RESUMO
BACKGROUND: Nasal congestion could affect the absorption of an epinephrine nasal spray (ENS). OBJECTIVE: To compare the pharmacokinetics of 13.2 mg ENS with nasal congestion vs without congestion and vs intramuscular (IM) treatments. METHODS: This phase I, open-label, 4-period randomized crossover study enrolled 51 healthy adults with seasonal allergies into cohorts that received a single dose of 13.2 mg ENS (NDS1C; Bryn Pharma, Lebanon, New Jersey) administered as 2 consecutive sprays in either opposite nostrils (cohort 1) or the same nostril (cohort 2). Both cohorts received 13.2 mg ENS with and without nasal allergen challenge (NAC), 0.3 mg IM epinephrine by autoinjector, and 0.5 mg IM epinephrine by manual syringe (MS). RESULTS: The ENS after NAC resulted in higher extent and peak exposures and more rapid time to maximum plasma concentration vs ENS without NAC and IM treatments. In cohort 1, the maximum observed baseline-adjusted epinephrine plasma concentration (pg/mL) of ENS with NAC, IM autoinjector, IM MS, or ENS without NAC was 458.0, 279.0, 364.2, and 270.1, respectively, and in cohort 2 was 436.3, 228.2, 322.3, and 250.8, respectively. The maximum observed baseline-adjusted epinephrine plasma concentration geometric mean ratio (90% CI) for ENS with NAC vs without NAC in cohort 1 was 170% (123%-234%), and in cohort 2 was 174% (115%-263%). In cohort 1, the time to maximum plasma concentration was 15, 21, 45, and 25 minutes, respectively, and in cohort 2 was 18, 20, 45, and 20 minutes, respectively (P < .01 for ENS with NAC vs IM MS). The postdose mean heart rate and blood pressure remained stable and relatively similar to predose values regardless of plasma epinephrine concentration. Mild nausea and headache were the most common adverse events with ENS. CONCLUSION: The 13.2 mg ENS with congestion exhibited enhanced absorption vs IM treatments and ENS without congestion and seemed to be well tolerated. There was no clinically impactful relationship between pharmacodynamic effects and plasma epinephrine concentration.
Assuntos
Administração Intranasal , Estudos Cross-Over , Epinefrina , Humanos , Epinefrina/farmacocinética , Epinefrina/administração & dosagem , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Adulto Jovem , Sprays Nasais , Rinite Alérgica Sazonal/tratamento farmacológico , Obstrução Nasal/tratamento farmacológico , Adolescente , Alérgenos/imunologia , Alérgenos/administração & dosagem , Alérgenos/farmacocinética , Injeções IntramuscularesRESUMO
Japanese allergic subjects are commonly sensitized to both house dust mite (HDM) and Japanese cedar pollen (JCP) and combined treatment with sublingual immunotherapy (SLIT) tablets is desirable. However, mixing extracts of two non-homologous allergens may compromise allergen stability and affect the clinical outcome. Therefore, we investigated the stability of major allergens and total allergenic reactivity of HDM and JCP SLIT-tablets following dissolution in human saliva or artificial gastric juice. Two fast-dissolving freeze-dried SLIT-tablets were completely dissolved and incubated at 37 °C. Major allergen concentrations and total allergenic reactivity were measured. After mixing and co-incubation of HDM and JCP SLIT tablets in human saliva for 10 min at 37°C, there were no statistically significant changes in major allergen concentrations. In addition, no loss of allergenic reactivity of the mixed two SLIT-tablet solutions was seen. In contrast, complete loss of allergenic reactivity and detectable major allergen concentrations occurred when the two SLIT-tablets were dissolved and incubated in artificial gastric juice. These results demonstrate that HDM or JCP major allergens and the total allergenic reactivity of both SLIT-tablets measured here remain intact after dissolution and co-incubation in human saliva, supporting the possibility of a dual HDM and JCP SLIT-tablet administration regimen if clinically indicated. The complete loss of allergenic reactivity after incubation in artificial gastric juice can furthermore be taken to indicate that the immunological activity of the allergen extracts contained in the two SLIT-tablets is likely to be lost or severely compromised upon swallowing.
