Search PubMed⌕ Search

Biomedical subjects

J L Nilsson

Publications and source records attributed to J L Nilsson.

At least 19 recordsLinked to original sources
PubMed2001

Identification and allergenic activity of hydroxyaldehydes - a new type of oxidation product from an ethoxylated non-ionic surfactant.

Ethoxylated alcohols, which are widely used as surfactants, are susceptible to oxidation on air exposure. A complex mixture of oxidation products is formed, among which alkylated aldehydes, alkylated formates, formaldehyde and peroxides have previously been identified by our group. In the present study, we have identified a new class of oxidation product from the nonionic ethoxylated surfactant C12E5. These oxidation products are highly water-soluble hydroxyaldehydes with the general formula HO(CH2CH2O)nCH2CHO, n=1-4. To facilitate the identification of the hydroxyaldehydes in oxidized C12E5, reference compounds were synthesized. The sensitizing potential of 1 of the identified hydroxyaldehydes, HO(CH2CH2O)3CH2CHO, was studied in guinea pigs and was found to be weak. A significant cross-reactivity between this aldehyde and the next shorter homologue, HO(CH2CH2O)2CH2CHO, was observed. Irritant components, present in the oxidation mixture, facilitate the skin penetration of allergens, which further accentuates the importance of controlling the conditions of storage and handling of ethoxylated surfactants, to reduce the formation of allergenic and irritant oxidation products.

Aldehydes↗
PubMed2001

Mechanism of the antigen formation of carvone and related alpha, beta-unsaturated ketones.

In the present study, the mechanism for the antigen formation of alpha, beta-unsaturated ketones was investigated. A series of analogues of carvone ((5R)-5-isopropenyl-2-methyl-2-cyclohexenone) with altered chemical reactivity and with retained overall structure or with retained reactivity and altered three-dimensional structure were synthesized. These analogues were tested for cross-reactivity in carvone-sensitized animals. Cross-reactivity was observed for analogue 3 ((5R)-5-isopropyl-2-methyl-2-cyclohexen-1-one). No cross-reactions were observed for analogues 1 ((2R,5R)-5-isopropenyl-2-methyl cyclohexanone) and 4 ((5R)-2,3-dimethyl-5-isopropenyl-2-cyclohexene-1-one). Both those compounds also failed to induce sensitization. These findings demonstrate that alpha, beta-unsaturated ketones form antigens after a nucleophilic attack at the beta-carbon with soft nucleophiles such as thiol in cysteine and not with the formation of a Schiff's base after a nucleophilic attack at the carbonyl carbon with nitrogen nucleophiles. Furthermore, no cross-reactivity was observed between R- and S-carvone indicating the importance of the 3-dimensional structure of haptens (and antigens) in T-cell recognition. The analogues were also tested for cross-reactivity on patients allergic to carvone. The results from the animal study were confirmed.

Allergens↗
PubMed2000

Skin irritation from air-oxidized ethoxylated surfactants.

Surfactants are known to be skin irritants, but change in their irritant potential due to change in composition during handling and storage has not previously been investigated. The aim of this study was to investigate the influence of oxidation products on the irritant potential of a non-ionic ethoxylated alcohol, C12E5. Pure and oxidized C12E5 were tested, using 2 different patch test procedures; 1 with a single 24 h exposure and 1 with repeated exposures. 18 healthy volunteers participated in each of these studies. Evaluations were made by visual scoring and by measurement of transepidermal water loss and skin blood flow. In the single exposure study, no significant difference in skin irritation was observed between pure C12E5 and a sample of oxidized C12E5 at the concentrations tested (1, 3, 9 and 27%). After repeated exposures, however, the oxidized C12E5 was significantly more irritant than pure C12E5 at the concentrations 9% and 27% (p<0.05). Non-ionic ethoxylated surfactants are known for their weak skin irritant effect and are, due to this, often included in products with prolonged contact with the skin, i.e., skin care products. An increased irritant potential after oxidation might be of importance due to the conditions of use.

Adult↗
PubMed1999

Atmospheric oxidation of poly(oxyethylene) alcohols. Identification of ethoxylated formates as oxidation products and study of their contact allergenic activity.

