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Local anesthetics (LA) are common elicitors of adverse reactions and the clinical symptoms often correspond to anaphylaxis with tachycardia, hypotension and subjective feelings of weakness, heat or vertigo. The pathomechanism of immediate hypersensitivity reactions to LA is largely unknown -they are commonly regarded as 'pseudo-allergic' or 'non-immune type' anaphylaxis. Immunologically mediated reactions have rarely been observed with positive skin prick tests. Other ingredients in LA preparations have to be considered as elicitors, e.g. preservatives like benzoates or sulfites or latex contaminants in injection bottles. Practical management of patients with a history of LA reaction includes a careful allergy history, skin-prick and intradermal tests. Undiluted LA solutions may elicit false-positive intradermal test reactions. If prick and intradermal tests are negative, the procedure of subcutaneous provocation testing is applied in a placebo-controlled manner. When patients are constantly reacting to placebo, a regimen of 'reverse placebo provocation' with injection of a LA (verum) is applied while the patient is informed about receiving placebo in order to 'rule out psychosomatic involvement'. With this regimen it is possible to eliminate anxiousness and fear, and the patient has proof that he has tolerated the respective LA substance., (Copyright 2010 S. Karger AG, Basel.)

The effects of 7-[3-[4-(2-quinolinylmethyl)- 1-piperazinyl]propoxy]-2,3-dihydro-4H-1,4- benzothiazin-3-one (VUF-K-8788) on experimental asthmatic reactions in guinea pigs were investigated. VUF-K-8788 inhibited histamine-induced bronchoconstriction at the doses of 0.3 and 1 mg/kg per os (p.o.). VUF-K-8788 inhibited anaphylactic bronchoconstriction at doses between 0.01 and 1 mg/kg in passively sensitized guinea pigs. Terfenadine used as a reference drug also inhibited an antigen-induced bronchoconstriction. VUF-K-8788 at the doses of 0.3 and 1 mg/kg inhibited immediate- and late-phase asthmathic reactions in actively sensitized guinea pigs. Terfenadine inhibited only the immediate phase reaction. Moreover, VUF-K-8788 inhibited the infiltration of eosinophils and macrophages into bronchoalveolar lavage fluid in guinea pigs. These results indicate that VUF-K-8788 may be useful for the treatment of bronchial asthma.

Tuberculin reactivity decreases with age despite epidemiologic evidence that the elderly are more likely to have been infected. Whether this phenomenon is due to lack of antigenic stimulus or host inability to mount a delayed type hypersensitivity (DTH) response is unclear. In order to determine if the DTH response to tetanus toxoid in an exposed population is a useful tool to understand the phenomenon of lack of tuberculin reactivity in the remotely exposed elderly, a trial of skin testing was undertaken. Seventy-seven residents of a Veterans Affairs domiciliary were skin-tested using solutions of tetanus toxoid, candida and mumps skin test antigen. The 35 subjects who had negative reaction to the tetanus skin test were randomized into two groups: one which received tetanus vaccination before repeat skin testing and one which did not. Positive skin test reactions occurred in 42 patients to tetanus toxoid, 44 to mumps and 37 to candida. Of the 35 randomized, 27 were available for repeat skin tests. None reacted to the repeat tetanus skin test although 5 reacted to other antigens to which they had previously been nonreactive. Tetanus toxoid was equal to other antigens in its ability to elicit a DTH response originally; however antigenic stimulation with vaccination did not elicit positive skin test in nonreactors. Lack of DTH response to tetanus toxoid in recently vaccinated patients implies that nonresponse was secondary to host factors rather than lack of antigenic stimulation.

We describe a new case of a seldom reported subset of fixed drug eruption, the nonpigmenting type. Aside from their fixed nature and their well-demarcated margins, pigmenting and non-pigmenting subsets of fixed drug eruption exhibit well-separated clinical and histological features allowing easy recognition. The precise physiopathology is currently unknown in both conditions, but a delayed hypersensitivity mechanism is likely. The nature of the inducing drugs of the nonpigmenting eruption is discussed.