Assuntos
Alérgenos/química , Antígenos de Dermatophagoides/química , Pólen/imunologia , Rinite Alérgica/terapia , Imunoterapia Sublingual/métodos , Administração Sublingual , Alérgenos/administração & dosagem , Alérgenos/farmacocinética , Antígenos de Dermatophagoides/administração & dosagem , Cryptomeria/imunologia , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Japão , Mucosa Bucal/química , Mucosa Bucal/metabolismo , Absorção pela Mucosa Oral , Rinite Alérgica/etiologia , Saliva/química , Comprimidos , Resultado do TratamentoRESUMO
Inflammatory response in the skin is important for host defense against a broad spectrum of insults including microorganisms, chemicals, radiation and physical trauma. When the inflammatory process becomes prolonged and self-perpetuating, illness occurs. In this review, we discuss recent findings regarding the complex inflammatory mechanisms in allergic contact dermatitis, atopic dermatitis and psoriasis.
Assuntos
Dermatite Alérgica de Contato/patologia , Dermatite Atópica/patologia , Psoríase/patologia , Alérgenos/efeitos adversos , Alérgenos/farmacocinética , Biotransformação , Citocinas/fisiologia , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/genética , Dermatite Alérgica de Contato/imunologia , Dermatite Atópica/etiologia , Dermatite Atópica/genética , Dermatite Atópica/imunologia , Estudo de Associação Genômica Ampla , Humanos , Inflamação/patologia , Microbiota , Modelos Imunológicos , Psoríase/induzido quimicamente , Psoríase/genética , Psoríase/imunologia , Pele/imunologia , Pele/patologia , Subpopulações de Linfócitos T/imunologiaRESUMO
This study was performed to determine Parvalbumin (PV), a well-known fish allergenic protein, digestion kinetics and immunoreactivity of digestion products with Immunoglobulin G/Immunoglobulin E recognition to understand its allergic potential with or without lipid emulsion process. PV was subjected to simulated gastrointestinal digestion in emulsified condition. Digestion kinetics of the protein was analysed by electrophoresis, IgG/IgE binding ability by immunoblotting and indirect ELISA. Lipid emulsion significantly (pâ¯<â¯0.01) reduced the degree of PV hydrolysis by 52.10% for gastric digestion. Immune fragments of gastric digestion were detectable for 90-120â¯min longer in emulsified condition showing resistance. Consequently, lipid emulsion decreased the digestive ability of PV in stomach, increasing resistance to gastrointestinal digestion by pepsin proteases. It also altered IgG/IgE binding ability of digestion products, thereby indicating that PV with lipid emulsion was resistant to digestion and possessed increased IgE binding ability resulting in higher risk of allergy among sensitized individuals.
Assuntos
Alérgenos/farmacocinética , Emulsões/farmacocinética , Proteínas de Peixes da Dieta/farmacocinética , Hipersensibilidade Alimentar/imunologia , Parvalbuminas/farmacocinética , Alérgenos/imunologia , Alérgenos/metabolismo , Animais , Digestão , Emulsões/química , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas de Peixes da Dieta/imunologia , Linguados , Hipersensibilidade Alimentar/etiologia , Immunoblotting , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Lipídeos/química , Lipídeos/farmacocinética , Camundongos Endogâmicos BALB C , Parvalbuminas/imunologia , Parvalbuminas/metabolismo , Pepsina A/metabolismoRESUMO
Introduction: Allergen bioavailability underpins the efficacy and safety of SLIT tablets. Three product-related factors are likely to influence this: tablet potency, formulation and sublingual holding time. Areas covered: Tablet formulation determines the rate and extent of solubilized allergen release. Using validated in vitro dissolution assays, the two licensed grass pollen SLIT tablets are shown to release ≥85% of their total allergenic activity within several minutes. Sublingual holding time affects the contact duration between solubilized allergens and sublingual tissue. Maximal uptake of allergens by sublingual tissue requires ~5 minutes, with little uptake occurring within the first minute. A higher potency tablet with longer sublingual holding time would provide higher bioavailability, while faster rates of allergen release in vitro are unlikely to translate to a greater increase in bioavailability. Differences in dissolution times cannot serve as a surrogate of in vivo bioavailability, and are not related to differences in efficacy at the marketed tablet dosages. Rapid in vitro dissolution is likely not a key requirement for inducing a potent immune response. Expert opinion: In vitro dissolution cannot predict the clinical efficacy of SLIT tablets but could be important in immune tolerance and safety. In addition, a discontinuous administration regimen may have benefits for adherence and cost without compromising efficacy.
