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Sample records for mediated hypersensitivity reaction

  1. HLA Associations and Clinical Implications in T-Cell Mediated Drug Hypersensitivity Reactions: An Updated Review

    PubMed Central

    Cheng, Chi-Yuan; Chen, Chi-Hua; Chen, Wei-Li; Deng, Shin-Tarng; Chung, Wen-Hung

    2014-01-01

    T-cell mediated drug hypersensitivity reactions may range from mild rash to severe fatal reactions. Among them, drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS), Stevens-Johnson syndrome/ toxic epidermal necrolysis (SJS/TEN), are some of the most life-threatening severe cutaneous adverse reactions (SCARs). Recent advances in pharmacogenetic studies show strong genetic associations between human leukocyte antigen (HLA) alleles and susceptibility to drug hypersensitivity. This review summarizes the literature on recent progresses in pharmacogenetic studies and clinical application of pharmacogenetic screening based on associations between SCARs and specific HLA alleles to avoid serious conditions associated with drug hypersensitivity. PMID:24901010

  2. Hypersensitivity reactions to corticosteroids.

    PubMed

    Vatti, Rani R; Ali, Fatima; Teuber, Suzanne; Chang, Christopher; Gershwin, M Eric

    2014-08-01

    Hypersensitivity reactions to corticosteroids (CS) are rare in the general population, but they are not uncommon in high-risk groups such as patients who receive repeated doses of CS. Hypersensitivity reactions to steroids are broadly divided into two categories: immediate reactions, typically occurring within 1 h of drug administration, and non-immediate reactions, which manifest more than an hour after drug administration. The latter group is more common. We reviewed the literature using the search terms "hypersensitivity to steroids, adverse effects of steroids, steroid allergy, allergic contact dermatitis, corticosteroid side effects, and type I hypersensitivity" to identify studies or clinical reports of steroid hypersensitivity. We discuss the prevalence, mechanism, presentation, evaluation, and therapeutic options in corticosteroid hypersensitivity reactions. There is a paucity of literature on corticosteroid allergy, with most reports being case reports. Most reports involve non-systemic application of corticosteroids. Steroid hypersensitivity has been associated with type I IgE-mediated allergy including anaphylaxis. The overall prevalence of type I steroid hypersensitivity is estimated to be 0.3-0.5%. Allergic contact dermatitis (ACD) is the most commonly reported non-immediate hypersensitivity reaction and usually follows topical CS application. Atopic dermatitis and stasis dermatitis of the lower extremities are risk factors for the development of ACD from topical CS. Patients can also develop hypersensitivity reactions to nasal, inhaled, oral, and parenteral CS. A close and detailed evaluation is required for the clinician to confirm the presence of a true hypersensitivity reaction to the suspected drug and choose the safest alternative. Choosing an alternative CS is not only paramount to the patient's safety but also ameliorates the worry of developing an allergic, and potentially fatal, steroid hypersensitivity reaction. This evaluation becomes

  3. Immunoglobulin E-mediated hypersensitivity reaction after intraperitoneal administration of vancomycin.

    PubMed

    Hwang, Mun-Ju; Do, Jun-Young; Choi, Eun-Woo; Seo, Joon-Hyuk; Nam, Yoon-Jung; Yoon, Kyung-Woo; Park, Jong-Won; Cho, Kyu-Hyang; Kang, Seok-Hui; Jin, Hyun-Jung

    2015-03-01

    Intraperitoneal (IP) vancomycin is widely used to treat Gram-positive peritonitis associated with peritoneal dialysis. There have been two cases of red man syndrome (RMS), a vancomycin-specific nonimmunologic reaction, associated with IP vancomycin. However, immune-mediated hypersensitivity reaction to IP vancomycin has not yet been reported. A 49 year old woman on continuous ambulatory peritoneal dialysis developed her first peritonitis episode. The patient was treated with IP vancomycin once/wk for 4 weeks. She experienced mild itching and flushing throughout her body for 1 day after the second treatment. Whenever vancomycin was administered, generalized urticaria and a prickling sensation developed, and the intensity increased gradually; however, these symptoms improved after vancomycin was discontinued. An allergic skin test was performed 6 weeks after the previous urticarial episode, and an intradermal skin test revealed a positive response to vancomycin. To our knowledge, this is the first case report of immunoglobulin E-mediated hypersensitivity reaction to IP vancomycin administration. PMID:26484021

  4. Immunoglobulin E-mediated hypersensitivity reaction after intraperitoneal administration of vancomycin

    PubMed Central

    Hwang, Mun-Ju; Do, Jun-Young; Choi, Eun-Woo; Seo, Joon-Hyuk; Nam, Yoon-Jung; Yoon, Kyung-Woo; Park, Jong-Won; Cho, Kyu-Hyang; Kang, Seok-Hui; Jin, Hyun-Jung

    2014-01-01

    Intraperitoneal (IP) vancomycin is widely used to treat Gram-positive peritonitis associated with peritoneal dialysis. There have been two cases of red man syndrome (RMS), a vancomycin-specific nonimmunologic reaction, associated with IP vancomycin. However, immune-mediated hypersensitivity reaction to IP vancomycin has not yet been reported. A 49 year old woman on continuous ambulatory peritoneal dialysis developed her first peritonitis episode. The patient was treated with IP vancomycin once/wk for 4 weeks. She experienced mild itching and flushing throughout her body for 1 day after the second treatment. Whenever vancomycin was administered, generalized urticaria and a prickling sensation developed, and the intensity increased gradually; however, these symptoms improved after vancomycin was discontinued. An allergic skin test was performed 6 weeks after the previous urticarial episode, and an intradermal skin test revealed a positive response to vancomycin. To our knowledge, this is the first case report of immunoglobulin E-mediated hypersensitivity reaction to IP vancomycin administration. PMID:26484021

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

    PubMed Central

    Erkes, Dan A.; Selvan, Senthamil R.

    2014-01-01

    Haptens are small molecule irritants that bind to proteins and elicit an immune response. Haptens have been commonly used to study allergic contact dermatitis (ACD) using animal contact hypersensitivity (CHS) models. However, extensive research into contact hypersensitivity has offered a confusing and intriguing mechanism of allergic reactions occurring in the skin. The abilities of haptens to induce such reactions have been frequently utilized to study the mechanisms of inflammatory bowel disease (IBD) to induce autoimmune-like responses such as autoimmune hemolytic anemia and to elicit viral wart and tumor regression. Hapten-induced tumor regression has been studied since the mid-1900s and relies on four major concepts: (1) ex vivo haptenation, (2) in situ haptenation, (3) epifocal hapten application, and (4) antigen-hapten conjugate injection. Each of these approaches elicits unique responses in mice and humans. The present review attempts to provide a critical appraisal of the hapten-mediated tumor treatments and offers insights for future development of the field. PMID:24949488

  6. Immunohistochemical appearance of corticosteroid contact hypersensitivity reactions.

    PubMed

    Wilkinson, S M; Andrew, S M; Maseruka, H; Beck, M H

    1994-11-01

    We have studied, immunohistochemically, hypersensitivity reactions to corticosteroids and compared them with allergic contact dermatitis from nickel and appropriate controls. We could find no qualitative differences between nickel and corticosteroid contact reactions, providing further evidence that hypersensitivity to corticosteroids is an immunologically mediated reaction. PMID:7532558

  7. Animal models of complement-mediated hypersensitivity reactions to liposomes and other lipid-based nanoparticles.

    PubMed

    Szebeni, János; Alving, Carl R; Rosivall, László; Bünger, Rolf; Baranyi, Lajos; Bedöcs, Péter; Tóth, Miklós; Barenholz, Yezheckel

    2007-01-01

    Intravenous injection of some liposomal drugs, diagnostic agents, micelles and other lipid-based nanoparticles can cause acute hypersensitivity reactions (HSRs) in a high percentage (up to 45%) of patients, with hemodynamic, respiratory and cutaneous manifestations. The phenomenon can be explained with activation of the complement (C) system on the surface of lipid particles, leading to anaphylatoxin (C5a and C3a) liberation and subsequent release reactions of mast cells, basophils and possibly other inflammatory cells in blood. These reactions can be reproduced and studied in pigs, dogs and rats, animal models which differ from each other in sensitivity and spectrum of symptoms. In the most sensitive pig model, a few miligrams of liposome (phospholipid) can cause anaphylactoid shock, characterized by pulmonary hypertension, systemic hypotension, decreased cardiac output and major cardiac arrhythmias. Pigs also display cutaneous symptoms, such as flushing and rash. The sensitivity of dogs to hemodynamic changes is close to that of pigs, but unlike pigs, dogs also react to micellar lipids (such as Cremophor EL) and their response includes pronounced blood cell and vegetative neural changes (e.g., leukopenia followed by leukocytosis, thrombocytopenia, fluid excretions). Rats are relatively insensitive inasmuch as hypotension, their most prominent response to liposomes, is induced only by one or two orders of magnitude higher phospholipid doses (based on body weight) compared to the reactogenic dose in pigs and dogs. It is suggested that the porcine and dog models are applicable for measuring and predicting the (pseudo)allergic activity of particulate "nanodrugs". PMID:17613700

  8. Hypersensitivity reaction associated with phenytoin

    PubMed Central

    Indu, T. H.; Basutkar, Roopa Satyanarayan

    2015-01-01

    Hypersensitivity reactions with antiepileptic drugs (AEDs) are generally associated with aromatic AEDs. We present a case of hypersensitivity reactions followed by administration of phenytoin with diazepam and ranitidine in a patient with generalized tonic-clonic seizures. Antigen-antibody reactions or decreased levels of epoxide hydrolase are well known with phenytoin. Increased level of serum phenytoin causing toxicities due to competitive inhibition with diazepam on co-administration was also reported in the literature. Prevention of the adverse effects with AEDs is a multi-stage process, which requires implementation of preventive measures through careful monitoring and prompts interventions. PMID:26692739

  9. Hypersensitivity reaction associated with phenytoin.

    PubMed

    Indu, T H; Basutkar, Roopa Satyanarayan

    2015-09-01

    Hypersensitivity reactions with antiepileptic drugs (AEDs) are generally associated with aromatic AEDs. We present a case of hypersensitivity reactions followed by administration of phenytoin with diazepam and ranitidine in a patient with generalized tonic-clonic seizures. Antigen-antibody reactions or decreased levels of epoxide hydrolase are well known with phenytoin. Increased level of serum phenytoin causing toxicities due to competitive inhibition with diazepam on co-administration was also reported in the literature. Prevention of the adverse effects with AEDs is a multi-stage process, which requires implementation of preventive measures through careful monitoring and prompts interventions. PMID:26692739

  10. Hypersensitivity reaction after administration of rivaroxaban (Xarelto).

    PubMed

    Vernon, Hampton M; Nielsen, Andrew K; O'Bryan, Edward C

    2016-07-01

    Little has been documented regarding hypersensitivity reactions with rivaroxaban or other factor Xa inhibitors. We report the development of a hypersensitivity reaction to rivaroxaban in a 64-year-old African American male patient who presented to the emergency department and was subsequently evaluated in dermatology consultation and follow-up. This case highlights the vigilance required by health care workers in recognizing potential adverse effects of newer anticoagulation therapy and in making medication changes where necessary. PMID:26809930

  11. Hypersensitivity reactions associated with oxaliplatin.

    PubMed

    Saif, M Wasif

    2006-09-01

    The reported incidence of hypersensitivity reactions (HSRs) associated with oxaliplatin in patients with colorectal cancer (CRC) is approximately 12%, with 1 - 2% of patients developing grade 3 or 4 in severity. However, the recent rising incidence of HSR to oxaliplatin observed is the result of increasing clinical use. HSR to oxaliplatin may manifest as facial flushing, rash/hives, tachycardia, dyspnoea, erythema, pruritus, fever, tongue swelling, headache, chills, weakness, vomiting, burning sensations, dizziness and oedema. Anaphylactic shock is rare but serious, and must be considered in the event of hypotension. No definitive approaches to prevent and treat HSR associated with oxaliplatin are available; however, few successful strategies have been reported. Such strategies include: slowing the infusion rate, use of steroids and antagonists of type 1 and 2 histamine receptors, and desensitisation. Successful implementation of oxaliplatin desensitisation protocols based on other platinum-containing compounds have been reported, which could enable a small number of patients who experience severe HSR to further receive an effective therapy for CRC. However, reintroductions have only been reported as single case studies or small cohorts. Large-scale validation on desensitisation strategies are still missing. Recently, subcutaneous adrenaline has also been utilised as an alternative approach to manage HSR to oxaliplatin. Knowledge of this rare but real toxicity of oxaliplatin is paramount because the use of this drug continues to increase not only for the treatment of patients with stage II-IV CRC, but also other solid malignancies. In this article, the author discusses the incidence, clinical presentation, pathogenesis, risk factors and current strategies of management of HSR associated with oxaliplatin. PMID:16907658

  12. IgE-mediated food hypersensitivity disorders.

    PubMed

    Gotua, M; Lomidze, N; Dolidze, N; Gotua, T

    2008-04-01

    Food allergy has become a serious health concern especially in developed countries in the past two decades. In general population approximately 4-6% of children and 1-3% of adults experience food allergy. The article reviews IgE-mediated food hypersensitivity disorders. Epidemiology, Mechanism, Clinical manifestations, Genetically modified crops (GMOs), Diagnosis, Prevention and Treatment of IgE-mediated food allergies are discussed. The investigations show that over 90% of IgE-mediated food allergies in childhood are caused by: cow's milk, hen's egg, soy, peanuts, tree nuts, wheat, fish and shellfish. Also the causes of food allergy are food additives, genetically modified crops. Risk factors for food-dependent exercise-induced anaphylaxis include asthma and previous allergic reactions to the causative food. Food allergy is one of the most common causes of systematic anaphylaxis and anaphylactoid reactions, with an annual incidence of four cases per million populations and estimated 500 deaths annually. In addition to gastrointestinal symptoms, individuals may experience urticaria, angioedema, atopic dermatitis, oral syndrome, asthma, rhinitis, conjunctivitis, hypotension, shock and cardiac arrhythmias, caused by the massive release of mediators from mast cells and basophiles. Diagnosis of food allergy is based on history, detailed dietary analysis, skin testing, measuring specific IgE in blood serum and challenge tests. Treatment and prevention includes: avoidance diet, application of auto-injectable epinephrine, H1 and H2 antihistamines, corticosteroids, antileukotrienes, prostaglandin synthetase inhibitors, cromolyn sodium, etc. PMID:18487689

  13. Immediate-type hypersensitivity drug reactions

    PubMed Central

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

    2014-01-01

    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. PMID:24286446

  14. Pharmacogenetic determinants of immediate and delayed reactions of drug hypersensitivity.

    PubMed

    Guéant, J L; Guéant-Rodriguez, R M; Gastin, I Aimone; Cornejo-García, J A; Viola, M; Barbaud, A; Mertes, P M; Blanca, M; Romano, A

    2008-01-01

    Drug allergy refers to a hypersensitivity reaction for which either an IgE or T-cell-mediated mechanism is demonstrated. The recognition of the drug by B and T cells is influenced by variants of HLA genes. The genetic factors involved in IgE-mediated mechanisms have been studied mainly in beta-lactam reactions, and they appear to be related to human leukocyte antigen presentation (HLA A2 and DRw52), TNFA -308G>A, class switching to IgE by B cells (variants of IL-13 and of IL-4RA), and expression of IgE receptors on target cells (variant of the FcepsilonRIbeta gene). Delayed T-cell-mediated reactions are also associated with HLA alleles. Studies have reported an association of HLA-B*1502 and HLA-B*5801 in patients with the Stevens-Johnson syndrome or toxic epidermal necrolysis provoked by carbamazepine, as well as of HLA-B*5701 with abacavir hypersensitivity. HLA-B*5701 seems to be a strong predictor in whites, but not in Hispanics or Africans. Carbamazepine hypersensitivity is also influenced by gene variants of cytochrome P450 enzymes on the generation of reactive metabolites, while CYP2C9*2 and CYP2C9*3 polymorphisms influence the bioactivation of sulfamethoxazole in prohapten. Pharmacogenetic studies on aspirin hypersensitivity have identified distinct types of predictors, such as HLA genotypes, a polymorphism in the promoter of the FcepsilonRIalpha gene, and variants in genes of enzymes from the arachidonic acid pathway. In the future, identification of genetic predictors will benefit from genomewide association studies that also take ethnic differences into account. Ideally, predictors will help to prevent adverse reactions, as suggested by a recent study on the effectiveness of prospective HLA-B*5701 screening to prevent hypersensitivity reactions to abacavir in HIV patients. PMID:18991696

  15. Clindamycin-induced hypersensitivity reaction.

    PubMed

    Bulloch, Marilyn N; Baccas, Jonathan T; Arnold, Scott

    2016-06-01

    Drug-induced anaphylaxis is an unpredictable adverse reaction. Although it may occur with any medication, antibiotics induce more cases of anaphylaxis than any other medication class with most cases being induced by β-lactam antibiotics. Clindamycin is an antibiotic with good gram-positive and anaerobe coverage which is often used in patients with β-lactam allergies. We report the case of a 46-year-old female who experienced anaphylaxis after a dose of intravenous (IV) clindamycin. Following treatment with methylprednisolone, epinephrine, diphenhydramine, and albuterol, the patient stabilized. The patient's score on the Naranjo's algorithm was 8 (probable); a score of 9 (definite) limited only by absence of drug re-challenge. To our knowledge, this is the first report of a clindamycin-induced anaphylaxis where the patient was not exposed to any other agent that may have triggered the response, the first case in the United States, and only the third documented case in the literature. Clinicians should be aware of the potential for drug-induced anaphylaxis in all medications. PMID:26216470

  16. CD22 expression mediates the regulatory functions of peritoneal B-1a cells during the remission phase of contact hypersensitivity reactions1

    PubMed Central

    Nakashima, Hiroko; Hamaguchi, Yasuhito; Watanabe, Rei; Ishiura, Nobuko; Kuwano, Yoshihiro; Okochi, Hitoshi; Takahashi, Yoshimasa; Tamaki, Kunihiko; Sato, Shinichi; Tedder, Thomas F.; Fujimoto, Manabu

    2013-01-01

    While contact hypersensitivity (CHS) has been considered a prototype of T cell-mediated immune reactions, recently a significant contribution of regulatory B cell subsets in the suppression of CHS has been demonstrated. CD22, one of the Siglecs, is a B cell-specific molecule that negatively regulates B cell receptor signaling. To clarify the roles of B cells in CHS, CHS in CD22-/- mice was investigated. CD22-/- mice showed delayed recovery from CHS reactions compared with wild type mice. Transfer of wild type peritoneal B-1a cells reversed the prolonged CHS reaction seen in CD22-/- mice, and this was blocked by the simultaneous injection with IL-10 receptor Ab. While CD22-/- peritoneal B-1a cells were capable of producing IL-10 at wild type levels, intraperitoneal injection of differentially labeled wild type/CD22-/- B cells demonstrated that a smaller number of CD22-/- B cells resided in lymphoid organs 5 days after CHS elicitation, suggesting a defect in survival or retention in activated CD22-/- peritoneal B-1 cells. Thus, our current study reveals a regulatory role for peritoneal B-1a cells in CHS. Two distinct regulatory B cell subsets cooperatively inhibit CHS responses. While splenic CD1dhiCD5+ B cells have a crucial role in suppressing the acute exacerbating phase of CHS, peritoneal B-1a cells are likely to suppress the late remission phase as “regulatory B cells”. CD22 deficiency results in disturbed CHS remission by impaired retention or survival of peritoneal B-1a cells that migrate into lymphoid organs. PMID:20335532

  17. Type I hypersensitivity reaction as a complication of lepa.

    PubMed

    Janthli, Deepa Manjunath; Chaturvedi, Ashutosh; Somashekar, Shruthi; Lohith, B A

    2015-12-01

    Adverse drug reaction is defined as response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for the modification of physiological functions. Type I hypersensitivity reaction is known as anaphylactic reaction which is due to immediate immunoglobulin E-mediated reaction. It is characterized by symptoms such as fever nausea, back pain, angiodema, rash, flushing, etc. Lepa generally refers to the application of pastes formed by mixing powder of herbs with water, milk, etc., and liquids. Complementary and alternative medicines are frequently used by the general population. Many people consider them to be without side effects. Ayurvedic treatment involves Shodhana (biopurification), Shaman (pacification), Bahya (external therapy), and Abhyantara karma's (internal therapy) for treating different diseases. One such bahya karma or external therapy is lepa. Even though lepa is said as "Aadhya Upakrama," undue hypersensitivity is observed in many patients. A 60-year-old woman had an adverse reaction to lepa after being administered as an external medication. The observations were erythema, eruptions, and itching. Such case of hypersensitivity is discussed in the present study. PMID:26792959

  18. Type I hypersensitivity reaction as a complication of lepa

    PubMed Central

    Janthli, Deepa Manjunath; Chaturvedi, Ashutosh; Somashekar, Shruthi; Lohith, B. A.

    2015-01-01

    Adverse drug reaction is defined as response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for the modification of physiological functions. Type I hypersensitivity reaction is known as anaphylactic reaction which is due to immediate immunoglobulin E-mediated reaction. It is characterized by symptoms such as fever nausea, back pain, angiodema, rash, flushing, etc. Lepa generally refers to the application of pastes formed by mixing powder of herbs with water, milk, etc., and liquids. Complementary and alternative medicines are frequently used by the general population. Many people consider them to be without side effects. Ayurvedic treatment involves Shodhana (biopurification), Shaman (pacification), Bahya (external therapy), and Abhyantara karma's (internal therapy) for treating different diseases. One such bahya karma or external therapy is lepa. Even though lepa is said as “Aadhya Upakrama,” undue hypersensitivity is observed in many patients. A 60-year-old woman had an adverse reaction to lepa after being administered as an external medication. The observations were erythema, eruptions, and itching. Such case of hypersensitivity is discussed in the present study. PMID:26792959

  19. The Genetics of Drug Hypersensitivity Reactions.

    PubMed

    Cornejo-García, J A; Jurado-Escobar, R; Doña, I; Perkins, J R; Agúndez, J A; García-Martín, E; Viguera, E; Blanca-López, N; Canto, G; Blanca, M

    2016-01-01

    DHRs are induced by various mechanisms and encompass a heterogeneous set of potentially life-threatening clinical entities. In addition to environmental effects, individual factors play a key role in this intricate puzzle. However, despite commendable efforts in recent years to identify individual predisposing factors, our knowledge of the genetic basis of these reactions remains incomplete. In this manuscript, we summarize current research on the genetics of DHRs, focusing on specific immune-mediated reactions (immediate and nonimmediate) and on pharmacologically mediated reactions (cross-intolerance to nonsteroidal anti-inflammatory drugs). We also provide some thoughts on potential technological approaches that would help us to decipher the molecular mechanisms underlying DHRs. We believe this manuscript will be of interest not only for allergists and basic researchers in the field, but also for clinicians from various areas of expertise who manage these reactions in their clinical practice. PMID:27375032

  20. Flare-up reactions in severe drug hypersensitivity: infection or ongoing T-cell hyperresponsiveness

    PubMed Central

    Jörg-Walther, Lukas; Schnyder, Benno; Helbling, Arthur; Helsing, Karin; Schüller, Alexandra; Wochner, Annette; Pichler, Werner

    2015-01-01

    Key Clinical Message “Flare-up” reactions are late manifestations of severe T-cell-mediated drug hypersensitivity reactions. Management is anti-inflammatory treatment and avoiding unnecessary medicines. Symptoms like fever, lymph node swelling, and blood count abnormalities may lead to confusion with bacterial infections. For prompt recognition it is important to keep the differential diagnosis in mind. PMID:26509009

  1. Hypersensitivity reactions to radiocontrast media: the role of complement activation.

    PubMed

    Szebeni, Janos

    2004-01-01

    Although intravenous use of radiocontrast media (RCM) for a variety of radiographic procedures is generally safe, clinically significant acute hypersensitivity reactions still occur in a significant percentage of patients. The mechanism of these anaphylactoid, or "pseudoallergic," reactions is complex, involving complement activation, direct degranulation of mast cells and basophils, and modulation of enzymes and proteolytic cascades in plasma. In this review, basic information on different RCMs and their reactogenicity is summarized and updated, and the prevalence, pathomechanism, prediction, prevention, treatment, and economic impact of hypersensitivity reactions are discussed. Particular attention is paid to the in vitro and in vivo evidence supporting complement activation as an underlying cause of RCM reactions. PMID:14680617

  2. Ant allergens and hypersensitivity reactions in response to ant stings.

    PubMed

    Potiwat, Rutcharin; Sitcharungsi, Raweerat

    2015-12-01

    Hypersensitivity reactions caused by ant stings are increasingly recognized as an important cause of death by anaphylaxis. Only some species of ants ( e.g. Solenopsis spp., Myrmecia spp., and Pachycondyla spp.) cause allergic reactions. Ant species are identified by evaluating the morphologic structures of worker ants or by molecular techniques. Ant venom contains substances, including acids and alkaloids, that cause toxic reactions, and those from Solenopsis invicta or the imported fire ant have been widely studied. Piperidine alkaloids and low protein contents can cause local reactions (sterile pustules) and systemic reactions (anaphylaxis). Imported fire ant venoms are cross-reactive; for example, the Sol i 1 allergen from S. invicta has cross-reactivity with yellow jacket phospholipase. The Sol i 3 allergen is a member of the antigen 5 family that has amino acid sequence identity with vespid antigen 5. The clinical presentations of ant hypersensitivity are categorized into immediate and delayed reactions: immediate reactions, such as small local reactions, large local reactions, and systemic reactions, occur within 1-4 hours after the ant stings, whereas delayed reactions, such as serum sickness and vasculitis, usually occur more than 4 hours after the stings. Tools for the diagnosis of ant hypersensitivity are skin testing, serum specific IgE, and sting challenge tests. Management of ant hypersensitivity can be divided into immediate (epinephrine, corticosteroids), symptomatic (antihistamines, bronchodilators), supportive (fluid resuscitation, oxygen therapy), and preventive (re-sting avoidance and immunotherapy) treatments. PMID:26708389

  3. An unexpected positive hypersensitive reaction to eugenol.

    PubMed

    Tammannavar, Praveen; Pushpalatha, C; Jain, Shrenik; Sowmya, S V

    2013-01-01

    Eugenol is an active, principal aromatic liquid responsible for several pharmacological activities. It is widely used in dental practice to relieve pain arising from various sources, such as pulpitis and dentinal hypersensitivity. As a primary irritant and sensitiser, it is known to cause contact urticaria as well as chronic urticaria. However, eugenol causes allergic contact dermatitis, possibly because it can react directly with proteins to form conjugate and reactive haptens. It is found that eugenol in various dental preparations-especially in the case of some zinc oxide-contains preparations such as periodontal dressings and root canal cements. This can cause hypersensitivity when it comes in contact with gingiva or teeth. This article presents a case of immediate allergic contact urticaria to eugenol during dental treatment. PMID:24049087

  4. Management of hypersensitivity reactions to anti-D immunoglobulin preparations.

    PubMed

    Rutkowski, K; Nasser, S M

    2014-11-01

    RhD immunoglobulin G (anti-D) administered to pregnant Rh(-) women prevents Rh isoimmunization. Its use has significantly reduced the incidence of haemolytic disease of the foetus and newborn previously responsible for one death in every 2200 births. In pregnancy, acute drug-induced hypersensitivity reactions including anaphylaxis can have serious deleterious effects on the mother and foetus/neonate. Women can be erroneously labelled as drug allergic as the investigation of hypersensitivity reactions in pregnancy is complex and drug challenges are usually contraindicated. We present three cases of suspected anti-D hypersensitivity clinically presenting as anaphylaxis and delayed transfusion-related reaction. We also propose a new algorithm for the investigations of such reaction. It relies on detailed history, cautious interpretation of skin tests, foetal Rh genotyping from maternal blood and, in some cases, anti-D challenges. This is not to deprive women of anti-D which might put their future pregnancies at risk. PMID:25066207

  5. Hypersensitivity reaction to cisplatin during chemoradiation therapy for gynecologic malignancy.

    PubMed

    Koren, Claude; Yerushalmi, Rinat; Katz, Alan; Malik, Hana; Sulkes, Aaron; Fenig, Eyal

    2002-12-01

    Hypersensitivity reactions to intravenous cisplatin are rare. The appearance of hypersensitivity reactions in 4 of 25 consecutive patients treated with concomitant pelvic radiation and weekly intravenous cisplatin for gynecologic malignancies is reported. The reactions appeared within hours of cisplatin delivery and included primarily fever, rash, and pruritus. Infection was ruled out by blood cultures and other laboratory studies. Affected patients were treated prophylactically with an antihistamine before subsequent courses of cisplatin, with excellent results. The high rate of hypersensitivity reactions in our series may be attributable to tumor necrosis and cytokine release caused by the pelvic irradiation. Clinicians should be aware of this potential side effect so that early premedication regimens can be instituted to prevent unnecessary toxicity. PMID:12478013

  6. Diagnosis and management of immediate hypersensitivity reactions to cephalosporins.

    PubMed

    Dickson, Scott D; Salazar, Kimberly C

    2013-08-01

    Cephalosporins are one of the most commonly prescribed classes of antibiotics. Immediate IgE-mediated hypersensitivity reactions have been reported with use of a specific cephalosporin, as a cross-reaction between different cephalosporins or as a cross-reaction to other β-lactam antibiotics, namely, penicillin. Historically, frequent reports of anaphylaxis following administration of first- and second-generation cephalosporins to patients with a history of penicillin allergy led to the belief of a high degree of allergic cross-reactivity. More recent evidence reveals a significantly lower risk of cross-reactivity between penicillins and the newer-generation cephalosporins. The current thought is that a shared side chain, rather than the β-lactam ring structure, is the determining factor in immunologic cross-reactivity. Understanding the chemical structure of these agents has allowed us to identify the allergenic determinants for penicillin; however, the exact allergenic determinants of cephalosporins are less well understood. For this reason, standardized diagnostic skin testing is not available for cephalosporins as it is for penicillin. Nevertheless, skin testing to the cephalosporin in question, using a nonirritating concentration, provides additional information, which can further guide the work-up of a patient suspected of having an allergy to that drug. Together, the history and the skin test results can assist the allergist in the decision to recommend continued drug avoidance or to perform a graded challenge versus an induction of tolerance procedure. PMID:23546989

  7. Atypical presentation of fever as hypersensitivity reaction to oxaliplatin.

    PubMed

    Khurana, Arushi; Mitsis, Demytra; Kowlgi, Gurukripa N; Holle, Lisa M; Clement, Jessica M

    2016-04-01

    Oxaliplatin, a third-generation, platinum-based agent is widely used, most commonly in the FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) regimen, which is the first-line therapy in metastatic colorectal adenocarcinoma and adjuvant chemotherapy in stage III colorectal cancer. Platinum-based products are well known for causing hypersensitivity reactions. Fever associated with oxaliplatin-hypersensitivity reactions typically follows a specific pattern. It usually starts during the oxaliplatin infusion or immediately after (within hours instead of days) and happens after several administrations (mean 2-25) with unpredictable clinical presentations. We report a case of oxaliplatin-induced hypersensitivity reaction manifesting as fever but with unusual presentation than the aforementioned features. PMID:25361599

  8. Hemolysate-mediated renal vasoconstriction and hypersensitization.

    PubMed

    Burke, T J; Falk, S; Conger, J D; Voelkel, N F

    1999-01-01

    The present studies measured vessel diameter, before and after addition of hemolysate, in isolated afferent arterioles (AA) and efferent arterioles (EA) obtained from the rat kidney. Human red blood cells (RBC) were hemolyzed in distilled water and membranes were discarded after centrifugation. Hemolysate added to the bath solution caused vigorous AA and EA contraction and, after washout, hypersensitized the AA and EA to doses of angiotensin II (AII) which would normally only elicit 50% contraction (EC50). Neither the contraction nor the hypersensitization were mimicked by pure human hemoglobin. The vasoconstrictive responses in the AA and EA were accompanied by increased cytosolic-free calcium concentration. Further purification (desalting) of the hemolysate to remove substance of < or = 1000 Da (which include ATP) did not eliminate the vasoconstrictive component from the hemolysate. Finally, cultured rat aortic vascular smooth muscle cells also demonstrated a rapid increase in (Ca2+i) when exposed to hemolysate. This increase in (Ca2+i) was, in part, dependent on Ca2+ influx since it could be attenuated with diltiazem (10(-5) M). In conclusion, hemolysate contains a factor which induces contractions of the isolated rat kidney AA and EA and rapid elevations in (Ca2+i). This factor, from hemolyzed RBC, is not hemoglobin itself. PMID:10048115

  9. Pragmatism and the evaluation of metal hypersensitivity reactions.

    PubMed

    Schalock, Peter C

    2013-01-01

    Evaluating patients with potential metal hypersensitivity reactions is challenging. Clear evidence-based guidelines based on randomized studies are lacking. A pragmatic approach to evaluation of these patients is useful due to this lack of evidence. Patch testing remains the gold standard for evaluating type IV reactions on the skin and is also likely the best test for metal reactions to implanted devices until more hard data is available. PMID:23665837

  10. Monoclonal antibodies: longitudinal prescribing information analysis of hypersensitivity reactions.

    PubMed

    Kleyman, Konstantin; Weintraub, Debra S

    2012-01-01

    Monoclonal antibodies (mAbs) are known to cause hypersensitivity reactions (HSRs). The reactions pose a significant challenge to investigators, regulators, and health providers. Because HSRs cannot be predicted through the pharmacological basis of a therapy, clinical data are often relied upon to detect the reactions. Unfortunately, clinical studies are often unable to adequately characterize HSRs especially in therapies for orphan diseases. HSRs can go undetected until post-marketing safety surveillance when a large number of patients have been exposed to the therapy. The presented data demonstrates how hypersensitivity reaction warnings have changed over time in the prescribing information (PI), i.e., the drug package insert, through August 1, 2011 for 28 US-marketed mAbs. Tracking all PI revisions for each mAb over time revealed that hypersensitivity warning statements were expanded to include more severe manifestations. Over the course of a mAb therapy's life cycle, the hypersensitivity warning is twice more likely to be upgraded than downgraded in priority. Approximately 85% of hypersensitivity-associated fatality warnings were added in PI revisions as a result of post-marketing experience. Over 60% (20/33) of revisions to hypersensitivity warnings occurred within 3-4 y of product approval. While HSRs are generally recognized and described in the initial PI of mAbs, fatal HSRs are most commonly observed in post-marketing surveillance. Results of this study suggest that initial product labeling information may not describe rare but clinically significant occurrences of severe or fatal HSRs, but subsequent label revisions include rare events observed during post-marketed product use. PMID:22531444

  11. Type IV hypersensitivity reaction to a temporary tattoo

    PubMed Central

    2007-01-01

    A 6-year-old boy developed a skin eruption 10 days after application of a temporary tattoo advertised as a “natural black henna tattoo.” The eruption was a delayed hypersensitivity reaction to the tattoo ink. The textile dye paraphenylenediamine (PPD) is a common industrial allergen and can be found in some temporary tattoo inks. This case describes the reaction and reviews the international literature pertaining to PPD and temporary tattoos. PMID:17256041

  12. The effects of thiopentone and propofol on delayed hypersensitivity reactions.

    PubMed

    Devlin, E G; Clarke, R S; Mirakhur, R K; McNeill, T A

    1995-06-01

    The effects of thiopentone and propofol on delayed hypersensitivity reactions and T lymphocyte proliferation were studied in nine healthy volunteers (five women and four men). Thiopentone 5 mg.kg-1 and propofol 2.5 mg kg-1 were given as a 10 min infusion on two separate occasions. The volunteers were exposed to a skin multitest antigen before and after administration of the two agents and their skin reactions assessed. T lymphocyte responses were studied using phytohaemagglutinin (PHA)-induced proliferation. Results showed that both drugs caused a significant depression of skin reactions in vivo but no depression in the T lymphocyte proliferation. PMID:7618660

  13. Cutaneous and systemic hypersensitivity reactions to metallic implants.

    PubMed

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

    2011-01-01

    Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous, and vasculitic eruptions may occur. Also, more complex immune reactions may develop around the implants, resulting in pain, inflammation, and loosening. Nickel, cobalt, and chromium are the three most common metals that elicit both cutaneous and extracutaneous allergic reactions from chronic internal exposure. However, other metal ions as well as bone cement components can cause such hypersensitivity reactions. To complicate things, patients may also develop delayed-type hypersensitivity reactions to metals (ie, in-stent restenosis, prosthesis loosening, inflammation, pain, or allergic contact dermatitis) following the insertion of intravascular stents, dental implants, cardiac pacemakers, or implanted gynecologic devices. Despite repeated attempts by researchers and clinicians to further understand this difficult area of medicine, the association between metal sensitivity and cutaneous allergic reactions remains to be fully understood. This review provides an update of the current knowledge in this field and should be valuable to health care providers who manage patients with conditions related to this field. PMID:21504692

  14. T-cell-mediated drug hypersensitivity: immune mechanisms and their clinical relevance

    PubMed Central

    Cai, Fenfen; Lee, Frederick J; Pichler, Werner J

    2016-01-01

    T-cell-mediated drug hypersensitivity represents a significant proportion of immune mediated drug hypersensitivity reactions. In the recent years, there has been an increase in understanding the immune mechanisms behind T-cell-mediated drug hypersensitivity. According to hapten mechanism, drug specific T-cell response is stimulated by drug-protein conjugate presented on major histocompatibility complex (MHC) as it is presented as a new antigenic determinant. On the other hand, p-i concept suggests that a drug can stimulate T cells via noncovalent direct interaction with T-cell receptor and/or peptide-MHC. The drug binding site is quite variable and this leads to several different mechanisms within p-i concept. Altered peptide repertoire can be regarded as an 'atypical' subset of p-i concept since the mode of the drug binding and the binding site are essentially identical to p-i concept. However, the intracellular binding of abacavir to HLA-B*57:01 additionally results in alteration in peptide repertoire. Furthermore the T-cell response to altered peptide repertoire model is only shown for abacavir and HLA-B*57:01 and therefore it may not be generalised to other drug hypersensitivity. Danger hypothesis has been postulated to play an important role in drug hypersensitivity by providing signal 2 but its experimental data is lacking at this point in time. Furthermore, the recently described allo-immune response suggests that danger signal may be unnecessary. Finally, in view of these new understanding, the classification and the definition of type B adverse drug reaction should be revised. PMID:27141480

  15. T-cell-mediated drug hypersensitivity: immune mechanisms and their clinical relevance.

    PubMed

    Yun, James; Cai, Fenfen; Lee, Frederick J; Pichler, Werner J

    2016-04-01

    T-cell-mediated drug hypersensitivity represents a significant proportion of immune mediated drug hypersensitivity reactions. In the recent years, there has been an increase in understanding the immune mechanisms behind T-cell-mediated drug hypersensitivity. According to hapten mechanism, drug specific T-cell response is stimulated by drug-protein conjugate presented on major histocompatibility complex (MHC) as it is presented as a new antigenic determinant. On the other hand, p-i concept suggests that a drug can stimulate T cells via noncovalent direct interaction with T-cell receptor and/or peptide-MHC. The drug binding site is quite variable and this leads to several different mechanisms within p-i concept. Altered peptide repertoire can be regarded as an 'atypical' subset of p-i concept since the mode of the drug binding and the binding site are essentially identical to p-i concept. However, the intracellular binding of abacavir to HLA-B(*)57:01 additionally results in alteration in peptide repertoire. Furthermore the T-cell response to altered peptide repertoire model is only shown for abacavir and HLA-B(*)57:01 and therefore it may not be generalised to other drug hypersensitivity. Danger hypothesis has been postulated to play an important role in drug hypersensitivity by providing signal 2 but its experimental data is lacking at this point in time. Furthermore, the recently described allo-immune response suggests that danger signal may be unnecessary. Finally, in view of these new understanding, the classification and the definition of type B adverse drug reaction should be revised. PMID:27141480

  16. Pathogenesis and diagnosis of delayed-type drug hypersensitivity reactions, from bedside to bench and back.

    PubMed

    Schrijvers, Rik; Gilissen, Liesbeth; Chiriac, Anca Mirela; Demoly, Pascal

    2015-01-01

    Drug hypersensitivity reactions (DHR) have been present since the advent of drugs. In particular T-cell mediated delayed-type hypersensitivity reactions represent a heterogeneous clinical entity with a diverse pathogenesis and result in a considerable burden of morbidity and mortality not only driven by the reactions themselves but also by the use of alternatives which are sometimes less effective or even more dangerous. Diagnostic procedures rely on clinical history, skin testing and potential provocation testing, whereas validated in vitro diagnostic procedures are still lacking for most of them. Recent work in the field of pharmacogenomics combined with basic scientific research has provided insights in the pathogenesis of abacavir and carbamazepine hypersensitivities linked with certain human leucocyte antigen risk alleles. Nevertheless, important scientific questions on how other DHR arise and how host-drug interactions occur, remain unanswered. Recent work indicates an intricate relation between host, drug and pathogens in severe cutaneous and systemic reactions and provides more insights in the role of regulatory T-cells and viral reactivation in these reactions. In this review we focus on type IV delayed-type DHR, and address recent advances in the pathogenesis, pharmacogenomics, and diagnosis of these reactions with an emphasis on the understandings arising from basic research. PMID:26339470

  17. Hypersensitivity Reactions to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Selective Reactions.

    PubMed

    Blanca-López, N; Cornejo-García, J A; Pérez-Alzate, D; Pérez-Sánchez, N; Plaza-Serón, M C; Doña, I; Torres, M J; Canto, G; Kidon, M; Perkins, J R; Blanca, M

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used throughout the world to treat pain and inflammation; however, they can trigger several types of drug hypersensitivity reactions (DHRs) in all age groups. Although most such reactions occur through activation of the leukotriene pathway without specific immunological recognition (cross-intolerance), a significant number of DHRs to NSAIDs are due to immunological mechanisms (selective reactions [SRs]). SRs are thought to be induced by specific IgE antibodies or by T cells. In this manuscript, we focus on SRs, which are of great concern in children and adolescents and comprise a heterogeneous set of clinical pictures ranging from mild entities such as urticaria/angioedema to potentially life-threatening conditions such as Stevens-Johnson syndrome/toxic epidermal necrolysis. Paracetamol and ibuprofen are the most frequent elicitors of IgE-mediated SRs, although pyrazolones have also been implicated. T cell-mediated reactions are infrequent in children but have been associated with ibuprofen, naproxen, and dipyrone. In this review, we analyze the available literature on SRs in children and adolescents, with emphasis on epidemiological data, mechanisms, and drugs involved, as well as on diagnostic procedures. PMID:26817135

  18. [Hypersensitivity reactions to implantable cardiac pacemakers and defibrillators].

