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J L Nilsson

Publications and source records attributed to J L Nilsson.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

15-hydroperoxydehydroabietic acid--a contact allergen in colophony from pinus species.

A new hydroperoxide, 15-hydroperoxydehydroabietic acid (15-HPDA), with contact allergenic properties has been detected in rosin obtained from Pinus species. Detection was facilitated using a synthetic preparation of 15-HPDA for reference purposes. The synthesis and the detection (HPLC and GC) of 15-HPDA in rosin are described. The allergenic activity of 15-HPDA was studied in an experimental sensitization test on guinea-pigs.

Abietanes

Pharmaceutical care for patients with skin diseases: a campaign year at Swedish pharmacies.

A pharmaceutical care programme for pharmacy customers/patients with skin disorders was carried out at all Swedish pharmacies in 1993 (Skin Year). The objective of the campaign was to increase awareness, compliance and appropriateness of the treatment of skin diseases in patients attending pharmacies. The campaign was carried out primarily at pharmacies and in close contact with other health-care professionals. A variety of promotional material was produced and made available to the pharmacies. The activities were primarily directed towards pharmacy customers but also towards the staff of local health-care centres. To avoid large-scale and costly population surveys in the national evaluation of the Skin Year campaign, evaluation was carried out indirectly by following four disease groups and monitoring the influence that the campaign may have had on the use of medicines by patients with those disorders. The groups chosen were dry skin, eczema, athlete's foot and acne. There was a substantial increase in the use of medication for skin disorders in the campaign year 1993 and in 1994. If it is assumed that the level of drug use is a reflection of the level of treatment it can be concluded that treatment of the four diseases increased substantially, indirectly demonstrating 'increased awareness, compliance and appropriateness of treatment' as stated in the objectives. It is estimated that the campaign may have reduced the number of physician consultations for skin problems and that this has led to a cost reduction of at least SK100 million (equivalent to $15 million) or 5-10% of the health-care costs for skin disorders. Comparable data on patient outcome as a result of the campaign are not available.

Acne Vulgaris

Hydroperoxides in oxidized d-limonene identified as potent contact allergens.

Hydroperoxides of d-limonene were shown to be potent contact allergens when studied in guinea-pigs. Limonene-2-hydroperoxide (2-hydroperoxy-p-mentha-6,8-diene, a mixture of trans and cis isomers) was synthesized for the first time. The ratio between the trans and cis forms was 3:1. These two hydroperoxides were identified as the major hydroperoxides in autoxidized d-limonene. In photo-oxidized d-limonene, they constituted a minor part of the hydroperoxide fraction. Hydroperoxides may bind to proteins of the skin to make antigens either via a radical mechanism or after reactions to give epoxides. The cross-reactivity between the epoxide limonene-1,2-oxide, a potent contact allergen, and the hydroperoxides was therefore studied. No significant pattern of cross-reactivity was found. Further studies to identify and test the allergenicity of single hydroperoxides are needed to elucidate the mechanism of the allergenicity.

Allergens

Allergenicity of rosin (colophony) esters (II). Glyceryl monoabietate identified as contact allergen.

In the esterification of rosin with glycerol, the main compound formed, glyceryl triabietate, shows low allergenic activity. In this study, compounds formed in smaller amounts, when abietic acid (main component in rosin) was esterified with glycerol, were identified as glyceryl-1-monoabietate (GMA), glyceryl-1,2-diabietate (GDA1,2) and glyceryl-1,3-diabietate (GDA1,3), using nuclear magnetic resonance (NMR), infra-red (IR) and mass spectrometry (MS) analyses. According to animal experiments, GMA was a contact allergen. No cross-reactivity was seen to allergens in unmodified rosin. Some patients allergic to unmodified rosin reacted when tested with GMA. No reactions were seen to the 2 diabietates. Some patients also reacted to commercial glycerol-modified rosins. GMA together with unmodified abietic acid were identified in these rosin samples. The reactions seen in rosin-sensitive patients to commercial glycerol-esterified rosins probably derive from the unmodified material still present in the product, but could also be the result of GMA obtained from the glycerol derivatization.

Abietanes

The allergenicity of glycerol esters and other esters of rosin (colophony).

To investigate whether esterification of rosin with polyalcohols changes its allergenic potential, abietic acid, the main component of rosin, was esterified with glycerol at high temperature. The major product formed was isolated and identified, using nuclear magnetic resonance (NMR), infra-red (IR) and mass spectrometry (MS) analyses, as glyceryl triabietate (GTA), an ester between one glycerol molecule and 3 abietic acid molecules. According to animal experiments GTA was not allergenic and no cross-reactivity was seen to allergens in unmodified rosin. When testing patients allergic to unmodified rosin, no reactions were found to GTA. Some of the patients reacted to glycerol- and pentaerythritol-esterified rosins. According to HPLC analyses, these esterified rosins still contained unmodified material to which the patients may have reacted. It seems that the esterification of rosin with polyalcohols such as glycerol reduces its allergenic activity, possibly because of the formation of much larger molecules with reduced bioavailability. However, making methyl esters of rosin causes little alteration in the molecular weights of the components and, when unmodified and methylated rosin were tested in patients, we saw no difference between the 2 forms.

Abietanes

Rosin allergy: identification of a dehydroabietic acid peroxide with allergenic properties.

A peroxide of dehydroabietic acid was isolated from rosin using flash chromatography and preparative HPLC. It was identified by 1H-NMR and MS. In animal experiments, this peroxide cross-reacted with a previously identified allergen in rosin, 15-hydroperoxyabietic acid (15-HPA), despite differences in molecular weight and unsaturation. Both substances are able to react via a radical mechanism generating structurally similar molecules. In patch testing of patients, no reactions were observed to the peroxide. Low skin penetration of the peroxide could be the explanation for this. The peroxide seems of little clinical importance. The observed cross-reactivity is an indication of antigen generation via a radical mechanism. Only a few compounds that react with radical mechanisms to form antigens are described in the literature.

Abietanes