Assuntos
Alérgenos/uso terapêutico , Poaceae/imunologia , Rinite Alérgica/terapia , Imunoterapia Sublingual/métodos , Administração Sublingual , Alérgenos/administração & dosagem , Alérgenos/farmacocinética , Disponibilidade Biológica , Liberação Controlada de Fármacos , Humanos , Rinite Alérgica/imunologia , Rinite Alérgica/metabolismo , Comprimidos , Resultado do TratamentoRESUMO
Turbot can induce allergy in susceptible individuals due to the presence of parvalbumin (PV), a major fish allergen. This study aimed at evaluating the digestibility and the ability of PV to elicit the release of cellular degranulation, following treatment with tyrosinase (PV-Tyr), caffeic acid (PV-CA) and in combination (PV-Tyr/CA), using in vitro digestion and RBL-2H3 (passive rat basophil leukemia) cell line. The digestion assay products revealed that the stability of PV in simulated gastric fluid (SGF) was stronger, while in simulated intestinal fluid (SIF) was rather weak. Western blot analysis revealed that the IgG-binding abilities of the cross-linked PV were markedly reduced. Moreover, crosslinking hampered the release of cellular degranulation process in RBL-2H3 cell lines. PV-Tyr/CA showed highly significant reduction in the release rate of ß-hexosaminidase (66.02%), histamine (35.01%), tryptase (29.25%), cysteinyl leukotrienes (29.72%), prostaglandin D2 (34.96%), IL-4 (43.99%) and IL-13 (38.93%) and shown potential in developing hypoallergenic fish products.
Assuntos
Ácidos Cafeicos/química , Citocinas/metabolismo , Hipersensibilidade Alimentar/imunologia , Monofenol Mono-Oxigenase/química , Parvalbuminas/química , Alérgenos/química , Alérgenos/farmacocinética , Animais , Degranulação Celular/efeitos dos fármacos , Linhagem Celular , Digestão , Proteínas de Peixes da Dieta/química , Linguados , Suco Gástrico , Histamina/metabolismo , Humanos , Parvalbuminas/imunologia , Parvalbuminas/farmacologia , Ratos , beta-N-Acetil-Hexosaminidases/metabolismoRESUMO
BACKGROUND: Aspirin enhances food allergy symptoms by increasing absorption of ingested allergens. The objective of this study is to elucidate the role of aspirin in facilitating intestinal absorption of the wheat allergen, gliadin, in rats. METHODS: Plasma concentrations of gliadin were determined after oral administration by gavage or administration into a closed intestinal loop in rats. We used an in situ intestinal re-circulating perfusion experiment to examine the effect of pepsin on aspirin-facilitated gliadin absorption. Fluorescein isothiocyanate (FITC)-labeled dextran-40 (FD-40) was used as a marker of non-specific absorption. The molecular size of gliadin and its allergenicity in plasma were examined using immunoblot analysis and intradermal reaction tests with Evans blue dye (EBD) extravasation, respectively. RESULTS: Aspirin increased plasma concentrations of gliadin after oral administration but had no effect in the closed intestinal loop study. An in situ intestinal re-circulating perfusion study showed that FITC-labeled gliadin was absorbed similarly to FD-40. Aspirin increased absorption of both intact and pepsin-digested gliadin, with a more significant effect on absorption of pepsin-treated gliadin. Immunoblotting showed that most gliadin was absorbed in intact form. When the gliadin fraction was extracted from rat plasma after gavage and injected intradermally into gliadin-sensitized rats, EBD extravasation was observed at injection sites in a gliadin dose-dependent manner. CONCLUSIONS: Aspirin increased the absorption of intact and pepsin-digested gliadin via the paracellular pathway, maintaining their allergenicity. Moreover, the effect of aspirin on gliadin absorption was enhanced by modification and digestion of gliadin in the stomach.
