed for association with SMX-induced hypersensitivity, in a cohort of 171 HIV/AIDS patients. SNP rs761142 T > G, in glutamate cysteine ligase catalytic subunit (GCLC), was significantly associated with SMX-induced hypersensitivity, with an adjusted p value of 0.045. This result was replicated in a second cohort of 249 patients (p = 0.025). In the combined cohort, heterozygous and homozygous carriers of the minor G allele were at increased risk of developing hypersensitivity (GT vs TT, odds ratio = 2.2, 95% CL 1.4-3.7, p = 0.0014; GG vs TT, odds ratio = 3.3, 95% CL 1.6 - 6.8, p = 0.0010). Each minor allele copy increased risk of developing hypersensitivity 1.9 fold (95% CL 1.4 - 2.6, p = 0.00012). Moreover, in 91 human livers and 84 B-lymphocytes samples, SNP rs761142 homozygous G allele carriers expressed significantly less GCLC mRNA than homozygous TT carriers (p hypersensitivity in HIV/AIDS patients. Catalyzing a critical step in glutathione biosynthesis, GCLC may play a broad role in idiosyncratic drug reactions.

  4. Contact sensitizers induce skin inflammation via ROS production and hyaluronic acid degradation.

    Directory of Open Access Journals (Sweden)

    Philipp R Esser

    Full Text Available BACKGROUND: Allergic contact dermatitis (ACD represents a severe health problem with increasing worldwide prevalence. It is a T cell-mediated skin disease induced by protein-reactive organic and inorganic chemicals. A key feature of contact allergens is their ability to trigger an innate immune response that leads to skin inflammation. Previous evidence from the mouse contact hypersensitivity (CHS model suggests a role for endogenous activators of innate immune signaling. Here, we analyzed the role of contact sensitizer induced ROS production and concomitant changes in hyaluronic acid metabolism on CHS responses. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed in vitro and in vivo ROS production using fluorescent ROS detection reagents. HA fragmentation was determined by gel electrophoresis. The influence of blocking ROS production and HA degradation by antioxidants, hyaluronidase-inhibitor or p38 MAPK inhibitor was analyzed in the murine CHS model. Here, we demonstrate that organic contact sensitizers induce production of reactive oxygen species (ROS and a concomitant breakdown of the extracellular matrix (ECM component hyaluronic acid (HA to pro-inflammatory low molecular weight fragments in the skin. Importantly, inhibition of either ROS-mediated or enzymatic HA breakdown prevents sensitization as well as elicitation of CHS. CONCLUSIONS/SIGNIFICANCE: These data identify an indirect mechanism of contact sensitizer induced innate inflammatory signaling involving the breakdown of the ECM and generation of endogenous danger signals. Our findings suggest a beneficial role for anti-oxidants and hyaluronidase inhibitors in prevention and treatment of ACD.

  5. Carboplatin-induced severe hypersensitivity reaction: Role of IgE-dependent basophil activation and FcεRI

    OpenAIRE

    Iwamoto, Takuya; Hirai, Hiroyuki; Yamaguchi, Nozomi; Kobayashi, Natsuki; Sugimoto, Hiroko; Tabata, Tsutomu; Okuda, Masahiro

    2014-01-01

    Basophil activation was observed in patients with a history of carboplatin-induced severe hypersensitivity reaction (HR). However, the precise mechanism by which carboplatin induces basophil activation and the associated surrogate markers remains to be elucidated. To investigate whether IgE-dependent mechanisms, including the overexpression of FcεRI, participate in carboplatin-induced basophil activation, 13 ovarian cancer patients were enrolled: 5 with a history of carboplatin-induced severe...

  6. 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

    this concept being tested in humans. Prior to assessing the efficacy of GABA-A receptor PAMs in a human volunteer pain model we have compared compounds capable of variously modulating GABA-A receptor function in comparable rat models of capsaicin-induced acute nocifensive flinching behaviour and secondary...... mechanical hypersensitivity. The subtype-selective PAM NS11394 (0.3-10 mg/kg), and the non-selective PAM diazepam (1-5 mg/kg) variously reduced capsaicin-induced secondary mechanical hypersensitivity (180 min post-injection). However, the low efficacy subtype-selective PAM TPA023 (3-30 mg/kg) was completely......, albeit at doses previously shown to impair locomotor function. Our data indicate that GABA-A receptor PAMs with optimal selectivity and efficacy profiles reduce centrally-mediated mechanical hypersensitivity in capsaicin-injected rats, an observation that we expect can translate directly to human...

  7. Serotonin-Induced Hypersensitivity via Inhibition of Catechol O-Methyltransferase Activity

    Science.gov (United States)

    2012-01-01

    The subcutaneous and systemic injection of serotonin reduces cutaneous and visceral pain thresholds and increases responses to noxious stimuli. Different subtypes of 5-hydroxytryptamine (5-HT) receptors are suggested to be associated with different types of pain responses. Here we show that serotonin also inhibits catechol O-methyltransferase (COMT), an enzyme that contributes to modultion the perception of pain, via non-competitive binding to the site bound by catechol substrates with a binding affinity comparable to the binding affinity of catechol itself (Ki = 44 μM). Using computational modeling, biochemical tests and cellular assays we show that serotonin actively competes with the methyl donor S-adenosyl-L-methionine (SAM) within the catalytic site. Binding of serotonin to the catalytic site inhibits the access of SAM, thus preventing methylation of COMT substrates. The results of in vivo animal studies show that serotonin-induced pain hypersensitivity in mice is reduced by either SAM pretreatment or by the combined administration of selective antagonists for β2- and β3-adrenergic receptors, which have been previously shown to mediate COMT-dependent pain signaling. Our results suggest that inhibition of COMT via serotonin binding contributes to pain hypersensitivity, providing additional strategies for the treatment of clinical pain conditions. PMID:22500608

  8. [A case of chronic hypersensitivity pneumonitis induced by shiitake mushroom spores].

    Science.gov (United States)

    Fujiwara, K; Sato, T; Yonei, T; Genba, K; Nogami, N; Yamadori, I

    2000-12-01

    A 73-year-old woman was admitted to our hospital with a low-grade fever, dry cough and dyspnea on exertion as the chief complaints. She had been a professional shiitake mushroom grower for 50 years. Three years before visiting our hospital, she had been suspected of having hypersensitivity pneumonitis as a result of chest X-ray examination, bronchoalveolar lavage and transbronchial lung biopsy performed at another clinic. No antigens were identified at that time, but prednisolone was administered. On admission to our hospital, chest radiography and chest computed tomography revealed an interstitial shadow with subpleural honey-combing in both lower lung fields. After steroid pulse therapy, dyspnea on exertion and hypoxia improved moderately. Because of recurrence of the dyspnea, however, she was admitted on four separate occasions. On the second admission, an increase in lymphocytes was found by bronchoalveolar lavage, and septal lymphocytic infiltration accompanying fibrosis was demonstrated by transbronchial lung biopsy. On the fourth admission, a detailed immunological examination and an environmental survey were performed. The environmental provocation test yielded clinical symptoms similar to those experienced at the mushroom farm. Furthermore, tests of precipitation and lymphocyte proliferation in response to shiitake mushroom extracts were positive. Finally a diagnosis of chronic hypersensitivity pneumonitis induced by shiitake mushrooms was confirmed.

  9. Cloning of a putative hypersensitive induced reaction gene from wheat infected by stripe rust fungus.

    Science.gov (United States)

    Yu, Xiu-Mei; Yu, Xiu-Dao; Qu, Zhi-Peng; Huang, Xin-Jie; Guo, Jun; Han, Qing-Mei; Zhao, Jie; Huang, Li-Li; Kang, Zhen-Sheng

    2008-01-15

    The hypersensitive response (HR) is one of the most efficient forms of plant defense against biotrophic pathogens and results in localized cell death and the formation of necrotic lesions. In this study, a novel putative hypersensitive induced reaction (HIR) gene from wheat leaves infected by incompatible stripe rust pathogen CY23, designated as Ta-hir1, was identified by using rapid amplification of cDNA ends (RACE). Ta-hir1 encodes 284 amino acids, with a predicted molecular mass of 31.31 KDa. A phylogenetic analysis showed that Ta-hir1 was highly homologous to Hv-hir1 from barley at both cDNA and deduced amino-acid levels. Amino-acid sequence analysis of the wheat HIR protein indicated the presence of the SPFH (Stomatins, Prohibitins, Flotillins and HflK/C) protein domain typical for stomatins which served as a negative regulator of univalent cation permeability, especially for potassium. The expression profile of the Ta-hir1 transcript detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time polymerase chain reaction (real time-PCR), respectively, showed that the highest expression occurred 48 h post inoculation (hpi), which is consistent with our previous histopathology observations during the stripe rust fungus-wheat incompatible reaction.

  10. Serotonin-Induced Hypersensitivity via Inhibition of Catechol O-Methyltransferase Activity

    Directory of Open Access Journals (Sweden)

    Tsao Douglas

    2012-04-01

    Full Text Available Abstract The subcutaneous and systemic injection of serotonin reduces cutaneous and visceral pain thresholds and increases responses to noxious stimuli. Different subtypes of 5-hydroxytryptamine (5-HT receptors are suggested to be associated with different types of pain responses. Here we show that serotonin also inhibits catechol O-methyltransferase (COMT, an enzyme that contributes to modultion the perception of pain, via non-competitive binding to the site bound by catechol substrates with a binding affinity comparable to the binding affinity of catechol itself (Ki = 44 μM. Using computational modeling, biochemical tests and cellular assays we show that serotonin actively competes with the methyl donor S-adenosyl-L-methionine (SAM within the catalytic site. Binding of serotonin to the catalytic site inhibits the access of SAM, thus preventing methylation of COMT substrates. The results of in vivo animal studies show that serotonin-induced pain hypersensitivity in mice is reduced by either SAM pretreatment or by the combined administration of selective antagonists for β2- and β3-adrenergic receptors, which have been previously shown to mediate COMT-dependent pain signaling. Our results suggest that inhibition of COMT via serotonin binding contributes to pain hypersensitivity, providing additional strategies for the treatment of clinical pain conditions.

  11. The roles of iPLA2, TRPM8 and TRPA1 in chemically induced cold hypersensitivity

    Directory of Open Access Journals (Sweden)

    Andersson David A

    2010-01-01

    Full Text Available Abstract Background The cooling agents menthol and icilin act as agonists at TRPM8 and TRPA1. In vitro, activation of TRPM8 by icilin and cold, but not menthol, is dependent on the activity of a sub-type of phospholipase A2, iPLA2. Lysophospholipids (e.g. LPC produced by PLA2 activity can also activate TRPM8. The role of TRPA1 as a primary cold sensor in vitro is controversial, although there is evidence that TRPA1 plays a role in behavioural responses to noxious cold stimuli. In this study, we have investigated the roles of TRPM8 and TRPA1 and the influence of iPLA2 on noxious cold sensitivities in naïve animals and after local administration of menthol, icilin and LPC. The roles of the channels in cold sensitivity were investigated in mice lacking either TRPM8 (Trpm8-/- or TRPA1 (Trpa1-/-. Results Intraplantar administration of icilin evoked a dose-dependent increase in sensitivity to a 10°C stimulus that was inhibited by iPLA2 inhibition with BEL. In contrast the cold hypersensitivities elicited by intraplantar menthol and LPC were not inhibited by BEL treatment. BEL had no effect on basal cold sensitivity and mechanical hypersensitivities induced by the TRPV1 agonist, capsaicin, and the P2X3 agonist α,β-methylene ATP. Both Trpm8-/- and Trpa1-/- mice showed longer latencies for paw withdrawal from a 10°C stimulus than wild-type littermates. Cold hypersensitivities induced by either icilin or LPC were absent in Trpm8-/- mice but were retained in Trpa1-/- mice. In contrast, cold hypersensitivity evoked by menthol was present in Trpm8-/- mice but was lost in Trpa1-/- mice. Conclusions The findings that iPLA2 inhibition blocked the development of cold hypersensitivity after administration of icilin but failed to affect menthol-induced hypersensitivity agree well with our earlier in vitro data showing a differential effect of iPLA2 inhibition on the agonist activities of these agents. The ability of LPC to induce cold hypersensitivity

  12. Delayed-type hypersensitivity reactions induced by proton pump inhibitors: A clinical and in vitro T-cell reactivity study.

    Science.gov (United States)

    Lin, C-Y; Wang, C-W; Hui, C-Y R; Chang, Y-C; Yang, C-H; Cheng, C-Y; Chen, W-W; Ke, W-M; Chung, W-H

    2017-06-28

    Proton pump inhibitors (PPIs) have been known to induce type I hypersensitivity reactions. However, severe delayed-type hypersensitivity reactions (DHR) induced by PPI, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI-related DHR, followed up their tolerability to alternative anti-ulcer agents, and investigated the T-cell reactivity to PPI in PPI-related DHR patients. We retrospectively analyzed patients with PPI-related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross-hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon-γ to confirm the causalities. There were 69 cases of PPI-related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI-related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross-hypersensitivity reactions, whereas three patients developed cross-hypersensitivity reactions to alternative structurally similar PPI. The cross-reactivity to structurally similar PPI was also observed in LAT assay. PPIs have the potential to induce life-threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  13. Infection with Dermatophilus congolensis at a contact hypersensitivity site and its relevance to chronic streptothricosis lesions in the cattle of West Africa.

    Science.gov (United States)

    Davis, D

    1984-01-01

    Guinea-pigs were sensitized to CDNB and infected with D. congolensis at the site of a subsequent application of this chemical. The bacterium was recovered from the skin over a longer period of time in sensitized individuals than in nonsensitized controls. Animals rendered tolerant to the chemical gave lower yields of bacteria than sensitized animals. However, the lesions produced at the site of infection did not become chronic. The growth of D. congolensis at a contact hypersensitivity site may possibly simulate infection in skin following an arthropod bite and be relevant to the pathogenesis of chronic streptothricosis lesions in the cattle of West Africa.

  14. Pretreatment with different doses of dexamethasone in the prevention of docetaxel-induced hypersensitivity.

    Science.gov (United States)

    Zhang, Mingjun; Chen, Zhendong; Yang, Yang; Cheng, Huaidong; Li, Chao; He, Qian

    2017-01-01

    This study aimed to evaluate the efficacy and safety of dexamethasone pretreatment regimen with different doses in the prevention of docetaxel-induced hypersensitivity reaction (HSR). One hundred and sixty-two patients who had malignant tumors as determined by histology and/or cytology and received docetaxel treatments at least 2 cycles, were randomized into two groups. There were 90 patients in the study group and 72 patients in the control group. In the study group, patients received 4.5mg of oral dexamethasone once a day. Patients in the control group received 8 mg of dexamethasone twice a day. All patients received dexamethasone for 3 days, from the day before docetaxel treatment to the day after docetaxel treatment. The endpoints were hypersensitivity reaction (HSR) and other adverse effects, which were determined according to common terminology criteria for adverse event v3.0 (CTCAE 3.0). In the study group, 10 patients had HSRs (11.1%). While in the control group, 7 patients had HSRs (9.7%), and the main clinical symptoms of HSR were rash (3.1%), fever/chill (2.5%), angioedema (1.9%), chest discomfort (1.9%) and hypotension (0.6%). There was no statistically significant difference between these two groups (P=0.774). There was no significant difference in the incidence rate of adverse effect between patients in the study group and in the control group. Those adverse effects included neutropenia, decreased hemoglobin, nausea, vomiting, fatigue and fluid retention. Since no significant difference in the HSR incidence between these two groups has been found, 4.5mg of dexamethasone (qd) is as efficient and safe as 8mg (bid).

  15. A critical role of spinal Shank2 proteins in NMDA-induced pain hypersensitivity.

    Science.gov (United States)

    Yoon, Seo-Yeon; Kwon, Soon-Gu; Kim, Yong Ho; Yeo, Ji-Hee; Ko, Hyoung-Gon; Roh, Dae-Hyun; Kaang, Bong-Kiun; Beitz, Alvin J; Lee, Jang-Hern; Oh, Seog Bae

    2017-01-01

    Background Self-injurious behaviors (SIBs) are devastating traits in autism spectrum disorder (ASD). Although deficits in pain sensation might be one of the contributing factors underlying the development of SIBs, the mechanisms have yet to be addressed. Recently, the Shank2 synaptic protein has been considered to be a key component in ASD, and mutations of SHANK2 gene induce the dysfunction of N-methyl-D-aspartate (NMDA) receptors, suggesting a link between Shank2 and NMDA receptors in ASD. Given that spinal NMDA receptors play a pivotal role in pain hypersensitivity, we investigated the possible role of Shank2 in nociceptive hypersensitivity by examining changes in spontaneous pain following intrathecal NMDA injection in S hank2-/- ( Shank2 knock-out, KO) mice. Results Intrathecal NMDA injection evoked spontaneous nociceptive behaviors. These NMDA-induced nociceptive responses were significantly reduced in Shank2 KO mice. We also observed a significant decrease of NMDA currents in the spinal dorsal horn of Shank2 KO mice. Subsequently, we examined whether mitogen-activated protein kinase or AKT signaling is involved in this reduced pain behavior in Shank2 KO mice because the NMDA receptor is closely related to these signaling molecules. Western blotting and immunohistochemistry revealed that spinally administered NMDA increased the expression of a phosphorylated form of extracellular signal-regulated kinase (p-ERK) which was significantly reduced in Shank2 KO mice. However, p38, JNK, or AKT were not changed by NMDA administration. The ERK inhibitor, PD98059, decreased NMDA-induced spontaneous pain behaviors in a dose-dependent manner in wild-type mice. Moreover, it was found that the NMDA-induced increase in p-ERK was primarily colocalized with Shank2 proteins in the spinal cord dorsal horn. Conclusion Shank2 protein is involved in spinal NMDA receptor-mediated pain, and mutations of Shank2 may suppress NMDA-ERK signaling in spinal pain transmission. This study

  16. NMDA receptor subunit expression and PAR2 receptor activation in colospinal afferent neurons (CANs) during inflammation induced visceral hypersensitivity.

    Science.gov (United States)

    Suckow, Shelby K; Caudle, Robert M

    2009-09-22

    Visceral hypersensitivity is a clinical observation made when diagnosing patients with functional bowel disorders. The cause of visceral hypersensitivity is unknown but is thought to be attributed to inflammation. Previously we demonstrated that a unique set of enteric neurons, colospinal afferent neurons (CANs), co-localize with the NR1 and NR2D subunits of the NMDA receptor as well as with the PAR2 receptor. The aim of this study was to determine if NMDA and PAR2 receptors expressed on CANs contribute to visceral hypersensitivity following inflammation. Recently, work has suggested that dorsal root ganglion (DRG) neurons expressing the transient receptor potential vanilloid-1 (TRPV1) receptor mediate inflammation induced visceral hypersensitivity. Therefore, in order to study CAN involvement in visceral hypersensitivity, DRG neurons expressing the TRPV1 receptor were lesioned with resiniferatoxin (RTX) prior to inflammation and behavioural testing. CANs do not express the TRPV1 receptor; therefore, they survive following RTX injection. RTX treatment resulted in a significant decrease in TRPV1 expressing neurons in the colon and immunohistochemical analysis revealed no change in peptide or receptor expression in CANs following RTX lesioning as compared to control data. Behavioral studies determined that both inflamed non-RTX and RTX animals showed a decrease in balloon pressure threshold as compared to controls. Immunohistochemical analysis demonstrated that the NR1 cassettes, N1 and C1, of the NMDA receptor on CANs were up-regulated following inflammation. Furthermore, inflammation resulted in the activation of the PAR2 receptors expressed on CANs. Our data show that inflammation causes an up-regulation of the NMDA receptor and the activation of the PAR2 receptor expressed on CANs. These changes are associated with a decrease in balloon pressure in response to colorectal distension in non-RTX and RTX lesioned animals. Therefore, these data suggest that CANs

  17. NMDA receptor subunit expression and PAR2 receptor activation in colospinal afferent neurons (CANs during inflammation induced visceral hypersensitivity

    Directory of Open Access Journals (Sweden)

    Caudle Robert M

    2009-09-01

    Full Text Available Abstract Background Visceral hypersensitivity is a clinical observation made when diagnosing patients with functional bowel disorders. The cause of visceral hypersensitivity is unknown but is thought to be attributed to inflammation. Previously we demonstrated that a unique set of enteric neurons, colospinal afferent neurons (CANs, co-localize with the NR1 and NR2D subunits of the NMDA receptor as well as with the PAR2 receptor. The aim of this study was to determine if NMDA and PAR2 receptors expressed on CANs contribute to visceral hypersensitivity following inflammation. Recently, work has suggested that dorsal root ganglion (DRG neurons expressing the transient receptor potential vanilloid-1 (TRPV1 receptor mediate inflammation induced visceral hypersensitivity. Therefore, in order to study CAN involvement in visceral hypersensitivity, DRG neurons expressing the TRPV1 receptor were lesioned with resiniferatoxin (RTX prior to inflammation and behavioural testing. Results CANs do not express the TRPV1 receptor; therefore, they survive following RTX injection. RTX treatment resulted in a significant decrease in TRPV1 expressing neurons in the colon and immunohistochemical analysis revealed no change in peptide or receptor expression in CANs following RTX lesioning as compared to control data. Behavioral studies determined that both inflamed non-RTX and RTX animals showed a decrease in balloon pressure threshold as compared to controls. Immunohistochemical analysis demonstrated that the NR1 cassettes, N1 and C1, of the NMDA receptor on CANs were up-regulated following inflammation. Furthermore, inflammation resulted in the activation of the PAR2 receptors expressed on CANs. Conclusion Our data show that inflammation causes an up-regulation of the NMDA receptor and the activation of the PAR2 receptor expressed on CANs. These changes are associated with a decrease in balloon pressure in response to colorectal distension in non-RTX and RTX lesioned

  18. Spinal histamine in attenuation of mechanical hypersensitivity in the spinal nerve ligation-induced model of experimental neuropathy.

    Science.gov (United States)

    Wei, Hong; Viisanen, Hanna; You, Hao-Jun; Pertovaara, Antti

    2016-02-05

    Here we studied whether and through which mechanisms spinal administration of histamine dihydrochloride (histamine) attenuates pain behavior in neuropathic animals. Experiments were performed in rats with spinal nerve ligation-induced neuropathy and a chronic intrathecal catheter for spinal drug delivery. Mechanical hypersensitivity was assessed with monofilaments while radiant heat was used for assessing nociception. Ongoing neuropathic pain and its attenuation by histamine was assessed using conditioned place-preference test. Following spinal administration, histamine at doses 0.1-10µg produced a dose-related mechanical antihypersensitivity effect. With prolonged treatment (twice daily 10µg for five days), the antihypersensitivity effect of spinal histamine was reduced. In place-preference test, neuropathic animals preferred the chamber paired with histamine (10µg). Histamine (10µg) failed to influence heat nociception in neuropathic animals or mechanically induced pain behavior in a group of healthy control rats. Histamine-induced mechanical antihypersensitivity effect was prevented by spinal pretreatment with zolantidine (histamine H2 receptor antagonist), prazosine (α1-adrenoceptor antagonist) and bicuculline (γ-aminobutyric acid subtype A, GABA(A), receptor antagonist), but not by pyrilamine (histamine H1 receptor antagonist), atipamezole (α2-adrenoceptor antagonist), or raclopride (dopamine D2 receptor antagonist). A-960656, a histamine H3 receptor antagonist alone that presumably increased endogenous histamine levels reduced hypersensitivity. Additionally, histamine prevented central (presumably postsynaptically-induced) facilitation of hypersensitivity induced by N-methyl-d-aspartate. The results indicate that spinal histamine at the dose range of 0.1-10µg selectively attenuates mechanical hypersensitivity and ongoing pain in neuropathy. The spinal histamine-induced antihypersensitivity effect involves histamine H2 and GABA(A) receptors and

  19. 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.

  20. Hypersensitivity reactions to heparins.

    Science.gov (United States)

    Gonzalez-Delgado, Purificación; Fernandez, Javier

    2016-08-01

    This article provides an update on hypersensitivity reactions to heparins and novel oral anticoagulants, with special emphasis on diagnostic methods and management of patients. Although heparins are drugs widely used, hypersensitivity reactions are uncommon. Cutaneous delayed hypersensitivity reactions after subcutaneous administration affects up to 7.5% of patients. Heparin-induced thrombocytopenia is another unusual but severe condition in which early recognition is crucial. Immediate hypersensitivity reactions to heparins have been also reported, but with the novel oral anticoagulants are much more uncommon, although reports of exanthemas have been notified.Skin tests and subcutaneous provocation test are useful tools in the diagnosis of hypersensitivity reactions, except in heparin-induced thrombocytopenia in which biopsy of lesional skin and in-vitro tests are the modalities of choice to confirm the diagnosis.Management of hypersensitivity reactions includes finding an alternative depending on the type of reaction. Fondaparinux and novel oral anticoagulants may be safe alternatives. Delayed skin lesions after subcutaneous heparin are the most common type of hypersensitivity reactions, followed by life-threatening heparin-induced thrombocytopenia. Immediate reactions are uncommon. Allergologic studies may be useful to find an alternative option in patients with skin lesions in which heparin-induced thrombocytopenia has been previously excluded, as well as in heparin immediate reactions.

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

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    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

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

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    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

  3. Neuronal NOS Activates Spinal NADPH Oxidase 2 Contributing to Central Sigma-1 Receptor-Induced Pain Hypersensitivity in Mice.

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    Choi, Sheu-Ran; Kwon, Soon-Gu; Choi, Hoon-Seong; Han, Ho-Jae; Beitz, Alvin James; Lee, Jang-Hern

    2016-12-01

    We recently demonstrated that activation of spinal sigma-1 receptors (Sig-1Rs) induces pain hypersensitivity via the activation of neuronal nitric oxide synthase (nNOS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2). However, the potential direct interaction between nNOS-derived nitric oxide (NO) and Nox2-derived reactive oxygen species (ROS) is poorly understood, particularly with respect to the potentiation of N-methyl-D-aspartate (NMDA) receptor activity in the spinal cord associated with the development of central sensitization. Thus, the main purpose of this study was to investigate whether Sig-1R-induced and nNOS-derived NO modulates spinal Nox2 activation leading to an increase in ROS production and ultimately to the potentiation of NMDA receptor activity and pain hypersensitivity. Intrathecal pretreatment with the nNOS inhibitor, 7-nitroindazole or with the Nox inhibitor, apocynin significantly inhibited the mechanical and thermal hypersensitivity induced by intrathecal administration of the Sig-1R agonist, 2-(4-morpholinethyl) 1-phenylcyclohexanecarboxylate hydrochloride (PRE084). Conversely, pretreatment with 5,10,15,20-tetrakis-(4-sulphonatophenyl)-porphyrinato iron(III) (FeTPPS; a scavenger of peroxynitrite, a toxic reaction product of NO and superoxide) had no effect on the PRE084-induced pain hypersensitivity. Pretreatment with 7-nitroindazole significantly reduced the PRE084-induced increase in Nox2 activity and concomitant ROS production in the lumbar spinal cord dorsal horn, whereas apocynin did not alter the PRE084-induced changes in nNOS phosphorylation. On the other hand pretreatment with apocynin suppressed the PRE084-induced increase in the protein kinase C (PKC)-dependent phosphorylation of NMDA receptor GluN1 subunit (pGluN1) at Ser896 site in the dorsal horn. These findings demonstrate that spinal Sig-1R-induced pain hypersensitivity is mediated by nNOS activation, which leads to an increase in Nox2 activity

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

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    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.

  5. Inhibitory effect of the selective serotonin 5-HT₃ receptor antagonist ramosetron on duodenal acidification-induced gastric hypersensitivity in rats.

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    Nakata-Fukuda, Mari; Hirata, Takuya; Keto, Yoshihiro; Yamano, Mayumi; Yokoyama, Toshihide; Uchiyama, Yasuo

    2014-05-15

    Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are both functional gastrointestinal disorders and frequently co-occur in patients. While one cause of FD appears to be gastric hypersensitivity, whether the hypersensitivity is affected by IBS treatments remains unclear, given the lack of appropriate animal models for testing. Here, we established an experimental model of duodenal acidification-induced gastric hypersensitivity in conscious rats. The model involved duodenal acidification induced by the infusion of hydrochloric acid into the proximal duodenum, with the nociceptive response being determined as the change in mean arterial pressure (MAP) during gastric distension via an indwelling latex balloon. Using our model we evaluated the effects of duodenal acidification, increased distension pressure, and orally administered therapeutic agents for IBS with diarrhea (IBS-D). Duodenal acidification enhanced the pressor response during gastric distension, and pretreatment with the opioid κ-receptor agonist fedotozine (10mg/kg, intra-arterial) inhibited the pressor response. Pressure levels of 15-60 mm Hg increased MAP in response to gastric distension. The serotonin 5-HT3 receptor antagonist ramosetron (30 μg/kg) inhibited MAP increase induced by duodenal acidification, with no other IBS-D therapeutic agents showing any effect. In contrast, the serotonin 5-HT3 receptor agonist m-chlorophenylbiguanide (1mg/kg) significantly enhanced the pressor response during gastric distension. These findings indicate that the serotonin 5-HT3 receptor plays a key role in duodenal acidification-induced gastric hypersensitivity in rats, suggesting that ramosetron may reduce FD symptoms by ameliorating sensitized gastric perception. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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    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

  7. Tissue-specific expression of a soybean hypersensitive-induced response (HIR) protein gene promoter.

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    Koellhoffer, Jessica P; Xing, Aiqiu; Moon, Bryan P; Li, Zhongsen

    2015-02-01

    A Glycine max gene encoding a putative protein similar to hypersensitive-induced response proteins (HIR) was identified as a gene with preferred expressions in flowers and developing seeds by whole transcriptome gene expression profiling. Its promoter gm-hir1 was cloned and revealed to strongly express a fluorescence reporter gene primarily in integuments, anther tapetum, and seed coat with unique tissue-specificity. Expression in the inner integument was apparent prior to pollination, while expression in the outer integument started to develop from the micropylar end outward as the embryo matured. A 5'-deletion study showed that the promoter can be truncated to 600 bp long relative to the translation start site without affecting expression. A positive regulatory element was identified between 600 and 481 bp that controls expression in the inner integument, with no noticeable effect on expression in the outer integument or tapetum. Additionally, removal of the 5'UTR intron had no effect on levels or location of gm-hir1 expression while truncation to 370 bp resulted in a complete loss of expression suggesting that elements controlling both the outer integument and tapetum expression are located within the 481-370 bp region.

  8. Immunologic responses against hydrolyzed soy protein in dogs with experimentally induced soy hypersensitivity.

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    Puigdemont, Anna; Brazís, Pilar; Serra, Montserrat; Fondati, Alessandra

    2006-03-01

    To assess whether dogs with experimentally induced type I hypersensitivity against soy protein would respond to soy hydrolysate and develop cutaneous or gastrointestinal tract reactions after intradermal and oral challenge exposure. 12 naïve Beagle pups (9 sensitized and 3 control dogs). 9 dogs were sensitized against soy protein by administration of allergens during a 90-day period. After the sensitization period, serum concentrations of soy-specific IgE were determined and an intradermal test was performed to confirm the dogs were sensitized against soy protein. An intradermal challenge test and an oral challenge test with native and hydrolyzed soy protein were conducted on 6 sensitized and 2 control dogs. High serum concentrations of soy-specific IgE and positive results for the intradermal test were observed for the 9 sensitized dogs after completion of the sesitization process. Sensitized dogs challenge exposed with hydrolyzed soy protein had a reduced inflammatory response after intradermal injection and no clinical response after an oral challenge exposure, compared with responses after intradermal and oral challenge exposure with native soy protein. Soy-sensitized dogs did not respond to oral administration of hydrolyzed soy protein. Thus, hydrolyzed soy protein may be useful in diets formulated for the management of dogs with adverse reactions to food.

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

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    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.

  10. Inducible nitric oxide synthase inhibition by 1400W limits pain hypersensitivity in a neuropathic pain rat model.

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    Staunton, C A; Barrett-Jolley, R; Djouhri, L; Thippeswamy, T

    2018-02-13

    Peripheral neuropathic pain (PNP) resulting from injury or dysfunction to a peripheral nerve, is a major health problem affecting 7-8% of the population. It is inadequately controlled by current drugs, and is characterized by pain hypersensitivity which is believed to be due to sensitization of peripheral and CNS neurons by various inflammatory mediators. Here we examined, in a rat model of PNP: a) whether reducing levels of nitric oxide (NO), with 1400 W, a highly selective inhibitor of inducible NO synthase (iNOS), would prevent/attenuate pain hypersensitivity, and b) the effects of 1400 W on plasma levels of several cytokines that are secreted post iNOS upregulation during chronic pain states. The L5-spinal nerve axotomy (SNA) model of PNP was used, and 1400 W (20 mg kg -1 ) administered intraperitoneally at 8 hour intervals for three days starting at 18 hours post-SNA. Changes in plasma concentrations of 12 cytokines in SNA rats treated with 1400 W were examined using multiplex ELISA. SNA rats developed behavioural signs of mechanical and heat hypersensitivity. Compared with the vehicle/control, 1400 W significantly: (a) limited development of mechanical hypersensitivity at 66 hours post-SNA, as well as heat hypersensitivity at 42 hours and at several time-points tested thereafter, and (b) increased the plasma concentrations of IL-1α, IL-1β, and IL-10 in the SNA rats. The findings suggest that 1400 W may exert its analgesic effects by reducing iNOS and altering the balance between the pro-inflammatory (IL-1β and IL-1α) and anti-inflammatory (IL-10) cytokines and that therapies targeting NO or its enzymes may be effective for the treatment of PNP. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. N-Arylsulfonyl-α-amino carboxamides are potent and selective inhibitors of the chemokine receptor CCR10 that show efficacy in the murine DNFB model of contact hypersensitivity.

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    Abeywardane, Asitha; Caviness, Gary; Choi, Younggi; Cogan, Derek; Gao, Amy; Goldberg, Daniel; Heim-Riether, Alexander; Jeanfavre, Debra; Klein, Elliott; Kowalski, Jennifer A; Mao, Wang; Miller, Craig; Moss, Neil; Ramsden, Philip; Raymond, Ernest; Skow, Donna; Smith-Keenan, Lana; Snow, Roger J; Wu, Frank; Wu, Jiang-Ping; Yu, Yang

    2016-11-01

    Compound 1 ((4-amino-3,5-dichlorophenyl)-1-(4-methylpiperidin-1-yl)-4-(2-nitroimidazol-1-yl)-1-oxobutane-2-sulfonamido) was discovered to be a 690nM antagonist of human CCR10 Ca2+ flux. Optimization delivered (2R)-4-(2-cyanopyrrol-1-yl)-S-(1H-indol-4-yl)-1-(4-methylpiperidin-1-yl)-1-oxobutane-2-sulfonamido (eut-22) that is 300 fold more potent a CCR10 antagonist than 1 and eliminates potential toxicity, mutagenicity, and drug-drug-interaction liabilities often associated with nitroaryls and anilines. eut-22 is highly selective over other GPCR's, including a number of other chemokine receptors. Finally, eut-22 is efficacious in the murine DNFB model of contact hypersensitivity. The efficacy of this compound provides further evidence for the role of CCR10 in dermatological inflammatory conditions. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Spinal release of tumour necrosis factor activates c-Jun N-terminal kinase and mediates inflammation-induced hypersensitivity.

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    Bas, D B; Abdelmoaty, S; Sandor, K; Codeluppi, S; Fitzsimmons, B; Steinauer, J; Hua, X Y; Yaksh, T L; Svensson, C I

    2015-02-01

    Mounting evidence points to individual contributions of tumour necrosis factor-alpha (TNF) and the c-Jun N-terminal kinase (JNK) pathway to the induction and maintenance of various pain states. Here we explore the role of spinal TNF and JNK in carrageenan-induced hypersensitivity. As links between TNF and JNK have been demonstrated in vitro, we investigated if TNF regulates spinal JNK activity in vivo. TNF levels in lumbar cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay, spinal TNF gene expression by real-time polymerase chain reaction and TNF protein expression, JNK and c-Jun phosphorylation by western blotting. The role of spinal TNF and JNK in inflammation-induced mechanical and thermal hypersensitivity was assessed by injecting the TNF inhibitor etanercept and the JNK inhibitors SP600125 and JIP-1 intrathecally (i.t.). TNF-mediated regulation of JNK activity was examined by assessing the effect of i.t. etanercept on inflammation-induced spinal JNK activity. TNF levels were increased in CSF and spinal cord following carrageenan-induced inflammation. While JNK phosphorylation followed the same temporal pattern as TNF, c-jun was only activated at later time points. Intrathecal injection of TNF and JNK inhibitors attenuated carrageenan-induced mechanical and thermal hypersensitivity. TNF stimulation induced JNK phosphorylation in cultured spinal astrocytes and blocking the spinal actions of TNF in vivo by i.t. injection of etanercept reduced inflammation-induced spinal JNK activity. Here we show that spinal JNK activity is dependent on TNF and that both TNF and the JNK signalling pathways modulate pain-like behaviour induced by peripheral inflammation. © 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

  13. Stat5 gene dosage in T cells modulates CD8+ T-cell homeostasis and attenuates contact hypersensitivity response in mice.

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    Nivarthi, H; Prchal-Murphy, M; Swoboda, A; Hager, M; Schlederer, M; Kenner, L; Tuckermann, J; Sexl, V; Moriggl, R; Ermakova, O

    2015-01-01

    Contact hypersensitivity assay (CHS) faithfully models human allergies. The Stat5 transcription factors are essential for both lymphocyte development and acute immune responses. Although consequences of Stat5 ablation and transgenic overexpression for the lymphocyte development and functions have been extensively studied, the role of Stat5 gene dosage in contact allergies has not been addressed. We investigated the effect of Stat5 gene dosage modulation in contact allergies using CHS in mice. Transgenic animals heterozygous for the germline Stat5 null allele were subjected to CHS. To dissect cell type sensitive to Stat5 gene dosage, animals with Stat5 haplo-insufficiency in T cells, where one Stat5 allele was removed by Lck-Cre-mediated deletion (Stat5(ΔT/+)), were tested by CHS. Frequency of T cells, B cells, and monocytes were analyzed in Stat5(ΔT/+) and wild-type animals by flow cytometry. Proliferation of Stat5(ΔT/+) CD8(+) T cells was studied in vitro by stimulation with IL-4 and IL-2 cytokines, and changes in the expression of Stat5 target genes were assayed by quantitative real-time PCR assay. Haplo-insufficiency of Stat5 in T cells leads to the reduction in CD8(+) T cells in all lymphoid organs and attenuates CHS response. Stat5(ΔT/+) CD8(+) T cells failed to fully activate Stat5-dependent expression of cell cycle/survival target genes, such as Bcl2 and Pim1, and to proliferate efficiently in response to IL-2 and IL-4 cytokine. Our data identify Stat5 as a dose-dependent regulator of CD8(+) T-cell functions in contact allergies and suggest that modulation of Stat5 dosage could be used to target contact allergies in humans. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Activation of cannabinoid CB1 receptors suppresses the ROS-induced hypersensitivity of rat vagal lung C-fiber afferents.

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    Yeh, Chou-Ming; Ruan, Ting; Lin, Yu-Jung; Hsu, Tien-Huan

    2016-10-01

    Reactive oxygen species (ROS), including H2O2, have been shown to induce hypersensitivity of vagal lung C-fibers (VLCFs) mainly through receptor potential ankyrin 1 (TRPA1) and P2X receptors. Cannabinoids (CBs) exert antinociceptive effects by binding to specific CB receptors, designated CB1 and CB2 (type 2) for type 1 and type 2, respectively. We investigated whether activation of CB receptors can suppress ROS-mediated VLCF hypersensitivity and, if so, what type(s) of CB receptors are involved. Aerosolized H2O2 (0.05%) was inhaled by anesthetized spontaneously breathing rats (n = 304) to sensitize VLCFs. Airway reflex reactivity to intravenous capsaicin, a VLCF stimulant, was measured. Perivagal pretreatments with various types of agonists and antagonists, a technique that can modulate VLCF sensitivity, were made to delineate the roles of the CB receptors. Aerosolized H2O2 induced an augmented apneic response to capsaicin, which was blocked by bilateral vagotomy or by perivagal capsaicin treatment, suggesting that the response is mediated through VLCFs. Perivagal treatment with HU210 (a nonselective CB agonist) or ACPA (a selective CB1 receptor agonist), but not JWH133 (a CB2 receptor agonist), attenuated this H2O2-induced VLCF hypersensitivity. The suppressive effects of HU210 and ACPA were prevented by an additional treatment with AM251 (a selective CB1 antagonist), but not with AM630 (a selective CB2 antagonist). Perivagal treatment with a combination of ACPA, HC030031 (a TRPA1 receptor antagonist), and iso-PPADS (a P2X receptor antagonist) further attenuated the H2O2-induced VLCF hypersensitivity, as compared with treatment with a combination of HC030031 and iso-PPADS. Our results suggest that activation of CB1 receptors may suppress the ROS-mediated VLCF hypersensitivity through a mechanism that is at least partly distinct from the function of TRPA1 and P2X receptors. Copyright © 2016. Published by Elsevier Ltd.

  15. 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.

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    Tamura, Akitoshi; 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 28days 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Soft-contact-lenses-induced complications

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    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.

  17. Drug-induced hypersensitivity syndrome caused by valproic acid as a monotherapy for epilepsy: First case report in Asian population.

    Science.gov (United States)

    Wu, X T; Hong, P W; Suolang, D J; Zhou, D; Stefan, H

    2017-01-01

    Valproic acid (VPA) is a broad-spectrum antiseizure drug used for a variety of clinical conditions, such as epilepsy and mood disorders. Drug-induced hypersensitivity syndrome (DRESS) accompanied by hyponatremia, thrombocytopenia, hypoalbuminemia and elevated aminotransferase has never been reported as an adverse effect of VPA monotherapy during titration for epilepsy in Asian population. Hereby, we present the case of a 73-year-old Chinese male who suffered from DRESS and other complications two weeks after initiating VPA treatment for epilepsy. Understanding the risk associated with VPA-induced DRESS, and taking effective measures to avoid the severe side effects are necessary.

  18. Ralstonia solanacearum type III secretion system effector Rip36 induces a hypersensitive response in the nonhost wild eggplant Solanum torvum.

    Science.gov (United States)

    Nahar, Kamrun; Matsumoto, Iyo; Taguchi, Fumiko; Inagaki, Yoshishige; Yamamoto, Mikihiro; Toyoda, Kazuhiro; Shiraishi, Tomonori; Ichinose, Yuki; Mukaihara, Takafumi

    2014-04-01

    Ralstonia solanacearum is a Gram-negative soil-borne bacterium that causes bacterial wilt disease in more than 200 plant species, including economically important Solanaceae species. In R. solanacearum, the hypersensitive response and pathogenicity (Hrp) type III secretion system is required for both the ability to induce the hypersensitive response (HR) in nonhost plants and pathogenicity in host plants. Recently, 72 effector genes, called rip (Ralstonia protein injected into plant cells), have been identified in R. solanacearum RS1000. RS1002, a spontaneous nalixidic acid-resistant derivative of RS1000, induced strong HR in the nonhost wild eggplant Solanum torvum in an Hrp-dependent manner. An Agrobacterium-mediated transient expression system revealed that Rip36, a putative Zn-dependent protease effector of R. solanacearum, induced HR in S. torvum. A mutation in the putative Zn-binding motif (E149A) completely abolished the ability to induce HR. In agreement with this result, the RS1002-derived Δrip36 and rip36E149A mutants lost the ability to induce HR in S. torvum. An E149A mutation had no effect on the translocation of Rip36 into plant cells. These results indicate that Rip36 is an avirulent factor that induces HR in S. torvum and that a putative Zn-dependent protease motif is essential for this activity.

  19. Nav1.9 channel contributes to mechanical and heat pain hypersensitivity induced by subacute and chronic inflammation.

    Directory of Open Access Journals (Sweden)

    Stéphane Lolignier

    Full Text Available Inflammation is known to be responsible for the sensitization of peripheral sensory neurons, leading to spontaneous pain and invalidating pain hypersensitivity. Given its role in regulating neuronal excitability, the voltage-gated Nav1.9 channel is a potential target for the treatment of pathological pain, but its implication in inflammatory pain is yet not fully described. In the present study, we examined the role of the Nav1.9 channel in acute, subacute and chronic inflammatory pain using Nav1.9-null mice and Nav1.9 knock-down rats. In mice we found that, although the Nav1.9 channel does not contribute to basal pain thresholds, it plays an important role in heat pain hypersensitivity induced by subacute paw inflammation (intraplantar carrageenan and chronic ankle inflammation (complete Freund's adjuvant-induced monoarthritis. We showed for the first time that Nav1.9 also contributes to mechanical hypersensitivity in both models, as assessed using von Frey and dynamic weight bearing tests. Consistently, antisense-based Nav1.9 gene silencing in rats reduced carrageenan-induced heat and mechanical pain hypersensitivity. While no changes in Nav1.9 mRNA levels were detected in dorsal root ganglia (DRGs during subacute and chronic inflammation, a significant increase in Nav1.9 immunoreactivity was observed in ipsilateral DRGs 24 hours following carrageenan injection. This was correlated with an increase in Nav1.9 immunolabeling in nerve fibers surrounding the inflamed area. No change in Nav1.9 current density could be detected in the soma of retrolabeled DRG neurons innervating inflamed tissues, suggesting that newly produced channels may be non-functional at this level and rather contribute to the observed increase in axonal transport. Our results provide evidence that Nav1.9 plays a crucial role in the generation of heat and mechanical pain hypersensitivity, both in subacute and chronic inflammatory pain models, and bring new elements for the

  20. Nav1.9 channel contributes to mechanical and heat pain hypersensitivity induced by subacute and chronic inflammation.

    Science.gov (United States)

    Lolignier, Stéphane; Amsalem, Muriel; Maingret, François; Padilla, Françoise; Gabriac, Mélanie; Chapuy, Eric; Eschalier, Alain; Delmas, Patrick; Busserolles, Jérôme

    2011-01-01

    Inflammation is known to be responsible for the sensitization of peripheral sensory neurons, leading to spontaneous pain and invalidating pain hypersensitivity. Given its role in regulating neuronal excitability, the voltage-gated Nav1.9 channel is a potential target for the treatment of pathological pain, but its implication in inflammatory pain is yet not fully described. In the present study, we examined the role of the Nav1.9 channel in acute, subacute and chronic inflammatory pain using Nav1.9-null mice and Nav1.9 knock-down rats. In mice we found that, although the Nav1.9 channel does not contribute to basal pain thresholds, it plays an important role in heat pain hypersensitivity induced by subacute paw inflammation (intraplantar carrageenan) and chronic ankle inflammation (complete Freund's adjuvant-induced monoarthritis). We showed for the first time that Nav1.9 also contributes to mechanical hypersensitivity in both models, as assessed using von Frey and dynamic weight bearing tests. Consistently, antisense-based Nav1.9 gene silencing in rats reduced carrageenan-induced heat and mechanical pain hypersensitivity. While no changes in Nav1.9 mRNA levels were detected in dorsal root ganglia (DRGs) during subacute and chronic inflammation, a significant increase in Nav1.9 immunoreactivity was observed in ipsilateral DRGs 24 hours following carrageenan injection. This was correlated with an increase in Nav1.9 immunolabeling in nerve fibers surrounding the inflamed area. No change in Nav1.9 current density could be detected in the soma of retrolabeled DRG neurons innervating inflamed tissues, suggesting that newly produced channels may be non-functional at this level and rather contribute to the observed increase in axonal transport. Our results provide evidence that Nav1.9 plays a crucial role in the generation of heat and mechanical pain hypersensitivity, both in subacute and chronic inflammatory pain models, and bring new elements for the understanding of its

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-08-01

    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 ..mu..gml. 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

  2. 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.

  3. 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

  4. 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

  5. Comparative expression analysis of genes induced during development of bacterial rot and induction of hypersensitive cell death in lettuce.

    Science.gov (United States)

    Kiba, Akinori; Lee, Kyon-Ye; Ohnishi, Kouhei; Hikichi, Yasufumi

    2008-11-28

    The development of bacterial rot disease caused by Pseudomonas cichorii is closely associated with programmed cell death. To investigate the molecular events occurring during the development of bacterial rot, we isolated 20 P. cichorii-responsive genes (PcRGs) in lettuce by differential display. Among these PcRGs, signal transduction-, transcription/translation- and defense/stress responses-related PcRGs were subjected to a comparative expression study. We used RNA samples isolated from lettuce leaves inoculated with P. cichorii and hypersensitive response-inducing Pseudomonas syringae pv. syringae. Expression of PcRG1-5-5 (spliceosomal protein), 2-9-2 (protein kinase) and 1-6-2 (ACC oxidase), 7-5 (alternative oxidase) and BI-I (bax inhibitor I) significantly increased in lettuce leaves inoculated with both P. cichorii and P. syringae pv. syringae. Intriguingly, PcRG 1-2-6 (protein phosphatase 2C) and 4-D-5 (protein kinase) were only up-regulated in P. cichorii-inoculated lettuce, whereas expression of PcRG1-3-2 (ribonucleoprotein) was only enhanced in P. syringae pv. syringae-inoculated lettuce. Expressions of PcRG1-3-2, 1-5-5, 1-6-2, 2-9-2, 7-5 and BI-I were induced by treatments with salicylic acid and/or methyl jasmonate. However, expression of PcRG1-2-6 and 4-D-5, which were specifically up-regulated by P. cichorii, were scarcely affected by these chemicals. Pharmacological studies suggested that ethylene and alternative oxidase were commonly related to disease development and hypersensitive responses. By contrast, there may be a different role for protein synthesis and protein kinase during disease development and in hypersensitive responses. These results suggested the overall similarity of genes expressed during disease development and in hypersensitive responses. However, there were differences not only in induction kinetics and the level of gene expression but also in the signal transduction pathway between hypersensitive responses and disease development.

  6. Allergen-specific cytokine polarization protects shetland ponies against culicoides obsoletus-induced insect bite hypersensitivity

    NARCIS (Netherlands)

    Meulenbroeks, C.; Lugt, van der J.J.; Meide, van der N.M.A.; Willemse, T.; Rutten, V.P.M.G.; Zaiss, D.M.W.

    2015-01-01

    The immunological mechanisms explaining development of an allergy in some individuals and not in others remain incompletely understood. Insect bite hypersensitivity (IBH) is a common, seasonal, IgE-mediated, pruritic skin disorder that affects considerable proportions of horses of different breeds,

  7. 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...

  8. 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

  9. A Case of Anaphylaxis Induced by Contact with Young Radish (Raphanus sativus L).

    Science.gov (United States)

    Lee, Yung-Hee; Lee, Jae-Hyoung; Kang, Hye-Ran; Ha, Jung-Hoon; Lee, Byoung-Hoon; Kim, Sang-Hoon

    2015-01-01

    Young radish (Raphanus sativus L), a member of the mustard family (Cruciferae), is a common ingredient of Kimchi. Although few reports have described anaphylaxis to cruciferous vegetables, we report the case of anaphylaxis induced by contact with young radish. A 46-year-old female with a history of contact allergy to metal presented to our emergency room (ER) with dizziness, generalized eruption and gastrointestinal upset. Her symptoms developed after re-exposure to young radish while chopping it. Hypotensive blood pressures were noted. Three days prior, the patient had experienced generalized urticaria with pruritus immediately after chopping the fresh young radish, which resolved spontaneously. In the ER, her symptoms improved by the administration of epinephrine (0.3 mL), antihistamine (chlorpheniramine) and isotonic saline hydration. A skin prick test with young radish extract showed positive reactivity. The same skin test was negative in five adult controls. IgE-mediated hypersensitivity could be an important immunologic mechanism in the development of young radish-induced anaphylaxis.