    PubMed

    Kreft, B

    2016-05-01

    Nowadays, for modern electrotherapy of cardiac arrhythmias different pacemaker systems are used. Antibradycardia pacing systems (e. g. single-chamber, two-chamber, three-chamber systems, frequency-adapted pacemaker) can be distinguished from antitachycardia pacing systems like implantable or portable cardioverter defibrillators and combined antibradycardia/antitachycardia systems. Cutaneous reactions overlying a pacemaker or defibrillator are often termed "pacemaker dermatitis". In terms of the differential diagnostic workup, these cutaneous reactions can have various causes. After exclusion of infection by analyzing clinical and laboratory-chemical results, "pressure dermatitis" or the often clinically asymptomatic "reticular telangiectatic erythema" (synonym "postimplantation erythema") must be considered. Histological examination of the affected skin can contribute to the diagnosis. In case of suspected contact hypersensitivity to implant material, allergological exploration should be realized. In addition to patch testing with commercially available contact allergens, product-related material metal alloy discs are often available from the pacemaker manufacturer for epicutaneous testing. Due to the lack of additional benefit compared to standardized patch testing, a clear recommendation for such metal alloy discs cannot be given. In selected cases of suspected hypersensitivity reaction, sensitization can eventually be analyzed by the lymphocyte transformation test. Positive reactions must always be critically interpreted taking into consideration the corresponding clinical signs. Depending on the cause, cutaneous reactions are occasionally self-limiting. In many cases, however, removal of the pacemaker is inevitable. PMID:26943358

  19. Cutaneous hypersensitivity reactions to freshwater cyanobacteria – human volunteer studies

    PubMed Central

    Stewart, Ian; Robertson, Ivan M; Webb, Penelope M; Schluter, Philip J; Shaw, Glen R

    2006-01-01

    Background Pruritic skin rashes associated with exposure to freshwater cyanobacteria are infrequently reported in the medical and scientific literature, mostly as anecdotal and case reports. Diagnostic dermatological investigations in humans are also infrequently described. We sought to conduct a pilot volunteer study to explore the potential for cyanobacteria to elicit hypersensitivity reactions. Methods A consecutive series of adult patients presenting for diagnostic skin patch testing at a hospital outpatient clinic were invited to participate. A convenience sample of volunteers matched for age and sex was also enrolled. Patches containing aqueous suspensions of various cyanobacteria at three concentrations were applied for 48 hours; dermatological assessment was made 48 hours and 96 hours after application. Results 20 outpatients and 19 reference subjects were recruited into the study. A single outpatient produced unequivocal reactions to several cyanobacteria suspensions; this subject was also the only one of the outpatient group with a diagnosis of atopic dermatitis. No subjects in the reference group developed clinically detectable skin reactions to cyanobacteria. Conclusion This preliminary clinical study demonstrates that hypersensitivity reactions to cyanobacteria appear to be infrequent in both the general and dermatological outpatient populations. As cyanobacteria are widely distributed in aquatic environments, a better appreciation of risk factors, particularly with respect to allergic predisposition, may help to refine health advice given to people engaging in recreational activities where nuisance cyanobacteria are a problem. PMID:16584576

  20. Hypersensitivity to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Cross-Intolerance Reactions.

    PubMed

    Blanca-López, N; Cornejo-García, J A; Plaza-Serón, M C; Doña, I; Torres-Jaén, M J; Canto, G; Padilla-España, L; Kidon, M; Perkins, J R; Blanca, M

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used worldwide and are responsible for several types of drug hypersensitivity reactions (DHRs) in all age groups. The 2 major groups of DHRs to NSAIDs are those induced by immunological mechanisms (selective reactions) and those where inflammatory mediators are released through activation of the prostaglandin-leukotriene pathway without specific immunological recognition (cross-intolerance). In the present review, we focus on cross-intolerance reactions, which are the most frequent DHRs and are becoming a topic of major interest in children and adolescents. Paracetamol and ibuprofen are the drugs that most frequently cause DHRs in children; other NSAIDs are responsible for reactions in adolescents. In vivo and in vitro tests are of limited diagnostic value, with some exceptions for the less common selective reactions. In cross-intolerance, the clinical history and controlled administration are in many instances the only way to establish a diagnosis and look for alternatives. The clinical history is diagnostic when consistent symptoms occur repeatedly after exposure to NSAIDs with different chemical structures. Cutaneous and respiratory symptoms often co-occur in young children. The natural history of these reactions in children is unknown, and some patients can develop tolerance over time. Atopy remains a major risk factor for cross-intolerant reactions. The increasing interest in hypersensitivity to NSAIDs with improvements in patient phenotyping and the information provided by pharmacogenetics will improve our understanding and management of these reactions in the near future. PMID:26310040

  1. IgE-Mediated Hypersensitivity and Desensitisation with Recombinant Enzymes in Pompe Disease and Type I and Type VI Mucopolysaccharidosis.

    PubMed

    Capanoglu, Murat; Dibek Misirlioglu, Emine; Azkur, Dilek; Vezir, Emine; Guvenir, Hakan; Gunduz, Mehmet; Toyran, Muge; Civelek, Ersoy; Kocabas, Can Naci

    2016-01-01

    Enzyme replacement therapy (ERT) is important for the treatment of lysosomal storage disorders. Hypersensitivity reactions with ERT have been reported, and in these cases, desensitisation with the enzyme is necessary. Here we report the cases of 3 patients with lysosomal storage disorders, including Pompe disease and mucopolysaccharidosis type I and VI, who had IgE-mediated hypersensitivity reactions and positive skin tests. Successful desensitisation protocols with the culprit enzyme solution were used for these patients. All 3 patients were able to safely receive ERT with the desensitisation protocol. PMID:27144408

  2. Hypersensitivity reaction to the ingestion of mango flesh.

    PubMed

    Thoo, Caroline H F; Freeman, Susi

    2008-05-01

    A 42-year-old woman presented with a hypersensitivity reaction after the ingestion of a small amount of fresh mango gelato. She developed itchy palpable purpuric lesions over her arms, legs, neck and abdomen 4 days after ingestion. The lesions persisted for 5 weeks despite treatment with betamethasone-17 valerate 0.05% ointment and avoidance of mango. Resolution of these lesions was eventually achieved with continuing treatment. The patient denied any prior contact with mango skin but had experienced previous sensitizing reactions to mango flesh. Patch testing was strongly positive to mango skin and mango flesh. Skin-prick testing was negative. This case describes a systemic contact dermatitis to mango flesh, an entity less common than allergic contact dermatitis. PMID:18412816

  3. [The reactions of hypersensitivity: the mechanisms of development, clinical manifestations, principles of diagnostic (a lecture)].

    PubMed

    Tukavkina, S Yu; Kharseyeva, G G

    2014-05-01

    The article considers the principles of modern classification of hypersensitivity, pathogenic mechanisms of formation of its various types resulting in development of typical clinical symptoms and syndromes. The knowledge and comprehension of these issues is important for physicians of different specializations since it permits to properly make out and formulate diagnosis and timely send patient for examination and treatment to such specialist as allergist-immunologist. The particular attention was paid to description of pathogenesis of diseases and syndromes underlaid by IgE-mediated type of hypersensitivity since their share is highest and clinical manifestations frequently require emergency medical care. The diagnostic of allergic diseases is to be implemented sequentially (step-by-step) and include common clinical and special (specific) methods. In case of choosing of extent of specialized allergological examination the diagnostic significance of techniques and their safety is to be taken into account concerning condition of patient. The diagnosis is objectively formulated only by complex of examination results. It is worth to remember about possibility of development of syndromes similar to IgE-mediated allergy by their clinical manifestations but belonging to non-allergic type of hypersensitivity. It is important to know main causes, mechanisms and ways of formation of such reactions previously named as anaphylactoid ones. PMID:25338461

  4. Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management

    PubMed Central

    Rampton, David; Folkersen, Joergen; Fishbane, Steven; Hedenus, Michael; Howaldt, Stefanie; Locatelli, Francesco; Patni, Shalini; Szebeni, Janos; Weiss, Guenter

    2014-01-01

    Intravenous iron is widely used for the treatment of iron deficiency anemia when oral iron is inappropriate, ineffective or poorly tolerated. Acute hypersensitivity reactions during iron infusions are very rare but can be life-threatening. This paper reviews their frequency, pathogenesis and risk factors, and provides recommendations about their management and prevention. Complement activation-related pseudo-allergy triggered by iron nanoparticles is probably a more frequent pathogenetic mechanism in acute reactions to current formulations of intravenous iron than is an immunological IgE-mediated response. Major risk factors for hypersensitivity reactions include a previous reaction to an iron infusion, a fast iron infusion rate, multiple drug allergies, severe atopy, and possibly systemic inflammatory diseases. Early pregnancy is a contraindication to iron infusions, while old age and serious co-morbidity may worsen the impact of acute reactions if they occur. Management of iron infusions requires meticulous observation, and, in the event of an adverse reaction, prompt recognition and severity-related interventions by well-trained medical and nursing staff. PMID:25420283

  5. Cytotoxicity Is Mandatory for CD8+ T Cell–mediated Contact Hypersensitivity

    PubMed Central

    Kehren, Jeanne; Desvignes, Cyril; Krasteva, Maya; Ducluzeau, Marie-Thérèse; Assossou, Olga; Horand, Françoise; Hahne, Michael; Kägi, David; Kaiserlian, Dominique; Nicolas, Jean-François

    1999-01-01

    Contact hypersensitivity (CHS) is a T cell–mediated skin inflammation induced by epicutaneous exposure to haptens in sensitized individuals. We have previously reported that CHS to dinitrofluorobenzene in mice is mediated by major histocompatibility complex (MHC) class I–restricted CD8+ T cells. In this study, we show that CD8+ T cells mediate the skin inflammation through their cytotoxic activity. The contribution of specific cytotoxic T lymphocytes (CTLs) to the CHS reaction was examined both in vivo and in vitro, using mice deficient in perforin and/or Fas/Fas ligand (FasL) pathways involved in cytotoxicity. Mice double deficient in perforin and FasL were able to develop hapten-specific CD8+ T cells in the lymphoid organs but did not show CHS reaction. However, they did not generate hapten-specific CTLs, demonstrating that the CHS reaction is dependent on cytotoxic activity. In contrast, Fas-deficient lpr mice, FasL-deficient gld mice, and perforin-deficient mice developed a normal CHS reaction and were able to generate hapten-specific CTLs, suggesting that CHS requires either the Fas/FasL or the perforin pathway. This was confirmed by in vitro studies showing that the hapten-specific CTL activity was exclusively mediated by MHC class I–restricted CD8+ T cells which could use either the perforin or the Fas/FasL pathway for their lytic activity. Thus, cytotoxic CD8+ T cells, commonly implicated in the host defence against tumors and viral infections, could also mediate harmful delayed-type hypersensitivity reactions. PMID:10049941

  6. In vitro diagnosis of immediate IgE-mediated drug hypersensitivity: warnings and (unmet) needs.

    PubMed

    Uyttebroek, Astrid P; Sabato, Vito; Bridts, Chris H; Ebo, Didier G

    2014-08-01

    Immediate drug hypersensitivity reactions (DHR) constitute an important health condition, with serious consequences of inadequate diagnosis. In this article, some of the most important issues related to in vitro diagnosis of IgE-mediated allergies are discussed. In vitro diagnostics will benefit from expanded and novel insights and understandings in drug chemical reactivity, protein binding, biotransformation, degradation, identification of (cross-reactive) drug antigenic determinants, and deeper understanding of sensitization routes. Collective efforts should be undertaken to activate fundamental and clinical investigations. PMID:25017685

  7. Hypersensitivity reactions to oxaliplatin and other antineoplastic agents.

    PubMed

    Syrigou, Ekaterini; Syrigos, Kostas; Saif, M Wasif

    2008-03-01

    Although the reported incidence of hypersensitivity reactions (HSR) to antineoplastic agents is considered to be uncommon, it is difficult to evaluate their exact prevalence, mainly because their definition is vast and pathogenic mechanisms are vague. HSR include facial flushing, erythema, pruritus, fever, tachycardia, dyspnea, tongue swelling, rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. Treatment and prevention consists of slowing the infusion rate, steroids, and type 1 and 2 histamine receptor antagonists. Desensitization could allow the small number of patients who experience severe HSR to receive effective therapy for their cancer. Reintroductions have only been reported as single case studies or small cohorts. Large-scale validation on desensitization strategies is still missing. With regard to oxaliplatin, knowledge of its rare but eminent toxicity is paramount, because this drug is widely used in treating colorectal cancer, the second-highest cause of cancer mortality in the United States. PMID:18377776

  8. Successful desensitization protocol for hypersensitivity reaction probably caused by dabrafenib in a patient with metastatic melanoma.

    PubMed

    Bar-Sela, Gil; Abu-Amna, Mahmoud; Hadad, Salim; Haim, Nissim; Shahar, Eduardo

    2015-09-01

    Vemurafenib and dabrafenib are both orally bioavailable small molecule agents that block mitogen activated protein kinase signalling in patients with melanoma and BRAF(V600E) mutation. Generalized hypersensitivity reactions to vemurafenib or dabrafenib have not been described. Continuing vemurafenib or dabrafenib therapy despite hypersensitivity reaction is especially important in patients with melanoma and BRAF(V600E) mutation, in whom this mutation plays a critical role in tumour growth. Desensitization protocols to overcome hypersensitivity reactions by gradual reintroduction of small amounts of the offending drug up to full therapeutic doses are available for many anti-cancer agents, including vemurafenib but, to the best of our knowledge, have not been reported for dabrafenib. We describe a patient with metastatic melanoma who developed Type I hypersensitivity reaction to vemurafenib and to subsequent treatment with dabrafenib, and who was successfully treated by drug desensitization which allowed safe prolonged continuation of dabrafenib. The development of hypersensitivity reactions for both dabrafenib and vemurafinib in the current case could be because these drugs have a similar chemical structure and cause a cross-reactivity. However, hypersensitivity reaction to a non-medicinal ingredient shared by the two drugs is also possible. Oral desensitization appears to be an option for patients with hypersensitivity Type I to dabrafenib. This approach may permit clinicians to safely administer dabrafenib to patients who experience hypersensitivity reactions to this life-prolonging medication. PMID:26056325

  9. Clinical Abacavir Hypersensitivity Reaction among Children in India.

    PubMed

    Chakravarty, Jaya; Sharma, Saurabh; Johri, Anuradha; Chourasia, Ankita; Sundar, Shyam

    2016-08-01

    Abacavir is currently recommended as a part of first line regimen by National AIDS Control Organization. The objective of this study was to observe the incidence of clinically diagnosed abacavir Hypersensitivity reaction (HSR) among children on abacavir based therapy in the National program. In this observational study, all children started on abacavir were included and HSR reaction was diagnosed clinically as per National guidelines. HLA- B*5701 testing was done in children diagnosed with clinical abacavir HSR. Among 101 children started on abacavir during the study period, 8 [7.9 % (95 % CI 3.5-15.0 %)] children developed clinically diagnosed abacavir HSR. All children with concomitant illness (4/8) were HLA-B*5701 negative. Only 2 (25 %, 2/8) carried HLA-B*5701 allele. Fever with abdominal symptoms as compared to respiratory symptoms were more common in HLA-B*5701 positive cases. Overdiagnosis of clinically diagnosed abacavir HSR is common and could be decreased by treating concomitant illness before starting abacavir. PMID:26887762

  10. An unexpected cause of an acute hypersensitivity reaction during recovery from anaesthesia.

    PubMed

    Thong, C L; Lambros, M; Stewart, M G; Kam, P C A

    2005-08-01

    Acute hypersensitivity reactions to chlorhexidine in the operating room are probably more likely to occur during the early phases of anaesthesia because chlorhexidine is often used for cleaning the surgical field or during placement of indwelling catheters. We report a case of an acute hypersensitivity reaction that occurred in the post anaesthetic care unit. Subsequent skin testing suggested sensitivity to chlorhexidine, which had been applied over the vaginal mucosa at the end of surgery. Relevant issues in the investigation of acute hypersensitivity reactions in the post anaesthetic period are discussed. PMID:16119497

  11. Clinical Features of Oxaliplatin Induced Hypersensitivity Reactions and Therapeutic Approaches.

    PubMed

    Bano, Nusrat; Najam, Rahila; Qazi, Faaiza; Mateen, Ahmed

    2016-01-01

    Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan. PMID:27221832

  12. Peripheral NMDA Receptors Mediate Antidromic Nerve Stimulation-Induced Tactile Hypersensitivity in the Rat

    PubMed Central

    Jang, Jun Ho; Nam, Taick Sang; Jun, Jaebeom; Jung, Se Jung; Kim, Dong-Wook; Leem, Joong Woo

    2015-01-01

    We investigated the role of peripheral NMDA receptors (NMDARs) in antidromic nerve stimulation-induced tactile hypersensitivity outside the skin area innervated by stimulated nerve. Tetanic electrical stimulation (ES) of the decentralized L5 spinal nerve, which induced enlargement of plasma extravasation, resulted in tactile hypersensitivity in the L4 plantar dermatome of the hind-paw. When intraplantar (i.pl.) injection was administered into the L4 dermatome before ES, NMDAR and group-I metabotropic Glu receptor (mGluR) antagonists and group-II mGluR agonist but not AMPA/kainate receptor antagonist prevented ES-induced hypersensitivity. I.pl. injection of PKA or PKC inhibitors also prevented ES-induced hypersensitivity. When the same injections were administered after establishment of ES-induced hypersensitivity, hypersensitivity was partially reduced by NMDAR antagonist only. In naïve animals, i.pl. Glu injection into the L4 dermatome induced tactile hypersensitivity, which was blocked by NMDAR antagonist and PKA and PKC inhibitors. These results suggest that the peripheral release of Glu, induced by antidromic nerve stimulation, leads to the expansion of tactile hypersensitive skin probably via nociceptor sensitization spread due to the diffusion of Glu into the skin near the release site. In addition, intracellular PKA- and PKC-dependent mechanisms mediated mainly by NMDAR activation are involved in Glu-induced nociceptor sensitization and subsequent hypersensitivity. PMID:26770021

  13. Multi-Scale Optical Imaging of the Delayed Type Hypersensitivity Reaction Attenuated by Rapamycin

    PubMed Central

    Luo, Meijie; Zhang, Zhihong; Li, Hui; Qiao, Sha; Liu, Zheng; Fu, Ling; Shen, Guanxin; Luo, Qingming

    2014-01-01

    Neutrophils and monocytes/macrophages (MMs) play important roles in the development of cell-mediated delayed type hypersensitivity (DTH). However, the dynamics of neutrophils and MMs during the DTH reaction and how the immunosuppressant rapamycin modulates their behavior in vivo are rarely reported. Here, we take advantage of multi-scale optical imaging techniques and a footpad DTH reaction model to non-invasively investigate the dynamic behavior and properties of immune cells from the whole field of the footpad to the cellular level. During the classic elicitation phase of the DTH reaction, both neutrophils and MMs obviously accumulated at inflammatory foci at 24 h post-challenge. Rapamycin treatment resulted in advanced neutrophil recruitment and vascular hyperpermeability at an early stage (4 h), the reduced accumulation of neutrophils (> 50% inhibition ratio) at 48 h, and the delayed involvement of MMs in inflammatory foci. The motility parameters of immune cells in the rapamycin-treated reaction at 4 h post-challenge displayed similar mean velocities, arrest durations, mean displacements, and confinements as the classic DTH reaction at 24 h. These results indicate that rapamycin treatment shortened the initial preparation stage of the DTH reaction and attenuated its intensity, which may be due to the involvement of T helper type 2 cells or regulatory T cells. PMID:24465276

  14. Basophil Reactivity as Biomarker in Immediate Drug Hypersensitivity Reactions-Potential and Limitations.

    PubMed

    Steiner, Markus; Harrer, Andrea; Himly, Martin

    2016-01-01

    Immediate drug hypersensitivity reactions (DHRs) resemble typical immunoglobulin E (IgE)-mediated symptoms. Clinical manifestations range from local skin reactions, gastrointestinal and/or respiratory symptoms to severe systemic involvement with potential fatal outcome. Depending on the substance group of the eliciting drug the correct diagnosis is a major challenge. Skin testing and in vitro diagnostics are often unreliable and not reproducible. The involvement of drug-specific IgE is questionable in many cases. The culprit substance (parent drug or metabolite) and potential cross-reacting compounds are difficult to identify, patient history and drug provocation testing often remain the only means for diagnosis. Hence, several groups proposed basophil activation test (BAT) for the diagnosis of immediate DHRs as basophils are well-known effector cells in allergic reactions. However, the usefulness of BAT in immediate DHRs is highly variable and dependent on the drug itself plus its capacity to spontaneously conjugate to serum proteins. Stimulation with pure solutions of the parent drug or metabolites thereof vs. drug-protein conjugates may influence sensitivity and specificity of the test. We thus, reviewed the available literature about the use of BAT for diagnosing immediate DHRs against drug classes such as antibiotics, radio contrast media, neuromuscular blocking agents, non-steroidal anti-inflammatory drugs, and biologicals. Influencing factors like the selection of stimulants or of the identification and activation markers, the stimulation protocol, gating strategies, and cut-off definition are addressed in this overview on BAT performance. The overall aim is to evaluate the suitability of BAT as biomarker for the diagnosis of immediate drug-induced hypersensitivity reactions. PMID:27378928

  15. Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Contrast Media.

    PubMed

    Rosado Ingelmo, A; Doña Diaz, I; Cabañas Moreno, R; Moya Quesada, M C; García-Avilés, C; García Nuñez, I; Martínez Tadeo, J I; Mielgo Ballesteros, R; Ortega-Rodríguez, N; Padial Vilchez, M A; Sánchez-Morillas, L; Vila Albelda, C; Moreno Rodilla, E; Torres Jaén, M J

    2016-01-01

    The objective of these guidelines is to ensure efficient and effective clinical practice. The panel of experts who produced this consensus document developed a research protocol based on a review of the literature. The prevalence of allergic reactions to iodinated contrast media (ICM) is estimated to be 1:170 000, that is, 0.05%-0.1% of patients undergoing radiologic studies with ICM (more than 75 million examinations per year worldwide). Hypersensitivity reactions can appear within the first hour after administration (immediate reactions) or from more than 1 hour to several days after administration (nonimmediate or delayed reactions). The risk factors for immediate reactions include poorly controlled bronchial asthma, concomitant medication (eg, angiotensin-converting enzyme inhibitors, ß-blockers, and proton-pump inhibitors), rapid administration of the ICM, mastocytosis, autoimmune diseases, and viral infections. The most common symptoms of immediate reactions are erythema and urticaria with or without angioedema, which appear in more than 70% of patients. Maculopapular rash is the most common skin feature of nonimmediate reactions (30%-90%). Skin and in vitro tests should be performed for diagnosis of both immediate and nonimmediate reactions. The ICM to be administered will therefore be chosen depending on the results of these tests, the ICM that induced the reaction (when known), the severity of the reaction, the availability of alternative ICM, and the information available on potential ICM cross-reactivity. Another type of contrast media, gadolinium derivatives, is used used for magnetic resonance imaging. Although rare, IgE-mediated reactions to gadolinium derivatives have been reported. PMID:27326981

  16. [Etiology of hypersensitivity reactions following Chinese or Indonesian meals].

    PubMed

    de Maat-Bleeker, F

    1992-02-01

    Various authors have criticised or confirmed the relation between adverse reactions to Chinese food ('The Chinese Restaurant Syndrome') and the use of monosodium glutamate (Vetsin). In our experience the occurrence of urticaria, angioedema or anaphylaxis after meals in Chinese or Indonesian restaurants is more often due to IgE-mediated Type I food allergy, caused by consumption of shrimp, peanut or spices, in particular those of the parsley family (e.g. coriander). A detailed description of four such cases is presented. PMID:1571051

  17. Copper mediated carbometalation reactions.

    PubMed

    Müller, D S; Marek, I

    2016-08-01

    Since the first discovery of carbocupration of alkynes in the 1970s a tremendous amount of research has been carried out in this field. The exceptionally high selectivities obtained attribute to the great synthetic value of carbocupration reactions. This tutorial review will present the most important features of carbocupration of alkynes and highlight the most relevant reviews. Then a comprehensive review of copper mediated carbometalation of cyclopropenes will follow. The latter method has received much attention over the last decade as it allows the highly selective construction of poly-substituted cyclopropanes which can be transformed into acyclic derivatives bearing one or multiple tertiary or quaternary carbon stereocenters. PMID:26808300

  18. Oral administration of IL-12 suppresses anaphylactic reactions in a murine model of peanut hypersensitivity.

    PubMed

    Lee, S Y; Huang, C K; Zhang, T F; Schofield, B H; Burks, A W; Bannon, G A; Sampson, H A; Li, X M

    2001-11-01

    There is no satisfactory therapeutic intervention for peanut allergy, which accounts for most life-threatening food allergic reactions. Since IL-12 has been found to inhibit allergic airway responses in a mouse model of asthma and to cure Th2 cytokine-mediated murine schistosomiasis, we hypothesized that IL-12 treatment might also inhibit peanut allergic reactions. Consequently, we investigated the effects of oral IL-12 treatment in a murine model of peanut allergy and found that oral administration of liposome encapsulated rIL-12 could both prevent and reverse peanut hypersensitivity and could reduce histamine release, peanut-specific serum IgE and IgG1, and fecal IgA levels. Oral IL-12 treatment also increased IFN-gamma but did not decrease IL-4 or IL-5 levels. We conclude that oral rIL-12 treatment has therapeutic as well as preventive effects on peanut allergy, which are associated with increased IFN-gamma production. PMID:11683581

  19. [Immediate and delayed hypersensitivity reactions to iodinated radiographic contrast agents: an update].

    PubMed

    Khachman, Dalia; Gandia, Peggy; Sallerin, François; Mailly, Nicolas

    2009-01-01

    Diagnostic and interventional radiology of patients is nowadays crucial with increasing requirement for iodinated contrast agents infusion. Besides adverse reactions after administration of the iodinated contrast agents due to their toxicity, immediate hypersensitivity reactions and reactions resembling delayed hypersensitivity appearing from 1 hour to several days later, have been reported. Patients at high risk to develop such adverse events have to be detected on the basis of their risk factors in order to prevent or limit serious outcomes. Previous reactions to contrast media, asthma, atopy and cardiovascular disorders are risk factors for anaphylactic or anaphylactoid reactions. Female gender, age and beta-blockers increase the severity. This article aims to summarize the risk of allergic reactions related to the use of iodinated contrast agents and to suggest a way for diagnosis, treatment and prevention according to each clinical situation. PMID:19863909

  20. A plant vacuolar protease, VPE, mediates virus-induced hypersensitive cell death.

    PubMed

    Hatsugai, Noriyuki; Kuroyanagi, Miwa; Yamada, Kenji; Meshi, Tetsuo; Tsuda, Shinya; Kondo, Maki; Nishimura, Mikio; Hara-Nishimura, Ikuko

    2004-08-01

    Programmed cell death (PCD) in animals depends on caspase protease activity. Plants also exhibit PCD, for example as a response to pathogens, although a plant caspase remains elusive. Here we show that vacuolar processing enzyme (VPE) is a protease essential for a virus-induced hypersensitive response that involves PCD. VPE deficiency prevented virus-induced hypersensitive cell death in tobacco plants. VPE is structurally unrelated to caspases, although VPE has a caspase-1 activity. Thus, plants have evolved a regulated cellular suicide strategy that, unlike PCD of animals, is mediated by VPE and the cellular vacuole. PMID:15297671

  1. Hypersensitivity reaction to ranitidine: description of a case and review of the literature.

    PubMed

    Foti, Caterina; Cassano, Nicoletta; Panebianco, Rosanna; Calogiuri, Gian Franco; Vena, Gino A

    2009-01-01

    Ranitidine is an H2-receptor antagonist which is usually well tolerated. Hypersensitivity reactions to ranitidine, as well as other H2 antihistamines, have been rarely described. We report the case of a 47-year-old woman who developed an anaphylactic reaction to ranitidine used as intravenous premedication before anesthesia induction. The patient's history revealed that previous use of oral ranitidine for a peptic ulcer disease did not cause any adverse reaction. Intradermal test with ranitidine at a dilution of 1:100 gave an intense positive reaction. The protective role of H2-receptor antagonists as premedication is still unclear and should be carefully reconsidered on the basis of the available controversial evidence and the possible risk of hypersensitivity reactions. PMID:19694603

  2. An effective and more convenient drug regimen for prophylaxis against paclitaxel-associated hypersensitivity reactions.

    PubMed

    Markman, M; Kennedy, A; Webster, K; Peterson, G; Kulp, B; Belinson, J

    1999-07-01

    "Standard" prophylaxis for paclitaxel-associated hypersensitivity reactions has included the systemic administration of H1 and H2 histamine antagonists, along with oral dexamethasone taken both the night prior to, and the morning of, each paclitaxel treatment. To improve patient convenience and compliance with steroid delivery, the Gynecologic Cancer Program of the Cleveland Clinic Foundation has treated patients with an all-intravenous prophylaxis regimen (diphenhydramine 50 mg, famotidine 20 mg, dexamethasone 20 mg) given 30 min prior to paclitaxel (without any earlier oral steroid dosing). To date, we have treated more than 200 patients who received all courses of paclitaxel with this simplified prophylactic regimen, of whom approximately 9% developed hypersensitivity reactions (major or minor). This incidence is comparable to our previously reported experience with hypersensitivity reactions in a similar number of patients receiving the standard prophylaxis (including oral dexamethasone) with their initial course of paclitaxel, and subsequent cycles employing this all-intravenous program. We conclude that this "modified" regimen for paclitaxel-associated hypersensitivity reactions (with all drugs administered approximately 30 min prior to the delivery of paclitaxel) is as effective as, and more convenient than, the standard regimen, and avoids delaying chemotherapy as a result of a patient failing to remember to take one or both oral steroid doses. PMID:10394964

  3. Immediate and delayed hypersensitivity reactions to intravascular iodine based radiocontrast media -- an update.

    PubMed

    Bumbăcea, Roxana Silvia; Petruţescu, Brînduşa; Bumbăcea, Dragoş; Strâmbu, Irina

    2013-01-01

    Used since 1929 in medical practice, nowadays four chemical varieties of intravascular iodine based radiocontrast media (I-RCM) are available: ionic monomers with high osmolarity, ionic dimers with low osmolarity, non-ionic monomers with low osmolarity and non-ionic iso-osmolar dimers. Increasing prescription of l-RCMs augments the number of reported hypersensitivity reactions. I-RCM induced hypersensitivity reactions can be dclasified in two types: immediate hypersensitivity reactions (IHRs - occurring within the first hour) and delayed hypersensitivity reactions (DHRs - occurring between 1 hour and 7 days). IHRs usually present as urticaria and angioedema but may associate severe respiratory and cardiovascular symptoms. Risk factors for an IHRs include a prior immediate reaction, personal history of atopic diseases (mainly asthma) and treatment with beta blocking agents. Diagnostic tests for IHRs include blood tests (serum tryptase) and skin tests (prick and intradermal) performed 2 to 6 months after IHR. High osmolarity of the I-RCM is the factor most strongly associated with IHRs. Primary prevention of IHRs involves the use of non-ionic low-osmolar or iso-osmolar agents for all intravascular procedures. DHRs are usually mild to moderate in severity, transient and self-limiting, presenting as maculopapular rash in more than 50% of cases. As with IHRs, the most important risk factor for DHRs is a previous reaction to I-RCM. Assessment of DHRs includes skin prick tests, intradermal and patch tests. Due to extensive cross-reactivity between I-RCM, a change of product is no guarantee against a repeated reaction. Current premedication procedures in patients with previous severe reactions can reduce symptoms, but may not prevent recurrent reactions. PMID:23781574

  4. [Immediate hypersensitivity reactions to iodinated contrast agents used in radiology: a review].

