Biomedical subjects
Publications and source records attributed to G Agrup.
The preservative Euxyl K 400 consists of the 2 active ingredients, 2-phenoxyethanol and 1,2-dibromo-2,4-dicyanobutane. Sensitization studies with the guinea pig maximization test were performed with these substances, but no sensitizing capacity was demonstrated in the case of either compound.
The prevalence of allergy to laboratory animals (LAA) was investigated in laboratory technicians and animal keepers. In a questionnaire 41 of 101 technicians reported symptoms provoked by work with laboratory animals. On clinical investigation 30 were found to have symptoms and signs related to contact with animals, and allergy was confirmed by radioallergosorbent tests (RAST) and skin tests in 19. All had rhinitis and 10 also had bronchial asthma. Forty seven other technicians who had stopped working with laboratory animals showed the same relative numbers of respiratory tract symptoms and of confirmed allergy to laboratory animals as did those currently handling animals. Seven of 23 animal keepers had work related symptoms. LAA symptoms were found in four and confirmed animal allergy in two. All four animal keepers with animal related symptoms had rhinitis, none had bronchial asthma. Positive animal RAST and skin tests were found only among people with animal related symptoms. A history of atopic disease was commoner among those with positive animal test results than among those with negative test results. No relation between smoking and the development of allergy to laboratory animals emerged. Simple prophylactic measures often sufficed to help technicians with animal related symptoms to remain at work.
The occurrence of contact urticaria was studied in 101 laboratory technicians investigated for allergy to laboratory animals. Fourteen cases of contact urticaria caused by rat were found. Other animals causing contact urticarial reactions were mouse (7), guinea-pig (4), and cat (2). Hand eczema was not found in laboratory technicians with contact urticaria and IgE-antibodies to laboratory animals.
During one year 68 patients with pompholyx attending the outpatient clinic at the Department of Dermatology, Lund, were examined with special regard to occupational disability. Owing to pompholyx 56 patients had sick-leave, and in 48 sick-leave lasted more than 1 month. No patient needed change of occupation because of pompholyx, and no disability pension was granted because of the disease.
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An extract of bovine retina and choroid with tyrosine hydroxylating and dopa-oxidizing capacity also showed marked formation of 6-OH-dopa on incubation with tyrosine and ascorbic acid. The extract contained appreciable amounts of methaemoglobin as determined spectrophotometrically, and boiled extracts also showed catalytic activity. The effect of methaemoglobin on the oxidation of tyrosine and dopa was therefore investigated. Methaemoglobin catalysed the formation of dopa and 6-OH-dopa in the presence of tyrosine and ascorbic acid. Hydrogen peroxide plays an important role in this reaction: the rates of formation of both dopa and 6-OH-dopa were increased by addition of hydrogen peroxide but diminished by addition of catalase. Methaemoglobin also catalysed the formation of cysteinyldopa from dopa and cysteine.
Diastereomers of 5-S-cysteinyldopa formed from D-dopa and L-cysteine or from L-dopa and D-cysteine can be separated from 5-S-cysteinyldopa formed from L-dopa and L-cysteine by liquid chromatography. The diastereomers have a great potential as internal standards in the analysis of 5-S-cysteinyldopa. They can be used as reference substances in the differentiation of stereospecific enzymatic oxidation of dopa from non-specific oxidation.
The formation of 5-OH-dopa on incubation of tyrosine or dopa with mushroom tyrosinase was studied. Dopa oxidase activity was defined by measuring the formation of 5-S- and 2-S-cysteinyldopa from dopa in the presence of excess amounts of cysteine. This procedure quantitating the immediate nucleophilic reaction products of dopaquinone constitutes a new method for assessing tyrosinase activity. The rate of 5-OH-dopa formation from dopa was similar to that of the formation of dopa from tyrosine. The rate of dopaquinone formation was one order of magnitude higher. When tyrosine was oxidized in the presence of ascorbic acid, 5-OH-dopa formation represented 14% of the original amount of tyrosine. At low concentration of dopa, formation of 5-OH-dopa was proportional to the dopa concentration. At high concentrations the relative quantity of 5-OH-dopa formed decreased. Tyrosine in high concentrations inhibited the formation of 5-OH-dopa from dopa. 5-OH-dopa proved to be a substrate for tyrosinase. The rate of oxidation of 5-OH-dopa was similar to that of dopa. The oxidation products of 5-OH-dopa were transformed into relatively stable fluorophores.
In a double-blind, randomized multi-centre study, 116 patients with psoriasis have been treated for 1-3 weeks with budesonide ointment (Preferid, Draco/Tika; a subsidiary of AB ASTRA), a new non-halogenated topical steroid. In a series of 11 patients a 0.025% budesonide ointment was significantly superior to placebo. In a second series, of 54 patients, a 0.025% fluocinolone acetonide ointment (Synalar, ICI). In a third series, of 51 patients, a 0.010% budesonide ointment was compared with 0.025% fluocinolone acetonide ointment. No statistically significant difference between these two preparations was found to exist. No adverse reactions were observed.