  10. Epidermal RelA specifically restricts contact allergen-induced inflammation and apoptosis in skin.

    Science.gov (United States)

    Kumari, Snehlata; Herzberg, Benjamin; Pofahl, Ruth; Krieg, Thomas; Haase, Ingo

    2014-10-01

    Strong inhibition of NF-κB signaling in the epidermis results in spontaneous skin inflammation in mice and men. As there is evidence for linkage between polymorphisms within the NF-κB signaling pathway and human inflammatory skin phenotypes, we asked whether partial functional inhibition of NF-κB signaling in epidermal keratinocytes can modulate clinically relevant skin inflammation. We therefore mutated rela specifically in the epidermis of mice (RelA(E-MUT) mice). These mice show no inflammatory phenotype. Induction of contact allergy, but not croton oil-induced irritant dermatitis, resulted in stronger ear swelling and increased epidermal thickness in RelA(E-MUT) mice. Both contact allergen and croton oil treatment led to increased expression of calgranulins A and B (S100A8/A9) in RelA(E-MUT) mice. Epidermal hyperproliferation in RelA(E-MUT) mice was non-cell autonomous as cultured primary epidermal keratinocytes from RelA(E-MUT) mice showed reduced proliferation compared with controls. These results demonstrate that epidermal RelA specifically regulates delayed-type hypersensitivity-induced skin inflammation. In addition, we describe here an essential but nonspecific function of RelA in the protection of epidermal keratinocytes from apoptosis. Our study identifies functions of NF-κB signaling in the epidermis and corroborates a specific role of epidermal keratinocytes in the regulation of skin inflammation.

  11. Genetic variants associated with drugs-induced immediate hypersensitivity reactions: a PRISMA-compliant systematic review

    OpenAIRE

    Oussalah, A.; Mayorga, C.; Blanca, M.; Barbaud, A.; Nakonechna, A.; Cernadas, J.; Gotua, M.; Brockow, K.; Caubet, Jean-Christoph Roger J-P; Bircher, A.; Atanaskovic, M.; Demoly, P.; K. Tanno, L.; Terreehorst, I.; Laguna, J. J.

    2016-01-01

    Drug hypersensitivity includes allergic (AR) and nonallergic reactions (NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE-mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations, the search selected 53 studies, 42 of which remained eligible. These eligible studies have evaluated genetic determinants of immediate reactions (IR) to beta-lactams (n = 19), NAR against aspirin (n ...

  12. Comparison of CD63 Upregulation Induced by NSAIDs on Basophils and Monocytes in Patients with NSAID Hypersensitivity

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    N. Abuaf

    2012-01-01

    Full Text Available Background. An in vitro basophil activation test, based on the detection of CD63 upregulation induced by NSAIDs, has been described. Its clinical significance remains controversial. Objectives. In patients with a history of nonallergic NSAID hypersensitivity, stratified according to the severity of the symptoms, to assess with NSAIDs the predictive value of basophil (BAT and monocyte (MAT activation tests. Patients/Methods. Sixty patients who had NSAIDs-induced or exacerbated urticaria/angiooedema and 20 controls was included. After incubation with NSAIDs or acetaminophen, leukocytes were analysed for CD63 upregulation. Results. With aspirin, the sensitivity (37% and specificity (90% of BAT agree with already published results. In contrast, when patients had had cutaneous and visceral reactions, the frequency of positive BAT 14/22 (64%, P<0.001 or MAT 10/22 (46%, P<0.01 were increased. Conclusions. Positive tests were more frequent among patients having a severe hypersensitivity contrasting with the other patients who had results similar to controls.

  13. Heat hyperalgesia and mechanical hypersensitivity induced by calcitonin gene-related peptide in a mouse model of neurofibromatosis.

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    Stephanie White

    Full Text Available This study examined whether mice with a deficiency of neurofibromin, a Ras GTPase activating protein, exhibit a nociceptive phenotype and probed a possible contribution by calcitonin gene-related peptide. In the absence of inflammation, Nf1+/- mice (B6.129S6 Nf1/J and wild type littermates responded comparably to heat or mechanical stimuli, except for a subtle enhanced mechanical sensitivity in female Nf1+/- mice. Nociceptive phenotype was also examined after inflammation induced by capsaicin and formalin, which release endogenous calcitonin gene-related peptide. Intraplantar injection of capsaicin evoked comparable heat hyperalgesia and mechanical hypersensitivity in Nf1+/- and wild type mice of both genders. Formalin injection caused a similar duration of licking in male Nf1+/- and wild type mice. Female Nf1+/- mice licked less than wild type mice, but displayed other nociceptive behaviors. In contrast, intraplantar injection of CGRP caused greater heat hyperalgesia in Nf1+/- mice of both genders compared to wild type mice. Male Nf1+/- mice also exhibited greater mechanical hypersensitivity; however, female Nf1+/- mice exhibited less mechanical hypersensitivity than their wild type littermates. Transcripts for calcitonin gene-related peptide were similar in the dorsal root ganglia of both genotypes and genders. Transcripts for receptor activity-modifying protein-1, which is rate-limiting for the calcitonin gene-related peptide receptor, in the spinal cord were comparable for both genotypes and genders. The increased responsiveness to intraplantar calcitonin gene-related peptide suggests that the peripheral actions of calcitonin gene-related peptide are enhanced as a result of the neurofibromin deficit. The analgesic efficacy of calcitonin gene-related peptide receptor antagonists may therefore merit investigation in neurofibromatosis patients.

  14. Heat hyperalgesia and mechanical hypersensitivity induced by calcitonin gene-related peptide in a mouse model of neurofibromatosis.

    Science.gov (United States)

    White, Stephanie; Marquez de Prado, Blanca; Russo, Andrew F; Hammond, Donna L

    2014-01-01

    This study examined whether mice with a deficiency of neurofibromin, a Ras GTPase activating protein, exhibit a nociceptive phenotype and probed a possible contribution by calcitonin gene-related peptide. In the absence of inflammation, Nf1+/- mice (B6.129S6 Nf1/J) and wild type littermates responded comparably to heat or mechanical stimuli, except for a subtle enhanced mechanical sensitivity in female Nf1+/- mice. Nociceptive phenotype was also examined after inflammation induced by capsaicin and formalin, which release endogenous calcitonin gene-related peptide. Intraplantar injection of capsaicin evoked comparable heat hyperalgesia and mechanical hypersensitivity in Nf1+/- and wild type mice of both genders. Formalin injection caused a similar duration of licking in male Nf1+/- and wild type mice. Female Nf1+/- mice licked less than wild type mice, but displayed other nociceptive behaviors. In contrast, intraplantar injection of CGRP caused greater heat hyperalgesia in Nf1+/- mice of both genders compared to wild type mice. Male Nf1+/- mice also exhibited greater mechanical hypersensitivity; however, female Nf1+/- mice exhibited less mechanical hypersensitivity than their wild type littermates. Transcripts for calcitonin gene-related peptide were similar in the dorsal root ganglia of both genotypes and genders. Transcripts for receptor activity-modifying protein-1, which is rate-limiting for the calcitonin gene-related peptide receptor, in the spinal cord were comparable for both genotypes and genders. The increased responsiveness to intraplantar calcitonin gene-related peptide suggests that the peripheral actions of calcitonin gene-related peptide are enhanced as a result of the neurofibromin deficit. The analgesic efficacy of calcitonin gene-related peptide receptor antagonists may therefore merit investigation in neurofibromatosis patients.

  15. Obesity Takes Its Toll on Visceral Pain: High-Fat Diet Induces Toll-Like Receptor 4-Dependent Visceral Hypersensitivity.

    Directory of Open Access Journals (Sweden)

    Mónica Tramullas

    Full Text Available Exposure to high-fat diet induces both, peripheral and central alterations in TLR4 expression. Moreover, functional TLR4 is required for the development of high-fat diet-induced obesity. Recently, central alterations in TLR4 expression have been associated with the modulation of visceral pain. However, it remains unknown whether there is a functional interaction between the role of TLR4 in diet-induced obesity and in visceral pain. In the present study we investigated the impact of long-term exposure to high-fat diet on visceral pain perception and on the levels of TLR4 and Cd11b (a microglial cell marker protein expression in the prefrontal cortex (PFC and hippocampus. Peripheral alterations in TLR4 were assessed following the stimulation of spleenocytes with the TLR4-agonist LPS. Finally, we evaluated the effect of blocking TLR4 on visceral nociception, by administering TAK-242, a selective TLR4-antagonist. Our results demonstrated that exposure to high-fat diet induced visceral hypersensitivity. In parallel, enhanced TLR4 expression and microglia activation were found in brain areas related to visceral pain, the PFC and the hippocampus. Likewise, peripheral TLR4 activity was increased following long-term exposure to high-fat diet, resulting in an increased level of pro-inflammatory cytokines. Finally, TLR4 blockage counteracted the hyperalgesic phenotype present in mice fed on high-fat diet. Our data reveal a role for TLR4 in visceral pain modulation in a model of diet-induced obesity, and point to TLR4 as a potential therapeutic target for the development of drugs to treat visceral hypersensitivity present in pathologies associated to fat diet consumption.

  16. Corneal Biomechanical Findings in Contact Lens Induced Corneal Warpage

    OpenAIRE

    Fateme Alipour; Mojgan Letafatnejad; Amir Hooshang Beheshtnejad; Seyed-Farzad Mohammadi; Seyed Reza Ghaffary; Narges Hassanpoor; Mehdi Yaseri

    2016-01-01

    Purpose. To evaluate the difference in biomechanical properties between contact lens induced corneal warpage and normal and keratoconic eyes. Method. Prospective observational case control study, where 94 eyes of 47 warpage suspicious and 46 eyes of 23 keratoconic patients were included. Warpage suspected cases were followed until a definite diagnosis was made (warpage, normal, or keratoconus). Results. 44 eyes of 22 patients had contact lens related corneal warpage. 46 eyes of 23 people were...

  17. Selective class I histone deacetylase inhibitors suppress persistent spontaneous nociception and thermal hypersensitivity in a rat model of bee venom-induced inflammatory pain.

    Science.gov (United States)

    Yang, Fan; Yang, Yan; Wang, Yan; Yang, Fei; Li, Chun-Li; Wang, Xiao-Liang; Li, Zhen; Chen, Jun

    2015-10-25

    To confirm whether class I histone deacetylase inhibitors (HDACIs) are effective in relief of peripheral inflammatory pain, the effects of two selective inhibitors, MS-275 and MGCD0103, were studied in rats inflamed by subcutaneous (s.c.) injection of bee venom (BV). The BV test is characterized by displaying both persistent spontaneous nociception (PSN) and primary hypersensitivity. Intrathecal (i.t.) pre-treatment of either MS-275 or MGCD0103 with a single dose of 60 nmol/20 μL resulted in profound suppression of both PSN and primary thermal hypersensitivity but without significant influence upon the primary mechanical hypersensitivity and mirror-image thermal hypersensitivity. Moreover, the up-regulation of both HDAC1 and HDAC2 induced by s.c. BV injection was completely suppressed by i.t. pre-treatment of MS-275. The present results provide with another new line of evidence showing involvement of epigenetic regulation of chromatin structure by HDAC1/2-mediated histone hypoacetylation in the BV-induced PSN and thermal hypersensitivity and demonstrate the beneficial effects of class I HDACIs in prevention of peripheral inflammatory pain from occurring.

  18. Combined dermal exposure to permethrin and cis-urocanic acid suppresses the contact hypersensitivity response in C57BL/6N mice in an additive manner.

    Science.gov (United States)

    Prater, M R; Blaylock, B L; Holladay, S D

    2005-01-14

    Cutaneous exposure to the pyrethroid insecticide permethrin significantly suppresses contact hypersensitivity (CH) response to oxazolone in C57BL/6N mice. Additionally, cis-urocanic acid (cUCA), an endogenous cutaneous chromophore isomerized to its active form following exposure to ultraviolet radiation, modulates cell-mediated cutaneous immune responses. This study describes cutaneous immune alterations following combined topical permethrin and intradermal cUCA exposure. Female C57BL/6N mice were administered 5, 50 or 100 microg cUCA daily for 5 consecutive days. CH was then evaluated by the mouse ear swelling test (MEST) response to oxazolone. Decreased responses of 52.3%, 76.3% and 76.3%, respectively, as compared to controls were observed. Then, mice were co-exposed to 5 microg cUCA daily for 5 days and 1.5, 5, 15, or 25 microL permethrin, on either day 1, 3 or 5 of the cUCA treatment to evaluate combined immunomodulatory effects of the two chemicals, or cUCA daily for 5 days followed by permethrin on day 3, 5, or 7 after the last cUCA injection to demonstrate prolonged immunosuppressive effects. Two days after final treatment, mice were sensitized with oxazolone and MEST was performed. Mice receiving five cUCA injections and permethrin topically on cUCA injection day 1 showed up to 93.3% suppression of MEST compared to vehicle control. CH was suppressed by 87.5%, 86.6% and 74.2% in mice treated with 25 muL permethrin on days 3, 5 and 7 after cUCA, respectively, compared to vehicle control. Taken together, these data indicate co-exposure to cUCA and permethrin profoundly suppresses cell-mediated cutaneous immunity.

  19. 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...

  20. 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.

  1. 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.

  2. Risk factors for contact lens-induced papillary conjunctivitis associated with silicone hydrogel contact lens wear.

    Science.gov (United States)

    Tagliaferri, Angela; Love, Thomas E; Szczotka-Flynn, Loretta B

    2014-05-01

    Contact lens-induced papillary conjunctivitis (CLPC) continues to be a major cause of dropout during extended wear of contact lenses. This retrospective study explores risk factors for the development of CLPC during extended wear of silicone hydrogel lenses. Data from 205 subjects enrolled in the Longitudinal Analysis of Silicone Hydrogel Contact Lens study wearing lotrafilcon A silicone hydrogel lenses for up to 30 days of continuous wear were used to determine risk factors for CLPC in this secondary analysis of the main cohort. The main covariates of interest included substantial lens-associated bacterial bioburden and topographically determined lens base curve-to-cornea fitting relationships. Additional covariates of interest included history of adverse events, time of year, race, education level, gender, and other subject demographics. Statistical analyses included univariate logistic regression to assess the impact of potential risk factors on the binary CLPC outcome and Cox proportional hazards regression to describe the impact of those factors on time-to-CLPC diagnosis. Across 12 months of follow-up, 52 subjects (25%) experienced CLPC. No associations were found between the CLPC development and the presence of bacterial bioburden, lens-to-cornea fitting relationships, history of adverse events, gender, or race. Contact lens-induced papillary conjunctivitis development followed the same seasonal trends as the local peaks in environmental allergens. Lens fit and biodeposits, in the form of lens-associated bacterial bioburden, were not associated with the development of CLPC during extended wear with lotrafilcon A silicone hydrogel lenses.

  3. 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.

  4. Malaria-Induced NLRP12/NLRP3-Dependent Caspase-1 Activation Mediates Inflammation and Hypersensitivity to Bacterial Superinfection

    Science.gov (United States)

    Ataide, Marco A.; Andrade, Warrison A.; Zamboni, Dario S.; Wang, Donghai; Souza, Maria do Carmo; Franklin, Bernardo S.; Elian, Samir; Martins, Flaviano S.; Pereira, Dhelio; Reed, George; Fitzgerald, Katherine A.; Golenbock, Douglas T.; Gazzinelli, Ricardo T.

    2014-01-01

    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 CD14dimCD16+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. PMID:24453977

  5. Hypersensitivity pneumonitis induced by spores of Penicillium citrinum in a worker cultivating Enoki mushroom.

    Science.gov (United States)

    Yoshikawa, Sumiko; Tsushima, Kenji; Koizumi, Tomonobu; Kubo, Keishi; Kumagai, Toshiko; Yamazaki, Yoshitaka

    2006-01-01

    A 47-year-old Japanese woman was admitted to our hospital with a 2-week history of dry cough and shortness of breath. She had been engaged in Enoki mushroom production for 22 years. Chest X-ray and chest computed tomography (CT) scan showed bilateral fine-nodular shadows and ground glass opacity. Bronchoalveolar lavage fluid demonstrated an increase of total cell counts with predominant lymphocytosis. Pathological specimens obtained by video-assisted thoracoscopic surgery revealed alveolitis and noncaseating granuloma with giant cells. Lymphocyte stimulation test showed positive responses with Enoki mushroom, culture medium, and Penicillium citrinum. On double immunodiffusion test, a precipitation line was observed between patient's serum and Penicillium citrinum antigen. She was found to have hypersensitivity pneumonitis caused by Penicillium citrinum. This is the first report of mushroom worker's lung caused by Penicillium citrinum.

  6. 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.

  7. Azathioprine Hypersensitivity Syndrome: Two Cases of Febrile Neutrophilic Dermatosis Induced by Azathioprine

    Directory of Open Access Journals (Sweden)

    Majed Aleissa

    2017-01-01

    Full Text Available Background: Azathioprine is an immunosuppressive agent used in the treatment of immune-mediated diseases. Azathioprine hypersensitivity syndrome is a rare adverse reaction occurring a few days to weeks after the administration of azathioprine. Case 1: A 36-year-old male with ulcerative colitis presented with erythematous plaques, pustules and erosions on the lower back, buttocks and thighs associated with high fever (39°C 2 weeks after the initiation of azathioprine 100 mg/day. Additional findings included leukocytosis (18.6 g/L with neutrophilia (11.1 g/L and elevated C-reactive protein (128 mg/L. Histopathology showed a dense infiltrate of neutrophils in the hair follicles. We increased the dose of prednisone to 1 mg/kg/day (60 mg/day and azathioprine was discontinued. He had marked improvement within 3 weeks and did not have any relapse with a 1-year follow-up. Case 2: A 57-year-old male with ulcerative colitis presented with erythematous plaques and pustules on the lower limbs associated with high fever (40°C 1 week after the initiation of azathioprine 75 mg/day. Leukocytosis with neutrophilia (13.6 g/L and elevated C-reactive protein (344 mg/L were among the laboratory findings. Histopathology showed a dense infiltrate of neutrophils in the hair follicles. The dose of prednisone was increased to 20 mg/day and azathioprine was discontinued, which led to complete remission within 7 days. He did not have any relapse with a 6-month follow-up. Conclusion: The development of acute neutrophilic dermatitis 2 weeks after the initiation of azathioprine and the complete resolution after its withdrawal were in favor of azathioprine hypersensitivity syndrome. It should not be confused with Sweet syndrome associated with inflammatory bowel disease, as maintenance of azathioprine treatment may lead to life-threatening reactions.

  8. [Chromium-induced vasculitis-like purpuric allergic contact dermatitis].

    Science.gov (United States)

    Grange, A; Roth, B; Tortel, M-C; Guillaume, J-C

    2005-12-01

    Purpuric allergic contact dermatitis is a rare and poorly understood condition. A 27-year-old male patient with a personal history of atopic dermatitis since childhood consulted for chronic papular-purpuric rash present for 7 years. Moderate pruritus was seen. Profuse lesions were observed on the palms and soles and on the upper and lower limbs, with sparing of the trunk. These lesions consisted of purpuric papules, in some cases with crusts, forming large plaques. The clinical picture was initially suggestive of vasculitis, but this diagnosis was ruled out by histological examination and laboratory tests. Skin patch tests were evocative of chromium-induced contact dermatitis. Retrospective directed history-taking confirmed the relevance of the latter test since it revealed regular wearing of leather clothing. Lasting cure was achieved following eradication of the allergen. Reports of contact purpuric dermatitis are rare. This condition has been described principally for allergens consisting of rubber or dyes used in clothing. Our case was notable on account of the severity of the lesions, mimicking vasculitis, as well as the novelty of the incriminated allergen, chromium, found in leather garments. It underlines the value of routine skin patch tests in the event of chronic non-specific dermatitis. To our knowledge, this is the first reported case of chromium-induced purpuric allergic contact dermatitis.

  9. Airway hypersensitivity induced by Ascaris suum extract in New Zealand Romney sheep.

    Science.gov (United States)

    Chen, W; Pack, R J; Alley, M R; Carr, D H; Manktelow, B W

    1990-06-01

    Sheep from local farms with and without previous exposure to pigs were tested for their skin and airway responses to a commercial Ascaris suum antigen. There was an immediate reaction to intradermal injection of the antigen in 90% of 101 sheep. A bronchial provocation test by aerosol of the same antigen was undertaken on 43 of the sheep with a positive skin reaction. About 70% of sheep showed an immediate airway response to the antigen as an aerosol, reflected as a significant increase in airway resistance and/or decrease of dynamic lung compliance. The mean peak airway resistance and mean lowest dynamic lung compliance were 165% above and 61% below their baselines, respectively. No significant changes were recorded when the same animals were given an aerosol of phosphate buffered saline. Similarly, no correlation was found between the degree of skin reaction and the magnitude of bronchoconstriction (p>0.05). The sheep with previous exposure to pigs showed no significant differences in airway responses to antigen challenge, although they showed significantly greater skin reactions than those without exposure to pigs. These results indicate that the majority of Romney sheep in the Manawatu have a natural skin and airway sensitivity to A. suum antigen and may therefore be used as an animal model to study human airway hypersensitivity. The origin of this sensitivity has yet to be determined.

  10. Oral nickel exposure may induce Type I hypersensitivity reaction in nickel-sensitized subjects.

    Science.gov (United States)

    Büyüköztürk, Suna; Gelincik, Aslı; Ünal, Derya; Demirtürk, Mustafa; Çelik, Dolay Damla; Erden, Sacide; Çolakoğlu, Bahattin; Erdem Kuruca, Serap

    2015-05-01

    Little is known about the clinical and immunological changes in the nickel allergic patients with systemic symptoms. We aimed to evaluate T helper cell responses of patients with different clinical presentations due to nickel. Patients having various allergic symptoms and positive patch test results to nickel and 20 controls underwent skin prick tests with nickel. IL-10, IL-4, IL-5 and IFN-gamma were measured in the culture supernatants of PBMC stimulated by nickel during lymphocyte proliferation test (LTT). 69 patients (56 female, mean age: 49.2 ± 13.1), 97% having nickel containing dental devices and 20 controls (8 female, mean age 34.9 ± 12.06) were evaluated. Skin prick tests with nickel were positive in 70% of the patients (pType I hypersensitivity in addition to a Type IV immune reaction in patients with chronic systemic symptoms related to nickel. Nickel containing dental alloys and oral nickel intake seem to trigger systemic symptoms in previously nickel sensitized patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. [Contact urticaria induced by hydrolyzed wheat proteins in cosmetics].

    Science.gov (United States)

    Olaiwan, A; Pecquet, C; Mathelier-Fusade, P; Francès, C

    2010-04-01

    Hydrolyzed wheat protein, produced by hydrolysis of gluten, is used in certain cosmetics and foods as emulsifiers and stabilizers. It can induce contact urticaria to cosmetics and/or anaphylaxis to food via an immunologic mechanism. A 28-year-old female beautician presented recurrent contact urticaria, initially on the hands and then more diffused, immediately after applying cosmetics of the same brand containing hydrolyzed wheat protein. Skin tests were positive with the cosmetics and with the hydrolyzed wheat protein contained therein. A 34-year-old woman presented four episodes of generalized urticaria after eating industrially prepared foods. She had also experienced contact urticaria with cosmetics. Skin tests with hydrolyzed wheat protein were positive. For both patients, withdrawal of cosmetics and foods containing hydrolyzed wheat protein led to the regression of symptoms. They were both tolerant to traditional wheat products, such as bread and pastries. Although contact urticaria to hydrolyzed wheat protein is rarely described, it must be understood since treatment by eradication of this product is simple and because contact urticaria may precede food allergy. Patients are tolerant to products containing unmodified wheat protein. 2010 Elsevier Masson SAS. All rights reserved.

  12. Dapsone hypersensitivity syndrome with myocarditis.

    Science.gov (United States)

    Pereira, Carmen M; Vaz, Marina; Kotha, Sindhoora; Santosh, N H

    2014-08-01

    Drug hypersensitivity with myocarditis is known to occur with many drugs especially with antiepileptics, sulpha-compounds and daposne. Dapsone (4, 4 diaminodiphenyl sulphone) induced hypersensitivity is known to occur in about 2% of leprosy patients on treatment and an incidence of 1.66% in non-leprosy patients. We report this rare case of dapsone hypersensitivity syndrome in a girl on dapsone who presented with fever, anaemia, jaundice, skin rash, lymphadenopathy, and hepatomegaly and later developed myocarditis. The drug was withdrawn and the patient was treated with steroids. She improved and was discharged. She relapsed after the corticosteroids were discontinued at home.

  13. Hypersensitivity to antihistamines.

    Science.gov (United States)

    Shakouri, Alireza A; Bahna, Sami L

    2013-01-01

    Antihistamines are the cornerstone of allergy therapy and are not expected to cause hypersensitivity reactions. We describe two cases, one had urticaria to multiple anti-H1-preparations and the other had anaphylaxis to hydroxyzine. We also provide a review of the English literature on reported reactions regarding causative preparations and manifestations. The latter showed a wide range; most commonly urticaria/angioedema, contact dermatitis, anaphylaxis, and fixed drug eruption (FDE). Most reported cases were young to middle age adults, with apparent predilection to female subjects. The onset of reactions varied from a few minutes for anaphylaxis and urticaria/angioedema, several hours for maculopapular rashes, or longer for contact dermatitis and FDE. Almost all antihistamines have been reported as causing reactions; cetirizine was the most common oral preparation followed by its parent drug, hydroxyzine. Doxepin cream was the most commonly implicated topical preparation in causing contact dermatitis. A causal relationship is often difficult to recognize because the reaction may be similar to the disease being treated with that antihistamine preparation. Reactions to one preparation are likely to occur, but not always, to other members of the same class. Diagnosis is based on clinical suspicion and may be verified by challenge testing. Except for patch testing in contact dermatitis or fixed eruption, other tests have not shown optimal reliability. In most cases, challenge testing with multiple preparations would identify one or more preparations that can be tolerated. Although hypersensitivity to antihistamines seems to be very rare, awareness of the problem would reduce its misdiagnosis.

  14. Repeated water avoidance stress induces visceral hypersensitivity: Role of interleukin-1, interleukin-6, and peripheral corticotropin-releasing factor.

    Science.gov (United States)

    Nozu, Tsukasa; Miyagishi, Saori; Nozu, Rintaro; Takakusaki, Kaoru; Okumura, Toshikatsu

    2017-12-01

    Repeated water avoidance stress (WAS) induces visceral hypersensitivity. Additionally, it is also known to activate corticotropin-releasing factor (CRF), mast cells, and pro-inflammatory cytokines systems, but their precise roles on visceral sensation have not been determined definitely. The aim of the study was to explore this issue. Abdominal muscle contractions induced by colonic balloon distention, that is, visceromotor response (VMR) was detected electrophysiologically in conscious rats. WAS or sham stress as control for 1 h daily was loaded, and the threshold of VMR was determined before and at 24 h after the stress. Repeated WAS for three consecutive days reduced the threshold of VMR, but sham stress did not induce any change. Astressin, a CRF receptor antagonist (50 μg/kg) intraperitoneally (ip) at 10 min before each WAS session, prevented the visceral allodynia, but the antagonist (200 μg/kg) ip at 30 min and 15 h before measurement of the threshold after completing 3-day stress session did not modify the response. Ketotifen, a mast cell stabilizer (3 mg/kg), anakinra, an interleukin (IL)-1 receptor antagonist (20 mg/kg) or IL-6 antibody (16.6 μg/kg) ip for two times before the measurement abolished the response. Repeated WAS for three consecutive days induced visceral allodynia, which was mediated through mast cells, IL-1, and IL-6 pathways. Inhibition of peripheral CRF signaling prevented but did not reverse this response, suggesting that peripheral CRF may be an essential trigger but may not contribute to the maintenance of repeated WAS-induced visceral allodynia. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  15. Genetic variants associated with drugs-induced immediate hypersensitivity reactions: a PRISMA-compliant systematic review.

    Science.gov (United States)

    Oussalah, A; Mayorga, C; Blanca, M; Barbaud, A; Nakonechna, A; Cernadas, J; Gotua, M; Brockow, K; Caubet, J-C; Bircher, A; Atanaskovic, M; Demoly, P; K Tanno, L; Terreehorst, I; Laguna, J J; Romano, A; Guéant, J-L

    2016-04-01

    Drug hypersensitivity includes allergic (AR) and nonallergic reactions (NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE-mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations, the search selected 53 studies, 42 of which remained eligible. These eligible studies have evaluated genetic determinants of immediate reactions (IR) to beta-lactams (n = 19), NAR against aspirin (n = 12) and other nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 8), and IR to biologics (n = 3). We reported two genomewide association studies and four case-control studies on candidate genes validated by replication. Genes involved in IR to beta-lactams belonged to HLA type 2 antigen processing, IgE production, atopy, and inflammation, including 4 genes validated by replications, HLA-DRA, ILR4, NOD2, and LGALS3. Genes involved in NAR to aspirin belonged to arachidonic acid pathway, membrane-spanning 4A gene family, histamine production pathway, and pro-inflammatory cytokines, while those involved in NAR to all NSAIDs belonged to arachidonic acid pathway and HLA antigen processing pathway. ALOX5 was a common predictor of studies on NAR to both aspirin and NSAIDs. Although these first conclusions could be drawn, this review highlights also the lack of reliable data and the need for replicating studies in contrasted populations, taking into account worldwide allele frequencies, gene-gene interactions, and contrasted situations of environmental exposure. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Allergen-Specific Cytokine Polarization Protects Shetland Ponies against Culicoides obsoletus-Induced Insect Bite Hypersensitivity

    Science.gov (United States)

    Meulenbroeks, Chantal; van der Lugt, Jaco J.; van der Meide, Nathalie M. A.; Willemse, Ton; Rutten, Victor P. M. G.; Zaiss, Dietmar M. W.

    2015-01-01

    The immunological mechanisms explaining development of an allergy in some individuals and not in others remain incompletely understood. Insect bite hypersensitivity (IBH) is a common, seasonal, IgE-mediated, pruritic skin disorder that affects considerable proportions of horses of different breeds, which is caused by bites of the insect Culicoides obsoletus (C. obsoletus). We investigated the allergen-specific immune status of individual horses that had either been diagnosed to be healthy or to suffer of IBH. Following intradermal allergen injection, skin biopsies were taken of IBH-affected and healthy ponies and cytokine expression was determined by RT-PCR. In addition, allergen-specific antibody titers were measured and cytokine expression of in vitro stimulated, allergen-specific CD4 T-cells was determined. 24 hrs after allergen injection, a significant increase in mRNA expression of the type-2 cytokine IL-4 was observed in the skin of IBH-affected Shetland ponies. In the skin of healthy ponies, however, an increase in IFNγ mRNA expression was found. Analysis of allergen-specific antibody titers revealed that all animals produced allergen-specific antibodies, and allergen-specific stimulation of CD4 T-cells revealed a significant higher percentage of IFNγ-expressing CD4 T-cells in healthy ponies compared to IBH-affected ponies. These data indicate that horses not affected by IBH, in contrast to the so far established dogma, are not immunologically ignorant but have a Th1-skewed allergen-specific immune response that appears to protect against IBH-associated symptoms. To our knowledge this is the first demonstration of a natural situation, in which an allergen-specific immune skewing is protective in an allergic disorder. PMID:25901733

  17. Allergen-Specific Cytokine Polarization Protects Shetland Ponies against Culicoides obsoletus-Induced Insect Bite Hypersensitivity.

    Directory of Open Access Journals (Sweden)

    Chantal Meulenbroeks

    Full Text Available The immunological mechanisms explaining development of an allergy in some individuals and not in others remain incompletely understood. Insect bite hypersensitivity (IBH is a common, seasonal, IgE-mediated, pruritic skin disorder that affects considerable proportions of horses of different breeds, which is caused by bites of the insect Culicoides obsoletus (C. obsoletus. We investigated the allergen-specific immune status of individual horses that had either been diagnosed to be healthy or to suffer of IBH. Following intradermal allergen injection, skin biopsies were taken of IBH-affected and healthy ponies and cytokine expression was determined by RT-PCR. In addition, allergen-specific antibody titers were measured and cytokine expression of in vitro stimulated, allergen-specific CD4 T-cells was determined. 24 hrs after allergen injection, a significant increase in mRNA expression of the type-2 cytokine IL-4 was observed in the skin of IBH-affected Shetland ponies. In the skin of healthy ponies, however, an increase in IFNγ mRNA expression was found. Analysis of allergen-specific antibody titers revealed that all animals produced allergen-specific antibodies, and allergen-specific stimulation of CD4 T-cells revealed a significant higher percentage of IFNγ-expressing CD4 T-cells in healthy ponies compared to IBH-affected ponies. These data indicate that horses not affected by IBH, in contrast to the so far established dogma, are not immunologically ignorant but have a Th1-skewed allergen-specific immune response that appears to protect against IBH-associated symptoms. To our knowledge this is the first demonstration of a natural situation, in which an allergen-specific immune skewing is protective in an allergic disorder.

  18. The nitric oxide donor, isosorbide dinitrate, induces a cephalic cutaneous hypersensitivity, associated with sensitization of the medullary dorsal horn.

    Science.gov (United States)

    Flores Ramos, José María; Devoize, Laurent; Descheemaeker, Amélie; Molat, Jean-Louis; Luccarini, Philippe; Dallel, Radhouane

    2017-03-06

    Nitric oxide donors are known to produce headache in healthy as well as migraine subjects, and to induce extracephalic cutaneous hypersensitivity in rodents. However, little is known on the effect of nitric oxide donors on cephalic cutaneous sensitivity. Combining behavioral, immunohistochemical, and in vivo electrophysiological approaches, this study investigated the effect of systemic administration of the nitric oxide donor, isosorbide dinitrate (ISDN), on cephalic and extracephalic cutaneous sensitivity and on neuronal activation within the medullary dorsal horn (MDH) in the rat. Systemic administration of ISDN increased selectively the first phase and interphase of the facial formalin test, but had no effect on the hindpaw formalin one. Monitoring neuronal activity within the MDH with phospho-ERK1/2 immunoreactivity revealed that ISDN alone did not activate MDH neurons, but significantly increased the number of formalin-evoked phospho-ERK1/2-immunoreactive cells in the ipsilateral, but not contralateral, MDH. Using in vivo electrophysiological unit recordings, we show that ISDN administration never affected the spontaneous activity of trigeminal wide dynamic range neurons, but, facilitated C-fiber-evoked responses in half the neurons tested. This research demonstrates that a nitric oxide donor, isosorbide dinitrate, induces selectively cephalic hyperalgesia that arises as a consequence of central sensitization in pain pathways that subserve meningeal nociception. This model better mimics the clinical condition and offers another possibility of studying the role of nitric oxide donor in the physiopathology of headache. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Shirani M K Widana Gamage

    Full Text Available 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

  20. Current-induced dynamics in carbon atomic contacts

    DEFF Research Database (Denmark)

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

    2011-01-01

    of molecular-scale contacts. Systems based on molecules bridging electrically gated graphene electrodes may offer an interesting test-bed for these effects. Results: We employ a semi-classical Langevin approach in combination with DFT calculations to study the current-induced vibrational dynamics of an atomic......Background: The effect of electric current on the motion of atoms still poses many questions, and several mechanisms are at play. Recently there has been focus on the importance of the current-induced nonconservative forces (NC) and Berry-phase derived forces (BP) with respect to the stability...... 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...

  1. 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.

  2. Purification and characterization of a novel hypersensitive response-inducing elicitor from Magnaporthe oryzae that triggers defense response in rice.

    Directory of Open Access Journals (Sweden)

    Mingjia Chen

    Full Text Available BACKGROUND: Magnaporthe oryzae, the rice blast fungus, might secrete certain proteins related to plant-fungal pathogen interactions. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we report the purification, characterization, and gene cloning of a novel hypersensitive response-inducing protein elicitor (MoHrip1 secreted by M. oryzae. The protein fraction was purified and identified by de novo sequencing, and the sequence matched the genomic sequence of a putative protein from M. oryzae strain 70-15 (GenBank accession No. XP_366602.1. The elicitor-encoding gene mohrip1 was isolated; it consisted of a 429 bp cDNA, which encodes a polypeptide of 142 amino acids with a molecular weight of 14.322 kDa and a pI of 4.53. The deduced protein, MoHrip1, was expressed in E. coli. And the expression protein collected from bacterium also forms necrotic lesions in tobacco. MoHrip1 could induce the early events of the defense response, including hydrogen peroxide production, callose deposition, and alkalization of the extracellular medium, in tobacco. Moreover, MoHrip1-treated rice seedlings possessed significantly enhanced systemic resistance to M. oryzae compared to the control seedlings. The real-time PCR results indicated that the expression of some pathogenesis-related genes and genes involved in signal transduction could also be induced by MoHrip1. CONCLUSION/SIGNIFICANCE: The results demonstrate that MoHrip1 triggers defense responses in rice and could be used for controlling rice blast disease.

  3. 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...

  4. Drug reaction with eosinophilia and systemic symptoms: A drug-induced hypersensitivity syndrome with variable clinical features

    Directory of Open Access Journals (Sweden)

    Yi-Chun Chen

    2013-12-01

    Full Text Available Drug reaction with eosinophilia and systemic symptoms (DRESS or drug-induced hypersensitivity syndrome (DIHS involves a unique and severe adverse drug reaction. Patients present with fever, rash, lymphadenopathy, hematological abnormalities, systemic illness, and may suffer from prolonged courses. Although the precise pathogenesis of DRESS/DIHS is not fully understood, it is widely considered to be an immunological reaction to a drug or drug metabolites. In this review article, we discuss the historical aspects of nosology, variable clinical and histopathological features, advantages and disadvantages of using an international Registry of Severe Cutaneous Adverse Reactions (RegiSCAR and Japanese DIHS criteria, pathogenesis, treatment, and long-term sequelae of DRESS/DIHS. Early recognition of this syndrome, withdrawal of suspected culprit drugs, and adequate supportive care are mainstays of improving patient prognosis and reducing morbidities and mortality. Moreover, some DRESS/DIHS patients may develop long-term sequelae, especially autoimmune diseases and end organ failure. Physicians should be aware of these possibilities in patients after DRESS/DIHS and cautiously follow-up symptoms and laboratory tests for early detection of these sequelae.

  5. Acyclovir Has Low but Detectable Influence on HLA-B*57:01 Specificity without Inducing Hypersensitivity.

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    Imir G Metushi

    Full Text Available Immune mediated adverse drug reactions (IM-ADRs remain a significant source of patient morbidity that have more recently been shown to be associated with specific class I and/or II human leukocyte antigen (HLA alleles. Abacavir-induced hypersensitivity syndrome is a CD8+ T cell dependent IM-ADR that is exclusively mediated by HLA-B*57:01. We and others have previously shown that abacavir can occupy the floor of the peptide binding groove of HLA-B*57:01 molecules, increasing the affinity of certain self peptides resulting in an altered peptide-binding repertoire. Here, we have identified another drug, acyclovir, which appears to act in a similar fashion. As with abacavir, acyclovir showed a dose dependent increase in affinity for peptides with valine and isoleucine at their C-terminus. In agreement with the binding studies, HLA-B*57:01 peptide-elution studies performed in the presence of acyclovir revealed an increased number of endogenously bound peptides with a C-terminal isoleucine. Accordingly, we have hypothesized that acyclovir acts by the same mechanism as abacavir, although our data also suggest the overall effect is much smaller: the largest changes of peptide affinity for acyclovir were 2-5 fold, whereas for abacavir this effect was as much as 1000-fold. Unlike abacavir, acyclovir is not known to cause IM-ADRs. We conclude that the modest effect of acyclovir on HLA binding affinity in contrast to the large effect of abacavir is insufficient to trigger a hypersensitivity syndrome. We further support this by functional in vitro studies where acyclovir, unlike abacavir, was unable to produce an increase in IFN-γ upon expansion of HLA-B*57:01+ PBMCs from healthy donors. Using abacavir and acyclovir as examples we therefore propose an in vitro pre-clinical screening strategy, whereby thresholds can be applied to MHC-peptide binding assays to determine the likelihood that a drug could cause a clinically relevant IM-ADR.

  6. Hypersensitivity pneumonitis.

    Science.gov (United States)

    Yi, Eunhee S

    2002-11-01

    Hypersensitivity pneumonitis (HP) is a group of immunologically mediated lung diseases caused by the inhalation of environmental agents in susceptible individuals. Most HP patients are non-smokers and have been exposed to organic dusts from vegetable or animal products. Some HP cases are associated with exposures to relatively simple chemical compounds. HP may present as an acute, subacute, or chronic disease and may follow various clinical courses. The type of exposure is thought to be more important in the clinical outcome than the nature of the antigen. A diagnosis of HP is often considered on the basis of clinical history of exposure with resulting respiratory symptoms, but the definitive diagnosis requires a constellation of clinical, radiologic, laboratory, and pathologic findings. The characteristic histologic triad in HP includes bronchiolitis, interstitial lymphocytic infiltration, and granulomas; however, biopsy in HP cases may lack the diagnostic triad and manifest as nonspecific interstitial pneumonia (NSIP). Avoiding exposure to the offending antigen(s) is usually sufficient to resolve symptoms and physiological abnormalities. Pulmonary fibrosis and physiological abnormalities occurring in chronic HP may be irreversible. Steroid therapy is helpful for symptomatic relief, but probably does not affect the long-term prognosis. Type III and type IV hypersensitivity reactions are involved in the pathogenesis; alveolar macrophages and T cells (Th-1 type) play a central role in the immune responses after antigen exposure via their increased interaction and secretion of regulatory mediators.

  7. 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.

  8. 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

    OpenAIRE

    Chembolli Lakshmi

    2014-01-01

    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.

  9. 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...

  10. Human Monocyte-Derived Dendritic Cells Exposed to Microorganisms Involved in Hypersensitivity Pneumonitis Induce a Th1-Polarized Immune Response

    Science.gov (United States)

    Pallandre, Jean-René; Borg, Christophe; Loeffert, Sophie; Gbaguidi-Haore, Houssein; Millon, Laurence

    2013-01-01

    Hypersensitivity pneumonitis (HP) is an immunoallergic disease characterized by a prominent interstitial infiltrate composed predominantly of lymphocytes secreting inflammatory cytokines. Dendritic cells (DCs) are known to play a pivotal role in the lymphocytic response. However, their cross talk with microorganisms that cause HP has yet to be elucidated. This study aimed to investigate the initial interactions between human monocyte-derived DCs (MoDCs) and four microorganisms that are different in nature (Saccharopolyspora rectivirgula [actinomycetes], Mycobacterium immunogenum [mycobacteria], and Wallemia sebi and Eurotium amstelodami [filamentous fungi]) and are involved in HP. Our objectives were to determine the cross talk between MoDCs and HP-causative agents and to determine whether the resulting immune response varied according to the microbial extract tested. The phenotypic activation of MoDCs was measured by the increased expression of costimulatory molecules and levels of cytokines in supernatants. The functional activation of MoDCs was measured by the ability of MoDCs to induce lymphocytic proliferation and differentiation in a mixed lymphocytic reaction (MLR). E. amstelodami-exposed (EA) MoDCs expressed higher percentages of costimulatory molecules than did W. sebi-exposed (WS), S. rectivirgula-exposed (SR), or M. immunogenum-exposed (MI) MoDCs (P < 0.05, Wilcoxon signed-rank test). EA-MoDCs, WS-MoDCs, SR-MoDCs, and MI-MoDCs induced CD4+ T cell proliferation and a Th1-polarized immune response. The present study provides evidence that, although differences were initially observed between MoDCs exposed to filamentous fungi and MoDCs exposed to bacteria, a Th1 response was ultimately promoted by DCs regardless of the microbial extract tested. PMID:23720369

  11. Susceptibility to stress induced visceral hypersensitivity in maternally separated rats is transferred across generations

    NARCIS (Netherlands)

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

    2013-01-01

    In irritable bowel syndrome (IBS), familial clustering and transfer across generations may largely depend on environmental factors but this is difficult to establish in the human setting. Therefore, we aimed to set up a relevant animal model. We investigated whether susceptibility to stress induced

  12. Exogenous and endogenous opioid-induced pain hypersensitivity in different rat strains.

    Science.gov (United States)

    Laboureyras, Emilie; Aubrun, Frédéric; Monsaingeon, Maud; Corcuff, Jean-Benoît; Laulin, Jean-Paul; Simonnet, Guy

    2014-01-01

    Opioid-induced hyperalgesia (OIH) is a recognized complication of opioid use that may facilitate the development of exaggerated postoperative pain. To examine the role of genetic factors on OIH by comparing four rat strains. Because the authors previously reported that the endogenous opioids released during non-nociceptive environmental stress induce latent pain sensitization, genetic and environmental factor interactions were also evaluated. First, the propensity of Sprague Dawley, Wistar, Lewis and Fischer rats to develop OIH following single or repeated fentanyl exposures was compared by measuring the nociceptive threshold using the paw pressure vocalization test. Second, Sprague Dawley and Fischer rats were exposed to a series of three non-nociceptive environmental stress sessions to evaluate the ability of endogenous opioids to enhance hyperalgesia associated with a carrageenan-induced hind-paw inflammation test performed two weeks later. Sprague Dawley, Wistar and Lewis rats exhibited OIH, although differences were observed. OIH was not observed in Fischer rats. Inflammatory hyperalgesia enhancement induced through previous stress in Sprague Dawley rats was not observed in Fischer rats. The pain level not only reflects nociceptive inputs but also depends on both the history and genetic factors of the individual. Genetic and environmental models may provide new insights into the mechanisms that underlie individual differences observed in postoperative pain.

  13. 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

    Different neurobiological mechanism(s) might contribute to evoked and non-evoked pains and to limited translational drug discovery efforts. Other variables including the pain model and sensory testing method used, dose/route/preadministration time of compound(s), lack of adverse effect profiling...... and level of observer experience might also contribute. With these points in mind, we tested three mechanistically distinct analgesics in rat models of algogen-induced and neuropathic pain. In chronic constriction injury (CCI) rats evoked hindpaw mechanical hypersensitivity and spontaneous weight bearing...... by morphine (3-10 mg/kg, s.c.) and gabapentin (50-200 mg/kg, i.p.). Weight bearing deficits and cold hypersensitivity were reversed only by high doses of each drug. Surprisingly, duloxetine (10-60 mg/kg, s.c.) was largely ineffective in neuropathic rats although it partially reduced formalin...

  14. Current-induced dynamics in carbon atomic contacts

    Directory of Open Access Journals (Sweden)

    Jing-Tao Lü

    2011-12-01

    Full Text Available Background: The effect of electric current on the motion of atoms still poses many questions, and several mechanisms are at play. Recently there has been focus on the importance of the current-induced nonconservative forces (NC and Berry-phase derived forces (BP with respect to the stability of molecular-scale contacts. Systems based on molecules bridging electrically gated graphene electrodes may offer an interesting test-bed for these effects.Results: We employ a semi-classical Langevin approach in combination with DFT calculations to study the current-induced vibrational dynamics of an atomic 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 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. Molecular dynamics including current-induced forces enables an energy redistribution mechanism among the modes, mediated by anharmonic interactions, which is found to be vital in the description of the electrical heating.Conclusion: We have developed a semiclassical Langevin equation approach that can be used to explore current-induced dynamics and instabilities. We find instabilities at experimentally relevant bias and gate voltages for the carbon-chain system.

  15. Inhibitory effect of eupatilin and jaceosidin isolated from Artemisia princeps in IgE-induced hypersensitivity.

    Science.gov (United States)

    Lee, Seung Hoon; Bae, Eun-Ah; Park, Eun-Kyung; Shin, Yong-Wook; Baek, Nam-In; Han, Eun-Joo; Chung, Hae-Gon; Kim, Dong-Hyun

    2007-12-15

    To understand the antiallergic effect of Artemisia princeps (AP), which has been found to show inhibitory activity against degranulation and a passive cutaneous anaphylaxis (PCA) reaction, eupatilin and jaceosidin, as the active components, were isolated by degranulation-inhibitory activity-guided fractionation, with their antiallergic activity investigated. These isolated components potently inhibited the release of beta-hexosaminidase from RBL-2H3 cells induced by the IgE-antigen complex, with IC(50) values of 3.4 and 4.5muM, respectively. Eupatilin and jaceosidin potently inhibited the PCA reaction and scratching behaviors induced by IgE- antigen complex and compound 48/80, respectively. Orally administered jaceosidin more potently inhibited the PCA reaction than that of eupatilin, although the PCA reaction-inhibitory activity of intraperitoneally administered jaceosidin was nearly the same as that of eupatilin. Eupatilin and jaceosidin inhibited the gene expressions of TNF-alpha and IL-4 in RBL-2H3 cells stimulated by IgE-antigen complex. Eupatilin and jaceosidin inhibited the activation of NF-kB. Based on these findings, eupatilin and jaceosidin may be useful for protection from the PCA and itching reactions, which are IgE-mediated representative skin allergic diseases.

  16. De novo foliar transcriptome of Chenopodium amaranticolor and analysis of its gene expression during virus-induced hypersensitive response.

    Science.gov (United States)

    Zhang, Yongqiang; Pei, Xinwu; Zhang, Chao; Lu, Zifeng; Wang, Zhixing; Jia, Shirong; Li, Weimin

    2012-01-01

    The hypersensitive response (HR) system of Chenopodium spp. confers broad-spectrum virus resistance. However, little knowledge exists at the genomic level for Chenopodium, thus impeding the advanced molecular research of this attractive feature. Hence, we took advantage of RNA-seq to survey the foliar transcriptome of C. amaranticolor, a Chenopodium species widely used as laboratory indicator for pathogenic viruses, in order to facilitate the characterization of the HR-type of virus resistance. Using Illumina HiSeq™ 2000 platform, we obtained 39,868,984 reads with 3,588,208,560 bp, which were assembled into 112,452 unigenes (3,847 clusters and 108,605 singletons). BlastX search against the NCBI NR database identified 61,698 sequences with a cut-off E-value above 10(-5). Assembled sequences were annotated with gene descriptions, GO, COG and KEGG terms, respectively. A total number of 738 resistance gene analogs (RGAs) and homology sequences of 6 key signaling proteins within the R proteins-directed signaling pathway were identified. Based on this transcriptome data, we investigated the gene expression profiles over the stage of HR induced by Tobacco mosaic virus and Cucumber mosaic virus by using digital gene expression analysis. Numerous candidate genes specifically or commonly regulated by these two distinct viruses at early and late stages of the HR were identified, and the dynamic changes of the differently expressed genes enriched in the pathway of plant-pathogen interaction were particularly emphasized. To our knowledge, this study is the first description of the genetic makeup of C. amaranticolor, providing deep insight into the comprehensive gene expression information at transcriptional level in this species. The 738 RGAs as well as the differentially regulated genes, particularly the common genes regulated by both TMV and CMV, are suitable candidates which merit further functional characterization to dissect the molecular mechanisms and regulatory

  17. High frequency of HLA B62 in fulminant type 1 diabetes with the drug-induced hypersensitivity syndrome.

    Science.gov (United States)

    Onuma, Hiroshi; Tohyama, Mikiko; Imagawa, Akihisa; Hanafusa, Toshiaki; Kobayashi, Tetsuro; Kano, Yoko; Ohashi, Jun; Hashimoto, Koji; Osawa, Haruhiko; Makino, Hideichi

    2012-12-01

    Fulminant type 1 diabetes (FT1D) is a subtype of type 1 diabetes characterized by an extremely abrupt onset. FT1D cases associated with the drug-induced hypersensitivity syndrome (DIHS) have recently been reported. The clinical characteristics of FT1D associated with DIHS were investigated in this study. Case reports of FT1D associated with DIHS in Japanese subjects were collected and analyzed by means of a questionnaire to the authors. A nationwide questionnaire survey was administered to dermatology specialists, concerning the frequency of FT1D associated with DIHS. In 15 case reports, the mean age at onset of FT1D was 53.4 yr and the mean time for its development from the onset of DIHS was 39.9 d. A higher frequency of human leukocyte antigen (HLA) B62, but not of HLA DR was found in FT1D with DIHS than that for cases without DIHS (P < 0.001). The reactivation of herpes virus 6 and cytomegalovirus was detected in 11 and four cases, respectively. Among 746 patients with DIHS in the nationwide survey, four developed FT1D during a 3-yr period. The frequency of FT1D in DIHS (0.54%) was much higher than that in the general Japanese population (0.010%). The clinical characteristics of FT1D with DIHS were similar to those without DIHS except for the high frequency of HLA B62, which may be involved in the pathogenesis of FT1D with DIHS. Because the frequency was much higher than that in the general Japanese population, FT1D should be kept in mind when DIHS develops.