Assuntos
Alérgenos/farmacocinética , Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Gliadina/farmacocinética , Absorção Intestinal/efeitos dos fármacos , Administração Oral , Alérgenos/sangue , Alérgenos/química , Animais , Gliadina/sangue , Gliadina/química , Masculino , Pepsina A/química , Ratos Sprague-Dawley , TriticumRESUMO
SCOPE: During food processing, the Maillard reaction (ÐR) may occur, resulting in the formation of glycated proteins. Glycated proteins are of particular importance in food allergies because glycation may influence interactions with the immune system. This study compared native and extensively glycated milk allergen ß-lactoglobulin (BLG), in their interactions with cells crucially involved in allergy. METHODS AND RESULTS: BLG was glycated in MR and characterized. Native and glycated BLG were tested in experiments of epithelial transport, uptake and degradation by DCs, T-cell cytokine responses, and basophil cell degranulation using ELISA and flow cytometry. Glycation of BLG induced partial unfolding and reduced its intestinal epithelial transfer over a Caco-2 monolayer. Uptake of glycated BLG by bone marrow-derived dendritic cells (BMDC) was increased, although both BLG forms entered BMDC via the same mechanism, receptor-mediated endocytosis. Once inside the BMDC, glycated BLG was degraded faster, which might have led to observed lower cytokine production in BMDC/CD4+ T-cells coculture. Finally, glycated BLG was less efficient in induction of degranulation of BLG-specific IgE sensitized basophil cells. CONCLUSIONS: This study suggests that glycation of BLG by MR significantly alters its fate in processes involved in immunogenicity and allergenicity, pointing out the importance of food processing in food allergy.
Assuntos
Alérgenos/química , Lactoglobulinas/química , Lactoglobulinas/imunologia , Hipersensibilidade a Leite/imunologia , Alérgenos/imunologia , Alérgenos/farmacocinética , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Células CACO-2 , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Endocitose/efeitos dos fármacos , Endocitose/fisiologia , Feminino , Manipulação de Alimentos , Humanos , Lactoglobulinas/farmacocinética , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Reação de Maillard , Camundongos Endogâmicos C3H , Leite/química , Leite/imunologiaRESUMO
The aim of this work was to evaluate the potential application of an original oral immunotherapy, based on the use of nanoparticles, against an experimentally induced peanut allergy. In this context, a roasted peanut extract, containing the main allergenic proteins, were encapsulated into poly(anhydride) nanoparticles. The resulting peanut-loaded nanoparticles (PE-NP) displayed a mean size of about 150nm and a significantly lower surface hydrophobicity than empty nanoparticles (NP). This low hydrophobicity correlated well with a higher in vitro diffusion in pig intestinal mucus than NP and an important in vivo capability to reach the intestinal epithelium and Peyer's patches. The immunotherapeutic capability of PE-NP was evaluated in a model of pre-sensitized CDI mice to peanut. After completing therapy of three doses of peanut extract, either free or encapsulated into nanoparticles, mice underwent an intraperitoneal challenge. Anaphylaxis was evaluated by means of assessment of symptom scores and mouse mast cell protease-1 levels (mMCPT-1). PE-NP treatment was associated with significant lower levels of mMCPT-1, and a significant survival rate after challenge, confirming the protective effect of this formulation against the challenge. In summary, this nanoparticle-based formulation might be a valuable strategy for peanut-specific immunotherapy.
Assuntos
Alérgenos , Arachis/química , Dessensibilização Imunológica/métodos , Nanopartículas , Hipersensibilidade a Amendoim/tratamento farmacológico , Proteínas de Plantas , Administração Oral , Alérgenos/química , Alérgenos/farmacocinética , Alérgenos/farmacologia , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Nanopartículas/química , Nanopartículas/uso terapêutico , Hipersensibilidade a Amendoim/imunologia , Hipersensibilidade a Amendoim/patologia , Proteínas de Plantas/química , Proteínas de Plantas/farmacocinética , Proteínas de Plantas/farmacologiaRESUMO
BACKGROUND: In spite of extensive regulation to limit exposure, nickel remains the main cause of contact allergy in the general population. More detailed knowledge on the skin uptake of haptens is required. So far, no method exists for the visualization of this clinically relevant hapten and its distribution in the skin. OBJECTIVES: To show, in terms of a proof of concept, that imaging mass spectrometry [time of flight secondary ion mass spectrometry (ToF-SIMS)] can be applied for investigation of the penetration and distribution of nickel in human skin. METHOD: Full-thickness human skin obtained from breast reduction surgery was exposed to nickel sulfate (5% in deionized water) for 24 h in Franz-type diffusion cells. Biopsies were obtained from nickel-treated samples and control (deionized water). The tissue was sliced, and analysed with ToF-SIMS, generating high-resolution images of ion distribution in the epidermis and upper dermis. RESULTS: The skin layers could be discerned from the ToF-SIMS data, particularly on the basis of the collagen signal. Nickel ions were localized to the stratum corneum and upper epidermis. CONCLUSIONS: This is the first time that ToF-SIMS has been applied to trace the distribution of a hapten in human skin. Proof of principle was shown for nickel, and the technique can, in the future, be expanded for investigation of the skin distribution of clinically relevant sensitizers in general.
