Hymenoptera

Insect Pheromones A Critical Review of Recent Advances Pd(OAc)2 

Several saturated C32, C33, and C34 hydrocarbons with methyl branches in the Cl 1 -13 positions have been identified from the tobacco horn-worm (Heliothis virescens) (Lepidoptera Noctuidae) that elicit a hostseeking response of its parasitoid, Cardiochiles nigriceps. These kairo-mones have been synthesized by Vinson et ai (170) using appropriate methyl ketones and Wittig reagents followed by catalytic reduction. 

The alarm pheromones of ants are often simple readily available ketones. Syntheses of some of the less trivial pheromones are described below. 

With only a few exceptions, the majority of the Lepidopteran sex pheromones identified thus far are unsaturated, even-numbered, straight-chain acetates, alcohols or aldehydes, produced as a precise mixture of E- and Z-isomers. Thus stereospecificity in the formation of the desired isomer is the ideal, or at least one hopes for sufficient stereoselectivity to attain the desired blend. Hendrick (90) has recently reviewed in great detail the syntheses of these compounds, so only a summary of the various methods will be given here. 

Lindlar catalyst stereoselectively gives the Z-isomer contaminated with up to 5% of the -isomer. Reduction of acetylenes to yield 98% Z-olefins has been accomplished by hydroboration with hindered reagents such as disiamylborane (188) or 9-BBN (189) followed by hydrolysis with acetic acid. 

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Materials produced by crystalliferous bacilli which elicit a toxic response in susceptible insects may be separated into two types. The first type, the true toxins, include the crystalline protein inclusion body the parasporal body of Hannay (14)], a heat-stable, water-soluble exotoxin active against flies, a heat-stable, dialyzable water-soluble exotoxin, toxic to Lepidoptera on injection (23), and a heat-labile, water-soluble, filterable exotoxin, toxic toward larch sawfly larvae (Hymenoptera) which was reported by Smirnoff (31). 

Berger J, Ring J Efficacy of antihistamine pretreat- 15 ment in the prevention of adverse reactions to Hymenoptera venom immunotherapy a prospective randomized placebo-controlled trial. J Allergy 16 Clin Immunol 1997 100 458-463. 

Hermann K, Ring J The renin-angiotensin system in patients with repeated anaphylactic reactions during Hymenoptera venom hyposensitization and sting challenge. Int Arch Allergy Immunol 1997 11 251-256. 

Antonicelli L, Bilb MB, Bonifazi F Epidemiology of Hymenoptera allergy. Curr Opin Allergy Clin Immunol 2002 2 341-346. 

Bonifazi F, Jutel M, Bilo BM. Bimbaum J. Muller U EAACI Interest Group on Insect Venom Hypersensitivity Prevention and treatment of Hymenoptera venom allergy guidelines for chnical practice. Allergy 2005 60 1459-1470. 

Rueff F, Placzek M, Przybilla B Mastocytosis and 44 Hymenoptera venom allergy. Curr Opin Allergy Clin Immunol 2006 6 284-288. 

Sturm GJ, Heinemann A, Schuster C, et al Influence 46 of total IgE levels on the severity of sting reactions in Hymenoptera venom allergy. Allergy 2007 62 884-889. 

Hymenoptera venom is a prominent trigger of systemic reactions. Severe and fatal reactions have been described in patients with mastocytosis [9, 30, 31]. In few cases with urticaria pigmentosa and Hymenoptera venom anaphylaxis, no sensitization could be detected by means of skin tests and determination of specific IgE antibodies [32]. However, larger series found evidence that these systemic reactions are normally IgE-mediated insect sting allergies [7,33]. 

Diet should be modified only in cases where foods have been proven to elicit symptoms. Patients with mastocytosis and Hymenoptera venom exposure are at risk for severe anaphylaxis. Thus, specific immunotherapy should be considered in patients with Hymenoptera venom allergy and then administered under close supervision [31]. The majority of patients with mastocytosis reportedly tolerate immunotherapy without significant side effects and appear protected following this approach [33,40]. However, there does appear to be some increased risk for adverse reactions during initiation of immunotherapy, as well as for therapy failures [31, 33]. An increased maintenance dose of insect venom has been reported to carry better success rates by sting provocation [41]. Also, in the light of 2 fatal cases of anaphylaxis after discontinuation of SIT in patients with mastocytosis [30], lifelong immunotherapy should be considered [26]. 

Bonadonna P, Perbellini O, Passalacqua G, et al Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels. J Allergy Clin Immunol 2009 123 680-686. 

Gonzalez de Olano D, Alvarez-Xwose I, Esteban-Lopez MI, et al Safety and effectiveness of immunotherapy in patients with indolent systemic mastocytosis present- 44 ing with Hymenoptera venom anaphylaxis. J Allergy Clin Immunol 2008 121 519-526. 

Carter MC, Uzzaman A, Scott LM, et al Pediatric mastocytosis routine anesthetic management for a complex disease. Anesth Analg 2008 107 422-427. Bonadonna R Zanotti R, Caruso B, et al Allergen-specific immunotherapy is safe and effective in patients with systemic mastocytosis and Hymenoptera allergy. J Allergy Clin Immunol 2008 121 256-257. 

