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Immunopharmacological actions of the new antiallergic drug butyl 3'-(1H-tetrazol-5-yl)oxanilate. 1st communication: effects on type I to type IV allergic reactions in animal models.

The effects of butyl 3'-(1H-tetrazol-5-yl)oxanilate (WP-833), a new antiallergic drug, on type I to type IV allergic reactions were investigated by employing various animal models. WP-833 (i.v. and p.o.) dose-dependently inhibited homologous or heterologous passive cutaneous anaphylaxis (PCA) mediated by rat or mouse immunoglobulin E (IgE) in rats. Homologous PCA caused by guinea pig IgE was also inhibited by WP-833. In addition, WP-833 had inhibitory actions upon homologous PCA induced by rat or guinea pig IgG. However, WP-833 showed no inhibition of rat skin reactions caused by histamine, serotonin and bradykinin, contrasting with the inhibition of prostaglandin E1-induced skin reaction. Furthermore, both adrenalectomy and propranolol treatment exerted no influences on the inhibition of IgE-mediated homologous PCA in rats by WP-833. In contrast to above findings demonstrating that WP-833 clearly inhibited type I allergic reaction, systemic Forssman shock in guinea pigs and reversed cutaneous anaphylaxis in rats (type II), passive Arthus reaction in rats (type III), and contact dermatitis and tuberculin reaction in mice (type IV) were unaffected by WP-833 even in higher doses than in those capable of completely inhibiting type I allergic reaction.

Adrenalectomy↗

Pharmacological effects of urinary products obtained after treatment with saiboku-to, a herbal medicine for bronchial asthma, on type IV allergic reaction.

To define the anti-allergic components in Saiboku-To, a herbal medicine for bronchial asthma, we examined the effects of 11 compounds found in post-administrative urine of Saiboku-To on concanavalin A-induced human lymphocyte blastogenesis in vitro and picryl chloride (PC)-induced mouse ear swelling in vivo. The urinary products of Saiboku-To were flavonoids and lignans derived from the constitutional herbs and their hydrogenated metabolites. Medicarpin derived from Glycyrrhiza glabra, magnolol and 8,9-dihydroxydihydromagnolol from Magnolia officinalis, baicalein, wogonin and oroxylin A from Suctellaria baicalensis inhibited lymphocyte blastogenesis in dose-dependent fashion with IC50 values ranging from 3.0 to 7.7 micrograms/mL, which corresponded to 20-100 times that of prednisolone IC50 (0.08 microgram/mL). Davidigenin, dihydrowogonin and dihydrooroxylin A, which are hydrogenated metabolites of liquiritigenin, wogonin and oroxylin A, respectively, had no or little effects on lymphocyte blastogenesis. Oral administration of Saiboku-To, medicarpin, baicalein, magnolol and baicalin (100 mg/kg), inhibited PC-induced ear swelling significantly by 23.5, 40.1, 30.5, 23.6 and 20.9%, respectively, though the effects were weaker than that of 5 mg/kg of prednisolone (52.9%). The results suggested that flavonoids and lignans tested in the present study were implicated in anti-asthmatic effect of Saiboku-To through suppression of type IV allergic reaction.

Animals↗

Cytochemical and ultrastructural studies of the Langerhans' cells. Sequential observations in experimental contact allergic reaction.

In the guinea pig, experimental allergic contact dermatitis (ACD) and primary irritant contact dermatitis (PICD) were induced with different concentrations of dinitrochlorobenzene (DNCB). The epidermal Langerhans' cells (LCs) were observed sequentially by both adenosine triphosphatase (ATPase) and electron microscopy. Light microscopically, in ACD, the density and dendritic processes of LC decreased markedly within 12 h after antigen challenge. Almost no recognization LCs could be seen within 2 to 5 days. Later, LCs began to repopulate in the epidermis. Within 14 days, the density and shape of the LCs returned to normal. On the contrary, LCs changed more rapidly in PICD. The dendritic processes of LC decreased within 2 h and cell density decreased dramatically within 6 h after DNCB application. LCs also repopulated more rapidly in the epidermis. Electron microscopically, in ACD, we observed that lymphocyte-like cells apposed to LCs; LCs were activated and damaged; however, in PICD, we found neither the apposition of lymphocyte-like cells to LCs, nor the activation of LCs. LCs play an important role in the convalescence phase as well as in the early and later phases of contact allergic reaction.

Adenosine Triphosphatases↗

Peculiarities of serotonin metabolism during allergic reactions.