    PubMed

    Moussa, Lina Menassa; Nabhane, Linda; Smayra, Tarek; Zebouni, Soha Haddad; Mohanna, Assaad; Abi Khalil, Samer; Aoun, Noel

    2012-01-01

    The use of iodinated contrast agents (IC) has become common practice nowadays in the daily diagnostic and therapeutic procedures in radiology. Immediate hypersensitivity reactions occurring up to the first hour after injection of IC, can be of serious consequences, occasionally leading to death. This justifies the establishment of a prevention algorithm, including a sharp identification of those at risk and the implementation of premedication with corticosteroids. A history of previous reaction to IC is the major risk factor of a new reaction. Other risk factors include asthma, atopy and cardiomyopathy. The factors that influence the severity of the hypersensitivity allergic reactions are female gender, age, and taking beta blockers or ACE inhibitor drugs. PMID:23198457

  5. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2013.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2014-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2013. Studies on food allergy suggest that (1) 7.6% of the US population is affected, (2) a "healthy" early diet might prevent food allergy, (3) the skin might be an important route of sensitization, (4) allergen component testing might aid diagnosis, (5) the prognosis of milk allergy might be predictable through early testing, (6) oral or sublingual immunotherapy show promise but also have caveats, and (7) preclinical studies show promising alternative modes of immunotherapy and desensitization. Studies on eosinophilic esophagitis show a relationship to connective tissue disorders and that dietary management is an effective treatment for adults. Markers of anaphylaxis severity have been determined and might inform potential diagnostics and therapeutic targets. Insights on serum tests for drug and insect sting allergy might result in improved diagnostics. Genetic and immune-mediated defects in skin epithelial differentiation contribute to the severity of atopic dermatitis. Novel management approaches to treatment of chronic urticaria, including use of omalizumab, are being identified. PMID:24373349

  6. Systemic Immediate Hypersensitive Reactions after Treatment with Sweet Bee Venom: A Case Report

    PubMed Central

    2015-01-01

    Objectives: A previous study showed that bee venom (BV) could cause anaphylaxis or other hypersensitivity reactions. Although hypersensitivity reactions due to sweet bee venom (SBV) have been reported, SBV has been reported to be associated with significantly reduced sensitization compared to BV. Although no systemic immediate hypersensitive response accompanied by abnormal vital signs has been reported with respect to SBV, we report a systemic immediate hypersensitive response that we experienced while trying to use SBV clinically. Methods: The patient had undergone BV treatment several times at other Oriental medicine clinics and had experienced no adverse reactions. She came to acupuncture & moxibustion department at Semyung university hospital of Oriental medicine (Je-cheon, Korea) complaining of facial hypoesthesia and was treated using SBV injections, her first SBV treatment. SBV, 0.05 cc, was injected at each of 8 acupoints, for a total of 0.40 cc: Jichang (ST4), Daeyeong (ST5), Hyeopgeo (ST6), Hagwan (ST7), Yepung (TE17), Imun (TE21), Cheonghoe (GB2), and Gwallyeo (SI18). Results: The patient showed systemic immediate hypersensitive reactions. The main symptoms were abdominal pain, nausea and perspiration, but common symptoms associated with hypersensitivity, such as edema, were mild. Abdominal pain was the most long-lasting symptom and was accompanied by nausea. Her body temperature decreased due to sweating. Her diastolic blood pressure could not be measured on three occasions. She remained alert, though the symptoms persisted. The following treatments were conducted in sequence; intramuscular epinephrine, 1 mg/mL, injection, intramuscular dexamethasone, 5 mg/mL, injection, intramuscular buscopan, 20 mg/mL, injection, oxygen (O2) inhalation therapy, 1 L/minutes, via a nasal prong, and intravascular injection of normal saline, 1 L. After 12 hours of treatment, the symptoms had completely disappeared. Conclusion: This case shows that the use of SBV does not

  7. Delayed hypersensitivity reaction resulting in maculopapular-type eruption due to entecavir in the treatment of chronic hepatitis B.

    PubMed

    Kim, Jeong Tae; Jeong, Hye Won; Choi, Ki Hwa; Yoon, Tae Young; Sung, Nohyun; Choi, Young Ki; Kim, Eun Ha; Chae, Hee Bok

    2014-11-14

    Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions (ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immune-mediated responses (i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic (type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-year-old woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had self-discontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type IVb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare

  8. Herbex-kid Inhibits Immediate Hypersensitivity Reactions in Mice and Rats

    PubMed Central

    Prasad, Rawal; Jogge, Nanjan Mulla; Bhojraj, Suresh; Emerson, Solomon F.; Prabakar, S.

    2008-01-01

    Herbex-kid (HK), a polyherbal formulation was evaluated in various experimental allergic models of Type I hypersensitivity reactions. Compound 48/80 (C 48/80) has been shown to induce rat mesentery mast cell degranulation and HK (1.07, 10.75 and 107.5 mg ml−1) inhibited the mast cell degranulation in a dose dependent manner. HK (1.07, 10.75 and 107.5 mg kg−1; p.o.) showed dose-dependent protection against C 48/80 induced systemic anaphylaxis in male Balb/C mice. In active anaphylaxis model, male Wistar rats orally administered with 10.75 and 107.5 mg kg−1 of HK showed significant (P < 0.01) protection against mast cell degranulation, while in passive anaphylaxis model, only at 107.5 mg kg−1 showed significant (P < 0.01) reduction in mast cell degranulation. HK at all dose levels was able to significantly decrease the time spent in nasal rubbing in Wistar rats sensitized to ovalbumin, while only at 107.5 mg kg−1 it showed significant (P < 0.01) reduction in number of sneezes. In C 48/80-induced skin itch model, all dose levels of HK significantly (P < 0.001) decreased the time spent in itching and the number of itches. HK did not produce any significant inhibition in histamine induced contraction in guinea pig ileum. From the above findings we conclude that the HK possesses antiallergic activity mediated by reducing of the release mediators from mast cells and also by 5-HT antagonism without the involvement of histamine (H1) receptors. PMID:18830458

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

    PubMed

    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. PMID:26678823

  10. Phytoalexin Accumulation in Arabidopsis thaliana during the Hypersensitive Reaction to Pseudomonas syringae pv syringae 1

    PubMed Central

    Tsuji, Jun; Jackson, Evelyn P.; Gage, Douglas A.; Hammerschmidt, Raymond; Somerville, Shauna C.

    1992-01-01

    Inoculation of leaves of Arabidopsis thaliana (L.) Heynh. with the wheat pathogen, Pseudomonas syringae pv syringae, resulted in the expression of the hypersensitive reaction and in phytoalexin accumulation. No phytoalexin accumulation was detected after infiltration of leaves with a mutant of P. s. syringae deficient in the ability to elicit a hypersensitive reaction; with the crucifer pathogen, Xanthomonas campestris pv campestris; or with 10 millimolar potassium phosphate buffer (pH 6.9). Phytoalexin accumulation was correlated with the restricted in vivo growth of P. s. syringae. A phytoalexin was purified by a combination of reverse phase flash chromatography, thin layer chromatography, followed by reverse phase high performance liquid chromatography. The Arabidopsis phytoalexin was identified as 3-thiazol-2′-yl-indole on the basis of ultraviolet, infrared, mass spectral, 1H-nuclear magnetic resonance, and 13C-nuclear magnetic resonance data. PMID:16668792

  11. [Hypersensitive reaction after application of heparin with activation heparin induced trombocytopenia in initiation of intermittent haemodialysis].

    PubMed

    Masopust, Jan; Charvát, Jiří; Mokrá, Dana; Hloch, Ondřej; Háša, Jan

    2015-03-01

    Our report describes the case of patient with hypersensitive reaction regularly arising early after initiation of haemodialysis. This characteristic reaction with pletoric face coloration, bronchospasm, increase of blood pressure, anxiety and decrease of blood oxygen saturation at the consequence and central cyanosis was regularly present without dependence on type of dialysis membrane, drug premedication or prophylactic flushing haemodialysis system by isotonic natrium chloride solution. Low platelet value and trouble-free haemodialysis realized without heparin showed real cause of patients problem. Resolution of this state was regional citrate anticoagulation during intermitent haemodialysis. PMID:25873123

  12. Cutaneous hypersensitivity reactions to vitamin K: 2 case reports and a review of the literature.

    PubMed

    Bruynzeel, I; Hebeda, C L; Folkers, E; Bruynzeel, D P

    1995-02-01

    Between 1964 and 1994, at least 52 patients with cutaneous adverse effects of vitamin K have been described in the European and North American literature. A review of the details of these patients is given and 2 new cases reported. Adverse effects are seen not only in patients with liver-function disturbances but also in patients without liver diseases, and occur mostly after intramuscular or subcutaneous administration of vitamin K1, independent of the total dose. Patch and intracutaneous tests often give positive reactions. The mechanism of action is probably in many patients a delayed-type hypersensitivity reaction. PMID:7758325

  13. Safe administration of iron sucrose in a patient with a previous hypersensitivity reaction to ferric gluconate.

    PubMed

    Sane, Radhika; Baribeault, David; Rosenberg, Carol L

    2007-04-01

    A 67-year-old woman with iron deficiency anemia required parenteral iron therapy and was treated with intravenous ferric gluconate. She tolerated the first dose, but after the second dose, she developed a tingling feeling all over her body, along with swelling in her hands and feet, and a rash with hives over most of her body. It was thought that she had likely experienced a hypersensitivity reaction to ferric gluconate. The decision was made to continue therapy; however, two modifications were made. The patient was given dexamethasone, diphenhydramine, and ibuprofen 1 hour before administering the third dose, and the infusion time was prolonged by 1 hour. Approximately 45 minutes after the infusion was completed, the patient developed hives on her arms and legs. At the patient's next clinic visit, it was decided that continuation of parenteral iron repletion was necessary, and the decision was made to attempt a challenge with iron sucrose. The patient was given dexamethasone 8 mg to be taken the night before and the morning of treatment. She successfully completed the iron repletion therapy with iron sucrose. Three parenteral iron products are available in the United States: iron dextran, sodium ferric gluconate complex, and iron sucrose. Iron dextran, the oldest of these products, carries the highest risk for hypersensitivity reactions. Available data suggest that either iron sucrose or ferric gluconate can be safely administered to patients with known hypersensitivity to iron dextran. Our patient's experience implies that it may be possible to safely administer iron sucrose to a patient with hypersensitivity to ferric gluconate. This finding has clinical implications and warrants confirmation in a larger population. PMID:17381390

  14. Pharmacogenetics of drug hypersensitivity

    PubMed Central

    Phillips, Elizabeth J; Mallal, Simon A

    2010-01-01

    Drug hypersensitivity reactions and severe cutaneous adverse drug reactions, such as Stevens–Johnson syndrome and toxic epidermal necrolysis, are examples of serious adverse drug reactions mediated through a combination of metabolic and immunological mechanisms that could traditionally not have been predicted based on the pharmacological characteristics of the drug alone. The discovery of new associations between these syndromes and specific HLA has created the promise that risk for these reactions could be predicted through pharmacogenetic screening, thereby avoiding serious morbidity and mortality associated with these types of drug reactions. Despite this, several hurdles exist in the translation of these associations into pharmacogenetic tests that could be routinely used in the clinical setting. HLA-B*5701 screening to prevent abacavir hypersensitivity syndrome is an example of a test now in widespread routine clinical use in the developed world. PMID:20602616

  15. The Incidence of Hypersensitivity Reactions to Pegylated Asparaginase in Children With Acute Lymphoblastic Leukemia: A City-wide Experience.

    PubMed

    Alrazzak, Muaz; Beaupin, Lynda K; Kinyoun, Peter; Barth, Matthew

    2016-01-01

    Asparaginase (ASNase) is an imperative component of pediatric acute lymphoblastic leukemia (ALL) therapy. Pegylating the ASNase extends its biological half-life in vivo and has become the only ASNase available in the United States for frontline therapy of ALL and lymphoblastic lymphoma. It is either infused intravenously (IV) or injected intramuscularly (IM), administrations of which are associated with hypersensitivity reaction ranging from localized skin reaction to severe anaphylaxis. A retrospective review of 96 medical records of pediatric ALL patients was performed. We compared the incidence of hypersensitivity reaction associated with IV versus IM administration of pegylated ASNase. Ninety-one patients were included in the final analysis; 31 having received pegylated ASNase IV and 60 receiving it IM. The incidence of any grade ≥ 2 hypersensitivity reaction in patients who received IV ASNase was 32.2% compared with 13.3% in the IM group (P=0.032). There was no difference in higher grade hypersensitivity reactions (19.4% vs. 11.7%). Most reactions tended to occur during periods of leukemia therapy that did not include concomitant steroid therapy. Our retrospective analysis indicates that IV administration of pegylated ASNase increases the incidence of low-grade, but not grade 3-4, hypersensitivity reactions compared with IM administration. PMID:26558809

  16. Impact of Prophylactic Conversion to an Extended Infusion Schedule to Prevent Hypersensitivity Reactions in Ovarian Cancer Patients during Carboplatin Retreatment

    PubMed Central

    O’Cearbhaill, Roisin; Zhou, Qin; Iasonos, Alexia; Hensley, Martee L.; Tew, William P.; Aghajanian, Carol; Spriggs, David R.; Lichtman, Stuart M.; Sabbatini, Paul J.

    2015-01-01

    Objective Repeated exposure to carboplatin can lead to hypersensitivity reactions during retreatment with carboplatin. This may prevent its further use in platinum-sensitive ovarian cancer patients. At our institution, an increasing proportion of patients are prophylactically converted to an extended schedule of infusion after 8 cycles of carboplatin. We sought to determine whether an incrementally increasing, extended 3-hour infusion of carboplatin was associated with a lower rate of hypersensitivity reactions compared to the standard 30-minute schedule in sequentially treated patients. Methods We performed a retrospective electronic medical record review of patients with recurrent ovarian cancer retreated with carboplatin at our institution from 01/98–12/08. Results Seven hundred seventy-seven patients with relapsed ovarian, fallopian tube, or primary peritoneal cancer were retreated with carboplatin and met study inclusion criteria. Of these, 117 (17%) developed hypersensitivity reactions during second-line or greater carboplatin-based treatment for recurrent disease. Only 6 (3.4%) of the 174 patients who received the extended schedule developed hypersensitivity reactions (0% grade 4; 1.7% grade 3) compared to 111 (21%) of 533 patients in the standard schedule group (12% grade 4; 77% grade 3). The first hypersensitivity episode occurred after a median of 16 platinum (carboplatin and cisplatin) treatments in the extended group compared to 9 in the standard group. Using the Fisher-exact test, there was an association with a reduced incidence of hypersensitivity reactions with the extended infusion schedule (P<0.001). Conclusion Our data suggest appropriate premedication and prophylactic conversion to an extended infusion during carboplatin retreatment may reduce hypersensitivity reactions. PMID:19944454

  17. Changes in delayed hypersensitivity reaction in mice exposed to O/sub 3/

    SciTech Connect

    Fujimaki, H.; Shiraishi, F.; Ashikawa, T.; Murakami, M.

    1987-06-01

    BALB/c mice were continuously exposed to 0.8 ppm O/sub 3/ for 1, 3, 7, and 14 days. Ozone exposure suppressed the delayed hypersensitivity (DH) reaction to sheep red blood cells (SRBC). The maximum effect was seen after 7 days of exposure. To estimate the suppression of the DH reaction by O/sub 3/ exposure, the numbers of lymphocytes in thymus and blood of exposed mice were compared with those of control mice. A decrease in the numbers of lymphocytes in both thymus and blood was observed in O/sub 3/-exposed mice. The percentage of T and B lymphocytes in blood of exposed mice was the same as that in blood of control mice. These results suggest that 0.8 ppm O/sub 3/ exposure affects the T lymphocytes required for DH reactions.

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

    PubMed Central

    Yoshida, Yoichiro; Hirata, Keiji; Matsuoka, Hiroshi; Iwamoto, Shigeyoshi; Kotaka, Masahito; Fujita, Hideto; Aisu, Naoya; Hoshino, Seiichiro; Kosaka, Takeo; Maeda, Kotaro; Kiyomi, Fumiaki; Yamashita, Yuichi

    2015-01-01

    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 hypersensitivity reactions. Results Hypersensitivity reactions occurred in three patients (4.1%); all three experienced a cutaneous reaction (grade 1 erythema). None of the 73 patients developed respiratory symptoms, ocular symptoms, or anaphylaxis. Grade 3 or higher hemotoxicity occurred in 13.7% of the patients and grade 3 or higher nonhematological toxicity occurred in 13.7%. The response rate to treatment was 64.4%. Conclusion The coinfusion of dexamethasone and oxaliplatin effectively reduced oxaliplatin-induced hypersensitivity reactions in patients with colorectal cancer. This approach should be considered for all patients treated with oxaliplatin, allowing treatment to be completed as planned. PMID:26648694

  19. Medical hazards of the tear gas CS. A case of persistent, multisystem, hypersensitivity reaction and review of the literature.

    PubMed

    Hill, A R; Silverberg, N B; Mayorga, D; Baldwin, H E

    2000-07-01

    A 30-year-old incarcerated man was sprayed with the "tear gas" ortho-chlorobenzylidene malononitrile (CS). He was hospitalized 8 days later with erythroderma, wheezing, pneumonitis with hypoxemia, hepatitis with jaundice, and hypereosinophilia. During the subsequent months he continued to suffer from generalized dermatitis, recurrent cough and wheezing consistent with reactive airways dysfunction syndrome, and eosinophilia. These abnormalities responded to brief courses of systemic corticosteroid but recurred off therapy. The dermatitis resolved gradually over 6-7 months, but the patient still had asthma-like symptoms a year following exposure. Patch testing confirmed sensitization to CS. The mechanism of the patient's prolonged reaction is unknown but may involve cell-mediated hypersensitivity, perhaps to adducts of CS (or a metabolite) and tissue proteins. This is the first documented case in which CS apparently caused a severe, multisystem illness by hypersensitivity rather than direct tissue toxicity. Both the ethics and safety of CS use remain controversial, in part because of the difficulty documenting sporadic injuries received in the field, and also because the charged circumstances surrounding CS use may lead to both underreporting and exaggerated claims of medical harm. The medical literature on CS focuses mainly on its immediate irritant effects and on transient dermal and ocular injuries, with only 2 prior case reports of acute lung injury related to CS exposure. Given the paucity of documented lasting effects despite its widespread use for more than 3 decades, CS appears to be safe when deployed (outdoors) in a controlled manner, but it can cause important injuries if misused or if applied to a sensitized individual. PMID:10941352

  20. [Administration of premedication with fexofenadine for paclitaxel-induced hypersensitive reactions in breast cancer patients complicated with closed-angle glaucoma].

    PubMed

    Komatsubara, Kazuo; Miyoshi, Kyoko; Kogure, Yuuki; Matsuhisa, Tetsuaki; Eguchi, Hisae

    2010-01-01

    Paclitaxel (PTX) is one of the most important breast cancer treatment drugs. However, severe hypersensitivity reactions such as decreases in blood pressure and impaired breathing occur with high frequency. For the prevention of such hypersensitivity reactions, administration of a premedication composed of three components, diphenhydramine, ranitidine (or famotidine), and dexamethasone, has been advised in package insert information of medicine. Administration of diphenhydramine is difficult in breast cancer patients complicated with closed-angle glaucoma, because diphenhydramine has a weak anticholinergic adverse effect which can induce mydriasis and glaucoma attack. We studied the prevention of severe hypersensitivity reactions and of glaucoma attack in 2 breast cancer patients complicated with closed angle glaucoma at our hospital from April 2007 to March 2008. We switched from diphenhydramine to fexofenadine as the medicine to prevent hypersensitivity reactions. Hypersensitivity reactions were not observed throughout all courses in both patients, and no glaucoma attack was observed. PMID:20087041

  1. Molecular cloning and characterization of two hypersensitive induced reaction genes from wheat infected by stripe rust pathogen

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel gene induced during hypersensitive reaction (HIR) in wheat was identified using in silico cloning and designated as TaHIR2. The TaHIR2 gene was deduced to encode a 284-amino acid protein, whose molecular mass and isoelectric point (pI) were 31.05 kD and 5.18, respectively. Amino acid sequenc...

  2. Potential Mechanisms for IgG4 Inhibition of Immediate Hypersensitivity Reactions.

    PubMed

    James, Louisa K; Till, Stephen J

    2016-03-01

    IgG4 is the least abundant IgG subclass in human serum, representing less than 5 % of all IgG. Increases in IgG4 occur following chronic exposure to antigen and are generally associated with states of immune tolerance. In line with this, IgG4 is regarded as an anti-inflammatory antibody with a limited ability to elicit effective immune responses. Furthermore, IgG4 attenuates allergic responses by inhibiting the activity of IgE. The mechanism by which IgG4 inhibits IgE-mediated hypersensitivity has been investigated using a variety of model systems leading to two proposed mechanisms. First by sequestering antigen, IgG4 can function as a blocking antibody, preventing cross-linking of receptor bound IgE. Second IgG4 has been proposed to co-stimulate the inhibitory IgG receptor FcγRIIb, which can negatively regulate FcεRI signaling and in turn inhibit effector cell activation. Recent advances in our understanding of the structural features of human IgG4 have shed light on the unique functional and immunologic properties of IgG4. The aim of this review is to evaluate our current understanding of IgG4 biology and reassess the mechanisms by which IgG4 functions to inhibit IgE-mediated allergic responses. PMID:26892721

  3. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2009.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2010-01-01

    This review highlights some of the research advances in anaphylaxis and hypersensitivity reactions to foods, drugs, and insects, as well as advances in allergic skin disease that were reported in the Journal in 2009. Among key epidemiologic observations, several westernized countries report that more than 1% of children have peanut allergy, and there is some evidence that environmental exposure to peanut is a risk factor. The role of regulatory T cells, complement, platelet-activating factor, and effector cells in the development and expression of food allergy were explored in several murine models and human studies. Delayed anaphylaxis to mammalian meats appears to be related to IgE binding to the carbohydrate moiety galactose-alpha-1,3-galactose, which also has implications for hypersensitivity to murine mAb therapeutics containing this oligosaccharide. Oral immunotherapy studies continue to show promise for the treatment of food allergy, but determining whether the treatment causes tolerance (cure) or temporary desensitization remains to be explored. Increased baseline serum tryptase levels might inform the risk of venom anaphylaxis and might indicate a risk for mast cell disorders in persons who have experienced such episodes. Reduced structural and immune barrier function contribute to local and systemic allergen sensitization in patients with atopic dermatitis, as well as increased propensity of skin infections in these patients. The use of increased doses of nonsedating antihistamines and potential usefulness of omalizumab for chronic urticaria was highlighted. These exciting advances reported in the Journal can improve patient care today and provide insights on how we can improve the diagnosis and treatment of these allergic diseases in the future. PMID:20109740

  4. Classification and pathophysiology of radiocontrast media hypersensitivity.

    PubMed

    Brockow, Knut; Ring, Johannes

    2010-01-01

    Hypersensitivity reactions to radiocontrast media (RCM) are unpredictable and are a concern for radiologists and cardiologists. Immediate hypersensitivity reactions manifest as anaphylaxis, and an allergic IgE-mediated mechanism has been continuously discussed for decades. Non-immediate reactions clinically are exanthemas resembling other drug-induced non-immediate hypersensitivities. During the past years, evidence is increasing that some of these reactions may be immunological. Repeated reactions after re-exposure, positive skin tests, and presence of specific IgE antibodies as well as positive basophil activation tests in some cases, and positive lymphocyte transformation or lymphocyte activation tests in others, indicate that a subgroup of both immediate and non-immediate reactions are of an allergic origin, although many questions remain unanswered. Recently reported cases highlight that pharmacological premedication is not safe to prevent RCM hypersensitivity in patients with previous severe reactions. These insights may have important consequences. A large multicenter study on the value of skin tests in RCM hypersensitivity concluded that skin testing is a useful tool for diagnosis of RCM allergy. It may have a role for the selection of a safe product in previous reactors, although confirmatory validation data is still scarce. In vitro tests to search for RCM-specific cell activation still are in development. In conclusion, recent data indicate that RCM hypersensitivity may have an allergic mechanism and that allergological testing is useful and may indicate tolerability. PMID:20519888

  5. Different immune cells mediate mechanical pain hypersensitivity in male and female mice

    PubMed Central

    Sorge, Robert E.; Mapplebeck, Josiane C.S.; Rosen, Sarah; Beggs, Simon; Taves, Sarah; Alexander, Jessica K.; Martin, Loren J.; Austin, Jean-Sebastien; Sotocinal, Susana G.; Chen, Di; Yang, Mu; Shi, Xiang Qun; Huang, Hao; Pillon, Nicolas J.; Bilan, Philip J.; Tu, Yu Shan; Klip, Amira; Ji, Ru-Rong; Zhang, Ji; Salter, Michael W.; Mogil, Jeffrey S.

    2016-01-01

    A large and rapidly increasing body of evidence indicates that microglia-neuron signaling is essential for chronic pain hypersensitivity. Here we show using multiple approaches that microglia are not required for mechanical pain hypersensitivity in female mice; female mice achieve similar levels of pain hypersensitivity using adaptive immune cells, likely T-lymphocytes. This sexual dimorphism suggests that male mice cannot be used as proxies for females in pain research. PMID:26120961

  6. Long-chain polyunsaturated fatty acids are consumed during allergic inflammation and affect T helper type 1 (Th1)- and Th2-mediated hypersensitivity differently.

    PubMed

    Johansson, S; Lönnqvist, A; Ostman, S; Sandberg, A-S; Wold, A E

    2010-06-01

    Studies have shown that atopic individuals have decreased serum levels of n-3 fatty acids. Indicating these compounds may have a protective effect against allergic reaction and/or are consumed during inflammation. This study investigated whether fish (n-3) or sunflower (n-6) oil supplementation affected T helper type 1 (Th1)- and Th2-mediated hypersensitivity in the skin and airways, respectively, and whether the fatty acid serum profile changed during the inflammatory response. Mice were fed regular chow, chow + 10% fish oil or chow + 10% sunflower oil. Mice were immunized with ovalbumin (OVA) resolved in Th1 or Th2 adjuvant. For Th1 hypersensitivity, mice were challenged with OVA in the footpad. Footpad swelling, OVA-induced lymphocyte proliferation and cytokine production in the draining lymph node were evaluated. In the airway hypersensitivity model (Th2), mice were challenged intranasally with OVA and the resulting serum immunoglobulin (Ig)E and eosinophilic lung infiltration were measured. In the Th1 model, OVA-specific T cells proliferated less and produced less interferon (IFN)-gamma, tumour necrosis factor (TNF) and interleukin (IL)-6 in fish oil-fed mice versus controls. Footpad swelling was reduced marginally. In contrast, mice fed fish oil in the Th2 model produced more OVA-specific IgE and had slightly higher proportions of eosinophils in lung infiltrate. A significant fall in serum levels of long-chain n-3 fatty acids accompanied challenge and Th2-mediated inflammation in Th2 model. Fish oil supplementation affects Th1 and Th2 immune responses conversely; significant consumption of n-3 fatty acids occurs during Th2-driven inflammation. The latter observation may explain the association between Th2-mediated inflammation and low serum levels of n-3 fatty acids. PMID:20148912

  7. Psoriasis is characterized by deficient negative immune regulation compared to transient delayed-type hypersensitivity reactions.

    PubMed

    Gulati, Nicholas; Suárez-Fariñas, Mayte; Correa da Rosa, Joel; Krueger, James G

    2015-01-01

    Diphencyprone (DPCP) is a hapten that causes delayed-type hypersensitivity (DTH) reactions in human skin, and is used as a topical therapeutic for alopecia areata, warts, and cutaneous melanoma metastases.  We examined peak DTH reactions induced by DPCP (3 days post-challenge) by comprehensive gene expression and histological analysis.  To better understand how these DTH reactions naturally resolve, we compared our DPCP biopsies to those from patients with psoriasis vulgaris, a chronic inflammatory disease that does not resolve.  By both microarray and qRT-PCR, we found that psoriasis lesional skin has significantly lower expression of many negative immune regulators compared to peak DPCP reactions.  These regulators include: interleukin-10, cytotoxic T lymphocyte-associated 4 (CTLA4), programmed cell death 1 (PD1), programmed cell death 1 ligand 1 (PDL1), programmed cell death 1 ligand 2 (PDL2), and indoleamine 2,3-dioxygenase (IDO1).  Their decreased expression was confirmed at the protein level by immunohistochemistry.  To more completely determine the balance of positive vs. negative immune regulators in both DPCP reactions and psoriasis, we developed one comprehensive gene list for positive regulatory (inflammatory) genes, and another for negative regulatory (immunosuppressive) genes, through Gene Ontology terms and literature review.  With this approach, we found that DPCP reactions have a higher ratio of negative to positive regulatory genes (both in terms of quantity and expression levels) than psoriasis lesional skin.  These data suggest that the disease chronicity that distinguishes psoriasis from transient DTH reactions may be related to absence of negative immune regulatory pathways, and induction of these is therefore of therapeutic interest.  Further study of these negative regulatory mechanisms that are present in DPCP reactions, but not in psoriasis, could reveal novel players in the pathogenesis of chronic inflammation.  The DPCP system

  8. Psoriasis is characterized by deficient negative immune regulation compared to transient delayed-type hypersensitivity reactions

    PubMed Central

    Gulati, Nicholas; Suárez-Fariñas, Mayte; Correa da Rosa, Joel; Krueger, James G.

    2015-01-01

    Diphencyprone (DPCP) is a hapten that causes delayed-type hypersensitivity (DTH) reactions in human skin, and is used as a topical therapeutic for alopecia areata, warts, and cutaneous melanoma metastases.  We examined peak DTH reactions induced by DPCP (3 days post-challenge) by comprehensive gene expression and histological analysis.  To better understand how these DTH reactions naturally resolve, we compared our DPCP biopsies to those from patients with psoriasis vulgaris, a chronic inflammatory disease that does not resolve.  By both microarray and qRT-PCR, we found that psoriasis lesional skin has significantly lower expression of many negative immune regulators compared to peak DPCP reactions.  These regulators include: interleukin-10, cytotoxic T lymphocyte-associated 4 (CTLA4), programmed cell death 1 (PD1), programmed cell death 1 ligand 1 (PDL1), programmed cell death 1 ligand 2 (PDL2), and indoleamine 2,3-dioxygenase (IDO1).  Their decreased expression was confirmed at the protein level by immunohistochemistry.  To more completely determine the balance of positive vs. negative immune regulators in both DPCP reactions and psoriasis, we developed one comprehensive gene list for positive regulatory (inflammatory) genes, and another for negative regulatory (immunosuppressive) genes, through Gene Ontology terms and literature review.  With this approach, we found that DPCP reactions have a higher ratio of negative to positive regulatory genes (both in terms of quantity and expression levels) than psoriasis lesional skin.  These data suggest that the disease chronicity that distinguishes psoriasis from transient DTH reactions may be related to absence of negative immune regulatory pathways, and induction of these is therefore of therapeutic interest.  Further study of these negative regulatory mechanisms that are present in DPCP reactions, but not in psoriasis, could reveal novel players in the pathogenesis of chronic inflammation.  The DPCP system

  9. Proposal of a skin tests based approach for the prevention of recurrent hypersensitivity reactions to iodinated contrast media.

    PubMed

    Della-Torre, E; Berti, A; Yacoub, M R; Guglielmi, B; Tombetti, E; Sabbadini, M G; Voltolini, S; Colombo, G

    2015-05-01

    The purpose of the present work is to evaluate the efficacy of an approach that combines clinical history, skin tests results, and premedication, in preventing recurrent hypersensitivity reactions to iodinated contrast media (ICM). Skin Prick tests, Intradermal tests, and Patch tests were performed in 36 patients with a previous reaction to ICM. All patients underwent a second contrast enhanced radiological procedure with an alternative ICM selected on the basis of the proposed approach. After alternative ICM re-injection, only one patient presented a mild NIR. The proposed algorithm, validated in clinical settings where repeated radiological exams are needed, offers a safe and practical approach for protecting patients from recurrent hypersensitivity reactions to ICM. PMID:25951145

  10. TRPV1, but not TRPA1, in primary sensory neurons contributes to cutaneous incision-mediated hypersensitivity

    PubMed Central

    2013-01-01

    Background 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. Results 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

  11. Virus-induced gene silencing reveals signal transduction components required for the Pvr9-mediated hypersensitive response in Nicotiana benthamiana.

    PubMed

    Tran, Phu-Tri; Choi, Hoseong; Choi, Doil; Kim, Kook-Hyung

    2016-08-01

    Resistance to pathogens mediated by plant resistance (R) proteins requires different signaling transduction components and pathways. Our previous studies revealed that a potyvirus resistance gene in pepper, Pvr9, confers a hypersensitive response (HR) to pepper mottle virus in Nicotiana benthamiana. Our results show that the Pvr9-mediated HR against pepper mottle virus infection requires HSP90, SGT1, NDR1, but not EDS1. These results suggest that the Pvr9-mediated HR is possibly related to the SA pathway but not the ET, JA, ROS or NO pathways. PMID:27236305

  12. Self-reported sulphonamide hypersensitivity reactions in adults living in Ibadan, Nigeria: A cross-sectional, community-based study

    PubMed Central

    Mary, Akpan Richard; Olayinka, Kotila Adejoke; Onoja, Akpa Matthew; Olufunmilayo, Fawole; Adeyinka, Falusi Gladys; Chinedum, Babalola Peace

    2015-01-01

    Background: Documentation of adverse drug reactions (ADRs) is critical to a safe health delivery system. The aim of our study was to explore the prevalence of self-reported sulphonamide hypersensitivity reactions in a community-based sample of the general population in Ibadan, Nigeria. We also examined sociodemographic factors associated with ADRs in the sample. Patients and Methods: The study was cross-sectional in design with study sites in urban, semiurban, and rural settlement areas. Pretested questionnaires were administered on a one-on-one basis by trained interviewers. Frequency tables and percentages were computed for various levels of the variables. Chi-square test was used to assess the relationship between sulphonamide hypersensitivity and variables such as sociodemographic characteristics of respondents, respondents' knowledge of drugs, as well as drug sources. Variables found to be significantly associated with sulphonamide hypersensitivity were further investigated using multiple logistic regressions analysis. Results: Out of the 1062 respondents, 15.5% reported hypersensitivity to sulphonamides with skin reactions being the most prevalent. The proportion reporting ADRs was significantly higher among respondents with tertiary education (23.1%) than any other level of education (P = 0.008). In addition, individuals who were very knowledgeable about drug use (odds ratio[OR]: 2.07; 95% confidence interval [CI]: 1.15–3.73) and persons who got drugs from hospitals (OR: 2.00; 95% CI: 1.10–3.65) were more likely to report ADRs than those who were ignorant about drugs and those who purchased drugs from open markets, respectively. Conclusion: Prevalence of sulphonamide hypersensitivity is high among respondents, and ADRs is likely to be reported by people who are knowledgeable about drug use. PMID:26903698

  13. Hypersensitivity to topical corticosteroids.

    PubMed

    Wilkinson, S M

    1994-01-01

    Contact hypersensitivity from topical corticosteroids is becoming increasingly recognized; it is present in 2-5% of the patients attending contact dermatitis clinics. The use of a corticosteroid series containing tixocortal pivalate 1% (petrolatum), to detect hypersensitivity to hydrocortisone, and other steroids 1% (ethanol), depending on local corticosteroid usage, detects the majority of cases of corticosteroid hypersensitivity. In selected cases, the use of intradermal tests further improves the diagnosis of corticosteroid hypersensitivity. Corticosteroid hypersensitivity occurs most frequently among patients with stasis dermatitis. However, corticosteroid hypersensitivity is also common in other types of dermatitis, occurring as frequently as hypersensitivity to several allergens (e.g. wool alcohols and colophony) in the European standard battery. Although hypersensitivity has mainly been reported with corticosteroids applied to the skin, reactions may also occur on mucosal surfaces, following systemic administration and with sex steroids. PMID:8313630

  14. Colon distention induces persistent visceral hypersensitivity by mechanotranscription of pain mediators in colonic smooth muscle cells.

    PubMed

    Lin, You-Min; Fu, Yu; Wu, Chester C; Xu, Guang-Yin; Huang, Li-Yen; Shi, Xuan-Zheng

    2015-03-01

    Abdominal pain and distention are major complaints in irritable bowel syndrome. Abdominal distention is mainly attributed to intraluminal retention of gas or solid contents, which may cause mechanical stress to the gut wall. Visceral hypersensitivity (VHS) may account for abdominal pain. We sought to determine whether tonic colon distention causes persistent VHS and if so whether mechanical stress-induced expression (mechanotranscription) of pain mediators in colonic smooth muscle cells (SMCs) plays a role in VHS. Human colonic SMCs were isolated and stretched in vitro to investigate whether mechanical stress upregulates expression of the pain mediator cyclooxygenase-2 (COX-2). Rat colon was distended with a 5-cm-long balloon, and gene expression of COX-2, visceromotor response (VMR), and sensory neuron excitability were determined. Static stretch of colonic SMCs induced marked expression of COX-2 mRNA and protein in a force- and time-dependent manner. Subnoxious tonic distention of the distal colon at ∼30-40 mmHg for 20 or 40 min induced COX-2 expression and PGE2 production in colonic smooth muscle, but not in the mucosa layer. Lumen distention also increased VMR in a force- and time-dependent manner. The increase of VMR persisted for at least 3 days. Patch-clamp experiments showed that the excitability of colon projecting sensory neurons in the dorsal root ganglia was markedly augmented, 24 h after lumen distention. Administration of COX-2 inhibitor NS-398 partially but significantly attenuated distention-induced VHS. In conclusion, tonic lumen distention upregulates expression of COX-2 in colonic SMC, and COX-2 contributes to persistent VHS. PMID:25540231

  15. Immunomodulatory gene therapy prevents antibody formation and lethal hypersensitivity reactions in murine pompe disease.

