Humans ; Dapsone/adverse effects* ; Drug Hypersensitivity/etiology* ; Hypersensitivity ; Syndrome

BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.
Biomarkers/blood* ; Child ; Child Health ; Child, Preschool ; Cohort Studies ; Environmental Exposure/adverse effects* ; Environmental Health ; Environmental Pollutants/adverse effects* ; Female ; Fetal Blood/chemistry* ; Follow-Up Studies ; Growth/drug effects* ; Humans ; Hypersensitivity/etiology* ; Infant ; Japan/epidemiology* ; Male ; Neurodevelopmental Disorders/etiology* ; Pregnancy ; Prenatal Exposure Delayed Effects/etiology* ; Prevalence ; Smoking/adverse effects*

Alopecia ; chemically induced ; diagnosis ; Antirheumatic Agents ; administration & dosage ; adverse effects ; Arthritis, Rheumatoid ; drug therapy ; Biopsy ; methods ; Cyclosporine ; administration & dosage ; Dermatologic Agents ; administration & dosage ; Drug Hypersensitivity Syndrome ; diagnosis ; etiology ; physiopathology ; therapy ; Humans ; Male ; Middle Aged ; Prednisolone ; administration & dosage ; Skin ; pathology ; Sulfasalazine ; administration & dosage ; adverse effects ; Symptom Flare Up ; Treatment Outcome ; Vitiligo ; chemically induced ; diagnosis

Shuang-huang-lian Injection (SHLI) is the first successfully developed drug from traditional Chinese medicine (TCM) powder for injection, since its use for the treatment of acute respiratory tract infection, pneumonia, influenza, etc. At the same time, its allergic reactions have also emerged, which limits clinical applications. However, few scholars pay attention to the mechanism of allergic reactions. In this present study, metabonomics technology was used to explore the changes in endogenous metabolites in urine of the rat model of SHLI induced allergic reaction; we and analyzed the metabolites, metabolic pathway, and the mechanism which were closely related to the allergic reactions. The levels of serum histamine and tryptase were examined and changes in histomorphology were also observed. Based on the UPLC-Q-TOF/MS metabonomics, we carried out the pattern recognition analysis, selected potential biomarkers associated with allergic reactions, and explored the pathological mechanism for SHLI induced allergic reaction, which laid the foundation for the safety research of SHLI. Our results showed that SHLI increased the levels of serum histamine and tryptase in rats with allergic reaction; we determined 15 biomarkers in rat allergic reaction model induced by SHLI and found multiple metabolic pathways involved, such as metabolism of linolenic acid, phenylalanine, amino acid, 2-oxo acid, and purine and other metabolic pathways.
Animals ; Biomarkers ; urine ; Chromatography, High Pressure Liquid ; Drug Hypersensitivity ; etiology ; urine ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Histamine ; urine ; Male ; Metabolomics ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry

BACKGROUNDDrug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, life-threatening disorder caused by drugs. In the present study, we tried to explore the types of DRESS-inducing drugs, incubation period, features of skin rashes, accompanying visceral damage, and effectiveness of glucocorticoid therapy so as to inform clinical practice.

METHODSPatients diagnosed with a drug-induced rash, dermatitis, and DRESS admitted to our hospital from January 2006 to December 2015 were included in the study. The diagnosis followed the criteria and scoring system set by the European Registry of Severe Cutaneous Adverse Reactions. Statistical analyses were carried out using SPSS version 17.0 (IBM, Armonk, NY, USA), and a value of P < 0.05 was considered statistically significant.

RESULTSAmong 104 patients, 38 were male and 66 female (aged 18-83 years). The latent period was 13 (interquartile range [IQR]: 10-17) days. The most common allergy-inducing drugs were antibiotics (n = 37, 35.6%), followed by antiepileptic drugs and traditional Chinese medicines (TCMs). Eighty-two cases (78.8%) had rash with area >50% body surface area (BSA). Liver damage occurred in 90% of cases. Patients were divided into oral antihistamine group and glucocorticoid/immunosuppressive agent/intravenous immunoglobulin (IVIG) group. Sex, age, incubation period, duration of hospital stay, and the number of patients with body temperature ≥38.5°C were not significantly different between the two groups. However, the number of patients meeting the criteria of "definite" and "probable" (χ2 = 5.852, P = 0.016), with an eosinophilic granulocyte count of ≥1.5 × 109/L (χ2 = 7.129, P = 0.008), and with rash area of >50% BSA (χ2 = 4.750, P = 0.029), was significantly different.