  18. Visceral hypersensitivity induced by activation of transient receptor potential vanilloid type 1 is mediated through the serotonin pathway in rat colon.

    Science.gov (United States)

    Qin, Hong-yan; Luo, Jia-lie; Qi, Sheng-da; Xu, Hong-xi; Sung, Joseph J Y; Bian, Zhao-xiang

    2010-11-25

    This study aimed to clarify the relationship between TRPV1 activation-induced visceral pain and the serotonin pathway in the colon of rats. The effects of para-chlorophenylalanine (pCPA) on visceral pain threshold pressure were assessed in capsaicin -induced visceral pain of rats. The expression of TRPV1 in the colon was examined by immunohistochemistry and Western blot analysis, and TRPV1 excitability in dorsal root ganglion (DRG) neurons was examined by whole-cell patch-clamp recording in pCPA-treated rats. Calcineurin and Ca(2+)-calmodulin-dependent kinase II (CaMKII), the important proteins in maintaining TRPV1 function in the colon, were also tested by Western blot analysis and immunofluorescence staining. Results showed that pCPA significantly increased the capsaicin-induced visceral pain threshold by 2.3-fold, and the enhanced visceral pain threshold corresponded with decreased 5-HT content (58% depleted) and enterochromaffin cell number (80% reduced). The reduced excitability of TRPV1 in DRG neurons, instead of changed TRPV1 expression, is responsible for the enhanced visceral pain threshold in 5-HT-depleted rats, and the mechanism may be related to the decreased expression of pCaMKII. These results indicate that visceral hypersensitivity induced by TRPV1 activation is modulated through 5-HT pathways and the attenuated function of TRPV1 and decreased protein expression of pCaMKII may play an important role in capsaicin-induced TRPV1 desensitization under 5-HT-depleted condition. The important role of TRPV1 and 5-HT in generating and maintaining visceral hypersensitivity may provide insights for the treatment of visceral hypersensitivity. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Coronatine inhibits stomatal closure and delays hypersensitive response cell death induced by nonhost bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Seonghee Lee

    2013-02-01

    Full Text Available Pseudomonas syringae is the most widespread bacterial pathogen in plants. Several strains of P. syringae produce a phytotoxin, coronatine (COR, which acts as a jasmonic acid mimic and inhibits plant defense responses and contributes to disease symptom development. In this study, we found that COR inhibits early defense responses during nonhost disease resistance. Stomatal closure induced by a nonhost pathogen, P. syringae pv. tabaci, was disrupted by COR in tomato epidermal peels. In addition, nonhost HR cell death triggered by P. syringae pv. tabaci on tomato was remarkably delayed when COR was supplemented along with P. syringae pv. tabaci inoculation. Using isochorismate synthase (ICS-silenced tomato plants and transcript profiles of genes in SA- and JA-related defense pathways, we show that COR suppresses SA-mediated defense during nonhost resistance.

  20. Odor provocation test for laryngeal hypersensitivity.

    Science.gov (United States)

    Gartner-Schmidt, Jackie L; Rosen, Clark A; Radhakrishnan, Nandhakumar; Ferguson, Berrylin J

    2008-05-01

    This study was to present an odor provocation/challenge test for laryngeal hypersensitivity in a suspected odor induced dysphonic patient. The second aim was to rule out secondary gain from organic laryngeal hypersensitivity. Two steps were taken for this purpose. First, because the evaluation of hypersensitivity may be affected by the perception of odor, the study investigated laryngeal hypersensitivity during nasal and oral breathing separately to disentangle possible cognitive reactions to odors. Second, a healthy control (HC) participant was used with the identical testing protocol for nasal breathing to minimize unbiased results. The HC's response to nasal breathing of the odors showed no response to all the stimuli. The participant with possible secondary gain issues responded differently to the odors when presented nasally versus orally. Oral breathing showed less severe and less frequent laryngeal hypersensitive reactions. This suggests that laryngeal hypersensitivity was either due to the odor, cognitive information, sensory changes in olfaction leading to psychological conditioning, or for any possible secondary gain. Hence, it is difficult to indicate the precise reason (cause and effect) for the participant's laryngeal hypersensitivity; however, this study describes the first structured, controlled, repeatable, and randomized design to investigate odor induced laryngeal hypersensitivity and decipher possible secondary gain from true laryngeal hypersensitivity.

  1. Allergen endotoxins induce T-cell-dependent and non-IgE-mediated nasal hypersensitivity in mice.

    Science.gov (United States)

    Iwasaki, Naruhito; Matsushita, Kazufumi; Fukuoka, Ayumi; Nakahira, Masakiyo; Matsumoto, Makoto; Akasaki, Shoko; Yasuda, Koubun; Shimizu, Takeshi; Yoshimoto, Tomohiro

    2017-01-01

    Allergen-mediated cross-linking of IgE on mast cells/basophils is a well-recognized trigger for type 1 allergic diseases such as allergic rhinitis (AR). However, allergens may not be the sole trigger for AR, and several allergic-like reactions are induced by non-IgE-mediated mechanisms. We sought to describe a novel non-IgE-mediated, endotoxin-triggered nasal type-1-hypersensitivity-like reaction in mice. To investigate whether endotoxin affects sneezing responses, mice were intraperitoneally immunized with ovalbumin (OVA), then nasally challenged with endotoxin-free or endotoxin-containing OVA. To investigate the role of T cells and mechanisms of the endotoxin-induced response, mice were adoptively transferred with in vitro-differentiated OVA-specific TH2 cells, then nasally challenged with endotoxin-free or endotoxin-containing OVA. Endotoxin-containing, but not endotoxin-free, OVA elicited sneezing responses in mice independent from IgE-mediated signaling. OVA-specific TH2 cell adoptive transfer to mice demonstrated that local activation of antigen-specific TH2 cells was required for the response. The Toll-like receptor 4-myeloid differentiation factor 88 signaling pathway was indispensable for endotoxin-containing OVA-elicited rhinitis. In addition, LPS directly triggered sneezing responses in OVA-specific TH2-transferred and nasally endotoxin-free OVA-primed mice. Although antihistamines suppressed sneezing responses, mast-cell/basophil-depleted mice had normal sneezing responses to endotoxin-containing OVA. Clodronate treatment abrogated endotoxin-containing OVA-elicited rhinitis, suggesting the involvement of monocytes/macrophages in this response. Antigen-specific nasal activation of CD4+ T cells followed by endotoxin exposure induces mast cell/basophil-independent histamine release in the nose that elicits sneezing responses. Thus, environmental or nasal residential bacteria may exacerbate AR symptoms. In addition, this novel phenomenon might explain

  2. 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.

  3. 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.

  4. Oxaliplatin-induced changes in expression of transient receptor potential channels in the dorsal root ganglion as a neuropathic mechanism for cold hypersensitivity.

    Science.gov (United States)

    Chukyo, Akiko; Chiba, Terumasa; Kambe, Toshie; Yamamoto, Ken; Kawakami, Kazuyoshi; Taguchi, Kyoji; Abe, Kenji

    2017-12-15

    Transient receptor potential (TRP) receptors are involved in the development of chemotherapy-induced peripheral neuropathic pain, which is a common side effect of selected chemotherapeutic agents such as oxaliplatin. However, the precise contribution of TRPs to this condition remains unknown. Cold hypersensitivity is the hallmark of oxaliplatin-induced neuropathy, so we used a preclinical model of oxaliplatin-induced cold hypersensitivity in rats to determine the effects of oxaliplatin on TRP channels. To this end, immunohistochemistry was used to examine TRP vanilloid 1 (TRPV1), TRP ankyrin 1 (TRPA1), and TRP melastatin 8 (TRPM8) expression in the rat dorsal root ganglion (DRG) after 4days of oxaliplatin treatment. Behavioral assessment using the acetone spray test showed that oxaliplatin significantly increased acute cold hypersensitivity after 4days of treatment. Double-staining immunohistochemistry showed that 4days after oxaliplatin treatment, there was increased co-expression of TRPA1 and TRPV1 in isolectin B4-positive small-sized DRG neurons, as well as a significant increase in the co-localization of TRPM8 and neurofilament 200 in medium-sized DRG neurons. In addition, in situ hybridization revealed that TRPV1 protein was co-expressed with TRPA1 mRNA on day 4 after oxaliplatin administration. Thus, at an early stage following oxaliplatin treatment there is an increased expression of TRPA1 and TRPV1 in small-sized DRG neurons and of TRPM8 in medium-sized DRG neurons. Collectively, these changes may contribute to the development of oxaliplatin-induced peripheral neuropathic pain. Copyright © 2017. Published by Elsevier Ltd.

  5. Effects of TAK-480, a novel tachykinin NK(2)-receptor antagonist, on visceral hypersensitivity in rabbits and ricinoleic acid-induced defecation in guinea pigs.

    Science.gov (United States)

    Tanaka, Takahiro; Tanaka, Akiko; Nakamura, Akihiro; Matsushita, Kozo; Imanishi, Akio; Matsumoto-Okano, Shiho; Inatomi, Nobuhiro; Miura, Kasei; Toyoda, Masao; Mizojiri, Gaku; Tsukimi, Yasuhiro

    2012-01-01

    TAK-480, 4-(difluoromethoxy)-N-((1R,2S)-2-(((3aR,4R,9bR)-4-(methoxymethyl)-2, 3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl)carbonyl)cyclohexyl)benzamide, is a novel tachykinin NK(2)-receptor antagonist. In this study, we investigated its antagonistic activity and efficacy in animal models of visceral hypersensitivity and stimulated bowel function which have been implicated to underlie the symptoms in irritable bowel syndrome (IBS). TAK-480 showed potent binding affinity for human NK(2) receptors with a marked species difference and a 10,000-fold selectivity versus NK(1) and NK(3) receptors. TAK-480 dose-dependently antagonized colonic contractions induced by administration of the NK(2) receptor-selective agonist beta-Ala(8)-NKA(4-10) (βA-NKA) in anesthetized rabbits. In a rabbit model of intracolonic zymosan-induced visceral hypersensitivity, TAK-480 markedly inhibited the visceromotor response to colorectal distension, in contrast to the moderate inhibition by the serotonin 5-HT(3)-receptor antagonist alosetron. In addition, TAK-480 suppressed ricinoleic acid-induced defecation without affecting spontaneous defecation in guinea pigs, whereas alosetron suppressed both. Furthermore, TAK-480 inhibited smooth muscle contractions produced by natural tachykinins (substance P, neurokinin A, and neurokinin B) as well as βA-NKA in an isolated human colon. In conclusion, the novel NK(2)-receptor antagonist TAK-480 improved visceral hypersensitivity and accelerated defecation without causing constipation in experimental animals. Furthermore, the potent functional blockade of NK(2) receptors in human colon might suggest the potential effectiveness of TAK-480 in IBS patients.

  6. Patch Test Results with Standard and Cosmetic Series in Patients with Suspected Cosmetic-Induced Contact Dermatitis

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    Şenay Hacıoğlu

    2010-12-01

    Full Text Available Background and Design: Our aim was to evaluate the hypersensitivity to cosmetic chemicals in patients with clinically suspected cosmetic-induced contact dermatitis in Bursa and the South Marmara Region (Turkey by patch testing with standard and cosmetic series.Material and Method: Seventy-three patients with clinically suspected contact dermatitis due to cosmetics were patch tested by the European standard series and cosmetic series. The patch test results were analyzed as percentages. x2 test was used to demonstrate the relationship between cosmetic products and cosmetic allergens.Results: 90.4% of patients in our study group were female and 9.6% were male; the median age was 37.5 (range 16-71 years. The most commonly involved parts of the body were the face (49.3%, hands (16.4%, periocular region (6.8%, lips (6.8%, and the neck (5.5%. The most common offending cosmetic products causing allergic contact dermatitis were soaps and cleansing lotions (32.8%, moisturizer creams (21.9%, make-up (15.0%, and hair dyes (9.6%. 41.0% of patients showed positive reaction to at least one cosmetic allergen included in either standard or cosmetic series. The cosmetic allergens in the standard series and the rates of positivity were as follows: fragrance mix (6.8%, lanolin alcohols (5.5%, paraphenylenedaimine (2.7%, colophony (1.4%, paraben mix (1.4%, formaldehyde (1.4%, and methylchloroisothiazolinone (Kathon CG in descending order. The most common offending cosmetic allergen groups were preservatives (21.9%, antioxidants (8.2% and fragrances (6.8%. Conclusion: Allergic or irritant contact dermatitis due to cosmetics should be considered in cases of eczema involving face, neck, eyelids, lips, scalp or hands. Patch testing with cosmetic series beside standard series would be more helpful in detecting the responsible allergen(s.

  7. Activation of the RAGE/STAT3 Pathway in the Dorsal Root Ganglion Contributes to the Persistent Pain Hypersensitivity Induced by Lumbar Disc Herniation.

    Science.gov (United States)

    Zhang, Xin-Sheng; Li, Xiao; Luo, Hai-Jie; Huang, Zhu-Xi; Liu, Cui-Cui; Wan, Qing; Xu, Shu-Wei; Wu, Shao-Ling; Ke, Song-Jian; Ma, Chao

    2017-07-01

    Clinically, chronic low back pain and sciatica associated with lumbar disc herniation (LDH) is a common musculoskeletal disorder. Due to the unawareness of detailed mechanisms, it is difficult to get an effective therapy. The aim of the present study was to identify the role of the RAGE/STAT3 pathway in the dorsal root ganglion (DRG) on the formation and development of persistent pain hypersensitivity induced by LDH. Controlled animal study. University laboratory. After LDH induced by implantation of autologous nucleus pulposus (NP, harvested from animal tail) on the left L5 nerve root was established, mechanical thresholds and electrophysiological tests were conducted at relevant time points during an observation period of 28 days. Protein levels and localization of RAGE and p-STAT3 were performed by using Western blotting and immunohistochemistry, respectively. LDH induced persistent pain hypersensitivity, increased excitability of DRG neurons, and upregulated the expression of RAGE and p-STAT3 in the DRG. Consecutive injection of both RAGE antagonist FPS-ZM1 (i.t.) and STAT3 activity inhibitor S3I-201 (i.t.) inhibited the enhanced excitability of DRG neurons and mechanical allodynia induced by NP implantation. Furthermore, local knockdown of STAT3 by intrathecal injection of AAV-Cre-GFP into STAT3flox/flox mice markedly alleviated NP implantation-induced mechanical allodynia in mice. Importantly, the expression of p-STAT3 was colocalized with that of RAGE in the DRG and inhibition of RAGE with FPS-ZM1 prevented NP implantation-induced STAT3 activation. More underlying mechanism(s) of the role of the RAGE/STAT3 pathway on the formation and development of persistent pain hypersensitivity induced by LDH will be needed to be explored in future research. These findings suggest activation of the RAGE/STAT3 pathway plays a critical role in persistent pain induced by LDH, and this pathway may represent novel therapeutic targets for the treatment of LDH-induced

  8. De novo foliar transcriptome of Chenopodium amaranticolor and analysis of its gene expression during virus-induced hypersensitive response.

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    Yongqiang Zhang

    Full Text Available BACKGROUND: The hypersensitive response (HR system of Chenopodium spp. confers broad-spectrum virus resistance. However, little knowledge exists at the genomic level for Chenopodium, thus impeding the advanced molecular research of this attractive feature. Hence, we took advantage of RNA-seq to survey the foliar transcriptome of C. amaranticolor, a Chenopodium species widely used as laboratory indicator for pathogenic viruses, in order to facilitate the characterization of the HR-type of virus resistance. METHODOLOGY AND PRINCIPAL FINDINGS: Using Illumina HiSeq™ 2000 platform, we obtained 39,868,984 reads with 3,588,208,560 bp, which were assembled into 112,452 unigenes (3,847 clusters and 108,605 singletons. BlastX search against the NCBI NR database identified 61,698 sequences with a cut-off E-value above 10(-5. Assembled sequences were annotated with gene descriptions, GO, COG and KEGG terms, respectively. A total number of 738 resistance gene analogs (RGAs and homology sequences of 6 key signaling proteins within the R proteins-directed signaling pathway were identified. Based on this transcriptome data, we investigated the gene expression profiles over the stage of HR induced by Tobacco mosaic virus and Cucumber mosaic virus by using digital gene expression analysis. Numerous candidate genes specifically or commonly regulated by these two distinct viruses at early and late stages of the HR were identified, and the dynamic changes of the differently expressed genes enriched in the pathway of plant-pathogen interaction were particularly emphasized. CONCLUSIONS: To our knowledge, this study is the first description of the genetic makeup of C. amaranticolor, providing deep insight into the comprehensive gene expression information at transcriptional level in this species. The 738 RGAs as well as the differentially regulated genes, particularly the common genes regulated by both TMV and CMV, are suitable candidates which merit further

  9. Pharmacogenetics of hypersensitivity drug reactions.

    Science.gov (United States)

    Negrini, Simone; Becquemont, Laurent

    2017-04-01

    Adverse drug reactions are a significant cause of morbidity and mortality and represent a major burden on the healthcare system. Some of those reactions are immunologically mediated (hypersensitivity reactions) and can be clinically subdivided into two categories: immediate reactions (IgE-related) and delayed reactions (T-cell-mediated). Delayed hypersensitivity reactions include both systemic syndromes and organ-specific toxicities and can be triggered by a wide range of chemically diverse drugs. Recent studies have demonstrated a strong genetic association between human leukocyte antigen alleles and susceptibility to delayed drug hypersensitivity. Most notable examples include human leukocyte antigen (HLA)-B*57:01 allele and abacavir hypersensitivity syndrome or HLA-B*15:02 and HLA-B*58:01 alleles related to severe cutaneous reactions induced by carbamazepine and allopurinol, respectively. This review aims to explore our current understanding in the field of pharmacogenomics of HLA-associated drug hypersensitivities and its translation into clinical practice for predicting adverse drug reactions. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  10. Apical clearance rigid contact lenses induce corneal steepening.

    Science.gov (United States)

    Swarbrick, Helen A; Hiew, Ross; Kee, Ai Vy; Peterson, Sophia; Tahhan, Nina

    2004-06-01

    Anecdotal reports suggest that steeply fitted rigid contact lenses can induce corneal steepening and myopic shifts in refraction. This study investigated changes in corneal topography, corneal thickness, and refraction after short-term wear of apical clearance lenses. : Ten young adults participated in the study in which apical clearance lenses (Conoid, Hydron Pty. Ltd., Frenchs Forest, NSW, Australia), fitted approximately 0.3 mm steeper than the flattest keratometric reading, were worn for 4 h. A polymethyl methacrylate (PMMA) lens was worn in one eye, and a Boston XO lens (Bausch & Lomb, Rochester, NY) was worn in the other. Lenses were nonfenestrated in the first trial, and a single midperipheral fenestration was incorporated for a second trial. Corneal topography was monitored using the EyeSys topographic analysis system (EyeSys Vision, Inc., Houston, TX); central corneal thickness was quantified using ultrasonic pachometry; and refraction and anterior ocular response were also monitored. Significant central corneal edema (8.2 +/- 2.2%) was demonstrated in the PMMA lens-wearing eye only. Fenestration did not reduce the edema response. We found significant corneal steepening over a 5- to 6-mm central zone, which was more pronounced in the PMMA lens-wearing eye and was modified by lens fenestration. The curvature changes altered central corneal shape from prolate (Q = -0.06 +/- 0.10) to oblate (Q = -0.26 +/- 0.31). A slight myopic shift in refraction (-0.38 +/- 0.60 D) was found with the PMMA lenses only. : Apical clearance lenses induce corneal steepening after short-term wear. Although corneal molding is implicated as the primary factor driving the shape change, corneal edema and postlens tear film pressures can modify this response.

  11. Experimental periodontal disease. Immediate hypersensitivity.

    Science.gov (United States)

    Asaro, J P; Nisengard, R; Beutner, E H; Neiders, M

    1983-01-01

    Immediate hypersensitivity reactions were induced in the periodontium and skin of monkeys sensitized with novo alcalase. Animals were challenged in the gingival papillae with 0.1, 1.0, and 10 micrograms of antigen for 1, 3, 5, or 7 consecutive days prior to sacrifice. At the same time, skin sites were challenged with 1 microgram of antigen. With repetitive immediate hypersensitivity reactions, the inflammatory infiltrate changed from one characterized by polymorphonuclear leukocytes to one characterized by plasma cells and lymphocytes. The repetitive gingival exposure to bacterial antigens which occur in periodontal disease could lead to repetitive immediate hypersensitivity reactions. Such reactions could play a role in the histopathology of human periodontal disease.

  12. Nav1.9 Channel Contributes to Mechanical and Heat Pain Hypersensitivity Induced by Subacute and Chronic Inflammation

    OpenAIRE

    Stéphane Lolignier; Muriel Amsalem; François Maingret; Françoise Padilla; Mélanie Gabriac; Eric Chapuy; Alain Eschalier; Patrick Delmas; Jérôme Busserolles

    2011-01-01

    Inflammation is known to be responsible for the sensitization of peripheral sensory neurons, leading to spontaneous pain and invalidating pain hypersensitivity. Given its role in regulating neuronal excitability, the voltage-gated Nav1.9 channel is a potential target for the treatment of pathological pain, but its implication in inflammatory pain is yet not fully described. In the present study, we examined the role of the Nav1.9 channel in acute, subacute and chronic inflammatory pain using ...

  13. Contact lens management of aniseikonia and photophobia induced by trauma.

    Science.gov (United States)

    Migneco, Mary K

    2005-11-01

    To describe a case of a contact lens fitting to relieve aniseikonia and photophobia resulting from trauma. A 61-year-old man suffered a blunt injury to his left eye resulting in glaucoma and a traumatic cataract with a fixed pupil and iris defects. A vitrectomy, lensectomy, and iris repair were performed leaving him with significant anisometropia. The patient was fitted with a prosthetic contact lens. Contact lenses can provide significant visual improvement in cases of aniseikonia and photophobia.

  14. Cutaneous Manifestation of Drug Allergy and Hypersensitivity.

    Science.gov (United States)

    Zalewska-Janowska, Anna; Spiewak, Radoslaw; Kowalski, Marek L

    2017-02-01

    Drug hypersensitivity reactions may manifest with either organ-specific or systemic symptoms, but cutaneous eruptions are the most common manifestations. Different medications may cause identical skin symptoms, whereas hypersensitivity to a single drug may manifest with various patterns of symptoms depending on the pathomechanism of hypersensitivity. Drug reactions should be also taken into account in the differential diagnosis of numerous skin rashes. Analysis of morphology of drug-induced lesions, about potential immunologic or nonimmunological mechanisms, is important for the final diagnosis. Thus, here the authors present a morphologic approach to the diagnosis of cutaneous drug-induced eruptions. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. 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

    2016-01-01

    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. PMID:27399778

  16. Assessment of IgE binding to native and hydrolyzed soy protein in serum obtained from dogs with experimentally induced soy protein hypersensitivity.

    Science.gov (United States)

    Serra, Montserrat; Brazís, Pilar; Fondati, Alessandra; Puigdemont, Anna

    2006-11-01

    To assess binding of IgE to native, whole hydrolyzed, and separated hydrolyzed fractions of soy protein in serum obtained from dogs with experimentally induced soy protein hypersensitivity. 8 naïve Beagles (6 experimentally sensitized to native soy protein and 2 control dogs). 6 dogs were sensitized against soy protein by administration of allergens during a 90-day period. After the sensitization protocol was completed, serum concentrations of soy-specific IgE were measured and intradermal skin tests were performed in all 6 dogs to confirm that the dogs were sensitized against soy protein. Serum samples from each sensitized and control dog underwent western blot analysis to assess the molecular mass band pattern of the different allergenic soy fractions and evaluate reactivities to native and hydrolyzed soy protein. In sera from sensitized dogs, a characteristic band pattern with 2 major bands (approx 75 and 50 kd) and 2 minor bands (approx 31 and 20 kd) was detected, whereas only a diffuse band pattern associated with whole hydrolyzed soy protein was detected in the most reactive dog. Reactivity was evident only for the higher molecular mass peptide fraction. In control dogs, no IgE reaction to native or hydrolyzed soy protein was detected. Data suggest that the binding of soy-specific IgE to the hydrolyzed soy protein used in the study was significantly reduced, compared with binding of soy-specific IgE to the native soy protein, in dogs with experimentally induced soy hypersensitivity.

  17. The long and winding road: contact lens-induced ptosis.

    Science.gov (United States)

    Tossounis, Charalambos M; Saleh, George M; McLean, Chris J

    2007-01-01

    Intrapalpebral migration is a rare complication of hard contact lens use. We report a case of a 52-year-old man who presented with right upper eyelid ptosis and requested cosmetic correction. He had no ocular history apart from myopia, which was corrected with the use of hard contact lenses. Prior to the ptosis he recalled losing his right contact lens during a bout of sneezing. He replaced the missing lens and continued to wear contact lenses as usual. After careful clinical examination, an ipsilateral small, mobile eyelid mass was detected, and orbital MRI verified the suspected presence of a hard contact lens. Following surgical removal and ptosis correction, the patient made a full recovery. The phenomenon of hard contact lens migration in the periocular tissues has been reported in the literature before, but most patients experienced symptoms of variable severity. In this patient, however, there were no symptoms to indicate the presence of a contact lens. This case highlights the importance of including intrapalpebral contact lens migration in the differential diagnosis of an eyelid mass or ptosis in patients.

  18. 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.

  19. MicroRNA-182-5p Regulates Nerve Injury-induced Nociceptive Hypersensitivity by Targeting Ephrin Type-b Receptor 1.

    Science.gov (United States)

    Zhou, Xuelong; Zhang, Chenjing; Zhang, Congjuan; Peng, Yunan; Wang, Yin; Xu, Hongjiao

    2017-05-01

    The authors and others have previously shown that the up-regulation of spinal ephrin type-b receptor 1 plays an essential role in the pathologic process of nerve injury-induced nociceptive hypersensitivity, but the regulatory mechanism remains unclear. Radiant heat and von Frey filaments were applied to assess nociceptive behaviors. Real-time quantitative polymerase chain reaction, Western blotting, fluorescence in situ hybridization, immunofluorescence, immunohistochemistry, dual-luciferase reporter gene assays, recombinant lentivirus, and small interfering RNA were used to characterize the likely mechanisms. Periphery nerve injury induced by chronic constriction injury of the sciatic nerve significantly reduced spinal microRNA-182-5p (miR-182-5p) expression levels, which were inversely correlated with spinal ephrin type-b receptor 1 expression (R = 0.90; P type-b receptor 1 (recombinant lentiviruses containing pre-microRNA-182: 1.91 ± 0.34 vs. 1.24 ± 0.31, n = 4; miR-182-5p mimic: 2.90 ± 0.48 vs. 1.51 ± 0.25, n = 4). In contrast, the down-regulation of spinal miR-182-5p facilitated the nociceptive behaviors induced by sciatic nerve injury and increased the expression of spinal ephrin type-b receptor 1 (1.0 ± 0.26 vs. 1.74 ± 0.31, n = 4). Moreover, the down-regulation of miR-182-5p and up-regulation of ephrin type-b receptor 1 caused by sciatic nerve injury were mediated by the N-methyl-D-aspartate receptor. Collectively, our findings reveal that the spinal ephrin type-b receptor 1 is regulated by miR-182-5p in nerve injury-induced nociceptive hypersensitivity.

  20. Outcome following surgery for contact lens-induced ptosis.

    Science.gov (United States)

    de Silva, D Julian; Collin, J Richard O

    2011-01-01

    To assess the outcome of surgery in patients with a history of contact lens wear. Retrospective, comparative interventional case series. A total of 419 patients underwent ptosis surgery during a 1-year period (2005-2006) at Moorfields Eye Hospital. Those included in this study had a diagnosis of aponeurotic ptosis and history of contact lens wear. The outcome was considered a success if the following criteria were met: 1) a margin reflex distance of between 3 and 5 mm, 2) an interlid difference of 1 mm or less, and 3) absence of redo surgery. Thirty patients (7.2%) were identified with a history of contact lens wear and were matched against a control group of 46 patients. The mean margin-reflex distance at presentation was 0.5 ± 2.4 mm. This equated to a ptosis graded as mild (≥1.5 mm) for 32% of patients, moderate (0.5-1.0 mm) for 29%, and severe (≤0.0 mm) for 39%, with similar proportions in the control group (36% mild, 39% moderate, and 25% severe). The power of the refractive correction (p contact lens-related ptosis was related to the degree of myopia and the age of the patient but not to the duration of contact lens wear. There was a higher level of failure and requirement for redo surgery in patients with contact lens-related ptosis compared with matched controls.

  1. Functional regions of HpaXm as elicitors with specific heat tolerance induce the hypersensitive response or plant growth promotion in nonhost plants.

    Science.gov (United States)

    Liu, Yue; Zhou, Xiaoyun; Liu, Wenbo; Xiong, Xiaohui; Lv, Chuyang; Zhou, Xiang; Miao, Weiguo

    2018-01-01

    HpaXm produced by the cotton leaf blight bacterium Xanthomonas citri subsp. malvacearum is a novel harpin elicitor of the induced hypersensitive response (HR) in tobacco. We investigated whether fragments of HpaXm, compared with fragments of Hpa1Xoo, are sufficient for HR or plant growth promotion (PGP) elicitation using four synthetic peptides (HpaXm35-51, HpaXm10-39, Hpa1Xoo36-52 and Hpa1Xoo10-40). We also heated the fragments to determine the heat tolerance of the functional fragments. HpaXm35-51 and Hpa1Xoo36-52 induced hypersensitive response (HR). Bursts of reactive oxygen intermediates (ROI) induced by HpaXm35-51 and Hpa1Xoo36-52 were earlier and stronger than those induced by HpaXm and Hpa1Xoo. In plants treated with HpaXm35-51 or Hpa1Xoo36-52, the expression of the HR marker genes Hin1 and Hsr203J and the active oxygen metabolism related gene AOX were significantly upregulated. These findings suggest that the predicted α-helical structures of the HpaXm35-51 and Hpa1Xoo36-52 fragments are crucial for HR. PGP result by soaking seeds in unheated/heated HpaXm10-39 or Hpa1Xoo10-40 solution prior to transfer, which obviously enhances root growth and the aerial parts of plants. The PGP related gene NtEXP6 was greatly enhanced when plants were sprayed with a solution of HpaXm10-39 or Hpa1Xoo10-40; heated fragment treatments induced higher levels of NtEXP6 expression than unheated HpaXm fragments. In addition, HR marker genes induced by the heated fragments had lower expression levels than when induced with unheated HpaXm fragments. Moreover, the expression levels of HR marker genes and PGP related genes induced by treatment with Hpa1Xoo fragments before or after heating were the opposite of those induced by HpaXm fragments. Different functional fragments of harpin and different harpins with the same functional region have different degrees of heat tolerance. Therefore, the heat resistance of harpin is conservative, but the degree of heat tolerance of the

  2. Frequency of the HLA-B*1502 allele contributing to carbamazepine-induced hypersensitivity reactions in a cohort of Malaysian epilepsy patients.

    Science.gov (United States)

    Then, Sue-Mian; Rani, Zam Zureena Mohd; Raymond, Azman Ali; Ratnaningrum, Safrina; Jamal, Rahman

    2011-09-01

    We describe the association of the HLA-B*1502 allele in 27 epilepsy patients (19 Malays, 8 Chinese) treated with carbamazepine (CBZ) at the UKM Medical Center (UKMMC), 6 with CBZ-Steven Johnson Syndrome (CBZ-SJS), 11 with CBZ-induced rash, 2 with suspected phenytoin-induced rash and 8 negative controls. Our study showed that 10 (6 Malay, 4 Chinese) patients were positive for HLA-B*1502. Out of the 10 patients, six were confirmed to have CBZ-SJS (p = 0.0006), while four patients developed a skin rash. However there were 6 Malay patients and 1 Chinese patient that developed a skin rash after CBZ administration who were not positive for the allele, indicating that there might be more that one allele associated with CBZ-induced hypersensitivity. Another 2 patients were suspected of having phenytoin-induced rash, instead of CBZ, and these patients did not have HLA-B*1502. In conclusion, this study confirmed the association of HLA-B*1502 with CBZ-SJS among Malaysian epilepsy patients, however there might be other genes that could be responsible for the CBZ-induced rash.

  3. 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.

  4. Role of voltage gated Ca2+ channels in rat visceral hypersensitivity change induced by 2,4,6-trinitrobenzene sulfonic acid.

    Science.gov (United States)

    Qian, Aihua; Song, Dandan; Li, Yong; Liu, Xinqiu; Tang, Dong; Yao, Weiyan; Yuan, Yaozong

    2013-03-28

    Visceral pain is common symptom involved in many gastrointestinal disorders such as inflammatory bowel disease. The underlying molecular mechanisms remain elusive. We investigated the molecular mechanisms and the role for voltage gated calcium channel (VGCC) in the pathogenesis in a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced visceral inflammatory hypersensitivity. Using Agilent cDNA arrays, we found 172 genes changed significantly in dorsal root ganglia (DRG) of TNBS treated rats. Among these changed genes, Cav1.2 and Cav2.3 were significantly up-regulated. Then the RT-PCR and Western blot further confirmed the up-regulation of Cav1.2 and Cav2.3. The whole cell patch clamp recording of acutely dissociated colonic specific DRG neurons showed that the peak IBa density was significantly increased in colonic neurons of TNBS treated rats compared with control rats (-127.82 ± 20.82 pA/pF Vs -91.67 ± 19.02 pA/pF, n = 9, *P type of calcium currents with the corresponding selective channel blockers, we found that L-type (-38.56 ± 3.97 pA/pF Vs -25.75 ± 3.35 pA/pF, n = 9, * P type (-13.31 ± 1.36 pA/pF Vs -8.60 ± 1.25 pA/pF, n = 9, * P type antagonist (nimodipine) and R-type antagonist (SNX-482) with intrathecal injection attenuates visceral pain in TNBS induced inflammatory visceral hypersensitivity. Cav1.2 and Cav2.3 in colonic primary sensory neurons play an important role in visceral inflammatory hyperalgesia, which maybe the potential therapeutic targets.

  5. Hard contact lens-induced metabolic changes in rabbit corneas.

    Science.gov (United States)

    Tsubota, K; Kenyon, K R; Cheng, H M

    1989-11-01

    The biochemistry of contact lens-cornea interaction is not well understood, although previous studies have suggested that corneal metabolic changes may be the underlying factor in morphological alterations. Using a rabbit model, this interaction has been examined with 31P nuclear magnetic resonance (NMR) spectroscopy, which detects signals principally from the epithelium. The examination was supplemented with electron microscopy and histochemistry. Polymethylmethacrylate lenses caused reversible changes, including activation of anaerobic glycolysis and disturbance of membrane metabolite levels. These changes were far more severe than those occurring during prolonged eye closure. There appears to be an association between cellular deterioration and loss of membrane metabolites. On the other hand, oxygen-permeable silicone lenses allowed maintenance of nearly normal metabolic patterns. These results show multifaceted corneal response to hard contact lens wear.

  6. Does allergen-specific immunotherapy induce contact allergy to aluminium?

    Science.gov (United States)

    Netterlid, Eva; Hindsén, Monica; Siemund, Ingrid; Björk, Jonas; Werner, Sonja; Jacobsson, Helene; Güner, Nuray; Bruze, Magnus

    2013-01-01

    Persistent, itching nodules have been reported to appear at the injection site after allergen-specific immuno-therapy with aluminium-precipitated antigen extract, occasionally in conjunction with contact allergy to aluminium. This study aimed to quantify the development of contact allergy to aluminium during allergen-specific immunotherapy. A randomized, controlled, single-blind multicentre study of children and adults entering allergen-specific immunotherapy was performed using questionnaires and patch-testing. A total of 205 individuals completed the study. In the 3 study groups all subjects tested negative to aluminium before allergen-specific immunotherapy and 4 tested positive after therapy. In the control group 4 participants tested positive to aluminium. Six out of 8 who tested positive also had atopic dermatitis. Positive test results were found in 5/78 children and 3/127 adults. Allergen-specific immunotherapy was not shown to be a risk factor for contact allergy to aluminium. Among those who did develop aluminium allergy, children and those with atopic dermatitis were more highly represented.

  7. The Major Soybean Allergen Gly m Bd 28K Induces Hypersensitivity Reactions in Mice Sensitized to Cow's Milk Proteins.

    Science.gov (United States)

    Candreva, Ángela María; Smaldini, Paola Lorena; Curciarello, Renata; Fossati, Carlos Alberto; Docena, Guillermo Horacio; Petruccelli, Silvana

    2016-02-24

    Reactions to soy have been reported in a proportion of patients with IgE-mediated cow's milk allergy (CMA). In this work, we analyzed if Gly m Bd 28K/P28, one of the major soybean allergens, is a cross-reactive allergen with cow milk proteins (CMP). We showed that P28 was recognized by IgE sera from CMA patients and activated human peripheral basophils degranulation. Moreover, IgE sera of mice exclusively sensitized to CMP recognized P28. Splenocytes from sensitized animals secreted IL-5 and IL-13 when incubated with CMP or soy proteins, but only IL-13 when treated with P28. In addition, a skin test was strongly positive for CMP and weakly positive for P28. Remarkably, milk-sensitized mice showed hypersensitivity symptoms following sublingual challenge with P28 or CMP. With the use of bioinformatics' tools seven putative cross-reactive epitopes were identified. In conclusion, using in vitro and in vivo tests we demonstrated that P28 is a novel cross-reactive allergen with CMP.

  8. Epidemiology of contact lens-induced infiltrates: an updated review.

    Science.gov (United States)

    Steele, Kelsy R; Szczotka-Flynn, Loretta

    2017-09-01

    Corneal infiltrative events (CIEs) are well established as a risk associated with soft contact lens wear. The incidence of symptomatic CIEs during extended soft lens wear ranges from 2.5 to six per cent; when asymptomatic CIEs are included, the incidence can be as high as 20-25 per cent. In daily soft lens wear, the annual incidence of symptomatic CIEs is about three per cent. There are various accepted methods of categorising CIEs, and a scoring system based on clinical signs and symptoms is a good approach to grade severity. Lens-related risk factors include extended wear, silicone hydrogel material, the use of multipurpose solutions, bacterial bioburden and reusable lenses. Recent studies report that daily disposable lenses reduce the risk of CIEs. © 2017 Optometry Australia.

  9. ERK MAP kinase activation in spinal cord regulates phosphorylation of Cdk5 at serine 159 and contributes to peripheral inflammation induced pain/hypersensitivity.

    Directory of Open Access Journals (Sweden)

    Xiaoqin Zhang

    Full Text Available Cyclin-dependent kinase 5 is a proline-directed serine/threonine kinase and its activity participates in the regulation of nociceptive signaling. Like binding with the activators (P35 or P25, the phosphorylation of Cdk5 plays a critical role in Cdk5 activation. However, it is still unclear whether Cdk5 phosphorylation (p-Cdk5 contributes to pain hyperalgesia. The aim of our current study was to identify the roles of p-Cdk5 and its upstream regulator in response to peripheral inflammation. Complete Freund's adjuvant (CFA injection induced acute peripheral inflammation and heat hyperalgesia, which was accompanied by sustained increases in phospho-ERK1/2 (p-ERK1/2 and phospho-Cdk5(S159 (p-Cdk5(S159 in the spinal cord dorsal horn (SCDH. CFA-induced p-ERK primarily colocalized with p-Cdk5(S159 in superficial dorsal horn neurons. Levels in p-ERK and p-Cdk5 were also increased in the 2(nd phase of hyperalgesia induced by formalin injection, which can produce acute and tonic inflammatory pain. MAP kinase kinase inhibitor U0126 intrathecal delivery significantly suppressed the elevation of p-Cdk5(S159, Cdk5 activity and pain response behavior (Heat hyperalgesia, Spontaneous flinches induced by CFA or formalin injection. Cdk5 inhibitor roscovitine intrathecal administration also suppressed CFA-induced heat hyperalgesia and Cdk5 phosphorylation, but did not attenuate ERK activation. All these findings suggested that p-Cdk5(S159 regulated by ERK pathway activity may be a critical mechanism involved in the activation of Cdk5 in nociceptive spinal neurons contributes to peripheral inflammatory pain hypersensitivity.

  10. 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.

  11. HLA-B allele and haplotype diversity among Thai patients identified by PCR-SSOP: evidence for high risk of drug-induced hypersensitivity

    Directory of Open Access Journals (Sweden)

    CHONLAPHAT eSUKASEM

    2015-01-01

    Full Text Available BACKGROUND: There are 3 classes of HLA molecules; HLA class I, II and III, of which different classes have different functions. HLA-B gene which belongs to HLA class I play an important role predicting drug hypersensitivity. MATERIALS AND METHODS: Nine hundred and eighty-six Thai subjects who registered at a pharmacogenomics laboratory were determined for HLA-B genotype using a two-stage sequence-specific oligonucleotide probe system (PCR-SSOP. RESULTS: In this study, HLA-B alleles did not deviate from Hardy-Weinberg equilibrium (P>0.05. The most common HLA-B alleles observed in this population were HLA-B*46:01 (11.51%, HLA-B*58:01 (8.62%, HLA-B*40:01 (8.22%, HLA-B*15:02 (8.16% and HLA-B*13:01 (6.95%. This finding revealed that HLA-B allele frequency in the Thai population was consistent with the Chinese population (p>0.05, however, differed from the Malaysian population (p<0.05. The top five HLA-B genotypes were HLA-B*40:01/46:01 (2.13%, HLA-B*46:01/46:01 (2.03%, HLA-B*40:01/58:01 (2.03%, HLA-B*46:01/58:01 (1.93% and HLA-B*15:02/46:01 (1.83%. This study found that 15.92% of Thai subjects carry HLA-B*15:02, which has been associated with carbamazepine-induced severe cutaneous adverse drug reactions (SCARs. Moreover, 16.33% of Thai subjects carry the HLA-B*58:01 allele, which has been associated with allopurinol-induced SCARs. CONCLUSION: This study demonstrates a high diversity of HLA-B polymorphisms in this Thai population. The high frequency of HLA-B pharmacogenomic markers in the population emphasizes the importance of such screening to predict/avoid drug hypersensitivity.

  12. 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.

  13. Artificial Agrobacterium tumefaciens strains exhibit diverse mechanisms to repress Xanthomonas oryzae pv. oryzae-induced hypersensitive response and non-host resistance in Nicotiana benthamiana.

    Science.gov (United States)

    Li, Wen; Cao, Jia-Yi; Xu, You-Ping; Cai, Xin-Zhong

    2017-05-01

    Xanthomonas oryzae pv. oryzae (Xoo) rapidly triggers a hypersensitive response (HR) and non-host resistance in its non-host plant Nicotiana benthamiana. Here, we report that Agrobacterium tumefaciens strain GV3101 blocks Xoo-induced HR in N. benthamiana when pre-infiltrated or co-infiltrated, but not when post-infiltrated at 4 h after Xoo inoculation. This suppression by A. tumefaciens is local and highly efficient to Xoo. The HR-inhibiting efficiency of A. tumefaciens is strain dependent. Strain C58C1 has almost no effect on Xoo-induced HR, whereas strains GV3101, EHA105 and LBA4404 nearly completely block HR formation. Intriguingly, these three HR-inhibiting strains employ different strategies to repress HR. Strain GV3101 displays strong antibiotic activity and thus suppresses Xoo growth. Comparison of the genotype and Xoo antibiosis activity of wild-type A. tumefaciens strain C58 and a set of C58-derived strains reveals that this Xoo antibiosis activity of A. tumefaciens is negatively, but not solely, regulated by the transferred-DNA (T-DNA) of the Ti plasmid pTiC58. Unlike GV3101, strains LBA4404 and EHA105 exhibit no significant antibiotic effect on Xoo, but rather abolish hydrogen peroxide accumulation. In addition, expression assays indicate that strains LBA4404 and EHA105 may inhibit Xoo-induced HR by suppression of the expression of Xoo type III secretion system (T3SS) effector genes hpa1 and hrpD6. Collectively, our results unveil the multiple levels of effects of A. tumefaciens on Xoo in N. benthamiana and provide insights into the molecular mechanisms underlying the bacterial antibiosis of A. tumefaciens and the non-host resistance induced by Xoo. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  14. Cladosporium fulvum CfHNNI1 induces hypersensitive necrosis, defence gene expression and disease resistance in both host and nonhost plants.

    Science.gov (United States)

    Cai, Xin-Zhong; Zhou, Xin; Xu, You-Ping; Joosten, Matthieu H A J; de Wit, Pierre J G M

    2007-05-01

    Nonhost resistance as a durable and broad-spectrum defence strategy is of great potential for agricultural applications. We have previously isolated a cDNA showing homology with genes encoding bZIP transcription factors from tomato leaf mould pathogen Cladosporium fulvum. Upon expression, the cDNA results in necrosis in C. fulvum host tomato and nonhost tobacco plants and is thus named CfHNNI1 (for C . f ulvum host and nonhost plant necrosis inducer 1). In the present study we report the induction of necrosis in a variety of nonhost plant species belonging to three families by the transient in planta expression of CfHNNI1 using virus-based vectors. Additionally, transient expression of CfHNNI1 also induced expression of the HR marker gene LeHSR203 and greatly reduced the accumulation of recombinant Potato virus X. Stable CfHNNI1 transgenic tobacco plants were generated in which the expression of CfHNNI1 is under the control of the pathogen-inducible hsr203J promoter. When infected with the oomycetes pathogen Phytophthora parasitica var. nicotianae, these transgenic plants manifested enhanced expression of CfHNNI1 and subsequent accumulation of CfHNNI1 protein, resulting in high expression of the HSR203J and PR genes, and strong resistance to the pathogen. The CfHNNI1 transgenic plants also exhibited induced resistance to Pseudomonas syringae pv. tabaci and Tobacco mosaic virus. Furthermore, CfHNNI1 was highly expressed and the protein was translocated into plant cells during the incompatible interactions between C. fulvum and host and nonhost plants. Our results demonstrate that CfHNNI1 is a potential general elicitor of hypersensitive response and nonhost resistance.

  15. 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 ... electromagnetic fields such as mobile phones and their base stations, mobile phone jammers, laptop ... dental amalgams cause health problems in the majority of the population, the effects of dental amalgam on ...

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

    African Journals Online (AJOL)

    Department of Oral Medicine, Diagnosis and Radiology, Dayananda Sagar College of Dental Sciences and Hospital, ... black patch in the right side of the mouth in the cheek region, ... it, incisional biopsy was done under local anesthesia and.

  17. In vitro surfactant mitigation of gas bubble contact-induced endothelial cell death.

    Science.gov (United States)

    Kobayashi, Shunji; Crooks, Steven D; Eckmann, David M

    2011-01-01

    Interactions of gas embolism bubbles with endothelial cells, as can occur during decompression events or other forms of intravascular gas entry, are poorly characterized. Endothelial cells respond to microbubble contact via mechanotransduction responses that can lead to cell death or aberrant cellular function. Cultured bovine aortic endothelial cells were individually contacted with microbubbles. Cells were loaded with fluorescent dyes indicating calcium- and nitric oxide-signaling and cell viability. A surfactant, Pluronic F-127, and/or albumin were added to the culture media. Control experiments utilized calcium-free media as well as probe-poking in place of microbubble contact. We acquired fluorescence microscopy time-lapse images of cell responses to bubble and probe contact and determined contact effects on cell signaling and cell death. Calcium influx was essential for cell death to occur with bubble contact. Bubble contact stimulated extracellular calcium entry without altering nitric oxide levels unless cell death was provoked. Cell responses were independent of bubble contact duration lasting either one or 30 seconds. Microbubble contact provoked cell death over seven times more frequently than micropipette poking. Albumin and the surfactant each attenuated the calcium response to bubble contact and also reduced the lethality of microbubble contact by 67.4% and 76.0%, respectively, when used alone, and by 91.2% when used together. This suggests that surface interactions between the bubble or probe interface and plasma- and cell surface-borne macromolecules differentially modulate the mechanism of calcium trafficking such that microbubble contact more substantially induces cell death or aberrant cellular function. The surfactant findings provide a cytoprotective approach to mitigate this form of mechanical injury.

  18. Virulent ¤Blumeria graminis¤ infection induces penetration susceptibility and suppresses race-specific hypersensitive resistance against avirulent attack in ¤Mla1¤-barley

    DEFF Research Database (Denmark)

    Lyngkjær, M.L.; Carver, T.L.W.; Zeyen, R.J.

    2001-01-01

    Leaves of near isogenic barley lines containing the race-specific resistance alleles. Mla1 or mla1 were subjected to double inoculation treatments with virulent and avirulent Blumeria graminis isolates. Attack by the avirulent isolate alone frequently caused hypersensitive death of individual Mla1....... It appears that suppressive factors released during virulent inducer infection prevented the hypersensitive epidermal cell death that normally is induced by the race-specific avirulence elicitor. However, suppression of Mla1 race-specific resistance vas confined to the epidermis. The presence of successful...... avirulent fungus infection of the epidermis often: led to the death of the underlying mesophyll cells, thus generating a novel cellular response phenotype in B. graminis attacked Mla1 barley. (C) 2001 Academic Press....

  19. Hypersensitivity to Suture Anchors

    OpenAIRE

    Masafumi Goto; Masafumi Gotoh; Yasuhiro Mitsui; Ryo Tanesue; Takahiro Okawa; Fujio Higuchi; Naoto Shiba

    2013-01-01

    Hypersensitivity to suture anchor is extremely rare. Herein, we present a case in which hypersensitivity to suture anchor was strongly suspected. The right rotator cuff of a 50-year-old woman was repaired with a metal suture anchor. Three weeks after the surgery, she developed erythema around her face, trunk, and hands, accompanied by itching. Infection was unlikely because no abnormalities were detected by blood testing or by medical examination. Suspicious of a metallic allergy, a dermatolo...