    PubMed

    Sun, Baodong; Kulis, Michael D; Young, Sarah P; Hobeika, Amy C; Li, Songtao; Bird, Andrew; Zhang, Haoyue; Li, Yifan; Clay, Timothy M; Burks, Wesley; Kishnani, Priya S; Koeberl, Dwight D

    2010-02-01

    Infantile Pompe disease progresses to a lethal cardiomyopathy in absence of effective treatment. Enzyme-replacement therapy (ERT) with recombinant human acid alpha-glucosidase (rhGAA) has been effective in most patients with Pompe disease, but efficacy was reduced by high-titer antibody responses. Immunomodulatory gene therapy with a low dose adeno-associated virus (AAV) vector (2 x 10(10) particles) containing a liver-specific regulatory cassette significantly lowered immunoglobin G (IgG), IgG1, and IgE antibodies to GAA in Pompe disease mice, when compared with mock-treated mice (P < 0.05). AAV-LSPhGAApA had the same effect on GAA-antibody production whether it was given prior to, following, or simultaneously with the initial GAA injection. Mice given AAV-LSPhGAApA had significantly less decrease in body temperature (P < 0.001) and lower anaphylactic scores (P < 0.01) following the GAA challenge. Mouse mast cell protease-1 (MMCP-1) followed the pattern associated with hypersensitivity reactions (P < 0.05). Regulatory T cells (Treg) were demonstrated to play a role in the tolerance induced by gene therapy as depletion of Treg led to an increase in GAA-specific IgG (P < 0.001). Treg depleted mice were challenged with GAA and had significantly stronger allergic reactions than mice given gene therapy without subsequent Treg depletion (temperature: P < 0.01; symptoms: P < 0.05). Ubiquitous GAA expression failed to prevent antibody formation. Thus, immunomodulatory gene therapy could provide adjunctive therapy in lysosomal storage disorders treated by enzyme replacement. PMID:19690517

  16. Immunomodulatory Gene Therapy Prevents Antibody Formation and Lethal Hypersensitivity Reactions in Murine Pompe Disease

    PubMed Central

    Sun, Baodong; Kulis, Michael D; Young, Sarah P; Hobeika, Amy C; Li, Songtao; Bird, Andrew; Zhang, Haoyue; Li, Yifan; Clay, Timothy M; Burks, Wesley; Kishnani, Priya S; Koeberl, Dwight D

    2009-01-01

    Infantile Pompe disease progresses to a lethal cardiomyopathy in absence of effective treatment. Enzyme-replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) has been effective in most patients with Pompe disease, but efficacy was reduced by high-titer antibody responses. Immunomodulatory gene therapy with a low dose adeno-associated virus (AAV) vector (2 × 1010 particles) containing a liver-specific regulatory cassette significantly lowered immunoglobin G (IgG), IgG1, and IgE antibodies to GAA in Pompe disease mice, when compared with mock-treated mice (P < 0.05). AAV-LSPhGAApA had the same effect on GAA-antibody production whether it was given prior to, following, or simultaneously with the initial GAA injection. Mice given AAV-LSPhGAApA had significantly less decrease in body temperature (P < 0.001) and lower anaphylactic scores (P < 0.01) following the GAA challenge. Mouse mast cell protease-1 (MMCP-1) followed the pattern associated with hypersensitivity reactions (P < 0.05). Regulatory T cells (Treg) were demonstrated to play a role in the tolerance induced by gene therapy as depletion of Treg led to an increase in GAA-specific IgG (P < 0.001). Treg depleted mice were challenged with GAA and had significantly stronger allergic reactions than mice given gene therapy without subsequent Treg depletion (temperature: P < 0.01; symptoms: P < 0.05). Ubiquitous GAA expression failed to prevent antibody formation. Thus, immunomodulatory gene therapy could provide adjunctive therapy in lysosomal storage disorders treated by enzyme replacement. PMID:19690517

  17. Chronic delayed-type hypersensitivity reaction as a means to treat alopecia areata

    PubMed Central

    ZÖLLER, M; FREYSCHMIDT-PAUL, P; VITACOLONNA, M; McELWEE, K J; HUMMEL, S; HOFFMANN, R

    2004-01-01

    The acute phase of alopecia areata (AA) is characterized by an increase in CD44v3+ and CD44v10+ skin-infiltrating leucocytes (SkIL). Induction of a contact eczema, one of the therapeutic options in AA, can be mitigated strongly by a blockade of CD44v10. The observation that induction of a delayed type hypersensitivity (DTH) reaction abrogates an autoimmune reaction, where both responses apparently use similar effector mechanisms, is surprising and prompted us to search for the underlying mechanisms. AA-affected C3H/HeJ mice were treated with the contact sensitizer SADBE (squaric acid dibutylester) and leucocyte subpopulations and their activation state was evaluated in SkIL and draining lymph nodes. AA-affected mice exhibited an increased number of SkIL with a predominance of T lymphocytes. After treatment with the contact sensitizer SADBE recovery of SkIL was reduced and monocytes predominated. However, a significantly increased number of leucocytes was recovered from draining lymph nodes. Draining lymph node cells from untreated and treated AA mice exhibited all signs of recent activation with high-level expression of co-stimulatory and accessory molecules and an increased percentage of CD44v3+ and CD44v10+ leucocytes. In contrast, SkIL of SADBE-treated AA mice contained relatively few activated T cells and reduced numbers of CD44v3+ and CD44v10+ cells. Thus, the activation state and the distribution of leucocyte subsets in SADBE-treated AA mice are consistent with a blockade of leucocyte extravasation. Accordingly, the therapeutic effect of long-term SADBE treatment may rely on impaired leucocyte traffic. PMID:15008971

  18. Endogenous opioids mediate the sexual inhibition but not the drug hypersensitivity induced by sexual satiation in male rats.

    PubMed

    Garduño-Gutiérrez, René; Guadarrama-Bazante, Lorena; León-Olea, Martha; Rodríguez-Manzo, Gabriela

    2013-06-01

    Ejaculation promotes endogenous opioid release. Copulation to exhaustion produces several enduring behavioral and physiological changes, among which a long-lasting sexual behavior inhibition and generalized drug hypersensitivity are the most conspicuous. Because copulation to exhaustion involves multiple successive ejaculations, in this work we hypothesized that the endogenous opioids released by multiple ejaculations during the copulation to exhaustion process might mediate the abovementioned sexual satiation-induced changes. To test this hypothesis, sexually experienced male rats were injected with the opioid receptor antagonist naltrexone before copulation to exhaustion and were tested for sexual behavior or drug hypersensitivity 24 h later. The latter was assessed by the appearance of the flat body posture sign of the serotonergic syndrome, in response to doses of the 5-hydroxytryptamine-1A (5-HT1A) receptor agonist 8-hydroxy-2-di-n-propylamino-tetralin (8-OH-DPAT), lower than those normally inducing this sign. The effect of administering naltrexone to already sexually exhausted animals (i.e., 24 h after the sexual satiation process) on both responses was also tested. Results showed that endogenous opioids mediate the establishment and maintenance of the long-lasting sexual behavior inhibition but not the drug hypersensitivity (to 8-OH-DPAT) characteristic of sexually exhausted male rats. It is concluded that although both phenomena appear as a consequence of copulation to satiation and follow a same time course of recovery, they are produced by distinct mechanisms. PMID:23544597

  19. Role of the potassium chloride cotransporter isoform 2-mediated spinal chloride homeostasis in a rat model of visceral hypersensitivity.

    PubMed

    Tang, Dong; Qian, Ai-Hua; Song, Dan-Dan; Ben, Qi-Wen; Yao, Wei-Yan; Sun, Jing; Li, Wei-Guang; Xu, Tian-Le; Yuan, Yao-Zong

    2015-05-01

    Visceral hypersensitivity represents an important hallmark in the pathophysiology of irritable bowel syndrome (IBS), of which the mechanisms remain elusive. The present study was designed to examine whether cation-chloride cotransporter (CCC)-mediated chloride (Cl(-)) homeostasis of the spinal cord is involved in chronic stress-induced visceral hypersensitivity. Chronic visceral hypersensitivity was induced by exposing male Wistar rats to water avoidance stress (WAS). RT-PCR, Western blotting, and immunohistochemistry were used to assess the expression of CCCs in the spinal cord. Patch-clamp recordings were performed on adult spinal cord slices to evaluate Cl(-) homeostasis and Cl(-) extrusion capacity of lamina I neurons. Visceral sensitivity was estimated by measuring the abdominal withdrawal reflex in response to colorectal distension (CRD). After 10 days of WAS exposure, levels of both total protein and the oligomeric form of the K(+)-Cl(-) cotransporter isoform 2 (KCC2), but not Na(+)-K(+)-2Cl(-) transporter isoform 1 (NKCC1), were significantly decreased in the dorsal horn of the lumbosacral spinal cord. The downregulation of KCC2 resulted in a depolarizing shifted equilibrium potential of GABAergic inhibitory postsynaptic current and impaired Cl(-) extrusion capacity in lamina I neurons of the lumbosacral spinal cord from WAS rats. Acute noxious CRD disrupted spinal KCC2 expression and function 2 h after the final distention in sham rats, but not in WAS rats. Pharmacological blockade of KCC2 activity by intrathecal injection of a KCC2 inhibitor [(dihydroindenyl)oxy] alkanoic acid enhanced visceral nociceptive sensitivity in sham rats, but not in WAS rats. These results suggest that KCC2 downregulation-mediated impairment of spinal cord Cl(-) homeostasis may play an important role in chronic stress-induced visceral hypersensitivity. PMID:25792562

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

    PubMed

    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. Genotyping for Severe Drug Hypersensitivity

    PubMed Central

    Karlin, Eric; Phillips, Elizabeth

    2014-01-01

    Over the past decade, there have been significant advances in our understanding of the immunopathogenesis and pharmacogenomics of severe immunologically-mediated adverse drug reactions. Such T-cell-mediated adverse drug reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug-induced liver disease (DILI) and other drug hypersensitivity syndromes have more recently been shown to be mediated through interactions with various class I and II HLA alleles. Key examples have included the associations of HLA-B*15:02 and carbamazepine induced SJS/TEN in Southeast Asian populations and HLA-B*57:01 and abacavir hypersensitivity. HLA-B*57:01 screening to prevent abacavir hypersensitivity exemplifies a successful translational roadmap from pharmacogenomic discovery through to widespread clinical implementation. Ultimately, our increased understanding of the interaction between drugs and the MHC could be used to inform drug design and drive pre-clinical toxicity programs to improve drug safety. PMID:24429903

  2. CD32a antibodies induce thrombocytopenia and type II hypersensitivity reactions in FCGR2A mice.

    PubMed

    Meyer, Todd; Robles-Carrillo, Liza; Davila, Monica; Brodie, Meghan; Desai, Hina; Rivera-Amaya, Mildred; Francis, John L; Amirkhosravi, Ali

    2015-11-01

    The CD32a immunoglobulin G (IgG) receptor (Fcγ receptor IIa) is a potential therapeutic target for diseases in which IgG immune complexes (ICs) mediate inflammation, such as heparin-induced thrombocytopenia, rheumatoid arthritis, and systemic lupus erythematosus. Monoclonal antibodies (mAbs) are a promising strategy for treating such diseases. However, IV.3, perhaps the best characterized CD32a-blocking mAb, was recently shown to induce anaphylaxis in immunocompromised "3KO" mice. This anaphylactic reaction required a human CD32a transgene because mice lack an equivalent of this gene. The finding that IV.3 induces anaphylaxis in CD32a-transgenic mice was surprising because IV.3 had long been thought to lack the intrinsic capacity to trigger cellular activation via CD32a. Such an anaphylactic reaction would also limit potential therapeutic applications of IV.3. In the present study, we examine the molecular mechanisms by which IV.3 induces anaphylaxis. We now report that IV.3 induces anaphylaxis in immunocompetent CD32a-transgenic "FCGR2A" mice, along with the novel finding that IV.3 and 2 other well-characterized CD32a-blocking mAbs, AT-10 and MDE-8, also induce severe thrombocytopenia in FCGR2A mice. Using recombinant variants of these same mAbs, we show that IgG "Fc" effector function is necessary for the induction of anaphylaxis and thrombocytopenia in FCGR2A mice. Variants of these mAbs lacking the capacity to activate mouse IgG receptors not only failed to induce anaphylaxis or thrombocytopenia, but also very potently protected FCGR2A mice from near lethal doses of IgG ICs. Our findings show that effector-deficient IV.3, AT-10, and MDE-8 are promising candidates for developing therapeutic mAbs to treat CD32a-mediated diseases. PMID:26396093

  3. CD32a antibodies induce thrombocytopenia and type II hypersensitivity reactions in FCGR2A mice

    PubMed Central

    Robles-Carrillo, Liza; Davila, Monica; Brodie, Meghan; Desai, Hina; Rivera-Amaya, Mildred; Francis, John L.; Amirkhosravi, Ali

    2015-01-01

    The CD32a immunoglobulin G (IgG) receptor (Fcγ receptor IIa) is a potential therapeutic target for diseases in which IgG immune complexes (ICs) mediate inflammation, such as heparin-induced thrombocytopenia, rheumatoid arthritis, and systemic lupus erythematosus. Monoclonal antibodies (mAbs) are a promising strategy for treating such diseases. However, IV.3, perhaps the best characterized CD32a-blocking mAb, was recently shown to induce anaphylaxis in immunocompromised “3KO” mice. This anaphylactic reaction required a human CD32a transgene because mice lack an equivalent of this gene. The finding that IV.3 induces anaphylaxis in CD32a-transgenic mice was surprising because IV.3 had long been thought to lack the intrinsic capacity to trigger cellular activation via CD32a. Such an anaphylactic reaction would also limit potential therapeutic applications of IV.3. In the present study, we examine the molecular mechanisms by which IV.3 induces anaphylaxis. We now report that IV.3 induces anaphylaxis in immunocompetent CD32a-transgenic “FCGR2A” mice, along with the novel finding that IV.3 and 2 other well-characterized CD32a-blocking mAbs, AT-10 and MDE-8, also induce severe thrombocytopenia in FCGR2A mice. Using recombinant variants of these same mAbs, we show that IgG “Fc” effector function is necessary for the induction of anaphylaxis and thrombocytopenia in FCGR2A mice. Variants of these mAbs lacking the capacity to activate mouse IgG receptors not only failed to induce anaphylaxis or thrombocytopenia, but also very potently protected FCGR2A mice from near lethal doses of IgG ICs. Our findings show that effector-deficient IV.3, AT-10, and MDE-8 are promising candidates for developing therapeutic mAbs to treat CD32a-mediated diseases. PMID:26396093

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

    PubMed Central

    Stewart, Ian; Seawright, Alan A; Schluter, Philip J; Shaw, Glen R

    2006-01-01

    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 sensitising potential of

  5. CD11b+Ly6G− myeloid cells mediate mechanical inflammatory pain hypersensitivity

    PubMed Central

    Ghasemlou, Nader; Chiu, Isaac M.; Julien, Jean-Pierre; Woolf, Clifford J.

    2015-01-01

    Pain hypersensitivity at the site of inflammation as a result of chronic immune diseases, pathogenic infection, and tissue injury is a common medical condition. However, the specific contributions of the innate and adaptive immune system to the generation of pain during inflammation have not been systematically elucidated. We therefore set out to characterize the cellular and molecular immune response in two widely used preclinical models of inflammatory pain: (i) intraplantar injection of complete Freund’s adjuvant (CFA) as a model of adjuvant- and pathogen-based inflammation and (ii) a plantar incisional wound as a model of tissue injury-based inflammation. Our findings reveal differences in temporal patterns of immune cell recruitment and activation states, cytokine production, and pain in these two models, with CFA causing a nonresolving granulomatous inflammatory response whereas tissue incision induced resolving immune and pain responses. These findings highlight the significant differences and potential clinical relevance of the incisional wound model compared with the CFA model. By using various cell-depletion strategies, we find that, whereas lymphocyte antigen 6 complex locus G (Ly)6G+CD11b+ neutrophils and T-cell receptor (TCR) β+ T cells do not contribute to the development of thermal or mechanical pain hypersensitivity in either model, proliferating CD11b+Ly6G− myeloid cells were necessary for mechanical hypersensitivity during incisional pain, and, to a lesser extent, CFA-induced inflammation. However, inflammatory (CCR2+Ly6Chi) monocytes were not responsible for these effects. The finding that a population of proliferating CD11b+Ly6G− myeloid cells contribute to mechanical inflammatory pain provides a potential cellular target for its treatment in wound inflammation. PMID:26598697

  6. Trichloroethylene Hypersensitivity Syndrome Is Potentially Mediated through Its Metabolite Chloral Hydrate

    PubMed Central

    Huang, Yongshun; Xia, Lihua; Wu, Qifeng; Zeng, Zifang; Huang, Zhenlie; Zhou, Shanyu; Jin, Jiachun; Huang, Hanlin

    2015-01-01

    Background We documented previously the entity of trichloroethylene (TCE) hypersensitivity syndrome (THS) in occupational workers. Objectives To identify the culprit causative compound, determine the type of hypersensitivity of THS, and establish a screening test for subjects at risk of THS. Methods TCE and its main metabolites chloral hydrate (CH), trichloroethanol (TCOH) and trichloroacetic acid (TCA) were used as allergens at different concentrations in skin patch tests. The study included 19 case subjects diagnosed with occupational THS, 22 control healthy workers exposed to TCE (exposure >12 weeks), and 20 validation new workers exposed to TCE for <12 weeks free of THS. All subjects were followed-up for 12 weeks after the patch test. Results The highest patch test positive rate in subjects with THS was for CH, followed by TCOH, TCA and TCE. The CH patch test positive rate was 100% irrespective of CH concentrations (15%, 10% and 5%). The TCOH patch test positive rate was concentration-dependent (89.5%, 73.7% and 52.6% for 5%, 0.5% and 0.05%, respectively). Lower patch test positive rates were noted for TCA and TCE. All patch tests (including four allergens) were all negative in each of the 22 control subjects. None of the subjects of the validation group had a positive 15% CH patch test. Conclusions Chloral hydrate seems to be the culprit causative compound of THS and type IV seems to be the major type of hypersensitivity of THS. The CH patch test could be potentially useful for screening workers at risk of THS. PMID:26020924

  7. CD11b+Ly6G- myeloid cells mediate mechanical inflammatory pain hypersensitivity.

    PubMed

    Ghasemlou, Nader; Chiu, Isaac M; Julien, Jean-Pierre; Woolf, Clifford J

    2015-12-01

    Pain hypersensitivity at the site of inflammation as a result of chronic immune diseases, pathogenic infection, and tissue injury is a common medical condition. However, the specific contributions of the innate and adaptive immune system to the generation of pain during inflammation have not been systematically elucidated. We therefore set out to characterize the cellular and molecular immune response in two widely used preclinical models of inflammatory pain: (i) intraplantar injection of complete Freund's adjuvant (CFA) as a model of adjuvant- and pathogen-based inflammation and (ii) a plantar incisional wound as a model of tissue injury-based inflammation. Our findings reveal differences in temporal patterns of immune cell recruitment and activation states, cytokine production, and pain in these two models, with CFA causing a nonresolving granulomatous inflammatory response whereas tissue incision induced resolving immune and pain responses. These findings highlight the significant differences and potential clinical relevance of the incisional wound model compared with the CFA model. By using various cell-depletion strategies, we find that, whereas lymphocyte antigen 6 complex locus G (Ly)6G(+)CD11b(+) neutrophils and T-cell receptor (TCR) β(+) T cells do not contribute to the development of thermal or mechanical pain hypersensitivity in either model, proliferating CD11b(+)Ly6G(-) myeloid cells were necessary for mechanical hypersensitivity during incisional pain, and, to a lesser extent, CFA-induced inflammation. However, inflammatory (CCR2(+)Ly6C(hi)) monocytes were not responsible for these effects. The finding that a population of proliferating CD11b(+)Ly6G(-) myeloid cells contribute to mechanical inflammatory pain provides a potential cellular target for its treatment in wound inflammation. PMID:26598697

  8. Aspirin hypersensitivity.

    PubMed

    Sánchez-Borges, Mario

    2014-01-01

    Hypersensitivity reactions to acetylsalicylic acid and non-steroidal anti-inflammatory drugs constitute a major medical concern worldwide. This article presents an overview of the observations that led to the discovery of cyclooxygenase inhibitors, as a prerequisite to better understand the basic concepts supporting seminal investigations carried out in order to elucidate the clinical features, pathogenic mechanisms, diagnosis and modern management of these common conditions. There are some unmet needs in this clinical area which will have to be solved in the future, especially concerning the pathogenesis of these reactions and the availability of novel in vitro diagnostic methods sparing both patient and physician of the risks inherent to in vivo provocation tests. PMID:24925393

  9. Effect of disodium cromoglycate on mast cell-mediated immediate-type allergic reactions.

    PubMed

    Shin, Hye-Young; Kim, Jung-Sook; An, Nyeon-Hyoung; Park, Rae-Kil; Kim, Hyung-Min

    2004-04-23

    We investigated the effect of disodium cromoglycate (DSCG) on mast cell-mediated immediate-type hypersensitivity. DSCG inhibited systemic allergic reaction induced by compound 48/80 dose-dependently. Passive cutaneous anaphylaxis was inhibited by 71.6% by oral administration of DSCG (1 g/kg). When DSCG was pretreated at concentration rang from 0.01-1000 g/kg, the serum histamine levels were reduced in a dose dependent manner. DSCG also significantly inhibited histamine release from rat peritoneal mast cell (RPMC) by compound 48/80. We confirmed that DSCG inhibited compound 48/80-induced degranulation of RPMC by alcian blue/nuclear fast red staining. In addition, DSCG showed a significant inhibitory effect on anti-dinitrophenyl IgE-mediated tumor necrosis factor-alpha production. These results indicate that DSCG inhibits mast cell-mediated immediate-type allergic reaction. PMID:15050425

  10. Role of dendritic cell-mediated abnormal immune response in visceral hypersensitivity

    PubMed Central

    Li, Meng; Zhang, Lu; Lu, Bin; Chen, Zhe; Chu, Li; Meng, Lina; Fan, Yihong

    2015-01-01

    The role of dendritic cells (DCs) in irritable bowel syndrome (IBS) is unclear. This study tested the hypothesis that intestinal DCs induced visceral hypersensitivity in IBS rats through mast cell (MC) activation. The IBS rat model was established by combining colorectal distension with restraint stress. The number of CD103-positive cells in colon was higher in the IBS group. Expression of PAR-2, IL-4 and IL-9 in the colonic mucosa was higher in the IBS group. Mesenteric lymph node DCs (MLNDCs) and splenic CD4+/CD8+ T cells were isolated and purified by a magnetic labeling-based technique; they were cultured alone or co-cultured (T4+DC/T8+DC). The coculture of MLNDCs and CD4+ T cells had the highest IL-4 secretion in the IBS group, while IL-9 expression was higher in the cultures containing CD8+ T cells. Our findings indicate that an increased number of DCs in the colon stimulated CD4+ T cells to secrete high levels of IL-4, which led to the activation of MCs and subsequently resulted in visceral hypersensitivity. PMID:26550249

  11. A single gene, AIN, in Medicago truncatula mediates a hypersensitive response to both bluegreen aphid and pea aphid, but confers resistance only to bluegreen aphid

    PubMed Central

    Klingler, John P.; Nair, Ramakrishnan M.; Edwards, Owain R.; Singh, Karam B.

    2009-01-01

    Biotic stress in plants frequently induces a hypersensitive response (HR). This distinctive reaction has been studied intensively in several pathosystems and has shed light on the biology of defence signalling. Compared with microbial pathogens, relatively little is known about the role of the HR in defence against insects. Reference genotype A17 of Medicago truncatula Gaertn., a model legume, responds to aphids of the genus Acyrthosiphon with necrotic lesions resembling a HR. In this study, the biochemical nature of this response, its mode of inheritance, and its relationship with defence against aphids were investigated. The necrotic lesion phenotype and resistance to the bluegreen aphid (BGA, Acyrthosiphon kondoi Shinji) and the pea aphid (PA, Acyrthosiphon pisum (Harris)) were analysed using reference genotypes A17 and A20, their F2 progeny and recombinant inbred lines. BGA-induced necrotic lesions co-localized with the production of H2O2, consistent with an oxidative burst widely associated with hypersensitivity. This HR correlated with stronger resistance to BGA in A17 than in A20; these phenotypes cosegregated as a semi-dominant gene, AIN (Acyrthosiphon-induced necrosis). In contrast to BGA, stronger resistance to PA in A17, compared with A20, did not cosegregate with a PA-induced HR. The AIN locus resides in a cluster of sequences predicted to encode the CC-NBS-LRR subfamily of resistance proteins. AIN-mediated resistance presents a novel opportunity to use a model plant and model aphid to study the role of the HR in defence responses to phloem-feeding insects. PMID:19690018

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

    PubMed Central

    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

  13. Draft Genome Sequence of a Hypersensitive Reaction-Inducing Pantoea agglomerans Strain Isolated from Olive Knots Caused by Pseudomonas savastanoi pv. savastanoi.

    PubMed

    Moretti, Chiaraluce; Cortese, Chiara; Passos da Silva, Daniel; Venturi, Vittorio; Torelli, Emanuela; Firrao, Giuseppe; Buonaurio, Roberto

    2014-01-01

    Pantoea agglomerans strains inducing a hypersensitive reaction in tobacco leaves are frequently isolated inside olive knots caused by Pseudomonas savastanoi pv. savastanoi. Here, we report the draft genome sequence of the Italian P. agglomerans strain, which is able to increase olive knot disease severity when coinoculated with P. savastanoi pv. savastanoi. PMID:25103763

  14. New approaches for predicting T cell-mediated drug reactions: A role for inducible and potentially preventable autoimmunity.

    PubMed

    Michels, Aaron W; Ostrov, David A

    2015-08-01

    Adverse drug reactions (ADRs) are commonplace and occur when a drug binds to its intended pharmacologic target (type A ADR) or an unintended target (type B ADR). Immunologically mediated type B ADRs, such as drug hypersensitivity syndrome, drug reaction with eosinophilia and systemic symptoms syndrome, and Stevens-Johnson syndrome/toxic epidermal necrolysis, can be severe and result in a diverse set of clinical manifestations that include fever and rash, as well as multiple organ failure (liver, kidney, lungs, and/or heart) in the case of drug hypersensitivity syndrome. There is increasing evidence that specific HLA alleles influence the risk of drug reactions. Several features of T cell-mediated ADRs are strikingly similar to those displayed by patients with autoimmune diseases like type I diabetes, such as strong HLA association, organ-specific adaptive immune responses, viral involvement, and activation of innate immunity. There is a need to better predict patient populations at risk for immunologically mediated type B ADRs. Because methods to predict type 1 diabetes by using genetic and immunologic biomarkers have been developed to a high level of accuracy (predicting 100% of subjects likely to progress), new research strategies based on these methods might also improve the ability to predict drug hypersensitivity. PMID:26254052

  15. NADPH Oxidase-Derived ROS Induced by Chronic Intermittent Hypoxia Mediates Hypersensitivity of Lung Vagal C Fibers in Rats

    PubMed Central

    Yang, Chang-Huan; Zhuang, Wei-Ling; Shen, Yan-Jhih; Lai, Ching Jung; Kou, Yu Ru

    2016-01-01

    Obstructive sleep apnea (OSA), manifested by exposure to chronic intermittent hypoxia (CIH) and excess production of reactive oxygen species (ROS) in the airways, is associated with hyperreactive airway diseases. ROS, particularly when created by NADPH oxidase, are known to sensitize lung vagal C fibers (LVCFs), which may contribute to airway hypersensitivity pathogenesis. We investigated whether CIH augments the reflex and afferent responses of LVCFs to chemical stimulants and the roles of ROS and NADPH oxidase in such airway hypersensitivity. Rats were exposed to room air (RA) or CIH with/without daily treatment with MnTMPyP (a superoxide anion scavenger), apocynin (an NADPH oxidase inhibitor), or vehicle. At 16 h after their last exposure, intravenous capsaicin, adenosine, or α,β-methylene-ATP evoked an augmented apneic response in anesthetized rats with 14-days CIH exposure, compared to anesthetized rats with 14-days RA exposure. The augmented apneic responses to these LVCF stimulants were abolished by bilateral vagotomy or perivagal capsaicin treatment, which block LVCFs neural conduction and were significantly suppressed by treatment with MnTMPyP or apocynin, but not vehicle. Electrophysiological studies revealed that 14-days CIH exposure potentiated the responses of LVCFs to these stimulants. This effect was inhibited by treatment with MnTMPyP or apocynin treatment and was not seen in rats who received 7-days of CIH exposure. Biochemical analysis indicated that 14-days CIH exposure increased both lung lipid peroxidation, which is indicative of oxidative stress, and expression of the p47phox subunit in the membrane fraction of lung tissue, which is an index of NADPH oxidase activation. The former was prevented by treatment with either MnTMPyP or apocynin, while the later was prevented by treatment with apocynin only. These results suggest that 14-days CIH exposure sensitizes LVCFs in rats, leading to an exaggerated reflex and afferent responses to

  16. Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons

    NASA Astrophysics Data System (ADS)

    Neumann, Simona; Doubell, Tim P.; Leslie, Tabi; Woolf, Clifford J.

    1996-11-01

    PAIN is normally evoked only by stimuli that are sufficiently intense to activate high-threshold Aδ and C sensory fibres, which relay the signal to the spinal cord. Peripheral inflammation leads to profoundly increased pain sensitivity: noxious stimuli generate a greater response and stimuli that are normally innocuous elicit pain. Inflammation increases the sensitivity of the peripheral terminals of Aδ and C fibres at the site of inflammation1. It also increases the excitability of spinal cord neurons2,3, which now amplify all sensory inputs including the normally innocuous tactile stimuli that are conveyed by low-threshold Aβ fibres. This central sensitization has been attributed to the enhanced activity of C fibres4, which increase the excitability of their postsynaptic targets by releasing glutamate and the neuropeptide substance P5-7. Here we show that inflammation results in Aβ fibres also acquiring the capacity to increase the excitability of spinal cord neurons. This is due to a phenotypic switch in a subpopulation of these fibres so that they, like C-fibres, now express substance P. Aβ fibres thus appear to contribute to inflammatory hypersensitivity by switching their phenotype to one resembling pain fibres, thereby enhancing synaptic transmission in the spinal cord and exaggerating the central response to innocuous stimuli.

  17. Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons.

    PubMed

    Neumann, S; Doubell, T P; Leslie, T; Woolf, C J

    1996-11-28

    Pain is normally evoked only by stimuli that are sufficiently intense to activate high-threshold A(delta) and C sensory fibres, which relay the signal to the spinal cord. Peripheral inflammation leads to profoundly increased pain sensitivity: noxious stimuli generate a greater response and stimuli that are normally innocuous elicit pain. Inflammation increases the sensitivity of the peripheral terminals of A(delta) and C fibres at the site of inflammation. It also increases the excitability of spinal cord neurons, which now amplify all sensory inputs including the normally innocuous tactile stimuli that are conveyed by low-threshold A(beta) fibres. This central sensitization has been attributed to the enhanced activity of C fibres, which increase the excitability of their postsynaptic targets by releasing glutamate and the neuropeptide substance P. Here we show that inflammation results in A(beta) fibres also acquiring the capacity to increase the excitability of spinal cord neurons. This is due to a phenotypic switch in a subpopulation of these fibres so that they, like C-fibres, now express substance P. A(beta) fibres thus appear to contribute to inflammatory hypersensitivity by switching their phenotype to one resembling pain fibres, thereby enhancing synaptic transmission in the spinal cord and exaggerating the central response to innocuous stimuli. PMID:8934522

  18. Prevalence of HLA-B*5701 and Its Relationship with Abacavir Hypersensitivity Reaction in Iranian HIV-Infected Patients

    PubMed Central

    Baniasadi, Shadi; Shokouhi, Shokoufeh Baradaran; Tabarsi, Payam; Alehashem, Maryam; Khalili, Hossein; Fahimi, Fanak

    2016-01-01

    Background: Hypersensitivity reaction (HSR) is a major adverse effect of abacavir (ABC), which occurs in 5–8% of Caucasians. The relationship between Human Leukocyte Antigen (HLA) and ABC HSR has been reported in various populations. It has been proposed to administer ABC only to HLA-B*5701 negative patients to avoid this reaction. The purpose of this study was to assess the prevalence of HLA-B*5701 in Iranian HIV positive patients. We also sought to find the relationship between this allele with ABC HSR in patients who received the medication. Materials and Methods: We screened patients for HLA-B*5701 allele using SybrGreen real time PCR-melting method on blood samples from HIV positive patients who were referred to our hospital. The quality of the extracted genome was evaluated by B-globin housekeeping gene as internal control prior to HLA-B*5701 allele screening. Results: Of 198 HIV-infected patients, 6 (3.0%) had the HLA-B*5701 allele (95% CI, 1%–5%). Among the 28 patients who were given ABC, one individual had the HLA-B*5701 allele and experienced ABC HSR. Conclusion: Prevalence of HLA-B*5701 in Iranian patients was lower than that in Caucasians but was comparable with that of other Middle Eastern populations. Screening for HLA-B*5701 before ABC administration as part of antiretroviral therapy may reduce the risk of HSR.

  19. Nonimmunoglobulin E-Mediated Immune Reactions to Foods

    PubMed Central

    2006-01-01

    Adverse food reactions are abnormal responses to ingested foods. Reactions vary from immunologic to nonimmunologic immune reactions and can be either immunoglobulin E (IgE) mediated or non-IgE mediated. Food-induced IgE-mediated reactions range from localized urticaria to anaphylaxis and have been well studied. However, in comparison, there has been significantly less research into non-IgE-mediated food reactions. Non-IgE-mediated reactions can cause respiratory, gastrointestinal, and cutaneous symptoms. The most recent evidence suggests that these reactions are probably T-cell mediated as evidenced in lymphocyte proliferation assays. This review will explore the symptoms and testing methods of the most common non-IgE-mediated reactions. PMID:20525161

  20. Type I allergic hypersensitivity reactions due to ethylene oxide sterilised leucocyte filters in patients with thalassaemia: report of four cases.

    PubMed

    Belen, Burcu; Polat, Meltem

    2015-01-01

    Ethylene oxide (EO) is a highly reactive gas used in sterilisation of heat sensitive medical devices, such as infusion sets, cannulae, intubation materials, ventriculoperitoneal shunts, dialysis catheters and stents. Allergic reactions due to EO have been reported in haemodialysis patients, patients undergoing extracorporeal photopheresis and donors of plasmapheresis. Clinical manifestations vary considerably and generally do not allow differentiation between IgE-mediated anaphylaxis and anaphylactoid reactions. We report four patients with thalassaemia who experienced anaphylaxis during transfusion due to ethylene oxide sterilised leucocyte filters. The aim of this report is to highlight the fact that frequently transfused patients can have allergic reactions due to EO particles left in leucocyte filters. PMID:25725028

  1. Contrast media hypersensitivity--scope of the problem.

    PubMed

    Brockow, Knut

    2005-04-15

    Hypersensitivity reactions to contrast media (CM) are frequent causes of anaphylactically induced fatalities. Adverse events after CM exposure are classified into immediate and non-immediate reactions, with differing pathomechanisms. In the majority of patients with immediate reactions, IgE-mediated allergy can not be demonstrated and the underlying mechanism remains unknown. However, recent data has provided evidence for skin test positivity and/or specific IgE in some patients with severe reactions. Cell-mediated hypersensitivity is the responsible mechanism for the majority of non-immediate skin eruptions. Skin tests have been employed to confirm this hypersensitivity. Previous reactors have an increased risk to develop new reactions upon repeated exposure, however, other risk factors are poorly defined. The use of skin tests for the selection of a "safe" CM is controversially discussed; information on sensitivity and specificity is lacking. New in-vitro assays have to be developed and/or validated. Premedication of previous reactors is common practice among radiologists, however, its precise role in the prevention of severe CM reactions to lower-osmolality CM has not been demonstrated. Thus, the main future tasks are to develop and validate allergic tests procedures, which may identify patients at risk and/or may confirm CM tolerance, and to reassess the value of different premedications in the prevention of hypersensitivity reactions. PMID:15767034

  2. Hypersensitivity Reaction to Insulin Glargine and Insulin Detemir in a Pediatric Patient: A Case Report

    PubMed Central

    Badik, Jennifer; Chen, Jimmy; Letvak, Kira

    2016-01-01

    Allergy to human insulin or its analogs is rare, but it is still a significant issue in current diabetes care. Allergic reactions can range from localized injection site reactions to generalized anaphylaxis, and they can be caused by excipients or the insulin molecules themselves. We presented a case of a 14-year-old male patient with generalized allergic reactions to insulin glargine and insulin detemir. The patient was successfully managed by being switched to a continuous subcutaneous insulin infusion with insulin aspart. Allergic reactions to insulin detemir and insulin glargine have both been well described, with insulin detemir allergy appearing to be more common. There are several potential mechanisms for insulin allergy, and immunologic characteristics vary among different insulin analogs. After confirming insulin allergy in practice, management involves treating symptoms and switching insulin preparations. This is the first documented case of allergies to both insulin glargine and insulin detemir in a pediatric patient. Exact mechanism of insulin allergy is unknown, and management strategies must be individualized for each patient. PMID:26997933

  3. Hypersensitivity Reaction to Insulin Glargine and Insulin Detemir in a Pediatric Patient: A Case Report.

    PubMed

    Badik, Jennifer; Chen, Jimmy; Letvak, Kira; So, Tsz-Yin

    2016-01-01

    Allergy to human insulin or its analogs is rare, but it is still a significant issue in current diabetes care. Allergic reactions can range from localized injection site reactions to generalized anaphylaxis, and they can be caused by excipients or the insulin molecules themselves. We presented a case of a 14-year-old male patient with generalized allergic reactions to insulin glargine and insulin detemir. The patient was successfully managed by being switched to a continuous subcutaneous insulin infusion with insulin aspart. Allergic reactions to insulin detemir and insulin glargine have both been well described, with insulin detemir allergy appearing to be more common. There are several potential mechanisms for insulin allergy, and immunologic characteristics vary among different insulin analogs. After confirming insulin allergy in practice, management involves treating symptoms and switching insulin preparations. This is the first documented case of allergies to both insulin glargine and insulin detemir in a pediatric patient. Exact mechanism of insulin allergy is unknown, and management strategies must be individualized for each patient. PMID:26997933

  4. Early skin testing is effective for diagnosis of hypersensitivity reactions occurring during anesthesia.

    PubMed

    Lafuente, A; Javaloyes, G; Berroa, F; Goikoetxea, M J; Moncada, R; Núñez-Córdoba, J M; Cabrera-Freitag, P; D'Amelio, C; Sanz, M L; Gastaminza, G

    2013-06-01

    Allergic skin tests have to be performed 4-6 weeks after an allergic anesthetic reaction. Patients with allergic reactions during anesthesia were prospectively included (n = 44). Skin tests were performed in two stages: (i) Stage 1 (S1), 0-4 days after the reaction; and (ii) Stage 2 (S2), 4-8 weeks after. Five (11.5%) surgical procedures were suspended due to the reaction. Positive skin tests were obtained in 25/44 patients (57%). Allergic diagnosis was carried out at S1 in 15/25 (60%) and at S2 in 10/25 (40%). Three patients resulted positive only in S1. Overall agreement among S1 and S2 skin tests was 70.45%. The kappa statistic was 0.41 (P-value = 0.002). Odds ratio of obtaining a false negative in S1 (compared with S2) was 3.33. Early allergological study is useful, could minimize false negatives, but should be considered as a complement to late skin tests. PMID:23646901

  5. Localization of hydrogen peroxide accumulation during the hypersensitive reaction of lettuce cells to Pseudomonas syringae pv phaseolicola.