CONCLUSIONSAntibiotics were associated with allergic reactions, but TCMs also had an important role. Allergy resulting from repeat use of the same drug was more severe with a shorter incubation period. The most typical rash was widespread erythematous papules. Liver damage accounted for >90% of cases.

Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; adverse effects ; Dermatitis ; diagnosis ; etiology ; Drug Hypersensitivity Syndrome ; diagnosis ; etiology ; Eosinophilia ; diagnosis ; etiology ; Exanthema ; diagnosis ; etiology ; Female ; Glucocorticoids ; adverse effects ; Humans ; Immunosuppressive Agents ; adverse effects ; Liver ; drug effects ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

: Anaphylaxis is a predominantly childhood disease. Most of the literature on anaphylaxis has emerged from Western countries. This study aimed to describe the incidence, triggers and clinical presentation of anaphylaxis among children in Singapore, look for predictors for anaphylaxis with severe outcomes, and study the incidence of biphasic reactions.: We retrospectively reviewed records of children presenting with anaphylaxis to our paediatric emergency department from 1 January 2007 to 31 December 2014.: We identified 485 cases of anaphylaxis in 445 patients. Cutaneous symptoms (urticarial/angio-oedema) were the most common across all age groups (481 cases, 99%), followed by respiratory (412, 85%), gastrointestinal (118, 24%) and cardiovascular (35, 7.2%) symptoms. Central nervous system symptoms (drowsiness/ irritability) were rare across all age groups (11, 2.2%). Food was identified as the most common trigger across all age groups (45% to 63%). Seafood was the most common food trigger (57, 25%). A total of 420 (86.6%) children were treated with adrenaline, 451 (93%) received steroids and 411 (85%) received antihistamines. Sixty-three (13%) children fulfilled the criteria of severe anaphylaxis. There was no statistically significant association between severe anaphylaxis and the type of trigger (= 0.851), nor an overall past history of atopy (= 0.428). The only independent predictor for severe anaphylaxis was a previous drug allergy (= 0.016). A very low prevalence of biphasic reactions (0.6% of study population) was noted in our study.: We described the presentation and management of anaphylaxis in the Singapore population. A history of drug allergy is associated with severe presentation. Biphasic reactions are rare in our population.
Adolescent ; Adrenal Cortex Hormones ; therapeutic use ; Anaphylaxis ; drug therapy ; epidemiology ; etiology ; physiopathology ; Angioedema ; epidemiology ; etiology ; physiopathology ; Child ; Child, Preschool ; Drug Hypersensitivity ; epidemiology ; Emergency Service, Hospital ; Epinephrine ; therapeutic use ; Female ; Food Hypersensitivity ; complications ; epidemiology ; Gastrointestinal Diseases ; epidemiology ; etiology ; physiopathology ; Histamine Antagonists ; therapeutic use ; Humans ; Hypotension ; etiology ; physiopathology ; Incidence ; Infant ; Male ; Pediatrics ; Prevalence ; Respiratory Tract Diseases ; epidemiology ; etiology ; physiopathology ; Retrospective Studies ; Risk Factors ; Seafood ; Severity of Illness Index ; Singapore ; epidemiology ; Sympathomimetics ; therapeutic use ; Tertiary Care Centers ; Urticaria ; epidemiology ; etiology ; physiopathology

Iodinated radiocontrast media (IRCM) is widely used in current clinical practice. Although IRCM is generally safe, serious adverse drug reactions (ADRs) may still occur. IRCM-induced ADRs may be subdivided into chemotoxic and hypersensitivity reactions. Several factors have been shown to be associated with an increased risk of ADRs, including previous contrast media reactions, history of asthma and allergic disease, etc. Contrast media with lower osmolality is generally recommended for at-risk patients to prevent ADRs. Current premedication prophylaxis in at-risk patients may reduce the risk of ADRs. However, there is still a lack of consensus on the prophylactic role of premedication. Contrast-induced nephropathy (CIN) is another component of IRCM-related ADRs. Hydration remains the mainstay of CIN prophylaxis in at-risk patients. Despite several preventive measures, ADRs may still occur. Treatment strategies for potential contrast reactions are also summarised in this article. This article summarises the pathophysiology, epidemiology and risk factors of ADRs with emphasis on prevention and treatment strategies. This will allow readers to understand the rationale behind appropriate patient preparation for diagnostic imaging involving IRCM.
Acute Kidney Injury ; chemically induced ; prevention & control ; therapy ; Contrast Media ; adverse effects ; Drug Hypersensitivity ; etiology ; prevention & control ; therapy ; Drug-Related Side Effects and Adverse Reactions ; etiology ; prevention & control ; therapy ; Fluid Therapy ; Humans ; Iodine Radioisotopes ; adverse effects

