Relationship between platelet activating factor acetylhydrolase activity and apolipoprotein B levels in patients with peanut allergy.

BACKGROUND: Platelet-activating factor (PAF) is a highly potent phospholipid mediator responsible for the life-threatening manifestations of anaphylaxis. PAF acetylhydrolase (PAF-AH) inactivates PAF and protects against severe anaphylaxis whereas deficiency of PAF-AH predisposes to severe or fatal anaphylaxis. Determinants of PAF-AH activity have not been studied in patients with peanut allergy. OBJECTIVES: To determine whether plasma PAF-AH activity in patients with peanut allergy is related to formation of circulating complexes with apolipoprotein B (apoB) the main surface protein on low density lipoprotein particles. METHODS: Plasma PAF-AH activity and apoB concentrations were measured in 63 peanut allergic patients (35 boys, 28 girls, ages 2 - 19 years). ApoB concentration was measured immunoturbidimetrically using goat anti-human apoB. The correlation between PAF-AH activity and apoB concentration was determined. RESULTS: A positive correlation was found between PAF-AH activity and apoB concentration (r(2) = 0.59, P < 0.0001). CONCLUSION: In peanut allergic patients, PAF-AH activity strongly correlates with apoB concentration, suggesting the presence of circulating PAF-AH- lipoprotein complexes.

Platelet-activating factor, histamine, and tryptase levels in human anaphylaxis.

BACKGROUND: Platelet-activating factor (PAF) is an important mediator and correlates with anaphylaxis severity. How well PAF correlates with severity relative to histamine or tryptase is not known. OBJECTIVE: To analyze the levels of PAF, histamine, and tryptase as a function of severity in patients with acute allergic reactions. METHODS: PAF, histamine, and tryptase levels were measured in blood samples collected from 23 healthy volunteers and from 41 patients during acute allergic reactions. Reactions were stratified by severity from grade 1 (least severe) to grade 3 (most severe). RESULTS: Among the 3 reaction grades, there were significant differences by ANOVA for PAF (P < .0001). The proportion of elevated PAF values increased across severity groups (P = .0009). Increased PAF levels were observed in 20%, 66.7%, and 100% of the patients with grades 1, 2, and 3 allergic reactions, respectively. While the proportion of elevated histamine values increased from 40% to 57% to 70% across grades 1, 2, and 3, respectively, these were not significantly different (P = .40). For tryptase, the proportion of elevated values increased monotonically from 0 in grade 1 to 4.8% in grade 2 to 60% in grade 3 (P = .0002). CONCLUSIONS: The PAF level was significantly elevated in proportion to the severity of acute allergic reactions. Whereas the PAF level was elevated in all patients with severe anaphylaxis, this was not true for either histamine or tryptase. Neither histamine nor tryptase showed as good correlations with severity scores as did PAF. These data are consistent with a pivotal role for PAF as a mediator of anaphylaxis.

Effect of epinephrine on platelet-activating factor-stimulated human vascular smooth muscle cells.

BACKGROUND: Animal and human data show that platelet-activating factor (PAF) mediates the life-threatening manifestations of anaphylaxis. Although administration of epinephrine is the mainstay of therapy of acute anaphylaxis, the interaction between epinephrine and PAF has not been studied. In particular, the effect of the timing of epinephrine administration on the action of PAF has not been examined. OBJECTIVE: Using human vascular smooth muscle cells (HVSMCs), we examined the effect of timing of epinephrine addition on the action of PAF. METHODS: The effect of epinephrine on PAF-mediated prostaglandin E(2) (PGE(2)) release from human aortic smooth muscle cells was examined. Epinephrine was added at various times before and after PAF stimulation. RESULTS: HVSMCs stimulated with PAF released PGE(2) in a concentration- and time-dependent manner. Whereas preincubation of HVSMCs with epinephrine before the addition of PAF suppressed PGE(2) release, treatment with epinephrine after PAF stimulation was less effective with time after PAF stimulation. PGE(2) release was suppressed by means of preincubation with 8-bromo-cyclic AMP and forskolin. CONCLUSIONS: PAF induced PGE(2) release from HVSMCs in a concentration- and time-dependent manner, and early addition of epinephrine was essential for the control of PAF-induced PGE(2) release. Epinephrine was most effective when administered before stimulation with PAF but was progressively less effective with time after PAF stimulation.

Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis.

BACKGROUND: Platelet-activating factor (PAF) is an important mediator of anaphylaxis in animals, and interventions that block PAF prevent fatal anaphylaxis. The roles of PAF and PAF acetylhydrolase, the enzyme that inactivates PAF, in anaphylaxis in humans have not been reported. METHODS: We measured serum PAF levels and PAF acetylhydrolase activity in 41 patients with anaphylaxis and in 23 control patients. Serum PAF acetylhydrolase activity was also measured in 9 patients with peanut allergy who had fatal anaphylaxis and compared with that in 26 nonallergic pediatric control patients, 49 nonallergic adult control patients, 63 children with mild peanut allergy, 24 patients with nonfatal anaphylaxis, 10 children who died of nonanaphylactic causes, 15 children with life-threatening asthma, and 19 children with non-life-threatening asthma. RESULTS: Mean (+/-SD) serum PAF levels were significantly higher in patients with anaphylaxis (805+/-595 pg per milliliter) than in patients in the control groups (127+/-104 pg per milliliter, P<0.001 after log transformation) and were correlated with the severity of anaphylaxis. The proportion of subjects with elevated PAF levels increased from 4% in the control groups to 20% in the group with grade 1 anaphylaxis, 71% in the group with grade 2 anaphylaxis, and 100% in the group with grade 3 anaphylaxis (P<0.001). There was an inverse correlation between PAF levels and PAF acetylhydrolase activity (P<0.001). The proportion of patients with low PAF acetylhydrolase values increased with the severity of anaphylaxis (P<0.001 for all comparisons). Serum PAF acetylhydrolase activity was significantly lower in patients with fatal peanut anaphylaxis than in control patients (P values <0.001 for all comparisons). CONCLUSIONS: Serum PAF levels were directly correlated and serum PAF acetylhydrolase activity was inversely correlated with the severity of anaphylaxis. PAF acetylhydrolase activity was significantly lower in patients with fatal anaphylactic reactions to peanuts than in patients in any of the control groups. Failure of PAF acetylhydrolase to inactivate PAF may contribute to the severity of anaphylaxis.