  20. Epidemiology of dentin hypersensitivity

    OpenAIRE

    Splieth, Christian H.; Tachou, Aikaterini

    2012-01-01

    Objective In contrast to the well-established caries epidemiology, data on dentin hypersensitivity seem to be scarce and contradictory. This review evaluates the available literature on dentin hypersensitivity and assesses its prevalence, distribution, and potential changes. Materials and methods The systematic search was performed to identify and select relevant publications with several key words in electronic databases. In addition, the articles? bibliographies were consulted. Results Prev...

  1. Therapeutic benefits of the methyl donor S-adenosylmethionine on nerve injury-induced mechanical hypersensitivity and cognitive impairment in mice.

    Science.gov (United States)

    Grégoire, Stéphanie; Millecamps, Magali; Naso, Lina; Do Carmo, Sonia; Cuello, A Claudio; Szyf, Moshe; Stone, Laura S

    2017-05-01

    Despite considerable advances in understanding mechanisms involved in chronic pain, effective treatment remains elusive. Comorbid conditions including anxiety, depression, and cognitive impairment further impact quality of life. Chronic pain is associated with reversible changes in brain anatomy and function and with long-term changes in gene expression. Epigenetic mechanisms, including DNA methylation, contribute to wide-spread and long-lasting reprogramming of gene expression. We previously reported decreases in global DNA methylation in the mouse frontal cortex 6 months after induction of neuropathic pain using the spared nerve injury (SNI) model. Here, we examined the therapeutic effect of increasing DNA methylation using the methyl donor S-adenosylmethionine (SAM). S-adenosylmethionine is marketed as a nutritional supplement for a range of conditions including liver disease, depression, osteoarthritis, fibromyalgia, and dementia. Three months after SNI or sham surgery, animals were treated with SAM (20 mg/kg, 3×/week) or saline orally for 4 months, and the impact on sensory, motor, motivational, and cognitive indices was measured. S-adenosylmethionine attenuated SNI-induced mechanical hypersensitivity and reduced active avoidance of mechanical stimuli but had no effect on cold sensitivity or motor capacity. S-adenosylmethionine completely blocked nerve injury-induced cognitive impairment and attenuated SNI-induced decreases in global DNA methylation in the frontal cortex. In summary, chronic oral administration of the methyl donor, SAM, attenuated sensory and cognitive symptoms associated with nerve injury in mice. These effects may be mediated, in part, through modulation of DNA methylation in the central nervous system by systemic administration of the methyl donor SAM.

  2. Daclatasvir and Asunaprevir Combination Therapy-induced Hepatitis and Cholecystitis with Coagulation Disorder due to Hypersensitivity Reactions.

    Science.gov (United States)

    Miyashima, Yuichi; Honma, Yuichi; Miyagawa, Koichiro; Oe, Shinji; Senju, Michio; Shibata, Michihiko; Hiura, Masaaki; Abe, Shintaro; Harada, Masaru

    A 70-year-old woman with chronic hepatitis C was admitted to our hospital due to liver injury, cholecystitis, and disseminated intravascular coagulation with a fever and skin rash. She had been on a combination regimen of daclatasvir and asunaprevir for 2 weeks of a 24-week regimen. Because of the symptoms, laboratory findings, results of a drug-induced lymphocyte stimulation test, and pathological findings of liver biopsy, we diagnosed her with drug-induced liver injury. Although daclatasvir and asunaprevir combination therapy is generally well-tolerated, some serious adverse effects have been reported. Our findings indicate that immunoallergic mechanisms were associated with daclatasvir and asunaprevir-induced liver injury.

  3. Cold and L-menthol-induced sensitization in healthy volunteers--a cold hypersensitivity analogue to the heat/capsaicin model.

    Science.gov (United States)

    Andersen, Hjalte H; Poulsen, Jeppe N; Uchida, Yugo; Nikbakht, Anahita; Arendt-Nielsen, Lars; Gazerani, Parisa

    2015-05-01

    Topical high-concentration L-menthol is the only established human experimental pain model to study mechanisms underlying cold hyperalgesia. We aimed at investigating the combinatorial effect of cold stimuli and topical L-menthol on cold pain and secondary mechanical hyperalgesia. Analogue to the heat-capsaicin model on skin sensitization, we proposed that cold/menthol enhances or prolong L-menthol-evoked sensitization. Topical 40% L-menthol or vehicle was applied (20 minutes) on the volar forearms of 20 healthy females and males (age, 28.7 ± 0.6 years). Cold stimulation of 5°C for 5 minutes was then applied to the treated area 3 times with 40-minute intervals. Cold detection threshold and pain, mechanical hyperalgesia (pinprick), static and dynamic mechanical allodynia (von Frey and brush), skin blood flow (laser speckle), and temperature (thermocamera) were assessed. Cold detection threshold and cold pain threshold (CPT) increased after L-menthol and remained high after the cold rekindling cycles (P menthol evoked secondary hyperalgesia to pinprick (P menthol (P menthol facilitated and prolonged L-menthol-induced cold pain and hyperalgesia. This model may prove beneficial for testing analgesic compounds when a sufficient duration of time is needed to see drug effects on CPT or mechanical hypersensitivity.

  4. 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

  5. Immunization against an IL-6 peptide induces anti-IL-6 antibodies and modulates the Delayed-Type Hypersensitivity reaction in cynomolgus monkeys.

    Science.gov (United States)

    Desallais, Lucille; Bouchez, Caroline; Mouhsine, Hadley; Moreau, Gabriel; Ratsimandresy, Rojo; Montes, Matthieu; Do, Hervé; Quintin-Colonna, Françoise; Zagury, Jean-François

    2016-01-19

    Interleukin-6 (IL-6) overproduction has been involved in the pathogenesis of several chronic inflammatory diseases and the administration of an anti-IL-6 receptor monoclonal antibody has been proven clinically efficient to treat them. However, the drawbacks of monoclonal antibodies have led our group to develop an innovative anti-IL-6 strategy using a peptide-based active immunization. This approach has previously shown its efficacy in a mouse model of systemic sclerosis. Here the safety, immunogenicity, and efficacy of this strategy was assessed in non human primates. No unscheduled death and clinical signs of toxicity was observed during the study. Furthermore, the cynomolgus monkeys immunized against the IL-6 peptide produced high levels of anti-IL-6 antibodies as well as neutralizing antibodies compared to control groups. They also showed an important decrease of the cumulative inflammatory score following a delayed-type hypersensitivity reaction induced by the Tetanus vaccine compared to control groups (minus 57,9%, P = 0.014). These findings are highly significant because the immunizing IL-6 peptide used in this study is identical in humans and in monkeys and this novel anti-IL-6 strategy could thus represent a promising alternative to monoclonal antibodies.

  6. Daclatasvir and Asunaprevir Combination Therapy-induced Hepatitis and Cholecystitis with Coagulation Disorder due to Hypersensitivity Reactions

    OpenAIRE

    Miyashima, Yuichi; Honma, Yuichi; Miyagawa, Koichiro; Oe, Shinji; Senju, Michio; Shibata, Michihiko; Hiura, Masaaki; Abe, Shintaro; Harada, Masaru

    2016-01-01

    A 70-year-old woman with chronic hepatitis C was admitted to our hospital due to liver injury, cholecystitis, and disseminated intravascular coagulation with a fever and skin rash. She had been on a combination regimen of daclatasvir and asunaprevir for 2 weeks of a 24-week regimen. Because of the symptoms, laboratory findings, results of a drug-induced lymphocyte stimulation test, and pathological findings of liver biopsy, we diagnosed her with drug-induced liver injury. Although daclatasvir...

  7. 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

  8. Assessment of corneal morphological changes induced by the use of daily disposable contact lenses.

    Science.gov (United States)

    Del Águila-Carrasco, Antonio J; Domínguez-Vicent, Alberto; Pérez-Vives, Cari; Ferrer-Blasco, Teresa; Montés-Micó, Robert

    2015-02-01

    To assess the effect of different disposable soft contact lenses upon corneal thickness, and upon anterior and posterior corneal curvatures using a dual-Scheimpflug imaging based device. Twenty-eight young, healthy subjects wore four different types of daily disposable soft contact lenses on four different days: Dailies Total1, Proclear 1 Day, Clariti 1-Day and 1-Day Acuvue Moist. The lenses had different material and water content. Pachymetry maps and keratometry values were obtained using the Galilei G4 twice a day: one before putting the lens on and one after an eight-hour period of contact-lens wear. Measurements were also recorded without any contact lenses being worn during a day. Clariti 1-Day lens caused the greatest thickening in the central (8.9±2.8 μm; plenses caused a slight flattening in the anterior corneal curvature, except Clariti 1-Day, which induced a very slight steepening. The four lenses caused a steepening of different magnitude in the posterior corneal curvature. The magnitude of the changes introduced by the use of soft contact lenses over the eight-hour wearing period was rather small. Thus it is probable it will not influence the vision nor the comfort of the subject. Also, variations on corneal parameters seem to depend on the type of contact lens used. Copyright © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  9. Contact lens-induced corneal endothelial polymegathism: functional significance and possible mechanisms.

    Science.gov (United States)

    Connor, C G; Zagrod, M E

    1986-07-01

    The corneal endothelium is principally responsible for maintenance of corneal deturgescence. Therefore, compromise of corneal endothelial functional integrity can result in corneal swelling and opacification. Contact lenses constitute a potential insult to the cornea because their wear reduces the oxygen available to that tissue. It has been reported that contact lens wear induces transient as well as permanent morphologic changes in the corneal endothelium. One of the permanent changes reported is referred to as polymegathism, which is a variation in cell size within the endothelial monolayer. Several investigators have suggested that polymegathism reflects a compromised endothelial functional status. Mechanisms proposed to explain contact lens-induced polymegathism include lactate accumulation, changes in pH, and elevation in CO2 content. We discuss these possibilities as well as speculate that these polymegathous shape changes may be a result of decreased endothelial ATP (adenosine triphosphate) levels and disturbed calcium homeostasis due to corneal endothelial hypoxia.

  10. General aspects of hypersensitivity pneumonitis in Turkey.

    Science.gov (United States)

    Cımrın, Arif Hikmet; Göksel, Ozlem; Demirel, Yavuz Selim

    2010-01-01

    Hypersensitivity pneumonitis prevalence rates are between 5 and 15% of the overall population exposed to known inciting antigens but a small number of cases have been reported from Turkey until now. We aimed to present a broad picture of hypersensitivity pneumonitis in Turkey, thus promoting interest in this relatively common disease in developing countries. Search engines were utilized to retrieve the cases reported from Turkey. Other published journals and meeting abstracts which have not been registered into electronic databases were manually reviewed. Twenty-two cases from 13 reports were characterized by demographics, clinical features, occupational and environmental exposures, diagnostic tools and prognostic data. The majority of the group consisted of women (68.2%) and had a positive history for contact with an avian (59%). Mean exposure period was 69 ± 77.6 months. The most common reported clinical form was chronic hypersensitivity pneumonitis (58.8%). Reticulonodular pattern was the basic pathological finding (45%). Restrictive impairments of the forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLCO) of the lungs were the basic pathologies observed in pulmonary function tests. Interstitial fibrosis was the most common pathological finding (61.5%). Few cases reported with preponderance of chronic hypersensitivity pneumonitis with avian exposure from 70 million populations suggest that many hypersensitivity pneumonitis cases, especially acute forms, have been ignored. Also, hypersensitivity pneumonitis somehow appears to be a neglected occupational disease. The present situation should be considered as a common problem currently faced by developing countries and occupational groups under risk must be investigated promptly.

  11. CXCR4 signaling in macrophages contributes to periodontal mechanical hypersensitivity in Porphyromonas gingivalis-induced periodontitis in mice.

    Science.gov (United States)

    Nagashima, Hidekazu; Shinoda, Masamichi; Honda, Kuniya; Kamio, Noriaki; Watanabe, Masahiro; Suzuki, Tatsuro; Sugano, Naoyuki; Sato, Shuichi; Iwata, Koichi

    2017-01-01

    Background Periodontitis is an inflammatory disease accompanied by alveolar bone loss and progressive inflammation without pain. However, the potential contributors eliminating pain associated with gingival inflammation are unknown. Results we examined the involvement of CXC chemokine receptor type 4 (CXCR4) on the mechanical sensitivity of inflamed periodontal tissue, using a mouse model of periodontitis established by the ligation of the tooth cervix of a maxillary second molar and inoculation with Porphyromonas gingivalis (P. gingivalis). Infiltration of inflammatory cells into gingival tissue was not observed following the inoculation. Under light anesthesia, the mechanical head withdrawal threshold (MHWT) on the buccal gingiva was measured using an electronic von Frey anesthesiometer. No significant changes in MHWT were observed in the mice with P. gingivalis-induced periodontitis during the experimental period. Continuous administration of CXCR4 neutralizing antibody to the gingival tissue significantly decreased MHWT and increased the number of gingival CXCR4 immunoreactive macrophages in the periodontitis group. Nitric oxide metabolites in the gingival tissue were significantly increased after the inoculation of P. gingivalis and were reduced by gingival CXCR4 neutralization. Gingival L-arginine administration induced gingival mechanical allodynia in naive animals. Moreover, the decrease in MHWT after treatment with P. gingivalis and CXCR4 neutralization was partially reversed by nitric oxide synthase inhibition in the gingival tissue. Nuclear factor-kappa B was expressed in infiltrating macrophages after inoculation of P. gingivalis and administration of the nuclear factor-kappa B activator betulinic acid induced gingival mechanical allodynia in naive mice. Conclusions These findings suggest that CXCR4 signaling inhibits nitric oxide release from infiltrating macrophages and is involved in modulation of the mechanical sensitivity in the periodontal tissue

  12. Hypersensitivity to fluoroquinolones

    Science.gov (United States)

    Fernández, Tahia D.; Ariza, Adriana; Palomares, Francisca; Montañez, María I.; Salas, María; Martín-Serrano, Angela; Fernández, Rubén; Ruiz, Arturo; Blanca, Miguel; Mayorga, Cristobalina; Torres, María J.

    2016-01-01

    Abstract Although fluoroquinolones (FQs) are generally well-tolerated antibiotics, increasing numbers of hypersensitivity reactions have been reported. These can be evaluated in vitro by basophil activation tests (BATs); however, sensitivity is not optimal. Many factors could influence sensitivity such as basophil activation markers. The objective of this study was to evaluate the influence of 2 different activations markers, CD63 and CD203c, on the sensitivity of BAT to FQ. We studied 17 patients with immediate allergic reactions to FQ. BAT was performed with moxifloxacin and ciprofloxacin using CD193 (CCR3) for basophil selection and CD203c or CD63 as activation markers. Stimulation with ciprofloxacin induced a significantly higher expression of CD63 in ciprofloxacin-allergic patients compared to moxifloxacin-allergic patients (P = 0.002). In patients allergic to moxifloxacin with anaphylactic shock, we have observed an increase in the percentage of cells that upregulate CD203c, whereas patients with anaphylaxis preferentially upregulate CD63. The best sensitivity–specificity was obtained using a cutoff of 3 and the culprit FQ, using CD203c for moxifloxacin-allergic patients (sensitivity = 36.4%; specificity = 94.4%), and CD63 for ciprofloxacin-allergic patients (sensitivity = 83.3%; specificity = 88.9%). A negative correlation was found between the upregulation of CD63 and CD203c and the time interval between the reaction occurrence and the performance of the test (Spearman r = −0.446; P < 0.001 for CD63 and Spearman r = −0.386; P < 0.001 for CD203c). The performance of BAT for FQ allergy must be optimized for each drug, taking into account possible differences in the stimulation mechanism that leads to the upregulation of different activation markers. PMID:27281069

  13. Genetics of hypersensitivity to aspirin and nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Kim, Seung-Hyun; Sanak, Marek; Park, Hae-Sim

    2013-05-01

    Various hypersensitivity reactions have been reported with aspirin and nonsteroidal anti-inflammatory drugs. Hypersensitivity can occur regardless of a chemical drug structure or its therapeutic potency. Allergic conditions include aspirin-exacerbated respiratory disease (AERD or aspirin-induced asthma), aspirin-induced urticaria/angioedema (AIU), and anaphylaxis. Several genetic studies on aspirin hypersensitivity have been performed to discover the genetic predisposition to aspirin hypersensitivity and to gain insight into the phenotypic diversity. This article updates data on the genetic mechanisms that govern AERD and AIU and summarizes recent findings on the molecular genetic mechanism of aspirin hypersensitivity. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. 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.

  15. Cell-free antigens from precocious Paracoccidioides brasiliensis culture induce a typical delayed-type hypersensitivity reaction

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    Fecchio CJ

    2011-01-01

    Full Text Available Cell-free antigens (CFAg derived from Paracoccidioides brasiliensis have typically been used in immunodiffusion reactions for serodiagnosis or therapeutic follow-up of paracoccidioidomycosis patients. Thus, we investigated the usefulness of CFAg obtained from cultures at different ages, to evaluate cellular immunity by the footpad test, in experimental murine paracoccidioidomycosis. Male mice infected with P. brasiliensis 265 strain were challenged in the footpad with CFAg obtained from four- (4d CFAg or 11-day-old cultures (11d CFAg. The increase in footpad swelling provoked by 4d CFAg and 11d CFAg was similar and showed significant difference in relation to control groups. However, the infiltrate pattern was strikingly different: 4d CFAg induced a predominant mononuclear infiltrate whereas 11d CFAg provoked a predominant polymophonuclear infiltrate. These different inflammatory patterns were associated with distinct electrophoretic characteristics. By comparison with 11d CFAg, 4d CFAg showed more numerous and intense bands, including a strong one of 43 kDa (gp43. These results suggest that CFAg derived from Pb 265 isolate can be used as a reagent to evaluate cellular immunity; however, the culture's age is critical because only young cultures are able to induce a typical mononuclear infiltrate. The efficacy of this new paracoccidioidin to assay the cellular immunity in infections caused by other P. brasiliensis isolates is under investigation.

  16. Differential responses of primary auditory cortex in autistic spectrum disorder with auditory hypersensitivity.

    Science.gov (United States)

    Matsuzaki, Junko; Kagitani-Shimono, Kuriko; Goto, Tetsu; Sanefuji, Wakako; Yamamoto, Tomoka; Sakai, Saeko; Uchida, Hiroyuki; Hirata, Masayuki; Mohri, Ikuko; Yorifuji, Shiro; Taniike, Masako

    2012-01-25

    The aim of this study was to investigate the differential responses of the primary auditory cortex to auditory stimuli in autistic spectrum disorder with or without auditory hypersensitivity. Auditory-evoked field values were obtained from 18 boys (nine with and nine without auditory hypersensitivity) with autistic spectrum disorder and 12 age-matched controls. Autistic disorder with hypersensitivity showed significantly more delayed M50/M100 peak latencies than autistic disorder without hypersensitivity or the control. M50 dipole moments in the hypersensitivity group were larger than those in the other two groups [corrected]. M50/M100 peak latencies were correlated with the severity of auditory hypersensitivity; furthermore, severe hypersensitivity induced more behavioral problems. This study indicates auditory hypersensitivity in autistic spectrum disorder as a characteristic response of the primary auditory cortex, possibly resulting from neurological immaturity or functional abnormalities in it. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

  17. The scorpion toxin Amm VIII induces pain hypersensitivity through gain-of-function of TTX-sensitive Na⁺ channels.

    Science.gov (United States)

    Abbas, Najwa; Gaudioso-Tyzra, Christelle; Bonnet, Caroline; Gabriac, Mélanie; Amsalem, Muriel; Lonigro, Aurélie; Padilla, Françoise; Crest, Marcel; Martin-Eauclaire, Marie-France; Delmas, Patrick

    2013-08-01

    Voltage-gated Na(+) channels (Nav) are the targets of a variety of scorpion toxins. Here, we investigated the effects of Amm VIII, a toxin isolated from the venom of the scorpion Androctonus mauretanicus mauretanicus, on pain-related behaviours in mice. The effects of Amm VIII were compared with the classic scorpion α-toxin AaH II from Androctonus australis. Contrary to AaH II, intraplantar injection of Amm VIII at relatively high concentrations caused little nocifensive behaviours. However, Amm VIII induced rapid mechanical and thermal pain hypersensitivities. We evaluated the toxins' effects on Nav currents in nociceptive dorsal root ganglion (DRG) neurons and immortalized DRG neuron-derived F11 cells. Amm VIII and AaH II enhanced tetrodotoxin-sensitive (TTX-S) Nav currents in DRG and F11 cells. Both toxins impaired fast inactivation and negatively shifted activation. AaH II was more potent than Amm VIII at modulating TTX-S Nav currents with EC50 of 5 nM and 1 μM, respectively. AaH II and Amm VIII also impaired fast inactivation of Nav1.7, with EC50 of 6.8 nM and 1.76 μM, respectively. Neither Nav1.8 nor Nav1.9 was affected by the toxins. AaH II and Amm VIII reduced first spike latency and lowered action potential threshold. Amm VIII was less efficient than AaH II in increasing the gain of the firing frequency-stimulation relationship. In conclusion, our data show that Amm VIII, although less potent than AaH II, acts as a gating-modifier peptide reminiscent of classic α-toxins, and suggest that its hyperalgesic effects can be ascribed to gain-of-function of TTX-S Na(+) channels in nociceptors. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  18. Cicatrizing Conjunctivitis in a Patient Diagnosed With Drug Reaction With Eosinophilia and Systemic Symptoms/Drug-Induced Hypersensitivity Syndrome but With Features of Stevens-Johnson Syndrome.

    Science.gov (United States)

    Bohm, Kelley J; Ciralsky, Jessica B; Harp, Joanna L; Bajaj, Shirin; Sippel, Kimberly C

    2016-06-01

    Severe cutaneous adverse reactions to drugs (SCARs) such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS) serve as one of the main reasons for inpatient ophthalmic consultation. Although it is well-recognized that SJS/TEN is associated with severe ocular mucosal inflammation and cicatrizing, potentially blinding, sequelae, this association has not been described in relation to other SCARs. We present a patient fulfilling the diagnostic criteria for probable DRESS/DIHS but not for SJS/TEN, yet exhibiting the severe ocular surface involvement characteristic of SJS/TEN. Case report. A 64-year-old man presented with bilateral pseudomembranous conjunctivitis and conjunctival denudation (sloughing) in the setting of a maculopapular rash, fever, liver dysfunction, and hematologic abnormalities 1 month after initiating several medications. A skin biopsy was not consistent with SJS/TEN. The patient was diagnosed with probable DRESS/DIHS and treated with high-dose systemic corticosteroids. The ocular surface inflammation was addressed with intensive topical corticosteroid ointment. The pseudomembranes resolved over a 6-week period, but the patient exhibited residual conjunctival scarring of all palpebral surfaces. The development of severe ocular surface mucosal inflammation and denudation with cicatrizing sequelae in a patient carrying a diagnosis of DRESS/DIHS has diagnostic and therapeutic implications for the ophthalmologist. Careful ophthalmic assessment is indicated in any SCAR patient with ophthalmic symptoms, regardless of formal diagnosis. Furthermore, the early therapeutic interventions recently recommended in SJS/TEN to limit the ophthalmic cicatricial sequelae, such as systemic or topical corticosteroids, may be indicated.

  19. 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.

  20. Hypersensitivity Induced by Activation of Spinal Cord PAR2 Receptors Is Partially Mediated by TRPV1 Receptors.

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    Petra Mrozkova

    Full Text Available Protease-activated receptors 2 (PAR2 and transient receptor potential vanilloid 1 (TRPV1 receptors in the peripheral nerve endings are implicated in the development of increased sensitivity to mechanical and thermal stimuli, especially during inflammatory states. Both PAR2 and TRPV1 receptors are co-expressed in nociceptive dorsal root ganglion (DRG neurons on their peripheral endings and also on presynaptic endings in the spinal cord dorsal horn. However, the modulation of nociceptive synaptic transmission in the superficial dorsal horn after activation of PAR2 and their functional coupling with TRPV1 is not clear. To investigate the role of spinal PAR2 activation on nociceptive modulation, intrathecal drug application was used in behavioural experiments and patch-clamp recordings of spontaneous, miniature and dorsal root stimulation-evoked excitatory postsynaptic currents (sEPSCs, mEPSCs, eEPSCs were performed on superficial dorsal horn neurons in acute rat spinal cord slices. Intrathecal application of PAR2 activating peptide SLIGKV-NH2 induced thermal hyperalgesia, which was prevented by pretreatment with TRPV1 antagonist SB 366791 and was reduced by protein kinases inhibitor staurosporine. Patch-clamp experiments revealed robust decrease of mEPSC frequency (62.8 ± 4.9%, increase of sEPSC frequency (127.0 ± 5.9% and eEPSC amplitude (126.9 ± 12.0% in dorsal horn neurons after acute SLIGKV-NH2 application. All these EPSC changes, induced by PAR2 activation, were prevented by SB 366791 and staurosporine pretreatment. Our results demonstrate an important role of spinal PAR2 receptors in modulation of nociceptive transmission in the spinal cord dorsal horn at least partially mediated by activation of presynaptic TRPV1 receptors. The functional coupling between the PAR2 and TRPV1 receptors on the central branches of DRG neurons may be important especially during different pathological states when it may enhance pain perception.

  1. Hypersensitivity Induced by Activation of Spinal Cord PAR2 Receptors Is Partially Mediated by TRPV1 Receptors.

    Science.gov (United States)

    Mrozkova, Petra; Spicarova, Diana; Palecek, Jiri

    2016-01-01

    Protease-activated receptors 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) receptors in the peripheral nerve endings are implicated in the development of increased sensitivity to mechanical and thermal stimuli, especially during inflammatory states. Both PAR2 and TRPV1 receptors are co-expressed in nociceptive dorsal root ganglion (DRG) neurons on their peripheral endings and also on presynaptic endings in the spinal cord dorsal horn. However, the modulation of nociceptive synaptic transmission in the superficial dorsal horn after activation of PAR2 and their functional coupling with TRPV1 is not clear. To investigate the role of spinal PAR2 activation on nociceptive modulation, intrathecal drug application was used in behavioural experiments and patch-clamp recordings of spontaneous, miniature and dorsal root stimulation-evoked excitatory postsynaptic currents (sEPSCs, mEPSCs, eEPSCs) were performed on superficial dorsal horn neurons in acute rat spinal cord slices. Intrathecal application of PAR2 activating peptide SLIGKV-NH2 induced thermal hyperalgesia, which was prevented by pretreatment with TRPV1 antagonist SB 366791 and was reduced by protein kinases inhibitor staurosporine. Patch-clamp experiments revealed robust decrease of mEPSC frequency (62.8 ± 4.9%), increase of sEPSC frequency (127.0 ± 5.9%) and eEPSC amplitude (126.9 ± 12.0%) in dorsal horn neurons after acute SLIGKV-NH2 application. All these EPSC changes, induced by PAR2 activation, were prevented by SB 366791 and staurosporine pretreatment. Our results demonstrate an important role of spinal PAR2 receptors in modulation of nociceptive transmission in the spinal cord dorsal horn at least partially mediated by activation of presynaptic TRPV1 receptors. The functional coupling between the PAR2 and TRPV1 receptors on the central branches of DRG neurons may be important especially during different pathological states when it may enhance pain perception.

  2. Lack of colonic-inflammation-induced acute visceral hypersensitivity to colorectal distension in Na(v)1.9 knockout mice.

    Science.gov (United States)

    Martinez, V; Melgar, S

    2008-10-01

    Tetrodotoxin-resistant voltage-gated sodium channels subtype 9 (Na(v)1.9) are expressed in small-diameter dorsal root ganglion neurons and have been involved in persistent somatic hyperalgesic responses associated with inflammation. We assessed the role of Na(v)1.9 channels on acute colonic inflammation-induced visceral hypersensitivity in conscious mice, using Na(v)1.9 knockout (KO) mice. Colorectal distension (CRD)-induced visceral pain was assessed in conscious wild-type and Na(v)1.9 KO mice (C57Bl/6 background). The mechanical activity of the abdominal muscles during isobaric colorectal distension was used as a measure of visceral pain. Acute colonic inflammation was induced by intracolonic administration of the toll-like receptor (TLR) 7 activator, R-848 (40mug/animal). CRD was performed 5h later, thereafter animals were euthanized and the colonic content of inflammatory mediators assessed. Normal pain responses were similar in Na(v)1.9 KO and wild-type mice. In wild-type mice, R-848 administration increased the response to phasic CRD by 62% compared with vehicle-treated animals (vehicle: 0.16+/-0.04, R-848: 0.26+/-0.03, n=6-7, P1.9 KO mice, intracolonic R-848 did not affect the response to CRD (0.11+/-0.02, n=7) compared to animals treated with vehicle (0.17+/-0.03, n=5; P>0.05). After R-848 administration, the colonic content of pro-inflammatory cytokines was increased in similar proportion in wild type and Na(v)1.9 KO mice, suggesting the presence of a similar acute inflammatory reaction in both groups of animals. These results suggest that Na(v)1.9 channels do not significantly contribute to normal visceral pain responses to acute colonic mechanical stimulation but may be important for the development of inflammation-related acute visceral hyperalgesic responses.

  3. 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.

  4. 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.

  5. Effects of fracture contact areas on seismic attenuation due to wave-induced fluid flow

    Science.gov (United States)

    Germán Rubino, J.; Müller, Tobias M.; Milani, Marco; Holliger, Klaus

    2014-05-01

    Wave-induced fluid flow (WIFF) between fractures and the embedding matrix is considered to be a predominant seismic attenuation mechanism in fractured rocks. That is, due to the strong compressibility contrast between fractures and embedding matrix, seismic waves induce strong fluid pressure gradients, followed by local fluid flow between such regions, which in turn produces significant energy dissipation. Natural fractures can be conceptualized as two surfaces in partial contact, containing very soft and highly permeable material in the inner region. It is known that the characteristics of the fracture contact areas control the mechanical properties of the rock sample, since as the contact area increases, the fracture becomes stiffer. Correspondingly, the detailed characteristics of the contact area of fractures are expected to play a major role in WIFF-related attenuation. To study this topic, we consider a simple model consisting of a horizontal fracture located at the center of a porous rock sample and represented by a number of rectangular cracks of constant height separated by contact areas. The cracks are modelled as highly compliant, porous, and permeable heterogeneities, which are hydraulically connected to the background material. We include a number of rectangular regions of background material separating the cracks, which represent the presence of contact areas of the fracture. In order to estimate the WIFF effects, we apply numerical oscillatory relaxation tests based on the quasi-static poro-elastic equations. The equivalent undrained, complex plane-wave modulus, which allows to estimate seismic attenuation and velocity dispersion for the vertical direction of propagation, is expressed in terms of the imposed displacement and the resulting average vertical stress at the top boundary. In order to explore the effects of the presence of fracture contact areas on WIFF effects, we perform an exhaustive sensitivity analysis considering different

  6. 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.

  7. Respiratory hypersensitivity reactions to NSAIDs in Europe

    DEFF Research Database (Denmark)

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

    2016-01-01

    . Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status, and history of NSAID-induced hypersensitivity reactions were sent to participants by mail. Totally, 62 737 participants completed the questionnaires. RESULTS: The mean......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...... 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...

  8. Complementary treatment of contact lens-induced corneal ulcer using honey: a case report.

    Science.gov (United States)

    Majtanova, Nora; Vodrazkova, Erika; Kurilova, Veronika; Horniackova, Miroslava; Cernak, Martin; Cernak, Andrej; Majtan, Juraj

    2015-02-01

    The aim of this study was to report the complementary use of honey for treatment of a contact lens-induced corneal ulcer. A 23-year-old contact lens user presented with a corneal ulcer in her left eye. She had visual acuity reduced to hand movement. There was a history of wearing contact lenses while swimming in a lake seven days before presentation. The cultures from corneal scrapings and contact lenses were positive for Klebsiella oxytoca, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Pseudomonas spp. The treatment with topical levofloxacin and 25% (w/v) γ-irradiated honeydew honey solution was effective and the patient achieved final best corrected visual acuity of affected eye. In addition to positive clinical outcome, honeydew honey was shown to be highly effective in vitro against ocular isolates, in particular S. maltophilia. The minimal inhibitory concentrations for honeydew honey ranged from 5% to 10%. These results demonstrate that honey is a promising antibacterial agent in management of corneal ulcers. Moreover, honey exhibits anti-biofilm and anti-inflammatory properties, and thus becomes an interesting ophthalmologic agent. Copyright © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  9. Neurosteroid Allopregnanolone Suppresses Median Nerve Injury-induced Mechanical Hypersensitivity and Glial Extracellular Signal-regulated Kinase Activation through γ-Aminobutyric Acid Type A Receptor Modulation in the Rat Cuneate Nucleus.

    Science.gov (United States)

    Huang, Chun-Ta; Chen, Seu-Hwa; Lue, June-Horng; Chang, Chi-Fen; Wen, Wen-Hsin; Tsai, Yi-Ju

    2016-12-01

    Mechanisms underlying neuropathic pain relief by the neurosteroid allopregnanolone remain uncertain. We investigated if allopregnanolone attenuates glial extracellular signal-regulated kinase (ERK) activation in the cuneate nucleus (CN) concomitant with neuropathic pain relief in median nerve chronic constriction injury (CCI) model rats. We examined the time course and cellular localization of phosphorylated ERK (p-ERK) in CN after CCI. We subsequently employed microinjection of a mitogen-activated protein kinase kinase (ERK kinase) inhibitor, PD98059, to clarify the role of ERK phosphorylation in neuropathic pain development. Furthermore, we explored the effects of allopregnanolone (by mouth), intra-CN microinjection of γ-aminobutyric acid type A receptor antagonist (bicuculline) or γ-aminobutyric acid type B receptor antagonist (phaclofen) plus allopregnanolone, and allopregnanolone synthesis inhibitor (medroxyprogesterone; subcutaneous) on ERK activation and CCI-induced behavioral hypersensitivity. At 7 days post-CCI, p-ERK levels in ipsilateral CN were significantly increased and reached a peak. PD98059 microinjection into the CN 1 day after CCI dose-dependently attenuated injury-induced behavioral hypersensitivity (withdrawal threshold [mean ± SD], 7.4 ± 1.1, 8.7 ± 1.0, and 10.3 ± 0.8 g for 2.0, 2.5, and 3.0 mM PD98059, respectively, at 7 days post-CCI; n = 6 for each dose). Double immunofluorescence showed that p-ERK was localized to both astrocytes and microglia. Allopregnanolone significantly diminished CN p-ERK levels, glial activation, proinflammatory cytokines, and behavioral hypersensitivity after CCI. Bicuculline, but not phaclofen, blocked all effects of allopregnanolone. Medroxyprogesterone treatment reduced endogenous CN allopregnanolone and exacerbated nerve injury-induced neuropathic pain. Median nerve injury-induced CN glial ERK activation modulated the development of behavioral hypersensitivity. Allopregnanolone attenuated

  10. Calibration and validation of nine objective vision screeners with contact lens-induced anisometropia.

    Science.gov (United States)

    Arnold, Robert W; Davis, Bethanne; Arnold, Laura E; Rowe, Kayla S; Davis, Jodi M

    2013-01-01

    New objective photoscreeners are emerging with encouraging national guidelines and pediatric providers can be reimbursed for photoscreening. Nine objective screeners were applied to two emmetropic subjects with or without known power contact lenses to induce spherical and cylindrical anisometropia close to American Association for Pediatric Ophthalmology and Strabismus (AAPOS) thresholds. The screeners produced near linear pupil crescents and estimated refractions for induced anisometropia. Most performed well with AAPOS 2003 validation; however, the iPhone (Apple, Cupertino, CA) was too sensitive, whereas the remote autorefractors using Vision in Preschoolers Study criteria were less sensitive. The new, interpreted objective screeners appear valid for detection of anismetropia. Copyright 2013, SLACK Incorporated.

  11. Contact lens induced Pseudomonas keratitis following descemet stripping automated endothelial keratoplasty.

    Science.gov (United States)

    Dhiman, Rebika; Singh, Archita; Tandon, Radhika; Vanathi, M

    2015-10-01

    To report a case of bandage contact lens induced infectious keratitis caused by Pseudomonas aeruginosa following DSAEK. A 56-year-old female who underwent DSAEK at our institute for pseudophakic bullous keratopathy, developed contact lens induced keratitis in the fifth post operative week. Best corrected visual acuity (BCVA) reduced to perception of light in the left eye. Slit lamp examination revealed an epithelial ulcer measuring 4.7mm×6mm with surrounding infiltrates in the anterior stroma with hypopyon. The interface was clear. The corneoscleral rim culture of the donor tissue showed no growth on bacterial and fungal culture ruling out the possibility of donor-to-host transmission of infection. Microbiological evaluation identified the causative agent to be Pseudomonas aeruginosa. Based on culture and sensitivity report patient was started on hourly instillation of topical polymyxin B 20,000IU and fortified ceftazidime 5%. A response to treatment was noted and there was a complete resolution of keratitis with residual scarring. There have been case reports suggesting a host to donor transmission of infection which manifests during the postoperative period. To the best of our knowledge there are no reports of bandage contact lens associated Pseudomonas keratitis in a case that has undergone DSAEK. The prolonged use of bandage contact lens, lens contamination, stagnation of tear film behind the lens, compromised ocular surface and post operative use of topical steroids can contribute to infectious keratitis in DSAEK cases. Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  12. 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 Damgård; 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...... 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...... FAST as the probe can be used to detect local immune responses induced by contact allergens....

  13. Hypersensitivity to Suture Anchors

    Directory of Open Access Journals (Sweden)

    Masafumi Goto

    2013-01-01

    Full Text Available Hypersensitivity to suture anchor is extremely rare. Herein, we present a case in which hypersensitivity to suture anchor was strongly suspected. The right rotator cuff of a 50-year-old woman was repaired with a metal suture anchor. Three weeks after the surgery, she developed erythema around her face, trunk, and hands, accompanied by itching. Infection was unlikely because no abnormalities were detected by blood testing or by medical examination. Suspicious of a metallic allergy, a dermatologist performed a patch testing 6 months after the first surgery. The patient had negative reactions to tests for titanium, aluminum, and vanadium, which were the principal components of the suture anchor. The anchor was removed 7 months after the first surgery, and the erythema disappeared immediately. When allergic symptoms occur and persist after the use of a metal anchor, removal should be considered as a treatment option even if the patch test result is negative.

  14. Vaccine-associated hypersensitivity.

    Science.gov (United States)

    McNeil, Michael M; DeStefano, Frank

    2018-02-01

    Vaccine-associated hypersensitivity reactions are not infrequent; however, serious acute-onset, presumably IgE-mediated or IgG and complement-mediated anaphylactic or serious delayed-onset T cell-mediated systemic reactions are considered extremely rare. Hypersensitivity can occur because of either the active vaccine component (antigen) or one of the other components. Postvaccination acute-onset hypersensitivity reactions include self-limited localized adverse events and, rarely, systemic reactions ranging from urticaria/angioedema to full-blown anaphylaxis with multisystem involvement. Risk of anaphylaxis after all vaccines is estimated to be 1.31 (95% CI, 0.90-1.84) per million vaccine doses, respectively. Serious hypersensitivity reactions after influenza vaccines are particularly important because of the large number of persons vaccinated annually. Influenza vaccines are unique in requiring annual changes in the vaccines' antigenic composition to match the predicted circulating influenza strains. Recently, novel influenza vaccine types were introduced in the United States (recombinant vaccines, some with higher antigen content and a new adjuvanted vaccine). Providers should be aware of changing recommendations on the basis of recent published evidence for persons with a history of egg allergy to receive annual influenza vaccination. Further research is needed to elucidate the pathophysiology and risk factors for reported vaccine-associated adverse events. Further research is also needed to determine whether repeated annual inactivated influenza vaccination, the number of vaccine antigens administered at the same time, and the current timing of routine infant vaccinations are optimal for overall population well-being. Published by Elsevier Inc.

  15. [Food hypersensitivity in children].

    Science.gov (United States)

    Kolacek, Sanja

    2011-01-01

    Food hypersensitivity affects children and adults with an increasing prevalence, and is therefore an important public health problem in the majority of developed countries. Moreover, self-reported reactions to food are of several times higher prevalence, compared to hypersensitivity diagnosed following well established evidence-based diagnostic guidelines. In children, allergic food reactions are more common compared to non-allergic food hypersensitivity reactions, and 90% of them are caused with only 8 food allergens: cow's milk, soya, egg, fish, shellfish, peanut, tree-nuts and gluten. Diagnosis should be based on challenge tests with the potentially offending food allergens. Concerning other, more conservative diagnostic procedures, negative serology and negative skin-prick tests can exclude IgE-mediated food allergy, but positive tests, due to high rate of false positive reactions are not sufficient for diagnosis. Strict dietary avoidance of incriminated allergens is the only well established management strategy. However, this should be applied only if food allergy is well documented - following the exposition tests. Introducing elimination diet in a paediatric population, particularly with the elimination of multiple foods, could cause inappropriate growth and disturb organ maturation. Concerning allergy prevention, avoidance of allergens is not efficacious either during pregnancy and lactation or weaning period, and is therefore, not recommended neither as a population preventive measure, nor in children at risk.

  16. Immediate-type hypersensitivity drug reactions.

    Science.gov (United States)

    Stone, Shelley F; Phillips, Elizabeth J; Wiese, Michael D; Heddle, Robert J; Brown, Simon G A

    2014-07-01

    Hypersensitivity reactions including anaphylaxis have been reported for nearly all classes of therapeutic reagents and these reactions can occur within minutes to hours of exposure. These reactions are unpredictable, not directly related to dose or the pharmacological action of the drug and have a relatively high mortality risk. This review will focus on the clinical presentation, immune mechanisms, diagnosis and prevention of the most serious form of immediate onset drug hypersensitivity reaction, anaphylaxis. The incidence of drug-induced anaphylaxis deaths appears to be increasing and our understanding of the multiple and complex reasons for the unpredictable nature of anaphylaxis to drugs is also expanding. This review highlights the importance of enhancing our understanding of the biology of the patient (i.e. immune response, genetics) as well as the pharmacology and chemistry of the drug when investigating, diagnosing and treating drug hypersensitivity. Misdiagnosis of drug hypersensitivity leads to substantial patient risk and cost. Although oral provocation is often considered the gold standard of diagnosis, it can pose a potential risk to the patient. There is an urgent need to improve and standardize diagnostic testing and desensitization protocols as other diagnostic tests currently available for assessment of immediate drug allergy are not highly predictive. © 2013 The British Pharmacological Society.

  17. Occupational respiratory hypersensitivity caused by preparations containing acrylates in dental personnel.

    Science.gov (United States)

    Piirilä, P; Kanerva, L; Keskinen, H; Estlander, T; Hytönen, M; Tuppurainen, M; Nordman, H

    1998-11-01

    Allergic contact dermatitis caused by acrylate compounds is common in dental personnel; they also often complain of work-related respiratory or conjunctival symptoms. The aim of the present study was to report the cases of acrylates induced respiratory hypersensitivity in dental personnel diagnosed in Finland during the last 6 years. Occupational asthma, rhinitis, laryngitis and pharyngitis cases were diagnosed according to patient history, PEF monitoring, and a work-simulating provocation test. Twelve cases of respiratory hypersensitivity caused by acrylates diagnosed in dental personnel (six dentists and six dental nurses) in 1992-97 are reported. During this period one case of conjunctivitis and one of laryngitis have been published separately. Nine cases of occupational asthma, two rhinitis cases, and one laryngitis case were verified according to the challenge tests with dental acrylate compounds (acrylates, methacrylates and epoxy acrylates). Only three patients had positive skin-prick test reactions to common environmental allergens, and none reacted to acrylates in the skin-prick tests. Five patients had an elevated total IgE (>110 kU/L). PEF follow-up showed an occupational effect in all examined eight patients with diagnosed asthma. The mean duration of exposure to acrylates was 22 years, and the duration of respiratory symptoms 8 years. The results indicate that acrylates constitute an important hazard for dental workers. The mechanism of respiratory hypersensitivity is still unknown, and it is probably not IgE-mediated.

  18. The leucine-rich repeat (LRR) protein, CaLRR1, interacts with the hypersensitive induced reaction (HIR) protein, CaHIR1, and suppresses cell death induced by the CaHIR1 protein.

    Science.gov (United States)

    Jung, Ho Won; Hwang, Byung Kook

    2007-07-01

    Leucine-rich repeat proteins (LRRs) function in a number of signal transduction pathways via protein-protein interactions. The gene encoding a small protein of pepper, CaLRR1, is specifically induced upon pathogen challenge and treatment with pathogen-associated molecular patterns (PAMPs). We identified a pepper hypersensitive induced reaction (CaHIR1) protein that interacts with the LRR domain of the CaLRR1 protein using yeast two-hybrid screening. Ectopic expression of the pepper CaHIR1 gene induces cell death in tobacco and Arabidopsis, indicating that the CaHIR1 protein may be a positive regulator of HR-like cell death. Because transformation is very difficult in pepper plants, we over-expressed CaLRR1 and CaHIR1 in Arabidopsis to determine cellular functions of the two genes. The over-expression of the CaHIR1 gene, but not the CaLRR1 gene, in transgenic Arabidopsis confers disease resistance in response to Pseudomonas syringae infection, accompanied by the strong expression of PR genes, the accumulation of both salicylic acid and H(2)O(2), and K(+) efflux in plant cells. In Arabidopsis and tobacco plants over-expressing both CaHIR1 and CaLRR1, the CaLRR1 protein suppresses not only CaHIR1-induced cell death, but also PR gene expression elicited by CaHIR1 via its association with HIR protein. We propose that the CaLRR1 protein functions as a novel negative regulator of CaHIR1-mediated cell death responses in plants.

  19. 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; Mckinnin, Elizabeth; Ostrov, David; Peters, Bjoern

    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 ...

  20. Calibration of photoscreeners for single-subject, contact-induced hyperopic anisometropia.

    Science.gov (United States)

    Kovtoun, Tatiana A; Arnold, Robert W

    2004-01-01

    In 1999, the threshold anisometropic hyperopia for photoscreening toddlers and preschoolers was determined to be 1.50 D. We compared crescent size from induced anisometropic hyperopia using three commercially available photoscreeners and compared them with miniature digital video cameras, which have a flash-to-lens dimension similar to two of the three photoscreeners. Photoscreeners were compared with a remote autorefractor. Anisometropia was induced by placing several known minus contact lenses (-1.00, -1.50, and -2.00 D) in the nondominant eye of a visually healthy, orthophoric emmetrope older than 3 years. Photographs were taken in light and dim conditions with all three cameras with and without the contact lenses. Corneal diameter, pupil diameter, and crescent location were determined. A protocol for flash initiation, focus, and distance was determined for the digital cameras. Under light and dim ambient light, no camera yielded a significant hyperopic crescent for emmetropia (no contact lens) or induced 1.0-D anisometropia. We propose a simple measure, "delta center crescent" distance from the center of the pupil to the edge of the crescent. Delta center crescent less than 1.5 mm identified most examples of threshold hyperopic anisometropia. The ideal distance for photoscreening using the digital cameras is approximately 1.6 m, whereas the commercially available photoscreeners focus at 1.0 m. We have developed a protocol for photoscreening and its interpretation with a miniature digital video camera weighing 400 g and costing approximately dollar 1,000. Threshold anisometropic hyperopia can be determined from digital still or audio-labeled video flash images if the pupils are at least 4 mm.

  1. Deglutition-Induced Atrial Tachycardia Localised with Contact Force-Guided Activation Mapping.

    Science.gov (United States)

    McLellan, Alex J A; Bates, Matthew G D; Young, Shane D F; Sparks, Paul B

    2016-11-01

    Deglutition-induced atrial tachycardia is a rare arrhythmia with a poor response to medical therapy. Electrophysiological study is challenging due to the dependence of induction on swallowing. We present a novel approach to management of deglutition-induced atrial tachycardia arising from right superior pulmonary vein. Use of minimal conscious sedation and repeated swallow challenge inductions, together with contact force-guided mapping were key determinants of success. We review published cases, discussing potential mechanisms including oesophageal distension and neural reflexes. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  2. 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.

  3. P2X3 receptors mediate visceral hypersensitivity during acute chemically-induced colitis and in the post-inflammatory phase via different mechanisms of sensitization.

    Directory of Open Access Journals (Sweden)

    Annemie Deiteren

    Full Text Available Experiments using P2X3 knock-out mice or more general P2X receptor antagonists suggest that P2X3 receptors contribute to visceral hypersensitivity. We aimed to investigate the effect of the selective P2X3 antagonist A-317491 on visceral sensitivity under physiological conditions, during acute colitis and in the post-inflammatory phase of colitis.Trinitrobenzene sulphonic-acid colitis was monitored by colonoscopy: on day 3 to confirm the presence of colitis and then every 4 days, starting from day 10, to monitor convalescence and determine the exact timepoint of endoscopic healing in each rat. Visceral sensitivity was assessed by quantifying visceromotor responses to colorectal distension in controls, rats with acute colitis and post-colitis rats. A-317491 was administered 30 min prior to visceral sensitivity testing. Expression of P2X3 receptors (RT-PCR and immunohistochemistry and the intracellular signalling molecules cdk5, csk and CASK (RT-PCR were quantified in colonic tissue and dorsal root ganglia. ATP release in response to colorectal distension was measured by luminiscence.Rats with acute TNBS-colitis displayed significant visceral hypersensitivity that was dose-dependently, but not fully, reversed by A-317491. Hypersenstivity was accompanied by an increased colonic release of ATP. Post-colitis rats also displayed visceral hypersensitivity that was dose-dependently reduced and fully normalized by A-317491 without increased release of ATP. A-317491 did not modify visceral sensitivity in controls. P2X3 mRNA and protein expression in the colon and dorsal root ganglia were similar in control, acute colitis and post-colitis groups, while colonic mRNA expression of cdk5, csk and CASK was increased in the post-colitis group only.These findings indicate that P2X3 receptors are not involved in sensory signaling under physiological conditions whereas they modulate visceral hypersensitivity during acute TNBS-colitis and even more so in the post

  4. Specific IgG to Thermoactynomices vulgaris, Micropolyspora faeni and Aspergillus fumigatus in building workers exposed to esparto grass (plasterers) and in patients with esparto-induced hypersensitivity pneumonitis.

    Science.gov (United States)

    Gamboa, P M; Urbaneja, F; Olaizola, I; Boyra, J A; González, G; Antépara, I; Urrutia, I; Jáuregui, I; Sanz, M L

    2005-01-01

    Esparto is one the most frequent causes of hypersensitivity pneumonitis in Spain. Determination of risk factors in the working environment that could explain the sensitisation process, and assessment of the differences in specific IgG levels to Aspergillus fumigatus, Saccharopolyspora rectivirgula and Thermoactynomices vulgaris in patients with hypersensitivity pneumonitis induced by esparto, exposed healthy plasterers and control population. Determination of precipitins and specific IgG to Aspergillusfumigatus, Saccharopolyspora rectivirgula and Thermoactynomices vulgaris in the three previously mentioned groups. Questionnaire on possible risk occupational and extra-occupational factors. Both healthy and exposed plasterers have higher levels of specific IgG to Aspergillus fumigatus, Saccharopolyspora rectivirgula and Thermoactynomices vulgaris than the healthy controls. The patients had higher levels of IgG than exposed healthy plasterers only to Thermoactynomices vulgaris. Precipitins were detected in only two patients. There were no occupational factors influencing on the sensitisation process. Specific IgG is an occupational exposure marker among plasterers, but it has not been possible to establish a cut off point that differentiates exposed subjects from affected ones. This determination has a greater sensitivity than precipitins. We did not identify occupational or extra-occupational risk factors that facilitate the sensitisation process.

  5. 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...