Patients with mixed, infectious-allergic bronchial asthma and allergodermatoses showed suppression of serotonin metabolism. Allergic reactions in experimental animals were accompanied by changes in the activity of 5-hydroxytryptophandecarboxylase, mitochondrial and blood serum monoaminoxydase, and ceruloplasmin. These changes differed during primary and repeated anaphylactic shock. Quantitative changes in tissue serotonin varied with the activity of the enzymes taking part in its metabolism. During the 1st, 2nd, 5th and 7th days of the post-shock period, serotonin metabolism did not return to normal.

Anaphylaxis↗

Elicitation of the allergic reaction in beta-lactoglobulin-sensitized Balb/c mice: biochemical and clinical manifestations differ according to the structure of the allergen used for challenge.

BACKGROUND: Mouse models of allergy are used to study the mechanisms of induction and perpetuation of bronchopulmonary hyper-reactivity (BHR) as related to eosinophils and specific IgE. OBJECTIVE: Our aim was to adapt the current model for the study of bovine beta-lactoglobulin (BLG), a major cow's milk allergen, and to further analyse the mechanisms of the acute and late allergic reaction. METHODS: Female Balb/c mice were sensitized intraperitoneally with BLG and the influence of the adjuvant and of the BLG dose on the IgE response was analysed, IgE and IgG1 epitopes being characterized. Once optimized, this model was applied to the study of the active phase of allergy in the respiratory tract after a single airway challenge using native or denatured BLG, which contains only linear epitopes. RESULTS: An immediate allergic reaction was characterized by the rapid release of histamine into the bronchoalveolar lavage fluids. Prostaglandin (PG)D2 was only present when the standard histamine-releasing agent compound 48/80 or denatured BLG were used as triggers, whereas native BLG induced leukotriene release. Twenty-four hours after challenge, BHR, eosinophil influx, IL-4 and IL-5 production, plasma exudation and mucus production were very much increased, differently depending on the allergen structure, and indicated the occurrence of the late allergic reaction. Our results show that the murine model can be used to study the mechanisms of allergy to clinically relevant antigens, such as those contained in cow's milk. The acute allergic reaction, which depends on the structural feature of the allergen, is composed of two distinct pathways characterized by peptido-leukotrienes or PGD2 production, which may result from distinct activation intensities of mast cells, leading to distinct late reactions. CONCLUSION: This study thus demonstrates a clear link between the structural feature of a protein, and the physiopathology of the experimental asthmatic reaction.

Analysis of Variance↗

[Age-related changes of IgE-mediated allergic reaction in patients with late onset asthma--relationship between IgE-mediated allergy and age at onset].

We examined age-related changes in the IgE-mediated allergic reaction in patients with late onset asthma, whose asthma first occurred at over 40 years. 1. The number of patients with a high serum IgE level (over 300 IU/ml) was larger in patients with an age of onset between 40 and (40-49 years group) and in patients older than 60 at age of onset (60-year group) than in patients with an age of onset between 50 and 59 (50-59 year group). 2. A positive RAST score to house dust mite (HDm) allergen was more frequently found in the 40-49 year group and in the 60- year group than in the 50-59 year group. Frequency of positive RAST score to HDm in the 50-59 year group was significantly lower (p < 0.01) than in early-onset asthma patients (age at onset less than 39 years). 3 Frequency of family history of asthma in the 50-59 years group was high, being equal to that of early-onset asthma patients. 4 In the 50-59 year group, the frequency of severe asthma was comparatively higher than that of the other groups. The frequency of IgE-mediated allergic reaction changed in regard to age of onset of asthma, and allergic reactions in late-onset asthma partially resembled those of early-onset asthma. These results suggest that an atopic constitution is related to the onset of bronchial asthma in the elderly.

Adolescent↗

[Effects of YM-13650 on type I to type IV allergic reactions and immune responses in animals].