    PubMed Central

    Bestwick, C S; Brown, I R; Bennett, M H; Mansfield, J W

    1997-01-01

    The active oxygen species hydrogen peroxide (H2O2) was detected cytochemically by its reaction with cerium chloride to produce electron-dense deposits of cerium perhydroxides. In uninoculated lettuce leaves, H2O2 was typically present within the secondary thickened walls of xylem vessels. Inoculation with wild-type cells of Pseudomonas syringae pv phaseolicola caused a rapid hypersensitive reaction (HR) during which highly localized accumulation of H2O2 was found in plant cell walls adjacent to attached bacteria. Quantitative analysis indicated a prolonged burst of H2O2 occurring between 5 to 8 hr after inoculation in cells undergoing the HR during this example of non-host resistance. Cell wall alterations and papilla deposition, which occurred in response to both the wild-type strain and a nonpathogenic hrpD mutant, were not associated with intense staining for H2O2, unless the responding cell was undergoing the HR. Catalase treatment to decompose H2O2 almost entirely eliminated staining, but 3-amino-1,2,4-triazole (catalase inhibitor) did not affect the pattern of distribution of H2O2 detected. H2O2 production was reduced more by the inhibition of plant peroxidases (with potassium cyanide and sodium azide) than by inhibition of neutrophil-like NADPH oxidase (with diphenylene iodonium chloride). Results suggest that CeCl3 reacts with excess H2O2 that is not rapidly metabolized during cross-linking reactions occurring in cell walls; such an excess of H2O2 in the early stages of the plant-bacterium interaction was only produced during the HR. The highly localized accumulation of H2O2 is consistent with its direct role as an antimicrobial agent and as the cause of localized membrane damage at sites of bacterial attachment. PMID:9061952

  6. The N-terminal fragment of the tomato torrado virus RNA1-encoded polyprotein induces a hypersensitive response (HR)-like reaction in Nicotiana benthamiana.

    PubMed

    Wieczorek, Przemysław; Obrępalska-Stęplowska, Aleksandra

    2016-07-01

    The hypersensitive response (HR) is a defence reaction observed during incompatible plant-pathogen interactions in plants infected with a wide range of fungi, bacteria and viruses. Here, we show that an N-terminal polyprotein fragment encoded by tomato torrado virus RNA1, located between the first ATG codon and the protease cofactor (ProCo) motif, induces an HR-like reaction in Nicotiana benthamiana. Agrobacterium tumefaciens-mediated transient expression of the first 105 amino acids (the calculated molecular weight of the fragment was ca. 11.33 kDa, hereafter refered to as the 11K domain) from ToTV RNA1 induced an HR-like phenotype in infiltrated leaves. To investigate whether the 11K domain could influence the virulence and pathogenicity of a recombinant virus, we created a potato virus X (PVX) with the 11K coding sequence inserted under a duplicated coat protein promoter. We found that 11K substantially increased the virulence of the recombinant virus. Disease phenotype induced in N. benthamiana by PVX-11K was characterized by strong local and systemic necrosis. This was not observed when the 11K domain was expressed from PVX in an antisense orientation. Further analyses revealed that the 11K domain could not suppress posttranscriptional gene silencing (PTGS) of green fluorescent protein (GFP) in the N. benthamiana 16c line. In silico analysis of the predicted secondary structure of the 11K domain indicated the presence of two putative helices that are highly conserved in tomato-infecting representatives of the genus Torradovirus. PMID:27072852

  7. Fifty-six-year-old man with anaphylaxis: A novel delayed food hypersensitivity reaction.

    PubMed

    Wagner, Kendall D; Bell, Matthew C; Pesek, Robert D; Kennedy, Joshua L

    2015-11-01

    Anaphylaxis and urticaria are commonly seen in both primary care and allergy clinics. Foods, drugs, and insects are frequent culprits for immediate reactions; however, the trigger for recurring and/or chronic episodes is often unclear. We present a 56-year-old male with recurrent symptoms of urticaria, angioedema, and anaphylaxis found to be triggered by sensitization to galactose-alpha 1, 3-galactose (alpha-gal), a novel food allergen. PMID:26625604

  8. Hypersensitivity reaction in an infant fed hydrolyzed lactalbumin contained in a semielemental formula.

    PubMed

    Heyman, M B; Stoker, T W; Rudolph, C D; Frick, O L

    1990-02-01

    Following introduction of milk protein formula feedings, a 6-month-old male developed profuse, watery diarrhea progressing to shock, requiring cardiopulmonary resuscitation. Reinstitution of enteral feedings with a formula containing hydrolyzed lactalbumin (Travasorb STD) resulted in recurrence of diarrhea with fever. Intestinal and rectal biopsies showed only nonspecific inflammatory changes. He was discharged on an elemental formula (Vivonex). Twenty-three months later, while admitted for evaluation of hypophosphatemic rickets, immunologic testing using the lymphocyte migration inhibition factor (LIF) test demonstrated positive reactions, especially to alpha-lactalbumin (56% inhibition) and whole cow's milk (22%, normal of less than 20% inhibition). Skin tests revealed sensitivity to cow's milk and eggs. Soy formula also produced diarrhea and bloody stools. Protein hydrolysate formulas, touted as hypoallergenic diets, are useful in infants with intolerance to milk protein. This is the first documented case of an immunological reaction to the hydrolyzed whey protein, lactalbumin. Although protein hydrolysate formulas are effective treatment in most infants with milk protein intolerance, allergic reactions are possible. Caution and close observation should be exercised in immunologically sensitized infants rechallenged with any formula. PMID:2135732

  9. Involvement of calcitonin gene-related peptide and CCL2 production in CD40-mediated behavioral hypersensitivity in a model of neuropathic pain

    PubMed Central

    MALON, JENNIFER T.; MADDULA, SWATHI; BELL, HARMONY; CAO, LING

    2014-01-01

    The neuropeptide calcitonin gene-related peptide (CGRP) is known to play a pro-nociceptive role after peripheral nerve injury upon its release from primary afferent neurons in preclinical models of neuropathic pain. We previously demonstrated a critical role for spinal cord microglial CD40 in the development of spinal nerve L5 transection (L5Tx)-induced mechanical hypersensitivity. Herein, we investigated whether CGRP is involved in the CD40-mediated behavioral hypersensitivity. First, L5Tx was found to significantly induce CGRP expression in wild-type (WT) mice up to 14 days post-L5Tx. This increase in CGRP expression was reduced in CD40 knockout (KO) mice at day 14 post-L5Tx. Intrathecal injection of the CGRP antagonist CGRP8–37 significantly blocked L5Tx-induced mechanical hypersensitivity. In vitro, CGRP induced glial IL-6 and CCL2 production, and CD40 stimulation added to the effects of CGRP in neonatal glia. Further, there was decreased CCL2 production in CD40 KO mice compared to WT mice 21 days post-L5Tx. However, CGRP8–37 did not significantly affect spinal cord CCL2 production following L5Tx in WT mice. Altogether, these data suggest that CD40 contributes to the maintenance of behavioral hypersensitivity following peripheral nerve injury in part through two distinct pathways, the enhancement of CGRP expression and spinal cord CCL2 production. PMID:22377050

  10. Ten Weeks of Infection with a Tissue-Invasive Helminth Protects against Local Immune Complex-Mediated Inflammation, but Not Cutaneous Type I Hypersensitivity, in Previously Sensitized Mice.

    PubMed

    Evans, Holly; Killoran, Kristin E; Mitre, Blima K; Morris, C Paul; Kim, So-Young; Mitre, Edward

    2015-10-01

    In this study, we evaluated the effect chronic helminth infection has on allergic disease in mice previously sensitized to OVA. Ten weeks of infection with Litomosoides sigmodontis reduced immunological markers of type I hypersensitivity, including OVA-specific IgE, basophil activation, and mast cell degranulation. Despite these reductions, there was no protection against immediate clinical hypersensitivity following intradermal OVA challenge. However, late-phase ear swelling, due to type III hypersensitivity, was significantly reduced in chronically infected animals. Levels of total IgG2a, OVA-specific IgG2a, and OVA-specific IgG1 were reduced in the setting of infection. These reductions were most likely due to increased Ab catabolism as ELISPOT assays demonstrated that infected animals do not have suppressed Ab production. Ear histology 24 h after challenge showed infected animals have reduced cellular infiltration in the ear, with significant decreases in numbers of neutrophils and macrophages. Consistent with this, infected animals had less neutrophil-specific chemokines CXCL-1 and CXCL-2 in the ear following challenge. Additionally, in vitro stimulation with immune complexes resulted in significantly less CXCL-1 and CXCL-2 production by eosinophils from chronically infected mice. Expression of FcγRI was also significantly reduced on eosinophils from infected animals. These data indicate that chronic filarial infection suppresses eosinophilic responses to Ab-mediated activation and has the potential to be used as a therapeutic for pre-existing hypersensitivity diseases. PMID:26324775

  11. Visible Light Mediated Photoredox Catalytic Arylation Reactions.

    PubMed

    Ghosh, Indrajit; Marzo, Leyre; Das, Amrita; Shaikh, Rizwan; König, Burkhard

    2016-08-16

    Introducing aryl- and heteroaryl moieties into molecular scaffolds are often key steps in the syntheses of natural products, drugs, or functional materials. A variety of cross-coupling methods have been well established, mainly using transition metal mediated reactions between prefunctionalized substrates and arenes or C-H arylations with functionalization in only one coupling partner. Although highly developed, one drawback of the established sp2-sp2 arylations is the required transition metal catalyst, often in combination with specific ligands and additives. Therefore, photoredox mediated arylation methods have been developed as alternative over the past decade. We begin our survey with visible light photo-Meerwein arylation reactions, which allow C-H arylation of heteroarenes, enones, alkenes, and alkynes with organic dyes, such as eosin Y, as the photocatalyst. A good number of examples from different groups illustrate the broad application of the reaction in synthetic transformations. While initially only photo-Meerwein arylation-elimination processes were reported, the reaction was later extended to photo-Meerwein arylation-addition reactions giving access to the photoinduced three component synthesis of amides and esters from alkenes, aryl diazonium salts, nitriles or formamides, respectively. Other substrates with redox-active leaving groups have been explored in photocatalyzed arylation reactions, such as diaryliodonium and triarylsulfonium salts, and arylsulfonyl chlorides. We discus some examples with their scope and limitations. The scope of arylation reagents for photoredox reactions was extended to aryl halides. The challenge here is the extremely negative reduction potential of aryl halides in the initial electron transfer step compared to, e.g., aryl diazonium or diaryliodonium salts. In order to reach reduction potentials over -2.0 V vs SCE two consecutive photoinduced electron transfer steps were used. The intermediary formed colored radical

  12. Flavohaemoglobin HmpX from Erwinia chrysanthemi confers nitrosative stress tolerance and affects the plant hypersensitive reaction by intercepting nitric oxide produced by the host.

    PubMed

    Boccara, Martine; Mills, Catherine E; Zeier, Jürgen; Anzi, Chiara; Lamb, Chris; Poole, Robert K; Delledonne, Massimo

    2005-07-01

    Host cells respond to infection by generating nitric oxide (NO) as a cytotoxic weapon to facilitate killing of invading microbes. Bacterial flavohaemoglobins are well-known scavengers of NO and play a crucial role in protecting animal pathogens from nitrosative stress during infection. Erwinia chrysanthemi, which causes macerating diseases in a wide variety of plants, possesses a flavohaemoglobin (HmpX) whose function in plant pathogens has remained unclear. Here we show that HmpX consumes NO and prevents inhibition by NO of cell respiration, indicating a role in protection from nitrosative stress. Furthermore, infection of Saintpaulia ionantha plants with an HmpX-deficient mutant of E. chrysanthemi revealed that the lack of NO scavenging activity causes the accumulation of unusually high levels of NO in host tissue and triggers hypersensitive cell death. Introduction of the wild-type hmpX gene in an incompatible strain of Pseudomonas syringae had a dramatic effect on the hypersensitive cell death in soya bean cell suspensions, and markedly reduced the development of macroscopic symptoms in Arabidopsis thaliana plants. These observations indicate that HmpX not only protects against nitrosative stress but also attenuates host hypersensitive reaction during infection by intercepting NO produced by the plant for the execution of the hypersensitive cell death programme. PMID:15998309

  13. In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper.

    PubMed

    Mayorga, C; Celik, G; Rouzaire, P; Whitaker, P; Bonadonna, P; Rodrigues-Cernadas, J; Vultaggio, A; Brockow, K; Caubet, J C; Makowska, J; Nakonechna, A; Romano, A; Montañez, M I; Laguna, J J; Zanoni, G; Gueant, J L; Oude Elberink, H; Fernandez, J; Viel, S; Demoly, P; Torres, M J

    2016-08-01

    Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because in vivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available in vitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these in vitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available in vitro methods for DHR diagnosis. We have found that although there are many in vitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well-controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available in vitro tests in a large series of well-characterized patients with DHR and to develop new tests for diagnosis. PMID:26991315

  14. Current advances in ant venom proteins causing hypersensitivity reactions in the Asia-Pacific region.

    PubMed

    Srisong, Hathairat; Daduang, Sakda; Lopata, Andreas L

    2016-01-01

    The main insects causing allergy reactions to stinging insect in humans are Apidae (bees), Vespidae (wasps, yellow jackets and hornets) and Formicidae (ants). Their venom stings are composed of various biologically active peptides and protein components, some of which can cause toxicity or anaphylaxis in humans. The protein venom demonstrate some common allergenic activity such as for fire ants and vespids, which have two common allergens that are phospholipase A1 (enzymatic activity) and antigen 5 with unknown biological activity. The common allergens seem to share some degree of immunological cross-reactivity, particularly when the sequence homology is above 70%. Therefore immunotherapeutic approaches targeting more than one specific species are of interest. Recent widespread increases of various ant species in many countries have resulted in higher number of reported about serious allergic reactions to stings. Most insect-allergy related cases have been reported for species from Solenopsis, Myrmecia and Pachycondyla genera, and their stings can often result in human fatalities. In addition, stinging ants can have serious health effects on livestock, agricultural damage adversely affecting the biodiversity of the region. This review discusses the impact of important ant species on human health in the Asia-Pacific region along with the molecular immunological aspects of the identified venoms and current status of diagnostics and therapeutics. PMID:26641698

  15. Oral allergy syndrome (OAS): symptoms of IgE-mediated hypersensitivity to foods.

    PubMed

    Amlot, P L; Kemeny, D M; Zachary, C; Parkes, P; Lessof, M H

    1987-01-01

    Eighty highly atopic patients were selected for study because they had either atopic eczema (fifty cases) or atopic reactivity to foods, as judged by a positive skin-prick test (thirty cases). In all, sixty-five out of eighty subjects (81%) described symptoms of some kind provoked by foods, but correspondingly positive skin tests were found in only half of these, thirty-three out of eighty (41%). The symptoms experienced by thirty-one of the thirty-three patients with positive skin tests were immediate in onset (within 1 hr) and were at first confined to the upper gastrointestinal tract, the most frequent symptoms being oral irritation and throat tightness. In a proportion of these patients, further symptoms such as urticaria, asthma or anaphylaxis developed following the initial oral symptoms, which suggested the term 'oral allergy syndrome'. In the absence of the oral allergy, symptoms such as asthma, urticaria, migraine or eczema starting later than 1 hr after food were seldom associated with positive skin tests. In the oral allergy syndrome, the characteristic symptoms (strong association with positive skin tests and RAST, time of onset and sites at which symptoms are expressed) suggest a causative relationship between exposure to food antigens and specific IgE-induced release of mediators. In cases of food intolerance that lack a characteristic symptom pattern and a positive skin test or radio-allergo-sorbent test, it seems appropriate to consider non-IgE-mediated causes. PMID:3829369

  16. Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity.

    PubMed

    Simon, D; Cianferoni, A; Spergel, J M; Aceves, S; Holbreich, M; Venter, C; Rothenberg, M E; Terreehorst, I; Muraro, A; Lucendo, A J; Schoepfer, A; Straumann, A; Simon, H-U

    2016-05-01

    Eosinophilic esophagitis (EoE) is a chronic disease characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil-predominant inflammation. EoE is frequently associated with concomitant atopic diseases and immunoglobulin E (IgE) sensitization to food allergens in children as well as to aeroallergens and cross-reactive plant allergen components in adults. Patients with EoE respond well to elemental and empirical food elimination diets. Recent research has, however, indicated that the pathogenesis of EoE is distinct from IgE-mediated food allergy. In this review, we discuss the individual roles of epithelial barrier defects, dysregulated innate and adaptive immune responses, and of microbiota in the pathogenesis of EoE. Although food has been recognized as a trigger factor of EoE, the mechanism by which it initiates or facilitates eosinophilic inflammation appears to be largely independent of IgE and needs to be further investigated. Understanding the pathogenic role of food in EoE is a prerequisite for the development of specific diagnostic tools and targeted therapeutic procedures. PMID:26799684

  17. Hypersensitivity pneumonitis

    MedlinePlus

    Hypersensitivity pneumonitis usually occurs in people who work in places where there are high levels of organic dusts, fungus, or molds. Long-term exposure can lead to lung inflammation and acute lung disease . ...

  18. Hypersensitivity Pneumonitis

    MedlinePlus

    ... Hypersensitivity Pneumonitis Also known as extrinsic allergic alveolitis, bird fancier’s lung, farmer’s lung, hot tub lung, and ... May 27, 2016 Twitter Facebook YouTube Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA OIG CONTACT US National ...

  19. Oral Hypersensitivity Reactions

    MedlinePlus

    ... Executive Committee Board of Trustees Governance Past Presidents Staff/Contact History Awards Our Partners Membership Membership Categories Renew Your Membership Login Fellowship Academic Fellowship Affiliate Fellowship (AFAOM) Application Process Fellowship Study ...

  20. Targeting a Cross-Reactive Gly m 5 Soy Peptide as Responsible for Hypersensitivity Reactions in a Milk Allergy Mouse Model

    PubMed Central

    Curciarello, Renata; Smaldini, Paola L.; Candreva, Angela M.; González, Virginia; Parisi, Gustavo; Cauerhff, Ana; Barrios, Ivana; Blanch, Luis Bruno; Fossati, Carlos A.

    2014-01-01

    Background Cross-reactivity between soybean allergens and bovine caseins has been previously reported. In this study we aimed to map epitopes of the major soybean allergen Gly m 5 that are co-recognized by casein specific antibodies, and to identify a peptide responsible for the cross-reactivity. Methods Cow's milk protein (CMP)-specific antibodies were used in different immunoassays (immunoblotting, ELISA, ELISA inhibition test) to evaluate the in vitro recognition of soybean proteins (SP). Recombinant Gly m 5 (α), a truncated fragment containing the C-terminal domain (α-T) and peptides of α-T were obtained and epitope mapping was performed with an overlapping peptide assay. Bioinformatics tools were used for epitope prediction by sequence alignment, and for modelling the cross-recognized soy proteins and peptides. The binding of SP to a monoclonal antibody was studied by surface Plasmon resonance (SPR). Finally, the in vivo cross-recognition of SP was assessed in a mouse model of milk allergy. Results Both α and α-T reacted with the different CMP-specific antibodies. α-T contains IgG and IgE epitopes in several peptides, particularly in the peptide named PA. Besides, we found similar values of association and dissociation constants between the α-casein specific mAb and the different milk and soy components. The food allergy mouse model showed that SP and PA contain the cross-reactive B and T epitopes, which triggered hypersensitivity reactions and a Th2-mediated response on CMP-sensitized mice. Conclusions Gly m 5 is a cross-reactive soy allergen and the α-T portion of the molecule contains IgG and IgE immunodominant epitopes, confined to PA, a region with enough conformation to be bound by antibodies. These findings contribute to explain the intolerance to SP observed in IgE-mediated CMA patients, primarily not sensitised to SP, as well as it sets the basis to propose a mucosal immunotherapy for milk allergy using this soy peptide. PMID:24416141

  1. Hypersensitivity to antineoplastic agents.

    PubMed

    Castells, M C

    2008-01-01

    The need to offer first line therapy for primary and recurrent cancers has spurred the clinical development of rapid desensitizations for chemotherapy and monoclonal antibodies. Rapid desensitizations allow patients to be treated with medications to which they have presented with hypersensitivity reactions (HSRs), including anaphylaxis. Rapid desensitization achieves temporary tolerization to full therapeutic doses by slow administration of incremental doses of the drug inducing the HSR. Protocols are available for most chemotherapy agents, including taxanes, platins, doxorubicin, monoclonal antibodies, and others. Candidate patients include those who present with type I HSRs, mast cell/IgE dependent, including anaphylaxis, and non-IgE mediated HSRs, during the chemotherapy infusion or shortly after. Idiosyncratic reactions, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis are not amenable to rapid desensitization. The recommendation for rapid desensitization can only be made by allergy and immunology specialists and can only be performed in settings with one-to-one nurse-patient care and where resuscitation personnel and resources are readily available. Repeated desensitizations can be safely performed in outpatient settings with similar conditions, which allow cancer patients to remain in clinical studies. We have generated a universal 12-step protocol that was applied to 413 cases of intravenous and intraperitoneal rapid desensitizations using taxanes, platins, liposomal doxorubicin, doxorubicin, rituximab, and other chemotherapy drugs. Under this protocol all patients were able to complete their target dose, and 94% of the patients had limited or no reactions. No deaths or codes were reported, indicating that the procedure was safe and effective in delivering first line chemotherapy drugs. PMID:18991707

  2. Azathioprine hypersensitivity syndrome: a case report.

    PubMed

    Fenaux, S; Tintillier, M; Cuvelier, Ch; Migali, G; Pochet, J M

    2013-01-01

    We report here the case of a 51-year-old man presenting to the Emergency Department with a febrile cutaneous eruption with diffuse arthralgia 10 days after the onset of azathioprine therapy. The clinical examination did not reveal any inflammatory syndrome and the results of all bacteriological tests were negative. A skin biopsy was performed, which revealed a granulocytary pustula with superficial dermal oedema and a neutrophil infiltration without sign of vasculitis. A side effect of azathioprine was suspected, and treatment was discontinued. Fortunately, the patient recovered within a few days. Azathioprine hypersensitivity syndrome is a rare side effect of azathioprine. Hypersensitivity syndrome is an idiosyncratic, non-IgE-mediated reaction that appears to be unrelated to thiopurine methyltransferase levels. Diagnosis is mainly clinical and requires an exclusion of other processes. The only treatment option available is to stop azathioprine intake. PMID:24156226

  3. TRPV1-mediated presynaptic transmission in basolateral amygdala contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation

    PubMed Central

    Xiao, Ying; Chen, Xiaoqi; Zhang, Ping-An; Xu, Qiya; Zheng, Hang; Xu, Guang-Yin

    2016-01-01

    The central mechanisms of visceral hypersensitivity remain largely unknown. It’s reported that there are highest densities of TRPV1 labeled neurons within basolateral amygdala (BLA). The aim of this study was to explore the role and mechanisms of TRPV1 in BLA in development of visceral hypersensitivity. Visceral hypersensitivity was induced by neonatal maternal deprivation (NMD) and was quantified by abdominal withdrawal reflex. Expression of TRPV1 was determined by Western blot. The synaptic transmission of neurons in BLA was recorded by patch clamping. It was found that the expression of TRPV1 in BLA was significantly upregulated in NMD rats; glutamatergic synaptic activities in BLA were increased in NMD rats; application of capsazepine (TRPV1 antagonist) decreased glutamatergic synaptic activities of BLA neurons in NMD slices through a presynaptic mechanism; application of capsaicin (TRPV1 agonist) increased glutamatergic synaptic activities of BLA neurons in control slices through presynaptic mechanism without affecting GABAergic synaptic activities; microinjecting capsazepine into BLA significantly increased colonic distension threshold both in control and NMD rats. Our data suggested that upregulation of TRPV1 in BLA contributes to visceral hypersensitivity of NMD rats through enhancing excitation of BLA, thus identifying a potential target for treatment of chronic visceral pain. PMID:27364923

  4. TRPV1-mediated presynaptic transmission in basolateral amygdala contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation.

    PubMed

    Xiao, Ying; Chen, Xiaoqi; Zhang, Ping-An; Xu, Qiya; Zheng, Hang; Xu, Guang-Yin

    2016-01-01

    The central mechanisms of visceral hypersensitivity remain largely unknown. It's reported that there are highest densities of TRPV1 labeled neurons within basolateral amygdala (BLA). The aim of this study was to explore the role and mechanisms of TRPV1 in BLA in development of visceral hypersensitivity. Visceral hypersensitivity was induced by neonatal maternal deprivation (NMD) and was quantified by abdominal withdrawal reflex. Expression of TRPV1 was determined by Western blot. The synaptic transmission of neurons in BLA was recorded by patch clamping. It was found that the expression of TRPV1 in BLA was significantly upregulated in NMD rats; glutamatergic synaptic activities in BLA were increased in NMD rats; application of capsazepine (TRPV1 antagonist) decreased glutamatergic synaptic activities of BLA neurons in NMD slices through a presynaptic mechanism; application of capsaicin (TRPV1 agonist) increased glutamatergic synaptic activities of BLA neurons in control slices through presynaptic mechanism without affecting GABAergic synaptic activities; microinjecting capsazepine into BLA significantly increased colonic distension threshold both in control and NMD rats. Our data suggested that upregulation of TRPV1 in BLA contributes to visceral hypersensitivity of NMD rats through enhancing excitation of BLA, thus identifying a potential target for treatment of chronic visceral pain. PMID:27364923

  5. Hypersensitivity Pneumonitis.

    PubMed

    Wysong, Kristi; Phillips, Jennan A; Hammond, Stephanie

    2016-06-01

    Chronic exposure to a broad array of antigens after workers inhale aerosolized organic dust particles from mold, animal dander, bird droppings, and chemicals, especially pesticides or herbicides, increases risk for hypersensitivity pneumonitis. Several demographic characteristics of immigrant workers in farming, poultry processing, construction, and landscaping increase this worker population's risk. PMID:27067273

  6. Presence of corrosion products and hypersensitivity-associated reactions in periprosthetic tissue after aseptic loosening of total hip replacements with metal bearing surfaces.

    PubMed

    Huber, Monika; Reinisch, Georg; Trettenhahn, Günter; Zweymüller, Karl; Lintner, Felix

    2009-01-01

    Aseptic loosening of articular implants is frequently associated with tissue reactions to wear particles. Some patients, who had received metal-on-metal articulations, present early symptoms including persistent pain and implant failure. These symptoms raise the suspicion about the development of an immunological response. Furthermore, the generation of rare corrosion products in association with metallic implants has been observed. Corrosion products are known to enhance third-body wear and contribute to the loss of the implant. The purpose of this study was to investigate periprosthetic tissue containing solid corrosion products after aseptic loosening of second-generation metal-on-metal total hip replacements made of low-carbon cobalt-chromium-molybdenum alloy for the presence of immunologically determined tissue changes. Periprosthetic tissue of 11 cases containing uncommon solid deposits was investigated by light microscopy. In order to confirm the presence of corrosion products, additional methods including scanning electron microscopy (SEM) investigation, energy dispersive X-ray (EDX) and Fourier transform infrared microspectroscopy (FTIR) analysis were used. All investigated cases revealed solid chromium orthophosphate corrosion products as well as metallic wear particles to a various extent. Moreover, various intense tissue reactions characteristic of immune response were observed in all cases. The simultaneous presence of corrosion products and hypersensitivity-associated tissue reaction indicates that a relationship between corrosion development and implant-related hypersensitivity may exist. PMID:18725188

  7. Real-time PCR mapping of DNaseI-hypersensitive sites using a novel ligation-mediated amplification technique

    PubMed Central

    Follows, George A.; Janes, Mary E.; Vallier, Ludovic; Green, Anthony R.; Gottgens, Berthold

    2007-01-01

    Mapping sites within the genome that are hypersensitive to digestion with DNaseI is an important method for identifying DNA elements that regulate transcription. The standard approach to locating these DNaseI-hypersensitive sites (DHSs) has been to use Southern blotting techniques, although we, and others, have recently published alternative methods using a range of technologies including high-throughput sequencing and genomic array tiling paths. In this article, we describe a novel protocol to use real-time PCR to map DHS. Advantages of the technique reported here include the small cell numbers required for each analysis, rapid, relatively low-cost experiments with minimal need for specialist equipment. Presented examples include comparative DHS mapping of known TAL1/SCL regulatory elements between human embryonic stem cells and K562 cells. PMID:17389645

  8. Nude mice produce a T cell-derived antigen-binding factor that mediates the early component of delayed-type hypersensitivity.

    PubMed

    Herzog, W R; Meade, R; Pettinicchi, A; Ptak, W; Askenase, P W

    1989-03-15

    The elicitation of delayed-type hypersensitivity (DTH) reactions in mice is caused by the sequential action of two different T cells. An early-acting, DTH-initiating T cell produces an Ag-specific T cell factor, that is analogous to IgE antibody and initiates DTH by sensitizing the local tissues for release of the vasoactive amine serotonin. In picryl chloride or oxazolone contact sensitivity, this T cell factor is Ag-specific, but MHC unrestricted. We, therefore, hypothesized that DTH-initiating T cells are primitive T cells with Ag receptors that can bind Ag without MHC restriction. In order to characterize the origin of this DTH-initiating T cell and the conditions that are necessary for its development, we contact-sensitized various strains of immunodeficient mice. Surprisingly, we found that the early phase of DTH was present in athymic nude mice. In contrast, the early component of DTH was absent in mice with severe combined immunodeficiency. These mice lack T and B cells, but have NK cells. These findings suggested that the early component of DTH was not caused by NK cells, and was caused by cells belonging to a lineage from a rearranging gene family. The early component of DTH in nude mice was Ag specific, was caused by MHC unrestricted Thy-1+ T cells, and was mediated by Ag-binding, Ag-specific T cell factors. We found that DTH-initiating, T cell-derived, Ag-binding molecules from nude mice and normal CBA/J mice had the same functional properties. The early component of DTH was elicited in two different systems (contact sensitivity and SRBC-specific DTH) in two strains of nude mice (BALB/c athymic nudes and CByB6F1/J-nu) from two different suppliers, but not in BALB/c and athymic nudes from a third supplier. From these findings we concluded that DTH-initiating T cells, which produce IgE-like Ag-specific T cell factors, are present in some strains of athymic nude mice and thus are relatively thymic independent T cells. PMID:2466077

  9. Sulfite hypersensitivity. A critical review

    SciTech Connect

    Gunnison, A.F.; Jacobsen, D.W.

    1987-01-01

    Sulfiting agents (sulfur dioxide and the sodium and potassium salts of bisulfite, sulfite, and metabisulfite) are widely used as preservatives in foods, beverages, and pharmaceuticals. Within the past 5 years, there have been numerous reports of adverse reactions to sulfiting agents. This review presents a comprehensive compilation and discussion of reports describing reactions to ingested, inhaled, and parenterally administered sulfite. Sulfite hypersensitivity is usually, but not exclusively, found within the chronic asthmatic population. Although there is some disagreement on its prevalence, a number of studies have indicated that 5 to 10% of all chronic asthmatics are sulfite hypersensitive. This review also describes respiratory sulfur dioxide sensitivity which essentially all asthmatics experience. Possible mechanisms of sulfite hypersensitivity and sulfur dioxide sensitivity are discussed in detail. Sulfite metabolism and the role of sulfite oxidase in the detoxification of exogenous sulfite are reviewed in relationship to the etiology of sulfite hypersensitivity. 147 references.

  10. The predictive value of the in vitro platelet toxicity assay (iPTA) for the diagnosis of hypersensitivity reactions to sulfonamides.

    PubMed

    Elzagallaai, Abdelbaset A; Koren, Gideon; Rieder, Michael J

    2013-06-01

    Drug hypersensitivity reactions (DHRs) are rare but potentially fatal adverse drug reactions (ADRs). A reliable test to diagnose DHRs would be a major advance in the clinical care for patients and in the evaluation of ADRs during drug development as well as for mechanistic studies of drug hypersensitivity. Available in vitro tests including the lymphocyte toxicity assay (LTA) have been used but are time-consuming, cumbersome, and expensive. We have developed a novel diagnostic test for DHRs, the in vitro platelet toxicity assay (iPTA). The aim of this study was to evaluate the predictive value of the iPTA in diagnosis of DHRs to sulfonamides. We recruited 66 individuals (36 DHS-sulfa patients and 30 healthy controls) to participate in the study. Blood samples were obtained and LTA and iPTA were performed in parallel. There was concentration-dependent toxicity in the cells of patients when incubated with the reactive hydroxylamine metabolite of sulfamethoxazole for both the LTA and iPTA (P < .05). The iPTA was more sensitive than conventional LTA test in detecting susceptibility of patient cells to in vitro toxicity (P < .05). The novel iPTA has considerable potential as an investigative tool for DHS as it is more sensitive and cheaper, requiring no special reagents. PMID:23670648

  11. Hypersensitivity to antineoplastic agents: mechanisms and treatment with rapid desensitization.

    PubMed

    Castells, Mariana; Sancho-Serra, Maria del Carmen; Simarro, Maria

    2012-09-01

    Hypersensitivity reactions (HSRs) to chemotherapy drugs, such as taxanes and platins, and to monoclonal antibodies limit their therapeutic use due to the severity of some reactions and the fear of inducing a potentially lethal reaction in highly sensitized patients. Patients who experience hypersensitivity reactions face the prospect of abandoning first-line treatment and switching to a second-line, less effective therapy. Some of these reactions are mast cell-mediated hypersensitivity reactions, a subset of which occur through an immunoglobulin (IgE)-dependent mechanism, and are thus true allergies. Others involve mast cells without a demonstrable IgE mechanism. Whether basophils can participate in these reactions has not been demonstrated. Rapid drug desensitization (RDD) is a procedure that induces temporary tolerance to a drug, allowing a medication allergic patient to receive the optimal agent for his or her disease. Through RDD, patients with IgE and non-IgE HSRs can safely be administered important medications while minimizing or completely inhibiting adverse reactions. Due to the clinical expansion and success of RDD, the molecular mechanisms inducing the temporary tolerization have been investigated and are partially understood, allowing for safer and more effective protocols. This article reviews the current literature on molecular mechanisms of RDD with an emphasis in our recent contributions to this field as well as the indications, methods and outcomes of RDD for taxanes, platins, and monoclonal antibodies. PMID:22576054

  12. Antibody-mediated cofactor-driven reactions

    DOEpatents

    Schultz, Peter G.

    1993-01-01

    Chemical reactions capable of being rate-enhanced by auxiliary species which interact with the reactants but do not become chemically bound to them in the formation of the final product are performed in the presence of antibodies which promote the reactions. The antibodies contain regions within their antigen binding sites which recognize the auxiliary species in a conformation which promotes the reaction. The antigen binding site frequently recognizes a particular transition state complex or other high energy complex along the reaction coordinate, thereby promoting the progress of the reaction along the desired route as opposed to other less favorable routes. Various classes of reaction together with appropriate antigen binding site specificities tailored for each are disclosed.

  13. Immunologic Evaluation of Immediate Hypersensitivity to Cefaclor

    PubMed Central

    Yoo, Hye-Soo; Kim, Seung-Hyun; Kwon, Hyouk-Soo; Kim, Tae-Bum; Nam, Young-Hee; Ye, Young-Min

    2014-01-01

    Purpose Cefaclor is widely prescribed for various infectious diseases. As its consumption increases, the number of hypersensitivity reactions to cefaclor has increased. This study aimed to evaluate the immunologic findings of immediate hypersensitivity to cefaclor. Materials and Methods We enrolled 47 patients with immediate hypersensitivity to cefaclor from Ajou University Hospital and Asan Medical Center. Serum specific IgE, IgG1, and IgG4 antibodies to cefaclor-human serum albumin (HSA) conjugate were measured by enzyme-linked immunosorbent assay (ELISA). Results The most common phenotype was anaphylaxis (Group I, 78.7%), followed by urticaria (Group II, 21.3%). The detection of specific IgE, IgG1, and IgG4 to cefaclor-HSA conjugate by ELISA tended to be higher in Group I (40.5%, 41.7%, 21.6%) than in Group II (20.0%, 20.0%, 0%) with no statistical significance. Significant associations were found between specific IgE and IgG1 or IgG4 (p<0.001, p=0.019). ELISA inhibition tests showed significant inhibitions by both free cefaclor and cefaclor-HSA conjugate. For basophil activation tests in patients having no specific IgE antibody, the CD63 expression level on basophils increased with incubations of free cefaclor. Conclusion The most common manifestation of immediate hypersensitivity to cefaclor was anaphylaxis, most of which was mediated by IgE; however, a non-IgE mediated direct basophil activation mechanism was suggested in a subset of anaphylaxis patients. PMID:25323882

  14. Sensitization of P2X3 receptors by cystathionine β-synthetase mediates persistent pain hypersensitivity in a rat model of lumbar disc herniation.

