Low indoleamine 2,3-dioxygenase activity in persistent food allergy in children.

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (Trp) to kynurenine (Kyn), has been demonstrated to contribute to modulation of allergic responses. However, the role of IDO in food allergy has not yet been elucidated. METHODS: Serum Trp and Kyn concentrations were analyzed by high-pressure liquid chromatography. Expression of IDO gene was measured by real-time PCR. The levels of interleukin (IL)-4, IL-10, and interferon (IFN)-γ in cell culture supernatants were measured by ELISA. RESULTS: Kyn/Trp (IDO activity) was significantly lower in subjects with food allergy (n = 100) than in aged-matched healthy controls (n = 112) (P = 0.004). Kyn/Trp was decreased from healthy through completely tolerant, partially tolerant, and reactive ones [LN transformation (mean ± SEM) healthy: 3.9 ± 0.02 µM/mM; completely tolerant: 3.83 ± 0.04; partially tolerant: 3.8 ± 0.06; reactive: 3.7 ± 0.04] (P = 0.008). The frequency of genetic polymorphisms of IDO did not reveal a significant association with Trp, Kyn, and Kyn/Trp in healthy and food-allergic cases. Culture of PBMC experiments yielded that IDO mRNA expression was not different between tolerant and reactive groups. IL-4 synthesis when stimulated with casein increased significantly in subjects who are reactive and tolerant to foods (P = 0.042, P = 0.006, respectively). Increase in IL-10 synthesis was observed only in children tolerant to milk, but not in reactive ones. IFN-γ synthesis, when stimulated with IL-2 and ß-lactoglobulin in cell culture, was significantly higher in subjects tolerant to milk than in the reactive ones (P = 0.005 and P = 0.029, respectively). CONCLUSION: Our results imply the probability of involvement of IDO in development of tolerance process, and we presume that high IDO activity is associated with nonresponsiveness to food allergens despite allergen sensitization.

Effects of iRoot BP and white mineral trioxide aggregate on cell viability and the expression of genes associated with mineralization.

AIM: To evaluate the cytotoxicity and mineralization effects of iRoot BP in human dental pulp cells (hDPCs) and to compare them with those of white mineral trioxide aggregate (WMTA). METHODOLOGY: hDPCs were exposed to prepared dilutions (1 : 1-1 : 10) of the test materials. Cell viability was evaluated using the XTT assay after incubation periods of 24, 48 or 72 h. The expression of mineralization-related genes (bone morphogenic protein, osteonectin, bone sialoprotein, osteopontin, dentine sialophosphoprotein and collagen type 1) and heme oxygenase 1 was measured by quantitative real-time polymerase chain reaction (qRT-PCR) at 24 and 72 h. Statistical differences between test materials were analysed with the Mann-Whitney test. RESULTS: The 1 : 1 and 1 : 2 dilutions of iRoot BP were associated with higher cell viability after 24 h (P < 0.05). Only the 1 : 1 dilution of iRoot BP had higher cell viability after 48 h (P < 0.05), and there was no difference between iRoot BP and WMTA after 72 h (P > 0.05). Although somewhat variable, according to the gene expression results, iRoot BP had a mineralization potential similar to that of WMTA. WMTA revealed a higher heme oxygenase 1 (HO-1) mRNA level than iRoot BP (P < 0.001). CONCLUSIONS: iRoot BP and WMTA were biocompatible and facilitated odontoblastic differentiation of hDPCs.

Serum basal tryptase may be a good marker for predicting the risk of anaphylaxis in children with food allergy.

A relationship between serum basal tryptase (sBT) levels, anaphylactic reactions, and clonal mast cell diseases was shown recently in adults with venom allergy, but the relationship between sBT levels and IgE-mediated food allergy and anaphylaxis is not known. In this study, children with food allergy (FA; n = 167) were analyzed in two groups according to the presence (FA+/A+; n = 79) or absence of anaphylaxis (FA+/A-; n = 88) and were compared with a control group (n = 113). Median sBT values in FA+/A+, FA+/A-, and control groups were 4.0 ng/ml (2.8-5.8), 3.6 (2.3-4.5), and 3.3 (2.4-4.4), respectively (P = 0.022). sBT measurements higher than the cutoff values of 5.7 and 14.5 were associated with 50% and 90% predicted probabilities, respectively, of moderate to severe anaphylaxis. Children with tree nuts/peanut allergies had significantly higher levels of sBT than children with milk and egg allergy (P = 0.022). Results suggest that sBT levels may predict moderate to severe anaphylaxis in children with food allergy, which may follow a particular pattern according to the food allergy phenotype.