  6. Stress Induced Mechano-electrical Writing-Reading of Polymer Film Powered by Contact Electrification Mechanism

    Science.gov (United States)

    Goswami, Sumita; Nandy, Suman; Calmeiro, Tomás R.; Igreja, Rui; Martins, Rodrigo; Fortunato, Elvira

    2016-01-01

    Mechano-electrical writing and reading in polyaniline (PANI) thin film are demonstrated via metal-polymer contact electrification mechanism (CEM). An innovative conception for a non-destructive self-powered writable-readable data sheet is presented which can pave the way towards new type of stress induced current harvesting devices. A localized forced deformation of the interface has been enacted by pressing the atomic force microscopic probe against the polymer surface, allowing charge transfer between materials interfaces. The process yields a well-defined charge pattern by transmuting mechanical stress in to readable information. The average of output current increment has been influenced from 0.5 nA to 15 nA for the applied force of 2 nN to 14 nN instead of electrical bias. These results underscore the importance of stress-induced current harvesting mechanism and could be scaled up for charge patterning of polymer surface to writable-readable data sheet. Time evolutional current distribution (TECD) study of the stress-induced patterned PANI surface shows the response of readability of the recorded data with time.

  7. In vivo approaches for immune-mediated drug hypersensitivity research

    NARCIS (Netherlands)

    Kwast, L.M.

    2017-01-01

    Drug allergies, immune-mediated drug hypersensitivity reactions (IDHRs) or drug induced liver injury (DILI) are important causes of black box warnings and drug withdrawals, and thus a major problem in the development of drugs. Also drug induced liver injury Despite the high demand for preclinical

  8. Laser Induced Forward Transfer for front contact improvement in silicon heterojunction solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Colina, M., E-mail: monicacolinb@gmail.com; Morales-Vilches, A.; Voz, C.; Martín, I.; Ortega, P.; Orpella, A.; López, G.; Alcubilla, R.

    2015-05-01

    Highlights: • LIFT technique is investigated to improve heterojunction HJ solar cells. • Doped silicon films are adequate precursors for LIFT application in HJ cells. • LIFT leads to a reduction of the series resistance of a-Si HJ diodes. • LIFT allows the improvement of the front contact resistance in a-Si HJ solar cells. - Abstract: In this work the Laser Induced Forward Transfer (LIFT) technique is investigated to create n-doped regions on p-type c-Si substrates. The precursor source of LIFT consisted in a phosphorous-doped hydrogenated amorphous silicon layer grown by Plasma Enhanced Chemical Vapor Deposition (PECVD) onto a transparent substrate. Transfer of the doping atoms occurs when a sequence of laser pulses impinging onto the doped layer propels the material toward the substrate. The laser irradiation not only transfers the doping material but also produces a local heating that promotes its diffusion into the substrate. The laser employed was a 1064 nm, lamp-pumped system, working at pulse durations of 100 and 400 ns. In order to obtain a good electrical performance a comprehensive optimization of the applied laser fluency and number of pulses was carried out. Subsequently, arrays of n + p local junctions were created by LIFT and the resulting J–V curves demonstrated the formation of good quality n+ regions. These structures were finally incorporated to enhance the front contact in conventional silicon heterojunction solar cells leading to an improvement of conversion efficiency.

  9. 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.

  10. Coupling system dynamics and contact behaviour: Modelling bearings subjected to environmental induced vibrations and ‘false brinelling’ degradation

    Science.gov (United States)

    Massi, Francesco; Rocchi, J.; Culla, A.; Berthier, Y.

    2010-05-01

    During the last decades the increase in power of mechanical systems and the demand for increasing service life leads mechanical components of a system to work in extreme conditions. Moreover, actual mechanical systems include surfaces in sliding contact that are subjected to wear if exposed to high vibration. In fact, the vibration of components in contact results in large oscillations of the local contact stresses, due to the local deformation of the components at the contact interfaces. To approach correctly tribological problems, the coupling between the scale of the mechanism (system dynamics) and the scale of the contact needs to be accounted for. This paper presents an analysis concerning the influence of the vibrations induced by aircraft engines on the contact stresses of rolling bearings of the bleed system valves. To study the wear, resulting from false brinelling at the contact surfaces between balls and races of the bearings, it is then necessary to determine the forces due to the system vibrations and acting at the bearing connections with the structure. In order to perform a numerical transient analysis of the system dynamics a nonlinear simplified model of the valve (mechanism scale) is developed. The model is validated by comparing the numerical results with experimental tests. The time behaviour of the global forces on the bearings, and the respective displacements between the contact surfaces, are then used as inputs for a finite element model of the bearings (contact scale). The model is used to calculate and analyze the behaviour in time of the local contact constraints between race and balls. This analysis, developed in the framework of a European project, is an example of the proposed general approach to contact problems, by coupling the analysis of the mechanism and contact scales.

  11. HLA-associated drug hypersensitivity and the prediction of adverse drug reactions.

    Science.gov (United States)

    Negrini, Simone; Becquemont, Laurent

    2017-10-01

    Adverse drug reactions are an important cause of morbidity and mortality and constitute the leading reason of drug withdrawal from the market. Besides classical reactions that are related to pharmacologic activity of the drug, some reactions are unpredictable, not dose dependent, and seem to occur in genetically predisposed individuals. The majority of this reaction is immunologically driven and they are referred to as hypersensitivity reactions. A growing number of studies provided evidences that specific HLA alleles increase the risk of developing hypersensitivity drug reactions. In this context, drug hypersensitivities that have more robust pharmacogenetic data include abacavir hypersensitivity syndrome and severe cutaneous adverse reactions induced by allopurinol and carbamazepine.

  12. Cutaneous delayed-type hypersensitivity in patients with atopic dermatitis.

    Science.gov (United States)

    Malajian, Dana; Belsito, Donald V

    2013-08-01

    Literature on the relationship between atopic dermatitis (AD) and cutaneous delayed-type hypersensitivity is inconclusive. We sought to compare the rates of positive patch test reactions to allergens on the North American Contact Dermatitis Group (NACDG) standard tray among patients with and without AD, and, to assess whether atopic patients in our database were more likely to patch test positive to certain classes of allergens. A total of 2305 patients underwent patch testing to the NACDG standard screening series. The incidence of positive patch test reactions among patients with AD (n = 297) and without AD (n = 2008) was assessed. Statistical analysis was done using a χ(2) test with Yates continuity correction. Compared with nonatopic patients, those with AD were statistically more likely to have positive patch tests. AD was associated with contact hypersensitivity to nickel, cobalt, and chromium, but was not associated with contact sensitization to fragrances. Only patients suspected of having allergic contact dermatitis were tested. Our population was geographically limited to metropolitan Kansas City (including Kansas City, MO, Kansas City, KS, and the adjoining suburbs). Compared with nonatopics, patients with AD are significantly more likely to have at least 1 positive patch test reaction and to develop contact hypersensitivity to metal allergens. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  13. Local and systemic effects of co-stimulatory blockade using cytotoxic T lymphocyte antigen-4-immunoglobulin in dinitrofluorobenzene- and oxazolone-induced contact hypersensitivity in mice

    DEFF Research Database (Denmark)

    Christensen, A. D.; Skov, Søren; Haase, C.

    2013-01-01

    the maturation level of both dendritic cells and B cells. Furthermore, CTLA-4-Ig reduces infiltration of activated CD8(+) T cells into the inflamed ear tissue and suppresses both local and systemic inflammation, as illustrated by reduced expression of cytokines and chemokines in the inflamed ear and a reduced...

  14. Temperature and Stress Simulation of 4H-SiC during Laser-Induced Silicidation for Ohmic Contact Generation

    Directory of Open Access Journals (Sweden)

    Benedikt Adelmann

    2017-12-01

    Full Text Available We report here on the simulation of temperature and stress evolution of 4H-SiC during laser-induced silicidation to locally generate ohmic contacts between the semiconductor and nickel metallization. The simulation is based on optical free carrier absorption, thermal conduction, and thermal radiation. Our results show that, during laser irradiation, similar temperatures and correspondingly similar contact resistances, as compared to conventional oven-driven annealing processes, are achievable, yet with the advantageous potential to limit the temperature treatment spatially to the desired regions for electrical contacts and without the necessity of heating complete wafers. However, due to temperature gradients during local laser silicidation, thermal induced stress appears, which may damage the SiC wafer. Based on the simulated results for temperature and stress increase, we identify an optimized regime for laser-induced local silicidation and compare it to experimental data and observations.

  15. 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

  16. Absolute eosinophilia as dapsone hypersensitivity

    Directory of Open Access Journals (Sweden)

    Somani V

    1994-01-01

    Full Text Available A case of lepromatous leprosy (LL on multibacillary multidrug therapy (MBMDT presented with oedema of the acral parts and marked eosinophilia. The case is being reported because of this extremely rare manifestation of dapsone hypersensitivity.

  17. Evaluation of periprocedural hypersensitivity reactions.

    Science.gov (United States)

    Iammatteo, Melissa; Keskin, Taha; Jerschow, Elina

    2017-10-01

    Identifying the cause of periprocedural hypersensitivity reactions (HSRs) remains challenging because of the multitude of medications involved. Antibiotics are the most common cause in the United States, whereas neuromuscular blocking agents are most common in Europe. To identify causative agents for periprocedural HSRs. This study was a 7-year retrospective medical record review of patients evaluated between December 2009 and January 2017 at a drug allergy center in Bronx, New York for periprocedural HSRs, defined as occurring soon before, during, or soon after a medical procedure or operation with or without general anesthesia. Demographics, description of historical HSRs, results of testing to potential causative medications, and tolerance of subsequent anesthesia were reviewed. Thirty-four patients completed a comprehensive evaluation. Skin testing identified an IgE-mediated cause in 22 patients (64.7%). The most common causative class of medications was induction agents (n = 9 [36%]), with midazolam being the most frequently implicated (n = 6 [3 positive skin test results, 3 equivocal skin test results]). Cefazolin was the most common agent identified (n = 8 [32%]) followed by ondansetron (n = 3 [12%]). Sixteen of 22 contacted patients were exposed to subsequent anesthesia, including 3 patients with negative evaluations. One patient experienced a mild urticarial HSR. Induction agents were the most common causative agents in our patients, which differs from other studies. Given the variability in evaluations of periprocedural HSRs across the United States with data published on small sample sizes, there is a need to establish national guidelines to standardize evaluations and to create a national registry to allow for data sharing. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. 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.

  19. Metazoan Nuclear Pores Provide a Scaffold for Poised Genes and Mediate Induced Enhancer-Promoter Contacts.

    Science.gov (United States)

    Pascual-Garcia, Pau; Debo, Brian; Aleman, Jennifer R; Talamas, Jessica A; Lan, Yemin; Nguyen, Nha H; Won, Kyoung J; Capelson, Maya

    2017-04-06

    Nuclear pore complex components (Nups) have been implicated in transcriptional regulation, yet what regulatory steps are controlled by metazoan Nups remains unclear. We identified the presence of multiple Nups at promoters, enhancers, and insulators in the Drosophila genome. In line with this binding, we uncovered a functional role for Nup98 in mediating enhancer-promoter looping at ecdysone-inducible genes. These genes were found to be stably associated with nuclear pores before and after activation. Although changing levels of Nup98 disrupted enhancer-promoter contacts, it did not affect ongoing transcription but instead compromised subsequent transcriptional activation or transcriptional memory. In support of the enhancer-looping role, we found Nup98 to gain and retain physical interactions with architectural proteins upon stimulation with ecdysone. Together, our data identify Nups as a class of architectural proteins for enhancers and supports a model in which animal genomes use the nuclear pore as an organizing scaffold for inducible poised genes. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Dentin hypersensitive: Ethiology and treatment

    Directory of Open Access Journals (Sweden)

    Nuryanni Dihin Utami

    2017-08-01

    Full Text Available Dentin hypersensitivity is a response in exposed dentine with a symptom of clinically sharp and short pain. This condition may occur to exposed dentine due to gingival recession or enamel loss. Dentin hypersensitivity treatment aimed to either occlude the open dentinal tubules or block the neural response of the pulp. Invasive treatment are pulpectomy, restoration or surgery, while non invasive treatment are usually done by using tooth paste or mouthwash which is added by desensitizing agent

  1. Immediate-type hypersensitivity reaction to Mannitol as drug excipient (E421): a case report.

    Science.gov (United States)

    Calogiuri, G F; Muratore, L; Nettis, E; Casto, A M; Di Leo, E; Vacca, A

    2015-05-01

    Allergic reactions to mannitol have been reported rarely, despite its widespread use as a drug and as a food excipient. This is the first case report in which oral mannitol induces an immediate type hypersensitivity as a drug excipient, in a 42 year old man affected by rhinitis to olive tree pollen. Unusual and undervalued risk factors for mannitol hypersensitivity are examined.

  2. Current Knowledge and Management of Hypersensitivity to Aspirin and NSAIDs.

    Science.gov (United States)

    Laidlaw, Tanya M; Cahill, Katherine N

    Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most common culprits of drug-induced hypersensitivity reactions, and can lead to a wide array of adverse effects. The accurate and timely diagnosis of aspirin and NSAID-induced hypersensitivity reactions is important for both patient safety and for the initiation of appropriate disease-specific management and treatment. Because there are no reliably validated in vitro tests available, aspirin and NSAID challenges are considered to be the criterion standard for the diagnosis of these hypersensitivity reactions, though in some patients the diagnosis can be made on the basis of a clear clinical history. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. 7th Drug hypersensitivity meeting: part two

    OpenAIRE

    Elera, Javier Dionicio; Boteanu, Cosmin; Blanco, Maria Aranzazu Jimenez; Gonzalez-Mendiola, Rosario; García, Irene Carrasco; Alvarez, Antonio; Martinez, Jose Julio Laguna; Garrido, Jaume Martí; Barona, Carla Torán; Chorda, Carolina Perales; Salgueiro, Ramón López; Palacios, Miguel Díaz; Rojas,Dolores Hernández Fernández de; Acar, Emre Ali; Aktas, Ayse

    2016-01-01

    Table of contents Poster walk 11: miscellaneous drug hypersensitivity 2 (P92–P94, P96–P101) P92 16 years of experience with proton pump inhibitors (PPIs) Javier Dionicio Elera, Cosmin Boteanu, Maria Aranzazu Jimenez Blanco, Rosario Gonzalez-Mendiola, Irene Carrasco García, Antonio Alvarez, Jose Julio Laguna Martinez P93 Allergy evaluation of quinolone induced adverse reactions Jaume Martí Garrido, Carla Torán Barona, Carolina Perales Chorda, Ramón López Salgueiro, Miguel Díaz Palacios, Dolore...

  4. 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.

  5. Two-dimensional relative peripheral refractive error induced by Fractal Contact Lenses for myopia control

    CERN Document Server

    Rodriguez-Vallejo, Manuel; Monsoriu, Juan A; Ferrando, Vicente; Furlan, Walter D

    2016-01-01

    Purpose: To assess the peripheral refraction induced by Fractal Contact Lenses (FCLs) in myopic eyes by means of a two-dimensional Relative Peripheral Refractive Error (RPRE) map. Methods: FCLs prototypes were specially manufactured and characterized. This study involved twenty-six myopic subjects ranging from -0.50 D to -7.00 D. The two-dimensional RPRE was measured with an open-field autorefractor by means of tracking targets distributed in a square grid from -30 degrees (deg) nasal to 30 deg temporal and 15 deg superior to -15 deg inferior. Corneal topographies were taken in order to assess correlations between corneal asphericity, lens decentration and RPRE represented in vector components M, J0 and J45. Results: The mean power of the FCLs therapeutic zones was 1.32 +/- 0.28 D. Significant correlations were found between the corneal asphericity and vector components of the RPRE in the nacked eyes. FCLs were decentered a mean of 0.7 +/- 0.19 mm to the temporal cornea. M decreased asymmetrically between nas...

  6. From a spatial adposition to a grammatical relations' marker: contact- and context-induced grammaticalization

    Directory of Open Access Journals (Sweden)

    Leena Kolehmainen

    2010-10-01

    Full Text Available This paper is an investigation of grammatical relations' marking that combines the advances of monolingual analysis with cross-linguistic comparison. It examines adpositions as grammatical relations' markers and the linguistic change which leads to the rise of adpositional objects from freely insertable spatial adverbials. Th is study concentrates on the Finnish adposition perään 'after'. An empirical monolingual corpus analysis shows that perään as a grammatical relations' marker is a productive device for argument linking in contemporary Finnish. In a cross-linguistic comparison, the properties of Swedish, German and Finnish adpositional objects with efter, nach and perään 'after, are studied with regard to the continuum between prototypical freely insertable adverbials and prototypical adpositional objects. A diachronic comparison, in turn, focuses on the development of adpositional objects from spatial adverbials and examines three alternative possibilities for perään: native grammaticalization, contact-induced grammaticalization and the interaction of both language-internal and -external factors.

  7. A case report of fulminant type 1 diabetes mellitus associated with drug-induced hypersensitivity syndrome in an elderly patient with coxsackie B4 virus infection and human leukocyte antigen-A24 haplotype.

    Science.gov (United States)

    Takeno, Ayumu; Kanazawa, Ippei; Morita, Miwa; Takedani, Kai; Miyake, Hitomi; Yamamoto, Masahiro; Nogami, Kyoko; Kaneko, Sakae; Sugimoto, Toshitsugu

    2017-09-29

    Drug-induced hypersensitivity syndrome (DIHS) is a severe systemic adverse drug reaction. Previous studies showed that DIHS is associated with the onset of fulminant type 1 diabetes mellitus (FT1D). Although genetic background and abnormalities in immune response or viral infection are considered to be associated with pathogenesis of FT1D, it remains unclear whether virus infection and specific human leukocyte antigen (HLA) typing are involved in DIHS-associated FT1D. Here, we report a case of a 78-year-old female patient with FT1D after DIHS treatment. She was diagnosed as DIHS caused by carbamazepine, and treatment with predonisolone was initiated. After 46 days from the occurrence of DIHS, she was admitted to our hospital because of type 1 diabetes mellitus and diabetic ketoacidosis. Although her Hemoglobin A1c (HbA1c) was elevated by predonisolone treatment (HbA1c: 9.2%), we diagnosed her as fulminant type 1 diabetes mellitus considering the abrupt onset of the ketoacidosis. Her general condition was improved by treatment with fluid infusion and insulin administration. During her clinical course, the infection of coxsackie B4 virus was observed. In addition, the examination of HLA typing showed HLA-A24 haplotype. These findings suggest that the coxsackie B4 virus infection may be involved in the pathogenesis of DIHS-induced FT1D, and that HLA-A24 haplotype might relate to DIHS-associated FT1D.

  8. The indane diastereoisomers, PH2 and PH5: divergence between their effects in delayed-type hypersensitivity models and a model of colitis.

    Science.gov (United States)

    Frankish, Neil H; McHale, Brendan; Sheridan, Helen

    2017-10-23

    Compounds PH2 and PH5 are distereoisomers of novel indane compounds, synthesised as analogues of secondary metabolites of the fern, Onychium. In this study, we compare their effects on a variety of inflammatory models. In an effort to extend our knowledge of their anti-inflammatory profile, we have investigated their activity in two models of delayed-type hypersensitivity (DTH); the methylated bovine serum albumin model (mBSA) and the oxazolone contact hypersensitivity (CHS) model, on IL2 release from Jurkat cells and in the dextran sulphate sodium (DSS) murine model of inflammatory bowel disease. Both diastereoisomers are equipotent in reducing paw swelling in the mBSA model and in inhibiting interleukin (IL) 2 release from Jurkat cells. They are equally ineffective in the oxazolone contact hypersensitivity model (CHS). Only the diastereoisomer, PH5, protects against DSS-induced colitis and of its two enantiomers, only the S,S-enantiomer, PH22, possesses this activity. PH2 is ineffective in the DSS model. The results suggest that the beneficial effect of PH5, and its enantiomer PH22, in the DSS model is a consequence of an action on a target specific to the colitis model. The implications of such data suggest an unknown target in this disease model that may be exploited to therapeutic advantage. © 2017 Royal Pharmaceutical Society.

  9. Functional Characterization of At-Level Hypersensitivity in Patients With Spinal Cord Injury.

    Science.gov (United States)

    Vogel, Carola; Rukwied, Roman; Stockinger, Lenka; Schley, Marcus; Schmelz, Martin; Schleinzer, Wolfgang; Konrad, Christoph

    2017-01-01

    At-level and above-level hypersensitivity was assessed in patients with chronic complete thoracic spinal cord injury (SCI). Patients were classified using somatosensory mapping (brush, cold, pinprick) and assigned into 2 groups (ie, patients with at-level hypersensitivity [SCIHs, n = 8] and without at-level hypersensitivity [SCINHs, n = 7]). Gender and age-matched healthy subjects served as controls. Quantitative sensory testing (QST), electrically- and histamine-induced pain and itch, laser Doppler imaging, and laser-evoked potentials (LEP) were recorded at-level and above-level in SCI-patients. Six of 8 SCIHs, but 0 of 7 SCINHs patients suffered from neuropathic below-level pain. Clinical sensory mapping revealed spreading of hypersensitivity to more cranial areas (above-level) in 3 SCIHs. Cold pain threshold measures confirmed clinical hypersensitivity at-level in SCIHs. At-level and above-level hypersensitivity to electrical stimulation did not differ significantly between SCIHs and SCINHs. Mechanical allodynia, cold, and pin-prick hypersensitivity did not relate to impaired sensory function (QST), axon reflex flare, or LEPs. Clinically assessed at-level hypersensitivity was linked to below-level neuropathic pain, suggesting neuronal hyperexcitability contributes to the development of neuropathic pain. However, electrically evoked pain was not significantly different between SCI patients. Thus, SCI-induced enhanced excitability of nociceptive processing does not necessarily lead to neuropathic pain. QST and LEP revealed no crucial role of deafferentation for hypersensitivity development after SCI. At-level hypersensitivity after complete thoracic SCI is associated with neuropathic below-level pain if evoked by clinical sensory stimuli. QST, LEP, and electrically-induced axon reflex flare sizes did not indicate somatosensory deafferentation in SCIHs. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  10. Multiple Anesthetic Drug Sensitization in a Hairdresser With Previous Immediate-Type Hypersensitivity to Penicillin: A Case Report.

    Science.gov (United States)

    Petrişor, Cristina; Gherman, Nadia; Sfichi, Manuela; Mureşan, Marius; Hagău, Natalia

    2017-09-01

    Risk factors for intraoperative immediate-type hypersensitivity reactions may require allergological evaluation. We report the case of a hairdresser with a positive history of penicillin hypersensitivity and anaphylactic shock during previous general anesthesia, whose in vivo and in vitro allergy tests were positive for neuromuscular blocking agents, opioids, and midazolam. Immediate-type hypersensitivity reactions to antibiotics and professional exposure to hairdressing products might induce simultaneous cross-sensitization to multiple drugs that are commonly used during general anesthesia.

  11. The use of laboratory methods in contact dermatitis induced by composite materials.

    Science.gov (United States)

    Ayala, F; Lembo, G; Balato, N; Patruno, C; Scognamiglio, G; Strazzullo, G; de Stefano, S

    1990-05-01

    Thin-layer chromatography, column chromatography, mass spectrometry and nuclear magnetic resonance were used to investigate the chemical constituents and haptens responsible in 2 different circumstances where allergic contact dermatitis from composite materials was suspected. In an aircraft factory where epoxy resins were used, tetraglycidyl-4,4'-dimethyl dianiline and phenylglycidyl ether were identified as the haptens responsible for an outbreak of contact dermatitis. The role of abietic acid as the main sensitizer in colophony was confirmed in a case of contact dermatitis occurring in a sportsman with an acute eczematous reaction due to a leg bandage. Identification of the chemical sensitizers was possible only by using the aforementioned laboratory methods.

  12. Murine models of drug hypersensitivity.

    NARCIS (Netherlands)

    Nierkens, S.; Pieters, R.

    2005-01-01

    PURPOSE OF REVIEW: Drug hypersensitivity reactions are relatively rare but may result in severe morbidity and fatalities. Due to the idiosyncratic nature and multifactorial etiology of these reactions, development of a single animal model to study the immunosensitizing mechanisms of all drugs is

  13. Treating hypersensitivity with fluoride varnish.

    Science.gov (United States)

    Gaffar, A

    1999-01-01

    Dentinal hypersensitivity results when stimulation causes the fluid in open dentinal tubules to undergo pressure changes, which activates mechanoreceptor nerves and results in pain. Treatment with fluoride varnish forms a protective layer of calcium fluoride that prevents this fluid flow, thereby reducing dentinal sensitivity.

  14. Treating hypersensitivity with fluoride varnishes.

    Science.gov (United States)

    Gaffar, A

    1998-11-01

    Dentinal hypersensitivity results when stimulation causes the fluid in open dentinal tubules to undergo pressure changes, which activates mechanoreceptor nerves and results in pain. Treatment with fluoride varnish forms a protective layer of calcium fluoride that prevents this fluid flow, thereby reducing dentinal sensitivity.

  15. Anticonvulsant hypersensitivity syndrome | Shamad | Sudanese ...

    African Journals Online (AJOL)

    Anticonvulsant drug hypersensitivity syndrome (AHS) is a severe, life-threatening adverse drug reaction. AHS is a cutaneous eruption associated with the aromatic anticonvulsant drugs: carbamazepine, phenytoin, phenobarbital and lamotrigine. The clinical picture of AHS is characterized by a triad of fever, skin rash and ...

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

    Science.gov (United States)

    Nielsen, Morten M; Schmidt, Jonas D; Christensen, Jan P; Geisler, Carsten; Johansen, Jeanne D; Bonefeld, Charlotte M

    2017-04-01

    Contact allergy is characterized by local skin inflammation that, in some cases, can result in systemic immune activation. To investigate whether IVIS SpectrumCT analyses can be used to detect the immune response induced by contact allergens. 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. 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 FAST did not show any difference between allergen-exposed and control mice, although fluorescence-activated cell sorting analysis of the spleen showed increased numbers of γδ T cells and CD11b(+) CD11c(+) MHCII(+) cells in allergen-treated mice. IVIS SpectrumCT analyses with ProSense 750 FAST as the probe can be used to detect local immune responses induced by contact allergens. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Drug hypersensitivity syndrome caused by minocycline.

    Science.gov (United States)

    Tsuruta, Daisuke; Someda, Yukiko; Sowa, Junko; Kobayashi, Hiromi; Ishii, Masamitsu

    2006-01-01

    Minocycline is a commonly prescribed drug for the treatment of acne. Its use is generally not associated with systemic side effects. To describe a case of minocycline-induced drug hypersensitivity syndrome in a 20-year-old Japanese woman. Following 2 months of minocycline treatment, the patient developed skin lesions composed of exudative maculopapules, purpuratous macules, and target-like, erythema multiforme-like plaques over most of her body. In addition, she had fever, abnormal liver function tests, eosinophilia, and atypical lymphocytosis. Laboratory tests indicated no elevation of antibody titers against cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6. Her ongoing exposure to minocycline was stopped, and treatment with oral prednisolone was begun. Her signs, symptoms, and laboratory abnormalities then began to resolve. Subsequently, the syndrome was observed to return briefly in response to an oral challenge with minocycline. Minocycline is able to elicit a drug hypersensitivity syndrome that can resemble infectious mononucleosis. This drug reaction can be treated effectively by cessation of exposure to this drug and steroid therapy.

  18. Skin permeation and cutaneous hypersensitivity as a basis for making risk assessments of chromium as a soil contaminant

    Energy Technology Data Exchange (ETDEWEB)

    Bagdon, R.E. (UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ (United States) Rutgers, The State Univ. of New Jersey, Piscataway (United States)); Hazen, R.E. (New Jersey Dept. of Environmental Protection, Trenton (United States))

    1991-05-01

    A literature review of experimental and human exposure studies of skin permeation and cutaneous hypersensitivity reactions evoked by chromium was carried out to provide a basis for making a risk assessment of chromium as a soil contaminant. In vitro and in vivo studies demonstrated that 1 to 4% of the applied dose of hexavalent and trivalent chromium to guinea pig skin penetrated skin within 5 to 24 hours after application. Ultrastructural investigations showed that hexavalent chromium localized intracellularly and extracellularly in the upper layers of guinea pig epidermis. The potential of hexavalent chromium to produce a skin sensitization reaction is readily demonstrated using animal models. The incidence and characteristics of chromium-induced skin hypersensitivity as a clinical entity are described. A health effects survey of populations exposed to chromium slag in soil in Tokyo, Japan extending over 8 years indicated a tendency toward symptoms characterized as headache, chromic fatigue, and gastrointestinal complaints, positive occult blood tests, minute hematuria and albuminuria suggestive of incipient renal disease, and a tendency toward an increase in contact dermatitis that was seasonally related. Based on these data, the cleanup level of total chromium in soil is designated as 75 mg/kg. It is proposed that levels of total chromium lower than 75 mg/kg in soil would avoid undue risk of contact dermatitis.

  19. 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.

  20. 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 dorsal root ganglion inflammation.

    Science.gov (United States)

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

    2016-04-01

    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 isoforms in adult DRG, NaV1.6 is the main carrier of tetrodotoxin-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 DRG 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 tetrodotoxin-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.

  1. 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.

  2. Mechanisms of CDC-42 activation during contact-induced cell polarization.

    Science.gov (United States)

    Chan, Emily; Nance, Jeremy

    2013-04-01

    Polarization of early embryos provides a foundation to execute essential patterning and morphogenetic events. In Caenorhabditis elegans, cell contacts polarize early embryos along their radial axis by excluding the cortical polarity protein PAR-6 from sites of cell contact, thereby restricting PAR-6 to contact-free cell surfaces. Radial polarization requires the cortically enriched Rho GTPase CDC-42, which in its active form recruits PAR-6 through direct binding. The Rho GTPase activating protein (RhoGAP) PAC-1, which localizes specifically to cell contacts, triggers radial polarization by inactivating CDC-42 at these sites. The mechanisms responsible for activating CDC-42 at contact-free surfaces are unknown. Here, in an overexpression screen of Rho guanine nucleotide exchange factors (RhoGEFs), which can activate Rho GTPases, we identify CGEF-1 and ECT-2 as RhoGEFs that act through CDC-42 to recruit PAR-6 to the cortex. We show that ECT-2 and CGEF-1 localize to the cell surface and that removing their activity causes a reduction in levels of cortical PAR-6. Through a structure-function analysis, we show that the tandem DH-PH domains of CGEF-1 and ECT-2 are sufficient for GEF activity, but that regions outside of these domains target each protein to the cell surface. Finally, we provide evidence suggesting that the N-terminal region of ECT-2 may direct its in vivo preference for CDC-42 over another known target, the Rho GTPase RHO-1. We propose that radial polarization results from a competition between RhoGEFs, which activate CDC-42 throughout the cortex, and the RhoGAP PAC-1, which inactivates CDC-42 at cell contacts.

  3. Telegraph noise in coupled quantum dot circuits induced by a quantum point contact.

    Science.gov (United States)

    Taubert, D; Pioro-Ladrière, M; Schröer, D; Harbusch, D; Sachrajda, A S; Ludwig, S

    2008-05-02

    Charge detection utilizing a highly biased quantum point contact has become the most effective probe for studying few electron quantum dot circuits. Measurements on double and triple quantum dot circuits is performed to clarify a back action role of charge sensing on the confined electrons. The quantum point contact triggers inelastic transitions, which occur quite generally. Under specific device and measurement conditions these transitions manifest themselves as bounded regimes of telegraph noise within a stability diagram. A nonequilibrium transition from artificial atomic to molecular behavior is identified. Consequences for quantum information applications are discussed.

  4. 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.

  5. Severe type IV hypersensitivity to 'black henna' tattoo.

    Science.gov (United States)

    Vasilakis, Vasileios; Knight, Bernice; Lidder, Satnam; Frankton, Sarah

    2010-10-06

    A 16-year-old Bangladeshi girl presented with a 9-day history of an extensive pruritic, erythematous, papulovesicular skin eruption to both forearms. Appearance was 5 days following application of a home-made henna preparation. Examination revealed ulceration and scabbing along the whole henna pattern and early keloid formation. A diagnosis of type IV delayed hypersensitivity reaction superimposed by infection was initially made. As in this case, home-made henna preparations commonly combine commercial henna with black hair dye, paraphenylenediamine (PPD). PPD, widely known as 'black henna', darkens the pigment and precipitates the drying process. PPD is a potent contact allergen associated with a high incidence of hypersensitivity reactions. Despite treatment the patient was left with extensive keloid scarring in the pattern of the henna tattoo.

  6. Severe type IV hypersensitivity to ‘black henna’ tattoo

    Science.gov (United States)

    Vasilakis, Vasileios; Knight, Bernice; Lidder, Satnam; Frankton, Sarah

    2010-01-01

    A 16-year-old Bangladeshi girl presented with a 9-day history of an extensive pruritic, erythematous, papulovesicular skin eruption to both forearms. Appearance was 5 days following application of a home-made henna preparation. Examination revealed ulceration and scabbing along the whole henna pattern and early keloid formation. A diagnosis of type IV delayed hypersensitivity reaction superimposed by infection was initially made. As in this case, home-made henna preparations commonly combine commercial henna with black hair dye, paraphenylenediamine (PPD). PPD, widely known as ‘black henna’, darkens the pigment and precipitates the drying process. PPD is a potent contact allergen associated with a high incidence of hypersensitivity reactions. Despite treatment the patient was left with extensive keloid scarring in the pattern of the henna tattoo. PMID:22778139

  7. 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

  8. Contact-Induced Language Alternation in Tanzanian Ngoni--An Empirical Study of Frequency and Patterns

    Science.gov (United States)

    Rosendal, Tove; Mapunda, Gastor

    2017-01-01

    The codeswitching pattern is different in rural Tanzania compared to urban agglomerations around the world. Even in very rural areas people in Tanzania are bilingual in Swahili, the national and local lingua franca, and their own first language. The result of this language contact is understudied and has only recently been focused on. This paper…

  9. Changes in ultraviolet transmittance of hydrogel and silicone-hydrogel contact lenses induced by wear.

    Science.gov (United States)

    Osuagwu, Uchechukwu L; Ogbuehi, Kelechi C; Almubrad, Turki M

    2014-01-01

    To evaluate the ultraviolet (UV) transmittance spectra of different contact lenses and assess the effect of wear on UV transmittance values and ocular protection factor (PF). Transmittance in the UV range (200-400 nm) of 216 contact lenses was measured before and after wear, using a spectrophotometer. The contact lenses used were ACUVUE TruEye, ACUVUE MOIST, ACUVUE OASYS, ACUVUE 2, ACUVUE DEFINE, DAILIES AquaComfort Plus, AIR OPTIX for astigmatism, FreshLook ONE-DAY lens, and Neo Cosmo. This study indicates that the following contact lenses transmitted less than the American National Standards Institute (ANSI) of 5% or less of UVB: ACUVUE DEFINE, ACUVUE MOIST, ACUVUE 2, ACUVUE TruEye, and ACUVUE OASYS. All lenses also met the ANSI standard of less than 30% transmittance of UVA except for AquaComfort Plus, AIR OPTIX for astigmatism, and Neo Cosmo. FreshLook meets the UVA transmission standard but fell short of the UVB transmission standard by 3%. FreshLook and ACUVUE MOIST had the highest calculated PF (3.9) of the hydrogel group and were unaffected after wear. Of the silicone-hydrogels (SiHs), the PF for AIR OPTIX for astigmatism was the highest (10.6) before wear and increased after wear to a PF of 13.3. The results also show that, for the UVC region, significant differences exist in transmittance values before and after wear of all SiH lenses and all hydrogel lenses, except for Neo Cosmo. FreshLook and Neo Cosmo were the only lenses that showed no statistically significant differences in the UVA transmittance after wear. Ultraviolet-blocking contact lenses were effective in blocking ultraviolet radiation to safe levels recommended by ANSI, whereas non-UV blockers such as AquaComfort Plus and AIR OPTIX for astigmatism also showed UV-attenuation capabilities greater than the values previously reported. The Neo Cosmo contact lens transmitted greater than 86% UVB and 89% UVA, making it unsuitable for UV protection seekers. Transmission is modified after contact lens

  10. Selective immediate hypersensitivity reactions to NSAIDs.

    Science.gov (United States)

    Canto, Maria Gabriela; Andreu, Isabel; Fernandez, Javier; Blanca, Miguel

    2009-08-01

    Selective immediate reactions to NSAIDs imply that patients develop a urticarial/anaphylactic response to a single drug with good tolerance to other compounds. No systematic review of these reactions has yet been made. With the increase in consumption of NSAIDs, these have become one of the most common drugs inducing hypersensitivity reactions. Although cross-intolerance reactions are the most common, a significant proportion is selective responses. As specific IgE antibodies are not always found, there is only indirect evidence supporting an IgE-mediated mechanism in selective NSAID reactors. Selective immediate reactions to NSAIDs must be considered when a patient develops urticaria or anaphylaxis after intake of one drug with good tolerance to drugs from other groups or even a drug from the same group with a slightly different chemical structure. Further research is required to identify the antigenic determinant structures recognized.

  11. Hypersensitivity to pain in congenital blindness

    DEFF Research Database (Denmark)

    Slimani, Hocine; Danti, Sabrina; Ricciardi, Emiliano

    2013-01-01

    and responses to suprathreshold heat stimuli in 2 groups of congenitally blind and matched normal-sighted participants. We also assessed detection thresholds for innocuous warmth and cold, and participants' attitude toward painful encounters in daily life. Our results show that, compared to sighted subjects......, 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...... 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....

  12. Descending facilitatory pain pathways mediate ongoing pain and tactile hypersensitivity in a rat model of trigeminal neuropathic pain.

    Science.gov (United States)

    Nones, C F M; Claudino, R F; Ferreira, L E N; Dos Reis, R C; King, T; Chichorro, J G

    2017-03-22

    The Chronic Constriction Injury of the Infraorbital Nerve (CCI-ION) is a well-established model to study facial sensory changes related to trigeminal neuropathic pain. CCI-ION induces heat hypersensitivity that resolves within 2-3 weeks and a delayed mechanical hypersensitivity that emerges during the second week post-injury. The role of descending facilitatory pain pathways from the rostro ventromedial medulla (RVM) in mediating the heat and tactile hypersensitivity was examined. CCI-ION induced heat hypersensitivity observed 5days post-surgery was reversed by systemic, but not RVM lidocaine. CCI-ION-induced tactile hypersensitivity observed 15days post-surgery was reversed by systemic lidocaine and attenuated by RVM lidocaine. CCI-ION-induced spontaneous pain was determined using conditioned place preference (CPP) to pain relief at each time-point. At day 5 post-CCI-ION, neither systemic nor RVM lidocaine induced CPP. However, at 15days post-CCI-ION, CPP was observed to the chamber paired with RVM lidocaine, but not systemic lidocaine. These data indicate that CCI-ION induced heat hypersensitivity is not dependent on descending facilitatory pain pathways 5-days post-injury whereas descending facilitatory pain pathways mediate tactile allodynia and spontaneous pain 15days post-CCI-ION. This suggests that CCI-ION induces early peripheral sensitization followed by development of central sensitization that mediates spontaneous pain and contributes to mechanical hypersensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. 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

  14. Hepatic NK cell-mediated hypersensitivity to ConA-induced liver injury in mouse liver expressing hepatitis C virus polyprotein.

    Science.gov (United States)

    Fu, Qiuxia; Yan, Shaoduo; Wang, Licui; Duan, Xiangguo; Wang, Lei; Wang, Yue; Wu, Tao; Wang, Xiaohui; An, Jie; Zhang, Yulong; Zhou, Qianqian; Zhan, Linsheng

    2017-08-08

    The role of hepatic NK cells in the pathogenesis of HCV-associated hepatic failure is incompletely understood. In this study, we investigated the effect of HCV on ConA-induced immunological hepatic injury and the influence of HCV on hepatic NK cell activation in the liver after ConA administration. An immunocompetent HCV mouse model that encodes the entire viral polyprotein in a liver-specific manner based on hydrodynamic injection and φC31o integrase was used to study the role of hepatic NK cells. Interestingly, the frequency of hepatic NK cells was reduced in HCV mice, whereas the levels of other intrahepatic lymphocytes remained unaltered. Next, we investigated whether the reduction in NK cells within HCV mouse livers might elicit an effect on immune-mediated liver injury. HCV mice were subjected to acute liver injury models upon ConA administration. We observed that HCV mice developed more severe ConA-induced immune-mediated hepatitis, which was dependent on the accumulated intrahepatic NK cells. Our results indicated that after the administration of ConA, NK cells not only mediated liver injury through the production of immunoregulatory cytokines (IFN-γ, TNF-α and perforin) with direct antiviral activity, but they also killed target cells directly through the TRAIL/DR5 and NKG2D/NKG2D ligand signaling pathway in HCV mice. Our findings suggest a critical role for NK cells in oversensitive liver injury during chronic HCV infection.

  15. 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®

  16. A novel approach to the calculation of pothole-induced contact forces in MDOF vehicle models

    Science.gov (United States)

    Pesterev, A. V.; Bergman, L. A.; Tan, C. A.

    2004-08-01

    A technique is developed to predict the dynamic contact forces arising after passing road surface irregularities by a vehicle modelled as an undamped multiple-degrees-of-freedom (MDOF) system. An MDOF system moving along an uneven profile is decomposed into an aggregate of independent oscillators in the modal space, such that the response of each oscillator can be calculated independently. An equation relating the contact forces in the physical space to the modal forces is established. The technique developed is applied to the calculation of the coefficients of the harmonic components of the contact forces arising after the passage of a "cosine" pothole. The application of the technique to various problems, such as evaluation of the effect of parameter modifications on the vehicle dynamics and reduction of vehicle models in bridge-related problems, as well as its extension to the damped case, are also discussed. One interesting phenomenon reported in the DIVINE project [1], regarding the replacement of a steel suspension by an air suspension, resulting in an increase of the maximum response of short-span bridges, is explained by applying the technique suggested. The discussion is amply illustrated by examples of the application of the technique to the calculation of the tire forces due to a pothole for two simple—quarter-car and half-car—vehicle models.

  17. Local transfer of delayed-type hypersensitivity after Salmonella infection in mice.

    OpenAIRE

    Attridge, S R; Kotlarski, I

    1985-01-01

    An adoptive local transfer system has been used to study the mediators of delayed-type hypersensitivity induced in mice by infection with Salmonella enteritidis 11RX. The cells which transfer this state of hypersensitivity to untreated recipients are nonadherent T lymphocytes with the surface phenotype Lyt 1+2-, and successful transfer requires compatibility at the I-A subregion of the H-2 complex. In these and other respects these cells are indistinguishable from those previously found to be...

  18. Association of auditory hallucinations and anticonvulsant hypersensitivity syndrome with carbamazepine treatment. A case report.

    Science.gov (United States)

    Beitinger, P A; Kirmeier, T; Bronisch, T; Wetter, T C

    2006-09-01

    Carbamazepine is effective in the treatment of acute mania and in the prevention of episodes in bipolar disorder, and it may also be useful in depression, impulse-control disorder and withdrawal from alcohol and benzodiazepine dependence. A potentially life-threatening side effect is the anticonvulsant hypersensitivity syndrome. Here, we describe a patient who developed severe auditory hallucinations followed by a distinct hypersensitivity syndrome most likely induced by carbamazepine treatment.

  19. Therapeutic efficacy and immunological response of CCL5 antagonists in models of contact skin reaction.

    Directory of Open Access Journals (Sweden)

    Miriam Canavese

    Full Text Available Skin-infiltrating T-cells play a predominant role in allergic and inflammatory skin diseases such as atopic dermatitis, psoriasis and allergic contact dermatitis. These T-cells are attracted by several chemotactic factors including the chemokine CCL5/RANTES, a CC chemokine inducing both the migration and activation of specific leukocyte subsets. CCL5 has been found to be associated with various cell-mediated hypersensitive disorders such as psoriasis, atopic dermatitis and irritant contact dermatitis. We have used two antagonists, the first, Met-CCL5, a dual CCR1/CCR5 antagonist and the second, a variant in which GAG binding is abrogated, (44AANA(47-CCL5, which acts as a dominant negative inhibitor of CCL5. The antagonists were tested in two models of contact skin reaction. The first, irritant contact dermatitis (ICD is a pathological non-specific inflammatory skin condition arising from the release of pro-inflammatory cytokines by keratinocytes in response to haptens, usually chemicals. The second, contact hypersensitivity (CHS is a T-cell dependent model, mimicking in part the T-cell-mediated skin diseases such as psoriasis. In both models, the CCL5 antagonists showed therapeutic efficacy by reducing swelling by 50% as well as the reduction of soluble mediators in homogenates derived from challenged ears. These results demonstrate that blocking the receptor or the ligand are both effective strategies to inhibit skin inflammation.

  20. Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs: from phenotyping to genotyping.

    Science.gov (United States)

    Blanca-López, Natalia; Barrionuevo, Ester; Andreu, Inmaculada; Canto, María G

    2014-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequent drugs involved in hypersensitivity drugs reactions. Both immunological and nonimmunological mechanisms can be involved. We describe the different phenotypes as well as analyze the genetic basis for NSAIDs hypersensitivity. Five major clinical entities are currently accepted in the classification of hypersensitivity reactions to NSAIDs. Three are mediated by nonspecific immunological mechanisms: NSAIDs-exacerbated respiratory disease, NSAIDs-exacerbated cutaneous disease and NSAIDs-induced urticaria/angioedema. Two are mediated by specific immunological mechanisms: single-NSAID-induced urticaria/angioedema or anaphylaxis and single-NSAID-induced delayed hypersensitivity reactions. The classification becomes more complex if we consider that in an important number of cases skin and airway involvement can occur, as well as the participation of other organs. Hypersensitivity reactions to NSAIDs are more complex than for other drugs like betalactams in terms of the number and types of reactions elicited, and mechanisms involved. As NSAIDs are the most frequent cause of drug hypersensitivity, it is feasible to gather a sufficient number of cases for undertaking pharmacogenetic studies.

  1. Antisense expression of an Arabidopsis ran binding protein renders transgenic roots hypersensitive to auxin and alters auxin-induced root growth and development by arresting mitotic progress

    Science.gov (United States)

    Kim, S. H.; Arnold, D.; Lloyd, A.; Roux, S. J.

    2001-01-01

    We cloned a cDNA encoding an Arabidopsis Ran binding protein, AtRanBP1c, and generated transgenic Arabidopsis expressing the antisense strand of the AtRanBP1c gene to understand the in vivo functions of the Ran/RanBP signal pathway. The transgenic plants showed enhanced primary root growth but suppressed growth of lateral roots. Auxin significantly increased lateral root initiation and inhibited primary root growth in the transformants at 10 pM, several orders of magnitude lower than required to induce these responses in wild-type roots. This induction was followed by a blockage of mitosis in both newly emerged lateral roots and in the primary root, ultimately resulting in the selective death of cells in the tips of both lateral and primary roots. Given the established role of Ran binding proteins in the transport of proteins into the nucleus, these findings are consistent with a model in which AtRanBP1c plays a key role in the nuclear delivery of proteins that suppress auxin action and that regulate mitotic progress in root tips.

  2. 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.

  3. 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.

  4. [Hypersensitivity to fluindione (Previscan). Positive skin patch tests].

    Science.gov (United States)

    Frouin, E; Roth, B; Grange, A; Grange, F; Tortel, M-C; Guillaume, J-C

    2005-12-01

    Fluindione (Previscan) is an oral anticoagulant belonging to the vitamin K antagonist class and is very widely used in France. While bleeding is a common complication, severe immunoallergic reactions are less frequent. The authors report a case of drug-induced hypersensitivity syndrome. A 75 year-old woman was hospitalized for diffuse erythematous papular rash associated with facial oedema. These symptoms appeared 3 weeks after the beginning of treatment with fluindione, allopurinol and perindopril. Laboratory tests showed hyperleukocytosis, mixed hepatitis and moderate renal failure, with the entire picture being evocative of drug-induced hypersensitivity reaction. The eruption was associated with eosinophilia, hepatic cytolysis with cholestasis, and acute renale failure. While allopurinol and perindopril were stopped definitively, fluindione was only suspended temporarily following overdosage. On reintroduction, rapid recurrence of clinical and biologic signs was observed with increased severity. The skin rash resolved completely on withdrawal of the drug. Patch tests performed later were positive for fluindione and negative for allopurinol and perindopril. These manifestations were consistent with the diagnosis of drug-induced hypersensitivity syndrome due to fluindione. Very few cases have been described with fluindione despite widespread prescription of the treatment is in France. While there may be no skin involvement, immunoallergic signs such as fever, hepatitis and acute tubular interstitial nephritis have been described with fluindione and these may be related to this syndrome (DRESS - Drug Reaction with Eosinophilia and Systemic Symptoms). Skin patch testing, which is easily performed, can be extremely helpful in determining a causal relationship with medication.

  5. Proposed ICDRG Classification of the Clinical Presentation of Contact Allergy

    DEFF Research Database (Denmark)

    Pongpairoj, Korbkarn; Ale, Iris; Andersen, Klaus Ejner

    2016-01-01

    eczema, multifactorial dermatitis including allergic contact dermatitis, by proxy, mimicking angioedema, airborne contact dermatitis, photo-induced contact dermatitis, systemic contact dermatitis, noneczematous contact dermatitis, contact urticaria, protein contact dermatitis, respiratory...

  6. 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.

  7. A subset of AID-dependent B-1a cells initiates hypersensitivity and pneumococcal pneumonia resistance

    NARCIS (Netherlands)

    Askenase, Phillip W; Bryniarski, Krzysztof; Paliwal, Vipin; Redegeld, Frank; Groot Kormelink, Thomas; Kerfoot, Steven; Hutchinson, Andrew T; van Loveren, Henk; Campos, Regis; Itakura, Atsuko; Majewska-Szczepanik, Monika; Yamamoto, Natsuo; Nazimek, Katarzyn; Szczepanik, Marian; Ptak, Wold

    2015-01-01

    We propose that there is a special B-1a B cell subset ("sB-1a" cells) that mediates linked processes very early after immunization to initiate cutaneous contact sensitivity (CS), delayed-type hypersensitivity (DTH), and immune resistance to pneumococcal pneumonia. Our published data indicate that in

  8. Dietary Indoles Suppress Delayed-Type Hypersensitivity by Inducing a Switch from Proinflammatory Th17 Cells to Anti-Inflammatory Regulatory T Cells through Regulation of MicroRNA.

    Science.gov (United States)

    Singh, Narendra P; Singh, Udai P; Rouse, Michael; Zhang, Jiajia; Chatterjee, Saurabh; Nagarkatti, Prakash S; Nagarkatti, Mitzi

    2016-02-01

    Aryl hydrocarbon receptor (AhR) has been shown to have profound influence on T cell differentiation, and use of distinct AhR ligands has shown that whereas some ligands induce regulatory T cells (Tregs), others induce Th17 cells. In the present study, we tested the ability of dietary AhR ligands (indole-3-carbinol [I3C] and 3,3'-diindolylmethane [DIM]) and an endogenous AhR ligand, 6-formylindolo(3,2-b)carbazole (FICZ), on the differentiation and functions of Tregs and Th17 cells. Treatment of C57BL/6 mice with indoles (I3C or DIM) attenuated delayed-type hypersensitivity (DTH) response to methylated BSA and generation of Th17 cells while promoting Tregs. In contrast, FICZ exacerbated the DTH response and promoted Th17 cells. Indoles decreased the induction of IL-17 but promoted IL-10 and Foxp3 expression. Also, indoles caused reciprocal induction of Tregs and Th17 cells only in wild-type (AhR(+/+)) but not in AhR knockout (AhR(-/-)) mice. Upon analysis of microRNA (miR) profile in draining lymph nodes of mice with DTH, treatment with I3C and DIM decreased the expression of several miRs (miR-31, miR-219, and miR-490) that targeted Foxp3, whereas it increased the expression of miR-495 and miR-1192 that were specific to IL-17. Interestingly, treatment with FICZ had precisely the opposite effects on these miRs. Transfection studies using mature miR mimics of miR-490 and miR-1192 that target Foxp3 and IL-17, respectively, or scrambled miR (mock) or inhibitors confirmed that these miRs specifically targeted Foxp3 and IL-17 genes. Our studies demonstrate, to our knowledge for the first time, that the ability of AhR ligands to regulate the differentiation of Tregs versus Th17 cells may depend on miR signature profile. Copyright © 2016 by The American Association of Immunologists, Inc.