Assuntos
Alérgenos/farmacocinética , Dermatite Alérgica de Contato/etiologia , Haptenos , Níquel/farmacocinética , Pele/química , Espectrometria de Massa de Íon Secundário , Humanos , Técnicas In Vitro , Estudo de Prova de Conceito , Pele/diagnóstico por imagemRESUMO
BACKGROUND: ß-lactoglobulin (BLG), a major allergen in cow milk (CM) can be detected in human breast-milk (BM) and is associated with exacerbation of symptoms in breastfed infants with cow milk protein allergy (CMPA). Currently, it is not known how long lactating mothers who consume dairy products need to withhold breastfeeding. OBJECTIVE: To elucidate the kinetics of BLG in BM after maternal ingestion of a single dose of CM. METHODS: Nineteen lactating mothers, four of whom had infants with CMPA, were instructed to avoid CM for 7 days before ingesting a single dose of CM and to continue to withhold CM thereafter throughout the study period. BLG was measured by ELISA in BM from 15 mothers of healthy infants before and at 3, 6 and 24 h, and 3 and 7 days after CM ingestion. Four pairs of mothers and CMPA infants were enrolled for BM challenge after the mothers had ingested CM. RESULTS: After CM ingestion, the level of BLG in BM increased significantly from 0.58 ng/ml (0.58 g/L) (IQR 0.38-0.88) to a peak level of 1.23 ng/ml (IQR 1.03-2.29), p < 0.001. The BLG level on day 3 (1.15 ng/ml, IQR 0.89-1.45) and day 7 (1.08 ng/ml (IQR 0.86-1.25) after CM ingestion was significantly higher than baseline (p = 0.01 and p = 0.001, respectively). BLG was detected in all BM samples from the four mothers of CMPA infants after CM ingestion, and the level was not different from that in the mothers of the 15 healthy infants. Three of the four CMPA infants developed symptoms such as maculopapular rash and hypersecretion in the airways after BM challenge. CONCLUSIONS: BLG can be detected in BM up to 7 days after CM ingestion. Lactating mothers should suspend breastfeeding to CMPA infants more than 7 days after CM ingestion.
Assuntos
Alérgenos/análise , Alérgenos/farmacocinética , Dieta , Lactoglobulinas/análise , Lactoglobulinas/farmacocinética , Leite Humano/química , Animais , Bovinos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Fatores de TempoRESUMO
It is widely accepted that substances that cannot penetrate through the skin will not be sensitizers. LogKow and molecular weight (MW) have been used to set thresholds for sensitization potential. Highly hydrophilic substances e.g. LogKow ≤ 1 are expected not to penetrate effectively to induce sensitization. To investigate whether LogKow >1 is a true requirement for sensitization, a large dataset of substances that had been evaluated for their skin sensitization potential under Registration, Evaluation, Authorisation and restriction of CHemicals (REACH), together with available measured LogKow values was compiled using the OECD eChemPortal. The incidence of sensitizers relative to non-sensitizers above and below a LogKow of 1 was explored. Reaction chemistry principles were used to explain the sensitization observed for the subset of substances with a LogKow ≤0. 1482 substances were identified with skin sensitization data and measured LogKow values. 525 substances had a measured LogKow ≤ 1, 100 of those were sensitizers. There was no significant difference in the incidence of sensitizers above and below a LogKow of 1. Reaction chemistry principles that had been established for lower MW and more hydrophobic substances were found to be still valid in rationalizing the skin sensitizers with a LogKow ≤ 0. The LogKow threshold arises from the widespread misconception that the ability to efficiently penetrate the stratum corneum is a key determinant of sensitization potential and potency. Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Alérgenos/farmacocinética , Dermatite Alérgica de Contato/imunologia , Compostos Orgânicos/farmacocinética , Absorção Cutânea/efeitos dos fármacos , Alérgenos/imunologia , Alérgenos/toxicidade , Animais , Bases de Dados Factuais , Dermatite Alérgica de Contato/etiologia , Modelos Químicos , Compostos Orgânicos/imunologia , Compostos Orgânicos/toxicidade , PermeabilidadeRESUMO