Seventeen patients were given DTIC, 200 mg/m2/day in five-day courses every four to six weeks. In four patients (stage II) treated on an adjuvant basis, tumor recurrence has been verified in three. Four of the palliatively treated patients were also given DTIC by regional intra-arterial infusion with minimal positive tumor effect and minimal toxicity. 5-S-cysteinyldopa excretion in urine was checked continuously in all patients. Tumor recurrence was revealed in two patients given DTIC on an adjuvant basis three and four months before clinical signs of tumor. In the palliatively treated patients, 5-S-cysteinyldopa excretion increased in 5/6 patients judged to have stable disease, before tumor progression was clinically detectable. The use of 5-S-cysteinyldopa examination is a valuable adjunct to the follow-up of the effect of DTIC therapy in melanoma patients.
5-S-Cysteinyldopa, dopa, and dopamine levels were determined by HPLC and electrochemical detection in serum, urine, kidney, spleen, heart, and sympathetic ganglion of guinea-pig. The kidney showed high levels of 5-S-cysteinyldopa, but also of dopa and dopamine, thus demonstrating the role of the renal ti-sue in the excretion of these substances. The concentrations found in spleen and heart may indicate specific catechol-containing structures in these organs.
Dopa and 5-S-cysteinyldopa levels in serum of albino, red, and black guinea-pigs were quantified. The levels of both amino acids were lower in the albino than in the pigmented animals. It is suggested that the serum levels of dopa and 5-S-cysteinyldopa in pigmented animals reflect tyrosine and dopa oxidation activity in the melanocytes.
The catecholic amino acids, dopa, 2-S- and 5-S-cysteinyldopa, and 2,5-S,S-dicysteinyldopa were determined qualitatively in serum from patients with malignant melanoma by reversed-phase high-performance liquid chromatography, using electrochemical detection. In urine the catecholamines dopamine, noradrenaline and adrenaline were also determined qualitatively, as well as the above-mentioned compounds, in a single chromatographic run. The conditions were optimized by changing the pH of the mobile phase and by the addition of methanesulphonic acid. A comparison was made between the performance of four commercial reversed-phase packing materials containing chemically bonded octadecyl groups, using a standard mixture of catecholic amino acids. The influence of ionic strength, pH and amount of methanesulphonic acid on retention was investigated.
Urinary excretion of 5-S-cysteinyldopa was investigated in 12 genetically dark-skinned men living in Sweden. Ten subjects showed excretion values in the same range as persons of Swedish origin, whereas the excretion was higher in 2 subjects.
The hypothesis that only melanosomal catecholic amino acids contribute to melanin formation was tested by studying adult bovine eyes in which pigment synthesis is considered to be low or absent. Dopa and 5-S-cysteinyldopa were investigated in different cell fractions of the choroid and retinal pigment epithelium of cattle. Most of the dopa and 5-S-cysteinyldopa was found in the cytoplasm and very little in the large granule fraction. The presence of cysteinyldopa in the adult eye is evidence of tyrosinase activity, but the catechol amino acids in the cytoplasm probably do not give rise to melanin formation. It is assumed that they instead are excreted from the cells.
Determinations of the urinary excretion of 5-S-cysteinyldopa were performed in 571 patients previously treated by surgery for melanoma or melanoma metastasis. 90% of the 161 patients with metastases showed values exceeding 0.15 mg/24 h, and 9% of the 410 patients without metastases had such values. The increase in 5-S-cysteinyldopa excretion was generally more pronounced in men with metastases than in women, 98% of the men and 77% of the women with metastases showing values exceeding 0.15 mg/24 h. High levels of 5-S-cysteinyldopa are of grave prognostic significan4% died within one month, and only 3% survived for more than a year. In Sweden, determination of 5-S-cysteinyldopa in patients operated on for melanoma gives maximum information in the winter (October--March), when sun exposure does not influence the excretion levels.
ESR spectra of synthetic melanins formed from dopa and from 5-S-cysteinyldopa and of melanins isolated from human melanomas were studied. Alkali-soluble melanin synthesized from cysteinyldopa showed a signal similar to that of insoluble melanin synthesized from dopa, but also a simple fine structure. Trichochromes C and F synthesized from 5-S-cysteinyldopa had a broader signal than dopamelanin, and in addition a hyperfine structure that could be explained by the presence of manganous ions. An insoluble eumelanin from a human melanoma with a sulphur content of 5% showed an ESR spectrum consisting of one line like dopamelanin. An alkali-soluble phaeomelanin from a human melanoma with a sulphur content of 10% showed a very broad signal with a hyperfine structure that could be explained by the presence of manganous ions.