  9. Stipatosis or hypersensitivity pneumonitis caused by esparto (Stipa tenacissima) fibers.

    Science.gov (United States)

    Hinojosa, M

    2001-01-01

    Hypersensitivity pneumonitis or extrinsic allergic alveolitis may be defined as an immunological pulmonary disease caused by a variety of antigens reaching the lungs through inhaled organic and inorganic dusts derived from different sources, although they are usually occupational. Farmer's lung and pigeon breeder's lung are probably the most well-known types of hypersensitivity pneumonitis worldwide. Esparto grass (Stipa tenacissima), which is a grammineous plant which is commonly found in the Mediterranean countries, has a wide variety of uses. Esparto fiber is used for the manufacturing of ropes, hemp sandals, rush mats and parkets; for decorative stucco plates, used on walls and ceilings. Esparto supports a large industry in Spain. The first reports referring to esparto dust as a cause of respiratory disease did not appear until the 1960s, and it was first described as a byssinosis-like disorder. The first cases reported, in which immunologic and challenge tests were used to confirm this association, were described 14 years ago and referred as hypersensitivity pneumonitis nominated as stipatosis. Later, a large number of cases of esparto dust-induced hypersensitivity pneumonitis were reported by different authors, so that esparto may be nowadays considered as the main substance causing extrinsic allergic alveolitis in Spain. Afumigatus has been revealed to be the main inducing cause of stipatosis but probably is not the only one since other microorganisms could be implicated. On the other hand esparto fibers may also cause occupational asthma. In this article the prominent clinical findings of this disease as well as the results of serologic, bronchoalveolar lavage (BAL) and specific inhalation tests are shown. A complete historical review of esparto-induced allergic respiratory disease is also described.

  10. 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

  11. Central hypersensitivity in chronic musculoskeletal pain

    DEFF Research Database (Denmark)

    Curatolo, Michele; Arendt-Nielsen, Lars

    2015-01-01

    standards. Reference values in the pain-free population have been generated, but need replication. Research on pain biomarkers that reflect specific central hypersensitivity processes is warranted. Few studies have analyzed the prognostic value of central hypersensitivity. Most medications acting at central...

  12. Electromagnetic hypersensitivity: fact or fiction?

    Science.gov (United States)

    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. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Pain hypersensitivity and spinal nociceptive hypersensitivity in chronic pain: prevalence and associated factors.

    Science.gov (United States)

    Curatolo, Michele; Müller, Monika; Ashraf, Aroosiah; Neziri, Alban Y; Streitberger, Konrad; Andersen, Ole K; Arendt-Nielsen, Lars

    2015-11-01

    Hypersensitivity of pain pathways is considered a relevant determinant of symptoms in chronic pain patients, but data on its prevalence are very limited. To our knowledge, no data on the prevalence of spinal nociceptive hypersensitivity are available. We studied the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity in 961 consecutive patients with various chronic pain conditions. Pain threshold and nociceptive withdrawal reflex threshold to electrical stimulation were used to assess pain hypersensitivity and spinal nociceptive hypersensitivity, respectively. Using 10th percentile cutoff of previously determined reference values, the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity (95% confidence interval) was 71.2 (68.3-74.0) and 80.0 (77.0-82.6), respectively. As a secondary aim, we analyzed demographic, psychosocial, and clinical characteristics as factors potentially associated with pain hypersensitivity and spinal nociceptive hypersensitivity using logistic regression models. Both hypersensitivity parameters were unaffected by most factors analyzed. Depression, catastrophizing, pain-related sleep interference, and average pain intensity were significantly associated with hypersensitivity. However, none of them was significant for both unadjusted and adjusted analyses. Furthermore, the odds ratios were very low, indicating modest quantitative impact. To our knowledge, this is the largest prevalence study on central hypersensitivity and the first one on the prevalence of spinal nociceptive hypersensitivity in chronic pain patients. The results revealed an impressively high prevalence, supporting a high clinical relevance of this phenomenon. Electrical pain thresholds and nociceptive withdrawal reflex explore aspects of pain processing that are mostly independent of sociodemographic, psychological, and clinical pain-related characteristics.

  14. Acrylate-induced allergic contact dermatitis in a car windscreen repairer.

    Science.gov (United States)

    Fremlin, G; Sansom, J

    2014-10-01

    We report a case of an allergic skin reaction to ultraviolet-cured acrylates in a windscreen repair worker. The patient presented with a 6 month history of fingertip dryness, vesicles and desquamation. He had worked as a self-employed car windscreen repairer for 19 years. Previous management with vinyl glove protection and treatment with clobetasol propionate ointment had produced little improvement. He was patch tested to the British Society for Cutaneous Allergy standard and preservatives series and to the two acrylates used in his work environment, identified using safety data sheets, methyl methacrylate 2% pet and 2-hydroxyethylmethacrylate (2-HEMA) 2% pet. A positive reaction was seen at Day 4 to 2-HEMA, but all other patch tests were negative. An occupational allergic contact dermatitis to 2-HEMA was diagnosed. The patient was given avoidance advice and advised to use nitrile gloves. Although he was unable to give up his current work, he has continued his job using nitrile gloves with marked improvement. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Systemic contact dermatitis

    Directory of Open Access Journals (Sweden)

    Daria Nowak

    2016-02-01

    Full Text Available Systemic contact dermatitis (SCD is a skin inflammation occurring in a patient after systemic administration of a hapten, which previously caused an allergic contact skin reaction in the same person. Most frequently, hypersensitivity reactions typical for SCD occur after absorption of haptens with food or inhalation. Haptens occur mainly in the forms of metals and compounds present in natural resins, preservatives, food thickeners, flavorings and medicines. For many years, several studies have been conducted on understanding the pathogenesis of SCD in which both delayed type hypersensitivity (type IV and immediate type I are observed. Components of the complement system are also suspected to attend there. Helper T cells (Th (Th1 and Th2, cytotoxic T lymphocytes (Tc, and NK cells play a crucial role in the pathogenesis of SCD. They secrete a number of pro-inflammatory cytokines. In addition, regulatory T cells (Tregs have an important role. They control and inhibit activity of the immune system during inflammation. Tregs release suppressor cytokines and interact directly with a target cell through presentation of immunosuppressive particles at the cell surface. Diagnostic methods are generally the patch test, oral provocation test, elimination diet and lymphocyte stimulation test. There are many kinds of inflammatory skin reactions caused by systemic haptens’ distribution. They are manifested in a variety of clinical phenotypes of the disease.

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

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    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.

  17. Observation of superconductivity induced by a point contact on 3D Dirac semimetal Cd3 As2 crystals

    Science.gov (United States)

    Wang, He; Wang, Huichao; Liu, Haiwen; Lu, Hong; Yang, Wuhao; Jia, Shuang; Liu, Xiongjun; Xie, Xincheng; Wei, Jian; Wang, Jian

    The 3D Dirac semimetal state is located at the topological phase boundary and can potentially be driven into other topological phases including topological insulator, topological metal and the long-pursuit topological superconductor states. Crystalline Cd3As2 has been proposed and proved to be one of 3D Dirac semimetals which can survive in atmosphere. By precisely controlled point contact (PC) measurements, we observe the exotic superconductivity in the vicinity of the point contact region on the surface of Cd3As2 crystal, which might be induced by the local pressure in the out-of-plane direction from the metallic tip for PC. The observation of zero bias conductance peak (ZBCP) and double conductance peaks (DCPs) symmetric to zero bias further reveals p-wave like unconventional superconductivity in Cd3As2. Considering the special topological property of the 3D Dirac semimetal, our findings may indicate that the Cd3As2 crystal under certain conditions is a candidate of topological superconductor, which is predicted to support Majorana zero modes or gapless Majorana edge/surface modes on the boundary depending on the dimensionality of the material. This work was financially supported by the National Basic Research Program of China (Greanted Nos. 2012CB927400).

  18. Acupoint Specificity on Colorectal Hypersensitivity Alleviated by Acupuncture and the Correlation with the Brain-Gut Axis.

    Science.gov (United States)

    Wang, Shao-Jun; Yang, Hao-Yan; Wang, Fang; Li, Si-Ting

    2015-06-01

    This project was focused on the study of the effect of the different acupoints on visceral hypersensitivity and the correlation with the brain-gut axis. By using a mouse model of zymosan-induced colorectal hypersensitivity, and observing the response of hypersensitivity model to colorectal distension stimulation in acupuncture at different acupoints, we selected the specific acupoints. With immunohistochemical staining method, we observed c-fos expression, distribution and changes after acupuncture on sensory pathway, including colorectum, spinal dorsal horn and different regions of brain center in the model with colorectal distension stimulation, and evaluated the acupuncture effect on brain-gut axis. The results revealed that the effectiveness of acupuncture for alleviating visceral hypersensitivity was different at individual acupoint, meaning Tianshu (ST25), Zusanli (ST36) and Shangjuxu (ST37) > Quchi (LI11) and Dachangshu (BL25) > Ciliao (BL32). C-fos expression was concentrated in anterior cingulate cortex, hypothalamus, spinal dorsal horn and colorectum in model of zymosan-induced colorectal hypersensitivity and it was down-regulated after acupuncture. The results demonstrates that the acupoint specificity presents in acupuncture for relieving visceral hypersensitivity and the effects are more predominated at the acupoints on stomach meridian innervated by the same or adjacent spinal ganglion segments. The model of zymosan-induced colorectal hypersensitivity can be the animal model simulating brain-gut interaction.

  19. Aspergillus-associated hypersensitivity respiratory disorders.

    Science.gov (United States)

    Shah, Ashok

    2008-01-01

    The mould Aspergillus is responsible for a gamut of respiratory diseases ranging from saprobic colonisation to rapidly invasive disseminated disease. The clinical spectrum of Aspergillus-associated hypersensitivity respiratory disorders includes Aspergillus induced asthma, allergic bronchopulmonary aspergillosis (ABPA), allergic Aspergillus sinusitis (AAS) and hypersensitivity pneumonitis. Inhalant allergens, in patients with allergic asthma, play a key role in bringing about the inflammation present in the airways, and fungi are increasingly being recognised as important inhalant allergens. Aspergillus is linked to asthma in more ways than one. In the asthmatic subjects, the fungal spores are trapped in the thick and viscid secretions that are usually present in the airways. This generally develops in atopic subjects and is sustained by continuous inhalation of Aspergillus antigens, triggering asthma that may be more severe in form. Aspergillus induced asthma is yet to receive the recognition that it deserves. Allergic bronchopulmonary aspergillosis is the best known form of allergic aspergillosis and is an emerging disease in India. An immunologically mediated lung disease, ABPA occurs predominantly in patients with asthma. A set of diagnostic criteria is required as there is no single test that establishes the diagnosis apart from demonstration of central bronchiectasis with normal tapering bronchi, a feature considered to be pathognomonic of ABPA. Radiologically, ABPA is characterised by 'transient pulmonary infiltrates' or 'fleeting shadows', often confused with pulmonary tuberculosis. A comparatively more recently recognised clinical entity, AAS is characterised by mucoid impaction in the paranasal sinuses which is akin to that in ABPA. Although it appears that the patient with ABPA provides a favourable milieu for the occurrence of AAS, it is perhaps surprising that in spite of similar histopathological features the co-existence of both these diseases has

  20. Clinical heterogeneity of drug hypersensitivity.

    Science.gov (United States)

    Roujeau, Jean-Claude

    2005-04-15

    Skin is the most frequent target of drug reactions that are reported, may be because they are easily detected. Most (probably more than 90%) are related to drug hypersensitivity, i.e. an individually tailored, unexpected effect mediated by a drug specific activation of the immune response. The clinical presentation of "drug eruptions" is highly variable, from the most common transient and benign erythema that occurs 6-9 days after the introduction of a new drug in 1 to 3 % of users to the most severe forms, that fortunately affect less than 1/10,000 users. Even though there are some overlapping or unclassifiable cases, it is important for clinicians to recognize and categorize severe cutaneous adverse reactions/SCAR (bullous fixed drug eruptions/bFDE, acute generalized exanthematous pustulosis/AGEP, drug reaction with eosinophilia and systemic symptoms/DRESS, Stevens-Johnson syndrome/SJS, toxic epidermal necrolysis/TEN). First they must suspect rapidly that an unusual eruption with high fever and severe constitutional symptoms is caused by a medication and not by an infection. Second they have to look for involvement of organs that differ according to the type of reaction. Third they can determine a prognosis, the mortality rate being virtually 0 for bFDE, 5% for AGEP, 10% for "hypersensitivity syndrome"/DRESS and 25% for SJS or TEN. In addition if some medications are "usual suspects" for all types (e.g. anticonvulsants), some other are more specific of a given pattern (pristinamycine, hydroxychloroquine, diltiazem for AGEP, minocycline for DRESS, anti-infectious sulfonamides, allopurinol for epidermal necrolysis). The "phenotypic" diversity of the final expression drug reactions can be explained by the engagement of a variety of cytokines and inflammatory cells and by regulatory mechanisms. For example, memory cytotoxic T-Cells are key effectors in both localized blisters of bFDE and in extensive blisters of epidermal necrolysis.

  1. Physical disruption of cell-cell contact induces VEGF expression in RPE cells.

    Science.gov (United States)

    Farjood, Farhad; Vargis, Elizabeth

    2017-01-01

    To investigate the role of RPE cell-cell contact in vascular endothelial growth factor (VEGF) protein expression in cultures of primary human RPE (hRPE) cells and a human RPE cell line (ARPE-19). Two in vitro methods, scratching and micropatterning, were used to control the physical dissociation of RPE cell-cell junctions. Scratching was performed by scoring monolayers of RPE cells with a cell scraper. Micropatterning was achieved by using a stencil patterning method. Extracellular VEGF expression was assessed by using an enzyme-linked immunosorbent assay (ELISA) kit. Immunocytochemistry (ICC) was performed to visualize the expression and localization of VEGF and intercellular proteins zonula occludens-1 (ZO-1), N-cadherin, β-catenin, and claudin-1 in RPE cultures. Higher expression of VEGF protein by cells on the edges of the scratched RPE layers was confirmed with ICC in short-term (1 day after confluency) and long-term (4 weeks after confluency) cultures. According to the ICC results, ZO-1, N-cadherin, β-catenin, and claudin-1 successfully localized to cell-cell junctions in long-term cultures of ARPE-19 and hRPE cells. However, unlike N-cadherin, β-catenin, and claudin-1, only ZO-1 localized junctionally in short-term cultures of both cell types. Moreover, removing cell-cell junctions by scratching resulted in the delocalization of ZO-1 from tight junctions to the cytoplasm. The loss of tight junction formation and the accumulation of ZO-1 in the cytoplasm correlated with increased VEGF expression. Micropatterning RPE cells on different sized circular patterns produced varying concentrations of cells with lost cell-cell junctions. When fewer cells formed intercellular junctions, increased extracellular VEGF secretion was observed from the ARPE-19 and hRPE cells. VEGF expression increases after physical disruption of RPE cell-cell connections. This increase in VEGF expression correlates with the loss of intercellular junctions and the localization of ZO-1 in

  2. 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.

  3. 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.

  4. Regulation of murine hypersensitive responses by Fc receptors

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    Toshiyuki Takai

    1998-01-01

    Full Text Available Humoral and cellular immune responses communicate with each other via Fc receptors (FcR expressed on various hematopoietic cells. Recent studies on several FcR knockout mice demonstrated pivotal roles of an IgG/FcγR system in the regulation of immune responses and the onset of hypersensitivity. The γ subunit of FcR is an essential component of the complex and is required for both receptor assembly and signal transduction. FcR γ chain-deficient mice have lost the functional expression of FcεRI, FcγRI, and FcγRIII and are unable to mount several types of hypersensitive reactions, including the skin Arthus reaction. In contrast, FcγRII-deficient mice exhibit augmented humoral immune responses and IgG-mediated anaphylaxis reactions. Thus, the regulatory system of murine hypersensitive responses involves both positive and negative signaling through FcR. In B cells, FcγRIIb modulates membrane Ig-induced Ca2+ mobilization by inhibiting Ca2+ influx through phosphorylation of its immunoreceptor tyrosine-based inhibition motif and recruitment of cytoplasmic phosphatases. Elucidation of the detailed mechanisms of negative regulatory signaling in the inflammatory effector cells by FcγRIIb as well as several groups of potent inhibitory molecules expressed on such cells should be valuable in the development of novel therapeutic procedures for allergic disorders.

  5. Dynamic hydrolase activities precede hypersensitive tissue collapse in tomato seedlings.

    Science.gov (United States)

    Sueldo, Daniela; Ahmed, Ali; Misas-Villamil, Johana; Colby, Tom; Tameling, Wladimir; Joosten, Matthieu H A J; van der Hoorn, Renier A L

    2014-08-01

    Hydrolases such as subtilases, vacuolar processing enzymes (VPEs) and the proteasome play important roles during plant programmed cell death (PCD). We investigated hydrolase activities during PCD using activity-based protein profiling (ABPP), which displays the active proteome using probes that react covalently with the active site of proteins. We employed tomato (Solanum lycopersicum) seedlings undergoing synchronized hypersensitive cell death by co-expressing the avirulence protein Avr4 from Cladosporium fulvum and the tomato resistance protein Cf-4. Cell death is blocked in seedlings grown at high temperature and humidity, and is synchronously induced by decreasing temperature and humidity. ABPP revealed that VPEs and the proteasome are not differentially active, but that activities of papain-like cysteine proteases and serine hydrolases, including Hsr203 and P69B, increase before hypersensitive tissue collapse, whereas the activity of a carboxypeptidase-like enzyme is reduced. Similar dynamics were observed for these enzymes in the apoplast of tomato challenged with C. fulvum. Unexpectedly, these challenged plants also displayed novel isoforms of secreted putative VPEs. In the absence of tissue collapse at high humidity, the hydrolase activity profile is already altered completely, demonstrating that changes in hydrolase activities precede hypersensitive tissue collapse. © 2014 The Authors New Phytologist © 2014 New Phytologist Trust.

  6. Hypersensitivity Reactions to Non-Steroidal Anti-Inflammatory Drugs.

    Science.gov (United States)

    Dona, Inmaculada; Salas, Maria; Perkins, James R; Barrionuevo, Esther; Gaeta, Francesco; Cornejo-Garcia, Jose A; Campo, Paloma; Torres, Maria Jose

    2016-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the leading causes of hypersensitivity reactions to drugs, and they are classified in two groups: those induced by nonspecific immunological mechanisms (non-allergic or cross-intolerance (CI) reactions), or by specific immunological mechanisms (allergic or selective reactions (SR)). The pathogenesis of CI is associated with their pharmacological activity (COX-1 inhibition), with symptoms due to an imbalance in the arachidonic acid pathway, independently of their chemical structure. SRs are mediated by specific IgE- or by a T-cell response and can be induced by a single NSAID or a class of chemically related NSAIDs, with patients tolerating chemically unrelated compounds. NSAIDs hypersensitivity reactions have been classified in five main groups: i) NSAIDs-exacerbated respiratory disease (NERD); ii) NSAIDs-exacerbated cutaneous disease (NECD); iii) NSAIDs-induced urticaria/angioedema (NIUA); iv) Single NSAID-induced urticaria/angioedema or anaphylaxis (SNIUAA); v) Single NSAID-induced delayed reactions (SNIDRs). Although this classification described above is widely accepted by most authors some phenotypes such as blended reactions do not fit. Therefore more research is needed in this topic. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Staphylococcal α -toxin: Oligomerization of Hydrophilic Monomers to Form Amphiphilic Hexamers Induced through Contact with Deoxycholate Detergent Micelles

    Science.gov (United States)

    Bhakdi, Sucharit; Fussle, Roswitha; Tranum-Jensen, Jorgen

    1981-09-01

    Native staphylococcus aureus α -toxin is secreted as a hydrophilic polypeptide chain of Mr 34,000. The presence of deoxycholate above the critical micellar concentration induced the toxin monomers to self-associate, forming ring or cylindrical oligomers. The oligomers were amphiphilic and bound detergent. In deoxycholate solution, the protein-detergent complexes exhibited a sedimentation coefficient of 10.4 S. A Mr of 238,700 was determined by ultracentrifugation analyses at sedimentation equilibrium. Because quantitative detergent-binding studies indicated a protein/detergent ratio of approximately 5:1 (wt/wt), the protein moiety in each protein-detergent complex was determined to be approximately Mr 200 000, corresponding to a hexamer of the native molecule. The amphiphilic toxin hexamers were ultrastructurally indistinguishable from the cytolytic, annular toxin complexes that form on and in biological target membranes. They bound lipid and could be incorporated into artificial lecithin lipid vesicles. The transition of toxin protein molecules from a hydrophilic monomer to an amphiphilic oligomer through self-association has thus been shown to be inducible solely through contact of the native protein molecules with an appropriate amphiphilic substrate.

  8. Microarray analysis of gene expression induced by sexual contact in Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Carvalho Omar S

    2007-06-01

    related to gene expression induced by sexual maturation in female schistosome worms. They also increase the list of S. mansoni maturation associated transcripts considerably, therefore opening new and exciting avenues for the study of the conjugal biology and development of new drugs against schistosomes.

  9. 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...

  10. Seminal plasma hypersensitivity reactions: an updated review.

    Science.gov (United States)

    Sublett, J Wesley; Bernstein, Jonathan A

    2011-01-01

    Seminal plasma hypersensitivity manifests as a spectrum of systemic and/or localized clinical symptoms after exposure to specific protein components in seminal fluid. The prevalence of this disease is largely unknown, but it is believed to affect up to 40,000 women in the United States. Although no definitive risk factors have been confirmed, women with systemic reactions are frequently atopic. Prostate-specific antigen is believed to be the major allergen involved in the disorder, but other proteins are likely involved. Interestingly, up to 40%-50% of both systemic and localized seminal plasma hypersensitivity cases can occur after first-time intercourse. Diagnosis is based on clinical history. The gold standard for diagnosing seminal plasma hypersensitivity is prevention of symptoms with the use of a condom. Patients with seminal plasma hypersensitivity demonstrate positive prick skin test and/or serum-specific immunoglobulin E to whole seminal fluid or fractionated seminal plasma proteins. Treatment of seminal plasma hypersensitivity involves either avoidance with the use of condoms, intravaginal graded challenge using dilutions of whole seminal fluid, or subcutaneous desensitization to relevant fractionated seminal plasma proteins obtained from the woman's sexual partner. In most cases, treatment using one or more of the above approaches has been very successful. Infertility has not been demonstrated to be directly related to seminal plasma hypersensitivity, although women with the condition frequently have difficulty conceiving due to their inability to have unprotected sexual intercourse. © 2011 Mount Sinai School of Medicine.

  11. Enhance postoperative filtering bleb-induced vision difficulties with well-fitted GP contact (oxygen-permeable) lenses.

    Science.gov (United States)

    Pederson, Kaaryn

    2005-02-01

    Occasionally contact lenses need to be fit on patients with filtering blebs. Gas-permeable (GP) lens fitting is still controversial because, although the contact lens can improve visual acuity and satisfy a patient's visual need, it can also compromise the bleb and increase the risk of ocular infection. A retrospective review of charts evaluated patients wearing a GP contact lens a minimum of two months after trabeculectomy surgery. Seven optometrists and one ophthalmologist submitted data on 20 eyes (15 subjects). Success of the contact lenses on these eyes was evaluated, as well as patient history and ocular complications from the contact lens. Contact lens success was based on the patient's ability to wear a GP contact lens a minimum of 6 hours a day, at least 4 days a week, without permanent damage or significant compromise to the bleb. GP contact lenses were successfully fit and worn on 17 of 20 eyes with a functioning filtering bleb (85%). Two of the 17 eyes terminated GP contact lens use after a few years for reasons unrelated to contact lens wear. Three eyes (15%) were unsuccessful and discontinued GP contact lens wear. Of the three eyes that were not successful in wearing a GP contact lens, two eyes discontinued wear secondary to contact lens intolerance and one eye discontinued contact lens wear as a result of fitting difficulties. There were no complications of blebitis or endophthalmitis, but two eyes were treated for bleb laceration and staining of the bleb. GP contact lenses can be successfully worn in eyes with filtering blebs. However, to reduce the risk of complication and infection, proper fitting guidelines should be followed and patients should return for evaluations at intervals of 6 months or less.

  12. Contributions of Interleukin-33 and TSLP in a papain-soaked contact lens-induced mouse conjunctival inflammation model.

    Science.gov (United States)

    Sugita, Jobu; Asada, Yosuke; Ishida, Waka; Iwamoto, Satoshi; Sudo, Katsuko; Suto, Hajime; Matsunaga, Toru; Fukuda, Ken; Fukushima, Atsuki; Yokoi, Norihiko; Ohno, Tatsukuni; Azuma, Miyuki; Ebihara, Nobuyuki; Saito, Hirohisa; Kubo, Masato; Nakae, Susumu; Matsuda, Akira

    2017-12-01

    Pathological changes of severe chronic allergic conjunctivitis are driven not only via acquired immunity but also via innate immunity. Type 2 immune response-initiating cytokines may play some roles as innate immunity-dependent components of the ocular surface inflammation. To investigate the involvement of type 2 immune response-initiating cytokines in innate immunity-dependent, papain-induced conjunctival inflammation model using IL-25-, IL-33-, and TSLP receptor (TSLPR)-knockout (KO) mice with reference to basophils and ILC2. Papain-soaked contact lenses (papain-CLs) were installed in the conjunctival sacs of C57BL/6-IL-25 KO, IL-33 KO, TSLPR KO, Rag2 KO, Bas-TRECK, and wild-type mice and their eyes were sampled at day 5. The eosinophil and basophil infiltration in papain-CL model was evaluated histologically and cytokine expression was examined. To clarify the roles of basophils and ILC2, basophil/ILC2-depletion experiments were carried out. Papain-induced conjunctival inflammation exhibited eosinophil infiltration and upregulation of Th2 cytokine expression. Reduction of eosinophil and basophil infiltration and attenuated Th2 cytokine expression were observed in the papain-CL model using IL-33 KO and TSLPR KO mice. Depletion of basophils or ILC2s in the conjunctivae of the papain-CL model reduced eosinophil infiltration. Innate immunity-driven type 2 immune responses of the ocular surface are dependent on IL-33, TSLP, basophils, and ILC2. These components may be possible therapeutic targets for refractory allergic keratoconjunctivitis. © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

  13. Platelets induce apoptosis during sepsis in a contact-dependent manner that is inhibited by GPIIb/IIIa blockade.

    Directory of Open Access Journals (Sweden)

    Matthew Sharron

    Full Text Available PURPOSE: End-organ apoptosis is well-described in progressive sepsis and Multiple Organ Dysfunction Syndrome (MODS, especially where platelets accumulate (e.g. spleen and lung. We previously reported an acute sepsis-induced cytotoxic platelet phenotype expressing serine protease granzyme B. We now aim to define the site(s of and mechanism(s by which platelet granzyme B induces end-organ apoptosis in sepsis. METHODS: End-organ apoptosis in murine sepsis (i.e. polymicrobial peritonitis was analyzed by immunohistochemistry. Platelet cytotoxicity was measured by flow cytometry following 90 minute ex vivo co-incubation with healthy murine splenocytes. Sepsis progression was measured via validated preclinical murine sepsis score. MEASUREMENTS AND MAIN RESULTS: There was evident apoptosis in spleen, lung, and kidney sections from septic wild type mice. In contrast, there was a lack of TUNEL staining in spleens and lungs from septic granzyme B null mice and these mice survived longer following induction of sepsis than wild type mice. In co-incubation experiments, physical separation of septic platelets from splenocytes by a semi-permeable membrane reduced splenocyte apoptosis to a rate indistinguishable from negative controls. Chemical separation by the platelet GPIIb/IIIa receptor inhibitor eptifibatide decreased apoptosis by 66.6±10.6% (p = 0.008. Mice treated with eptifibatide in vivo survived longer following induction of sepsis than vehicle control mice. CONCLUSIONS: In sepsis, platelet granzyme B-mediated apoptosis occurs in spleen and lung, and absence of granzyme B slows sepsis progression. This process proceeds in a contact-dependent manner that is inhibited ex vivo and in vivo by the platelet GPIIb/IIIa receptor inhibitor eptifibatide. The GPIIb/IIIa inhibitors and other classes of anti-platelet drugs may be protective in sepsis.

  14. Platelets Induce Apoptosis during Sepsis in a Contact-Dependent Manner That Is Inhibited by GPIIb/IIIa Blockade

    Science.gov (United States)

    Sharron, Matthew; Hoptay, Claire E.; Wiles, Andrew A.; Garvin, Lindsay M.; Geha, Mayya; Benton, Angela S.; Nagaraju, Kanneboyina; Freishtat, Robert J.

    2012-01-01

    Purpose End-organ apoptosis is well-described in progressive sepsis and Multiple Organ Dysfunction Syndrome (MODS), especially where platelets accumulate (e.g. spleen and lung). We previously reported an acute sepsis-induced cytotoxic platelet phenotype expressing serine protease granzyme B. We now aim to define the site(s) of and mechanism(s) by which platelet granzyme B induces end-organ apoptosis in sepsis. Methods End-organ apoptosis in murine sepsis (i.e. polymicrobial peritonitis) was analyzed by immunohistochemistry. Platelet cytotoxicity was measured by flow cytometry following 90 minute ex vivo co-incubation with healthy murine splenocytes. Sepsis progression was measured via validated preclinical murine sepsis score. Measurements and Main Results There was evident apoptosis in spleen, lung, and kidney sections from septic wild type mice. In contrast, there was a lack of TUNEL staining in spleens and lungs from septic granzyme B null mice and these mice survived longer following induction of sepsis than wild type mice. In co-incubation experiments, physical separation of septic platelets from splenocytes by a semi-permeable membrane reduced splenocyte apoptosis to a rate indistinguishable from negative controls. Chemical separation by the platelet GPIIb/IIIa receptor inhibitor eptifibatide decreased apoptosis by 66.6±10.6% (p = 0.008). Mice treated with eptifibatide in vivo survived longer following induction of sepsis than vehicle control mice. Conclusions In sepsis, platelet granzyme B-mediated apoptosis occurs in spleen and lung, and absence of granzyme B slows sepsis progression. This process proceeds in a contact-dependent manner that is inhibited ex vivo and in vivo by the platelet GPIIb/IIIa receptor inhibitor eptifibatide. The GPIIb/IIIa inhibitors and other classes of anti-platelet drugs may be protective in sepsis. PMID:22844498

  15. Long-term Outcomes of Amniotic Membrane Transplantation in Contact Lens-Induced Pseudomonas Keratitis with Impending Corneal Perforation

    Science.gov (United States)

    Mohammadpour, Mehrdad; Sabet, Fatemeh Alsadat

    2016-01-01

    Purpose: To report the anatomical and visual outcomes of double layered amniotic membrane transplantation (AMT) in eyes with advanced Pseudomonas keratitis leading to Descemetocele formation. Methods: This prospective interventional case series included 6 eyes of 6 female patients with pseudomonas keratitis caused by contact lens-induced infection who underwent double layered AMT. Surgery was performed after the ulcers were found to be poorly responsive to antibiotics, and severe thinning or Descemetocele had developed. All patients underwent a complete examination pre- and postoperatively, as well as anterior segment optical coherence tomography (OCT) and pachymetry or Orbscan after the procedure. Results: Mean follow-up period was 24 months. There was neither frank corneal perforation nor a need for emergent corneal transplantation in any of the eyes. All patients had visual acuity of hand motions before the procedure which improved to 20/50 to 20/30 three months after surgery. No surgical or postoperative complication occurred in this series. Conclusion: Double layered AMT may result in acceptable anatomical outcomes in patients with advanced Pseudomonas keratitis with Descemetocele formation and can eliminate the need for emergent corneal transplantation. PMID:27195083

  16. 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.

  17. Genetic Predictors of Drug Hypersensitivity.

    Science.gov (United States)

    Cornejo-Garcia, Jose A; Oussalah, Abderrahim; Blanca, Miguel; Gueant-Rodriguez, Rosa-Maria; Mayorga, Cristobalina; Waton, Julie; Barbaud, Annick; Gaeta, Francesco; Romano, Antonino; Gueant, Jean-Louis

    2016-01-01

    Our knowledge of genetic predisposing factors of drug hypersensitivity reactions (DHRs) is still scarce. The analysis of the genetic basis of these reactions may contribute to dissect the underlying mechanisms. We will outline current knowledge of the genetic predictors of most common DHRs, including reactions to betalactam antibiotics (BLs), nonsteroidal anti-inflammatory drugs (NSAIDs) and biological agents. The predictors of DHRs to BLs are mostly linked to IgE-class switching, IgE pathway and atopy (IL4R, NOD2, LGALS3) in replicated candidate gene studies, and to antigen presentation (HLA-DRA) in the single replicated GWAS performed so far. The HLA-DRA variants are predictors of allergy to penicillins, but not to cephalosporins and they influence also the sensitization against prevalent allergens. The predictors of DHRs against NSAIDs are mostly linked to metabolism of eicosanoids (ALOX5, ALOX5AP, TBXAS1, PTGDR, CYSLTR1). Single nucleotide polymorphisms (SNPs) in genes involved in histamine biosynthesis and antigen presentation, HLA, could also have a role in DHRs against NSAIDs. The intriguing association of DHRs to NSAIDs with atopy should deserve further attention. Predictors of DHRs against asparaginase and other biological agents relate to antigen presentation (HLA-DRB1 and HLA-A alleles, respectively). The potential relationship of genetic predictors of DHRs with pathomechanisms also involved in environmental exposure and atopy highlights the need to perform GWAS in contrasted populations, taking into account world-wide variations of allele frequencies and contrasted situations of environmental exposure. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Hypersensitive teeth. Part II: Treatment.

    Science.gov (United States)

    Krauser, J T

    1986-09-01

    If the hydrodynamic theory for pain transmission were accepted, occlusion of the patent dentinal tubules would appear to be essential for treatment efficacy. There are many compounds with seemingly varied chemical forms that have been shown to be effective. Their exact mode of action however, is not clearly defined because well-designed, nonbiased, and controlled comparison studies between agents are lacking. The various toothpastes may have ingredients that actually occlude patent tubules or they may cause secondary desensitization by irrational or abrasive action. In any pain study, the nature of the placebo effect and other psychogenic factors play a significant role. Fluoride preparation with and without iontophoresis has been shown to alter tubule structure and form microprecipitates. The natural desensitization process, although slow, is nature's protection, allowing dentinal sclerosis of secondary dentin formation. Although the resin-adhesive systems, especially the new light-cured dentin bonding agents, appear immediately to be effective, the effect on the pulp remains unknown. Perhaps a combination of iontophoresis with sodium fluoride and light-cured dentin bonding material may yield protection and desensitization at a high level of predictability. With the population trends toward a more geriatric society, further research, knowledge, and understanding of dentinal hypersensitivity is of paramount importance. The expected increase in longevity of the dentition suggests that dentin exposure and sensitivity will increase as a clinical problem. There is a clear time-age relationship involved in gingival recession, erosion and attrition of the teeth, and the need for periodontal surgical therapy. For total comprehensive care, patient comfort is important and should be provided along with sound periodontal health and ideal restorative function.

  19. 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.

  20. Dosimetry of infant exposure to power-frequency magnetic fields: variation of 99th percentile induced electric field value by posture and skin-to-skin contact.

    Science.gov (United States)

    Li, Congsheng; Wu, Tongning

    2015-04-01

    Infant exposure to 50 Hz magnetic fields from power lines was numerically analyzed in this study. Dosimetric variability due to posture and skin-to-skin contact was evaluated using human anatomical models including a recently developed model of a 12-months-old infant. As proposed by the International Commission on Non-Ionizing Radiation Protection, the induced E-field strength (99th percentile value, E99 ) for the central nerve systems (E99_CNS ) and peripheral nerve system (E99_PNS ), were used as metrics. Results showed that the single (free of contact with others) infant model has lower E99 (E99_CNS and E99_PNS inclusive) compared with single adult and child models when exposed to the same power-frequency magnetic field. Also, studied postures of sitting, standing, or arm-up, would not change E99 _PNS . However, skin-to-skin contact with other models could significantly raise induced E-field strength in the infant (e.g., contact on 0.93% of the infant's total surface increased E99_PNS by 213%). Simulations with canonical models were conducted to assess different factors contributing to the E99 enhancement. Results indicated the importance of thoroughly investigating the conservativeness of current safety guidelines in the case of skin-to-skin contact, especially with infants. © 2015 Wiley Periodicals, Inc.

  1. Diagnosing and managing patients with drug hypersensitivity.

    Science.gov (United States)

    Fernandez, Javier; Doña, Inmaculada

    2018-01-01

    Diagnosing and managing drug hypersensitivity is challenging because there are no clear limits between different types of drug reactions. Distinguishing between type A (predictable) and type B (hypersensitivity) reactions when a drug is introduced on the market is not easy. When many people use a drug, adverse reactions can occur, conditioned by diverse genetic profiles, viral infections or concomitant therapy. Occasionally the only tool clinicians have on which to base the diagnosis is the clinical history. Skins tests or in vitro tests sometimes have low sensitivity or are unavailable, and drug provocation tests may be dangerous or strictly forbidden in case of severe cutaneous reactions. Areas covered: This paper reviews the diagnosis and management of the two main types of immunological reactions: IgE-mediated immediate drug hypersensitivity reactions (IDHRs) and non-immediate drug hypersensitivity reactions (NIDHRs). Expert commentary: Although Europe and the United States use different diagnostic methods, patients with history of drug hypersensitivity must avoid the suspicious drug, and clinicians must assess tolerance to safe alternatives under medical surveillance. Sometimes desensitization may be required. There is a consensus about the need to perform genetic testing for specific drugs and give patients proper documentation to prevent future exposure to culprit drugs.

  2. Calcitonin Gene-Related Peptide Regulates Type IV Hypersensitivity through Dendritic Cell Functions: e86367

    National Research Council Canada - National Science Library

    Norihisa Mikami; Kaori Sueda; Yusuke Ogitani; Ippei Otani; Miku Takatsuji; Yasuko Wada; Keiko Watanabe; Rintaro Yoshikawa; Satoshi Nishioka; Nagisa Hashimoto; Yayoi Miyagi; So-ichiro Fukada; Hiroshi Yamamoto; Kazutake Tsujikawa

    2014-01-01

    .... 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...

  3. Concordance of primary generalised epilepsy and carbamazepine hypersensitivity in monozygotic twins

    OpenAIRE

    Edwards, S.; Hubbard, V; Aylett, S.; Wren, D

    1999-01-01

    In this paper we describe the previously unreported phenomenon of a carbamazepine-induced mucocutaneous syndrome in identical twins. These twins had developed primary generalised epilepsy within 2 months of each other.


Keywords: carbamazepine; hypersensitivity; twins; epilepsy

  4. Saccharomyces cerevisiae accumulates GAPDH-derived peptides on its cell surface that induce death of non-Saccharomyces yeasts by cell-to-cell contact.

    Science.gov (United States)

    Branco, Patrícia; Kemsawasd, Varongsiri; Santos, Lara; Diniz, Mário; Caldeira, Jorge; Almeida, Maria Gabriela; Arneborg, Nils; Albergaria, Helena

    2017-05-01

    During wine fermentations, Saccharomyces cerevisiae starts to excrete antimicrobial peptides (AMPs) into the growth medium that induce death of non-Saccharomyces yeasts at the end of exponential growth phase (24-48 h). Those AMPs were found to derive from the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). On the other hand, the early death of non-Saccharomyces yeasts during wine fermentations was also found to be mediated by a cell-to-cell contact mechanism. Since GAPDH is a cell-wall-associated protein in S. cerevisiae, we put forward the hypothesis that the GAPDH-derived AMPs could accumulate on the cell surface of S. cerevisiae, thus inducing death of non-Saccharomyces yeasts by cell-to-cell contact. Here we show that 48-h grown (stationary phase) cells of S. cerevisiae induce death of Hanseniaspora guilliermondii and Lachancea thermotolerans by direct cell-to-cell contact, while 12-h grown cells (mid-exponential phase) do not. Immunological tests performed with a specific polyclonal antibody against the GAPDH-derived AMPs revealed their presence in the cell wall of S. cerevisiae cells grown for 48 h, but not for 12 h. Taken together, our data show that accumulation of GAPDH-derived AMPs on the cell surface of S. cerevisiae is one of the factors underlying death of non-Saccharomyces yeasts by cell-to-cell contact. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. 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.

  6. 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...

  7. 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...... 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......, 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...

  8. Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity.

    Science.gov (United States)

    Yin, Shijin; Luo, Jialie; Qian, Aihua; Du, Junhui; Yang, Qing; Zhou, Shentai; Yu, Weihua; Du, Guangwei; Clark, Richard B; Walters, Edgar T; Carlton, Susan M; Hu, Hongzhen

    2013-09-01

    Retinoids are structurally related derivatives of vitamin A and are required for normal vision as well as cell proliferation and differentiation. Clinically, retinoids are effective in treating many skin disorders and cancers. Application of retinoids evokes substantial irritating side effects, including pain and inflammation; however, the precise mechanisms accounting for the sensory hypersensitivity are not understood. Here we show that both naturally occurring and synthetic retinoids activate recombinant or native transient receptor potential channel vanilloid subtype 1 (TRPV1), an irritant receptor for capsaicin, the pungent ingredient of chili peppers. In vivo, retinoids produced pain-related behaviors that were either eliminated or significantly reduced by genetic or pharmacological inhibition of TRPV1 function. These findings identify TRPV1 as an ionotropic receptor for retinoids and provide cellular and molecular insights into retinoid-evoked hypersensitivity. These findings also suggest that selective TRPV1 antagonists are potential therapeutic drugs for treating retinoid-induced sensory hypersensitivity.

  9. [Delayed-type hypersensitivity to heparin: diagnosis and therapeutic management].

    Science.gov (United States)

    Nosbaum, A; Pralong, P; Rozieres, A; Dargaud, Y; Nicolas, J-F; Bérard, F

    2012-05-01

    Heparin is widely used as an anticoagulant and is indicated in the prevention and treatment of thromboembolic disorders. Heparin-induced delayed-type hypersensitivity presents as eczematous lesions, either at the injection site or generally, and affects 7.5% of patients on heparin. This poses diagnostic and therapeutic issues, since an alternative anticoagulant treatment is essential and the risk of cross-reactivity may be as high as 80%, depending on the type of heparin used. If delayed-type hypersensitivity is suspected, heparin-induced thrombocytopenia must first be ruled out, and heparin should be stopped. Fondaparinux is currently the first-line alternative, with a risk of cross-reactivity estimated at only 10%. The switch from a low-molecular-weight heparin (LMWH) to another LMWH is no longer recommended. The use of unfractionated heparin, danaparoid or hirudin may be warranted in the event of recurrence with fondaparinux, and an immuno-allergological work-up is needed to specify the exact profile of cross-allergies. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  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. Flagellate erythema as manifestation of food hypersensitivity

    Directory of Open Access Journals (Sweden)

    Jaheersha Pakran

    2017-07-01

    Full Text Available Food hypersensitivity can present in myriad forms leaving the physician baffled. Here we present a case of flagellate dermatitis in an elderly female with bronchial asthma on omalizumab injections, after ingestion of canned shiitake mushrooms. Knowledge about shiitake mushroom dermatitis is important due to increasing prevalence worldwide because of changing culinary preferences.

  12. Dentin hypersensitivity: prevalence, etiology, pathogenesis, and management

    NARCIS (Netherlands)

    van Loveren, C.; Schmidlin, P.R.; Martens, L.C.; Amaechi, B.T.; Amaechi, B.T.

    2015-01-01

    Dentin hypersensitivity is simply defined as a short sharply painful reaction of the exposed and innervated pulp-dentin complex in response to stimuli being typically thermal, evaporative, tactile, osmotic, or chemical and which reaction cannot be attributed to any dental defect or pathology. To be

  13. 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 ...

  14. Uptake of nickel from 316L stainless steel into contacting osteoblastic cells and metal ion interference with BMP-2-induced alkaline phosphatase.

    Science.gov (United States)

    Mölders, Martina; Felix, Joachim; Bingmann, Dieter; Hirner, Alfred; Wiemann, Martin

    2007-11-01

    Bone cells contacting nickel (Ni)-containing implant materials may be affected by Ni species via disturbed signaling pathways involved in bone cell development. Here we analyze effects of the Ni-containing steel 316L and major metal constituents thereof on bone morphogenetic protein-2 (BMP-2)-induced alkaline phosphatase (ALP) of MC3T3-E1 cells. While cells grew normally on 316L, cellular Ni content increased 10-fold vs. control within 4 days. With respect to the major components of 316L, Ni2+ (3-50 microM) was most inhibitory to BMP-2-induced ALP, whereas even 50 microM Fe3+, Cr3+, Mo5+, or Mn2+ had no such effect. In line with this, BMP-2-induced ALP was significantly reduced in cells on 316L. This effect was not prevented by the metal ion chelator diethylenetriaminepentaacetic acid (DTPA). Instead, DTPA abolished the stimulatory effect of BMP-2 on ALP, pointing to chelatable metal ions involved. Zn2+, as one possible candidate, antagonized the Ni2+ inhibition of BMP-2-induced ALP in both MC3T3-E1 and human bone marrow stromal cells. Results show that cells contacting 316L steel are exposed to increased concentrations of Ni which suffice to impair BMP-2-induced ALP activity. Zn2+, as a competitor of this inhibition, may help to restore normal osteoblastic function and bone development under these conditions. Copyright (c) 2007 Wiley Periodicals, Inc.

  15. [Multi-factoriality of dentine hypersensitivity].

    Science.gov (United States)

    Stojsin, Ivana; Petrović, Ljubomir; Stojanac, Igor; Drobac, Milan

    2008-01-01

    Dentine hypersensitivity has been defined as a sharp, short pain arising from exposed dentin in response to stimuli typically thermal, evaporative tactile, osmoticor, chemical and which cannot be ascribed to any other form of dental defect or pathology. The most affected patients range in age from 20 to 40. The following teeth tend to be most sensitive: cuspids, premnolars and incisors, location-concentrated on the facial surface. MORPHOLOGICAL BASES OF DENTINE HYPERSENSITIVITY: Sensitive teeth have much greater numbers of open tubules per unit area and the average diameter of tubules is almost 2 times greater than tubules in nonsensitive teeth. MECHANISMS OF DENTINE HYPERSENSITIVITY: The most widely accepted theory of how the pain occurs is Brannstroms theory. Dentine hypersensitivity represents a condition of presumable multifactorial pathology. Two processes are essential for its development: (1) dentin must be exposed through either genetic disturbance, enamel defect (lamellae, tufs and spindles), loss of enamel (erosion, abrasion, attrition, abfraction), gingival recession with rapid loss of cementum and (2) the dentin tubules must be open to both the oral cavity and the pulp. Diagnostic protocol for this condition consisted of Medical, Dental Dietary, Oral Hygiene History and Inra-oral examinations with air indexing method. Differential Dianosis: We must take into consideration a numnber of variables such as: dental caries, cracked tooth, restorative sensitivity, medication sensitivity, bleaching sensitivity and abscessed or non-vital tooth. Dentin hypersensitivity is a problem that bothers many patients. Many conditions share the symptoms of tooth sensitivity so differential diagnosis is essential for suitable treatment or preventive measures.

  16. Immediate hypersensitivity reactions to ibuprofen and other arylpropionic acid derivatives.

    Science.gov (United States)

    Blanca-López, N; Pérez-Alzate, D; Andreu, I; Doña, I; Agúndez, J A; García-Martín, E; Salas, M; Miranda, M Á; Torres, M J; Cornejo-García, J A; Blanca, M; Canto, G

    2016-07-01

    Although ibuprofen and other arylpropionic acid derivatives (APs) are the most common medicines involved in hypersensitivity drug reactions (HDRs) to NSAIDs, no patient series studies have been performed regarding immediate selective reactions (SRs) to these drugs. To characterize patients with immediate selective HDRs to ibuprofen and other APs through clinical history and challenge. Subjects who developed an HDR to APs less than 1 h after drug intake were included. Tolerance to aspirin was assessed and challenge was performed with ibuprofen in all cases, and additionally with the culprit drug (if different) in those patients that tolerated ibuprofen. Serum tryptase levels and tryptase immunohistochemical staining in skin biopsies were also assessed in some patients with a positive DPT to ibuprofen. From a total of 245 patients with a confirmed history of HDRs to APs, 17% were classified as selective immediate hypersensitivity reactors by both clinical history and challenge. A selective response to naproxen and dexketoprofen with tolerance to ibuprofen was found in 16 of 20 cases. Significant differences in serum tryptase levels were observed between 2 and 24 h in the 11 cases that were studied further. Within the group of patients with HDRs to NSAIDs, APs can induce immediate SRs. Within this group, selective responses to a single drug or responders to several APs may exist, suggesting potential immunological cross-reactivity. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Drug Hypersensitivity and Desensitizations: Mechanisms and New Approaches

    Directory of Open Access Journals (Sweden)

    Leticia de las Vecillas Sánchez

    2017-06-01

    Full Text Available Drug hypersensitivity reactions (HSRs are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs, as well as a personalized treatment approach for IgE (Immunoglobuline E and non-IgE mediated HSRs with drug desensitization (DS. DS induces a temporary hyporesponsive state by incremental escalation of sub-optimal doses of the offending drug. In vitro models have shown evidence that IgE desensitization is an antigen-specific process which blocks calcium flux, impacts antigen/IgE/FcεRI complex internalization and prevents the acute and late phase reactions as well as mast cell mediator release. Through a “bench to bedside” approach, in vitro desensitization models help elucidate the molecular pathways involved in DS, providing new insights to improved desensitization protocols for all patients. The aim of this review is to summarize up to date information on the drug HSRs, the IgE mediated mechanisms of desensitization, and their clinical applications.

  18. The clinical significance of immunological contact urticaria to processed grains

    Directory of Open Access Journals (Sweden)

    Michael Ismail

    2012-01-01

    Full Text Available Contact urticaria, is characterized by an urticarial wheal-and-flare reaction at the site of contact by an allergen. Immunological contact urticaria, while less common than non-immunological contact urticaria, has more potentially serious consequences, and therefore, its recognition and treatment is important. Immunological contact urticaria is a type I hypersensitivity reaction. Potential complications include organ system involvement other than skin and even anaphylaxis and death. A vast majority of immunological contact urticaria is work-related. We will discuss the definition of immunological contact urticaria, the mechanism of the contact urticarial reaction, contact urticaria in the occupational setting, and the role of grains in contact urticaria. Testing and treatment are also briefly discussed.