    PubMed

    Wang, Qianliang; Zhu, Hongyan; Zou, Kang; Yuan, Bo; Zhou, You-Lang; Jiang, Xinghong; Yan, Jun; Xu, Guang-Yin

    2015-01-01

    Lumbar disc herniation (LDH) is a major cause of discogenic low back pain and sciatica, but the underlying mechanisms remain largely unknown. Hydrogen sulfide (H2S) is becoming recognized for its involvement in a wide variety of processes including inflammation and nociception. The present study was designed to investigate the roles of the H2S signaling pathway in the regulation of expression and function of purinergic receptors (P2XRs) in dorsal root ganglion (DRG) neurons from rats with LDH. LDH was induced by implantation of autologous nucleus pulposus (NP), harvested from rat tail, in lumbar 5 and 6 spinal nerve roots. Implantation of autologous NP induced persistent pain hypersensitivity, which was partially reversed by an intrathecal injection of A317491, a potent inhibitor of P2X3Rs and P2X2/3Rs. The NP induced persistent pain hypersensitivity was associated with the increased expression of P2X3Rs, but not P2X1Rs and P2X2Rs, receptors in L5-6 DRGs. NP implantation also produced a 2-fold increase in ATP-induced intracellular calcium signals in DRG neurons when compared to those of controls (P < 0.05). Interestingly, NP implantation significantly enhanced expression of the endogenous hydrogen sulfide producing enzyme, cystathionine-β-synthetase (CBS). Systematic administration of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA), an inhibitor of CBS, suppressed the upregulation of P2X3R expression and the potentiation of ATP-induced intracellular calcium signals in DRG neurons (P < 0.05). Intrathecal injection of AOAA markedly attenuated NP induced- persistent pain hypersensitivity. Our results suggest that sensitization of P2X3Rs, which is likely mediated by CBS-H2S signaling in primary sensory neurons, contributes to discogenic pain. Targeting CBS/H2S-P2X3R signaling may represent a potential treatment for neuropathic pain caused by LDH. PMID:25885215

  15. Intact subepidermal nerve fibers mediate mechanical hypersensitivity via the activation of protein kinase C gamma in spared nerve injury

    PubMed Central

    Ko, Miau-Hwa; Yang, Ming-Ling; Youn, Su-Chung; Tseng, To-Jung

    2016-01-01

    Background Spared nerve injury is an important neuropathic pain model for investigating the role of intact primary afferents in the skin on pain hypersensitivity. However, potential cellular mechanisms remain poorly understood. In phosphoinositide-3 kinase pathway, pyruvate dehydrogenase kinase 1 (PDK1) participates in the regulation of neuronal plasticity for central sensitization. The downstream cascades of PDK1 include: (1) protein kinase C gamma (PKCγ) controls the trafficking and phosphorylation of ionotropic glutamate receptor; (2) protein kinase B (Akt)/the mammalian target of rapamycin (mTOR) signaling is responsible for local protein synthesis. Under these statements, we therefore hypothesized that an increase of PKCγ activation and mTOR-dependent PKCγ synthesis in intact primary afferents after SNI might contribute to pain hypersensitivity. Results The variants of spared nerve injury were performed in Sprague-Dawley rats by transecting any two of the three branches of the sciatic nerve, leaving only one branch intact. Following SNIt (spared tibial branch), mechanical hyperalgesia and mechanical allodynia, but not thermal hyperalgesia, were significantly induced. In the first footpad, normal epidermal innervations were verified by the protein gene product 9.5 (PGP9.5)- and growth-associated protein 43 (GAP43)-immunoreactive (IR) intraepidermal nerve fibers (IENFs) densities. Furthermore, the rapid increases of phospho-PKCγ- and phospho-mTOR-IR subepidermal nerve fibers (SENFs) areas were distinct gathered from the results of PGP9.5-, GAP43-, and neurofilament 200 (NF200)-IR SENFs areas. The efficacy of PKC inhibitor (GF 109203X) or mTOR complex 1 inhibitor (rapamycin) for attenuating mechanical hyperalgesia and mechanical allodynia by intraplantar injection was dose-dependent. Conclusions From results obtained in this study, we strongly recommend that the intact SENFs persistently increase PKCγ activation and mTOR-dependent PKCγ synthesis participate

  16. A redox-mediated chromogenic reaction and application in immunoassay.

    PubMed

    Yu, Ru-Jia; Ma, Wei; Peng, Mao-Pan; Bai, Zhi-Shan; Long, Yi-Tao

    2016-08-31

    A novel redox-mediated chromogenic reaction was demonstrated based on the reaction between HAuCl4 and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), which generate various color responses from red to green in the resulting solutions. Various redox substance could be used to mediate the reaction and trigger a distinct color response. We established a sensitive hydrogen peroxide colorimetric sensor based on the redox-mediated chromogenic reaction and depicted the application both in detection of enzyme and in an immunoassay. Combining the traditional chromogenic reagent with gold nanoparticles, our assay has the advantage in short response time (within three minutes), high sensitivity (10(-12) g mL(-1) for HBsAg) and stability. PMID:27506364

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

    PubMed Central

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

    1998-01-01

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

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

    PubMed

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

    1998-06-01

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

  19. Hypersensitivity to contrast media and dyes.

    PubMed

    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. PMID:25017677

  20. DWD HYPERSENSITIVE TO UV-B 1 is negatively involved in UV-B mediated cellular responses in Arabidopsis.

    PubMed

    Kim, Sang-Hoon; Kim, Hani; Seo, Kyoung-In; Kim, Soon-Hee; Chung, Sunglan; Huang, Xi; Yang, Panyu; Deng, Xing Wang; Lee, Jae-Hoon

    2014-12-01

    Among T-DNA insertion mutants of various cullin4-RING ubiquitin E3 ligase (CRL4) substrate receptors, one mutant that exhibits enhanced sensitivity in response to ultraviolet-B (UV-B) illumination has been isolated and its corresponding gene has been named DWD HYPERSENSITIVE TO UV-B 1 (DHU1) in Arabidopsis. dhu1 lines showed much shorter hypocotyls than those in wild type under low doses of UV-B. Other light did not alter hypocotyl growth patterns in dhu1, indicating the hypersensitivity of dhu1 is restricted to UV-B. DHU1 was upregulated by more than two times in response to UV-B application of 1.5 μmol m(-2) s(-1), implying its possible involvement in UV-B signaling. DHU1 is able to bind to DDB1, an adaptor of CRL4; accordingly, DHU1 is thought to act as a substrate receptor of CRL4. Microarray data generated from wild-type and dhu1 under low doses of UV-B revealed that 209 or 124 genes were upregulated or downregulated by more than two times in dhu1 relative to wild type, respectively. About 23.4 % of the total upregulated genes in dhu1 were upregulated by more than five times in response to UV-B based on the AtGenExpress Visualization Tool data, while only about 1.4 % were downregulated to the same degree by UV-B, indicating that loss of DHU1 led to the overall enhancement of the upregulation of UV-B inducible genes. dhu1 also showed altered responsiveness under high doses of UV-B. Taken together, these findings indicate that DHU1 is a potent CRL4 substrate receptor that may function as a negative regulator of UV-B response in Arabidopsis. PMID:25193399

  1. The Absence of CYP3A5*3 Is a Protective Factor to Anticonvulsants Hypersensitivity Reactions: A Case-Control Study in Brazilian Subjects

    PubMed Central

    dos Santos, Bernardo; Talib, Leda Leme; Yamaguti, Célia; Rodrigues, Helcio; Gattaz, Wagner Farid; Kalil, Jorge

    2015-01-01

    Although aromatic anticonvulsants are usually well tolerated, they can cause cutaneous adverse drug reactions in up to 10% of patients. The clinical manifestations of the antiepileptics-induced hypersensitivity reactions (AHR) vary from mild skin rashes to severe cutaneous drug adverse reactions which are related to high mortality and significant morbidity. Genetic polymorphisms in cytochrome P450 genes are associated with altered enzymatic activity and may contribute to the risk of AHR. Here we present a case-control study in which we genotyped SNPs of CYP2C19, 2C9 and 3A5 of 55 individuals with varying severities of AHR, 83 tolerant, and 366 healthy control subjects from São Paulo, Brazil. Clinical characterization was based on standardized scoring systems and drug patch test. All in vivo investigation followed the ENDA (European Network of Drug Allergy) recommendations. Genotype was determined by real time PCR using peripheral blood DNA as a template. Of all 504 subjects, 65% were females, 45% self-identified as Afro-American, 38% as Caucasian and 17% as having non-African mixed ascendancy. Amongst 55 subjects with AHR, 44 had severe cutaneous drug adverse reactions. Of the 46 drug patch tests performed, 29 (63%) were positive. We found a strong association between the absence of CYP3A5*3 and tolerant subjects when compared to AHR (p = 0.0002, OR = 5.28 [CI95% 2.09–14.84]). None of our groups presented positive association with CYP2C19 and 2C9 polymorphisms, however, both SNPs contributed to separation of cases and tolerants in a Classification and Regression Tree. Our findings indicate that drug metabolism genes can contribute in the tolerability of antiepileptics. CYP3A5*3 is the most prevalent CYP3A5 allele associated with reduced enzymatic function. The current study provides evidence that normal CYP3A5 activity might be a protective factor to aromatic antiepileptics-induced hypersensitivity reactions in Brazilian subjects. PMID:26291084

  2. Murine eosinophils labeled with indium-111 oxine: localization to delayed hypersensitivity reactions against a schistosomal antigen and to lymphokine in vivo

    SciTech Connect

    Rand, T.H.; Clanton, J.A.; Runge, V.; English, D.; Colley, D.G.

    1983-04-01

    We have evaluated a method for quantitation of eosinophil migration to stimuli in vivo. Upon transfusion into normal syngeneic mice, 111In-labeled eosinophils had an intravascular half-life of 9.5 hr and distributed predominantly into spleen, bone marrow, and liver. In either Schistosoma mansoni-infected mice or recipients of lymphoid cells from infected mice, intradermal (ear pinna) injection of the schistosomal egg antigenic preparation (SEA) elicited time-dependent accumulation of 111In-labeled eosinophils detectable by either gamma scintillation counting of tissue samples or by nuclear medicine external imaging. Intradermal administration of a lymphokine fraction (containing eosinophil stimulation promoter activity) similarly caused accumulation of 111In-labeled eosinophils. Both reactions depended on the concentration of stimulus (SEA or lymphokine). 111In-labeled neutrophils or macrophages or 125I-albumin did not preferentially accumulate at the reactions examined to the extent found with 111In-labeled eosinophils, indicating that localization of label depends on an active process and is due to eosinophils rather than a contaminating cell type. The method was used to estimate how long eosinotactic lymphokine remained at dermal sites: 60% of initial activity was present 12 hr after injection. The model is discussed with regard to the role of lymphokines in hypersensitivity reactions with eosinophil involvement, such as the granulomatous response to S. mansoni eggs.

  3. Unique microRNAs appear at different times during the course of a delayed-type hypersensitivity reaction in human skin.

    PubMed

    Gulati, Nicholas; Løvendorf, Marianne B; Zibert, John R; Akat, Kemal M; Renwick, Neil; Tuschl, Thomas; Krueger, James G

    2015-12-01

    Diphencyprone (DPCP) is a hapten that induces delayed-type hypersensitivity (DTH) reactions. MicroRNAs (miRNAs) are short non-coding RNAs that negatively regulate gene expression and have been implicated in various inflammatory skin diseases, but their role in DTH reactions is not well understood. We generated global miRNA expression profiles (using next-generation sequencing) of DPCP reactions in skin of seven healthy volunteers at 3, 14 and 120 days after challenge. Compared to placebo-treated sites, DPCP-challenged skin at 3 days (peak inflammation) had 127 miRNAs significantly deregulated. At 14 days (during resolution of inflammation), 43 miRNAs were deregulated and, at 120 days (when inflammation had completely resolved), six miRNAs were upregulated. While some miRNAs have been observed in psoriasis or atopic dermatitis, most of the deregulated miRNAs have not yet been studied in the context of skin biology or immunology. Across the three time points studied, many but not all miRNAs were uniquely expressed. As various miRNAs may influence T cell activation, this may indicate that the miRNAs exclusively expressed at different time points function to promote or resolve skin inflammation, and therefore, may inform on the paradoxical ability of DPCP to treat both autoimmune conditions (alopecia areata) and conditions of ineffective immunity (melanoma). PMID:26205579

  4. SbF(5)-mediated reactions of oxafluorodiazirines.

    PubMed

    Moss, R A; Fedé, J M; Yan, S

    2001-07-26

    [reaction: see text] The reaction of benzyloxyfluorodiazirine (3) with SbF(5) in benzene gives PhCH(2)OCF, which undergoes SbF(5)-mediated fragmentation to PhCH(2)(+), CO, and SbF(6)(-); the benzyl cation alkylates benzene to yield diphenylmethane. Phenoxyfluorodiazirine (4) reacts with SbF(5) in benzene to give PhOCF and (ultimately) triphenylmethane by a pathway that avoids fragmentation. PMID:11463302

  5. Phospholipase D-mediated hypersensitivity at central synapses is associated with abnormal behaviours and pain sensitivity in rats exposed to prenatal stress.

    PubMed

    Sun, Liting; Gooding, Hayley L; Brunton, Paula J; Russell, John A; Mitchell, Rory; Fleetwood-Walker, Sue

    2013-11-01

    Adverse events at critical stages of development can lead to lasting dysfunction in the central nervous system (CNS). To seek potential underlying changes in synaptic function, we used a newly developed protocol to measure alterations in receptor-mediated Ca(2+) fluorescence responses of synaptoneurosomes, freshly isolated from selected regions of the CNS concerned with emotionality and pain processing. We compared adult male controls and offspring of rats exposed to social stress in late pregnancy (prenatal stress, PS), which showed programmed behavioural changes indicating anxiety, anhedonia and pain hypersensitivity. We found corresponding increases, in PS rats compared with normal controls, in responsiveness of synaptoneurosomes from frontal cortex to a glutamate receptor (GluR) agonist, and from spinal cord to activators of nociceptive afferents. Through a combined pharmacological and biochemical strategy, we found evidence for a role of phospholipase D1 (PLD1)-mediated signalling, that may involve 5-HT2A receptor (5-HT2AR) activation, at both levels of the nervous system. These changes might participate in underpinning the enduring alterations in behaviour induced by PS. PMID:23932932

  6. Hypersensitive Response-Like Reaction Is Associated with Hybrid Necrosis in Interspecific Crosses between Tetraploid Wheat and Aegilops tauschii Coss

    PubMed Central

    Mizuno, Nobuyuki; Hosogi, Naoki; Park, Pyoyun; Takumi, Shigeo

    2010-01-01

    Background Hybrid speciation is classified into homoploid and polyploid based on ploidy level. Common wheat is an allohexaploid species that originated from a naturally occurring interploidy cross between tetraploid wheat and diploid wild wheat Aegilops tauschii Coss. Aegilops tauschii provides wide naturally occurring genetic variation. Sometimes its triploid hybrids with tetraploid wheat show the following four types of hybrid growth abnormalities: types II and III hybrid necrosis, hybrid chlorosis, and severe growth abortion. The growth abnormalities in the triploid hybrids could act as postzygotic hybridization barriers to prevent formation of hexaploid wheat. Methodology/Principal Findings Here, we report on the geographical and phylogenetic distribution of Ae. tauschii accessions inducing the hybrid growth abnormalities and showed that they are widely distributed across growth habitats in Ae. tauschii. Molecular and cytological characterization of the type III necrosis phenotype was performed. The hybrid abnormality causing accessions were widely distributed across growth habitats in Ae. tauschii. Transcriptome analysis showed that a number of defense-related genes such as pathogenesis-related genes were highly up-regulated in the type III necrosis lines. Transmission electron microscope observation revealed that cell death occurred accompanied by generation of reactive oxygen species in leaves undergoing type III necrosis. The reduction of photosynthetic activity occurred prior to the appearance of necrotic symptoms on the leaves exhibiting hybrid necrosis. Conclusions/Significance Taking these results together strongly suggests that an autoimmune response might be triggered by intergenomic incompatibility between the tetraploid wheat and Ae. tauschii genomes in type III necrosis, and that genetically programmed cell death could be regarded as a hypersensitive response-like cell death similar to that observed in Arabidopsis intraspecific and Nicotiana

  7. Chemical reaction mediated self-assembly of PTCDA into nanofibers.

    PubMed

    Sayyad, Arshad S; Balakrishnan, Kaushik; Ajayan, Pulickel M

    2011-09-01

    Uniform and crystalline nanofibers of perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA), an insoluble organic semiconducting molecule, have been achieved by self-assembling the molecules using chemical reaction mediated conversion of an appropriately designed soluble precursor, perylene tetracarboxylic acid (PTCA) using carbodiimide chemistry. PMID:21814688

  8. Investigation of immune and CNS-mediated effects of fingolimod in the focal delayed-type hypersensitivity multiple sclerosis model.

    PubMed

    Anthony, Daniel C; Sibson, Nicola R; Losey, Patrick; Meier, Daniela Piani; Leppert, David

    2014-04-01

    We examined the effect of fingolimod (0.1 and 0.3 mg/kg/day orally) on blood-brain barrier (BBB) function, demyelination and leukocyte recruitment at different stages of the focal delayed-type hypersensitivity (DTH) multiple sclerosis model in Lewis rats using immunohistochemistry and gadolinium (Gd)-enhancing magnetic resonance imaging (MRI). During DTH lesion formation, fingolimod reduced BBB breakdown (52%; p = 0.05), and lymphocyte (53%; p = 0.016) and macrophage/activated microglia (49%; p = 0.002) recruitment to the DTH lesion compared with vehicle-treated controls. Following DTH lesion establishment, fingolimod reduced the area of BBB breakdown (75%; p = 0.04), lymphocyte recruitment to the DTH lesion (41%; p = 0.01) and activated microglia outside of the lesion core (p = 0.01), but did not reduce recruitment of macrophages/activated microglia within the DTH lesion. During the chronic disease phase, when the BBB was resealed, fingolimod reduced the area of demyelination by 43% (p = 0.019) compared with vehicle-treated controls, while not affecting lymphocyte recruitment within the lesion. Fingolimod had different beneficial effects during different stages of DTH, reducing BBB breakdown and lesion development/brain tissue damage whilst reducing lymphocyte recruitment when BBB breakdown was apparent, but reducing demyelination independent of lymphocyte infiltration behind an intact BBB. These results suggest a direct CNS effect of fingolimod in this model. PMID:24412675

  9. Enhancement of delayed hypersensitivity inflammatory reactions in guinea pig skin by 12(R)-hydroxy-5,8,14-eicosatrienoic acid.

    PubMed

    Conners, M S; Schwartzman, M L; Quan, X; Heilman, E; Chauhan, K; Falck, J R; Godfrey, H P

    1995-01-01

    Delayed-type hypersensitivity (DTH) reactions are initiated by sensitized T cells. Their progression is dependent upon the local release of various autacoids, including cytokines and eicosanoids, by T cells, infiltrating inflammatory cells, and resident tissue cells. 12(R)-hydroxy-5,8,14-eicosatrienoic acid [12(R)-HETrE], an eicosanoid produced by skin and cornea, possesses potent proinflammatory properties at picomolar concentrations including vasodilation, increase in membrane permeability, neutrophil chemotaxis, and angiogenesis. Because DTH reactions are associated with many of these same phenomena, we examined the effect of 12(R)-HETrE and related 12-hydroxyeicosanoids on the expression of DTH to purified protein derivative of tuberculin in sensitized guinea pigs. In the absence of purified protein derivative of tuberculin, none of the eicosanoids evoked erythema or edema after intradermal injection at doses up to 100 pmol. When injected together with purified protein derivative of tuberculin, 12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid [12(R)-HETE], but not its enantiomer 12(S)-HETE, significantly inhibited macroscopic expression of delayed reactivity (erythema) only at the highest dose tested, 10 pmol. In contrast, 12(R)-HETrE significantly enhanced expression of DTH at doses between 1 fmol and 1 pmol (50% and 30% increases above control, respectively). Its stereoisomer, 12(S)-HETrE, did not enhance DTH at any tested dose, but was able to block the activity of 12(R)-HETrE when injected simultaneously. Enhancement or inhibition of visible skin responses was not associated with qualitative or quantitative changes in cellular infiltrates at the reaction site. 12(R)-HETrE had no effect on the nonimmunologic inflammatory skin reaction induced by phorbol myristate acetate, suggesting selectivity toward DTH. We conclude that 12(R)-HETrE enhances DTH via a yet to be determined mechanism and that its stereoisomer, 12(S)-HETrE, may be a useful antagonist for

  10. Drug hypersensitivity syndrome.

    PubMed

    Kumari, Rashmi; Timshina, Dependra K; Thappa, Devinder Mohan

    2011-01-01

    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. PMID:21220873

  11. Lesions in the mRNA cap-binding gene ABA HYPERSENSITIVE 1 suppress FRIGIDA-mediated delayed flowering in Arabidopsis.

    PubMed

    Bezerra, Isabel C; Michaels, Scott D; Schomburg, Fritz M; Amasino, Richard M

    2004-10-01

    Recessive mutations that suppress the late-flowering phenotype conferred by FRIGIDA (FRI) and FLOWERING LOCUS C (FLC) and which also result in serrated leaf morphology were identified in T-DNA and fast-neutron mutant populations. Molecular analysis showed that the mutations are caused by lesions in the gene encoding the large subunit of the nuclear mRNA cap-binding protein, ABH1 (ABA hypersensitive1). The suppression of late flowering is caused by the inability of FRI to increase FLC mRNA levels in the abh1 mutant background. The serrated leaf morphology of abh1 is similar to the serrate (se) mutant and, like abh1, se is also a suppressor of FRI-mediated late flowering although it is a weaker suppressor than abh1. Unlike se, in abh1 the rate of leaf production and the number of juvenile leaves are not altered. The abh1 lesion affects several developmental processes, perhaps because the processing of certain mRNAs in these pathways is more sensitive to loss of cap-binding activity than the majority of cellular mRNAs. PMID:15361145

  12. Spinal 5-HT3 receptors mediate descending facilitation and contribute to behavioral hypersensitivity via a reciprocal neuron-glial signaling cascade

    PubMed Central

    2014-01-01

    Background It has been recently recognized that the descending serotonin (5-HT) system from the rostral ventromedial medulla (RVM) in the brainstem and the 5-HT3 receptor subtype in the spinal dorsal horn are involved in enhanced descending pain facilitation after tissue and nerve injury. However, the mechanisms underlying the activation of the 5-HT3 receptor and its contribution to facilitation of pain remain unclear. Results In the present study, activation of spinal 5-HT3 receptors by intrathecal injection of a selective 5-HT3 receptor agonist SR 57227 induced spinal glial hyperactivity, neuronal hyperexcitability and pain hypersensitivity in rats. We found that there was neuron-to-microglia signaling via the chemokine fractalkine, microglia to astrocyte signaling via cytokine IL-18, astrocyte to neuronal signaling by IL-1β, and enhanced activation of NMDA receptors in the spinal dorsal horn. Glial hyperactivation in spinal dorsal horn after hindpaw inflammation was also attenuated by molecular depletion of the descending 5-HT system by intra-RVM Tph-2 shRNA interference. Conclusions These findings offer new insights into the cellular and molecular mechanisms at the spinal level responsible for descending 5-HT-mediated pain facilitation during the development of persistent pain after tissue and nerve injury. New pain therapies should focus on prime targets of descending facilitation-induced glial involvement, and in particular the blocking of intercellular signaling transduction between neurons and glia. PMID:24913307

  13. Chronic loss of noradrenergic tone produces β-arrestin2-mediated cocaine hypersensitivity and alters cellular D2 responses in the nucleus accumbens.

    PubMed

    Gaval-Cruz, Meriem; Goertz, Richard B; Puttick, Daniel J; Bowles, Dawn E; Meyer, Rebecca C; Hall, Randy A; Ko, Daijin; Paladini, Carlos A; Weinshenker, David

    2016-01-01

    Cocaine blocks plasma membrane monoamine transporters and increases extracellular levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT). The addictive properties of cocaine are mediated primarily by DA, while NE and 5-HT play modulatory roles. Chronic inhibition of dopamine β-hydroxylase (DBH), which converts DA to NE, increases the aversive effects of cocaine and reduces cocaine use in humans, and produces behavioral hypersensitivity to cocaine and D2 agonism in rodents, but the underlying mechanism is unknown. We found a decrease in β-arrestin2 (βArr2) in the nucleus accumbens (NAc) following chronic genetic or pharmacological DBH inhibition, and overexpression of βArr2 in the NAc normalized cocaine-induced locomotion in DBH knockout (Dbh -/-) mice. The D2/3 agonist quinpirole decreased excitability in NAc medium spiny neurons (MSNs) from control, but not Dbh -/- animals, where instead there was a trend for an excitatory effect. The Gαi inhibitor NF023 abolished the quinpirole-induced decrease in excitability in control MSNs, but had no effect in Dbh -/- MSNs, whereas the Gαs inhibitor NF449 restored the ability of quinpirole to decrease excitability in Dbh -/- MSNs, but had no effect in control MSNs. These results suggest that chronic loss of noradrenergic tone alters behavioral responses to cocaine via decreases in βArr2 and cellular responses to D2/D3 activation, potentially via changes in D2-like receptor G-protein coupling in NAc MSNs. PMID:25123018

  14. Phenylalanine ammonia-lyase in tobacco. Molecular cloning and gene expression during the hypersensitive reaction to tobacco mosaic virus and the response to a fungal elicitor.

    PubMed Central

    Pellegrini, L; Rohfritsch, O; Fritig, B; Legrand, M

    1994-01-01

    A tobacco (Nicotiana tabacum L. cv Samsun NN) cDNA clone coding the enzyme phenylalanine ammonia-lyase (PAL) was isolated from a cDNA library made from polyadenylated RNA purified from tobacco mosaic virus (TMV)-infected leaves. Southern analysis indicated that, in tobacco, PAL is encoded by a small family of two to four unclustered genes. Northern analysis showed that PAL genes are weakly expressed under normal physiological conditions, they are moderately and transiently expressed after wounding, but they are strongly induced during the hypersensitive reaction to TMV or to a fungal elicitor. Ribonuclease protection experiments confirmed this evidence and showed the occurrence of two highly homologous PAL messengers originating from a single gene or from two tightly co-regulated genes. By in situ RNA-RNA hybridization PAL transcripts were shown to accumulate in a narrow zone of leaf tissue surrounding necrotic lesions caused by TMV infection or treatment with the fungal elicitor. In this zone, no cell specificity was observed and there was a decreasing gradient of labeling from the edge of necrosis. Some labeling was also found in various cell types of young, healthy stems and was shown to accumulate in large amounts in the same cell types after the deposition of an elicitor solution at the top of the decapitated plant. PMID:7824656

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

    PubMed

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

    2016-01-01

    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. PMID:26782790

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

    PubMed Central

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

    2016-01-01

    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. PMID:26782790

  17. ABA-HYPERSENSITIVE BTB/POZ PROTEIN 1 functions as a negative regulator in ABA-mediated inhibition of germination in Arabidopsis.

    PubMed

    Kim, Hani; Kim, Soon-Hee; Seo, Dong Hye; Chung, Sunglan; Kim, Sang-Woo; Lee, Jeong-Soo; Kim, Woo Taek; Lee, Jae-Hoon

    2016-02-01

    To elucidate the contribution of CRL3-ABA-mediated responses, we attempted to find CRL3 substrate receptors involved in ABA signaling. One gene named ABA-HYPERSENSITIVE BTB/POZ PROTEIN 1 (AHT1) was upregulated more than 2.5 times by ABA, and its coding region possessed a BTB/POZ domain, which is the common feature of CRL3 substrate receptors. Loss of AHT1 led to retardation of the germination process, not inhibition of root growth. AHT1 transcripts also increased in response to mannitol, NaCl and drought treatments at the seedling stage and in dry seeds. High expression of AHT1 in dry seeds was inhibited by the defect of ABA signaling components such as ABI1, ABI3 and SRKs indicating that the expression of AHT1 is dependent on ABA signaling. Among bZIP transcription factors participating in ABA signaling, the losses of ABI5/DPBF1, AREB1/ABF2, EEL/DPBF4 and DPBF2/bZIP67 resulted in reduced AHT1 expression, showing that these transcription factors play a positive role in ABA-induced AHT1 expression. While loss of AHT1 did not affect the expression pattern of NCED3, ABI2, SRKs and AREB/ABF genes, it led to hyperinduction of ABI5/DPBF genes such as ABI5/DPBF1, EEL/DPBF4 and AREB3/DPBF3, which are mainly involved in seed development and germination, as well as ABA-inducible genes transactivated by ABI5. Overall, these findings indicate that AHT1 negatively regulates ABA-mediated inhibition of germination, possibly by repressing the expression of a subset of ABI5/DPBF subfamily genes, and that AHT1 may be regulated by a negative feedback process through its linkage with a part of ABI5/DPBF proteins. PMID:26667153

  18. Loss and Gain of Elicitor Function of Soybean Mosaic Virus G7 Provoking Rsv1-Mediated Lethal Systemic Hypersensitive Response Maps to P3

    PubMed Central

    Hajimorad, M. R.; Eggenberger, A. L.; Hill, J. H.

    2005-01-01

    Rsv1, a single dominant resistance gene in soybean PI 96983 (Rsv1), confers extreme resistance against all known American strains of Soybean mosaic virus (SMV), except G7 and G7d. SMV-G7 provokes a lethal systemic hypersensitive response (LSHR), whereas SMV-G7d, an experimentally evolved variant of SMV-G7, induces systemic mosaic. To identify the elicitor of Rsv1-mediated LSHR, chimeras were constructed by exchanging fragments between the molecularly cloned SMV-G7 (pSMV-G7) and SMV-G7d (pSMV-G7d), and their elicitor functions were assessed on PI 96983 (Rsv1). pSMV-G7-derived chimeras containing only P3 of SMV-G7d lost the elicitor function, while the reciprocal chimera of pSMV-G7d gained the function. The P3 regions of the two viruses differ by six nucleotides, of which two are translationally silent. The four amino acid differences are located at positions 823, 915, 953, and 1112 of the precursor polypeptide. Analyses of the site-directed point mutants of both the viruses revealed that nucleotide substitutions leading to translationally silent mutations as well as reciprocal amino acid substitution at position 915 did not influence the loss or gain of the elicitor function. pSMV-G7-derived mutants with amino acid substitutions at any of the other three positions lost the ability to provoke LSHR but induced SHR instead. Two concomitant amino acid substitutions at positions 823 (V to M) and 953 (K to E) abolished pSMV-G7 elicitor function, provoking Rsv1-mediated SHR. Conversely, pSMV-G7d gained the elicitor function of Rsv1-mediated LSHR by a single amino acid substitution at position 823 (M to V), and mutants with amino acid substitutions at position 953 or 1112 induced SHR instead of mosaic. Taken together, the data suggest that strain-specific P3 of SMV is the elicitor of Rsv1-mediated LSHR. PMID:15613348

  19. Occupational hypersensitivity pneumonitis: an EAACI position paper.

    PubMed

    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. PMID:26913451

  20. Hydrogen transfer in SAM-mediated enzymatic radical reactions.

    PubMed

    Hioe, Johnny; Zipse, Hendrik

    2012-12-14

    S-adenosylmethionine (SAM) plays an essential role in a variety of enzyme-mediated radical reactions. One-electron reduction of SAM is currently believed to generate the C5'-desoxyadenosyl radical, which subsequently abstracts a hydrogen atom from the actual substrate in a catalytic or a non-catalytic fashion. Using a combination of theoretical and experimental bond dissociation energy (BDE) data, the energetics of these radical processes have now been quantified. SAM-derived radicals are found to react with their respective substrates in an exothermic fashion in enzymes using SAM in a stoichiometric (non-catalytic) way. In contrast, the catalytic use of SAM appears to be linked to a sequence of moderately endothermic and exothermic reaction steps. The use of SAM in spore photoproduct lyase (SPL) appears to fit neither of these general categories and appears to constitute the first example of a SAM-initiated radical reaction propagated independently of the cofactor. PMID:23139189

  1. Antidrug antibodies against TNF-blocking agents: correlations between disease activity, hypersensitivity reactions, and different classes of immunoglobulins.

    PubMed

    Benucci, Maurizio; Li Gobbi, Francesca; Meacci, Francesca; Manfredi, Mariangela; Infantino, Maria; Severino, Maurizio; Testi, Sergio; Sarzi-Puttini, Piercarlo; Ricci, Cristian; Atzeni, Fabiola

    2015-01-01

    Although anti-TNF drugs have changed the clinical course of rheumatoid arthritis (RA), survival rates and resistance-to-therapy data confirm that about 30% of RA patients fail to respond. The aim of this study was to evaluate the correlations between the development of antidrug antibodies, specific IgG4 antibodies against TNF inhibitors, and resistance to therapy in RA patients. This retrospective study involved 129 patients with established RA naïve to biological agents (98 females and 32 males, mean age 56.7±12.3 years, disease duration 6.3±1.2 years, baseline Disease Activity Score [DAS]-28 3.2-5.6) who received treatment with anti-TNF agents after the failure of conventional disease-modifying antirheumatic drugs (32 received infliximab [IFX], 58 etanercept [ETN], and 39 adalimumab [ADA]). After 6 months of treatment, the patients were classified as being in remission (DAS28 <2.6), having low disease activity (LDA; DAS28 2.6-3.2), or not responding (NR: DAS28 >3.2). The patients were also tested for serum antidrug antibodies and IgG4 antibodies against TNF inhibitors. After 24 weeks of treatment, 38% of the ETN-treated patients and 28% of those treated with ADA had injection-site reactions; the rate of systemic reactions in the IFX group was 25%. The differences among the three groups were not statistically significant (P=0.382; ETN versus ADA P=0.319). The percentages of patients with adverse events stratified by drug response were: LDA 8% and NR 18% in the ADA group; in remission 3%, LDA 22%, and NR 10% in the ETN group; and LDA 6% and NR 16% in the IFX group (P=0.051). The percentages of patients with antidrug antibodies were: ADA 33.3%, ETN 11.5%, and IFX 10.3% (P=0.025; ADA versus ETN P=0.015). The percentages of patients with IgG4 antibodies were: ADA 6%, ETN 13%, and IFX 26% (P=0.017; ADA versus ETN P=0.437). Associations between antidrug antibodies, specific IgG4 antibodies, and adverse reactions were not significant for any of the three drugs. IgG4

  2. Statistical properties of multistep enzyme-mediated reactions

    SciTech Connect

    Nemenman, Ilya; Sinitsyn, Nikolai A; De Ronde, Wiet H; Daniels, Bryan C; Mugler, Andrew

    2008-01-01

    Enzyme-mediated reactions may proceed through multiple intermediate conformational states before creating a final product molecule, and one often wishes to identify such intermediate structures from observations of the product creation. In this paper, we address this problem by solving the chemical master equations for various enzymatic reactions. We devise a perturbation theory analogous to that used in quantum mechanics that allows us to determine the first () and the second (variance) cumulants of the distribution of created product molecules as a function of the substrate concentration and the kinetic rates of the intermediate processes. The mean product flux V=d/dt (or 'dose-response' curve) and the Fano factor F=variance/ are both realistically measurable quantities, and while the mean flux can often appear the same for different reaction types, the Fano factor can be quite different. This suggests both qualitative and quantitative ways to discriminate between different reaction schemes, and we explore this possibility in the context of four sample multistep enzymatic reactions. We argue that measuring both the mean flux and the Fano factor can not only discriminate between reaction types, but can also provide some detailed information about the internal, unobserved kinetic rates, and this can be done without measuring single-molecule transition events.

  3. Mesoscopic statistical properties of multistep enzyme-mediated reactions.

    PubMed

    de Ronde, W H; Daniels, B C; Mugler, A; Sinitsyn, N A; Nemenman, I

    2009-09-01

    Enzyme-mediated reactions may proceed through multiple intermediate conformational states before creating a final product molecule, and one often wishes to identify such intermediate structures from observations of the product creation. In this study, the authors address this problem by solving the chemical master equations for various enzymatic reactions. A perturbation theory analogous to that used in quantum mechanics allows the determination of the first (n) and the second (σ2) cumulants of the distribution of created product molecules as a function of the substrate concentration and the kinetic rates of the intermediate processes. The mean product flux V=d(n)/dt (or 'dose-response' curve) and the Fano factor F= σ2/(n) are both realistically measurable quantities, and whereas the mean flux can often appear the same for different reaction types, the Fano factor can be quite different. This suggests both qualitative and quantitative ways to discriminate between different reaction schemes, and the authors explore this possibility in the context of four sample multistep enzymatic reactions. Measuring both the mean flux and the Fano factor can not only discriminate between reaction types, but can also provide some detailed information about the internal, unobserved kinetic rates, and this can be done without measuring single-molecule transition events. PMID:21028932

  4. DOLICHOL PHOSPHATE MANNOSE SYNTHASE1 Mediates the Biogenesis of Isoprenyl-Linked Glycans and Influences Development, Stress Response, and Ammonium Hypersensitivity in Arabidopsis[W

    PubMed Central

    Jadid, Nurul; Mialoundama, Alexis Samba; Heintz, Dimitri; Ayoub, Daniel; Erhardt, Mathieu; Mutterer, Jérôme; Meyer, Denise; Alioua, Abdelmalek; Van Dorsselaer, Alain; Rahier, Alain; Camara, Bilal; Bouvier, Florence

    2011-01-01

    The most abundant posttranslational modification in nature is the attachment of preassembled high-mannose-type glycans, which determines the fate and localization of the modified protein and modulates the biological functions of glycosylphosphatidylinositol-anchored and N-glycosylated proteins. In eukaryotes, all mannose residues attached to glycoproteins from the luminal side of the endoplasmic reticulum (ER) derive from the polyprenyl monosaccharide carrier, dolichol P-mannose (Dol-P-Man), which is flipped across the ER membrane to the lumen. We show that in plants, Dol-P-Man is synthesized when Dol-P-Man synthase1 (DPMS1), the catalytic core, interacts with two binding proteins, DPMS2 and DPMS3, that may serve as membrane anchors for DPMS1 or provide catalytic assistance. This configuration is reminiscent of that observed in mammals but is distinct from the single DPMS protein catalyzing Dol-P-Man biosynthesis in bakers’ yeast and protozoan parasites. Overexpression of DPMS1 in Arabidopsis thaliana results in disorganized stem morphology and vascular bundle arrangements, wrinkled seed coat, and constitutive ER stress response. Loss-of-function mutations and RNA interference–mediated reduction of DPMS1 expression in Arabidopsis also caused a wrinkled seed coat phenotype and most remarkably enhanced hypersensitivity to ammonium that was manifested by extensive chlorosis and a strong reduction of root growth. Collectively, these data reveal a previously unsuspected role of the prenyl-linked carrier pathway for plant development and physiology that may help integrate several aspects of candidate susceptibility genes to ammonium stress. PMID:21558543

  5. Food hypersensitivity by inhalation

    PubMed Central

    Ramirez, Daniel A; Bahna, Sami L

    2009-01-01

    Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization. PMID:19232116

  6. The Multi-Resistant Reaction of Drought-Tolerant Coffee 'Conilon Clone 14' to Meloidogyne spp. and Late Hypersensitive-Like Response in Coffea canephora.

