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Biomedical subjects

J Spona

Publications and source records attributed to J Spona.

At least 145 records · Page 8Linked to original sources

The levels of androgen in serum in female acne patients.

Twenty six female acne patients aged between 27 and 42 years were investigated. Blood samples were taken and radioimmunoassayble testosterone, androstenedione and DHEA-S were determined. Seven out of 26 patients (27%) had normal androgen serum levels. In 19 patients one or more androgen serum levels were elevated. DHEA-S (23%) alone and testosterone, androstenedione plus DHEA-S (15%) showed the greatest incidences of elevated levels. Testosterone and androstenedione, respectively, were elevated in 3 patients whereas DHEA-S alone was elevated in 6 patients. 71% with normal androgen serum levels and 72% of patients with elevated androgens presented with premenstrual or menstrual exacerbation of acne. In addition, patients with elevated testosterone, androstenedione or with all measured androgens elevated had menstrual disorders and premenstrual formation of therapy resistant big nodules in the chin area. Present data combine to suggest that the determination of androgens is of importance for the evaluation of acne patients.

Acne Vulgaris↗

[Radioactive labeling of cytoplasmic hormone receptors. Determination and clinical significance of estrogen and progesterone receptors].

Neither autoradiography nor in vitro labeling of thin sections of tumor tissue can be used for the quantitative determination of radioactive labeled cytoplasmic hormone receptor. The acknowledged method for his purpose is the DCC (Dextran Coated Charcoal) method. Hormone receptor estimations are routinely used to predict those patients with hormone-dependent tumors who will respond to endocrine therapy. Some 80% of patients with positive estrogen and progesterone receptor show objective remissions after endocrine therapy. Receptor determinations are carried out routinely in patients with mammary, uterine or ovarian carcinoma to identify those subjects who would benefit most from endocrine therapy.

Breast Neoplasms↗

[Treatment of breast cancer at the 1st Gynecology Clinic at the University of Vienna].

Since 1979 diagnosis, operative therapy and postoperative treatment and follow-up is performed at the Ist University-Clinic of Obstetrics and Gynecology in Vienna. This management brought a close cooperation with radiologists and other oncotherapists. A standard operation method, in our case a modified radical mastectomy with a complete dissection of the axilla after radioisotope marking of the axillary lymph nodes enables us to perform a randomised prospective study of adjuvant therapy. Though the observation time is relatively short, first results show, that metastases or local recurrences were observed only in the non-treated control group. That leads in our opinion to the cautious conclusion, that any form of adjuvant therapy is of therapeutic value. Which form of adjuvant therapy should be qualified best cannot be decided yet because of the too short follow-up period.

Antineoplastic Combined Chemotherapy Protocols↗

Androgenic action of progestins and possible synandrogenic properties of antiandrogens used in oral contraceptives.

Relative binding affinities (RBA) for the androgen receptor were estimated for levonorgestrel, progesterone, dihydrotestosterone, cyproterone acetate, 17 alpha-propylmesterolone and 3-keto-desogestrel (13-ethinyl-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-17-ol-3-one) which is the biological active metabolite of desogestrel. Mouse kidney cytosol served as receptor source. In addition, stimulation of mouse kidney beta-glucuronidase by subcutaneous injection of various doses of these compounds was determined. RBA for the androgen receptor of 3-keto-desogestrel was significantly greater (p less than 0.02) than that of levonorgestrel, and 3-keto-desogestrel was registered to enhance beta-glucuronidase activity more than levonorgestrel at the highest dose level (p less than 0.005). Furthermore, cyproterone acetate in the presence of testosterone was found to exert synandrogenic action at the lower dose level but suppressed enzyme activity at the higher doses. On the other hand, 17 alpha-propylmesterolone which had RBA similar to the one noted for cyproterone acetate showed only synandrogenic properties at the dose levels tested. The data combine to suggest that biological activity of a compound cannot be accurately predicted by receptor assays. Desogestrel and levonorgestrel exhibit similar androgenic properties in this model system. These data correlate with clinical experience on oral contraceptives containing levonorgestrel and desogestrel, respectively, which do not differ from each other in their androgen-related side effects.

Androgen Antagonists↗

Diminished prolactin response to thyrotropin and insulin in anorexia nervosa.

