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Biomedical subjects

J Sondergaard

Publications and source records attributed to J Sondergaard.

At least 19 recordsLinked to original sources

A new technique for ranking vascular corticosteroid effects in humans using laser-Doppler velocimetry.

By combining laser-Doppler velocimetry with reactive hyperemia, induced by arterial occlusion of 4-min duration we have established a simple and atraumatic new ranking technique for assessing steroid potency. The experiments were performed in 19 healthy volunteers. Budesonide (Preferid) and placebo (vehicle) were applied under occlusion on the flexor aspect of the forearm for 2, 24, and 48 h. Blood flow was measured with a laser-Doppler flowmeter before and after arterial occlusion with a blood pressure cuff on the upper arm. The induced reactive hyperemia reaction was measured planimetrically on the registered curves. The steroid preparation caused a significant reduction of the hyperemia closely related to the application time. The reduction of the hyperemia was confirmed using the atraumatic 133Xe washout technique. In another group, hydrocortisone, hydrocortisone-butyrate (Locoid), budesonide (Preferid), and klobetasol (Dermovat) applied under occlusion for 1 h were compared. A significant dose-response relation corresponding to the expected rank-order efficacy was revealed. In 10 experiments, pretreatment with 50 mg indomethacin i.v. resulted in a significant reduction of the hyperemia reaction. As a hypothesis we therefore suggest that the reactive hyperemia reaction amplifies the vascular events and unmasks steroid-induced inhibition of the synthesis of arachidonic acid metabolites.

Adrenal Cortex Hormones

The effect of leukotrienes C4 and D4 on microcirculatory flow in humans.

By quantifying the flare response, leukotrienes LTC4 and LTD4 were shown to increase the microcirculatory flow in a sigmoidal dose-response relation over the dose-range of 6.25-800 pmol. LTD4 was found to be more potent than LTC4 after 5 min, but not after 15 min, as estimated by this method. Laser-Doppler flowmeter studies confirmed that LTD4 is a more potent vasodilator than LTC4.

Blood Flow Velocity

DNA in psoriatic epidermis.

An electron microscopic technique has been used to visualize crosslinks after total denaturation on DNA isolated from epidermis and dermis in patients with psoriasis treated with 8-methoxypsoralen (8-MOP) and irradiation with ultraviolet light at 360 nm (PUVA treatment). This technique facilitated accurate measurements of the number and density of DNA interstrand crosslinks. 30 biopsies from 14 patients were studied and a total of 9503 DNA molecules were scored in the electron-microscope, 6 patients were treated topically with 8-MOP and 10 were on systemic treatment. Two of the patients on topical treatment had previously been on systemic treatment. 1% of all DNA molecules contained 3 or more cross-links. The overall frequency of cross-links was almost identical in the epidermis (1.1%) and in the dermis (0.9%) and, furthermore, virtually the same in patients on topical and systemic PUVA treatment. The total number of crosslinks was of the same magnitude as that previously found in normal human skin. (V. Bohr et al., Acta Dermatovener, in press.) No significantly increased damage of the genetic material (DNA) was demonstrated in our study as a consequence of the PUVA treatment using 8-MOP. We have previously shown (V. Bohr & A. Lerche, Biochim Biophys Acta, in press) that 8-MOP induced crosslinks after irradiation at 360 nm in an in vitro system of pure DNA. In this system a correlation was established between the density of crosslinks formed and irradiation time, concentration of 8-MOP, and irradiation intensity.

DNA

Pathogenesis of erythromelalgia.

A defective prostaglandin metabolism in patients with erythromelalgia may explain several of the clinical features of this condition, such as the red discoloration and burning sensations of the skin. In two patients with erythromelalgia a grossly abnormal bullous reaction to intradermally injected PGE1, PGE2, and PGF1alpha occurred, whereas a normal reaction appeared after injection of histamine, serotonin, and bradykinin. Furthermore, prostaglandin-like material was detected in increased concentration in skin perfusates from these patient. In PGE1-equivalents the concentration amounted to 2.0 and 3.2 ng/ml of the original perfusate, as compared to 0.1 ng/ml in normal skin. The capacity of synthesizing prostaglandins was increased in skin biopsy material from both patients. At least part of the therapeutic effect of aspirin in these patients may be due to the influence of this drug on prostaglandin metabolism.

Adult

Synthesis of prostaglandins by psoriatic skin.

The biosynthesis of prostaglandins (PG) in biopsies from 9 patients with psoriasis was studied. The involved as well as the uninvolved psoriatic skin showed a statistically significant decrease of the ability to synthesize PG's. In PGE1-equivalents the concentration (mean +/- S.E.M.) was 4.41 +/- 0.48 ng/g wet weight in the psoriatic lesion, 5.41 +/- 0.64 ng/g wet weight in uninvolved psoriatic skin in the presence of exogenous arachidonic acid in the incubation medium as compared with 9.02 +/- 1.59 in normal human skin. When the skin was incubated without excess of exogenous precursor acid the activity formed was similarly significantly lower in psoriatic skin as compared with normal skin. A disturbed balance between E and F PG synthesis was not demonstrated, which might have accounted for the postulated altered intracellular ratio of cyclic AMP to cyclic GMP in psoriatic skin.