    PubMed

    Lima, Edriana A; Furlanetto, Cleber; Nicole, Michel; Gomes, Ana C M M; Almeida, Maria R A; Jorge-Júnior, Aldemiro; Correa, Valdir R; Salgado, Sônia Maria; Ferrão, Maria A G; Carneiro, Regina M D G

    2015-06-01

    Root-knot nematodes (RKN), Meloidogyne spp., have major economic impact on coffee production in Central and South America. Genetic control of RKN constitutes an essential part for integrated pest management strategy. The objective of this study was to evaluate the resistance of Coffea canephora genotypes (clones) to Meloidogyne spp. Sensitive and drought-tolerant coffee genotypes were used to infer their resistance using nematode reproduction factor and histopathology. Eight clonal genotypes were highly resistant to M. paranaensis. 'Clone 14' (drought-tolerant) and 'ESN2010-04' were the only genotypes highly resistant and moderately resistant, respectively, to both M. incognita races 3 and 1. Several clones were highly resistant to both avirulent and virulent M. exigua. Clone 14 and ESN2010-04 showed multiple resistance to major RKNs tested. Roots of 'clone 14' (resistant) and 'clone 22' (susceptible) were histologically studied against infection by M. incognita race 3 and M. paranaensis. Reduction of juvenile (J2) penetration in clone 14 was first seen at 2 to 6 days after inoculation (DAI). Apparent early hypersensitive reaction (HR) was seen in root cortex between 4 and 6 DAI, which led to cell death and prevention of some nematode development. At 12 to 20 DAI, giant cells formed in the vascular cylinder, besides normal development into J3/J4. From 32 to 45 DAI, giant cells were completely degenerated. Late, intense HR and cell death were frequently observed around young females and giant cells reported for the first time in coffee pathosystem. These results provide rational bases for future studies, including prospection, characterization, and expression profiling of genomic loci involved in both drought tolerance and resistance to multiple RKN species. PMID:25738554

  7. In vitro Models to Evaluate Drug-Induced Hypersensitivity: Potential Test Based on Activation of Dendritic Cells

    PubMed Central

    Galbiati, Valentina; Papale, Angela; Kummer, Elena; Corsini, Emanuela

    2016-01-01

    Hypersensitivity drug reactions (HDRs) are the adverse effect of pharmaceuticals that clinically resemble allergy. HDRs account for approximately 1/6 of drug-induced adverse effects, and include immune-mediated (“allergic”) and non-immune-mediated (“pseudo allergic”) reactions. In recent years, the severe and unpredicted drug adverse events clearly indicate that the immune system can be a critical target of drugs. Enhanced prediction in preclinical safety evaluation is, therefore, crucial. Nowadays, there are no validated in vitro or in vivo methods to screen the sensitizing potential of drugs in the pre-clinical phase. The problem of non-predictability of immunologically-based hypersensitivity reactions is related to the lack of appropriate experimental models rather than to the lack of -understanding of the adverse phenomenon. We recently established experimental conditions and markers to correctly identify drug associated with in vivo hypersensitivity reactions using THP-1 cells and IL-8 production, CD86 and CD54 expression. The proposed in vitro method benefits from a rationalistic approach with the idea that allergenic drugs share with chemical allergens common mechanisms of cell activation. This assay can be easily incorporated into drug development for hazard identification of drugs, which may have the potential to cause in vivo hypersensitivity reactions. The purpose of this review is to assess the state of the art of in vitro models to assess the allergenic potential of drugs based on the activation of dendritic cells. PMID:27462271

  8. In vitro Models to Evaluate Drug-Induced Hypersensitivity: Potential Test Based on Activation of Dendritic Cells.

    PubMed

    Galbiati, Valentina; Papale, Angela; Kummer, Elena; Corsini, Emanuela

    2016-01-01

    Hypersensitivity drug reactions (HDRs) are the adverse effect of pharmaceuticals that clinically resemble allergy. HDRs account for approximately 1/6 of drug-induced adverse effects, and include immune-mediated ("allergic") and non-immune-mediated ("pseudo allergic") reactions. In recent years, the severe and unpredicted drug adverse events clearly indicate that the immune system can be a critical target of drugs. Enhanced prediction in preclinical safety evaluation is, therefore, crucial. Nowadays, there are no validated in vitro or in vivo methods to screen the sensitizing potential of drugs in the pre-clinical phase. The problem of non-predictability of immunologically-based hypersensitivity reactions is related to the lack of appropriate experimental models rather than to the lack of -understanding of the adverse phenomenon. We recently established experimental conditions and markers to correctly identify drug associated with in vivo hypersensitivity reactions using THP-1 cells and IL-8 production, CD86 and CD54 expression. The proposed in vitro method benefits from a rationalistic approach with the idea that allergenic drugs share with chemical allergens common mechanisms of cell activation. This assay can be easily incorporated into drug development for hazard identification of drugs, which may have the potential to cause in vivo hypersensitivity reactions. The purpose of this review is to assess the state of the art of in vitro models to assess the allergenic potential of drugs based on the activation of dendritic cells. PMID:27462271

  9. α-Regioselective Barbier Reaction of Carbonyl Compounds and Allyl Halides Mediated by Praseodymium.

    PubMed

    Wu, San; Li, Ying; Zhang, Songlin

    2016-09-01

    The first utility of praseodymium as a mediating metal in the Barbier reaction of carbonyl compounds with allyl halides was reported in this paper. In contrast to the traditional metal-mediated or catalyzed Barbier reactions, exclusive α-adducts were obtained in this one-pot reaction with a broad scope of substrates and feasible reaction conditions. PMID:27490708

  10. Structural basis of metal hypersensitivity.

    PubMed

    Wang, Yang; Dai, Shaodong

    2013-03-01

    Metal hypersensitivity is a common immune disorder. Human immune systems mount the allergic attacks on metal ions through skin contacts, lung inhalation and metal-containing artificial body implants. The consequences can be simple annoyances to life-threatening systemic illness. Allergic hyper-reactivities to nickel (Ni) and beryllium (Be) are the best-studied human metal hypersensitivities. Ni-contact dermatitis affects 10 % of the human population, whereas Be compounds are the culprits of chronic Be disease (CBD). αβ T cells (T cells) play a crucial role in these hypersensitivity reactions. Metal ions work as haptens and bind to the surface of major histocompatibility complex (MHC) and peptide complex. This modifies the binding surface of MHC and triggers the immune response of T cells. Metal-specific αβ T cell receptors (TCRs) are usually MHC restricted, especially MHC class II (MHCII) restricted. Numerous models have been proposed, yet the mechanisms and molecular basis of metal hypersensitivity remain elusive. Recently, we determined the crystal structures of the Ni and Be presenting human MHCII molecules, HLA-DR52c (DRA*0101, DRB3*0301) and HLA-DP2 (DPA1*0103, DPB1*0201). These structures revealed unusual features of MHCII molecules and shed light on how metal ions are recognized by T cells. PMID:22983897

  11. Structural basis of metal hypersensitivity

    PubMed Central

    Wang, Yang

    2014-01-01

    Metal hypersensitivity is a common immune disorder. Human immune systems mount the allergic attacks on metal ions through skin contacts, lung inhalation and metal-containing artificial body implants. The consequences can be simple annoyances to life-threatening systemic illness. Allergic hyper-reactivities to nickel (Ni) and beryllium (Be) are the best-studied human metal hypersensitivities. Ni-contact dermatitis affects 10 % of the human population, whereas Be compounds are the culprits of chronic Be disease (CBD). αβ T cells (T cells) play a crucial role in these hypersensitivity reactions. Metal ions work as haptens and bind to the surface of major histocompatibility complex (MHC) and peptide complex. This modifies the binding surface of MHC and triggers the immune response of T cells. Metal-specific αβ T cell receptors (TCRs) are usually MHC restricted, especially MHC class II (MHCII) restricted. Numerous models have been proposed, yet the mechanisms and molecular basis of metal hypersensitivity remain elusive. Recently, we determined the crystal structures of the Ni and Be presenting human MHCII molecules, HLA-DR52c (DRA*0101, DRB3*0301) and HLA-DP2 (DPA1*0103, DPB1*0201). These structures revealed unusual features of MHCII molecules and shed light on how metal ions are recognized by T cells. PMID:22983897

  12. Mediator profiles in tears during the conjunctival response induced by allergic reaction in the nasal mucosa

    PubMed Central

    2013-01-01

    Background The allergic reaction occurring primarily in the nasal mucosa can induce a secondary conjunctival response of an immediate (SICR), late (SLCR), or delayed (SDYCR) type in some patients with allergic conjunctivitis (AC). Objectives To investigate the concentration changes of histamine, tryptase, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), leukotrienes (LTB 4, LTC4, LTE4), myeloperoxidase (MPO), interferon-γ (IFN-γ), and interleukins (IL-2, IL-4, IL-5) in tears during the SICR, SLCR, and SDYCR. Methods In 32 patients with AC, 11 SICR (p<0.01), 13 SLCR (p<0.001), and eight SDYCR (p<0.01) to nasal challenges with allergens (NPTs), the NPTs and 32 control tests with PBS were repeated and supplemented with the determination of these factors in tears. Results The SICRs were associated with significant concentration changes in tears (p<0.05) of histamine, tryptase, ECP, LTC4, and IL-4. The SLCRs were accompanied by significant changes in concentrations of histamine, ECP, LTB4, LTC4, MPO, IL-4, and IL-5. The SDYCRs were associated with significant concentration changes in tears (p<0.05) of LTB4, MPO, IFN-γ, and IL-2. No significant changes in these factors were recorded in tears during the 32 PBS controls (p>0.1) or in the ten control patients (p>0.1). Conclusions These results provide evidence for causal involvement of nasal allergy in some patients with AC, inducing secondary conjunctival response of immediate (SICR), late SLCR, or delayed SDYCR type, associated with different mediator, cytokine, and cellular profiles in the tears, suggesting involvement of different hypersensitivity mechanisms. These results also emphasize the diagnostic value of nasal allergen challenge combined with monitoring of the conjunctival response in some patients with AC. PMID:23869165

  13. Lyn is essential for fcgamma receptor III-mediated systemic anaphylaxis but not for the Arthus reaction.

    PubMed

    Yuasa, T; Ono, M; Watanabe, T; Takai, T

    2001-03-01

    The Src family kinase Lyn initiates intracellular signal transduction by associating with a variety of immune receptors such as antigen receptor on B cells and high-affinity Fc receptor (FcR) for immunoglobulin Ig(E) (FcepsilonRI) on mast cells. Involvement of Lyn in the IgE-mediated immediate-type hypersensitivity is well documented, but the physiological significance of Lyn in IgG-dependent, type III low-affinity FcR for IgG (FcgammaRIII)-mediated responses is largely unknown. In this study, we generated a double-mutant mouse strain deficient in both type II FcR for IgG (FcgammaRIIB) and Lyn to exclude any involvement of inhibitory signaling by FcgammaRIIB, which otherwise downregulates FcgammaRIII-mediated cellular responses. FcgammaRIIB-deficient but Lyn-sufficient mice served as controls. The Lyn deficiency attenuated IgG-mediated systemic anaphylaxis in vivo, and significantly reduced calcium mobilization and degranulation responses of bone marrow-derived mast cells (BMMCs) in vitro. However, we found that either interleukin 4 or tumor necrosis factor alpha release by BMMCs was comparable to that from Lyn-deficient and control mice, and the reverse-passive Arthus reaction was equally induced in both mutant mice, indicating that Lyn is not involved in the onset of the IgG-mediated, FcgammaRIII-dependent late phase responses of mast cells. These findings provide us with insight into distinct signaling mechanisms in mast cells underlying the development of diverse pathologies as well as a therapeutic potential for selective treatment of allergic disorders. PMID:11238587

  14. What we know about nonsteroidal anti-inflammatory drug hypersensitivity.

    PubMed

    Pham, Duy Le; Kim, Ji-Hye; Trinh, Tu Hoang Kim; Park, Hae-Sim

    2016-05-01

    Nonsteroidal anti-inf lammatory drugs (NSAIDs) are widely prescribed for the treatment of inflammatory diseases, but their use is frequently related to hypersensitivity reactions. This review outlines our current knowledge of NSAID hypersensitivity (NHS) with regard to its pathogenic, molecular, and genetic mechanisms, as well as diagnosis and treatment. The presentation of NHS varies from a local (skin and/or airways) reaction to systemic reactions, including anaphylaxis. At the molecular level, NHS reactions can be classified as cross-reactive (mediated by cyclooxygenase inhibition) or selective (specific activation of immunoglobulin E antibodies or T cells). Genetic polymorphisms and epigenetic factors have been shown to be closely associated with NHS, and may be useful as predictive markers. To diagnose NHS, inhalation or oral challenge tests are applied, with the exclusion of any cross-reactive NSAIDs. For patients diagnosed with NHS, absolute avoidance of NSAIDs/aspirin is essential, and pharmacological treatment, including biologics, is often used to control their respiratory and cutaneous symptoms. Finally, desensitization is recommended only for selected patients with NHS. However, further research is required to develop new diagnostic methods and more effective treatments against NHS. PMID:27030979

  15. What we know about nonsteroidal anti-inflammatory drug hypersensitivity

    PubMed Central

    Pham, Duy Le; Kim, Ji-Hye; Trinh, Tu Hoang Kim; Park, Hae-Sim

    2016-01-01

    Nonsteroidal anti-inf lammatory drugs (NSAIDs) are widely prescribed for the treatment of inflammatory diseases, but their use is frequently related to hypersensitivity reactions. This review outlines our current knowledge of NSAID hypersensitivity (NHS) with regard to its pathogenic, molecular, and genetic mechanisms, as well as diagnosis and treatment. The presentation of NHS varies from a local (skin and/or airways) reaction to systemic reactions, including anaphylaxis. At the molecular level, NHS reactions can be classified as cross-reactive (mediated by cyclooxygenase inhibition) or selective (specific activation of immunoglobulin E antibodies or T cells). Genetic polymorphisms and epigenetic factors have been shown to be closely associated with NHS, and may be useful as predictive markers. To diagnose NHS, inhalation or oral challenge tests are applied, with the exclusion of any cross-reactive NSAIDs. For patients diagnosed with NHS, absolute avoidance of NSAIDs/aspirin is essential, and pharmacological treatment, including biologics, is often used to control their respiratory and cutaneous symptoms. Finally, desensitization is recommended only for selected patients with NHS. However, further research is required to develop new diagnostic methods and more effective treatments against NHS. PMID:27030979

  16. The antinociception of oxytocin on colonic hypersensitivity in rats was mediated by inhibition of mast cell degranulation via Ca2+-NOS pathway

    PubMed Central

    Gong, Liping; Li, Jing; Tang, Yan; Han, Ting; Wei, Chuanfei; Yu, Xiao; Li, Jingxin; Wang, Rong; Ma, Xuelian; Liu, Kejing; Geng, Lingyun; Liu, Shaozhuang; Yan, Bing; Liu, Chuanyong

    2016-01-01

    This study was conducted to investigate the effects of oxytocin (OT) on visceral hypersensitivity/pain and mast cell degranulation and the underlying mechanisms. We found that oxytocin receptor (OTR) was expressed in colonic mast cells in humans and rats, as well as in human mast cell line-1 (HMC-1), rat basophilic leukemia cell line (RBL-2H3) and mouse mastocytoma cell line (P815). OT decreased 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced visceral hypersensitivity, colonic mast cell degranulation and histamine release after mast cell degranulation in rats. Also, OT attenuated the compound 48/80 (C48/80)-evoked histamine release in P815 cells and inward currents, responsible for the mast cell degranulation, in HMC-1, RBL-2H3 and P815 cells. Moreover, these protective effects of OT against visceral hypersensitivity and mast cell degranulation were eliminated by coadministration of OTR antagonist atosiban or a nonselective inhibitor of nitric oxide synthase (NOS), NG-Methyl-L-arginine acetate salt (L-NMMA). Notably, OT evoked a concentration-dependent increase of intracellular Ca2+ in HMC-1, RBL-2H3 and P815 cells, which was responsible for the activation of neuronal NOS (NOS1) and endothelial NOS (NOS3). Our findings strongly suggest that OT might exert the antinociception on colonic hypersensitivity through inhibition of mast cell degranulation via Ca2+-NOS pathway. PMID:27538454

  17. Antiepileptic drug hypersensitivity syndrome.

    PubMed

    Schlienger, R G; Shear, N H

    1998-01-01

    The antiepileptic drug hypersensitivity syndrome (AHS) is an adverse drug reaction associated with the aromatic antiepileptic drugs (AEDs) phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), and primidone. The syndrome is defined by the triad of fever, skin rash, and internal organ involvement. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, terbinafine, azathioprine, and allopurinol. Diagnosis of AHS 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 incidence is approximately 1 in 3,000 exposures. AHS starts with fever, rash, and lymphadenopathy, within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis, and myostitis. AHS is associated with a relative excess of reactive oxidative metabolites of the AED. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Crossreactivity among PHT, CBZ, and PB is as high as 70-80%. PMID:9798755

  18. Clinical Management of Nonsteroidal Anti-inflammatory Drug Hypersensitivity

    PubMed Central

    2008-01-01

    Hypersensitivity diseases caused by nonsteroidal anti-inflammatory agents are relatively common in the population. This article summarizes the present understanding on the various allergic and nonallergic clinical pictures produced through hypersensitivity to these drugs using the pathogenic classification of hypersensitivity reactions recently proposed by the Nomenclature Committee of the World Allergy Organization to guide clinicians in the diagnosis and management of patients with these conditions. PMID:23283307

  19. Radiocontrast media hypersensitivity in the Asia Pacific region.

    PubMed

    Lee, Suh-Young; Lim, Kyoung-Whan; Chang, Yoon-Seok

    2014-04-01

    Radiocontrast media (RCM) is a major cause of drug hypersensitivity reactions as the medical application of RCM is increasing recently. RCM induced hypersensitivity reactions are considered as unpredictable type B reactions. Underlying mechanism of RCM induced hypersensitivity was previously regarded as nonimmunological mechanisms but recent studies suggest that immunological mechanisms could also be involved. As a result, the roles of skin tests and premedication are revisiting. As there has been no report that comprehensively summarized and analyzed the results of the studies on RCM hypersensitivity in the Asia Pacific region, we aimed to review the literatures on hypersensitivity reactions to RCM in terms of prevalence clinical manifestations, diagnostic approach, and preventive measures in the Asia Pacific region. PMID:24809018

  20. Hypersensitivity to fluoroquinolones

    PubMed Central

    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

  1. Titanium hypersensitivity. A hidden threat for dental implant patients?

    PubMed

    Bilhan, Hakan; Bural, Canan; Geckili, Onur

    2013-01-01

    Titanium and its alloys have been widely used for dental prosthetic devices because of their superior mechanical properties and biocompatibility. However, the incidence of titanium hypersensitivity or allergy is still unknown and the discussion about its existence is ongoing. Unexplained implant failures have also forced dental clinicians to investigate the possibility of titanium hypersensitivity or allergy. This review focuses on the potential of dental implant-related titanium hypersensitivity or allergic reactions. It includes an examination of the existing scientific literature and current knowledge. Evidence-based data and studies related to titanium hypersensitivity in dental implant patients are also discussed. PMID:24027897

  2. Chronic cough hypersensitivity syndrome

    PubMed Central

    2013-01-01

    Chronic cough has been suggested to be due to three conditions, asthma, post nasal drip, and reflux disease. A different paradigm has evolved in which cough is viewed as the primary condition characterised by afferent neuronal hypersensitivity and different aspects of this syndrome are manifest in the different phenotypes of cough. There are several advantages to viewing cough hypersensitivity as the unifying diagnosis; Communication with patients is aided, aetiology is not restricted and therapeutic avenues opened. Cough Hypersensitivity Syndrome is a more applicable label to embrace the clinical manifestations of this disabling disease. PMID:23668427

  3. Sea urchin sperm antigens mediating the acrosome reaction

    SciTech Connect

    Trimmer, J.S.

    1987-01-01

    The study of sea urchin sperm antigens mediating the acrosome reactions (AR) has been undertaken. Monoclonal antibodies (mAbs) have been isolated reacting with a number of sperm surface antigens. These mAbs have been used in functional assays to attempt to infer the roles of these proteins in the induction of the AR. These mAbs have also been used to isolate protein for biochemical characterization and reconstitution studies. mAbs reacting with a 210 kD protein of the sea urchin sperm plasma membrane have been used to identify this protein as playing a role in the regulation of ion fluxes during the induction of the AR. mAbs reacting with certain extracellular regions inhibit the induction of: the AR, the long duration {sup 45}Ca{sup 2+} uptake into the mitochondrion, and H{sup +} efflux. Addition of these same mAbs, however, induces an increase in sperm (Ca{sup 2+}){sub i} to levels much higher than those induced by FSG, as monitored by the fluorescent Ca{sup 2+} indicators fura 2 and indo 1. This (Ca{sup 2+}){sub i} increase occurs without an increase in pH{sub i}, and thus allows for the first time the analysis of the effects of increasing sperm (Ca{sup 2+}){sub i} ion the absence of increased pH{sub i}.

  4. Genes Encoding Phospholipases A2 Mediate Insect Nodulation Reactions to Bacterial Challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We propose that expression of four genes encoding secretory phospholipases A2 (sPLA2) mediates insect nodulation responses to bacterial infection. Nodulation is the quantitatively predominant cellular defense reaction to bacterial infection. This reaction is mediated by eicosanoids, the biosynthesis...

  5. Carmine hypersensitivity masquerading as azithromycin hypersensitivity.

    PubMed

    Greenhawt, Matthew; McMorris, Marc; Baldwin, James

    2009-01-01

    Macrolide hypersensitivity is a rarely reported event. However, carmine dye has become increasingly important as a provocative agent. We present a case of a woman with documented carmine hypersensitivity, who reported anaphylaxis 90 minutes after ingestion of a generic azithromycin. Our investigations revealed that this was an allergy to the carmine dye in the tablet's coating rather than to the antibiotic. Seven extracts were prepared including carmine dye, crushed dried female cochineal insects, crushed tablets of Zithromax (Pfizer Inc.) and generic azithromycin (Teva Pharmaceuticals), and the crushed colored coatings from both tablets. These were suspended in preservative-free normal saline, and then applied as a skin-prick test and read at 30 minutes. The skin-prick skin test results were 4+ to histamine and carmine dye, but negative to cochineal insect extract, Pfizer crushed tablets, and negative control. The patient was 1+ to the Teva crushed tablet, but was 4+ to the Teva brand coating and negative to the Pfizer brand coating, which did not contain carmine. The patient subsequently ingested Pfizer Zithromax without any sequelae. To our knowledge, this is the first reported case of carmine anaphylaxis attributed to carmine-containing medication. Careful history and skin-prick testing to the appropriate agents allowed elucidation of the subtlety of the true offending agent without unnecessary avoidance of the medication class. Patients with a carmine hypersensitivity should actively check with their pharmacy or prescribing physician to verify their medications are free of this offending agent. PMID:19331724

  6. TRPA1 Contributes to Cold Hypersensitivity

    PubMed Central

    Camino, Donato del; Murphy, Sarah; Heiry, Melissa; Barrett, Lee B.; Earley, Taryn J.; Cook, Colby A.; Petrus, Matt J.; Zhao, Michael; D'Amours, Marc; Deering, Nate; Brenner, Gary J.; Costigan, Michael; Hayward, Neil J.; Chong, Jayhong A.; Fanger, Christopher M.; Woolf, Clifford J.; Patapoutian, Ardem; Moran, Magdalene M.

    2010-01-01

    TRPA1 is a non-selective cation channel expressed by nociceptors. While it is widely accepted that TRPA1 serves as a broad irritancy receptor for a variety of reactive chemicals, its role in cold sensation remains controversial. Here, we demonstrate that mild cooling markedly increases agonist-evoked rat TRPA1 currents. In the absence of an agonist, even noxious cold only increases current amplitude slightly. These results suggest that TRPA1 is a key mediator of cold hypersensitivity in pathological conditions where reactive oxygen species and pro-inflammatory activators of the channel are present, but likely plays a comparatively minor role in acute cold sensation. Supporting this, cold hypersensitivity can be induced in wild-type but not Trpa1-/- mice by subcutaneous administration of a TRPA1 agonist. Furthermore, the selective TRPA1 antagonist HC-030031 reduces cold hypersensitivity in rodent models of inflammatory and neuropathic pain. PMID:21068322

  7. Removal of triclosan via peroxidases-mediated reactions in water: Reaction kinetics, products and detoxification.

    PubMed

    Li, Jianhua; Peng, Jianbiao; Zhang, Ya; Ji, Yuefei; Shi, Huanhuan; Mao, Liang; Gao, Shixiang

    2016-06-01

    This study investigated and compared reaction kinetics, product characterization, and toxicity variation of triclosan (TCS) removal mediated by soybean peroxidase (SBP), a recognized potential peroxidase for removing phenolic pollutants, and the commonly used horseradish peroxidase (HRP) with the goal of assessing the technical feasibility of SBP-catalyzed removal of TCS. Reaction conditions such as pH, H2O2 concentration and enzyme dosage were found to have a strong influence on the removal efficiency of TCS. SBP can retain its catalytic ability to remove TCS over broad ranges of pH and H2O2 concentration, while the optimal pH and H2O2 concentration were 7.0 and 8μM, respectively. 98% TCS was removed with only 0.1UmL(-1) SBP in 30min reaction time, while an HRP dose of 0.3UmL(-1) was required to achieve the similar conversion. The catalytic performance of SBP towards TCS was more efficient than that of HRP, which can be explained by catalytic rate constant (KCAT) and catalytic efficiency (KCAT/KM) for the two enzymes. MS analysis in combination with quantum chemistry computation showed that the polymerization products were generated via CC and CO coupling pathways. The polymers were proved to be nontoxic through growth inhibition of green alga (Scenedesmus obliquus). Taking into consideration of the enzymatic treatment cost, SBP may be a better alternative to HRP upon the removal and detoxification of TCS in water/wastewater treatment. PMID:26921508

  8. Immunology of infusion reactions in the treatment of patients with acute lymphoblastic leukemia.

    PubMed

    Asselin, Barbara

    2016-07-01

    Infusion reactions are potentially dose-limiting adverse events associated with intravenous administration of several common agents used to treat patients with acute lymphoblastic leukemia. True clinical hypersensitivity reactions are antibody-mediated and can occur only after repeated exposure to an antigen. Conversely, anaphylactoid infusion reactions are nonantibody-mediated and often occur on the initial exposure to a drug. Cytokine-release syndrome comprises a subset of nonantibody-mediated infusion reactions associated with the use of monoclonal antibodies and immune therapies. Clinical symptoms of hypersensitivity reactions and nonantibody-mediated infusion reactions heavily overlap and can be difficult to distinguish in practice. Regardless of the underlying mechanism, any infusion reaction can negatively affect treatment efficacy and patient safety. These events require prompt response, and potentially, modification of subsequent therapy. PMID:27086555

  9. Oral immunotherapy induces IgG antibodies that act via FcγRIIb to suppress IgE-mediated hypersensitivity

    PubMed Central

    Burton, Oliver T.; Logsdon, Stephanie L.; Zhou, Joseph S.; Medina-Tamayo, Jaciel; Abdel-Gadir, Azza; Rivas, Magali Noval; Koleoglou, Kyle J.; Chatila, Talal A.; Schneider, Lynda C.; Rachid, Rima; Umetsu, Dale T.; Oettgen, Hans C.

    2014-01-01

    Background Food anaphylaxis is triggered by specific IgE antibodies. Paradoxically, some individuals with significant IgE levels can ingest allergenic foods without incident. Similarly, subjects completing oral immunotherapy (OIT) tolerate food challenges despite persistent high-titer food-specific IgE. Objective To test whether IgG antibodies induced by food immunotherapy prevent food-induced anaphylaxis, and whether this occurs via the inhibitory receptor FcγRIIb. Methods Food allergy-susceptible Il4raF709 mice were enterally sensitized to ovalbumin (OVA). Similarly sensitized IgE-deficient Il4raF709/IgE−/− mice, which can ingest OVA without anaphylaxis, were subjected to a high-dose enteral OVA desensitization protocol (OIT). Sera from both groups were tested for the ability to activate or inhibit bone marrow mast cells (BMMC) exposed to allergen, or to passively transfer allergy to naïve hosts. In parallel experiments, sera obtained from peanut allergic patients before and after undergoing OIT were interrogated for their ability to enhance or suppress peanut-induced activation in an indirect assay using basophils from non-allergic donors. Results Il4raF709 mice exhibited strong OVA-specific IgE responses. Their sera efficiently sensitized BMMC for activation by antigen challenge. Sera from Il4raF709/IgE−/− mice subjected to OVA OIT suppressed BMMC responses. This inhibition was IgG-mediated and FcγRIIb-dependent. Similarly, pre-OIT, but not post-OIT sera from patients efficiently sensitized basophils for peanut-induced activation. IgG antibodies in post-OIT sera suppressed basophil activation by pre-OIT sera. This inhibition was blocked by antibodies against FcγRII. Conclusion Food-specific IgG antibodies, such as those induced during OIT, inhibit IgE-mediated reactions. Strategies that favor IgG responses might prove useful in the management of food allergy. PMID:25042981

  10. Loss of Calmodulin Binding to Bax Inhibitor-1 Affects Pseudomonas-mediated Hypersensitive Response-associated Cell Death in Arabidopsis thaliana*

    PubMed Central

    Kawai-Yamada, Maki; Hori, Zenta; Ogawa, Taro; Ihara-Ohori, Yuri; Tamura, Katsunori; Nagano, Minoru; Ishikawa, Toshiki; Uchimiya, Hirofumi

    2009-01-01

    Bax inhibitor-1 (BI-1) is a cell death suppressor protein conserved across a variety of organisms. The Arabidopsis atbi1-1 plant is a mutant in which the C-terminal 6 amino acids of the expressed BI-1 protein have been replaced by T-DNA insertion. This mutant BI-1 protein (AtBI-CM) produced in Escherichia coli can no longer bind to calmodulin. A promoter-reporter assay demonstrated compartmentalized expression of BI-1 during hypersensitive response, introduced by the inoculation of Pseudomonas syringae possessing the avrRTP2 gene, Pst(avrRPT2). In addition, both BI-1 knockdown plants and atbi1-1 showed increased sensitivity to Pst(avrRPT2)-induced cell death. The results indicated that the loss of calmodulin binding reduces the cell death suppressor activity of BI-1 in planta. PMID:19674971

  11. Complexity of lectin-mediated reactions in bacteria-induced histamine release.

    PubMed

    Jensen, C; Stahl Skov, P; Norn, S; Espersen, F; Bøg-Hansen, T C; Lihme, A

    1984-08-01

    We have earlier suggested that bacteria-induced histamine release is caused by different mechanisms, including allergic and non-immunological mechanisms, and that the latter probably depends on lectin-mediated reactions. Two possibilities of lectin-mediated reactions were examined in this study, bacterial surface lectins bind to sugars on the basophil cell membrane leading to histamine release, and the reverse reaction where bacterial aminosugars react with lectins on the basophil cell surface. In the bacterial histamine release caused by the Staph. aureus strain Wood 46 it was possible to demonstrate a reverse reaction, but not a bacterial lectin-mediated reaction. The reaction seems to be complex, as lower concentrations of sugars might potentiate the release of histamine by binding to the target cell or bacteria, while the release is inhibited by higher concentrations. PMID:6208803

  12. Mg(II) -Mediated Catalytic Asymmetric Dearomatization (CADA) Reaction of β-Naphthols with Dialkyl Acetylenedicarboxylates.

    PubMed

    Wang, Linqing; Yang, Dongxu; Li, Dan; Wang, Pengxin; Wang, Kezhou; Wang, Jie; Jiang, Xianxing; Wang, Rui

    2016-06-13

    A Mg(II) -mediated catalytic asymmetric dearomatization (CADA) reaction of β-naphthols has been developed. The reaction proceeds under ambient temperature and give a series of chiral trisubstituted olefins with good chemoselectivities, Z/E ratios, and excellent enantioselectivities. A fluorinated β-naphthol was designed to generate chiral organofluorine skeletons through the current CADA reaction. Moreover, an interesting tandem cyclization reaction was observed in the following transformation process through an undiscovered intramolecular hydride transfer pathway. PMID:27139904

  13. Manganese-Mediated Coupling Reaction of Vinylarenes and Aliphatic Alcohols.

    PubMed

    Zhang, Wei; Wang, Nai-Xing; Bai, Cui-Bing; Wang, Yan-Jing; Lan, Xing-Wang; Xing, Yalan; Li, Yi-He; Wen, Jia-Long

    2015-01-01

    Alcohols and alkenes are the most abundant and commonly used organic building blocks in the large-scale chemical synthesis. Herein, this is the first time to report a novel and operationally simple coupling reaction of vinylarenes and aliphatic alcohols catalyzed by manganese in the presence of TBHP (tert-butyl hydroperoxide). This coupling reaction provides the oxyalkylated products of vinylarenes with good regioselectivity and accomplishes with the principles of step-economies. A possible reaction mechanism has also been proposed. PMID:26470633

  14. Manganese-Mediated Coupling Reaction of Vinylarenes and Aliphatic Alcohols

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Wang, Nai-Xing; Bai, Cui-Bing; Wang, Yan-Jing; Lan, Xing-Wang; Xing, Yalan; Li, Yi-He; Wen, Jia-Long

    2015-10-01

    Alcohols and alkenes are the most abundant and commonly used organic building blocks in the large-scale chemical synthesis. Herein, this is the first time to report a novel and operationally simple coupling reaction of vinylarenes and aliphatic alcohols catalyzed by manganese in the presence of TBHP (tert-butyl hydroperoxide). This coupling reaction provides the oxyalkylated products of vinylarenes with good regioselectivity and accomplishes with the principles of step-economies. A possible reaction mechanism has also been proposed.

  15. Manganese-Mediated Coupling Reaction of Vinylarenes and Aliphatic Alcohols

    PubMed Central

    Zhang, Wei; Wang, Nai-Xing; Bai, Cui-Bing; Wang, Yan-Jing; Lan, Xing-Wang; Xing, Yalan; Li, Yi-He; Wen, Jia-Long

    2015-01-01

    Alcohols and alkenes are the most abundant and commonly used organic building blocks in the large-scale chemical synthesis. Herein, this is the first time to report a novel and operationally simple coupling reaction of vinylarenes and aliphatic alcohols catalyzed by manganese in the presence of TBHP (tert-butyl hydroperoxide). This coupling reaction provides the oxyalkylated products of vinylarenes with good regioselectivity and accomplishes with the principles of step-economies. A possible reaction mechanism has also been proposed. PMID:26470633

  16. Anaphylaxis and Anaphylactoid Reactions: Diagnosis and Management.

    PubMed

    Luskin, Allan T.; Luskin, Susan S.