  19. Hypersensitivity to intravenous ondansetron: a case report

    Directory of Open Access Journals (Sweden)

    Mehra Karishma K

    2008-08-01

    Full Text Available Abstract Introduction Ondansetron, a 5-hydroxytryptamine3 receptor antagonist widely used in the prevention and treatment of chemotherapy-induced nausea and vomiting, is associated with various unusual adverse drug reactions. In this paper, we describe a hypersensitivity reaction to a single intravenous dose of ondansetron. Case presentation A 19-year-old woman presented to the emergency department of our institute with 3–4 episodes of nausea, vomiting and epigastric distress. She had a diagnosis of polycystic ovarian disease and had been on treatment with cyproterone acetate 2 mg, ethinyl estradiol 0.035 mg, finasteride 5 mg and metformin 500 mg for a month. She had been taking oral roxithromycin 500 mg per day for the past 3 days for treatment of a mild upper respiratory tract infection. She also occasionally took rabeprazole 10 mg for gastritis which had worsened after treatment with roxithromycin. She was treated with a single 4 mg dose of ondansetron intravenously. She immediately developed urticaria, which was treated with intravenous dexamethasone 4 mg and chlorpheniramine maleate 20 mg. The reaction abated within a few minutes and she was discharged within an hour. She was asymptomatic at 72 hours of follow-up. She had no history of ondansetron exposure, or drug or food allergies. On the Naranjo's causality assessment scale, the adverse event was 6 indicating a "probable" reaction to ondansetron. Conclusion 5-hydroxytryptamine3 receptor antagonists have been associated with life-threatening adverse reactions such as hypotension, seizures and anaphylaxis. The wide availability of these drugs in India has promoted their off label use in the treatment of gastritis, migraine and so on. Our case represents an off label use in a patient who could have been treated with a safer drug. Some authors have suggested that anaphylaxis may be a class effect while others think it may be drug specific. In our case, the reaction could be either

  20. Systemic contact dermatitis to corticosteroids.

    Science.gov (United States)

    Baeck, M; Goossens, A

    2012-12-01

    Although unexpected and paradoxical, allergic hypersensitivity to corticosteroids is a common finding, delayed-type reactions being much more frequently encountered than the immediate-type ones. Although the skin is the main sensitization and elicitation route, other routes, amongst them systemic administration of corticosteroids may exceptionally be involved. To determine the frequency, clinical presentation and cross-reactivity patterns for allergic reactions following systemic administration of corticosteroids amongst patients with identified and investigated 'contact allergy' to corticosteroids. We reviewed clinical data, patch test results and sensitization sources in patients who reacted positively to corticosteroids tested in the K.U. Leuven Dermatology department during an 18-year period. Sixteen subjects (out of 315 with CS delayed-type hypersensitivity) presented with allergic manifestations due to systemic administration of corticosteroids. Most patients reacted to molecules from the three groups of the recently reappraised classification. The reactions observed seem to be in most cases 'systemic contact dermatitis' due to oral or parenteral re-exposure of sensitized individuals with the respective corticosteroids previously applied topically. Moreover, most patients seem to be able to react to any corticosteroid molecules and therefore need a systematic individualized evaluation of their sensitization/tolerance profile. © 2012 John Wiley & Sons A/S.

  1. Factor XII Contact Activation.

    Science.gov (United States)

    Naudin, Clément; Burillo, Elena; Blankenberg, Stefan; Butler, Lynn; Renné, Thomas

    2017-11-01

    Contact activation is the surface-induced conversion of factor XII (FXII) zymogen to the serine protease FXIIa. Blood-circulating FXII binds to negatively charged surfaces and this contact to surfaces triggers a conformational change in the zymogen inducing autoactivation. Several surfaces that have the capacity for initiating FXII contact activation have been identified, including misfolded protein aggregates, collagen, nucleic acids, and platelet and microbial polyphosphate. Activated FXII initiates the proinflammatory kallikrein-kinin system and the intrinsic coagulation pathway, leading to formation of bradykinin and thrombin, respectively. FXII contact activation is well characterized in vitro and provides the mechanistic basis for the diagnostic clotting assay, activated partial thromboplastin time. However, only in the past decade has the critical role of FXII contact activation in pathological thrombosis been appreciated. While defective FXII contact activation provides thromboprotection, excess activation underlies the swelling disorder hereditary angioedema type III. This review provides an overview of the molecular basis of FXII contact activation and FXII contact activation-associated disease states. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. Laser-induced forward transfer of high-viscosity silver precursor ink for non-contact printed electronics

    NARCIS (Netherlands)

    Inui, T.; Mandamparambil, R.; Araki, T.; Abbel, R.J.; Koga, H.; Nogi, M.; Suganuma, K.

    2015-01-01

    Non-contact printing techniques are receiving increasing interest in the field of printed electronics, because they can be used to pattern various inks on arbitrary substrates without applying mechanical pressure or damaging pre-patterned components. The ink-jet process is frequently used for

  3. 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

    2015-11-18

    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.

  4. Fifteen minutes of daily contact with sexually active male induces ovulation but delays its timing in seasonally anestrous goats.

    Science.gov (United States)

    Ramírez, S; Bedos, M; Chasles, M; Hernández, H; Flores, J A; Vielma, J; Duarte, G; Retana-Márquez, M S; Keller, M; Chemineau, P; Delgadillo, J A

    2017-01-01

    The present experiment was conducted to determine (1) whether the sexually active bucks are able to stimulate the ovulatory activity of seasonal anestrous goats when the daily contact is reduced to 15 min/day during 15 days and (2) the exact ovulatory activity in anestrous goats exposed to bucks for 2 hours or less per day during 15 days. One group of goats (n = 15) was isolated from bucks. The other six groups (n = 15 each) were exposed to sexually active bucks (n = 1 each) for 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, or 24 hours during 15 days. Goats with plasma concentrations of progesterone greater than 0.5 ng/mL were considered to have ovulated. More than 93% of females exposed to bucks ovulated throughout the experiment regardless of the duration of contact with males, whereas none of them ovulated in the isolated group (P goats that displayed normal or short ovulatory cycles. The interval between the introduction of males and the first ovulation did not differ among groups of goats in contact with bucks for 15 minutes, 30 minutes, 1 hour, or 2 hours. However, in these groups, this ovulation occurred about 2 days later than in females in contact with males during 4 or 24 hours (6.3 vs. 4.4 days; P goats, but the first ovulation is delayed in goats exposed to males for 2 h/day or less during 15 days in comparison with those in contact with males for 4 or 24 h/day. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Rare case of type I hypersensitivity reaction to sodium hypochlorite solution in a healthcare setting.

    Science.gov (United States)

    Chia Shi Zhe, Gabriel; Green, Andrew; Fong, Yuke Tien; Lee, Haur Yueh; Ho, Sweet Far

    2016-10-21

    Sodium hypochlorite is a clear yellowish solution with a characteristic odour of chlorine and is commonly used as a disinfectant and a bleaching agent. It is used in various healthcare settings for its fast-acting and broad-spectrum antimicrobial activity. It is a known irritant and there are some reports that it can also cause allergic contact dermatitis of type IV hypersensitivity. We report a case of work-related type I hypersensitivity to sodium hypochlorite, presenting with recurrent urticarial rash and a positive prick test reaction to this chemical. He was subsequently excused from further exposure with no further recurrences of the urticarial rash. To the best of our knowledge, this is the first such reported case due to work in the healthcare setting. 2016 BMJ Publishing Group Ltd.

  6. Management of patients with nonaspirin-exacerbated respiratory disease aspirin hypersensitivity reactions.

    Science.gov (United States)

    Saff, Rebecca R; Banerji, Aleena

    2015-01-01

    Because of widespread use, nonsteroidal anti-inflammatory drugs (NSAIDs) are the second most common cause of all adverse drug reactions, with hypersensitivity reported in ∼1% of the population. NSAID hypersensitivity can be categorized into five types by the underlying disease, symptoms of reaction, and timing of reaction. These include rhinitis and asthma induced by NSAIDs (also known as aspirin-exacerbated respiratory disease), NSAID-exacerbated cutaneous disease (NECD), urticaria or angioedema induced by multiple NSAIDs, single NSAID-induced reactions, and delayed NSAID reactions. NECD occurs in one-third of patients with chronic urticaria who develop an exacerbation of their urticaria, sometimes with angioedema, typically beginning 30-90 minutes after ingestion of NSAIDs that inhibit cyclooxygenase (COX)-1. In urticaria or angioedema induced by multiple NSAIDs, patients without underlying disease develop urticaria or angioedema 30-90 minutes after ingestion of COX-1-inhibiting NSAIDs including aspirin. Single NSAID-induced reactions are immediate and specific to a single NSAID and are thought to occur because of an IgE-mediated reaction against a specific epitope of the NSAID. Delayed NSAID reactions occur days to weeks after initiating an NSAID. These are T-cell mediated and not amenable to desensitization or rechallenge. Classifying the type of NSAID hypersensitivity is important because many patients with a prior history of urticaria or angioedema induced by multiple NSAIDs will often tolerate aspirin test dose. This would allow the use of an aspirin for primary or secondary prevention in patients with coronary artery disease despite a presumed history of NSAID hypersensitivity.

  7. 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.

  8. Multi-factoriality of dentine hypersensitivity

    OpenAIRE

    Stojšin Ivana; Petrović Ljubomir; Stojanac Igor; Drobac Milan

    2008-01-01

    Introduction. Dentine hypersensitivity has been defined as a sharp, short pain arising from exposed dentin in response to stimuli typically thermal, evaporative tactile, osmoticor, chemical and which cannot be ascribed to any other form of dental defect or pathology. Prevalence. The most affected patients range in age from 20 to 40. The following teeth tend to be most sensitive: cuspids, premolars and incisors, location-concentrated on the facial surface. Morphological bases of dentine hypers...

  9. 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

  10. Role of transient receptor potential melastatin 2 (TRPM2) channels in visceral nociception and hypersensitivity.

    Science.gov (United States)

    Matsumoto, Kenjiro; Takagi, Kanako; Kato, Atsumi; Ishibashi, Takuya; Mori, Yasuo; Tashima, Kimihito; Mitsumoto, Atsushi; Kato, Shinichi; Horie, Syunji

    2016-11-01

    Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive, Ca(2+)-permeable cation channel. TRPM2 contributes to the pathogenesis of inflammatory bowel disease, and inflammatory and neuropathic pain. We hypothesized that TRPM2 is important for visceral nociception and the development of visceral hypersensitivity. Therefore, we investigated the expression of TRPM2 channels and their involvement in visceral nociception in normal physiology and under pathological conditions that cause visceral hypersensitivity in rats. TRPM2 immunoreactivities were detected in the mucosa and muscle layer of the rat gastrointestinal tract. TRPM2 immunopositive cell bodies were almost completely co-localized with calretinin- and NeuN-positive cells in the myenteric plexus. We found that the majority of the TRPM2-immunoreactive cells were double-labeled with the retrograde marker fluorogold in lumbar 6/sacral 1 dorsal root ganglia (DRG), indicating that TRPM2 is expressed in spinal primary afferents innervating the distal colon. Subtypes of TRPM2-immunopositive DRG neurons were labeled by the A-fiber marker NF200, the C-fiber marker IB4, substance P, calcitonin gene-related peptide, or P2X3 receptor. We found that oral administration of the TRPM2 inhibitor econazole (30mg/kg) reduced the visceromotor response (VMR) to noxious colorectal distention (CRD) at 80mmHg in control rats. Expression of TRPM2 in the mucosa of the distal colon was increased in a trinitrobenzene sulfonic acid-induced colitis model. The VMR to CRD significantly increased in colitis model rats compared with control rats at 40, 60, and 80mmHg. Econazole restored visceral hypersensitivity to the control level. Furthermore, TRPM2-deficient mice showed significantly attenuated trinitrobenzene sulfonic acid induced visceral hypersensitivity compared with wild-type mice. In conclusion, TRPM2 channels contribute to visceral nociception in response to noxious stimuli under normal conditions and visceral

  11. Autophagic components contribute to hypersensitive cell death in Arabidopsis

    DEFF Research Database (Denmark)

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

    2009-01-01

    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......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...

  12. Chapter 28: Classification of hypersensitivity reactions.

    Science.gov (United States)

    Uzzaman, Ashraf; Cho, Seong H

    2012-01-01

    The original Gell and Coomb's classification categorizes hypersensitivity reactions into four subtypes according to the type of immune response and the effector mechanism responsible for cell and tissue injury: type I, immediate or IgE mediated; type II, cytotoxic or IgG/IgM mediated; type III, IgG/IgM immune complex mediated; and type IV, delayed-type hypersensitivity or T-cell mediated. The classification has been improved so that type IIa is the former type II and type IIb is antibody-mediated cell stimulating (Graves Disease and the "autoimmune" type of chronic idiopathic urticaria). Type IV has four major categories: type IVa is CD4(+)Th1 lymphocyte mediated with activation of macrophages (granuloma formation and type I diabetes mellitus); type IVb is CD4(+)Th2 lymphocyte mediated with eosinophilic involvement (persistent asthma and allergic rhinitis); type IVc is cytotoxic CD8(+) T lymphocyte with involvement of perforin-granzme B in apoptosis (Stevens-Johnson syndrome and toxic epidermal necrolysis); type IVd is T-lymphocyte-driven neutrophilic inflammation (pustular psoriasis and acute generalized exanthematous pustulosis). Some diseases have multiple types of immunologic hypersensitivity.

  13. Gravity-induced four-fermion contact interaction: liberating the intermediate W and Z type gauge bosons

    CERN Document Server

    Boos, Jens

    2016-01-01

    Coupling fermions to gravity necessarily leads to a non-renormalizable, gravitational four-fermion contact interaction. In this essay, we argue that augmenting the Einstein--Cartan Lagrangian with suitable kinetic terms quadratic in the gauge field strengths gives rise to new, massive propagating gravitational degrees of freedom. This is to be seen in close analogy to Fermi's effective four-fermion interaction and its emergent W and Z bosons.

  14. Root Cause Analysis and Correction of Single Metal Contact Open-Induced Scan Chain Failure in 90nm node VLSI

    OpenAIRE

    Ting, Chao-Cheng; Liu, Ya-Chi; Chen, Hsuan-Hsien; Tsai, Chung-Ching; Shih, Liwen

    2018-01-01

    In this paper, the localization of open metal contact for 90nm node SOC is reported based on Electron Beam Absorbed Current (EBAC) technique and scan diagnosis for the first time. According to the detected excess carbon, silicon and oxygen signals obtained from X-ray energy dispersive spectroscopy (EDX), the failure was deemed to be caused by the incomplete removal of silicate photoresist polymer formed during the O2 plasma dry clean before copper plating. Based on this, we proposed to replac...

  15. Cytokine responses in metal-induced allergic contact dermatitis : Relationship to in vivo responses and implication for in vitro diagnosis

    OpenAIRE

    Minang, Jacob

    2005-01-01

    Transition metals such as nickel (Ni), cobalt (Co), palladium (Pd), chromium (Cr) and gold (Au) are widely used as alloys in jewelry and biomaterials such as orthodontic and orthopaedic appliances. These metals also cause cell-mediated allergic contact dermatitis (ACD) reactions in a significant proportion of the population upon prolonged direct exposure. The immune mechanisms underlying the response to these metals are not yet well defined. In the studies described in this thesis we therefor...

  16. 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.

  17. Lipid peroxidation in cotton: Xanthomonas interactions and the role of lipoxygenases during the hypersensitive reaction.

    Science.gov (United States)

    Jalloul, A; Montillet, J L; Assigbetsé, K; Agnel, J P; Delannoy, E; Triantaphylidès, C; Daniel, J F; Marmey, P; Geiger, J P; Nicole, M

    2002-10-01

    Lipid peroxidation, often associated with hypersensitive cell death, may be initiated either by active oxygen species (AOS) or lipoxygenases (LOX). Here we report a detailed analysis of this oxidative process in both incompatible and compatible interactions between the cotton cultivar Reba B50 and Xanthomonas campestris pv. malvacearum (Xcm). The hypersensitive reaction (HR) was characterized by a massive production of polyunsaturated fatty acid (PUFA) hydroperoxides together with typical tissue dehydration. Among these, isomers peroxidized on carbon 9, largely predominant, were chiral, showing an excess in the S enantiomer. The HR process was accompanied by an increase in 9S-LOX activity and preceded by transcription of a LOX gene (GhKLox1). These results showed that: (i) AOS produced during the oxidative burst were not involved in PUFA peroxidation during HR; and (ii) as previously described in elicited leaves of tobacco, the massive enzymatic lipid peroxidation was closely associated with hypersensitive cell death. During disease development in this cotton cultivar, the 9-lipoxygenation of PUFAs was late, weak, preceded by a faint accumulation of GhKLox1 transcripts, and associated with chlorosis but not with necrosis. Consequently, the main difference between incompatible and compatible interactions was in the precocity and intensity of the oxidative process, rather than in its nature. These data provide the evidence for a correlation between lipid peroxidation and hypersensitive cell death induced by pathogens.

  18. Delayed hypersensitivity to aminopenicillins is related to major histocompatibility complex genes.

    Science.gov (United States)

    Romano, A; De Santis, A; Romito, A; Di Fonso, M; Venuti, A; Gasbarrini, G B; Manna, R

    1998-05-01

    Although in some cases delayed hypersensitivity may be observed, beta-lactam antibiotics frequently induce immediate allergic IgE-mediated reactions with the specificity localized in the acyl-side chain structure. Generally, delayed immunologic reactions are related to sensitized T lymphocytes and major histocompatibility complex restricted. To investigate the prevalence of HLA class I and II antigens in patients with delayed hypersensitivity to aminopenicillins in order to evaluate a relationship between major histocompatibility complex immune response genes and aminopenicillins hypersensitivity. We assessed 24 patients with history of delayed hypersensitivity to aminopenicillins using (1) skin test with penicilloyl polylysine, minor determinant mixture, benzylpenicillin, amoxicillin, and ampicillin; (2) patch tests with benzylpenicillin, amoxicillin, and ampicillin; (3) RAST for penicilloyls G and V; and (4) oral challenges with amoxicillin, ampicillin, and penicillin V in 18/24 patients. All patients were typed by microlymphotoxicity standard test for HLA class I and II antigens. Statistical analysis by chi2 test 2 x 2 contingency tables, according to Svejgaard, were used for comparison between patients and random Italian population (522 subjects). In the patients group we found higher prevalence of HLA A2 (12/24 = 50%, RR = 6.76 P mechanisms involved in adverse reactions to aminopenicillins in vivo are related to genetic markers of immune response and confirms that the presentation of penicillin-hapten determinants to lymphocyte is major histocompatibility complex restricted.

  19. Hemoptysis and acute respiratory syndrome (ARDS) as delayed-type hypersensitivity after FOLFOX4 plus bevacizumab treatment.

    Science.gov (United States)

    Kobayashi, Takaaki; Masaki, Tadahiko; Kogawa, Koji; Matsuoka, Hiroyoshi; Sugiyama, Masanori

    2013-01-01

    As there have been many multidrug regimens introduced in colorectal cancer treatment, hypersensitivity is more often encountered than in the past. Though most allergic adverse events of oxaliplatin are mainly classified as type I reaction, a limited number of case reports of type IV reaction (delayed-type hypersensitivity) have been reported. A 73-year-old man was hospitalized for receiving the third cycle of FOLFOX4 plus bevacizumab. Forty-two hours after administration, he had dyspnea and hemoptysis. Acute respiratory distress syndrome was suspected, and the patient underwent mechanical ventilation and steroid pulse therapy. Delayed-type hypersensitivity is induced by induction of inflammation via IL-1, TNF-α and IL-6. The serum level of IL-6 in patients with advanced colorectal cancers is usually greater than the normal range. Therefore, delayed-type hypersensitivity may be easily induced in those patients. We should pay special attention to delayed-type hypersensitivity in advanced colorectal cancer patients undergoing FOLFOX treatment.

  20. 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

  1. Prevalence of self-reported hypersensitivity symptoms following intake of alcoholic drinks

    DEFF Research Database (Denmark)

    Linneberg, A.; Berg, N.D.; Gonzalez-Quintela, A.

    2008-01-01

    Background Although hypersensitivity symptoms following alcoholic drink consumption are common in asthmatics, the prevalence of such symptoms in the general population is not known. Objective To assess the prevalence of hypersensitivity symptoms following alcoholic drink consumption in an adult...... of alcoholic drinks are common. These symptoms were markedly more prevalent in persons with AR and asthma. The underlying mechanisms and the clinical significance of these symptoms remain to be elucidated Udgivelsesdato: 2008/1....../6000). Results The prevalence of alcohol-induced symptoms from the upper airways, lower airways, and skin was 7.6% [95% confidence interval (CI): 6.8-8.4%], 3.2% (95% CI: 2.7-3.8%), and 7.2% (95% CI: 6.4-8.9%), respectively. A total of 13.9% (95% CI: 12.9-15.0%) had ever experienced alcohol-induced symptoms from...

  2. Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians

    DEFF Research Database (Denmark)

    Linneberg, A; Gonzalez-Quintela, A; Vidal, C

    2010-01-01

    polymorphism (SNP), the acetaldehyde dehydrogenase 2 (ALDH2) 487lys, causing decreased acetaldehyde (the metabolite of ethanol) metabolism and high levels of histamine. However, the ALDH2 487lys is absent in Caucasians. OBJECTIVES: To investigate the genetic determinants of self-reported alcohol...... dehydrogenases (ADHs) and ALDHs. RESULTS: In both populations, alcohol drinkers with a genetically determined fast metabolism of ethanol (the A allele of the ADH1b rs1229984) had an increased risk of alcohol-induced hypersensitivity reactions (odds ratio AA/AG vs. GG in combined populations: 1.82, 95% CI 1......BACKGROUND: Although hypersensitivity reactions following intake of alcoholic drinks are common in Caucasians, the underlying mechanisms and clinical significance are not known. In contrast, in Asians, alcohol-induced asthma and flushing have been shown to be because of a single nucleotide...

  3. Non-contact micro-cantilevers detect photothermally induced vibrations that can segregate different categories of exfoliative cervical cytology.

    Science.gov (United States)

    Hammiche, Azzedine; Walsh, Michael J; Pollock, Hubert M; Martin-Hirsch, Pierre L; Martin, Francis L

    2007-06-10

    We implemented a non-contact photo-thermo-mechanical recording method whereby a silicon nitride atomic force microscopy cantilever is placed several micrometer above the surface of samples. Samples were illuminated with infrared (IR) radiation after which, cantilever mechanical vibrations were optically sensed. Following spectrometric acquisition and Fourier transformation, true IR absorption spectra were obtained. With multivariate analysis, segregation between different categories of exfoliative cervical cytology was obtained. This approach points towards the implementation of a novel near-field system that allows IR spectral analysis without probe contamination.

  4. Non-contact determination of arterial blood pressure alterations induced by blood loss using laser irradiation on the common carotid artery.

    Science.gov (United States)

    Matsui, T; Uenoyama, M; Ishimine, H; Suzuki, S; Yamanaka, K; Ishihara, M

    2008-01-01

    In order to avoid the secondary exposure of medical personnel to toxic materials under biochemical hazard conditions, we have reported a method for non-contact monitoring of heart and respiratory rates, using microwave radar or laser irradiation. In large-scale disasters, it is important to be able to diagnose shock without touching patients. We evaluated a non-contact method of monitoring arterial blood pressure alterations of New Zealand rabbits induced by blood loss, using He-Ne laser reflection on the common carotid artery. PVR was significantly correlated with systolic blood pressure (r = 0.95, p laser amplitude, and PVR = PV(present moment state)/PV(normal state). The following formula was derived using the least-squares linear fitting: SBP = 69.6 PVR + 8.2, in which SBP is the systolic blood pressure. Before blood withdrawal, the mean blood pressure, heart rate and haematocrit were 68 +/- 3 mmHg, 154 +/- 10 bpm and 40 +/- 2%, respectively. After intervention, the mean blood pressure, heart rate and haematocrit were 38 +/- 5 mmHg, 197 +/- 25 bpm and 30 +/- 2%, respectively. The proposed non-contact method appears promising for future clinical application in determining arterial blood pressure alterations. It is likely to be useful in reducing the risk of secondary exposure to toxic chemicals or infectious organisms in the case of large-scale disasters.

  5. Severe systemic allergic reaction induced by accidental skin contact with cow milk in a 16-year-old boy. A case report.

    Science.gov (United States)

    Liccardi, G; De Falco, F; Gilder, J A; D'Amato, M; D'Amato, G

    2004-01-01

    The symptoms of food allergy are rarely induced by skin contact. A 16-year-old boy was referred to our Allergology Centre after an episode of systemic symptoms triggered by accidental skin contact with a drop of cow milk (CM) dripped from a sandwich containing fresh cheese. The patient had been allergic to CM from the age of 24 months and had experienced several episodes of urticaria-angioedema after the ingestion of tiny or "hidden" amounts of CM proteins. In vivo and in vitro diagnostic procedures showed intense sensitisation to all CM proteins (1/100 dilutions of allergenic extracts produced large wheals, and class 4 specific IgE antibodies. Total IgE antibodies were elevate (770.0 UI/). A moderate degree of bronchial hyperresponsiveness was found (PC20 metacholine: 3.90 milligrams). This case report suggests that patients with a high degree of sensitisation to CM proteins should be alert to the danger of skin contact and should beware of "hidden" CM allergens.

  6. Occupational protein contact dermatitis caused by meat and fish.

    Science.gov (United States)

    Boehncke, W H; Pillekamp, H; Gass, S; Gall, H

    1998-05-01

    Protein contact dermatitis is a form of contact dermatitis possibly triggered by proteinaceous allergens. We report two patients with a history of erythematous and urticarial skin reactions followed by transformation into prolonged papular symptoms upon contact with proteinaceous material. The symptoms reported by the patients were reproducible by skin testing with meat (cow) and fish (salmon). Both patients experienced extracutaneous manifestations after ingestion of meat and fish, as proven by oral challenge. Specific immunoglobulin E (IgE) antibodies were detected in the patients' blood. Both cases meet all major criteria of protein contact dermatitis, suggesting IgE-mediated immediate-type hypersensitivity with late-phase cutaneous reactions.

  7. 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.

  8. High performance TiN gate contact on AlGaN/GaN transistor using a mechanically strain induced P-doping

    Energy Technology Data Exchange (ETDEWEB)

    Soltani, A., E-mail: ali.soltani@iemn.univ-lille1.fr; Rousseau, M.; Gerbedoen, J.-C.; Bourzgui, N. [Institut d' Electronique de Microélectronique et de Nanotechnologie, UMR-CNRS 8520, USTL, Avenue Poincaré, 59652 Villeneuve d' Ascq (France); Mattalah, M. [Laboratoire de Microélectronique, Université Djilali Liabès, 22000 Sidi Bel Abbès (Algeria); Bonanno, P. L.; Ougazzaden, A. [School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, Georgia 30324-0250 (United States); UMI 2958 Georgia Tech-CNRS, Georgia Tech Lorraine, 2-3 Rue Marconi, 57070 Metz-Technopôle (France); Telia, A. [LMI, Electronic Department, Faculty of Engineering, Mentouri University of Constantine, Constantine (Algeria); Patriarche, G. [Laboratoire de Photonique et Nanostructures, CNRS UPR 20, Route de Nozay, 91460 Marcoussis (France); BenMoussa, A. [Solar Terrestrial Center of Excellence, Royal Observatory of Belgium, Circular 3, B-1180 Brussels (Belgium)

    2014-06-09

    High performance titanium nitride sub-100 nm rectifying contact, deposited by sputtering on AlGaN/GaN high electron mobility transistors, shows a reverse leakage current as low as 38 pA/mm at V{sub GS} = −40 V and a Schottky barrier height of 0.95 eV. Based on structural characterization and 3D simulations, it is found that the polarization gradient induced by the gate metallization forms a P-type pseudo-doping region under the gate between the tensile surface and the compressively strained bulk AlGaN barrier layer. The strain induced by the gate metallization can compensate for the piezoelectric component. As a result, the gate contact can operate at temperatures as high as 700 °C and can withstand a large reverse bias of up to −100 V, which is interesting for high-performance transistors dedicated to power applications.

  9. 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...

  10. 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.

  11. Enhancement of delayed-type hypersensitivity and induction of interferon by the lipophilic agents DDA and CP-20,961

    NARCIS (Netherlands)

    Kraaijeveld, C.A.; Snippe, H.; Harmsen, T.; Benaissa-Trouw, B.

    1982-01-01

    The lipophilic amines dimethyl dioctadecyl ammonium bromide (DDA) and N,N-dioctadecyl-N′, N′-bis(2-hydroxyethyl)propanediamine (CP-20,961) are compared on their capacities to induce interferon, nonspecific protection to viral infection, and enhancement of delayed-type hypersensitivity (DH). DDA, a

  12. Delayed type hypersensitivity reaction as indicator of cellular immune competence in broiler chickens exposed to dietary corticosterone

    NARCIS (Netherlands)

    Post, J.; Gielkens, A.; Huurne, ter A.A.H.M.

    2004-01-01

    Three experiments were performed to evaluate the delayed type hypersensitivity test against keyhole limpet haemocyanin as a parameter to measure stress-induced cellular immune suppression. The test was optimised for broiler chickens and evaluated in a stress model in which plasma corticosterone

  13. Particle-induced x-ray emission: Instrumentation, calibration, and application to contact lens solutions and fulvic acid solutions

    Energy Technology Data Exchange (ETDEWEB)

    Jenson, D.D.

    1989-01-01

    An expression was derived describing the profile of the proton beam at the PIXE target position. The expression was used to predict the profile for several experimental configurations. The profile was experimentally measured. The PIXE system was calibrated using solutions and commercial foils. Experimental data was adjusted for all absorbers and interferences, and a quadratic relationship was determined relating calibration factor and atomic number for each series of X-ray transitions. Calibration factors were determined for all elements above aluminum, for both a pinhole filter and a 14-mil mylar filter. A group of contact lens solutions was analyzed using PIXE, ICP, and ISE. A digestion method was developed for removal. of chloride ion. Cluster analysis was used to classify the data. A commercial humic acid was separated into three fractions. The fulvic acid was characterized, and separations of metal-fulvic acid complexes from metal ions in solution were attempted using ultrafiltration.

  14. Hypersensitivity and nanoparticles: update and research trends.

    Science.gov (United States)

    Mocan, Teodora; Matea, Cristian T; Iancu, Cornel; Agoston-Coldea, Lucia; Mocan, Lucian; Orasan, Remus

    2016-01-01

    Nanotechnology holds a great promise for a wide range of medical-intent applications (diagnostic, treatment and prophylaxis of various diseases). Their advantages are due to their size, versatility and potential for multiple simultaneous applications. However, concerns have been formulated by scientific world due to insufficient data on toxicity of nanomaterials. One area of interest is represented by the interactions between nanoparticles and the components of the immune system. We review herein reported data on hypersensitivity reactions. The role exerted by nanoparticles in both immunostimulation and immunosuppression in allergen-driven mechanisms was studied, as well as future trends in worldwide research.

  15. [Hypersensitivity reactions to use of mebeverine].

    Science.gov (United States)

    in 't Veld, B A; van Puyenbroek, E; Stricker, B H

    1997-07-12

    Twenty-one cases of adverse reactions to mebeverine use were reported to the Inspectorate for Health Care in the Netherlands since 1978. In 12 patients (five men and seven women) this was an immunological hypersensitivity reaction. All patients recovered after drug withdrawal. The time between start and onset of symptoms varied from several minutes to 14 days. Most reactions consisted of urticaria or maculopapular rash, sometimes accompanied by fever, polyarthritis, thrombopenia or angioedema. In contradiction to the manufacturer's claims adverse reactions to the use of mebeverine do occur.

  16. Hypersensitivity Responses in the Central Nervous System

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Asgari, Nasrin; Mørch, Marlene Thorsen

    2015-01-01

    Immune-mediated tissue damage or hypersensitivity can be mediated by autospecific IgG antibodies. Pathology results from activation of complement, and antibody-dependent cellular cytotoxicity, mediated by inflammatory effector leukocytes include macrophages, natural killer cells, and granulocytes...... as a therapy for NMO, NMO-like pathology is significantly reduced in mice lacking the Type I IFN receptor. In MS, there is evidence for intrathecal synthesis of antibodies as well as blood-brain barrier (BBB) breakdown, whereas in NMO, IgG accesses the CNS from blood. Transfer models involve either direct...

  17. Pain hypersensitivity mechanisms at a glance.

    Science.gov (United States)

    Gangadharan, Vijayan; Kuner, Rohini

    2013-07-01

    There are two basic categories of pain: physiological pain, which serves an important protective function, and pathological pain, which can have a major negative impact on quality of life in the context of human disease. Major progress has been made in understanding the molecular mechanisms that drive sensory transduction, amplification and conduction in peripheral pain-sensing neurons, communication of sensory inputs to spinal second-order neurons, and the eventual modulation of sensory signals by spinal and descending circuits. This poster article endeavors to provide an overview of how molecular and cellular mechanisms underlying nociception in a physiological context undergo plasticity in pathophysiological states, leading to pain hypersensitivity and chronic pain.

  18. Cutaneous delayed-type hypersensitivity in patients with atopic dermatitis: reactivity to surfactants.

    Science.gov (United States)

    Shaughnessy, Cristin N; Malajian, Dana; Belsito, Donald V

    2014-04-01

    Patients with atopic dermatitis (AD) have abnormalities in skin barrier function, and are predisposed to developing cutaneous delayed-type hypersensitivity. Soap and detergents are known to exacerbate the breakdown of the skin barrier. We sought to assess whether atopic patients in our database were more likely than nonatopic patients to patch test positive to the surfactants cocamidopropyl betaine (CAPB) and cocamide diethanolamide (DEA), or to the surfactant precursor amidoamine. Between January 1, 2001, and the present, a total of 1674 patients underwent patch testing to the North American Contact Dermatitis Group standard screening series. The incidence of positive patch test results to CAPB, cocamide DEA, and amidoamine among patients with AD (n = 242) and without AD (n = 1422) was assessed. Statistical analysis was done using a χ(2) test. AD was associated with contact hypersensitivity to CAPB, but not to cocamide DEA or amidoamine. This was a retrospective study of patients evaluated for suspected allergic contact dermatitis and, therefore, matching for gender, age, or other parameters was not possible. Our population was geographically limited to metropolitan Kansas City, MO, and metropolitan New York City, NY. Patients with AD should avoid the use of skincare products containing the surfactant CAPB. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  19. Cutaneous delayed-type hypersensitivity in patients with atopic dermatitis: reactivity to topical preservatives.

    Science.gov (United States)

    Shaughnessy, Cristin N; Malajian, Dana; Belsito, Donald V

    2014-01-01

    Patients with atopic dermatitis (AD) have chronic dry skin to which they frequently apply skin care products containing preservatives, and they are predisposed to developing cutaneous delayed-type hypersensitivity. We sought to compare the rates of positive patch test reactions to allergens on the North American Contact Dermatitis Group (NACDG) standard tray among patients with and without AD and to assess whether atopic patients in our database were more likely to patch test positive to preservatives. A total of 2453 patients underwent patch testing to the NACDG standard screening series. The incidence of positive patch test reaction among patients with AD (n = 342) and without AD (n = 2111) was assessed. Statistical analysis was done using a χ(2) test. Compared with nonatopic patients, patients with AD were statistically more likely to have positive patch tests. AD was associated with contact hypersensitivity to quaternium-15, imidazolidinyl urea, DMDM hydantoin, and 2-bromo-2-nitropropane-1,3-diol but not to parabens, formaldehyde, or diazolidinyl urea. Only patients suspected of having allergic contact dermatitis were tested. Our population was geographically limited to metropolitan Kansas City, MO, and metropolitan New York City, NY. Patients with AD should avoid the use of skin care products preserved with formaldehyde releasers. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  20. Is cancer a severe delayed hypersensitivity reaction and histamine a blueprint?

    Science.gov (United States)

    Khatami, Mahin

    2016-12-01

    Longevity and accumulation of multiple context-dependent signaling pathways of long-standing inflammation (antigen-load or oxidative stress) are the results of decreased/altered regulation of immunity and loss of control switch mechanisms that we defined as Yin and Yang of acute inflammation or immune surveillance. Chronic inflammation is initiated by immune disruptors-induced progressive changes in physiology and function of susceptible host tissues that lead to increased immune suppression and multistep disease processes including carcinogenesis. The interrelated multiple hypotheses that are presented for the first time in this article are extension of author's earlier series of 'accidental' discoveries on the role of inflammation in developmental stages of immune dysfunction toward tumorigenesis and angiogenesis. Detailed analyses of data on chronic diseases suggest that nearly all age-associated illnesses, generally categorized as 'mild' (e.g., increased allergies), 'moderate' (e.g., hypertension, colitis, gastritis, pancreatitis, emphysema) or 'severe' (e.g., accelerated neurodegenerative and autoimmune diseases or site-specific cancers and metastasis) are variations of hypersensitivity responses of tissues that are manifested as different diseases in immune-responsive or immune-privileged tissues. Continuous release/presence of low level histamine (subclinical) in circulation could contribute to sustained oxidative stress and induction of 'mild' or 'moderate' or 'severe' (immune tsunami) immune disorders in susceptible tissues. Site-specific cancers are proposed to be 'severe' (irreversible) forms of cumulative delayed hypersensitivity responses that would induce immunological chaos in favor of tissue growth in target tissues. Shared or special features of growth from fetus development into adulthood and aging processes and carcinogenesis are briefly compared with regard to energy requirements of highly complex function of Yin and Yang. Features of Yang

  1. 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. This ...

  2. Frequency, treatment, and functional outcome in children with hypersensitivity pneumonitis

    DEFF Research Database (Denmark)

    Buchvald, Frederik; Petersen, Bodil Laub; Pedersen, Karen Damgaard

    2011-01-01

    Hypersensitivity pneumonitis is a rare interstitial lung disease and very few data regarding frequency, treatment and outcome exist for children. Children identified with hypersensitivity pneumonia from a Danish national cohort with diffuse interstitial lung disease form the basis of this study...

  3. [Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs].

    Science.gov (United States)

    Chalabianloo, Fatemeh

    2012-09-18

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered to be the second most frequent cause of adverse drug reactions, including drug hypersensitivity, after beta-lactam antibiotics. An understanding of the underlying mechanisms and clinical characteristics of hypersensitivity reactions to NSAIDs is necessary for the diagnosis and management of these undesirable reactions in the clinical setting.

  4. Central Hypersensitivity in Chronic Hemiplegic Shoulder Pain

    Science.gov (United States)

    Hoo, Jennifer Soo; Paul, Tracy; Chae, John; Wilson, Richard

    2013-01-01

    Objective This study aimed to examine the association of hemiplegic shoulder pain with central hypersensitivity through pressure-pain thresholds (PPT) at healthy, distant tissues. Design This study is a cross-sectional study. A total of 40 patients (n=20 hemiplegic shoulder pain (HSP), n=20 stroke without HSP) were enrolled in this study. Pressure-pain thresholds were measured at the affected deltoid and contralateral deltoid and tibialis anterior using a handheld algometer. Differences in PPTs were analyzed by Wilcoxon Rank Sum test and with linear regression analysis controlling for gender, a known confounder of PPTs. Results Subjects with hemiplegic shoulder pain had lower local PPTs than stroke control subjects when comparing the painful to dominant shoulders and comparing the non-painful shoulder and tibialis anterior to the non-dominant side controls. Similarly, those with hemiplegic shoulder pain had lower PPTs when comparing to controls in contralesional-to-contralesional comparisons as well as ipsilesional-to-ipsilesional comparisons. Conclusions Subjects with hemiplegic shoulder pain have lower local and distal PPTs than subjects without hemiplegic shoulder pain. Our study suggests that chronic shoulder pain may be associated with widespread central hypersensitivity, which has been previously found to be associated with other chronic pain syndromes. This further understanding can then help develop better treatment options for those with this hemiplegic shoulder pain. PMID:23255268

  5. Hypersensitivity reaction to nonanimal stabilized hyaluronic acid.

    Science.gov (United States)

    Matarasso, Seth L; Herwick, Robert

    2006-07-01

    Soft tissue augmentation has become a cornerstone of facial rejuvenation. The bovine collagens were historically considered the "gold standard" as they had an extensive safety history and were effective. However, because of their brief duration and the approximate 1.0% to 3.0% incidence of hypersensitivity, alternatives were sought. A new class of agents, the hyaluronans, was recently granted approval by the Food and Drug Administration. The hyaluronans are indicated for injection into the mid to deep dermis for correction of moderate to severe facial wrinkles and folds (eg, the nasolabial folds). The hyaluronans have two derivations: nonanimal stabilized hyaluronic acid (NASHA) and an additional formulation of avian origin. Both are considered major advancements as they are not species specific and therefore theoretically do not elicit humoral or cell-mediated immune reactions. To date there have been a few reports of allergic reactions to the NASHA hyaluronans, primarily to Restylane. We report what to our knowledge is the first hypersensitivity reaction to the second brand of NASHA, Captique.

  6. Antibiotic hypersensitivity in patients with CF.

    Science.gov (United States)

    Ramesh, Sujatha

    2002-08-01

    Antibiotic hypersensitivity reactions are relatively common in patients with cystic fibrosis (CF). The nature of the reactions and the mechanisms are no different in CF than the general population. Beta-lactam agents are the most common cause of these reactions. The risk depends on the specific beta-lactam agent used with Penicillins having a higher frequency of allergic reactions. There are several risk factors for developing these allergic responses, especially the increased usage. Since the available choices for antibiotic therapy is limited by the sensitivity of the organisms, management becomes a challenge. It is essential to classify the nature of the hypersensitivity reactions and determine the risks of repeat administration of the drug. Unfortunately, reliable skin tests are not available for all the antibiotics. RAST is of limited value. Recent data on cross-reactions between beta-lactam antibiotics and the option of newer agents offer useful alternative choices. Knowledge of the chemical structures of the antibiotics is useful for selecting suitable substitutes. Desensitization is a viable option in many of the reactions unless otherwise contradicted.

  7. Specific Aspects of Drug Hypersensitivity in Children.

    Science.gov (United States)

    Bergmann, Marcel; Caubet, Jean-Christoph

    2016-01-01

    Suspicion for drug hypersensitivity (DH) is a common reason for children's referral to an allergy department, with β-lactam antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) as the most frequently involved drugs. The prevalence of DH in children remains not well defined as epidemiologic studies in children are lacking, and the most of those take into account adverse drug reactions (ADR) without a systematic allergy work-up to confirm or exclude hypersensitivity. The clinical history is mandatory in order to classify the reaction as being immediate or non-immediate and then to subsequently adapt the allergy work-up. Mainly due to the lack of studies, the same guidelines used for diagnosis of drug allergy in adults are generally used in the pediatric population, and the diagnosis is based mainly on in vivo tests (i.e. skin tests and/or drug provocation test) and rarely on in vitro tests. However, specific aspects of management of DH in children have been recently highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Occupational hypersensitivity pneumonitis: an EAACI position paper.

    Science.gov (United States)

    Quirce, S; Vandenplas, O; Campo, P; Cruz, M J; de Blay, F; Koschel, D; Moscato, G; Pala, G; Raulf, M; Sastre, J; Siracusa, A; Tarlo, S M; Walusiak-Skorupa, J; Cormier, Y

    2016-06-01

    The aim of this document was to provide a critical review of the current knowledge on hypersensitivity pneumonitis caused by the occupational environment and to propose practical guidance for the diagnosis and management of this condition. Occupational hypersensitivity pneumonitis (OHP) is an immunologic lung disease resulting from lymphocytic and frequently granulomatous inflammation of the peripheral airways, alveoli, and surrounding interstitial tissue which develops as the result of a non-IgE-mediated allergic reaction to a variety of organic materials or low molecular weight agents that are present in the workplace. The offending agents can be classified into six broad categories that include bacteria, fungi, animal proteins, plant proteins, low molecular weight chemicals, and metals. The diagnosis of OHP requires a multidisciplinary approach and relies on a combination of diagnostic tests to ascertain the work relatedness of the disease. Both the clinical and the occupational history are keys to the diagnosis and often will lead to the initial suspicion. Diagnostic criteria adapted to OHP are proposed. The cornerstone of treatment is early removal from exposure to the eliciting antigen, although the disease may show an adverse outcome even after avoidance of exposure to the causal agent. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Cough reflex hypersensitivity: A role for neurotrophins.

    Science.gov (United States)

    El-Hashim, Ahmed Z; Jaffal, Sahar M

    2017-03-01

    Cough is one of the most common complaints for which sufferers seek medical assistance. However, currently available drugs are not very effective in treating cough, particularly that which follows an upper respiratory tract infection. Nonetheless, there has been a significant increase in our understanding of the mechanisms and pathways of the defensive cough as well as the hypersensitive/pathophysiological cough, both at airway and central nervous system (CNS) levels. Numerous molecules and signaling pathways have been identified as potential targets for antitussive drugs, including neurotrophins (NTs). NTs belong to a family of trophic factors and are critical for the development and maintenance of neurons in the central and peripheral nervous system including sympathetic efferents, sensory neuron afferents, and immune cells. Nerve growth factor (NGF) was the first member of the NT family to be discovered, with wide ranging actions associated with synapse formation, survival, proliferation, apoptosis, axonal and dendritic outgrowth, expression and activity of functionally important proteins such as ion channels, receptors, and neurotransmitters. In addition, NGF has been implicated in several disease states particularly neuropathic pain and most recently in the sensitization of the cough reflex. This review will briefly address the peripheral and central sensitization mechanisms of airway neurons and will then focus on NGF signaling and its role in cough hypersensitivity.

  10. Aggregated LDL in contact with macrophages induces local increases in free cholesterol levels that regulate local actin polymerization.

    Science.gov (United States)

    Grosheva, Inna; Haka, Abigail S; Qin, Chunbo; Pierini, Lynda M; Maxfield, Frederick R

    2009-10-01

    Interaction of macrophages with aggregated matrix-anchored lipoprotein deposits is an important initial step in atherogenesis. Aggregated lipoproteins require different cellular uptake processes than those used for endocytosis of monomeric lipoproteins. In this study, we tested the hypothesis that engagement of aggregated LDL (agLDL) by macrophages could lead to local increases in free cholesterol levels and that these increases in free cholesterol regulate signals that control cellular actin. AgLDL resides for prolonged periods in surface-connected compartments. Although agLDL is still extracellular, we demonstrate that an increase in free cholesterol occurs at sites of contact between agLDL and cells because of hydrolysis of agLDL-derived cholesteryl ester. This increase in free cholesterol causes enhanced actin polymerization around the agLDL. Inhibition of cholesteryl ester hydrolysis results in decreased actin polymerization. We describe a novel process that occurs during agLDL-macrophage interactions in which local release of free cholesterol causes local actin polymerization, promoting a pathological positive feedback loop for increased catabolism of agLDL and eventual foam cell formation.

  11. 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.

  12. Calcium-induced alteration of mitochondrial morphology and mitochondrial-endoplasmic reticulum contacts in rat brown adipocytes

    Directory of Open Access Journals (Sweden)

    I. Golic

    2014-09-01

    Full Text Available Mitochondria are key organelles maintaining cellular bioenergetics and integrity, and their regulation of [Ca2+]i homeostasis has been investigated in many cell types. We investigated the short-term Ca-SANDOZ® treatment on brown adipocyte mitochondria, using imaging and molecular biology techniques. Two-month-old male Wistar rats were divided into two groups: Ca-SANDOZ® drinking or tap water (control drinking for three days. Alizarin Red S staining showed increased Ca2+ level in the brown adipocytes of treated rats, and potassium pyroantimonate staining localized electron-dense regions in the cytoplasm, mitochondria and around lipid droplets. Ca-SANDOZ® decreased mitochondrial number, but increased their size and mitochondrial cristae volume. Transmission electron microscopy revealed numerous enlarged and fusioned-like mitochondria in the Ca-SANDOZ® treated group compared to the control, and megamitochondria in some brown adipocytes. The Ca2+ diet affected mitochondrial fusion as mitofusin 1 (MFN1 and mitofusin 2 (MFN2 were increased, and mitochondrial fission as dynamin related protein 1 (DRP1 was decreased. Confocal microscopy showed a higher colocalization rate between functional mitochondria and endoplasmic reticulum (ER. The level of uncoupling protein-1 (UCP1 was elevated, which was confirmed by immunohistochemistry and Western blot analysis. These results suggest that Ca-SANDOZ® stimulates mitochondrial fusion, increases mitochondrial-ER contacts and the thermogenic capacity of brown adipocytes

  13. Nano-stenciled RGD-gold patterns that inhibit focal contact maturation induce lamellipodia formation in fibroblasts.

    Directory of Open Access Journals (Sweden)

    Roman Lutz

    Full Text Available Cultured fibroblasts adhere to extracellular substrates by means of cell-matrix adhesions that are assembled in a hierarchical way, thereby gaining in protein complexity and size. Here we asked how restricting the size of cell-matrix adhesions affects cell morphology and behavior. Using a nanostencil technique, culture substrates were patterned with gold squares of a width and spacing between 250 nm and 2 µm. The gold was functionalized with RGD peptide as ligand for cellular integrins, and mouse embryo fibroblasts were plated. Limiting the length of cell-matrix adhesions to 500 nm or less disturbed the maturation of vinculin-positive focal complexes into focal contacts and fibrillar adhesions, as indicated by poor recruitment of α5-integrin. We found that on sub-micrometer patterns, fibroblasts spread extensively, but did not polarize. Instead, they formed excessive numbers of lamellipodia and a fine actin meshwork without stress fibers. Moreover, these cells showed aberrant fibronectin fibrillogenesis, and their speed of directed migration was reduced significantly compared to fibroblasts on 2 µm square patterns. Interference with RhoA/ROCK signaling eliminated the pattern-dependent differences in cell morphology. Our results indicate that manipulating the maturation of cell-matrix adhesions by nanopatterned surfaces allows to influence morphology, actin dynamics, migration and ECM assembly of adhering fibroblasts.

  14. Managing hypersensitivity to asparaginase in pediatrics, adolescents, and young adults.

    Science.gov (United States)

    Shinnick, Sara E; Browning, Mary L; Koontz, Susannah E

    2013-01-01

    Hypersensitivity reactions to chemotherapeutic drugs have been documented for numerous cancer therapies. Clinical hypersensitivity to Escherichia coli asparaginase has been reported to range from 0% to 75%. Throughout the United States, nurses assume frontline responsibility for the assessment of asparaginase-related hypersensitivity reactions. It is essential that nurses educate themselves on the signs and symptoms of asparaginase-related hypersensitivity reactions as well as current supportive care approaches. The purpose of this review is to summarize acute lymphoblastic leukemia and the role of asparaginase and the pathology of allergic reactions. We will also update nurses on the differences in asparaginase preparations including dosing, half-life, rates of hypersensitivity, and routes of administration. A summary of current management and supportive care strategies will be provided as will a discussion of the relationship between allergy, antibodies, and asparaginase activity.

  15. Identification of thymus and activation-regulated chemokine (TARC/CCL17) as a potential marker for early indication of disease and prediction of disease activity in drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS).