The effects of YM-13650 on experimental animal models of cell-mediated immune responses (type IV), antibody formation and type I to type III allergic reactions were investigated. YM-13650 in the dose range of 6.3 to 100 mg/kg, p.o., inhibited the picrylchloride-induced delayed type hypersensitivity (Pc-DTH) in mice when administered during the induction and the effector phases. The compound also inhibited the Pc-DTH enhanced by the pretreatment with cyclophosphamide, and even bilateral adrenalectomy failed to reduce the inhibitory effect of the compound on Pc-DTH in mice. YM-13650 in doses of 25 and 50 mg/kg, p.o., prolonged the survival time of allogenic skin grafts in mice. However, no significant effect was observed on hapten-specific IgE and HA antibody production and PFC formation in mice in doses up to 300 mg/kg, p.o. YM-13650 inhibited the passive Arthus reaction in guinea pigs and the reversed passive Arthus reaction in rats (type III). On the other hand, YM-13650 did not show any inhibitory effect on passive cutaneous anaphylaxis in rats (type I), Forssman shock in guinea pigs (type II) and carrageenin-induced paw edema in rats. These results indicate that YM-13650 suppresses not only cell-mediated immune responses but also type III allergic reactions without any influence on type I and type II allergic reactions as well as an acute inflammatory reaction.

Animals↗

Monocyte chemoattractant peptide-1 expression during cutaneous allergic reactions in mice is mast cell dependent and largely mediates the monocyte recruitment response.

BACKGROUND: Macrophages and infiltrating monocytes comprise the largest population of cells within the airways of patients with allergic asthma. Both become activated and thus contribute to the pathologic features of allergic reactions, but the mechanism by which they are recruited has not been well documented. OBJECTIVE: Our purpose was to assess the role of the CC chemokine monocyte chemotactic peptide-1 (MCP-1) in monocyte recruitment during allergic reactions in mice. METHOD: We used immunohistochemistry and Northern blotting to assess MCP-1 expression, selective mast cell reconstitution of mast cell-deficient W/W(v) mice to demonstrate the mast cell dependence of MCP-1 expression and monocyte recruitment and neutralizing anti-MCP-1 antibodies to block monocyte recruitment during cutaneous allergic reactions. RESULTS: MCP-1 was expressed largely by resident dermal cells within the allergic lesions at 4 hours after challenge, followed within several hours by an influx of monocytes; at 10 hours after challenge monocytes comprised a substantial proportion of the infiltrating cells at the nidus of the response. Mast cell-reconstituted, but not mast cell-deficient W/W(v) mice expressed MCP-1 transcripts and developed monocyte infiltrates after allergen challenge. Finally, anti-MCP-1 antibody treatments reduced by approximately 63% the influx of monocytes into the reaction sites. CONCLUSIONS: These data clearly demonstrate the mast cell dependence of the MCP-1 expression and the monocyte influx and establish a substantial, but not exclusive, causal relationship between these 2 events.

Animals↗

Peanut and tree nut allergic reactions in restaurants and other food establishments.

BACKGROUND: The clinical features of food-allergic reactions in restaurants and other food establishments have not been studied. Of the registrants in the United States Peanut and Tree Nut Allergy Registry (PAR), 13.7% have reported reactions associated with such establishments. OBJECTIVE: The purpose of this study was to determine the features of allergic reactions to peanut and tree nut in restaurant foods and foods purchased at other private establishments (eg, ice cream shops and bakeries). METHODS: Telephone interviews were conducted through use of a structured questionnaire. Subjects/parental surrogates were randomly selected from among the 706 PAR registrants who reported a reaction in a restaurant or other food establishment. RESULTS: Details were obtained for 156 episodes (29 first-time reactions) from 129 subjects/parental surrogates. Most reactions were caused by peanut (67%) or tree nut (24%); for some reactions (9%), the cause was a combination of peanut and another nut or was unknown. Symptoms began at a median of 5 minutes after exposure and were severe in 27% of reactions. Overall, 86% of reactions were treated (antihistamines, 86%; epinephrine, 40%). Establishments commonly cited were Asian food restaurants (19%), ice cream shops (14%), and bakeries/doughnut shops (13%). Among meal courses, desserts were a common cause (43%). Of 106 registrants with previously diagnosed allergy who ordered food specifically for ingestion by the allergic individual, only 45% gave prior notification about the allergy to the establishment. For 83 (78%) of these 106 reactions, someone in the establishment knew that the food contained peanut or tree nut as an ingredient; in 50% of these incidents, the food item was "hidden" (in sauces, dressings, egg rolls, etc), visual identification being prevented. In 23 (22%) of the 106 cases, exposures were reported from contamination caused primarily by shared cooking/serving supplies. In the remaining 21 subjects with previously diagnosed allergy, reactions resulted from ingestion of food not intended for them, ingestion of food selected from buffet/food bars, or skin contact/inhalation (residual food on tables, 2; peanut shells covering floors, 2; being within 2 feet of the cooking of the food, 1). CONCLUSIONS: Restaurants and other food establishments pose a number of dangers for peanut- and tree nut-allergic individuals, particularly with respect to cross-contamination and unexpected ingredients in desserts and Asian food. Failure to establish a clear line of communication between patron and establishment is a frequent cause of errors.