Although patients with anorexia nervosa (AN) have a variety of endocrine disturbances, it generally is believed that the PRL response to stimulation is not altered in this disorder. We measured basal serum PRL values and serum PRL values after stimulation either with TRH (200 micrograms/m2) or with insulin (4 IU/m2) in 27 women with AN and 9 normal women. Basal values in anorexic women and normal women did not differ significantly, whereas all stimulation variables (mean PRL stimulation values, maximum PRL values, sum of increments, and area under the stimulation curve) were significantly lower in AN patients than in normal women. Furthermore, after TRH stimulation most of these variables correlated positively with the percentage of ideal body wt of the patients, indicating that the diminished PRL response was wt dependent. This diminished PRL response in the patients may accompany starvation and low estradiol values. Both conditions per se are known for their association with diminished PRL responses. Hence, no hypothesis which posits hypothalamic dopamine excess as the basic disturbance in AN seems justified. Moreover, diminished PRL responses in AN are not consistent with an assumption of hypothalamic dopamine depletion in this disorder.

Adolescent↗

Decreased in vitro LH releasing activity of oligomeric LH-RH derivatives.

Primary rat pituitary cell culture system was used to investigate LH releasing activity of dimeric and oligomeric LH-RH agonists. In addition, peptides containing both agonistic as well as inhibitory segments were tested in order to find out which sequence overrules the other part of the molecule. In addition, intracellular cAMP levels were determined. All peptides but D-Phe2, D-Trp3, D-Lys6-LH-RH which was noted to be an inhibitor were found to increase intracellular cAMP contents. Only 72% LH releasing activity of LH-RH was registered for the analog which was composed of an agonistic and inhibitory chain. Dimeric and tetrameric derivatives of D-Lys6-LH-RH exhibited significantly lower LH releasing activity than the parent compound. But, no differences between the dimer and tetramer with agonistic chains was noted. The data show that cAMP may be involved in certain steps of LH-RH induced LH release, but does not play a role in overall LH release. In addition, dimerization and tetramerization of LH-RH agonist chains by short bridges is not sufficient for binding to more than one receptor molecule. Such derivatives could, however, reveal the length of the connecting bridge which is necessary for inducing receptor aggregation.

Animals↗

13-cis-Retinoic acid in rosacea. Clinical and laboratory findings.

The paper presents clinical and laboratory data on 13-CIS-retinoic acid treatment in rosacea. Good-to-excellent results are reported for severe forms of rosacea. Side effects were tolerable and could easily be controlled. The role of sebaceous gland function was documented by both histological and skin sebum parameters. Diminution of sebaceous gland size and the decrease of skin sebum with alteration of single sebum fractions correspond with findings in acne. According to the findings the alteration of sebaceous gland function is one model of drug action in rosacea. Thus sebaceous gland dysfunction may play an important role in the pathogenesis of rosacea.

Adult↗

Norethisterone and ethinylestradiol do not inhibit delta 5-3 beta-hydroxysteroid dehydrogenase in rat Leydig cells.

The effect of norethisterone, norethisterone acetate, ethinylestradiol and of a cyanoketone on the activity of HSD have been studied. Rat Leydig cells and extracts of Pseudomonas testosteroni were used as enzyme sources. Conversion of [3H]DHEA to A and [3H]pregnenolone to progesterone were used for the assay of enzyme activity. Km values for each substrate for Leydig cells and for bacterial enzyme were: 1.5 x 10(-5) mol l-1 and 6.0 x 10(-5) mol l-1 DHEA; 1.3 x 10(-5) mol and 7.7 x 10(-5) mol l-1 pregnenolone. For investigation of inhibition [3H]DHEA was used as substrate and apparent Ki values were calculated by Dixon plot analysis. In both systems norethisterone showed no inhibition of the enzyme. Norethisterone acetate proved also to be not inhibitory; only residual affinity to the enzyme was noted (Ki = 8.0 x 10(-5) mol l-1: Leydig cell preparation; Ki = 9.4 x 10(-5) mol l-1: bacterial enzyme). Different result sin the two systems were obtained for ethinylestradiol and for a combination with norethisterone acetate. Ethinylestradiol or the combination with the progestin (Ki = 0.5 x 10(-5) mol; 1.4 x 10(-5) mol l-1) showed noteworthy inhibition of the bacterial enzyme but only weak competition for binding to the active site of the enzyme in rat Leydig cells (Ki = 6.0 x 10(-5) mol l-1; 8.3 x 10(-5) mol l-1). It is concluded that there are greater differences between the two enzymes than considered previously. As expected, cyanoketone proved to be the most effective inhibitor in both systems. The most important result seems to be, that norethisterone does not inhibit HSD. This suggests that there is no causal relationship between hypospadias and progestins administered to females during pregnancy.

3-Hydroxysteroid Dehydrogenases↗

Action of inhibitory LH-RH analogs in rat pituitary and luteal cell cultures.