Adenosine Monophosphate

Oral zinc sulphate therapy for acne vulgaris.

A double-blind controlled clinical trial was performed to evaluate the effect of oral zinc sulphate, 0.6 g daily, on acne vulgaris. Twenty patients received zinc sulphate tablets and 19 were given placebo tablets. Thirteen of the zinc group and 12 of the placebo group received their medication throughout a 12-week period, while the remaining patients were treated for 4 or 8 weeks. In all patients the numbers or papular and pustular acne lesions on the face and the back were significantly reduced, while larger infiltrates remained practically unaltered during the trial, which was performed from March through May 1975. No statistically significant difference in the improvement of the groups was demonstrable. Pretreatment serum zinc values, which were normal in all patients, rose significantly in the zinc group as well as in the control group, but the increase in the former was significantly higher. The negative therapeutical results might be attributable to the limited number of patients or related to the zinc dosage. Furthermore, the results might have been influenced by the unexplained rise in serum zinc values in the control group. A possible weak beneficial effect of zinc might also have been camouflaged by the seasonal variation in the severity of acne which was noted in this study.

Acne Vulgaris

Electron microscopic cytochemistry for demonstration of sodium fluoride sensitive adenyl cyclase in normal human epidermis.

Adenyl cyclase activity in normal human epidermis was detected by an electron microscopic cytochemical technique. The sodium fluoride sensitive receptors were demonstrated on the outer sheath of the cell membranes. Adenyl cyclase activity was demonstrated in the basal cells and in the 4-5 lower layers of the Malpighian cells, while the superficial layers, stratum granulosum and stratum corneum showed no activity. The findings confirm and extend previous biochemical studies and provide a clue to the conception of the adenyl cyclase enzyme as a transmembrane arranged system.

Adenylyl Cyclases

Acquired hypertrichosis lanuginosa. A skin marker of internal malignancy.

A 54-year-old woman had acquired hypertrichosis lanuginosa. She developed excessive growth of lanugo-like hair all over her body two years prior to the sudden appearance of a rapidly growing, localized, solid mammary tumor. Of 12 published cases, nine have been associated with an internal malignant neoplasm and obviously, as in the present case, the cutaneous symptoms may serve as a skin marker by preceding the tumor diagnosis for up to two years.

Adult

Cutaneous reactions to propranolol (Inderal).

Six patients wit psoriasiform cutaneous eruptions that developed during long-term therapy with propranolol (Inderal) have been studied. The cutaneous changes closely resembled those seen during treatment with practolol (Eraldin). The duration of treatment before the rash was recognized averaged 10 months, which is about the same latency period as in patients with practolol-induced exanthemas. The exanthemas disappeared gradually within 1-5 weeks after treatment with propranolol had been stopped. In 4 of 5 patients the skin eruptions reappeared within 2-4 days after oral challenge with propranolol. In the fifth patient, who developed a rash after challenge with practolol and severe abdominal colics after challenge with oxprenolol, no further provocation tests with propranolol were attempted. Skin biopsies obtained from 3 patients showed a microscopical picture similar to that seen in practolol exanthemas. The pathogenetic mechanism responsible for these adverse cutaneous reactions is unknown. However, since the possibility exists, that these changes may be caused by blockade of the epidermal beta-receptors, it is recommended that all patients receiving beta-blocking drugs should be examined carefully for similar adverse reactions. Special attention should be drawn to the reversible skin changes, since during treatment with practolol these have often preceded serious complications from other organs.

Aged

Biosynthesis of prostaglandins by human inflamed skin.

The biosynthesis of prostaglandins by human inflamed skin was studied in 8 patients with primary irritant dermatitis induced by benzalconium-chloride. Inflamed skin from these patients evidenced an increased ability to synthesize prostaglandins. In the presence of exogenous arachidonic acid in the incubation medium, the activity formed was about 80% greater in inflamed skin than in non-inflamed control skin. In prostaglandin E1-equivalents the concentration amounted to 8.09 +/- 1.59 ng/mg protein nitrogen and 4.51 +/- 1.24 ng/mg protein nitrogen, respectively (mean values +/- S.E.). When inflamed skin was incubated without excess of exogenous precursor acids in the incubation medium the activity formed was about 80 times lower and the values were similar to those of non-inflamed skin. Thus, the present results support the view that the prostaglandin system is activated in primary irritant dermatitis, thereby providing a basis for future therapeutic attempts to control this disorder.

5,8,11,14-Eicosatetraynoic Acid

Aggravation of psoriasis and occurrence of psoriasiform cutaneous eruptions induced by practolol (Eraldin).

Twelve patients with cutaneous and/or eye symptoms caused by practolol have been studied. The morphological appearance of the skin eruptions was psoriasiform in 5, vesiculo-papular in one, and exfoliating dermatitis was seen in 2 patients. Keratoconjunctivitis sicca was the only adverse reaction to practolol in one and was present in 3 additional patients. Practolol was found to aggravate existing psoriasis in 3 patients and render it extremely refractory to therapy.

Adult