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Cytokine production induced by low-molecular-weight chemicals as a function of the stimulation index in a modified local lymph node assay: an approach to discriminate contact sensitizers from respiratory sensitizers.

In general, contact sensitizers have been shown to selectively induce Th1 immune responses, such as interferon-gamma (IFN-gamma) production, whereas Th2 responses, such as interleukin (IL)-4 production, were seen after exposure to respiratory allergens. However, these features may be dependent on the dose of the particular allergen. Therefore, the aim of the present study was to investigate the distinction between contact sensitizers and respiratory allergens, by establishing dose-dependent cytokine profiles. The contact allergens 2,4- dinitrochlorobenzene (DNCB), hexyl cinnamic aldehyde (HCA), and oxazolone (OXA, 4-ethoxymethylene 2-phenyloxazol-5-one) as well as the respiratory allergens fluorescein 5-isothiocyanate, phthalic anhydride, toluene diisocyanate, and trimellitic anhydride were tested. For a range of concentrations, both proliferative responses and cytokine production were established. Estimated concentrations were derived at several stimulation indices (SIs). From the estimated concentrations, IFN-gamma, IL-4, and IL-10 production as a function of stimulation indices were plotted. All four respiratory allergens showed significantly higher IL-4 and IL-10 production patterns compared to the contact allergens. Positive identification of DNCB, HCA, and OXA as contact allergens on the basis of IFN-gamma production was observed only at very high stimulation indices (SI >or= 35) for DNCB and OXA and at low SIs (SI <or= 7) for HCA. We propose that, by direct linkage of proliferation and cytokine production in a dose-response manner, distinguishing contact allergens from respiratory allergens may be improved compared to present approaches.

Administration, Inhalation↗

[The efficacy of combined medical treatment (antihistaminics, steroids, and macrolide antibiotics) in patients with nasal polyposis: preliminary results].

OBJECTIVES: We evaluated the efficacy of combined medical treatment in cases with bilateral nasal polyposis without a history of any surgical or medical treatment. PATIENTS AND METHODS: Twenty-five patients (19 males, 6 females; mean age 45 years; range 30 to 60 years) who had not received any treatment for bilateral nasal polyposis were included. Treatment was comprised of an oral anti-histaminic agent (single dose daily for 3 weeks), and a topical steroid (as a nasal spray, twice daily for 6 months) and a single dose of intramuscular systemic steroid. Patients who did not respond to this therapy at the end of three weeks were administered a macrolide antibiotic (clarithromycin). The results were evaluated before treatment, and three weeks and six months after treatment with the use of a patient questionnaire, computed tomography and endoscopic examination findings. RESULTS: The patients' complaints improved by 85.5% and 79% at the end of three weeks and six months, respectively (p<0.005). Radiologic improvement was found to be 64% at the end of six months (p<0.005). The overall decrease in the size of the polyps was significant (p<0.005). No treatment-associated complications were encountered. CONCLUSION: Significant improvement achieved favors the use of combined medical treatment before surgery in selected patients with nasal polyposis.

Administration, Inhalation↗

No growth suppression in children treated with the maximum recommended dose of fluticasone propionate aqueous nasal spray for one year.

This randomized, double-blind, placebo-controlled study of fluticasone propionate aqueous nasal spray (at a maximum recommended dose of 200 micrograms each day) administered daily for one year was conducted to evaluate its potential effects on growth, measured by stadiometry, in prepubescent children with perennial allergic rhinitis (n = 150; age 3.5 to 9.0 years). The results demonstrate equivalent growth velocity over a one-year treatment period between children receiving fluticasone propionate aqueous nasal spray and children receiving vehicle placebo. In addition, children in both treatment groups had similar increases in height over the same period. Baseline height was 119.1 cm (SE = 0.72) in the fluticasone propionate group (n = 56) and 119.0 cm (SE = 0.71) in the vehicle placebo group (n = 52). Mean height at the end of one year of treatment was 125.5 cm (SE = 0.18) in the fluticasone propionate group (n = 44) and 125.4 cm (SE = 0.19) in the vehicle placebo group (n = 39) (least-squares mean difference -0.12; 95% confidence interval [-0.600, 0.352]). The effects of fluticasone propionate on one-year growth velocity were also comparable to those of vehicle placebo. The confidence interval for the treatment difference lay within the prospectively defined equivalence bounds (of -0.8, +0.8 cm/year) and contained zero. The incidence of adverse events considered to be at least possibly drug-related did not differ between the fluticasone propionate group and the vehicle placebo group. The results of this one-year, double-blind study demonstrate that fluticasone propionate aqueous nasal spray at the maximum recommended dose of two sprays per nostril (200 micrograms) once daily was equivalent to vehicle placebo with no effects on growth rate in prepubescent children.

Administration, Inhalation↗

Influenza.

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Acetamides↗

[Interferon-based immunobiological preparations. An outlook of their use in the treatment of patients with infections].

The paper contains the generalizing results of many-year research related with using various ready-made medication forms (RMF) of human genetic-engineering interferon-alpha 2 and of methods of its administration into the body. Extensive clinical materials were made use of to show convincingly that the most effective therapy for infectious diseases is ensured within a short time period and with a consequent long-term rehabilitation effect by using separate RMFs and methods of application of interferon-alpha 2, when their impact on the lesion focus is monitored by the parameters of the cellular-and-humoral chains of the general and local immunity. It is noteworthy, that a selection of RMF adequate for an actual nosologic form or of an administration method can reduce the medication dose of interferon-alpha 2 (thus, the incidence of complications to the drug goes down), it can also eliminate the influenza-like syndrome and production of autoantibodies related with the intramuscular administration of interferon-alpha 2, besides, it essentially prolongs the presence of interferon-alpha 2 in the body. It is important that the application of interferon-based preparations for infectious diseases can eliminate, in a number of cases, the use of antibiotics and other antibacterial drugs, it enhances the efficacy of antibacterial and antiviral therapy within a comprehensive treatment scheme, it contributes to a higher resistance of normal flora to the action of antibiotic and antibacterial drugs, and, finally, it arrests quicker the manifestations of dysbacterioses of various localizations.

Administration, Inhalation↗

The acute toxicity, primary irritancy and skin sensitizing potential of glutaric anhydride.

Glutaric anhydride (GA), an industrial chemical, was found of moderate acute peroral lethal toxicity with LD50 values (95% confidence limits) in the rat of 1.41 (0.80-2.49) g/kg (males) and 0.54 (0.36-0.79) g/kg (females), with death being due in part to gastrointestinal irritancy. Dilution with water given by gavage after peroral dosing had no effect on lethal toxicity. Acute percutaneous LD50 values (rabbit) by 24-h occlusion were 6.25 (5.34-7.33) g/kg in males and 5.66 (3.21-9.95) g/kg in females; local skin effects included erythema, edema, necrosis and ulceration. A 6-h exposure to a statically generated saturated vapor atmosphere (rat) produced no signs of toxicity or irritancy. A 4-h, but not 1-h or 3-min occluded contact with 0.5 g of moistened GA (rabbit) produced erythema, edema and necrosis. Contamination of the eye (rabbit) with 10 mg GA produced conjunctivitis (hyperemia, chemosis and discharge) which persisted 7 to 14 d, mild iritis of 2 to 14 d duration, and mild to severe corneal injury which healed within 14 d. A maximization study in guinea pigs by the method of Magnusson and Kligman showed no potential for skin sensitization with GA. The major acute hazards of GA were by swallowing, eye contact and sustained skin contact.

Administration, Cutaneous↗