Hair dye products now represent one of the most rapidly growing beauty and personal care industries as both men and women commonly change hair color to enhance youth and beauty and to follow fashion trends. Irrespective of economic and education status, people dye their hair to emphasize the importance given to appearance. Despite adverse reactions, many people continue dyeing mainly for cosmetic purposes. This paper provides a comprehensive review on various aspects of hair dying products, especially with respect to the hair-coloring process, classification, chemical ingredients, possible human health impacts, and regulations. Permanent hair dye, which is the most commonly used product type, is formed by an oxidative process involving arylamines to bring about concerns with long-term exposure. Hence, significant efforts have been put to understand the possible side effects of such exposure including cancer risk. However, hair dyes and their ingredients are mainly identified to have moderate to low acute toxicity such as the cause of allergic contact dermatitis. Although some hair dye components are reported to be carcinogenic in animals, such evidence is not consistent enough in the case of human studies. Consequently, further research is desirable to critically address the significance of this issue, especially with respect to the safety of hair dye ingredients.
Assuntos
Alérgenos/efeitos adversos , Dermatite Alérgica de Contato , Tinturas para Cabelo/efeitos adversos , Adolescente , Alérgenos/química , Alérgenos/farmacocinética , Animais , Qualidade de Produtos para o Consumidor/legislação & jurisprudência , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/etiologia , Feminino , Regulamentação Governamental , Tinturas para Cabelo/química , Tinturas para Cabelo/farmacocinética , Humanos , Masculino , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/epidemiologiaRESUMO
BACKGROUND: Paediatric age, active eczema and high number of allergens tested in poly-sensitized patients have been pinpointed as possible risk factors of systemic reactions by skin prick testing. As far as atopic eczema concerns, the higher penetration of the allergens into the skin because of the scraping or micro-injuries is an intuitive rationalization. Purpose of the present study is to provide documentary evidence that adverse reactions elicited by anomalous absorption of allergens can occur also in adult patients with apparently normal skin. METHODS: Report of some exemplifying clinical and experimental observations. Measuring the inoculum volume into impaired skin and its variability in relation to the variation of the chemical-physical characteristic of the solutions used for the tests by means of a method of direct assay based on the use of a gamma-camera. RESULTS: Localized impairments of the skin permeability can cause a significant increase in inoculum volume by prick-test. Critical amounts of allergens can be introduced into the skin because of the possibility of direct absorption, also without pricking, of allergy diagnostic solutions. The greater water content of the solutions used for prick-testing can significantly increase the inoculum volume. CONCLUSIONS: This study adds clinical and experimental evidences that localized impairments of permeability can occur in adult patients with apparently normal skin. Special precautions should be taken when a change of the drops' normal shape and cohesion is seen, because allergy prick-testing in such areas is potentially associated with increased risk of large local or systemic reactions.
Assuntos
Alérgenos/farmacocinética , Absorção Cutânea , Testes Cutâneos/efeitos adversos , Adulto , Feminino , Humanos , MasculinoRESUMO
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.