Rueff F, Wenderoth A, Przybilla B Patients still reacting to a sting challenge while receiving conventional Hymenoptera venom immunotherapy are protected by increased venom doses. J Allergy Clin Immunol 2001 108 1027-1032. 

One limitation of serum-specific IgE is that given the cross-reactivity between different Hymenoptera venoms, and also due to the presence of anti-carbohydrate antibodies, it is frequent to find several simultaneous positive results in patients with non-identified insect stings, a situation which makes diagnosis of the same difficult. In these cases, RAST inhibition and the release of histamine occasionally provide data on the venom involved and when this is not the case, it is advisable to administer immunotherapy against both [44]. 

Ebo D, Hagendorens MM, Bridts CH, De Clerk LS, Stevens WJ Hymenoptera venom allergy taking the sting out of difficult cases. J Investig Allergol Clin Immunol 2007 17 357-360. 

Venoms causing anaphylaxis or other allergic reactions originate almost exclusively from social Hymenoptera, most often honeybees and vespids (fig. 1) [1], occasionally from bumble bees [2], in America [3] and in Australia [4], also from ants. Stings by other insects like mosquitoes, bedbugs, fleas, horse flies and midges can very rarely also cause systemic allergic reactions. These are however not due to venoms but to... 

We will concentrate in this chapter on venoms of social Hymenoptera which are certainly responsible for more than 99% of insect sting-induced anaphylaxis. 

Fig. 2. Species of Hymenoptera responsible for systemic allergic reactions (a) honey bee A. mellif-era), (b) bumble bee (Bombus spp.j, (c) wasp, in the USA yellow jacket (Vespula spp.j, (d) European paper wasp (P. gallicus), (e) European hornet (V. crabro), and (f) Australian jack jumper ant (M. pilo-sula) [by courtesy of Dr. S.G. Brown, Perth, Australia]. 

Hymenoptera venoms are composed of biogenic amines and other low molecular weight substances, of basic peptides and of proteins. Injection of venom by Hymenoptera stings has toxic effects, due to biogenic amines, peptides and proteins biogenic amines such as histamine cause pain, are vasodilatory and increase... 

Fatal reactions to Hymenoptera stings are rare they range from 0.09 to 0.48 per million inhabitants and year [31, 32]. However, the true number may be underestimated in one study, specific IgE antibodies to Hymenoptera venoms were detected in 23% of postmortem serum samples from patients who died outdoors from unknown reasons [33]. Between 1961 and 2004, 140 fatal Hymenoptera sting reactions were registered by the federal administration for statistics in Switzerland with about 7.5 million inhabitants, resulting in an average annual fatality rate of 3.18. If these data are extrapolated to Europe with a population of around 500 million, the annual death rate in Europe would amount to about 200. 

The natural history of Hymenoptera venom anaphylaxis, that is the risk to develop anaphylaxis again when re-stung, has been analyzed in several prospective studies (table 3) [35-37], and in placebo or whole-body extract treated controls of prospective studies on venom immunotherapy [38-40]. It is higher in patients with a history of severe as compared to mild systemic anaphylactic reactions, and in honey bee than in vespid venom-allergic patients - most likely because of the smaller and less constant amoimt of venom applied by vespids [10,41]. A short interval between two stings increases the risk of anaphylaxis [25], but severe anaphylaxis may occur again even after intervals of 10-20 years or more. 

After a painful sting the elicitor of Hymenoptera venom-induced anaphylaxis is usually clear. However the identification of the responsible species is often difficult. 

Table 3. Natural history of Hymenoptera venom allergy... 

While in anaphylaxis caused by other frequent elicitors like food and drugs, allergen-specific immunotherapy is not established, immimotherapy with Hymenoptera venoms has been shown to be effective in three prospective controlled trials (table 4) [38-40] and also in a number of studies where patients were submitted to a sting challenge with the responsible insect during venom immimotherapy (table 5) [44]. While over 90% of vespid venom-allergic patients are fully protected and do not develop any... 

The indication for venom immunotherapy is based on a history of systemic allergic reactions to Hymenoptera stings and positive diagnostic tests, skin tests and/or venom-specific serum IgE antibodies [45, 49]. In the presence of only mild systemic allergic reactions, limited to the skin, immunotherapy is not generally recommended in the USA not for children, in Europe not for children and adults, unless they are heavily exposed and had repeated such reactions. 

Hoffman DR Hymenoptera venoms composition, standardization, stabihty in Levine MI, Lockey RF (eds) Monograph on Insect Allergy. Pittsburgh, Lambert Assoc, 2003, pp 37-53. 

Hoffman DR, Jacobsen RS Allergens in Hymenoptera venoms. XII. How much protein is in a sting Ann Allergy 1984 52 276-278. 

MW, Grunwald T, Spillner E Identification, recom- 28 binant expression and characterization of the 100 kDa high molecular weight hymenoptera venom allergens Api m5 and Ves v3. Allergy 2008 63(Suppl 88) 13-14. 29... 

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