Levocetirizine is a second-generation nonsedative antihistaminic agent that has been demonstrated to be safe and effective for treating allergic disease. There was only one case report of levocetirizine-induced liver toxicity, but a liver biopsy was not performed. In this article, we present the first case of levocetirizine-induced liver injury with histologic findings. A 48-year-old man was hospitalized with jaundice and generalized pruritus that had developed after 2 months of therapy with levocetirizine for prurigo nodularis. Laboratory findings revealed acute hepatitis with cholestasis. A liver biopsy demonstrated portal inflammation and hepatitis with apoptotic hepatocytes. The patient fully recovered 3 weeks after withdrawing levocetirizine. Although levocetirizine is safe and effective, physicians should be aware of its potential hepatotoxicity.
Cetirizine/*adverse effects/therapeutic use ; Chemical and Drug Induced Liver Injury/*diagnosis/pathology ; Histamine H1 Antagonists, Non-Sedating/*adverse effects/therapeutic use ; Humans ; Hypersensitivity/drug therapy ; Jaundice/etiology ; Liver/pathology ; Male ; Middle Aged ; Pruritus/etiology

OBJECTIVETo evaluate the effect of diisononyl phthalate (DINP) exposure during gestation and lacta- tion on allergic response in pups and to explore the role of phosphoinositide 3-kinase/Akt pathway on it.

METHODSFemale Wistar rats were treated with DINP at different dosages (0, 5, 50, and 500 mg/kg of body weight per day). The pups were sensitized and challenged by ovalbumin (OVA). The airway response was assessed; the airway histological studies were performed by hematoxylin and eosin (HE) staining; and the relative cytokines in phosphoinositide 3-kinase (PI3K)/Akt pathway were measured by enzyme-linked immunosorbent assay (ELISA) and western blot analysis.

RESULTSThere was no significant difference in DINP's effect on airway hyperresponsiveness (AHR) between male pups and female pups. In the 50 mg/(kg·d) DINP-treated group, airway response to OVA significantly increased and pups showed dramatically enhanced pulmonary resistance (RI) compared with those from controls (P<0.05). Enhanced Akt phosphorylation and NF-κB translocation, and Th2 cytokines expression were observed in pups of 50 mg/(kg·d) DINP-treated group. However, in the 5 and 500 mg/(kg·d) DINP-treated pups, no significant effects were observed.

CONCLUSIONThere was an adjuvant effect of DINP on allergic airway inflammation in pups. Maternal DINP exposure could promote OVA-induced allergic airway response in pups in part by upregulation of PI3K/Akt pathway.

Animals ; Blotting, Western ; Bronchitis ; chemically induced ; Bronchoalveolar Lavage Fluid ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay ; Female ; Hypersensitivity ; etiology ; Male ; Maternal Exposure ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; Phthalic Acids ; toxicity ; Pregnancy ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Wistar

Allergic reactions caused by traditional Chinese medicine injections (TCMIs) become a greatest concern in the clinic application safety. The integral animal evaluation method commonly used in the preclinical evaluation for allergic reactions of TCMIs was not sensitive, specific, quick and objective in observation indexes. Therefore, more researchers have paid attention to the in vitro test method for evaluating allergic reactions induced by TCMIs. Currently, the methods for evaluating allergic reactions induced by TCMIs are mainly targeted at type I allergic reaction and anaphylactic reaction, with only a few in vitro methods for evaluating type II allergic reaction. In this paper, researchers summarized relevant literatures published about evaluation methods for allergic reactions induced by TCMIs in recent years.
Animals ; Complement Activation ; Drug Hypersensitivity ; diagnosis ; etiology ; Humans ; Injections ; Medicine, Chinese Traditional ; adverse effects