Assuntos
Alérgenos , Hidrato de Cloral , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/metabolismo , Exposição Ocupacional/efeitos adversos , Tricloroetileno , Adulto , Alérgenos/efeitos adversos , Alérgenos/farmacocinética , Hidrato de Cloral/efeitos adversos , Hidrato de Cloral/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tricloroetileno/efeitos adversos , Tricloroetileno/farmacocinéticaRESUMO
Chemical respiratory sensitization is an important occupational health problem which may lead to severely incapacitated human health, yet there are currently no validated or widely accepted models for identifying and characterizing the potential of a chemical to induce respiratory sensitization. This is in part due to the ongoing uncertainty about the immunological mechanisms through which respiratory sensitization may be acquired. Despite the lack of test method, regulations such as REACH still require an assessment of respiratory sensitization for risk assessment and/or for the purposes of classification and labeling. The REACH guidance describes an integrated evaluation strategy to characterize what information sources could be available to facilitate such an assessment. The components of this include a consideration of well-established structural alerts and existing data (whether it be derived from read-across, (quantitative) structure-activity relationships ((Q)SAR), in vivo studies etc.). There has been some progress in developing SARs as well as a handful of empirical QSARs. More recently, efforts have been focused on exploring whether the reaction chemistry mechanistic domains first characterized for skin sensitization are relevant for respiratory sensitization and to what extent modifications or refinements are needed to rationalize the differences between the two end points as far as their chemistry is concerned. This study has built upon the adverse outcome pathway (AOP) for skin sensitization that was developed and published by the OECD in 2012. We have structured a workflow to characterize the initiating events that are relevant in driving respiratory sensitization. OASIS pipeline technology was used to encode these events as components in a software platform to enable a prediction of respiratory sensitization potential to be made for new untested chemicals. This prediction platform could be useful in the assessment of respiratory sensitization potential or for grouping chemicals for subsequent read-across.
Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Alérgenos/toxicidade , Modelos Biológicos , Hipersensibilidade Respiratória/etiologia , Poluentes Ocupacionais do Ar/química , Poluentes Ocupacionais do Ar/farmacocinética , Alérgenos/química , Alérgenos/farmacocinética , Animais , Disponibilidade Biológica , Cisteína/química , Dermatite Alérgica de Contato/etiologia , Humanos , Fígado/metabolismo , Pulmão/metabolismo , Lisina/química , Peptídeos/química , Ligação Proteica , Medição de Risco/métodos , Pele/metabolismo , Relação Estrutura-AtividadeRESUMO
We investigated the mechanism of transplacental macromolecular transport in rats on the nineteenth day of pregnancy using tracers, transmission electron microscopy and immunohistochemistry. The blood-placental barrier of full-term rat placentas was composed of a trilaminar layer of trophoblast cells that separates the fetal capillaries from the maternal blood spaces: a layer of cytotrophoblasts lining the maternal blood space and a bilayer of syncytiotrophoblast surrounding the fetal capillaries. Horseradish peroxidase, intravenously injected into the maternal circulation, was found in the maternal blood spaces, the interspaces between the cytotrophoblasts and the syncytiotrophoblast I, many pits and small vesicles in the syncytiotrophoblast I, vesicles of the syncytiotrophoblast II, fetal connective tissue and fetal capillaries. Intravenously injected ovalbumin was detected in the maternal blood spaces, a trilaminar layer and the fetal capillaries. Neonatal Fc receptor (FcRn), a receptor for IgG, was localized at the maternal side of the blood-placental barrier. These results show that the structure of the rat blood-placental barrier is quite similar to the human blood-placental barrier, and non-specific macromolecules and food allergens may penetrate through the blood-placental barrier of the full-term placenta from the maternal to fetal circulation mediated by FcRn.
Assuntos
Troca Materno-Fetal , Ovalbumina/farmacocinética , Placenta/metabolismo , Trofoblastos/metabolismo , Alérgenos/administração & dosagem , Alérgenos/farmacocinética , Animais , Transporte Biológico , Feminino , Antígenos de Histocompatibilidade Classe I/metabolismo , Peroxidase do Rábano Silvestre/administração & dosagem , Peroxidase do Rábano Silvestre/farmacocinética , Humanos , Imuno-Histoquímica , Injeções Intravenosas , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Ovalbumina/administração & dosagem , Placenta/irrigação sanguínea , Placenta/embriologia , Gravidez , Ratos Wistar , Receptores Fc/metabolismo , Trofoblastos/ultraestruturaRESUMO
BACKGROUND: Allergic rhinitis and asthma are the more frequent allergic diseases. Dermatophagoides pteronyssinus is one of the more clinically relevant causes of allergic diseases. OBJECTIVE: To standardize the biological potency Allergenic Bioequivalent Units (BAU) of Dermatophagoides pteronyssinus allergen extracts of three national laboratories. METHODS: This experimental, prospective, transversal, quantitative study included patients allergic to house dust mites. According to the FDA protocol, allergenic extracts of Dermatophagoides pteronyssinus from three Mexican manufacturers, were injected intradermally in threefold dilutions, until get an midpoint orthogonal diameters 50 mm erythema sum. Statistical analysis was done using logistic regression, one-way analysis of variance and Bonferroni test. RESULTS: We included 20 adult patients, 11 women and 9 men, aged between 16 and 45 years. Four patients had allergic asthma and rhinitis and 16 only had allergic rhinitis. There were no systemic anaphylactic reactions. Correlation coefficients of linear regression of the dose/response were to Allerstand r=0.55, Allergomex r=0.54 and Allerquim r=0.57(p=0.001). Dilutions calculated for 100,000 BAU/ml for each extract were Allerstand 1:26295, Allergomex 1:26341 and Allerquim 1:73993. The protein concentration (mcg/mL) was: Allergomex: 63, Allerquim 65, Allerstand 154. CONCLUSIONS: It was established the biological potency for each tested extract. We have found significant differences in the biological equivalence among the extracts from the three manufacturers. The procedure showed an adequate safety profile.