Stevens-Johnson Syndrome triggered by a combination of clobazam, lamotrigine and valproic acid in a 7-year-old child.

Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are diseases within the spectrum of severe cutaneous adverse reactions affecting skin and mucous membranes. Antiepileptic drugs (AEDs) are used in combination, leading to potential pharmacokinetic or pharmacodynamic interactions, causing more adverse effects than might occur when the AED is taken as monotherapy. Here, we report a rare case of SJS triggered by a combination of clobazam, lamotrigine and valproic acid in a 7-year-old boy. Because of inadequate seizure control, lorazepam was replaced with clobazam. Four weeks after the addition of clobazam, the patient developed SJS with a generalized rash, fever, with liver and kidney involvement, and eosinophilia one week after the initiation of treatment. All antiepileptic drugs were discontinued, and intravenous methylprednisolone, prophylactic systemic antibiotics, intravenous fluid supplement, antipyretic, special wound care, and supportive medical care for SJS were administered. He was discharged in a stable condition on the 18th day. Our case suggests that a drug-drug interaction between valproate, lamotrigine and clobazam contributed to the development of SJS. When the clobazam was added to valproic acid and lamotrigine co-medication, the lamotrigine dose should have been decreased.

La syndrome de Stevens-Johnson (SJS) et la nécrolyse épidermique toxique sont des maladies dans le spectre de réactions cutanées graves affectant la peau et les muqueuses. Les médicaments antiépileptiques sont utilisés en combinaison, et ceci peut provoquer des effets indésirables. Ici, nous rapportons un cas rare de SJS déclenché par une combinaison de clobazam, la lamotrigine et l'acide valproïque chez un garçon de 7 ans. En raison de l' insuffisante maîtrise des crises, le lorazépam a été utilisé avec le clobazam. Quatre semaines après l'ajout de clobazam, le patient a développé SJS avec une éruption cutanée généralisée, de la fièvre. Il y avait la participation de la foie et les reins, et une éosinophilie, une semaine après le début du traitement. Tous les médicaments antiépileptiques ont été abandonnées, et la méthylprednisolone intraveineuse, des antibiotiques systémiques prophylactiques, supplément de liquide par voie intraveineuse, antipyrétique, les soins des plaies spécial, et de soutien pour les soins médicaux ont été administrés. Il a été libéré dans un état stable la 18ème journée. Notre cas suggère qu'une interaction médicamenteuse entre le valproate, la lamotrigine et clobazam ait contribué au développement de SJS. Lorsque le clobazam a été ajouté à l'acide valproïque et la lamotrigine, la dose de lamotrigine aurait dû être diminué.

Importance of serum basal tryptase levels in children with insect venom allergy.

BACKGROUND: The importance of serum basal tryptase (sBT) levels on patients with venom allergy is highlighted in recent adulthood studies. The aim of this study was to evaluate the sBT levels of venom-allergic children with varying severity of clinical reactions. We also aimed to document the association between sBT levels and severe systemic reactions (SR). METHODS: Serum basal tryptase levels were estimated by UniCAP (Pharmacia & Upjohn, Uppsala, Sweden). Children who suffered from large local reaction (LLR) or SR after insect stings were included along with healthy control subjects without a history of any local or SR after insect stings. RESULTS: A total of 128 children (55 with SR, 18 with LLR, and 55 age and sex-matched control subjects) with a median age of 8.9 years (range 3.2-17.4) were enrolled. Severe SR was encountered in 24 (44%) patients with SRs. The median level of sBT in children with SRs (median, interquartile range) [4.2 µg/l (3.6-4.9)] was significantly higher than in children with LLRs [3.1 µg/l (2.5-4.0)] and healthy control subjects [2.9 µg/l (2.3-3.4)] (P < 0.001). Logistic regression analysis revealed sBT ≥ 4.8 µg/l as a significant risk factor for severe SR (5.7 [1.5-21.4]; P = 0.01) in children with venom allergy. CONCLUSIONS: Our results indicate that sBT levels are associated with a higher risk of severe SR in children with insect venom hypersensitivity. Determination of sBT levels may help clinicians to identify patients under risk of severe SRs and optimal and timely use of therapeutic interventions in children with venom allergy.