Blocking low-wavelength light prevents nocturnal melatonin suppression with no adverse effect on performance during simulated shift work.

Decreases in melatonin production in human and animals are known to be caused by environmental lighting, especially short-wavelength lighting (between 470 and 525 nm). We investigated the novel hypothesis that the use of goggles with selective exclusion of all wavelengths less than 530 nm could prevent the suppression of melatonin in bright-light conditions during a simulated shift-work experiment. Salivary melatonin levels were measured under dim (<5 lux), bright (800 lux), and filtered (800 lux) light at hourly intervals between 2000 and 0800 h in 11 healthy young males and eight females (mean age, 24.7 +/- 4.6 yr). The measurements were performed during three nonconsecutive nights over a 2-wk period. Subjective sleepiness was measured by self-report scales, whereas objective performance was assessed with the Continuous Performance Test. All subjects demonstrated preserved melatonin levels in filtered light similar to their dim-light secretion profile. Unfiltered bright light drastically suppressed melatonin production. Normalization of endogenous melatonin production while wearing goggles did not impair measures of performance, subjective sleepiness, or alertness.

Acupuncture increases nocturnal melatonin secretion and reduces insomnia and anxiety: a preliminary report.

The response to acupuncture of 18 anxious adult subjects who complained of insomnia was assessed in an open prepost clinical trial study. Five weeks of acupuncture treatment was associated with a significant (p = 0.002) nocturnal increase in endogenous melatonin secretion (as measured in urine) and significant improvements in polysomnographic measures of sleep onset latency (p = 0.003), arousal index (p = 0.001), total sleep time (p = 0.001), and sleep efficiency (p = 0.002). Significant reductions in state (p = 0.049) and trait (p = 0.004) anxiety scores were also found. These objective findings are consistent with clinical reports of acupuncture's relaxant effects. Acupuncture treatment may be of value for some categories of anxious patients with insomnia.

Presence of undeclared peanut protein in chocolate bars imported from Europe.

Peanut allergens are both stable and potent and are capable of inducing anaphylactic reactions at low concentrations. Consequently, the consumption of peanuts remains the most common cause of food-induced anaphylactic death. Since accidental exposure to peanuts is a common cause of potentially fatal anaphylaxis in peanut-allergic individuals, we tested for the presence of peanut protein in chocolate bars produced in Europe and North America that did not list peanuts as an ingredient. Ninety-two chocolate bars, of which 32 were manufactured in North America and 60 were imported from Europe, were tested by the Veratox assay. None of the 32 North American chocolate products, including 19 with precautionary labeling, contained detectable peanut protein. In contrast, 30.8% of products from western Europe without precautionary labeling contained detectable levels of peanut protein. Sixty-two percent of products from eastern Europe without precautionary labeling contained detectable peanut protein at levels of up to 245 ppm. The absence of precautionary labeling and the absence of the declaration of "peanut" as an ingredient in chocolate bars made in eastern and central Europe were not found to guarantee that these products were actually free of contaminating peanut protein. In contrast, North American manufacturers have attained a consistent level of safety and reliability for peanut-allergic consumers.

Activated charcoal forms non-IgE binding complexes with peanut proteins.

BACKGROUND: Conventional management of peanut-induced anaphylaxis is composed of administration of epinephrine, antihistamine, and steroid and stabilization of airway, ventilatory, and circulatory function. Therapies directed toward slowing or preventing further absorption of peanut protein from the gastrointestinal tract after accidental ingestion have not been a routine part of management. OBJECTIVE: The purpose of this study was to determine the ability of activated charcoal to complex with peanut protein, thereby preventing its binding to either peanut-specific IgE or peanut-specific IgG. METHODS: Peanut protein was coincubated with micronized activated charcoal suspension at pH 3.5 or 7.4. Peanut protein complexed with charcoal was removed by centrifugation. Binding of residual peanut protein to peanut-specific IgG was measured by a sandwich ELISA assay. Also, ability of uncomplexed peanut protein to bind to peanut-specific IgE was determined by Western blot and by skin prick testing in subjects with peanut allergy. RESULTS: Activated charcoal (AC) formed complexes with peanut protein, effectively competing for binding with peanut-specific IgG in a sandwich ELISA assay. AC complexed efficiently with peanut protein at both neutral and acidic pH in as little as 60 seconds. AC was also able to remove IgE-binding peanut allergens from solution as determined by Western blot and by skin prick testing in subjects with peanut allergy. A ratio of 200 mg of AC to 1 mg peanut protein was required for complete removal of peanut protein from solution. AC was able to complex with peanut protein within food matrices such as ice cream and chocolate. CONCLUSION: The data presented herein show that AC removes both IgE-binding and IgG-binding peanut proteins from solution rapidly at both neutral and acidic pH. These data suggest that administration of AC may be useful as an adjunct to slow or to prevent further absorption of peanut protein from the gastrointestinal tract after accidental ingestion by individuals with peanut allergy.