    1996-07-01

    Anaphylaxis is an acute fatal or potentially fatal hypersensitivity reaction. Anaphylaxis represent a clinical diagnosis based on history and physical examination and includes symptoms of airway obstruction, generalized skin reactions, particularly flushing, itching, urticaria, angioedema cardiovascular symptoms including hypotension and gastrointestinal symptoms. These symptoms result from the action of mast cell mediators, especially histamine and lipid mediators such as leukotrienes and platelet activating factor on shock tissue. The shock tissue includes blood vessels, mucous glands, smooth muscle, and nerve endings. Anaphylaxis follows the typical immediate hypersensitivity time course, with a reaction beginning within minutes of antigen exposure. A late-phase reaction hours after the initial reaction may occur. Mast cell mediator release can be triggered by both IgE and non--IgE-mediated factors. Therefore, anaphylaxis may be termed anaphylaxis (IgE mediated) or anaphylactoid (non--IgE mediated). The most common IgE-mediated triggers are drugs, typically penicillin or other beta-lactam antibiotics, foods, most commonly nuts, peanuts, fish and shellfish, or hymenoptera stings. Non-IgE-mediated causes include factors causing marked complement activation such as plasma proteins or compounds which act directly on the mast cell membrane, such as vancomycin, quinolone antibiotics, or radiographic contrast media. The pathophysiology of some trigger factors, such as aspirin, remains unclear. Therapy of anaphylaxis revolves around patient education, avoidance, desensitization or pharmacologic pretreatment when agents causing anaphylaxis need to be readministered, and early recognition and prompt therapy of reactions should they occur. PMID:11862283

  17. Diagnostic testing of dogs for food hypersensitivity.

    PubMed

    Jeffers, J G; Shanley, K J; Meyer, E K

    1991-01-15

    Thirteen food-allergic dogs were studied to evaluate the efficacy of feeding a commercially available egg and rice diet, intradermal skin testing, and serologic testing by ELISA for diagnosing and/or characterizing food hypersensitivity. Feeding of a home-cooked whole lamb meat and rice diet for 3 weeks, followed by challenge with each dog's regular diet, served as the standard for diagnosing food hypersensitivity. Each dog underwent provocative testing with 6 individual ingredients to determine as many of its dietary allergens as possible. Prior to skin testing and serologic testing by ELISA, most dogs had been recently exposed to the offending diet and subsequently manifested clinical signs of allergy. All dogs that tolerated the aforementioned commercial diet were exposed to it for at least 7 weeks; 84.6% of food-hypersensitive dogs ate the commercial diet with impunity. Of the 2 reactors to the commercial diet, only 1 became pruritic in response to provocation testing with chicken eggs. Low sensitivity and high specificity were found for skin testing and the ELISA, indicating a lack of true- and false-positive reactions. Neither the positive nor negative predictive values adequately predicted positive and negative reactions, respectively, for either test. On the basis of these results, the commercial diet, skin testing, and anti-IgE ELISA cannot replace an owner-prepared food elimination diet for food hypersensitivity testing in dogs. PMID:2004984

  18. Benzoxazinone-Mediated Triazine Degradation: A Proposed Reaction Mechanism.

    PubMed

    Willett, C D; Lerch, R N; Lin, C-H; Goyne, K W; Leigh, N D; Roberts, C A

    2016-06-22

    The role of benzoxazinones (Bx, 2-hydroxy-2H-1,4-benzoxazin-3(4H)-one) in triazine resistance in plants has been studied for over half a century. In this research, fundamental parameters of the reaction between DIBOA-Glc (2-β-d-glucopyranosyloxy-4-hydroxy-1,4-benzoxazin-3-one) and atrazine (ATR, 6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine) were examined. Through a series of experiments employing a variety of chromatographic and spectroscopic techniques, the DIBOA-Glc/ATR reaction was characterized in terms of reactant and product kinetics, stoichiometry, identification of a reaction intermediate, and reaction products formed. Results of these experiments demonstrated that the reaction mechanism proceeds via nucleophilic attack of the hydroxamic acid moiety of DIBOA-Glc at the C-2 position of the triazine ring to form hydroxyatrazine (HA, 2-hydroxy-4-ethylamino-6-isopropylamino-s-triazine), with associated degradation of DIBOA-Glc. Degradation of reactants followed first-order kinetics with a noncatalytic role of DIBOA-Glc. A reaction intermediate was identified as a DIBOA-Glc-HA conjugate, indicating a 1:1 DIBOA-Glc:ATR stoichiometry. Reaction products included HA and Cl(-), but definitive identification of DIBOA-Glc reaction product(s) was not attained. With these reaction parameters elucidated, DIBOA-Glc can be evaluated in terms of its potential for a myriad of applications, including its use to address the problem of widespread ATR contamination of soil and water resources. PMID:27215133

  19. The frequency of HLA-B(∗)57:01 and the risk of abacavir hypersensitivity reactions in the majority population of Costa Rica.

    PubMed

    Arrieta-Bolaños, Esteban; Madrigal, J Alejandro; Marsh, Steven G E; Shaw, Bronwen E; Salazar-Sánchez, Lizbeth

    2014-11-01

    HLA-B(∗)57:01 is a well-known and cost-effective pharmacogenetic marker for abacavir hypersensitivity. As with other HLA alleles, there is widespread variation in its frequency across populations. The Costa Rica Central Valley Population (CCVP) is the major population in this country. The frequency of HLA-B(∗)57:01 in this population has not been described yet. Thus, our aim was to determine the frequency of this allele in the CCVP. 200 unrelated healthy volunteer donors born in the CCVP were typed. HLA-B(∗)57-positive samples identified by HLA intermediate resolution typing methods were further typed by SBT to high resolution. An HLA-B(∗)57:01 carrier frequency of 5.00% was determined in this sample. This frequency is relatively high in comparison to reports from other populations in Latin America. These results suggest that there is a considerable frequency of HLA-B(∗)57:01 in the CCVP and that pharmacogenetic testing for HIV+ patients who are going to receive abacavir-based treatment should be considered in this country. PMID:25286002

  20. Inflammatory Mediators of Leprosy Reactional Episodes and Dental Infections: A Systematic Review

    PubMed Central

    Cortela, D. C. B.; de Souza Junior, A. L.; Virmond, M. C. L.; Ignotti, E.

    2015-01-01

    Reactional episodes in leprosy are a result of complex interactions between the immune system, Mycobacterium leprae, and predisposing factors, including dental infections. To determine the main inflammatory mediators in the immunopathological process of dental infections and leprosy reactions, we conducted a systematic review of primary literature published between 1996 and 2013. A three-stage literature search was performed (Stage I, “leprosy reactions” and “inflammatory mediators”; Stage II, “dental infections” and “inflammatory mediators”; and Stage III, “leprosy reactions,” “dental infections,” and “inflammatory mediators”). Of the 911 eligible publications, 10 were selected in Stage I, 68 in Stage II, and 1 in Stage III. Of the 27 studied inflammatory mediators, the main proinflammatory mediators were IL-6, IFN-γ, TNF-α, IL-1β, and IL-17; the main anti-inflammatory mediators were IL-10 and IL-4. Serum IL-6 and TNF-α concentrations were significant during periodontal and reactional lesion evolution; IFN-γ and IL-1β were associated with types 1 and 2 reactions and chronic periodontal disease. The proinflammatory mediators in dental infections and leprosy reactions, especially IL-6 and TNF-α, were similar across studies, regardless of the laboratory technique and sample type. IFN-γ and IL-1β were significant for leprosy reactions and periodontal diseases. This pattern was maintained in serum. PMID:26339136

  1. Hypersensitivity of A8344G MERRF mutated cybrid cells to staurosporine-induced cell death is mediated by calcium-dependent activation of calpains.

    PubMed

    Rommelaere, Guillaume; Michel, Sébastien; Malaisse, Jérémy; Charlier, Sophie; Arnould, Thierry; Renard, Patricia

    2012-01-01

    Mutations in the mitochondrial DNA can lead to the development of mitochondrial diseases such as Myoclonic Epilepsy with Ragged Red Fibers (MERRF) or Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes (MELAS). We first show that human 143B-derived cybrid cells harboring either the A8344G (MERRF) or the A3243G (MELAS) mutation, are more prone to undergo apoptosis then their wild-type counterpart, when challenged with various apoptotic inducers such as staurosporine, etoposide and TRAIL. In addition, investigating the mechanisms underlying A8344G cybrid cells hypersensitivity to staurosporine-induced cell death, we found that staurosporine treatment activates caspases independently of cytochrome c release in both wild-type and mutated cells. Caspases are activated, at least partly, through the activation of calcium-dependent calpain proteases, a pathway that is more strongly activated in mutated cybrid cells than in wild-type cells exposed to staurosporine. These results suggest that calcium homeostasis perturbation induced by mitochondrial dysfunction could predispose cells to apoptosis, a process that could take part into the progressive cell degeneration observed in MERRF syndrome, and more generally in mitochondrial diseases. PMID:22037425

  2. Towards a General Understanding of Carbonyl-Stabilised Ammonium Ylide-Mediated Epoxidation Reactions.

    PubMed

    Novacek, Johanna; Roiser, Lukas; Zielke, Katharina; Robiette, Raphaël; Waser, Mario

    2016-08-01

    The key factors for carbonyl-stabilised ammonium ylide-mediated epoxidation reactions were systematically investigated by experimental and computational means and the hereby obtained energy profiles provide explanations for the observed experimental results. In addition, we were able to identify the first tertiary amine-based chiral auxiliary that allows for high enantioselectivities and high yields for such epoxidation reactions. PMID:27381752

  3. Notch-mediated lateral inhibition regulates proneural wave propagation when combined with EGF-mediated reaction diffusion.

    PubMed

    Sato, Makoto; Yasugi, Tetsuo; Minami, Yoshiaki; Miura, Takashi; Nagayama, Masaharu

    2016-08-30

    Notch-mediated lateral inhibition regulates binary cell fate choice, resulting in salt and pepper patterns during various developmental processes. However, how Notch signaling behaves in combination with other signaling systems remains elusive. The wave of differentiation in the Drosophila visual center or "proneural wave" accompanies Notch activity that is propagated without the formation of a salt and pepper pattern, implying that Notch does not form a feedback loop of lateral inhibition during this process. However, mathematical modeling and genetic analysis clearly showed that Notch-mediated lateral inhibition is implemented within the proneural wave. Because partial reduction in EGF signaling causes the formation of the salt and pepper pattern, it is most likely that EGF diffusion cancels salt and pepper pattern formation in silico and in vivo. Moreover, the combination of Notch-mediated lateral inhibition and EGF-mediated reaction diffusion enables a function of Notch signaling that regulates propagation of the wave of differentiation. PMID:27535937

  4. Synthesis of multisubstituted pyrroles from doubly activated cyclopropanes using an iron-mediated oxidation domino reaction.

    PubMed

    Zhang, Zhiguo; Zhang, Wei; Li, Junlong; Liu, Qingfeng; Liu, Tongxin; Zhang, Guisheng

    2014-11-21

    An alternative route has been developed for the construction of multisubstituted pyrrole derivatives from readily available, doubly activated cyclopropanes and anilines using an iron-mediated oxidation domino reaction (i.e., sequential ring-opening, cyclization, and dehydrogenation reactions). This reaction uses readily available reactants and is tolerant of a broad range of substrates, with the desired products being formed in good to excellent yields. PMID:25330125

  5. Benzoxazinone-mediated triazine degradation: A proposed reaction mechanism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The role of benzoxazinones (Bx, 2-hydroxy-2H-1,4-benzoxazin-3(4H)-one)) in triazine degradation and resistance has been studied for over half a century. In this research, the fundamental parameters of the reaction between DIBOA-Glc (2-ß-D-glucopyranosyloxy-4-hydroxy-1,4-benzoxazin-3-one) and atrazin...

  6. Dentin Hypersensitivity and Oxalates

    PubMed Central

    Cunha-Cruz, J.; Stout, J.R.; Heaton, L.J.; Wataha, J.C.

    2011-01-01

    Treatment of dentin hypersensitivity with oxalates is common, but oxalate efficacy remains unclear. Our objective was to systematically review clinical trials reporting an oxalate treatment compared with no treatment or placebo with a dentin hypersensitivity outcome. Risk-of-bias assessment and data extraction were performed independently by two reviewers. Standardized mean differences (SMD) were estimated by random-effects meta-analysis. Of 677 unique citations, 12 studies with high risk-of-bias were included. The summary SMD for 3% monohydrogen-monopotassium oxalate (n = 8 studies) was -0.71 [95% Confidence Interval: -1.48, 0.06]. Other treatments, including 30% dipotassium oxalate (n = 1), 30% dipotassium oxalate plus 3% monohydrogen monopotassium oxalate (n = 3), 6% monohydrogen monopotassium oxalate (n = 1), 6.8% ferric oxalate (n = 1), and oxalate-containing resin (n = 1), also were not statistically significantly different from placebo treatments. With the possible exception of 3% monohydrogen monopotassium oxalate, available evidence currently does not support the recommendation of dentin hypersensitivity treatment with oxalates. PMID:21191127

  7. SF5-Enolates in Ti(IV)-Mediated Aldol Reactions.

    PubMed

    Ponomarenko, Maksym V; Grabowsky, Simon; Pal, Rumpa; Röschenthaler, Gerd-Volker; Fokin, Andrey A

    2016-08-01

    The F···Ti bonding in the transition structures determines high trans- and syn-diastereoselectivities for aldol reactions of SF5-acetates with aldehydes in the presence of TiCl4 in the non-nucleophilic solvent CH2Cl2. Such bonding is canceled in nucleophilic solvents where opposite cis-stereochemistry is observed. The potential of thus obtained stereoisomeric SF5-aryl acrylates as dipolarophiles in the preparation of SF5-containing heterocycles is demonstrated. PMID:27384450

  8. Drug Hypersensitivity: Pharmacogenetics and Clinical Syndromes

    PubMed Central

    Phillips, Elizabeth J.; Chung, Wen-Hung; Mockenhaupt, Maja; Roujeau, Jean-Claude; Mallal, Simon A.

    2011-01-01

    Severe cutaneous adverse reactions (SCARs) include syndromes such as drug reaction, eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) and Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN). An important advance has been the discovery of associations between HLA alleles and many of these syndromes including abacavir hypersensitivity reaction, allopurinol DRESS/DIHS and SJS/TEN and SJS/TEN associated with aromatic amine anticonvulsants. These HLA associations have created the promise for prevention through screening and have additionally shed further light on the immunopathogenesis of SCARs. The roll-out of HLA-B*5701 into routine clinical practice as a genetic screening test to prevent abacavir hypersensitivity provides a translational roadmap for other drugs. Numerous hurdles exist in the widespread translation of several other drugs such as carbamazepine where the positive predictive value of HLA-B*1502 is low and the negative predictive value of HLA-B*1502 for SJS/TEN may not be 100% in all ethnic groups. International collaborative consortia have been formed with the goal of developing phenotype standardization and undertaking HLA and genome-wide analyses in diverse populations with these syndromes. PMID:21354501

  9. Relationship between Sympathetic Skin Responses and Auditory Hypersensitivity to Different Auditory Stimuli

    PubMed Central

    Kato, Fumi; Iwanaga, Ryoichiro; Chono, Mami; Fujihara, Saori; Tokunaga, Akiko; Murata, Jun; Tanaka, Koji; Nakane, Hideyuki; Tanaka, Goro

    2014-01-01

    [Purpose] Auditory hypersensitivity has been widely reported in patients with autism spectrum disorders. However, the neurological background of auditory hypersensitivity is currently not clear. The present study examined the relationship between sympathetic nervous system responses and auditory hypersensitivity induced by different types of auditory stimuli. [Methods] We exposed 20 healthy young adults to six different types of auditory stimuli. The amounts of palmar sweating resulting from the auditory stimuli were compared between groups with (hypersensitive) and without (non-hypersensitive) auditory hypersensitivity. [Results] Although no group × type of stimulus × first stimulus interaction was observed for the extent of reaction, significant type of stimulus × first stimulus interaction was noted for the extent of reaction. For an 80 dB-6,000 Hz stimulus, the trends for palmar sweating differed between the groups. For the first stimulus, the variance became larger in the hypersensitive group than in the non-hypersensitive group. [Conclusion] Subjects who regularly felt excessive reactions to auditory stimuli tended to have excessive sympathetic responses to repeated loud noises compared with subjects who did not feel excessive reactions. People with auditory hypersensitivity may be classified into several subtypes depending on their reaction patterns to auditory stimuli. PMID:25140103

  10. The methylthiolation reaction mediated by the Radical-SAM enzymes

    PubMed Central

    Atta, Mohamed; Arragain, Simon; Fontecave, Marc; Mulliez, Etienne; Hunt, John F.; Luff, Jon D.; Forouhar, Farhad

    2014-01-01

    Over the past ten years, considerable progress has been made in our understanding of the mechanistic enzymology of the Radical-SAM enzymes. It is now clear that these enzymes appear to be involved in a remarkably wide range of chemically challenging reactions. This review article highlights mechanistic and structural aspects of the methylthiotransferases (MTTases) sub-class of the Radical-SAM enzymes. The mechanism of methylthio insertion, now observed to be performed by three different enzymes is an exciting unsolved problem. PMID:22178611

  11. Laryngeal hypersensitivity in chronic cough.

    PubMed

    Hull, J H; Menon, A

    2015-12-01

    Patients with chronic cough often report symptoms arising in the throat, in response to non-specific stimuli. Accordingly, the concept of a 'hypersensitivity' of the larynx in chronic cough has evolved over the past ten years. Patients with cough and laryngeal hypersensitivity frequently report features that overlap other laryngeal dysfunction syndromes, including a tendency for the vocal cords to inappropriately adduct. The mechanisms underlying laryngeal hypersensitivity in chronic cough are currently unclear, however recent studies provide new clinical and physiological techniques to aid detection and monitoring of laryngeal hypersensitivity. This review provides an overview of the current state of knowledge in this field. PMID:26325433

  12. Alkali metal mediated C–C bond coupling reaction

    SciTech Connect

    Tachikawa, Hiroto

    2015-02-14

    Metal catalyzed carbon-carbon (C–C) bond formation is one of the important reactions in pharmacy and in organic chemistry. In the present study, the electron and hole capture dynamics of a lithium-benzene sandwich complex, expressed by Li(Bz){sub 2}, have been investigated by means of direct ab-initio molecular dynamics method. Following the electron capture of Li(Bz){sub 2}, the structure of [Li(Bz){sub 2}]{sup −} was drastically changed: Bz–Bz parallel form was rapidly fluctuated as a function of time, and a new C–C single bond was formed in the C{sub 1}–C{sub 1}′ position of Bz–Bz interaction system. In the hole capture, the intermolecular vibration between Bz–Bz rings was only enhanced. The mechanism of C–C bond formation in the electron capture was discussed on the basis of theoretical results.

  13. Alkali metal mediated C-C bond coupling reaction

    NASA Astrophysics Data System (ADS)

    Tachikawa, Hiroto

    2015-02-01

    Metal catalyzed carbon-carbon (C-C) bond formation is one of the important reactions in pharmacy and in organic chemistry. In the present study, the electron and hole capture dynamics of a lithium-benzene sandwich complex, expressed by Li(Bz)2, have been investigated by means of direct ab-initio molecular dynamics method. Following the electron capture of Li(Bz)2, the structure of [Li(Bz)2]- was drastically changed: Bz-Bz parallel form was rapidly fluctuated as a function of time, and a new C-C single bond was formed in the C1-C1' position of Bz-Bz interaction system. In the hole capture, the intermolecular vibration between Bz-Bz rings was only enhanced. The mechanism of C-C bond formation in the electron capture was discussed on the basis of theoretical results.

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

    SciTech Connect

    Fang, Feng; Tang, Yijun; Gao, Zhe; Xu, Qiang

    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.

  15. Site-specific C-terminal internal loop labeling of proteins using sortase-mediated reactions

    PubMed Central

    Guimaraes, Carla P.; Witte, Martin D.; Theile, Christopher S.; Bozkurt, Gunes; Kundrat, Lenka; Blom, Annet E.M.; Ploegh, Hidde L.

    2014-01-01

    Methods for site-specific modification of proteins are in high demand. Reactions that yield bioconjugates should be quantitative, site-specific, and versatile with respect to nature and size of the biological/chemical targets involved, require minimal modification of the target, display acceptable kinetics under physiological conditions, and be orthogonal to other labeling methods. Sortase-mediated transpeptidation reactions meet these criteria. Here we describe the expression and purification conditions for two orthogonal sortase A enzymes and provide the protocol that allows functionalization of any given protein at its C-terminus or for select proteins at an internal site. Sortase-mediated reactions take only a few minutes, but reaction times can be extended to increase yields. PMID:23989673

  16. Drug hypersensitivity in students from São Paulo, Brazil

    PubMed Central

    Ensina, Luis Felipe Chiaverini; Amigo, Maria Helena Lopes; Koch, Thais; Guzman, Evelyn; Paoli, Renata; Nunes, Inês Cristina Camelo

    2010-01-01

    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 non-steroidal anti-inflammatory drug and antibiotics (beta-lactams and sulfonamide) are the most frequently concerned drugs. PMID:21120302

  17. Hypersensitivity to intravenous iron: classification, terminology, mechanisms and management.

    PubMed

    Szebeni, J; Fishbane, S; Hedenus, M; Howaldt, S; Locatelli, F; Patni, S; Rampton, D; Weiss, G; Folkersen, J

    2015-11-01

    Intravenous (IV) iron therapy is widely used in iron deficiency anaemias when oral iron is not tolerated or ineffective. Administration of IV-iron is considered a safe procedure, but severe hypersensitivity reactions (HSRs) can occur at a very low frequency. Recently, new guidelines have been published by the European Medicines Agency with the intention of making IV-iron therapy safer; however, the current protocols are still non-specific, non-evidence-based empirical measures which neglect the fact that the majority of IV-iron reactions are not IgE-mediated anaphylactic reactions. The field would benefit from new specific and effective methods for the prevention and treatment of these HSRs, and the main goal of this review was to highlight a possible new approach based on the assumption that IV-iron reactions represent complement activation-related pseudo-allergy (CARPA), at least in part. The review compares the features of IV-iron reactions to those of immune and non-immune HSRs caused by a variety of other infused drugs and thus make indirect inferences on IV-iron reactions. The process of comparison highlights many unresolved issues in allergy research, such as the unsettled terminology, multiple redundant classifications and a lack of validated animal models and lege artis clinical studies. Facts and arguments are listed in support of the involvement of CARPA in IV-iron reactions, and the review addresses the mechanism of low reactogenic administration protocols (LRPs) based on slow infusion. It is suggested that consideration of CARPA and the use of LRPs might lead to useful new additions to the management of high-risk IV-iron patients. PMID:26265306

  18. Case of immediate hypersensitivity to beer.

    PubMed

    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. PMID:26661797

  19. Immediate-type hypersensitivity to polyethylene glycols: a review.

    PubMed

    Wenande, E; Garvey, L H

    2016-07-01

    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 of PEG's allergenic potential remains low, due to a general lack of suspicion towards excipients and insufficient product labelling. Information on immediate-type reactions to PEG is limited to anecdotal reports, and the potential for PEG sensitization and cross-sensitization to PEGylated drugs and structurally related derivatives is likely underestimated. Most healthcare professionals have no knowledge of PEG and thus do not suspect PEG's as culprit agents in hypersensitivity reactions. In consequence, patients are at risk of misdiagnosis and commonly present with a history of repeated, severe reactions to a range of unrelated products in hospital and at home. Increased awareness of PEG prevalence, PEG hypersensitivity, and improved access to PEG allergy testing, should facilitate earlier diagnosis and reduce the risk of inadvertent re-exposure. This first comprehensive review provides practical information for allergists and other healthcare professionals by describing the clinical picture of 37 reported cases of PEG hypersensitivity since 1977, summarizing instances where PEG hypersensitivity should be considered and proposing an algorithm for diagnostic management. PMID:27196817

  20. Stent hypersensitivity and infection in sinus cavities

    PubMed Central

    Soufras, George D.; Hahalis, George

    2013-01-01

    Persistent mucosal inflammation, granulation tissue formation, hypersensitivity, and multifactorial infection are newly described complications of retained drug-eluting stents from endoscopic sinus surgery for refractory rhinosinusitis. In an important report published in Allergy and Rhinology, a 45-year-old male patient suffering from recalcitrant chronic rhinosinusitis underwent functional endoscopic sinus surgery and was found, for the first time, to have steroid-eluting catheters that were inadvertently left in the ethmoid and frontal sinuses. The retained catheters had caused persistent mucosal inflammation and formation of granulation tissue denoting hypersensitivity reaction. These consequences had induced perpetuation of symptoms of chronic rhinosinusitis. Meticulous removal of the retained stents with the nitinol wings from inflamed tissues of the frontal, ethmoidal, and sphenoethmoidal recesses in which they were completely imbedded was successfully performed without polypoid regrowth. Cultures of specimens taken from both left and right stents showed heavy growth of Stenotrophomonas maltophilia and moderate growth of Klebsiella oxytoca, coagulase negative Staphylococcus, and beta-hemolytic Streptococcus anginosus. Fungal infection was not detected. The current knowledge and experience regarding stent hypersensitivity and infection in relation with the use of stents in sinus cavities is reviewed. PMID:24498522

  1. Xanthomonas filamentous hemagglutinin-like protein Fha1 interacts with pepper hypersensitive-induced reaction protein CaHIR1 and functions as a virulence factor in host plants.

    PubMed

    Choi, Hyong Woo; Kim, Dae Sung; Kim, Nak Hyun; Jung, Ho Won; Ham, Jong Hyun; Hwang, Byung Kook

    2013-12-01

    Pathogens have evolved a variety of virulence factors to infect host plants successfully. We previously identified the pepper plasma-membrane-resident hypersensitive-induced reaction protein (CaHIR1) as a regulator of plant disease- and immunity-associated cell death. Here, we identified the small filamentous hemagglutinin-like protein (Fha1) of Xanthomonas campestris pv. vesicatoria as an interacting partner of CaHIR1 using yeast two-hybrid screening. Coimmunoprecipitation and bimolecular fluorescence complementation experiments revealed that Fha1 specifically interacts with CaHIR1 in planta. The endocytic tracker FM4-64 staining showed that the CaHIR1-Fha1 complex localizes in the endocytic vesicle-like structure. The X. campestris pv. vesicatoria Δfha1 mutant strain exhibited significantly increased surface adherence but reduced swarming motility. Mutation of fha1 inhibited the growth of X. campestris pv. vesicatoria and X. campestris pv. vesicatoria ΔavrBsT in tomato and pepper leaves, respectively, suggesting that Fha1 acts as a virulence factor in host plants. Transient expression of fha1 and also infiltration with purified Fha1 proteins induced disease-associated cell death response through the interaction with CaHIR1 and suppressed the expression of pathogenesis-related (PR) genes. Silencing of CaHIR1 in pepper significantly reduced ΔavrBsT growth and Fha1-triggered susceptibility cell death. Overexpression of fha1 in Arabidopsis retarded plant growth and triggered disease-associated cell death, resulting in altered disease susceptibility. Taken together, these results suggest that the X. campestris pv. vesicatoria virulence factor Fha1 interacts with CaHIR1, induces susceptibility cell death, and suppresses PR gene expression in host plants. PMID:23931712

  2. [Type IV of hypersensitivity and its subtypes].

    PubMed

    Czarnobilska, Ewa; Obtułowicz, Krystyna; Wsołek, Katarzyna

    2007-01-01

    Type IV of hypersensitivity reaction is usually manifested in the skin in different clinical pattern. According to traditional Gell and Coombs classification, the mechanism of IV type of allergic reaction has been associated with contact allergy with the activity of lymphocytes Th1 secreting interferon gamma. Now, this vision seems to be too simplified. In the last years there were publications, which can throw a new light on these complicated mechanisms leading to the development of the type IV of allergy, especially to drugs, nickel and other haptens and also can explain the differentiation of clinical pattern in respective patients. The skin symptoms in type IV of hypersensitivity are triggered by activation of specific T-cell CD4+ and CD8+. Immunohistochemical and functional analysis of reactive T-cell has shown that the delayed hypersensitivity reaction depends on the secreted cytokines. For example maculo-papular exanthema may be either triggered by Th1 or Th2 in nature and cytokines interferon gamma, tumor necrosis factor alfa or interleukin-4, 5 and 13. Bullous reactions (i.e. Stevens-Johnsons Syndrome or toxic epidermal necrolysis) are characterized by widespread keratinocyte apoptosis, a consequence of high CD8+ T-cell involvement and the molecular cytotoxicity of Fas, perforin and granzyme B. Pustular exanthema reactions are stimulated via the T-cell release of 11-8 and granulocyte-monocyte colony-stimulatig factor (GM-CSF). For the better understanding of these inflammatory cascades deleted type IV of hypersensitivity reactions have been re-classified into four main subtypes: 1. IVa with Th1 and monocyte directed and cytokines: IFNgamma, IL-1, IL-2, 2. IVb with Th2 and eosinophils directed and cytokines: L-5, IL-4, IL-13, 3. IVc with T CD8+ directed and cytokines: perforin, granzyme B, Fas Ligand, 4. IVd with T CD4+, CD8+ and neutrophil directed and cytokines: IL8, GM-CSF. Clinically delayed hypersensitivity eruptions are often an overlap of cytokine

  3. Hypersensitivity and nanoparticles: update and research trends

    PubMed Central

    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. PMID:27152071

  4. Predicting gold-mediated catalytic oxidative-coupling reactions from single crystal studies.

    PubMed

    Xu, Bingjun; Madix, Robert J; Friend, Cynthia M

    2014-03-18

    Though metallic gold is chemically inert under ambient conditions, its surface is extremely reactive and selective for many key oxidative chemical transformations when activated by atomic oxygen. A molecular-level understanding of the mechanism of these processes could allow researchers to design "green" catalytic processes mediated by gold-based materials. This Account focuses on the mechanistic framework for oxidative-coupling reactions established by fundamental studies on oxygen-activated Au(111) and the application of these principles to steady-state catalytic conditions. We also discuss the importance of the paradigms discovered both for predicting new oxidative-coupling reactions and for understanding existing literature. The mechanistic framework for the oxidative coupling of alcohols on gold surfaces predicts that new oxidative-coupling reactions should occur between amines and aldehydes and amines and alcohols as well as through alcohol carbonylation. Adsorbed atomic oxygen on the gold surface facilitates the activation of the substrates, and nucleophilic attack and β-H elimination are the two fundamental reactions that propagate the versatile chemistry that ensues. In the self-coupling of primary alcohols, adsorbed atomic oxygen first activates the O-H bond in the hydroxyl group at ∼150 K, which forms the corresponding adsorbed alkoxy groups. The rate-limiting step of the self-coupling reaction is the β-H elimination reaction of alkoxy groups to form the corresponding aldehydes and occurs with an activation barrier of approximately 12 kcal/mol. The remaining alkoxy groups nucleophilically attack the electron-deficient aldehyde carbonyl carbon to yield the adsorbed "hemiacetal". This intermediate undergoes facile β-H elimination to produce the final coupling products, esters with twice the number of carbon atoms as the starting alcohols. This mechanistic insight suggests that cross-coupling occurs between alcohols and aldehydes, based on the logic

  5. Proteomics Study on Nonallergic Hypersensitivity Induced by Compound 4880 and Ovalbumin

    PubMed Central

    Xu, Yubin; Guo, Na; Dou, Deqiang; Ran, Xiaoku; Ma, Xiande; Kuang, Haixue

    2016-01-01

    Nonallergic hypersensitivity reaction (NHR) accounts for more than 77% of all immune-mediated immediate hypersensitivity reactions and has become a serious threat to public health. Here, proteomics was used to study the NHR mechanism of two typical substances, the compound 4880 and ovalbumin. Twelve different proteins were suggested as potential biomarkers for examining the NHR mechanism, and our results revealed that the mechanism mainly encompassed 2 processes, i.e., generation and effect processes. The generation process could be classified as direct stimulation, complement (classical and alternative), coagulation, kallikrein-kinin, and integrated pathways. Thus glutathione peroxidase 1, terminal complement complex (complement factor 4d and Bb), coagulation 13, kininogen-1, and IgE could be used as candidate biomarkers for the indication of the corresponding pathways respectively, the proteins were further confirmed by ELISA. And the effect process was mainly composed of histamine as well as proteins such as DCD and MYLPF, which could be used as important indices for the symptoms of NHR. Our study differs from previous studies in that C4880 was found to not only be involved in the direct stimulation pathway, but also in the activated complement and kallikrein-kinin pathways through the coagulation pathway. We also report for the first time that ovalbumin-induced NHR could be a combination of the coagulation, classical complement, and integrated pathways. PMID:26829397

  6. Vitamin D Deficiency Promotes Skeletal Muscle Hypersensitivity and Sensory Hyperinnervation

    PubMed Central

    Tague, Sarah E.; Clarke, Gwenaëlle L.; Winter, Michelle K.; McCarson, Kenneth E.; Wright, Douglas E.; Smith, Peter G.

    2012-01-01

    Musculoskeletal pain affects nearly half of all adults, most of whom are vitamin D deficient. Previous findings demonstrated that putative nociceptors (“pain-sensing” nerves) express vitamin D receptors (VDRs), suggesting responsiveness to 1,25-dihydroxyvitamin D. In the present study, rats receiving vitamin D-deficient diets for 2– 4 weeks showed mechanical deep muscle hypersensitivity, but not cutaneous hypersensitivity. Muscle hypersensitivity was accompanied by balance deficits and occurred before onset of overt muscle or bone pathology. Hypersensitivity was not due to hypocalcemia and was actually accelerated by increased dietary calcium. Morphometry of skeletal muscle innervation showed increased numbers of presumptive nociceptor axons (peripherin-positive axons containing calcitonin gene-related peptide), without changes in sympathetic or skeletal muscle motor innervation. Similarly, there was no change in epidermal innervation. In culture, sensory neurons displayed enriched VDR expression in growth cones, and sprouting was regulated by VDR-mediated rapid response signaling pathways, while sympathetic outgrowth was not affected by different concentrations of 1,25-dihydroxyvitamin D. These findings indicate that vitamin D deficiency can lead to selective alterations in target innervation, resulting in presumptive nociceptor hyperinnervation of skeletal muscle, which in turn is likely to contribute to muscular hypersensitivity and pain. PMID:21957236

  7. Systematic Investigation of EDC/sNHS-Mediated Bioconjugation Reactions for Carboxylated Peptide Substrates.

    PubMed

    Totaro, Kyle A; Liao, Xiaoli; Bhattacharya, Keshab; Finneman, Jari I; Sperry, Justin B; Massa, Mark A; Thorn, Jennifer; Ho, Sa V; Pentelute, Bradley L

    2016-04-20

    1-Ethyl-3-(3-(dimethylamino)propyl)carbodiimide (EDC) bioconjugations have been utilized in preparing variants for medical research. While there have been advances in optimizing the reaction for aqueous applications, there has been limited focus toward identifying conditions and side reactions that interfere with product formation. We present a systematic investigation of EDC/N-hydroxysulfosuccinimide (sNHS)-mediated bioconjugations on carboxylated peptides and small proteins. We identified yet-to-be-reported side products arising from both the reagents and substrates. Model peptides used in this study illustrate particular substrates are more susceptible to side reactions than others. From our studies, we found that bioconjugations are more efficient with high concentrations of amine nucleophile but not sNHS. Performing bioconjugations on a model affibody protein show that the trends established with model peptides hold for more complex systems. PMID:26974183

  8. Dapsone hypersensitivity syndrome not related to G6PD deficiency.

    PubMed

    Schulkes, Karlijn J G; Tervaert, J W Cohen; Rijken, Feiko; Haas, Lenneke E M

    2015-01-01

    Dapsone hypersensitivity syndrome (DHS) is a rare, but potentially life-threatening reaction to dapsone. We describe a 55-year-old Caucasian woman with normal glucose-6-phosphate dehydrogenase levels presenting with an extensive skin eruption, high-grade fever, pneumonitis and hepatitis, which occurred within 3 weeks after initiation of dapsone. In addition to supportive care, the patient was successfully treated with high-dose corticosteroids and antibiotics. The combination of high-grade fever, skin rash, lung and liver involvement made a dapsone hypersensitivity syndrome very likely. PMID:26682839

  9. Effect of Premedications in a Murine Model of Asparaginase Hypersensitivity

    PubMed Central

    Fernandez, Christian A.; Smith, Colton; Karol, Seth E.; Ramsey, Laura B.; Liu, Chengcheng; Pui, Ching-Hon; Jeha, Sima; Evans, William E.; Finkelman, Fred D.

    2015-01-01

    A murine model was developed that recapitulates key features of clinical hypersensitivity to Escherichia coli asparaginase. Sensitized mice developed high levels of anti-asparaginase IgG antibodies and had immediate hypersensitivity reactions to asparaginase upon challenge. Sensitized mice had complete inhibition of plasma asparaginase activity (P = 4.2 × 10−13) and elevated levels of mouse mast cell protease 1 (P = 6.1 × 10−3) compared with nonsensitized mice. We investigated the influence of pretreatment with triprolidine, cimetidine, the platelet activating factor (PAF) receptor antagonist CV-6209 [2-(2-acetyl-6-methoxy-3,9-dioxo-4,8-dioxa-2,10-diazaoctacos-1-yl)-1-ethyl-pyridinium chloride], or dexamethasone on the severity of asparaginase-induced allergies. Combining triprolidine and CV-6209 was best for mitigating asparaginase-induced hypersensitivity compared with nonpretreated, sensitized mice (P = 1.2 × 10−5). However, pretreatment with oral dexamethasone was the only agent capable of mitigating the severity of the hypersensitivity (P = 0.03) and partially restoring asparaginase activity (P = 8.3 × 10−4). To rescue asparaginase activity in sensitized mice without requiring dexamethasone, a 5-fold greater dose of asparaginase was needed to restore enzyme activity to a similar concentration as in nonsensitized mice. Our results suggest a role of histamine and PAF in asparaginase-induced allergies and indicate that mast cell–derived proteases released during asparaginase allergy may be a useful marker of clinical hypersensitivity. PMID:25573198

  10. Studies on the mechanism of systemic suppression of contact hypersensitivity by UVB radiation. II. Differences in the suppression of delayed and contact hypersensitivity in mice.

    PubMed

    Kripke, M L; Morison, W L

    1986-05-01

    Exposing mice to UV radiation in the UVB range (280-320 nm) causes a selective immune suppression that contributes to the development of UVB-induced skin cancers. Among the immune responses suppressed by UVB irradiation are contact and delayed hypersensitivity reactions to haptens administered at unexposed sites. In these studies we provide evidence that delayed and contact hypersensitivity to the same hapten are not equivalent reactions and that they are suppressed in UVB-irradiated mice by 2 different mechanisms. This conclusion is based on the findings that: suppression of contact hypersensitivity could not be overcome by immunizing UVB-irradiated mice with hapten-coupled antigen-presenting cells derived from normal donors; and treatment of UVB-irradiated mice with methylprednisolone before immunization prevented the suppression of delayed hypersensitivity but had no effect on the suppression of contact hypersensitivity. The decreased ability to induce contact hypersensitivity in UVB-irradiated mice could be transferred to x-irradiated mice by reconstituting them with spleen cells from UVB-irradiated donors. The induction of hapten-specific suppressor cells, however, required both UVB irradiation and priming with hapten. Based on these results, we postulate that UVB irradiation induces a population of suppressor-inducer cells with specificity for a modified skin antigen and that this antigen serves as a carrier molecule for haptens that induce contact hypersensitivity and for tumor-specific transplantation antigens on UVB-induced tumors. PMID:3745963