Ethoxylated alcohols are widely used as surfactants. In the present study we have continued our investigations on the degradation with time upon air exposure of the ethoxylated alcohols at normal storage and handling. As a result, a new group of ethoxylated formates with the general formula C12H25(OCH2CH2)nOCHO (n = 0-4) was identified in C12H25(OCH2CH2)5OH stored and handled at room temperature. To facilitate the identification work, reference compounds were synthesized. The formates showed no allergenic activity in the sensitization studies performed. In previous investigations on the same ethoxylated alcohol, we have identified formaldehyde and ethoxylated aldehydes among the oxidation products formed. Formaldehyde is a common contact allergen, and the ethoxylated aldehydes were shown to have a sensitizing capacity of the same magnitude as formaldehyde. The instability of the ethoxylated alcohols and formation of oxidation products may give an allergenic contribution to hand eczema caused by work with water and surfactants. To investigate the clinical significance in man an appropriate diagnostic patch testing in exposed humans is required.

Allergens↗
PubMed1999

Direct Ni2+ antigen formation on cultured human dendritic cells.

The possible direct antigen formation of Ni2+ on antigen-presenting cells (APCs) was studied with cultured human dendritic cells (DCs) obtained from 10 subjects contact allergic to Ni2+ and six non-allergic control individuals. All contact allergic subjects showed a significantly increased peripheral blood mononuclear cell (PBMC) response in vitro to Ni2+. DCs were expanded from the plastic-adherent cell fraction of PBMCs by culturing with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 7 days to obtain immature DCs, and with the addition of monocyte-conditioned medium for another 4 days, for DC maturation. The DCs were pulsed for 20 min with Ni2+ (50 micrometers) in protein-free Hank's balanced salt solution (HBSS) and added to freshly prepared autologous responder PBMCs. With five allergic subjects, immature DCs pulsed with Ni2+ demonstrated a significant capacity to activate Ni2+-reactive lymphocytes. With the remaining five patients and the six controls no difference in lymphocyte proliferation was observed between Ni2+-pulsed and non-pulsed immature DCs. In contrast, with mature Ni2+-pulsed DCs from both 'positive responder' (n=4) and 'non-responder' (n=4) patients, there was a significantly stimulated PBMC proliferation, whereas with the controls (n=4) still no activation was observed. Our results indicate that direct formation of the antigenic determinant of Ni2+ on APCs is possible and that Ni2+ uptake and processing mechanisms may not play a major role. Differences in the ease of activation of Ni2+-reactive lymphocytes are discussed in terms of a possible heterogeneity in the availability of Ni2+-reactive groups presented on endogenous peptides bound in the antigen binding groove of human leucocyte antigen (HLA) class-II molecules.

Adult↗
PubMed1998

Free radicals as potential mediators of metal-allergy: Ni2+- and Co2+-mediated free radical generation.

The generation of free radicals by Ni(2+) and Co(2+) was studied at physiological pH in H(2)O(2)-containing solutions in the absence and presence of various radical-mediating ligands and in human peripheral blood mononuclear cell (PBMC) cultures. With ESR spectroscopy, free radical species were identified and quantitated by spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Co(2+) generated hydroxyl radicals from H(2)O(2) in PBS solutions containing glutathione (GSH) or histidine (His). Omission of GSH or His from the reaction mixture significantly reduced the ESR-signal, indicating the importance of metal-chelation in free radical generation. Carnosine did not significantly enhance the reactivity of Co(2+) toward H(2)O(2), whereas cysteine (Cys) and N-acetylcysteine (NAC) suppressed free radical generation. Under identical reaction conditions, Ni(2+) was markedly less reactive toward H(2)O(2) in comparison with Co(2+). GSH, His, Cys and NAC did not enhance free radical generation of Ni(2+) from H(2)O(2). However, in the presence of carnosine weak but significantly enhanced ESR intensities were found. Incubation of PBMC cultures from healthy subjects with Co(2+) (10-50 microM) yielded the DMPO-.OH adduct, suggesting Co(2+)-mediated hydroxyl radical generation. In contrast, incubation of PBMC cultures with Ni(2+) (10-50 microM) did not produce a detectable ESR-signal. Ascorbic acid efficiently inhibited Co(2+)-mediated free radical generation in PBS solutions and PBMC cultures. The observed difference in free radical generating capacity between Ni(2+) and Co(2+) is of interest with respect to the absence of cross-reactivity between the two metal-ions in experimental allergic contact dermatitis.

Acetylcysteine↗
PubMed1998

Contact allergens from surfactants. Atmospheric oxidation of polyoxyethylene alcohols, formation of ethoxylated aldehydes, and their allergenic activity.

