The effects of biomolecules on peripheral tissues and their responsive machinery are not well understood. We examined MDM2 level in the plasma membrane (PM) and total MDM2 level of 3T3-L1 adipocytes treated with biomolecular anandamide, epinephrine, and other agents for 15 min. We also examined biomolecular responses in cells treated with mithramycin A, a binding inhibitor, or cells exposed to cooling and cell viability. Immunoblotting revealed that PM MDM2 level increased and total MDM2 level was not altered following treatment with anandamide, epinephrine, capsaicin, CL316243, and aluminum fluoride. PM MDM2 distribution caused by a biomolecular concentration was maintained by treatment with mithramycin A and exposure of cells to 28°C or 32°C but not to 18°C, and PM MDM2 levels after treatment with high concentrations of biomolecules were altered upon exposure to the inhibitor and mild hypothermia. These conditions did not decrease cell viability. Our findings indicate that 3T3-L1 adipocytes possess molecular machinery that responds differentially to anandamide and epinephrine under the inhibitor treatment and cool temperature conditions and that is sensitive to other agents (which mimic biomolecular responses); these machineries can induce subcellular alterations in molecular interactions. We provide information helpful for clarifying biomolecular responsive machinery present in 3T3-L1 adipocytes.

Monoamines are important neuromodulators that respond to social cues and that can, in turn, modify social responses. Yet we know very little about the ontogeny of monoaminergic systems and whether they contribute to the development of social behavior. Anurans are an excellent model for studying the development of social behavior because one of its primary components, phonotaxis, is expressed early in life. To examine the effect of social signals on monoamines early in ontogeny, we presented juvenile Mexican spadefoot toads (Spea multiplicata) with a male mating call or no sound and measured norepinephrine, epinephrine, dopamine, serotonin, and a serotonin metabolite, across the brain using high-pressure liquid chromatography. Our results demonstrate that adult-like monoaminergic systems are in place shortly after metamorphosis. Perhaps more interestingly, we found that mating calls increased the level of monoamines in the juvenile tegmentum, a midbrain region involved in sensory-motor integration and that contributes to brain arousal and attention. We saw no such increase in the auditory midbrain or in forebrain regions. We suggest that changes in monoamine levels in the juvenile tegmentum may reflect the effects of social signals on arousal state and could contribute to context-dependent modulation of social behavior.

Minor and major allergic reactions occur during oral and maxillofacial treatment. Immediate diagnosis and pharmacologic intervention are imperative. Signs and symptoms may be variable. The early administration of epinephrine is critical.

The differences of high on-treatment platelet reactivity (HPR) between the coronary arteries and peripheral veins might be associated with poor prediction of adverse cardiovascular events in patients with coronary artery diseases. HPR from the peripheral blood might not adequately reflect the platelet responses in the coronary artery. A total of 21 patients were recruited, and regional differences in HPR were compared between blood samples from the intra-coronary artery (IC), femoral artery (FA), and femoral vein (FV) by light aggregometry (agonists: arachidonic acid, LTA-AA; ADP, LTA-ADP), VerifyNow P2Y12 assays, and a platelet function analyser (PFA-100, collagen and epinephrine cartridge, PFA-CEPI). There were regional differences in the platelet reactivities observed by LTA-AA, VerifyNow P2Y12 assays, and PFA-CEPI. Platelets from the IC had higher platelet reactivities than those from the FV and FA by the VerifyNow P2Y12 assays but lower reactivities by LTA-AA and PFA-CEPI. HPR values from the blood in the FA were more similar to those from the IC than those from the FV by any test. The monocyte percentages were the only factors associated with differences in HPR between the FV and IC by the VerifyNow P2Y12 assays. Triglyceride levels were associated with the differences in HPR between the FV and IC by LTA-ADP. During the six-month follow-up period, two patients developed cardiovascular events and exhibited differences in HPR between different sites by VerifyNow P2Y12 assays. In conclusions, there were regional differences in HPR in patients with coronary artery diseases, which might prevent the adequate prediction of cardiovascular events.

PURPOSE OF REVIEW:

Allergic reactions to stinging insects may be unexpected, frightening, and severe. A clear understanding of recent advances in the field facilitates appropriate care of children who experience severe reactions to hymenoptera stings.

RECENT FINDINGS:

Recent investigations have underscored the importance of appropriate patient selection for potentially life-saving venom immunotherapy. Venom immunotherapy is effective in preventing future anaphylaxis from hymenoptera stings. Immunotherapy is indicated for patients with a history of anaphylaxis. Children who develop large local swelling or strictly cutaneous systemic reactions generally do not require immunotherapy. Component resolved diagnostic testing has been investigated to clarify the possibility of multiple venom allergies in patients with sensitization to multiple venoms.

SUMMARY:

Rapid recognition and treatment of anaphylaxis are critical. Subsequent education about avoiding future stings and attention to emergency preparedness with appropriate prescription of self-injectable epinephrine is important. Referral of patients who have experienced venom-associated anaphylaxis for possible venom immunotherapy can prevent future severe episodes of anaphylaxis resulting from stings.