Maximal complexing of alpha 2-macroglobulin (alpha 2M) and kallikrein (KK) occurs at a temperature of 22-24 rather than at 37 degrees C. The protease expressivity of the complex is also maximal at 22-24 degrees C. alpha 2M-KK complex, sustained permeability changes in guinea pig skin. These findings suggest that the complex, rather than free KK, could play a role in the kinin release reported in some late-phase reactions, some instances of delayed-type hypersensitivity and some cold-induced reactions.

Three models of ocular anaphylaxis containing 6 guinea pigs each were used to examine their effect on tear volume. In the first model, IgG1-rich anti-dinitrophenol (DNP) bovine gamma-globulin serum was injected subconjunctivally, and the animals were challenged 4 h later with topically applied di-DNP-lysine. In the second model, IgE-rich anti-egg albumin serum was injected subconjunctivally, and the animals were challenged 8 days later with topical instillation of egg albumin. In the third model, IgE-rich anti-egg albumin serum was injected intravenously, and animals were challenged 8 days later with topically applied egg albumin. Tears were collected before the procedure, 0.5 h after anaphylaxis was initiated, and then hourly for 8, 10, 12, 24, and 48 h after challenge. All animal eyes undergoing ocular anaphylaxis had significantly increased tearing. Tear volumes remained elevated in the first model beyond the observation period of 48 h.

The immunomodulating ability of fibrinogen fragment (Hol-DSK) and proteolytic enzyme with fibrinolytic activity from Aspergillus oryzae was analysed in CBA/Ca, C57Bl, C3H/HeJ and NMRI mice. Suppressive effects on the blastogenic response to mitogens were noted. No consistent suppressive effect, but sometimes an enhancing one, was recorded on the antibody responses to protein antigens. Administration of Hol-DSK or proteolytic enzyme shortly after the immunization resulted in a slight inhibition of the development of delayed hypersensitivity to picryl chloride in C57Bl but not in CBA mice. When similar administration was done simultaneously with administration of the challenging antigen of picryl chloride or sheep red blood cells in immunized mice, significant impairment of the delayed-type hypersensitivity reaction was noted. The modulating effects by Hol-DSK did not alter the in vitro bacteriocidal effects of peritoneal exudate cells from mice on Escherichia coli.

Enhancement of delayed-type hypersensitivity (DTH) reactions to ovalbumin (OVA) was demonstrated in guinea pigs given a single, high dose of cyclosporin A (CsA) intraperitoneally, 2 days before immunization. Courses of oral CsA, commencing at the time of immunization and lasting until day 4 or 13 also resulted in augmented DTH responses at days 14 and 28, respectively. However, the enhancing protocol (CsA; day 0-4) did not significantly affect circulating anti-OVA antibody titres. The capacity to express increased DTH could be adoptively transferred to naive recipients by systemic injection pooled spleen and peritoneal exudate cells. Moreover, the expression of augmented responses was inhibited by transfer of cells from normally immunized donors. Although augmentation of DTH was accompanied by increased lymphocyte proliferative responses to OVA in vitro, there was no similar effect on T cell responses to polyclonal mitogens. The data support the view that augmentation of DTH by CsA is attributable to suppressor cell dysfunction, but that this is unlikely to be a non-specific suppressor cell impairment.

The sheep model of allergic airway disease shares many pathophysiological similarities with allergic airway disease in humans. Studies performed in this animal model present strong evidence that the release of arachidonic acid metabolites plays an important role in the development of late bronchial responses to antigen challenge. The release of leukotrienes through the lipoxygenase pathway during the acute bronchial obstruction after inhalation of Ascaris suum antigen represents the key factor for the initiation of the subsequent events, namely the late phase response and the bronchial hyperreactivity. If this hypothesis can be substantiated in patients with bronchial asthma then pharmacologic modification of the lipoxygenase pathway and/or products may be important in the treatment of asthma.