The effect of LH-RH antagonists on LH-RH stimulated LH release was studied in primary rat pituitary cell culture and the inhibition by LH-RH antagonists of HCG provoked progesterone production was investigated in primary rat luteal cell culture. Antagonists used in this study were Ac-D-Trp1, D-Phe(Cl)2, D-Lys6, D-Ala10-LH-RH(I1) and the respective D-Lys6 isophthaloyl dimer (I2). LH-RH activity was noted to be reduced to 1/12 by I1 and to 1/23 by I2 in the pituitary cell culture system. The LH-RH inhibitors did not possess intrinsic LH releasing activity up to 10(-6) mol 1(-1). Incubation of rat luteal cells with HCG in the presence of LH-RH, I1 or I2 resulted in a smaller progesterone release than that observed in the absence of the peptides. ED50 of HCG was noted to be 5.7 X 10(-13) mol 1(-1) and 10(-8) mol 1(-1) LH-RH, I1 or I2 caused a shift of ED50 to 6.3 X 10(-12) mol 1(-1), 1.2 X 10(-12) mol 1(-1) and 7.9 X 10(-13) mol 1(-1), respectively. The present investigation is the first demonstration of reduction by LH-RH antagonists of gonadal steroid production. The present results suggest the use of such inhibitory LH-RH analogs in the treatment of hormone dependent tumors such as prostatic carcinoma and would not cause a transient rise of gonadal steroids as seen by the use of LH-RH agonists.

Animals↗

[Skin lipids in 13-cis-retinoic acid therapy of acne].

The study presents clinical data and results of skin sebum (SER) determinations during 13-cis-retinoic acid treatment in 15 patients suffering from severe conglobate and cystic acne. The striking clinical improvement was mostly accompanied by decreased SER as well as changes in the composition of the skin surface lipids. While the sebaceous gland lipids were generally reduced, the epidermal lipids showed irregular tendencies. Despite of good therapy effects, 3 patients showed increased SER. This indicates that other mechanisms than those of sebum suppression may be responsible for the treatment success. Sebum suppression and modulation are important and valuable aspects for documentation as well as for elucidation of the working mechanism of 13-cis-retinoic acid.

Acne Vulgaris↗

[Therapy of the surgical menopause syndrome with depot medroxyprogesterone acetate and its objective evaluation testing the reaction of the anterior pituitary gland to stimulation with gonadotropin-releasing hormone].

A randomized placebo-controlled double-blind study was conducted to evaluate the effect of 150 mg depot medroxyprogesterone acetate (DMPA) intramuscularly on the surgical menopause syndrome. The clinical material consisted of 30 hysterectomized and bilaterally salpingo-oophorectomized women between 38 and 54 years of age. Inclusion criteria were regular menstrual cycles until operation, the appearance of frequent vasomotor flushes (VMF) after operation, and serum FSH levels exceeding 20 mIU per ml. Since it has been shown that an increase in "LH pulses" and basal serum LH levels constitute objective parameters of VMF, determination of LH was chosen as biochemical criterion of therapeutic efficacy. DMPA was proven to reduce basal serum LH levels owing to its suppressive effect on the adenohypophysis. In order to clarify and quantify the suppressive potency of DMPA and obtain precise information on its mechanism of action, pituitary stimulation tests with gonadotropin releasing hormone (GnRH tests) were performed before and then at 2 and 6 weeks after initiation of therapy. Pituitary response to GnRH remained unaltered, however, at a level corresponding to the decreased basal concentrations, i.e. "LH peaks" dropped by more than 50% (p less than 0.005, Student t-test). The incidence of VMF decreased significantly and remained at a low level until 6 weeks after the administration of DMPA. Treatment with placebo resulted in a slight, but not significant decrease in VMF and did not affect the functional capacity of the adenohypophysis. A remarkable correlation was observed between the reduced size of "LH peaks" and the diminished incidence of VMF. Therefore, evaluation of pituitary response to stimulation with GnRH represents a helpful objective parameter in the assessment of the efficacy of DMPA.

Adult↗

[Hormonal interaction of androgen and estrogen receptors in normal skin and in acne].

Hormone metabolism in skin affected with acne has been investigated by determination of androgen and estrogen receptors with the help of saturation analysis. The results have been compared with data of an age-corresponding control group. The investigation has been performed on 55 male and 11 female volunteers with acne in their lesions as well as unaffected areas. Androgen and estrogen serum levels have been determined as additional endocrine parameters. Testosterone serum levels were slightly elevated in about 11 percent of the male patients, while the percentage for the female patients might be higher as far as can be judged on account of small number of patients. The lack of correlation between estrogen/androgen receptors and their corresponding serum levels leads to the conclusion that the hormone metabolism is situated in the periphery, being independent of the central endocrine regulation. Similar findings for distribution and receptor levels in both healthy and involved skin of acne patients revealed a significant discrepancy in comparison to corresponding evaluations found in healthy patients. There results point out to an elevated dependency on hormonal influences of the entire integument of acne patients. Estrogen receptors could be found in both acne patients and controls.

Acne Vulgaris↗