Although there has been increasing data on pediatric anaphylaxis, information about anaphylaxis in the 1st year of life is scarce. This study provides detailed information on clinical signs and symptoms of anaphylaxis in the 1st year of life. A retrospective review was performed of our pediatric allergy database between 2007 and 2011. Children who met the diagnostic criteria of anaphylaxis were included. They were categorized as "infant" if they were ≤12 months of age at the time of anaphylactic reaction and "children" if >12 months. There were 104 patients (60 male and 44 female subjects) who met the diagnosis criteria of anaphylaxis. From the 104 cases of anaphylaxis, 23 (22.1%) were infants. Boys (p = 0.043), atopic eczema (p = 0.049), and history of food allergy (p < 0.001) were significantly higher in infants than in children with anaphylaxis. Severe anaphylaxis was less frequent in infants than in children (p = 0.04). There was no significant difference between infants and children considering cutaneous and respiratory symptoms (p > 0.05 for both) but persistent vomiting was (p = 0.023). Irritability, persistent crying, and somnolence are the signs which are difficult to interpret in infants with anaphylaxis. Within these signs, irritability, persistent crying, and somnolence were present in 69.6, 43.5, and 26.1% of infants, respectively. Blood pressure was measured in 5 infants (21.7%) compared with 44 children (54.3%; p = 0.005). Four children (4.9%) required more than one epinephrine treatment, but no infant did. Median observation periods were 4 hours in both groups (p = 0.087) and no biphasic reactions occurred in either. Food (p < 0.001) was significantly more and drugs (p = 0.015) were a less frequent cause of anaphylaxis in infants than in children. Anaphylaxis in infants is not rare but many signs of anaphylaxis are overlooked and still undertreated.

Literature regarding biphasic reactions in the pediatric population is sparse. We aimed to determine the prevalence of biphasic reactions in children with food allergies undergoing oral food challenges (OFCs) and examine whether any clinical or treatment factors are associated with biphasic reactions. A retrospective chart review of OFCs conducted between July 2007 and March 2011 was performed. Charts were reviewed from time of challenge to 48 hours after challenge to capture data on any biphasic reactions. Uniphasic and biphasic reactions were compared in terms of specific clinical features and treatments. Of 614 positive challenges, 9 resulted in a biphasic reaction (1.5%). Six of the biphasic reactions occurred in challenges where the initial reaction met anaphylaxis criteria. The biphasic reactions were to eggs (4), peanuts (3), and milk (2). The symptom-free interval ranged from 2 to 24 hours. There were no statistically significant differences in clinical features between uniphasic and biphasic reactions, but there appeared to be a higher percentage of initial reactions with multiple organ involvement and meeting anaphylaxis criteria in the biphasic group. Biphasic reactors were significantly more likely to have received steroids for their initial reaction. A higher percentage of biphasic reactors also appeared to have received epinephrine, multiple doses of epinephrine, and antihistamines for their initial reactions. Biphasic reactions are rare in children undergoing OFCs and may be associated with more severe allergic reactions. Children with severe reactions may benefit from a 24-hour period of observation.

Oral immunotherapy (OIT) for peanut allergy is ready for clinical allergy practice. Some physicians, particularly at academic centers, believe that OIT is not ready for clinical practice. The shortcomings of the present general recommendations of food avoidance and provision of epinephrine autoinjectors for a select number of patients demand a different approach. In peanut-allergic patients, the rate of accidental reactions is ∼10% annually. Between 1 and 2% of these reactions require epinephrine or emergency department visits. Food allergy and peanut allergy, specifically, have a large negative impact on the quality of life (QOL) for patients and their families, which can be psychosocially debilitating. These decreases in health-related QOL continue into adulthood. There is only an ∼20% chance of spontaneous remission in peanut allergy. Given this climate, three private allergy practices have begun providing OIT to 150 patients with peanut anaphylaxis. One hundred eleven (74%) patients were able to tolerate eight peanuts (8 g, ∼2 g of protein). During outpatient dosing, epinephrine was used at a rate of 8 per 10,000 doses. To date, there have been no long-term (>24-36 months) unexpected reactions. OIT decreases risk and in one study, conducted in a practice setting, it was shown to improve QOL. OIT is a meaningful clinical procedure that can help our patients.

Food oral immunotherapy (OIT) is an investigational peanut allergy treatment aimed to achieve specific oral tolerance induction. Allergic children are given titrated oral (or sublingual) doses of their allergen on a daily basis, unlike in subcutaneous immunotherapy (SCIT). OIT is theorized to cause a shift from a Th2 to a Th1 regulatory environment, reflected by increases in food-specific IgG4/IgE, and the production of FoxP3. Peanut OIT holds special promise because peanut allergy has an unfavorable natural history and is rarely outgrown. A high percentage of the participants experience symptoms during peanut OIT, including anaphylaxis, warranting epinephrine and/or discontinuation of therapy. This is a concerning fact given that the studies have mostly targeted only older children, with less historical reactivity for enrollment. The handful of peanut OIT studies have shown that some participants can be desensitized to peanut, but none have shown that long-term tolerance can be reestablished. Factors predictive of which patients are most likely to succeed and become desensitized through OIT are unknown. Some private practices have begun offering peanut OIT as a therapy. Such practice is potentially dangerous given the safety and efficacy of OIT in randomized controlled clinical trials is still not well established. Therefore, until further investigation emerges that conclusively demonstrates OIT is safe, intermediate and long-term outcomes are better established, the number of participants that experience symptoms is reduced, and proof of concept established in patients of all ages, (irrespective of past reaction severity), OIT is not ready for use in the general allergy practice.