Ethoxylated surfactants are susceptible to oxidation upon air exposure. We have previously studied the rate of peroxidation and formaldehyde formation in the chemically well-defined ethoxylated alcohol C12H25(OCH2CH2)5OH. Formaldehyde is a common cause of contact allergy. The aim of the present study was to identify other oxidation products that could be formed upon air exposure of the ethoxylated alcohol and to determine their allergenic activity. It was shown that air oxidation of C12H25(OCH2CH2)5OH gave all the theoretically possible aldehydes of the general formula C12H25(OCH2CH2)nOCH2CHO (n = 0-4) and that the major oxidation product was C12H25(OCH2CH2)4OCH2CHO, dodecyltetraoxyethyleneoxyacetaldehyde. The structure elucidation and synthesis of these aldehydes are here presented for the first time. The major aldehyde was shown to be a contact allergen with the same sensitizing capacity as that of formaldehyde. A dose-response relationship was observed in the sensitization studies. The allergens were formed from the surfactant itself and the skin reactions cannot be explained due to any impurities that may be present in a technical quality of the surfactant. Cases of allergic contact dermatits to ethoxylated surfactants have been reported. To avoid the formation of allergenic oxidation products it is important to control the conditions for storage, handling, and transportation of ethoxylated surfactants.

Alcohols↗
PubMed1998

Free radicals as potential mediators of metal allergy: effect of ascorbic acid on lymphocyte proliferation and IFN-gamma production in contact allergy to Ni2+ and Co2+.

A possible free radical mechanism in metal allergy was investigated in peripheral blood mononuclear cell (PBMC) cultures from 6 subjects, contact allergic to Ni2+ and Co2+, and 6 control individuals. Ni2+ and Co(2+)-mediated free radical generation was studied with electron spin resonance spectroscopy. The immune response was characterized by cellular [methyl-3H]thymidine uptake and interferon-gamma (IFN-gamma) production Ni2+ and Co2+ (10-50 microM) significantly increased lymphocyte proliferation and IFN-gamma production in PBMC cultures from contact allergic subjects in comparison with cultures from controls. Inhibition of Co(2+)-mediated free radical generation by ascorbic acid did not influence cellular [methyl-3H]thymidine uptake and IFN production. Detectable amounts of free radicals were not obtained with Ni2+. We therefore conclude that it is unlikely that free radicals are involved in contact allergy to Ni2+ and Co2+.

Adult↗
PubMed1998

Lack of antagonism to Ni2+ and Co2+ contact allergy from other essential divalent metal ions.

The potential antagonistic effects of Ca2+, Cu2+, Fe2+, Mg2+, Mn2+ and Zn2+ on contact allergy to Co2+ and Ni2+ were studied. The immune response was characterized by the Co2+ or Ni2+ mediated cellular [methyl-3H]thymidine uptake in peripheral blood mononuclear cell (PBMC) cultures from 6 subjects contact-allergic to Co2+ and Ni2+ and 6 non-allergic control individuals. Results from the in vitro experiments were further evaluated with Co2+-sensitized guinea pigs according to the modified Freund's complete adjuvant test. Ni2+ and Co2+ (10-50 microM) significantly increased the lymphocyte proliferation in PBMC cultures from contact-allergic subjects in comparison with those from control individuals. Pretreatment of the PBMCs with Ca2+, Fe2+, Mg2+ (10-100 microM) or Mn2+ (1-10 microM) did not influence, while Zn2+ (100 microM) enhanced, and Cu2+ (5 and 10 microM) markedly reduced the Ni2+ and Co2+ mediated cellular [methyl-3H]thymidine uptake. The inhibition of the Ni2+- and Co2+-induced cell proliferation by Cu2+ in vitro was probably related to toxicity, since the viability of the cells was significantly reduced by applied combinations of Ni2+ or Co2+ with Cu2+. Topical pretreatment of Co2+-sensitized guinea pigs with maximum non-irritating doses of CuCl2 x 2H2O (0.8%) did not affect the challenge testing to CoCl2 x 6H2O (0.1 and 0.3%). In conclusion, our combined in vitro and in vivo results indicate that Ca2+, Cu2+, Fe2+, Mg2+, Mn2+ and Zn2+ are not able to antagonise the formation of Ni2+ and Co2+ antigens.