Humans↗

[Eosinophils in immediate allergic reactions].

Large numbers of eosinophils infiltrate the tissue in patients with various allergic disorders including asthma. Many appear to be degranulated to release mediators, granular proteins and superoxides, and are thereby considered to play an important role in tissue damage. Human eosinophils possess membrane receptors for IgE (Fc epsilon R II) and IgE-dependent eosinophil activation and following degranulation may be involved in immediate-type allergic reactions. Several lines of experimental evidence also suggest other eosinophil activation mechanisms by the stimulation of platelet-activating factor (PAF), leukotriene B4 and cytokines such as interleukin 5. Among these, PAF is a potent chemoattractant for eosinophils and is also capable of inducing activation such as a change from normodense into hypodense eosinophils. In animal models of allergic asthma, a specific PAF antagonist blocked eosinophil infiltration which was observed 6 hr after antigen challenge. However, another peak of tissue eosinophilia seen 24 hr after the challenge was not inhibited by PAF antagonist but was abolished by cyclosporin A, a T cell suppressant. These data suggested that PAF and T cell-derived factor(s) may be important in the pathogenesis of tissue eosinophilia observed in allergic reactions.

Animals↗

Hypersensitive allergic reactions to bismuth-iodoform-paraffin paste following ear surgery.

The case notes of 185 patients who had bismuth-iodoform-paraffin paste (BIPP) impregnated ribbon gauze used for packing following ear surgery were analysed retrospectively. The incidence of hypersensitive allergic reactions to BIPP was 5.9 per cent and a five-fold increase risk of developing allergic reactions was found in those with previous exposure to BIPP. Where temporalis fascia was used to repair tympanic membrane defects, the incidence of tympanic membrane graft perforations was higher when allergic reactions to BIPP developed post-operatively, compared to non-allergic cases.

Bismuth↗

[Anti-inflammatory activity of the dry distillation tar of delipidated soybean (Glyteer) (3). Effects on type I-type IV allergic reaction].

Effects of Glyteer (GL, 5%) on Type I-Type IV allergic reactions were investigated by its topical application to rats and mice, and the effects were compared with those of betamethasone 17-valerate (BV, 0.12%), indomethacin (ID, 1%), and bufexamac (BM, 5%), which were all prepared with the same ointment base. Type I: GL showed inhibitory effects on the 48 hr homologous passive cutaneous anaphylaxis (PCA) in rats. The inhibitory activity of GL on the PCA had the same potency as that of BV (0.12%). GL also inhibited the degranulation of mast cells induced by PCA. Type II: GL did not exert an inhibitory effect on the reversed cutaneous anaphylaxis (RCA) in rats, but BM, ID and BV had an inhibitory activity on the RCA. Type III: BV markedly inhibited the direct passive Arthus reaction in rats. On the other hand, GL, BM and ID had not an inhibitory activity on it. Type IV: GL (0.2, 1 and 5%) showed a concentration-dependent inhibition on the delayed-type hypersensitivity response induced by oxazolone in mice, and the activity was stronger than those of ID and BM. From these results, it is suggested that GL applied externally possesses a potent effect as an anti-allergic drug on Type I and Type IV allergic reactions.

Animals↗

An allergic reaction following intrauterine insemination.

Intrauterine insemination is a common procedure used for the treatment of different causes of infertility. Adverse reactions associated with this procedure are very rare and usually the procedure is well tolerated by the patient. We report a case of an allergic reaction after intrauterine insemination. The patient developed fever, difficulty breathing and wheezing in both lung fields. Although a low concentration of penicillin in the medium was used, it caused a significant allergic reaction. When intrauterine insemination was performed in subsequent cycles with an antibiotic-free medium, no allergic reaction occurred, and the procedure was well tolerated by the patient. A careful allergy history is essential in patients pursuing infertility treatment where antibiotics are utilized. Patients who are known to be allergic to penicillin should have semen prepared by an antibiotic-free medium.

Adult↗

Inhibitory effect of epinastine on the type II-IV allergic reactions in mice, rats and guinea pigs.

