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Biomedical subjects

J L Nilsson

Publications and source records attributed to J L Nilsson.

At least 37 records · Page 2Linked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1990

Maleopimaric acid--a potent sensitizer in modified rosin.

The allergenicity of the maleic-modified rosins and their esters has been studied. The unesterified resins are mainly used in paper size and the esters in printing inks, varnishes and adhesives. The levopimaric-maleic anhydride Diels-Alder adduct (maleopimaric acid) is the main component obtained in the maleic-modified rosins. This compound was synthesized and its structure was determined. Its sensitizing potential was investigated in guinea pigs according to different methods. It was shown that maleopimaric acid is a very potent sensitizer, comparable with the strongest allergen isolated from unmodified gum rosin. The allergen may also be present after esterification unless the process is carried out to completion. The animals sensitized to maleopimaric acid did not react to unmodified rosin, which shows that maleopimaric acid is structurally different from the allergens in rosin.

Allergens↗
PubMed1988

N,N-Dialkylated monophenolic trans-2-phenylcyclopropylamines: novel central 5-hydroxytryptamine receptor agonists.

N,N-Dialkylated monophenolic derivatives of trans-2-phenylcyclopropylamine were synthesized and tested for central 5-hydroxytryptamine (5-HT) and dopamine (DA) receptor stimulating activity by use of a biochemical test method in rats. A hydroxy substituent in the 2- or 3-position of the phenyl ring was required for 5-HT-receptor stimulation. N,N-Diethyl or N,N-di-n-propyl substitution gave the most potent 5-HT-receptor agonists. The 4-hydroxy and 3,4-dihydroxy derivatives of trans-2-phenyl-N,N-di-n-propylcyclopropylamine were inactive at central DA and 5-HT receptors. In contrast, the corresponding 3-hydroxy derivative 18 and some of its derivatives weakly affected both DA and NE synthesis. Two of the most potent 5-HT-receptor agonists, trans-2-(2-hydroxyphenyl)-N,N-di-n-propylcyclopropylamine (8) and the 3-hydroxy isomer 18 were resolved into the enantiomers. The 1R,2S enantiomers of 8 and 18 displayed 5-HT activity, while the 1S,2R enantiomers were inactive. Compound (1R,2S)-18, but not (1R,2S)-8, weakly affected rat brain DA and NE synthesis.

Alkylation↗
PubMed1988

Hydrogenation reduces the allergenicity of colophony (rosin).

Abietic acid is the main component of rosin. It is readily oxidized by air and its oxidation products are considered to be mainly responsible for the allergenic effect. Hydrogenation of the conjugated double bonds of abietic acid decreases its susceptibility to air oxidation and would thus reduce the allergenicity of rosin. Portuguese gum rosin was therefore hydrogenated and its allergenicity was compared with that of unmodified rosin in animal experiments and by patch testing in humans. Its sensitizing potential was determined in 2 studies. No response was found according to the FCAT method while the GPMT gave significant response in the animals challenged with the highest test concentration. Hydrogenated rosin showed no eliciting activity in animals induced with unmodified rosin according to the GPMT method. A marked decrease was found in the frequency of allergic reactions to hydrogenated rosin compared to the reactions to unmodified rosin in patients with known allergy to gum rosin. We conclude that elimination of the unsaturated non-aromatic compounds by hydrogenation considerably reduces the allergenicity of Portuguese gum rosin.

Abietanes↗
PubMed1988

Contact allergy to dehydroabietic acid derivatives isolated from Portuguese colophony.

7-oxodehydroabietic acid and 15-hydroxydehydroabietic acid were isolated as their methyl esters from Portuguese colophony of the gum rosin type and identified as contact allergens. Another oxidation product of dehydroabietic acid, 15-hydroxy-7-oxodehydroabietic acid, was synthesized and identified as a component of Portuguese gum rosin. 7-oxodehydroabietic acid was found to a be a grade III allergen according to the GPMT method. Guinea pigs induced with gum rosin showed only a low response to the isolated compounds, while patients with a known allergy to gum rosin reacted to a greater extent. The results imply that the content of oxidized dehydroabietic acids in gum rosin is too low to give a marked sensitization in the animals. However, the patients might have come in contact with the allergens in technically modified rosins. The compounds showed a pattern of cross-reactivity in the animal experiments as well as among the patch tested patients.

Abietanes↗
PubMed1988

Identification of 15-hydroperoxyabietic acid as a contact allergen in Portuguese colophony.

15-Hydroperoxyabietic acid (15-HPA) has been isolated from Portuguese colophony of the gum rosin type and identified as its methyl ester. The structure of the compound was elucidated using UV, IR, NMR and mass spectrometry. 15-HPA methyl ester was found to be an elicitor when tested in colophony-sensitized guinea-pigs. The sensitizing capacity was verified in the same species and 15-HPA methyl ester was considered to be a strong allergen. The eliciting potential was also verified in patients with known allergy to colophony. The Portuguese gum rosin investigated contained approximately 1% of 15-HPA. Based on its allergenicity and the amounts isolated, we conclude that 15-HPA is a main contact allergen in Portuguese gum rosin.