Adult↗
PubMed1998

Formation of formaldehyde and peroxides by air oxidation of high purity polyoxyethylene surfactants.

Ethoxylated alcohols are non-ionic surfactants. The majority are used in household cleaners, laundry products, toiletries and in industrial and institutional cleaners. In previous studies, an ethoxylated non-ionic surfactant of technical quality showed allergenic activity in guinea pig experiments. Chemical analysis revealed a content of formaldehyde, a well-known contact allergen, and peroxides in the surfactant. Most cases of occupational contact dermatitis are considered to be of irritant origin, caused by contact with water and surfactants, but if allergenic autoxidation products can be formed, allergic contact dermatitis cannot be excluded. The sensitizing potential of a chemically defined high purity ethoxylated alcohol was investigated and oxidation under various storage and handling conditions was studied for this and a homologous product. The pure surfactant showed no significant allergenic activity on predictive testing in guinea pigs. When ethoxylated alcohols were stored in the refrigerator, their deterioration was limited. At room temperature, their content of peroxides and formaldehyde increased with time. Levels of formaldehyde above those capable of causing positive patch test reactions were found. Since such surfactants have wide applications, resulting exposure to formaldehyde could be more frequent than is generally realized, contributing to persistence of dermatitis in individuals allergic to formaldehyde.

Aerobiosis↗
PubMed1997

Contact allergenic activity of Tween 80 before and after air exposure.

Tween 80 is an ethoxylated hydrophilic non-ionic surfactant, which is used for the preparation of oil-in-water emulsions in pharmaceutical products, cosmetics, and industrial detergents. Ethoxylated surfactants are polyethers and are thus easily oxidized by atmospheric oxygen to a variety of hydroperoxides, peroxides and carbonyl compounds. The aim was to investigate the formation of oxidation products and the allergenic potential of Tween 80 before and after air exposure. The formation of peroxides and formaldehyde was followed with chemical analyses during air and pure oxygen exposure of water solutions of Tween 80 of technical quality. A complex mixture of compounds was formed when Tween 80 was oxidized. Formaldehyde was detected in amounts that may be eliciting in allergic individuals. Acetaldehyde was identified in Tween 80 before oxygen exposure, whereafter the amount gradually decreased. The contact allergenic activity was determined in experimental sensitization studies in guinea pigs. Non-oxidized as well as oxidized Tween 80 of technical quality showed allergenic activity. The results indicate that allergens are present in Tween 80 before oxidation and that new allergens are formed in the oxidation process. No obvious dose-response relationship was found in the sensitization studies. The possibility that allergenic compounds can be formed during storage and handling of products containing ethoxylated surfactants should be taken into consideration.

Acetaldehyde↗
PubMed1996

The asthma year in Swedish pharmacies: a nationwide information and pharmaceutical care program for patients with asthma.

OBJECTIVE: To increase the understanding of asthma among patients and the general public in Sweden and to increase the collaboration among healthcare personnel for the benefit of asthma patients. DESIGN: Based on the results from problem detection studies, Apoteksbolaget, the national organization for pharmacies in Sweden, designed a program to educate healthcare professionals and the public about asthma. Entitled the "Asthma Year," all pharmacy staffs were offered education on asthma, patients were provided written information and audiovisual materials, and the general public was made more aware of asthma through local media. SETTING: Pharmacies, healthcare centers, hospital outpatient areas, libraries, places of work, and domestic airports. PARTICIPANTS: All pharmacy staffs (12,000 persons) were offered an education on asthma. Patients with asthma were offered brochures and leaflets in pharmacies and information in the pharmacy magazine Apoteket. The general public received information about asthma through posters, radio, and television. MAIN OUTCOME MEASURES: The evaluations of the Asthma Year indicate that the activities had an impact on the public, on patients with asthma, and on the pharmacy staffs. RESULTS: About 4.5 million people in Sweden (42% of the population) observed the Asthma Year or received information about asthma, and 49% of the patients learned something new about their disease. Twice as many patients used steroid therapy regularly after the campaign than before. Of the pharmacy staffs, 96% were favorable to the idea of working with campaign years and 85% believed that they were personally involved with the activities. CONCLUSIONS: Patient outcomes in terms of reduced morbidity have not been possible to document, but the number of deaths from asthma in Sweden decreased from 438 during the previous year to 398 during the Asthma Year.

Adolescent↗