The inhibitory effect of epinastine (WAL 801 CL, CAS 80012-43-7) on types II, III and IV allergic reactions was studied. Epinastine caused an inhibition of type II allergic reactions: 1. the swelling of rat foot pad induced by a subcutaneous injection of anti-rat rabbit antiserum, and 2. lethality induced by an intravenous injection of anti-SRBC (sheep red blood cells) rabbit serum into guinea pigs (Forssman systemic reaction). The drug also caused an inhibition of the early phase in active Arthus reaction in guinea pigs (type III reactions). However, no significant inhibition was detected in the delayed-hypersensitivity reaction (type IV allergic response) induced by sheep red blood cells or picryl chloride in mice.

Animals↗

[The pharmacological correction of recurrent immediate-type allergic reactions].

The effect of drugs on the early and late phases of repeated allergic reactions (RAR) was studied in experiments on rabbits. The action of the drugs was estimated by the number of challenge doses of antigen, endured by survived and dead rabbits, percentage of the animals' death, and by the place of each group on the lethality scale. Diphenhydramine, ouabain and their combinations, silver nitrate (20 mg/kg) and DOCA enhanced whereas histamine, unithiol, cholesterol, and silver nitrate (20 and 0.2 mg/kg) decreased allergization in the period of RAR. The characteristic features of the action of the drugs on RAR were revealed and compared to the first allergic reaction. Qualitative and quantitative differences were shown in the action of different drug doses and combinations on RAR. The authors provide evidence for the possibility of treating allergic diseases by drug administration in a quiet period.

Animals↗

Inhibitory effects of Selaginella tamariscina on immediate allergic reactions.

The anti-allergic effects of a 70% ethanol extract from Selaginella tamariscina herb (EST) were evaluated in this study. EST given at the doses of 500 and 1000 mg/kg can inhibit mouse systemic anaphylactic shock induced by compound 48/80 in a dose-dependent manner. It can also dose-dependently block rat homologous passive cutaneous anaphylaxis and skin reactions caused by exogenous histamine and serotonin with a significant difference observed at the dose of 1000 mg/kg. In addition, EST can reduce histamine release from rat peritoneal mast cells triggered by compound 48/80 and an antigen in vitro. When incubated with rat mast cells, the extract (200 microg/ml) can significantly elevate the intracellular cAMP levels. The finding suggests that EST inhibits mast cell-dependent, immediate allergic reactions. Its effects appear to be mediated by reducing the release of vasoactive amines such as histamine from mast cells via stabilizing the cell membrane and weakening the inflammatory action of these amines. Based on these results, Selaginella tamariscina and one of its active components flavonoids may be useful as potential remedies for allergic rhinitis and other allergy-related diseases.

Anaphylaxis↗

[The eye as an effector of allergic reaction].

In this work the symptoms of allergic diseases of the eye were shortly described. The role of mast cells, eosinophils and lymphocytes taking part in allergic reaction was presented. The cellular mechanisms which lead to symptoms of allergic diseases of the eye were discussed. Histopathological changes in the eye tissues and their clinical importance were taken into consideration. The analysis of allergic symptoms of the eye on the basis of the knowledge of pathophysiological processes gives important information both for ophthalmologists and allergologists.

Cytokines↗

[The psychoimmunological network og panic disorders, agoraphobia and allergic reactions].

While treating panic and agoraphobia patients with behaviour therapy, a high frequency of allergic reaction of the IgE-mediated type I was observed. Panic disorder, agoraphobia, allergic disorder, and vasomotor reactions are briefly discussed in the framework of psycho-endocrino-immunological research. A pilot study had shown a high correlation between panic disorder with and without agoraphobia and allergic reaction. A controlled study was then planned to test the hypothesized psychoimmunological relationship. 100 allergic patients, 79 panic/agoraphobic patients, and 66 controls underwent psychodiagnostic and allergic screening. 70% of the anxiety patients responded to test allergens with IgE-mediated type-I immediate reactions in comparison to 28% of the control persons. Another 15% of the panic patients reacted to nickle compound with type-IV delayed skin reactions (7% of the controls). Conversely, 10% of the allergic patients suffered from panic disorder (45% had experienced panic attacks) in contrast to 2% of the controls (24% of these reported panic attacks). The relative risk for allergic patients to develop panic disorder with and without agoraphobia is obviously five times as high as for controls. With this assumption of a psychoimmunological preparedness in mind, a behavioural medical diagnostic and therapeutic concept seems more adequate in coping both with panic/agoraphobia and allergic disorder.

Agoraphobia↗