ABSTRACT
OBJECTIVE: We tested the effect of various doses of bacterial lipopolysaccharide (LPS, endotoxin) on the expression of CD63 and the in vitro release of histamine by basophils stimulated with ragweed allergen in patients with or without ragweed and mite allergies. METHODS: The peripheral blood of 11 patients with ragweed allergy, 10 patients with mite allergy and 14 control patients was incubated with ragweed allergen extract following pretreatment with varying doses of LPS. The expression of CD63 in basophils was measured by flow cytometry, and the release of histamine was determined by ELISA. RESULTS: In the samples of patients with ragweed allergy that were exposed to specific allergen, only high doses of LPS significantly elevated the expression of CD63 (200 ng/ml; 1,000 EU/ml) and the release of histamine (2,000 ng/ml; 10,000 EU/ml). There was no effect of LPS in any other cases. CONCLUSIONS: Bacterial LPS (endotoxin) concentrations higher than 200 ng/ml (1,000 EU/ml), which rarely occurs in nature, could only activate the basophils from atopic patients whilst in the presence of the specific allergen. Thus, the restoration of the urban, "microbe-poor" milieu with endotoxin (as LPS) can be a promising and harmless approach for allergy prevention.
Subject(s)
Basophils/immunology , Histamine Release/immunology , Hypersensitivity/immunology , Tetraspanin 30/immunology , Adolescent , Adult , Ambrosia/immunology , Antigens, Dermatophagoides/immunology , Antigens, Plant/immunology , Child , Child, Preschool , Female , Humans , Lipopolysaccharides , Male , Plant Proteins/immunology , Young AdultABSTRACT
The major mechanism of removing cyanide from the body is its enzymatic conversion by a sulfurtransferase, e.g. rhodanese, to the less toxic thiocyanate in the presence of a sulfur donor. Earlier results demonstrated that externally administered encapsulated rhodanese significantly enhances the in vivo efficacy of the given sulfur donor. Present studies are focused on liposomal carrier systems encapsulating rhodanese. Physicochemical properties, e.g. membrane rigidity, size distribution, surface potential, osmolarity, and viscosity, were determined for various liposomal lipid compositions and hydrating buffers to establish in vitro stability and in vivo fate. Lipid composition was also optimized to achieve maximum encapsulation efficiency.
Subject(s)
Cyanides/antagonists & inhibitors , Thiosulfate Sulfurtransferase/administration & dosage , Thiosulfate Sulfurtransferase/chemistry , Cyanides/metabolism , Liposomes , Viscosity/drug effectsABSTRACT
Prophylactic and therapeutic efficacy against organophosphorus (OP) intoxication by pralidoxime (2-PAM) and atropine were studied and compared with sterically stabilized long-circulating liposomes encapsulating recombinant organophosphorus hydrolase (OPH), either alone or in various specific combinations, in paraoxon poisoning. Prophylactic and therapeutic properties of atropine and 2-PAM are diminished when they are used alone. However, their prophylactic effects are enhanced when they are used in combination. Present studies indicate that sterically stabilized liposomes (SL) encapsulating recombinant OPH (SL-OPH) alone can provide much better therapeutic and prophylactic protection than the classic 2-PAM + atropine combination. This protection was even more dramatic when SL-OPH was employed in combination with 2-PAM and/or atropine: the magnitude of prophylactic antidotal protection was an astounding 1022 LD(50) [920 mg/kg (LD(50) of paraoxon with antagonists)/ 0.95 mg/kg (LD(50) of control paraoxon)], and the therapeutic antidotal protection was 156 LD(50) [140 mg/kg (LD(50) of paraoxon with antagonists)/0.9 mg/kg (LD(50) of control paraoxon)]. The current study firmly establishes the value of using liposome encapsulating OPH.
Subject(s)
Aryldialkylphosphatase/administration & dosage , Atropine/pharmacology , Atropine/therapeutic use , Insecticides/poisoning , Neurotoxicity Syndromes/drug therapy , Neurotoxicity Syndromes/prevention & control , Paraoxon/poisoning , Pralidoxime Compounds/pharmacology , Pralidoxime Compounds/therapeutic use , Animals , Antidotes/administration & dosage , Antidotes/pharmacology , Antidotes/therapeutic use , Cholinesterase Reactivators/pharmacology , Cholinesterase Reactivators/therapeutic use , Drug Combinations , Lethal Dose 50 , Liposomes , Male , Mice , Mice, Inbred BALB C , Muscarinic Antagonists/pharmacology , Muscarinic Antagonists/therapeutic useABSTRACT
The objective of this study was to compare the changes in the values of allergen-specific serum IgE levels and zymosan-induced whole blood chemiluminescence (CL) in 41 patients who had exclusively only ragweed allergy in the season of acute symptoms of disease in July, August and September. All patients had allergic rhinitis or rhinoconjunctivitis. Each patient was investigated as a self-control. The ragweed-specific IgE levels were measured by enzyme immunoassay (EIA). The luminol amplified zymosan-induced CL of whole human blood was detected. The allergen-specific serum IgE levels showed slight, but not significant, gradually increasing elevations during the whole season. On the other hand, significant increases were found in the values of the basal but especially in the zymosan-stimulated CL of peripheral blood phagocytes during the acute phase of allergy. Both the basal and the zymosan-induced CL reflected significantly the activated state of the immune system. These observations clearly show that there are well detectable signs of the systemic activation of the immune system in allergic rhinoconjunctivitis beside the local alterations. In addition, the measurements of the basal and zymosan-induced CL of peripheral phagocytes could clearly reflect the clinical state of disease in vitro.