    Science.gov (United States)

    Ogawa, Kohei; Morito, Hironori; Hasegawa, Ayako; Daikoku, Natsuko; Miyagawa, Fumi; Okazaki, Aiko; Fukumoto, Takaya; Kobayashi, Nobuhiko; Kasai, Takahiko; Watanabe, Hideaki; Sueki, Hirohiko; Iijima, Masafumi; Tohyama, Mikiko; Hashimoto, Koji; Asada, Hideo

    2013-01-01

    Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) is a serious acute drug reaction with fever, cutaneous eruption, lymphadenopathy, and several visceral dysfunctions. Eosinophilia is a common hematological abnormality in DIHS/DRESS suggesting that the Th2-type immune response is involved. Thymus and activation-regulated chemokine (TARC/CCL17) is a family of CC chemokines known to play an important role in Th2-mediated immune-inflammatory processes. We investigated the pathogenic role of TARC in patients with DIHS. Sera were obtained from 8 patients with DIHS, 7 patients with Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN), and 14 patients with drug-induced maculopapular exanthema (MPE). Serum TARC levels were measured by ELISA. TARC levels were then compared with clinical symptoms and various hematological parameters. In addition, a biopsy was taken from the lesional skin of patients with DIHS and stained with anti-TARC Ab and anti-CD11c Ab. Serum TARC levels in patients with DIHS were significantly higher than those in patients with SJS/TEN and MPE during the acute phase. Serum TARC levels in DIHS patients correlated with skin eruptions, serum sIL-2R levels, eosinophil counts, and serum IL-5 levels. Immunohistochemical staining revealed that TARC was mainly expressed on CD11c+ dermal dendritic cells in patients with DIHS. Serum TARC levels may be associated with the initial presentation of DIHS as well as disease activity during the course. Thus, they could be useful as an indicator for early diagnosis and assessment of disease activity in DIHS. CD11c+ dendritic cells may be the main source of TARC in patients with DIHS. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  16. Micronucleus assay in human fibroblasts: a measure of spontaneous chromosomal instability and mutagen hypersensitivity

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    Rudd, N.L.; Hoar, D.I.; Greentree, C.L.; Dimnik, L.S.; Hennig, U.S.S.

    1988-01-01

    By comparing fibroblast strains derived from individuals exhibiting chromosome instability and/or mutagen hypersensitivity (Cockayne syndrome, ataxia telangiectasia, and Fanconi anemia) with strains derived from health donors, the fibroblast micronucleus assay has been established as a reproducible measure of the genotypic variation in spontaneous or mitomycin C (MMC)-induced chromosomal instability. The patient strains that were moderately or exquisitely sensitive to MMC could be distinguished readily from the control strains, both in levels of spontaneous micronuclei and in sensitivity to MMC, whereas the mildly sensitive strain (Cockayne syndrome) overlapped with the control range. The reproducibility of the assay was evaluated within and between experiments. In addition to its value as a test system for genotoxins, the fibroblast micronucleus assay may be useful for investigating genetically determined hypersensitivity to mutagens, elevated spontaneous chromosomal breakage, and chromosome segregation errors.

  17. Human Langerhans cells control Th cells via programmed death-ligand 1 in response to bacterial stimuli and nickel-induced contact allergy.

    Directory of Open Access Journals (Sweden)

    Manuel Hitzler

    Full Text Available Langerhans cells (LCs are suspected to initiate inflammatory immune responses to contact allergens and pathogenic bacteria. In chronic infectious diseases, programmed death ligand (PD-L 1 exhibits both inhibitory and costimulatory functions on T cell-mediated activation and tolerance. Here, we investigated the effects of contact allergens and bacterial stimuli on PD-L1 expression in LCs and the effects of altered PD-L1 expression on cytokine release of subsequently cocultured T cells. Monocyte-derived LCs (MoLCs, LCs, and skin sections of patients suffering from allergic contact dermatitis were challenged with nickel and then analyzed for PD-L1 expression by confocal laser scanning microscopy and flow cytometry. In blocking experiments, we found that the release of Th cell specific cytokines was dependent on both stimulation of LCs and inhibition of PD-L1-PD-1 interactions. Stimulation with peptidoglycan (PGN or lipopolysaccharide (LPS and blockage of PD-L1 with a specific antibody triggered the release of high levels of IL-17, IL-22, TNF-α, and IFN-γ in CD4(+T cells. If nickel was used as a stimulus, blockage of PD-L1 led to high amounts of TNF-α and IL-22. A closer look revealed PD-L1-dependent upregulation of IL-17 secretion in FACS-sorted CCR6(+/CCR4(+ T memory cells. In the presence of anti-PD-L1, PGN induced secretion of IFN-γ and IL-17 in total CCR6(+ cells, while nickel triggered secretion of IFN-γ and IL-17 exclusively in CCR6(+/CCR4(+ cells. Our findings suggest that PD-L1 on LCs plays a crucial role in type IV allergic reactions and in response to bacterial stimuli by controlling the nature of inflammatory Th cell responses.

  18. 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

  19. How common are long-lasting, intensely itching vaccination granulomas and contact allergy to aluminium induced by currently used pediatric vaccines? A prospective cohort study.

    Science.gov (United States)

    Bergfors, Elisabet; Hermansson, Göran; Nyström Kronander, Ulla; Falk, Lars; Valter, Lars; Trollfors, Birger

    2014-10-01

    The frequency of long-lasting, intensely itching subcutaneous nodules at the injection site for aluminium (Al)-adsorbed vaccines (vaccination granulomas) was investigated in a prospective cohort study comprising 4,758 children who received either a diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (Infanrix®, Pentavac®) alone or concomitant with a pneumococcal conjugate (Prevenar). Both vaccines were adsorbed to an Al adjuvant. Altogether 38 children (0.83 %) with itching granulomas were identified, epicutaneously tested for Al sensitisation and followed yearly. Contact allergy to Al was verified in 85 %. The median duration of symptoms was 22 months in those hitherto recovered. The frequency of granulomas induced by Infanrix® was >0.66 % and by Prevenar >0.35 %. The risk for granulomas increased from 0.63 to 1.18 % when a second Al-adsorbed vaccine was added to the schedule. Long-lasting itching vaccination granulomas are poorly understood but more frequent than previously known after infant vaccination with commonly used diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b and pneumococcal conjugate vaccines. The risk increases with the number of vaccines given. Most children with itching granulomas become contact allergic to aluminium. Itching vaccination granulomas are benign but may be troublesome and should be recognised early in primary health care to avoid unnecessary investigations, anxiety and mistrust.

  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. Parathyroid Hormone-Related Peptide Elicits Peripheral TRPV1-dependent Mechanical Hypersensitivity

    Science.gov (United States)

    Shepherd, Andrew J.; Mickle, Aaron D.; Kadunganattil, Suraj; Hu, Hongzhen; Mohapatra, Durga P.

    2018-01-01

    Bone metastasis in breast, prostate and lung cancers often leads to chronic pain, which is poorly managed by existing analgesics. The neurobiological mechanisms that underlie chronic pain associated with bone-metastasized cancers are not well understood, but sensitization of peripheral nociceptors by tumor microenvironment factors has been demonstrated to be important. Parathyroid hormone-related peptide (PTHrP) is highly expressed in bone-metastasized breast and prostate cancers, and is critical to growth and proliferation of these tumors in the bone tumor microenvironment. Previous studies have suggested that PTHrP could sensitize nociceptive sensory neurons, resulting in peripheral pain hypersensitivity. In this study, we found that PTHrP induces both heat and mechanical hypersensitivity, that are dependent on the pain-transducing transient receptor potential channel family vanilloid, member-1 (TRPV1), but not the mechano-transducing TRPV4 and TRPA1 ion channels. Functional ratiometric Ca2+ imaging and voltage-clamp electrophysiological analysis of cultured mouse DRG neurons show significant potentiation of TRPV1, but not TRPA1 or TRPV4 channel activation by PTHrP. Interestingly, PTHrP exposure led to the slow and sustained activation of TRPV1, in the absence of any exogenous channel agonist, and is dependent on the expression of the type-1 parathyroid hormone receptor (PTH1), as well as on downstream phosphorylation of the channel by protein kinase C (PKC). Accordingly, local administration of specific small-molecule antagonists of TRPV1 to mouse hindpaws after the development of PTHrP-induced mechanical hypersensitivity led to its significant attenuation. Collectively, our findings suggest that PTHrP/PTH1-mediated flow activation of TRPV1 channel contributes at least in part to the development and maintenance of peripheral mechanical pain hypersensitivity, and could therefore constitute a mechanism for nociceptor sensitization in the context of metastatic bone

  2. Eosinophilic tracheobronchitis with cough hypersensitivity caused by Streptomyces albus antigen

    Directory of Open Access Journals (Sweden)

    Haruhiko Ogawa

    2000-01-01

    Full Text Available A 52-year-old woman is reported with atopic cough, in whom bronchoprovocation with Streptomyces albus antigen induced cough and bronchoscopic biopsy revealed eosinophilic tracheobronchitis. She was admitted for the diagnosis and treatment of severe non-productive cough. Although her induced sputum contained 8% eosinophils of nucleated cells and bronchoscopic biopsy specimens revealed eosinophil infiltration in both tracheal and bronchial wall, she did not have bronchial hyperresponsiveness to methacholine or heightened bronchomotor tone. Bronchodilator therapy was not effective for her coughing. Her symptoms worsened on returning home, suggesting the existence of some etiologic agents in her house. Streptomyces albus was isolated from her house. A high titer of anti-S. albus antibody was detected in her serum and the bronchoprovocation test with S. albus antigen was positive: development of coughing 15 min later and decrease in cough threshold to inhaled capsaicin 24 h later (3.9 μmol/L from 31.3 μmol/L prechallenge. This is the first report on eosinophilic tracheobronchitis with cough hypersensitivity caused by allergic reaction to S. albus antigen.

  3. Prevalence of delayed-type and immediate-type hypersensitivity in healthcare workers with hand eczema.

    Science.gov (United States)

    Ibler, Kristina S; Jemec, Gregor B E; Garvey, Lene H; Agner, Tove

    2016-10-01

    Occupational contact dermatitis is common in healthcare workers. Although irritant contact dermatitis resulting from wet work is the most frequently reported cause, healthcare workers also constitute high-risk group for the development of allergic contact dermatitis and contact urticaria. To evaluate the prevalence of delayed-type and immediate-type hypersensitivity in 120 healthcare workers with hand eczema. One hundred and twenty healthcare workers from three major hospitals in Denmark with self-reported hand eczema within the last year participated in the study. Patch tests included baseline series plus selected allergens, and prick tests included standard inhalational allergens plus natural rubber latex and chlorhexidine. Levels of IgE specific for latex, chlorhexidine and ethylene oxide were measured. Of the participants, 53% had positive patch test reactions. The most frequent positive patch test reactions were to nickel, thiomersal, fragrances, rubber chemicals, and colophonium. The prevalence of natural rubber latex allergy as diagnosed by prick testing was 2.5%, and chlorhexidine allergy (both contact allergy and IgE-mediated allergy) was found in <1%. Ethylene oxide allergy was not identified in any of the participants. Our results confirm previous reports on contact allergy patterns in healthcare workers. Testing for natural rubber latex allergy is still important, but increased risks of chlorhexidine and ethylene oxide allergy could not be confirmed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Acute physical and psychological stress effects on visceral hypersensitivity in male rat: role of central nucleus of the amygdala

    OpenAIRE

    Afzali,Hamideh; Nabavizadeh, Fatemeh; Karimian,Seyed Morteza; Sohanaki, Hamid; Vahedian, Jalal; Mohamadi, Seyed Mehdi

    2017-01-01

    ABSTRACT Objective: The aim of this study was to investigate the effects of acute physical and psychological stress and temporary central nucleus of the amygdala (CeA) block on stress-induced visceral hypersensitivity. Methods: Forty two male Wistar rats were used in this study. Animals were divided into 7 groups (n = 6); 1 - Control, 2 - physical stress, 3 - psychological stress, 4 - sham, 5 - lidocaine, 6 - lidocaine + physical stress and 7 - lidocaine + psychological stress. Stress induc...

  5. Immediate-type drug hypersensitivity and associated factors in a general population.

    Science.gov (United States)

    Kurt, E; Demir, A U; Cadirci, O; Yildirim, H; Pinar Eser, T

    2011-01-01

    Our aim was to assess the prevalence and associated risk factors of common hypersensitivity reactions to drugs in the adult population, for which limited data are available. The data consisted of 1052 questionnaires obtained from adults. The questionnaires consisted of questions on immediate-type hypersensitivity reactions induced by drugs (itching, skin rash/hives, angio-oedema, shortness of breath, hypotension, and loss of consciousness). The questionnaire added knowledge on physician's diagnosis of asthma, allergic rhinitis, eczema, and other chronic systemic diseases. The prevalence of self-reported drug hypersensitivity reactions was 11.8% for all reactions. Hypersensitivity reactions to analgesics were the most common (37.2%) followed by antibiotics (24.2%). Multivariate analysis showed that female gender (Odds Ratio (OR) 95% Confidence Interval (CI) (2.00 (1.25-3.21)), physician-diagnosed allergic rhinitis (3.03 (1.64-5.59)), and eczema (3.22 (1.87-5.53)) were associated with any type of drug hypersensitivity reactions. Itching was associated with allergic rhinitis (4.50 (2.06-9.81)) and eczema diagnosis (4.24 (2.14-8.64)). Skin rash/hives were associated with female gender (2.67 (1.24-5.74)), allergic rhinitis (4.57 (1.99-10.05)), and eczema (5.36 (2.65-10.84)). Angio-oedema was higher in females (5.74 (1.69-18.5)). In addition, eczema (2.87 (1.12-7.32)) and systemic hypertension (2.60(1.03-6.10)) were associated with angio-oedema. Shortness of breath was only associated with ever asthma diagnosis (6.59 (2.09-20.83)). Factors associated with loss of consciousness were female gender (5.56 (1.27-24.30)), allergic rhinitis diagnosis (4.76 (1.73-13.14)), and systemic hypertension (2.74 (1.02-7.41)). The study showed that females and subjects with allergic diseases and hypertension were more susceptible to drug hypersensitivity reactions. Copyright © 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

  6. Multiple hypersensitivities including recurrent airway obstruction, insect bite hypersensitivity, and urticaria in 2 warmblood horse populations.

    Science.gov (United States)

    Kehrli, D; Jandova, V; Fey, K; Jahn, P; Gerber, V

    2015-01-01

    Multiple hypersensitivities (MHS) have been described in humans, cats, and dogs, but not horses. Horses suffering from recurrent airway obstruction (RAO), insect bite hypersensitivity (IBH), or urticaria (URT) will have an increased risk of also being affected by another one of these hypersensitivities. This predisposition for MHS also will be associated with decreased shedding of strongylid eggs in feces and with a single nucleotide polymorphism (SNP BIEC2-224511), previously shown to be associated with RAO. The first population (P1) included 119 randomly sampled horses representative of the Swiss sporthorse population; the replication population (P2) included 210 RAO-affected Warmblood horses and 264 RAO-unaffected controls. All horses were Warmbloods, 14 years or older. Associations between disease phenotypes (RAO, IBH, URT, MHS) fecal egg counts, the SNP BIEC2-224511 as well as management and environmental factors were investigated. In P1, RAO-affected horses had a 13.1 times higher odds ratio (OR) of also suffering from IBH (P = .004). In P2, the respective OR was 7.4 (P = .002) and IBH-affected horses also showed a 7.1 times increased OR of concomitantly suffering from URT (P < .001). IBH, URT, and MHS phenotypes were significantly associated with the absence of nematode eggs in the feces. This is the first report of MHS in horses. Specifically, an increased risk for IBH should be expected in RAO-affected horses. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  7. Numerical and ex vivo studies of a bioprobe developed for laser-induced thermotherapy (LITT) in contact with liver tissue.

    Science.gov (United States)

    Chartier, T; Carpentier, O; Genestie, B; Hornez, J-C; Monchau, F

    2016-08-01

    This work is based on the production of a bioprobe that is compatible with magnetic resonance imaging (MRI) for laser-induced thermotherapy (LITT) in liver cancer laser therapy. This probe is made of an alumina tube (3-mm diameter) in which an optical fibre is centred and fixed. A shooting window (20mm) is created using a mechanical rectifier. The device is then consolidated by the injection of a transparent and heat-resistant resin. Through numerical modelling, the thermal power damping of the laser source is evaluated as well as the propagation of the heat in the ex vivo liver tissue according to different heating scenarios. These analyses allow for an estimation of the irradiated volume. Ex vivo tests were performed on bovine liver to confirm the adequacy of the bioprobe for LITT and of the irradiated volumes predicted by the numerical model. There was a difference of 8% between the simulations and ex vivo experiments. The pulsed mode heating scenario was the most effective under the experimental conditions. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

  8. Disruption of zonula occludens-1 localization in the rabbit corneal epithelium by contact lens-induced hypoxia.

    Science.gov (United States)

    Yanai, Ryoji; Ko, Ji-Ae; Morishige, Naoyuki; Chikama, Tai-ichiro; Ichijima, Hideji; Nishida, Teruo

    2009-10-01

    Hypoxia impairs the barrier function of the corneal epithelium. This function depends on tight junctions, of which zonula occludens (ZO)-1 is a major component. The authors have investigated the effects of hypoxia on ZO-1 localization and expression in the rabbit corneal epithelium in vivo. A polymethylmethacrylate (PMMA) or rigid gas-permeable (RGP) lens was applied to one eye each of albino rabbits for 24 hours. The structure of the corneal epithelium was examined by in vivo confocal microscopy, and epithelial barrier function was evaluated by measurement of central corneal thickness. The distribution and expression of ZO-1 in the corneal epithelium were examined by immunofluorescence analysis and by immunoblot and reverse transcription-polymerase chain reaction analyses, respectively. Application of a PMMA lens, but not that of an RGP lens, resulted in a reduction in cell size at the surface of the corneal epithelium, compared with that in control eyes, and an increase in central corneal thickness. Immunofluorescence analysis revealed a continuous pattern of ZO-1 immunoreactivity around the perimeter of superficial corneal epithelial cells in control eyes or in eyes treated with an RGP lens. In contrast, the pattern of ZO-1 staining was discontinuous and patchy in eyes treated with a PMMA lens. Amounts of ZO-1 mRNA and protein in the corneal epithelium were reduced by application of a PMMA lens but not by that of an RGP lens. Hypoxia at the ocular surface induced the disruption of tight junctions between superficial cells in the rabbit corneal epithelium in vivo.

  9. Activation of spinal glucagon-like peptide-1 receptors specifically suppresses pain hypersensitivity.

    Science.gov (United States)

    Gong, Nian; Xiao, Qi; Zhu, Bin; Zhang, Chang-Yue; Wang, Yan-Chao; Fan, Hui; Ma, Ai-Niu; Wang, Yong-Xiang

    2014-04-09

    This study aims to identify the inhibitory role of the spinal glucagon like peptide-1 receptor (GLP-1R) signaling in pain hypersensitivity and its mechanism of action in rats and mice. First, GLP-1Rs were identified to be specifically expressed on microglial cells in the spinal dorsal horn, and profoundly upregulated after peripheral nerve injury. In addition, intrathecal GLP-1R agonists GLP-1(7-36) and exenatide potently alleviated formalin-, peripheral nerve injury-, bone cancer-, and diabetes-induced hypersensitivity states by 60-90%, without affecting acute nociceptive responses. The antihypersensitive effects of exenatide and GLP-1 were completely prevented by GLP-1R antagonism and GLP-1R gene knockdown. Furthermore, exenatide evoked β-endorphin release from both the spinal cord and cultured microglia. Exenatide antiallodynia was completely prevented by the microglial inhibitor minocycline, β-endorphin antiserum, and opioid receptor antagonist naloxone. Our results illustrate a novel spinal dorsal horn microglial GLP-1R/β-endorphin inhibitory pathway in a variety of pain hypersensitivity states.

  10. Role of nesfatin-1 in a rat model of visceral hypersensitivity.

    Science.gov (United States)

    Jia, Fang-Yuan; Li, Xue-Liang; Li, Tian-Nv; Wu, Jing; Xie, Bi-Yun; Lin, Lin

    2013-06-14

    To explore the role of nesfatin-1 on irritable bowel syndrome (IBS)-like visceral hypersensitivity. The animal model of IBS-like visceral hypersensitivity was induced by intracolonic infusion of 0.5% acetic acid (AA) in saline once daily from postnatal days 8-21. Experiments were performed when rats became adults. The visceral sensitivity of rats was evaluated by abdominal withdrawal reflex (AWR) and electromyographic (EMG) activity of the external oblique muscle to graded colorectal distension. The content of nesfatin-1 in serum was determined using enzyme-linked immunosorbent assay. After implantation of an intracerebroventricular (ICV) cannula and two electrodes into the external oblique muscle, model rats were randomly divided into four groups. Animals then received ICV injection of 8 μg of anti-nesfatin-1/nucleobindin-2 (NUCB2), 50 μg of α-helical corticotropin releasing factor (CRF) 9-41 (non-selective CRF receptor antagonist), 50 μg of NBI-27914 (selective CRF1 receptor antagonist) or 5 μL of vehicle. After 1 h of ICV administration, visceral sensitivity of each group was measured again, and comparisons between groups were made. Rats treated with AA showed higher mean AWR scores and EMG activity at all distension pressures compared with controls (P IBS-like visceral hypersensitivity, which may be implicated in brain CRF/CRF1 signaling pathways.

  11. Immunoproteomics for serological diagnosis of hypersensitivity pneumonitis caused by environmental microorganisms.

    Science.gov (United States)

    Millon, Laurence; Reboux, Gabriel; Barrera, Coralie; Rognon, Benedicte; Roussel, Sandrine; Monod, Michel

    2014-01-01

    Diagnosis of immunoallergenic pathologies due to microorganisms such as hypersensitivity pneumonitis includes detection of circulating specific antibodies. Detection of precipitins has classically been performed using immunoprecipitation techniques with crude antigenic extracts from microorganisms implicated as etiologic agents. However, these techniques lack standardization because of the different composition of fungal antigenic extracts from one batch to another. Therefore, there is high interest in developing standardized serological diagnostic methods using recombinant antigens. Immunoproteomics have proved to be useful for identifying the immunogenic proteins in several microorganisms linked to hypersensitivity pneumonitis. With this approach, the causative microorganisms are first isolated from the environment of patients. Then the proteins are separated by two-dimensional electrophoresis and revealed by Western blotting with sera of different patients suffering from the disease compared to sera of asymptomatic exposed controls. Immunoreactive proteins are identified by mass spectrometry. Identified immunoreactive proteins found to be specific markers for the disease could be subsequently produced as recombinant antigens using various expression systems to develop ELISA tests. Using recombinant antigens, standardized ELISA techniques can be developed, with sensitivity and specificity reaching 80% and 90%, respectively, and more if using a combination of several antigens. Immunoproteomics can be applied to any environmental microorganisms, with the aim of proposing panels of recombinant antigens able to improve the sensitivity and standardization of serologic diagnosis of hypersensitivity pneumonitis, but also other mold-induced allergic diseases such as allergic broncho pulmonary aspergillosis or asthma.

  12. Evaluation of Lymphocyte Transformation Test Results in Patients with Delayed Hypersensitivity Reactions following the Use of Anticonvulsant Drugs.

    Science.gov (United States)

    Karami, Zahra; Mesdaghi, Mehrnaz; Karimzadeh, Parvaneh; Mansouri, Mahboubeh; Taghdiri, Mohammad Mehdi; Kayhanidoost, Zarrintaj; Jebelli, Bita; Shekarriz Foumani, Reza; Babaie, Delara; Chavoshzadeh, Zahra

    2016-01-01

    Administration of the anticonvulsant drugs phenobarbital, phenytoin, carbamazepine and lamotrigine can be associated with severe hypersensitivity reactions. The lymphocyte transformation test (LTT) is a method to determine which drug has caused the hypersensitivity reaction. This study was done to evaluate the results of LTT in patients with delayed hypersensitivity reactions following the administration of anticonvulsants. Twenty-four patients with hypersensitivity reactions, e.g. drug-induced hypersensitivity syndrome/drug rash and eosinophilia with systemic symptoms (DIHS/DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), following the administration of anticonvulsant drugs, and 24 patients who had used anticonvulsant drugs but did not have hypersensitivity reactions (the control group) were included in this study. Peripheral blood mononuclear cells were isolated. The cells were stimulated with the drugs, phytohemagglutinin as a mitogen and Candida as an antigen (positive controls). Lymphocyte proliferation was measured using the BrdU proliferation assay kit (Roche, Germany). The stimulation index was calculated as the mean ratio of the OD of stimulated cells divided by the OD of unstimulated cells. The results in the case and control groups were compared. Of 24 patients in the test group, 14 (58.3%) had positive LTT results and 10 (41.7%) had negative results. Among patients in the control group, 1 (4.2%) had a positive LTT result and 23 (95.8%) had negative results. Among the patients who had received carbamazepine and phenytoin, there was a significant difference between the results of LTT in the case and control groups (p = 0.002 and p = 0.028, respectively). Although patients receiving lamotrigine and phenobarbital had more positive LTT results in the case group than in the control group, these differences were not statistically significant. The sensitivity, specificity, positive predictive value and negative predictive value of LTT

  13. Sodium permeable and "hypersensitive" TREK-1 channels cause ventricular tachycardia.

    Science.gov (United States)

    Decher, Niels; Ortiz-Bonnin, Beatriz; Friedrich, Corinna; Schewe, Marcus; Kiper, Aytug K; Rinné, Susanne; Seemann, Gunnar; Peyronnet, Rémi; Zumhagen, Sven; Bustos, Daniel; Kockskämper, Jens; Kohl, Peter; Just, Steffen; González, Wendy; Baukrowitz, Thomas; Stallmeyer, Birgit; Schulze-Bahr, Eric

    2017-04-01

    In a patient with right ventricular outflow tract (RVOT) tachycardia, we identified a heterozygous point mutation in the selectivity filter of the stretch-activated K2P potassium channel TREK-1 (KCNK2 or K2P2.1). This mutation introduces abnormal sodium permeability to TREK-1. In addition, mutant channels exhibit a hypersensitivity to stretch-activation, suggesting that the selectivity filter is directly involved in stretch-induced activation and desensitization. Increased sodium permeability and stretch-sensitivity of mutant TREK-1 channels may trigger arrhythmias in areas of the heart with high physical strain such as the RVOT We present a pharmacological strategy to rescue the selectivity defect of the TREK-1 pore. Our findings provide important insights for future studies of K2P channel stretch-activation and the role of TREK-1 in mechano-electrical feedback in the heart. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  14. Equine insect bite hypersensitivity: what do we know?

    Science.gov (United States)

    Schaffartzik, A; Hamza, E; Janda, J; Crameri, R; Marti, E; Rhyner, C

    2012-06-30

    Insect bite hypersensitivity (IBH) is an allergic dermatitis of the horse caused by bites of insects of the genus Culicoides and is currently the best characterized allergic disease of horses. This article reviews knowledge of the immunopathogenesis of IBH, with a particular focus on the causative allergens. Whereas so far hardly any research has been done on the role of antigen presenting cells in the pathogenesis of IBH, recent studies suggest that IBH is characterized by an imbalance between a T helper 2 (Th2) and regulatory T cell (T(reg)) immune response, as shown both locally in the skin and with stimulated peripheral blood mononuclear cells. Various studies have shown IBH to be associated with IgE-mediated reactions against salivary antigens from Culicoides spp. However, until recently, the causative allergens had not been characterized at the molecular level. A major advance has now been made, as 11 Culicoides salivary gland proteins have been identified as relevant allergens for IBH. Currently, there is no satisfactory treatment of IBH. Characterization of the main allergens for IBH and understanding what mechanisms induce a healthy or allergic immune response towards these allergens may help to develop new treatment strategies, such as immunotherapy. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Occupational asthma due to esparto hypersensitivity in a building worker.

    Science.gov (United States)

    Ruiz-Hornillos, Francisco Javier; De Barrio Fernández, Manuel; Molina, Pilar Tornero; Marcén, Itziar Sánchez; Fernandez, Galicia Davila; Sotés, María Rubio; de Ocariz, María Luisa Baeza Ochoa

    2007-01-01

    Esparto is a gramineous plant that has multiple applications in today's industry. Several cases of hypersensitivity pneumonitis (HP) caused by esparto inhalation have been reported, but only one case of asthma caused by Aspergillus fumigatus contaminating esparto has been communicated. We report a case of asthma induced by esparto inhalation in a 58-year-old man, who is a building industry worker, with subclinical sensitization to grass pollen. The relation between clinical symptoms and work activities was supported by peak expiratory flow (PEF) monitorization; PEF values decreased by 20% the days he handled esparto. Prick test with esparto was positive. Immunoblot analysis revealed several allergens in the esparto extract, some of them present in Lolium and A. fumigatus extracts. IgE immunoblot inhibition revealed a complete inhibition of lolium and A. fumigatus IgE reactive bands by esparto proteins. The patient then avoided the exposure to esparto at work and has remained asymptomatic for the last 2 years. In conclusion, this is a case of occupational asthma caused by esparto dust mediated by IgE antibodies. Proteins of A. fumigatus as well as proteins from this gramineous plant, which cross-reacted with esparto allergens, were responsible for the disease.

  16. Drug hypersensitivity in students from São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Luis Felipe Chiaverini Ensina

    2010-01-01

    Full Text Available BACKGROUND: Drug hypersensitivity is responsible for substantial mortality and morbidity, and increased health costs. However, epidemiological data on drug hypersensitivity in general or specific populations are scarce. METHODS: We performed a cross-sectional survey of 1015 university students, using a self-reported questionnaire. RESULTS: The prevalence of self-reported drug hypersensitivity was 12,11% (123/1015. The most frequently implicated drugs were non-steroidal anti-inflammatory drugs (45,9% and beta-lactam and sulfonamide antibiotics (25,40%. The majority of the patients reported dermatological manifestations (99, followed by respiratory (40, digestive (23 and other (19. Forty-five patients had an immediate type reaction, and 76,72% (89 had the drug by oral route. CONCLUSION: The results showed that drug hypersensitivity is highly prevalent in university students, and that nonsteroidal anti-inflammatory drug and antibiotics (beta-lactams and sulfonamide are the most frequently concerned drugs.

  17. Unpacking social hypersensitivity: vulnerability to the absence of positive feedback.

    Science.gov (United States)

    Cikara, Mina; Girgus, Joan S

    2010-10-01

    Navigating social life requires accurately calibrated sensitivity to external feedback, thus extreme sensitivity to external feedback may be maladaptive. Using a daily diary design, the authors investigated whether the relationship between social hypersensitivity and daily events predicted level, lability, and reactivity of both self-esteem and affect. Relative to their less sensitive peers, socially hypersensitive people exhibited lower levels of self-esteem and greater negative affect and experienced greater fluctuations in self-esteem and negative affect. Although most people were negatively reactive to the presence of negative feedback, socially hypersensitive people were negatively reactive to the absence of positive feedback as well. The authors argue that reactivity to the absence of positive feedback is a fundamental, heretofore untested aspect of what makes social hypersensitivity a pernicious orientation.

  18. Innovations for combating dentin hypersensitivity: current state of the art.

    Science.gov (United States)

    Li, Yiming

    2012-06-01

    Dentin hypersensitivity is a common dental complaint, and in severe cases it can impair eating, drinking, and even speaking, thus interfering with the normal daily life of an individual. Throughout years of research, there has been significant advancement in understanding dentin hypersensitivity, and various treatment regimens have been developed for combating the problem. The continued efforts have recently resulted in a novel technology that uses 8% arginine and calcium carbonate for treating dentin hypersensitivity. Formulations of oral care products using this technology--including toothpaste and prophylactic pastes--have demonstrated not only their effectiveness but also their ability to provide instant relief. This paper provides an overview of the etiology of dentin hypersensitivity, the discovery and development of measures for combating the problem, and the available data on the clinical efficacy of products based on 8% arginine and calcium carbonate.

  19. 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...

  20. The role for decorin in delayed-type hypersensitivity

    National Research Council Canada - National Science Library

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

    2011-01-01

    ... (oxazolone-mediated delayed-type hypersensitivity [DTH]) in decorin-deficient (Dcn(-/-)) and wild-type mice. Dcn(-/-) mice showed a reduced ear swelling 24 h after oxazolone treatment with a concurrent attenuation of leukocyte infiltration...

  1. Enhanced neuroinflammation and pain hypersensitivity after peripheral nerve injury in rats expressing mutated superoxide dismutase 1

    Directory of Open Access Journals (Sweden)

    Lavand'homme Patricia

    2011-04-01

    Full Text Available Abstract Background Neuroinflammation and nitroxidative stress are implicated in the pathophysiology of neuropathic pain. In view of both processes, microglial and astroglial activation in the spinal dorsal horn play a predominant role. The present study investigated the severity of neuropathic pain and the degree of glial activation in an inflammatory- and nitroxidative-prone animal model. Methods Transgenic rats expressing mutated superoxide dismutase 1 (hSOD1G93A are classically used as a model for amyotrophic lateral sclerosis (ALS. Because of the associated inflammatory- and nitroxidative-prone properties, this model was used to study thermal and mechanical hypersensitivity following partial sciatic nerve ligation (PSNL. Next to pain hypersensitivity assessment, microglial and astroglial activation states were moreover characterized, as well as inflammatory marker gene expression and the glutamate clearance system. Results PSNL induced thermal and mechanical hypersensitivity in both wild-type (WT and transgenic rats. However, the degree of thermal hypersensitivity was found to be exacerbated in transgenic rats while mechanical hypersensitivity was only slightly and not significantly increased. Microglial Iba1 expression was found to be increased in the ipsilateral dorsal horn of the lumbar spinal cord after PSNL but such Iba1 up-regulation was enhanced in transgenic rats as compared WT rats, both at 3 days and at 21 days after injury. Moreover, mRNA levels of Nox2, a key enzyme in microglial activation, but also of pro-inflammatory markers (IL-1β and TLR4 were not modified in WT ligated rats at 21 days after PSNL as compared to WT sham group while transgenic ligated rats showed up-regulated gene expression of these 3 targets. On the other hand, the PSNL-induced increase in GFAP immunoreactivity spreading that was evidenced in WT rats was unexpectedly found to be attenuated in transgenic ligated rats. Finally, GLT-1 gene expression and

  2. 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.

  3. A Case of Occupational Hypersensitivity Pneumonitis Associated with Trichloroethylene

    OpenAIRE

    Kim, Young Jae; Hwang, Eu Dong; Leem, Ah Young; Kang, Beo Deul; Chang, Soo Yun; Kim, Ho Keun; Park, In Kyu; Kim, Song Yee; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Park, Moo Suk; Kim, Young Sam; Kim, Se Kyu; Chang, Joon

    2014-01-01

    Trichloroethylene (TCE) is a toxic chemical commonly used as a degreasing agent, and it is usually found in a colorless or blue liquid form. TCE has a sweet, chloroform-like odor, and this volatile chlorinated organic chemical can cause toxic hepatitis, neurophysiological disorders, skin disorders, and hypersensitivity syndromes. However, the hypersensitivity pneumonitis (HP) attributed to TCE has rarely been reported. We hereby describe a case of HP associated with TCE in a 29-year-old man w...

  4. 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.

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

    OpenAIRE

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

    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...

  6. Hyaluronidase hypersensitivity: A rare complication of peribulbar block

    Directory of Open Access Journals (Sweden)

    A R Rajalakshmi

    2016-01-01

    Full Text Available Peribulbar block, though safe, can cause serious complications such as globe perforation and peribulbar hemorrhage. Hyaluronidase is an enzyme that is used as an adjuvant in peribulbar anesthesia, and it helps in rapid penetration of the anesthetic agent. Hypersensitivity to hyaluronidase is a rare but potentially sight-threatening complication. We report a case of hyaluronidase hypersensitivity following peribulbar injection for cataract surgery mimicking as peribulbar hematoma in the immediate postinjection phase and as orbital cellulitis 48 h later.

  7. Lung delayed-type hypersensitivity in stressed mice.

    OpenAIRE

    Blecha, F; Topliff, D

    1984-01-01

    The influence of an immobilization stressor on lung cellular immune responses was studied. Delayed-type hypersensitivity to sheep erythrocytes was used to evaluate in vivo lung cellular immunity. Mice were sensitized intravenously and challenged intratracheally with sheep erythrocytes. Three hours prior to challenge all mice were injected intravenously with chromium-51 labeled mononuclear cells from syngeneic mice. The delayed-type hypersensitivity response was measured by counting the radioa...

  8. 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.

  9. Sulfasalazine-Related Hypersensitivity Reactions in Patients With Rheumatic Diseases.

    Science.gov (United States)

    Cildag, Songul; Senturk, Taskin

    2017-03-01

    Sulfasalazine (SSZ), which has an arylamine sulfonamide structure, is an anti-inflammatory drug used in the treatment of many rheumatic diseases. Various adverse effects have been reported related to SSZ. In the present study, we aimed to define the frequency of SSZ-related hypersensitivity reaction in patients with rheumatoid arthritis and ankylosing spondylitis. A total of 136 patients were included in this study. During follow-ups, reaction type, reaction duration, and drug doses were recorded in patients who developed hypersensitivity reactions. Drugs were discontinued in patients who developed reactions, and they were treated with antihistaminics and/or corticosteroids, according to requirements. Drug provocation tests with the drugs and aminosalicylic acid were performed in patients with negative skin prick test individually. A total of 136 patients, with ages ranging from 19 to 71 years (mean, 41.97 [SD, 12.04] years), were included in the study. Hypersensitivity reactions according to the drug provocation test were found against SSZ in 12 patients (8.8%). The SSZ-related hypersensitivity reaction types were urticaria in 7 patients, urticaria and angioedema in 4 patients, and pruritus in 1 patient. Sulfasalazine is widely used by rheumatologists in the treatment of rheumatic diseases. Whereas the frequency of sulfonamide-related hypersensitivity reactions was reported as 3.0% in the population, we detected hypersensitivity reactions to be 8.8% with SSZ usage in rheumatic diseases.

  10. [Observation of cells tolerant of tobacco mosaic virus in virus-induced local lesions in Datura stramonium L. leaves].

    Science.gov (United States)

    Reunov, A V; Lega, S N; Nagorskaia, V P; Lapshina, L A

    2011-01-01

    Ultrastructural examination of tobacco mosaic virus-induced local lesions developing in leaves of Datura stramonium plants demonstrated that, in the central area of the lesions, the cell response to viral invasion was not uniform. Most cells exhibited an acute hypersensitive reaction and underwent rapid and complete necrosis. However, some cells, despite considerable virus accumulation and immediate contact with completely collapsed cells, maintained a certain degree of structural integrity. Analysis performed showed that the proportion of collapsed and uncollapsed cells in the lesion centre 3 to 5 days after infection did not change essentially. These data suggest that the absence of hypersensitive response in some cells in the lesion centre is not due to an early stage of infection but is likely caused by cell tolerance of the virus.

  11. TRPV1, but not TRPA1, in primary sensory neurons contributes to cutaneous incision-mediated hypersensitivity.

    Science.gov (United States)

    Barabas, Marie E; Stucky, Cheryl L

    2013-03-04

    Mechanisms underlying postoperative pain remain poorly understood. In rodents, skin-only incisions induce mechanical and heat hypersensitivity similar to levels observed with skin plus deep incisions. Therefore, cutaneous injury might drive the majority of postoperative pain. TRPA1 and TRPV1 channels are known to mediate inflammatory and nerve injury pain, making them key targets for pain therapeutics. These channels are also expressed extensively in cutaneous nerve fibers. Therefore, we investigated whether TRPA1 and TRPV1 contribute to mechanical and heat hypersensitivity following skin-only surgical incision. Behavioral responses to mechanical and heat stimulation were compared between skin-incised and uninjured, sham control groups. Elevated mechanical responsiveness occurred 1 day post skin-incision regardless of genetic ablation or pharmacological inhibition of TRPA1. To determine whether functional changes in TRPA1 occur at the level of sensory neuron somata, we evaluated cytoplasmic calcium changes in sensory neurons isolated from ipsilateral lumbar 3-5 DRGs of skin-only incised and sham wild type (WT) mice during stimulation with the TRPA1 agonist cinnamaldehyde. There were no changes in the percentage of neurons responding to cinnamaldehyde or in their response amplitudes. Likewise, the subpopulation of DRG somata retrogradely labeled specifically from the incised region of the plantar hind paw showed no functional up-regulation of TRPA1 after skin-only incision. Next, we conducted behavior tests for heat sensitivity and found that heat hypersensitivity peaked at day 1 post skin-only incision. Skin incision-induced heat hypersensitivity was significantly decreased in TRPV1-deficient mice. In addition, we conducted calcium imaging with the TRPV1 agonist capsaicin. DRG neurons from WT mice exhibited sensitization to TRPV1 activation, as more neurons (66%) from skin-incised mice responded to capsaicin compared to controls (46%), and the sensitization

  12. 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.

    2014-01-01

    Study Objectives: 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. Design: This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Methods: 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. Results: 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

  13. [Aspirin hypersensitivity: characteristics and diagnostic approach].

    Science.gov (United States)

    Baudrand, H; Zaouche, S; Dubost, R; Carsin, A; Chatte, G; Freymond, N; Piperno, D; Dubreuil, C; Froehlich, P; Pacheco, Y; Devouassoux, G

    2015-03-01

    In routine medical practice, the diagnosis of aspirin hypersensitivity (AH) remains difficult. No clinical feature or biomarker is available to reliably confirm this diagnosis and oral provocation tests (OPT) are rarely performed. To compare asthmatics with and without AH. The clinical characteristics of 21 asthmatics with and 24 without AH respectively were determined. AH was defined by a positive OPT. A full blood count was done before and 24 hours after the OPT. The medical history was associated with a weak sensitivity (52%) and a good specificity (96%) for assessing the diagnosis of AH. There was a higher prevalence of AH in women, and a higher frequency of allergic rhinitis in AH, but no characteristic was useful to facilitate the diagnosis of AH in asthmatic patients. Our results demonstrate higher values of platelets in AH patients. Following OPT, in AH patients only, a decrease in blood eosinophils and an increase in neutrophils was observed. These results confirm that the diagnosis of AH is challenging, with the history having only weak sensitivity. The observation that fluctuations in eosinophils and neutrophils occur following OPT in AH patients only warrants further investigations and suggests a rapid pro-inflammatory role for aspirin. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  14. 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.

  15. 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.

  16. Anti-allergic effect of a combination of Citrus unshiu unripe fruits extract and prednisolone on picryl chloride-induced contact dermatitis in mice.

    Science.gov (United States)

    Fujita, Tadashi; Shiura, Takehumi; Masuda, Megumi; Tokunaga, Masashi; Kawase, Atsushi; Iwaki, Masahiro; Gato, Takeshi; Fumuro, Masahiko; Sasaki, Katsuaki; Utsunomiya, Naoki; Matsuda, Hideaki

    2008-04-01

    Effect of 50% ethanolic extract of unripe fruits of Citrus unshiu (CU-ext) on type IV allergic reaction was examined by inhibitory activity of ear swelling of picryl chloride-induced contact dermatitis (PC-CD) in mice. Oral administration of CU-ext and subcutaneous administration of prednisolone showed inhibition of ear swelling during both induction and effector phases of PC-CD. The inhibitory activities of combinations of CU-ext (p.o.) and prednisolone (s.c.) during induction phase of PC-CD were more potent than those of CU-ext alone and prednisolone alone. Successive oral administration of hesperidin, a major flavanone glycoside of CU-ext, inhibited ear swelling during induction phase of PC-CD. The inhibitory activities of combinations of hesperidin (p.o.) and prednisolone (s.c.) were more potent than those of hesperidin alone and prednisolone alone. These results indicated that the combinations of prednisolone and CU-ext or hesperidin exerted a synergistic effect.

  17. Reduced frequency of nickel allergy upon oral nickel contact at an early age

    DEFF Research Database (Denmark)

    Van Hoogstraten, I M; Andersen, Klaus Ejner; Von Blomberg, B M

    1991-01-01

    From animal studies we know that oral administration of T-dependent antigens before sensitization effectively induces systemic immune unresponsiveness. Such 'oral tolerance' is persistent, dose-dependent, antigen-specific and presumably T suppressor cell-mediated. Oral tolerance induction could b...... of nickel hypersensitivity. Frequencies of other hypersensitivities, in particular to fragrance, were not affected. These results support our view that induction of specific systemic immunologic tolerance by timely oral administration of antigens is feasible in man....

  18. A novel bioactive glass-ceramic for treating dentin hypersensitivity

    Directory of Open Access Journals (Sweden)

    Camila Tirapelli

    2010-12-01

    Full Text Available Dentin hypersensitivity (DH is a painful response to stimulus applied to the open dentinal tubules of a vital tooth. It's a common oral condition, however, without an ideal treatment available yet. This work evaluated in vitro the effect of micron-sized particles from a novel bioactive glass-ceramic (Biosilicate in occluding open dentinal tubules. A dentin disc model was employed to observe comparatively, using scanning electron microscopy (SEM, dentinal tubule occlusion by different products and deposition of hydroxyl carbonate apatite (HCA on dentin surface by Biosilicate, after a single application: G1 - Dentifrice with potassium nitrate and fluoride; G2 - Two-step calcium phosphate precipitation treatment; G3 - Water-free gel containing Biosilicate particles (1%; G4 - Biosilicate particles mixed with distilled water in a 1:10 ratio; all of them after 1, 12 and 24 hours of immersion in artificial saliva. Fourier transform infrared spectroscopy (FTIR was performed to detect HCA formation on dentin discs filled with Biosilicate after 2 minutes, 30 minutes and 12 hours of immersion in artificial saliva. SEM showed a layer of HCA formed on dentin surface after 24 hours by G4. G1, G2 and G3 promoted not total occlusion of open dentinal tubules after 24 hours. FTIR showed HCA precipitation on the dentin surface induced by Biosilicate after 30 minutes. The micron-sized particles from the bioactive glass-ceramic thus were able to induce HCA deposition in open dentinal tubules in vitro. This finding suggests that Biosilicate may provide a new option for treating DH.

  19. 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.

  20. Induction of delayed-type hypersensitivity by the T cell line specific to bacterial peptidoglycans

    Energy Technology Data Exchange (ETDEWEB)

    Katsuki, M.; Kakimoto, K.; Kawata, S.; Kotani, S.; Koga, T.

    1987-12-01

    A T cell line specific for the chemically well-defined peptidoglycan of bacterial cell wall, disaccharide tetrapeptide, was established from Lewis rats immunized with the antigen covalently linked to the autologous rat serum albumin. The antigen specificity was examined with various analogues or derivatives of the peptidoglycan. The cell line was reactive to analogues with the COOH-terminal D-amino acid, but least reactive to those with L-amino acid as COOH terminus. Transferring of the T cell line into X-irradiated normal Lewis rats induced delayed-type hypersensitivity in an antigen specific manner.

  1. Ranitidine for improvement of delayed hypersensitivity response in patients with sepsis

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Witt, K; Moesgaard, F

    1989-01-01

    Twenty-five patients admitted to intensive or high-dependency surgical care units were randomized to receive ranitidine intravenously 50 mg every 6 hours for 8 days or no ranitidine. All had septicemia or intra-abdominal sepsis, with body temperature greater than or equal to 38.5 degrees C for more...... hypersensitivity improved in patients treated with ranitidine (p less than 0.001), but was unchanged in the untreated group (p greater than 0.7). These observations may suggest potential beneficial effects of ranitidine therapy in patients with trauma-induced immunosuppression....

  2. Combined Effect of Ocular and Multifocal Contact Lens Induced Aberrations on Visual Performance: Center-Distance Versus Center-Near Design.

    Science.gov (United States)

    Lopes-Ferreira, Daniela; Fernandes, Paulo; Queirós, António; González-Meijome, José M

    2017-01-04

    To evaluate the combined effects of inherent ocular aberrations and induced aberrations with a multifocal soft contact lens (MFCL) after 15 days of lens wear in presbyopic participants and their influence on visual performance at distance and near under high and low contrast conditions. Forty presbyopic participants (mean age, 48.7±3.4) presenting a mean addition of 1.53±0.58 D were fitted with Biofinity Multifocal (CooperVision) and included in the study. Measurements comprised distance and near monocular high (100%) and low contrast (10%) logMAR visual acuity (VA). Ocular aberrations were obtained with Hartmann-Shack aberrometer (IRX3, Imagine Eyes) and analyzed for 2 mm and maximum round natural pupil. Distance VA was significantly higher in dominant eye, whereas near VA was significantly better in the non-dominant eye (P<0.05 in all conditions). For a 2-mm pupil in the dominant eye fitted with MFCL, spherical-like aberration significantly increased (P=0.027) so as higher-order aberrations (HOA) (P=0.002). A significant increase was also observed in spherical-like aberrations (P=0.001), coma-like aberrations (P=0.006) and HOA (P=0.004) in non-dominant eye. For the maximum round natural pupil size, a significant decrease in vertical coma was observed (P=0.018) in dominant eye, whereas a significant increase in spherical-like (P<0.001) and coma-like aberrations (P=0.007) was observed in non-dominant eye. A negative significant correlation was found between vertical coma and high contrast VA (Rho=-0.405, P=0.011) in dominant eye; whereas in non-dominant eye, a significant correlation was found between induced secondary astigmatism and distance VA under high (Rho=0.556, P<0.001) and low contrast (Rho=0.448, P=0.005). On-eye visual performance of MFSCL is dependent on the high-order aberrations induced by dominant and non-dominant design coupled with the wearer's inherent aberrations.

  3. Butyrate promotes visceral hypersensitivity in an IBS-like model via enteric glial cell-derived nerve growth factor.

    Science.gov (United States)

    Long, X; Li, M; Li, L-X; Sun, Y-Y; Zhang, W-X; Zhao, D-Y; Li, Y-Q

    2017-10-20

    Altered visceral sensation is common in irritable bowel syndrome (IBS) and nerve growth factor (NGF) participates in visceral pain development. Sodium butyrate (NaB) could induce colonic hypersensitivity via peripheral up-regulation of NGF in animals. Enteric glial cells (EGCs) appear to be an important source of NGF. Whether butyrate could induce visceral hypersensitivity via increased EGC-derived NGF is still unknown. CRL-2690 cells were used for transcriptome analyses after butyrate treatment. Rats received butyrate enemas to induce colonic hypersensitivity. Colorectal distention test was performed to assess visceral sensitivity. Immunofluorescence studies were used to evaluate the co-expression of glial fibrillary acidic protein (GFAP) and NGF or growth associated protein 43 in animal model. NGF expression in rat colon was also investigated. In vitro, CRL-2690 cells were stimulated with NaB or trichostatin A (TSA). NGF or GFAP expression was also examined. Transcriptome analyses showed that butyrate induced marked changes of genes expression related to neurotrophic signaling pathways. NaB-treated rats showed increased visceral sensitivity. An improved NGF expression level was observed in NaB-treated rats. Meanwhile, a 2.1-fold increase in co-expression of GFAP and NGF was also determined in rats received NaB enemas. In cultured cells, both NaB and TSA treatment could cause obvious NGF expression. Thus, butyrate might regulate EGC function via histone deacetylase inhibition. Butyrate-EGC interplay may play a pivotal role in regulation of NGF expression and the development of colonic hypersensitivity in IBS-like animal model. © 2017 John Wiley & Sons Ltd.

  4. Selective cloning, characterization, and production of the Culicoides nubeculosus salivary gland allergen repertoire associated with equine insect bite hypersensitivity.

    OpenAIRE

    Schaffartzik Anna; Marti Eliane; Torsteinsdottir Sigurbjörg; Mellor Philip S; Crameri Reto; Rhyner Claudio

    2011-01-01

    Salivary gland proteins of Culicoides spp. have been suggested to be among the main allergens inducing IgE mediated insect bite hypersensitivit