Abietanes↗
PubMed1987

Resolved cis- and trans-2-amino-5-methoxy-1-methyltetralins: central dopamine receptor agonists and antagonists.

A series of 35 stereochemically well-defined C1-methyl-substituted derivatives of the potent dopamine (DA) receptor agonist 5-hydroxy-2-(di-n-propylamino)tetralin (5-OH-DPAT) have been synthesized. The compounds were tested for central DA receptor agonistic and antagonistic activity, by use of biochemical and behavioral tests in rats. In addition, the compounds were tested for in vivo interactions with 5,6-dihydroxy-2-(di-n-propylamino)tetralin (DiPr-5,6-ADTN). On the basis of pharmacological activity profiles, the active compounds have been classified into four groups: classical pre- and postsynaptic DA receptor agonists, DA receptor agonists with preferential action at presynaptic receptors, pre- and postsynaptic DA receptor antagonists, and DA receptor antagonists with preferential action at presynaptic receptors. Results obtained indicate that both 2R and 2S enantiomers of C5-oxygenated 2-aminotetralins may be able to bind to DA receptors but that only 2S antipodes are able to activate the receptors. O-Methylation of the C5-oxygenated (1S,2R)-2-amino-1-methyltetralin derivatives tends to increase their DA receptor antagonistic activity, whereas decrease of the size of the N-substituent(s) from n-propyl to ethyl or methyl appears to increase their activity at postsynaptic DA receptors.

Animals↗
PubMed1987

C3-methylated 5-hydroxy-2-(dipropylamino)tetralins: conformational and steric parameters of importance for central dopamine receptor activation.

C3-Methyl-substituted derivatives of the potent dopamine (DA) receptor agonist 5-hydroxy-2-(di-n-propylamino)tetralin (5-OH-DPAT) have been synthesized and their conformational preferences have been studied by use of NMR spectroscopy, X-ray crystallography, and molecular mechanics calculations (MMP2). The compounds were tested for activity at central DA receptors, by use of biochemical and behavioral tests in rats. (2R,3S)-5-Hydroxy-3-methyl-2-(di-n-propylamino)tetralin [(-)-8] was demonstrated to be a highly potent DA receptor agonist, while the other new compounds were of low potency or inactive. Results obtained confirmed the hypothesis that the tetralin inversion angle phi and the direction of the N-electron pair (N-H) tau N are conformational parameters of critical importance for DA D2 receptor activation in the 2-aminotetralin series. The high potency of (-)-8 allowed an extension of a previously defined "partial DA D2 receptor excluded volume".

Animals↗
PubMed1987

C1- and C3-methyl-substituted derivatives of 7-hydroxy-2-(di-n-propylamino)tetralin: activities at central dopamine receptors.

C1- and C3-methyl-substituted derivatives of the potent dopamine (DA) receptor agonist 7-hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT) have been synthesized, and their conformational preferences have been studied by use of NMR spectroscopy, X-ray crystallography, and molecular mechanics (MMP2) calculations. The compounds were tested for activity at central DA receptors, by use of biochemical and behavioral tests in rats. (1S,2R)-7-Hydroxy-1-methyl-2-(di-n-propylamino)tetralin [(+)-10] was demonstrated to be sevenfold less potent than (2R)-7-OH-DPAT as a DA receptor agonist. The other new compounds were of lower potency or inactive.

Animals↗
PubMed1987

Carbamate ester derivatives as potential prodrugs of the presynaptic dopamine autoreceptor agonist (-)-3-(3-hydroxyphenyl)-N-propylpiperidine.

Twenty derivatives bearing substituents on the phenolic function of (-)-3-(3-hydroxyphenyl)-N-propylpiperidine [(-)-3-PPP] were synthesized and tested as prodrugs. The carbamate ester derivatives were found to be the most suitable prodrugs, and especially the 4-isopropylphenylcarbamate 20 was capable of escaping the first-pass metabolism and still generating high plasma levels of the parent compound. Four hours after an oral dose of 100 mumol/kg to rats, a plasma level of 2400 nmol/L of (-)-3-PPP was detected by an HPLC method. This was 90 times the level reached after 4 h (27 nmol/L) when (-)-3-PPP itself was given orally at the same dose.

Animals↗
PubMed1987

(+)-cis-8-Hydroxy-1-methyl-2-(di-n-propylamino)tetralin: a potent and highly stereoselective 5-hydroxytryptamine receptor agonist.

C1-Methylated derivatives of the potent 5-hydroxytryptamine (5-HT) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 1) were synthesized and tested for central 5-HT and dopamine receptor activity by use of a biochemical test method in rats. cis-8-Hydroxy-1-methyl-2-(di-n-propylamino)tetralin (8) was found to be a 5-HT receptor agonist. The (+)-enantiomer of 8 had a potency equal to that of 1, whereas (-)-8 and the trans isomer (+/-)-9 were inactive.

8-Hydroxy-2-(di-n-propylamino)tetralin↗