Biomedical subjects
Publications and source records attributed to A S Jørgensen.
A series of pyrrolo[2,1,5-cd]indolizine derivatives has been synthesized and evaluated as ligands for the estrogen receptor. Properly substituted mono- and di-hydroxy derivatives showed binding in the low nanomolar range in accordance with their structural resemblance to estrogen.
1-Ethyl-2-(4-hydroxyphenyl)pyrrolo[2,1,5-cd]indolizine (NNC 45-0095) is a novel compound which represents the parent pharmacophore structure of a series of pyrrolo[2,1,5-cd]indolizine derivatives with mixed estrogen agonist/antagonist properties. NNC 45-0095 binds with high affinity to the estrogen receptor (IC50=9.5 nM) and exhibits full protection of bone loss in the ovariectomized mouse model for post-menopausal osteoporosis.
A series of different synthetic approaches to novel GABA uptake inhibitors are described, leading to examples which are derivatives of nipecotic acid and guvacine, substituted at nitrogen by 4,4-diaryl-3-butenyl or 2-(diphenylmethoxy)ethyl moieties. The in vitro value for inhibition of [3H]-GABA uptake in rat synaptosomes was determined for each compound. It was found that the most potent examples are those having a substituent in an "ortho" position in one or both aromatic/heteroaromatic groups. The majority of the compounds described are structurally related to tiagabine, (R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3- piperidinecarboxylic acid hydrochloride (NNC 05-0328) and some of the reasoning behind the selection of this compound as a drug candidate is summarized.
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22 cases of syphilis were diagnosed in the last part of 1982 in the Department of Dermatology and Venereology. Out of them 21 were male cases and 16 were homo- or bisexuals. Most cases were in the secondary stage and Herxheimer reaction only developed in these. Serological titers to both lipoidal and treponemal antigens were extremely high. All bisexual males were positive in herpes and CMV complement fixation test. Two of the homosexuals appeared with iridocyclitis and motile treponemes were isolated from the anterior chamber in one case.
In 85 patients with psoriasis vulgaris the efficacy and tolerance of domoprednate and betamethasone valerate were studied in a double-blind, randomized trial lasting 4 weeks. Complete or satisfactory remission was obtained in 36% in the domoprednate group and in 53% in the betamethasone group. This difference is not statistically significant (p greater than 0.10). 3 patients on each treatment experienced some local irritation. No laboratory abnormalities were found during the study.
The peripheral blood lymphocytes of 36 adult patients with moderate to severe atopic dermatitis had reduced natural killer (NK) cell activity when measured against 51Cr-labeled K 562 cells. The decrease in NK cells activity was not related to the serum IgE level, but was related to the severity of the skin disease. Addition of autologous monocytes of the assay reduced the NK cell activity and concealed the enhancing effect of gamma-interferon addition in a 4-h assay. The NK cell activity of lymphocytes could be reduced in vitro by addition of prostaglandin E1, or increased by addition of gamma-interferon similar to lymphocytes from persons without atopic disease. Our present findings raise the possibility that the reduced NK cell activity may be secondary to the skin disease, and due to in vivo interaction between NK cells and monocytes, or to low numbers of NK cells in peripheral blood.
Consecutive serum samples were obtained from patients with syphilis before and on three occasions after treatment. The sera contained immunosuppresive factors associated with the immunoglobulin fraction, which could depress the natural killer cell activity of healthy controls. There was no evidence that allogeneic or lymphocytotoxic antibodies played a role in immuno-suppression, which could be reproduced with both soluble and insoluble antigen-IgG-antibody complexes.