Assuntos
Alérgenos/imunologia , Alérgenos/uso terapêutico , Produtos Biológicos/imunologia , Produtos Biológicos/uso terapêutico , Dermatophagoides pteronyssinus/imunologia , Imunoterapia , Adolescente , Adulto , Alérgenos/farmacocinética , Animais , Produtos Biológicos/farmacocinética , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Equivalência Terapêutica , Adulto JovemRESUMO
The absorption pathway(s) of a representative food allergen, lysozyme, and the mechanisms of lysozyme absorption facilitated by non-steroidal anti-inflammatory drugs were examined by intestinal closed-loop and re-circulating perfusion methods in rats. The absorption rate of fluorescein isothiocyanate (FITC)-labeled lysozyme in the proximal intestine was higher than that for a marker of non-specific absorption, FD-10, and was suppressed by colchicine (endocytosis inhibitor). Aspirin increased the absorption of FITC-lysozyme in the proximal intestine with no effects on tissue accumulation. Diclofenac facilitated FITC-lysozyme absorption, but meloxicam and loxoprofen exerted no effects on absorption. Co-administration of misoprostol (synthetic prostaglandin-E1 analog) with aspirin significantly ameliorated the aspirin-facilitated absorption of FITC-lysozyme to the same level as that seen with controls. Thus, lysozyme absorption was mediated by endocytic and paracellular pathways in the proximal intestine, and was facilitated by aspirin and diclofenac after impairment of the paracellular pathway. Misoprostol may suppress the allergen absorption facilitated by aspirin.
Assuntos
Alérgenos/farmacocinética , Anti-Inflamatórios não Esteroides/administração & dosagem , Proteínas do Ovo/farmacocinética , Absorção Intestinal/efeitos dos fármacos , Absorção Intestinal/fisiologia , Muramidase/farmacocinética , Animais , Aspirina/administração & dosagem , Diclofenaco/administração & dosagem , Interações Medicamentosas , Masculino , Taxa de Depuração Metabólica/efeitos dos fármacos , Taxa de Depuração Metabólica/fisiologia , Misoprostol/administração & dosagem , Ratos , Ratos Sprague-DawleyRESUMO
Since its description by Noon in 1911, desensitization or allergen-specific immunotherapy (SIT) has been largely given by sub cutaneous injection in the treatment of allergic diseases. It remains the only treatment for allergic diseases aimed at the etiology. The development of sublingual route as an alternative to sub cutaneous injection, and of new forms of medication, has led to large-scale clinical trials, many of them performed with allergen tablets, particularly in the field of pollen allergy. These studies have confirmed that SIT is efficient in reducing allergic respiratory symptoms. Data on long term benefits and sustained efficacy after stopping treatment have also been published. These show an impact on the natural history of allergic disease and, in particular, a reduction in the risk of asthma in desensitized rhinitic subjects and in the acquisition of new sensitivities. The basic mechanisms of immunotherapy are becoming better understood and allow us to envisage improvements in this technique in the future. The sublingual route improves the risk/benefit ratio of desensitization and reduces the risk of serious side effects. These data suggest that the indications for SIT may be extended in a large number of patients with allergic respiratory diseases.