Biomedical subjects

W Kowalski

Publications and source records attributed to W Kowalski.

At least 19 recordsLinked to original sources

PubMed1994

Pharmacokinetics and pharmacodynamics of anordrin (2 alpha, 17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta, 17 beta-diol diproprionate).

In order to determine the pharmacokinetics of anordrin a dose of 0.2 mg/kg of [3-14 C]anordrin was administered i.v. to 5 cynomolgus monkeys; the same monkeys received the same dose i.m. at a later date. An additional 3 monkeys received 1.0 mg/kg of [3-14C]anordrin i.m. After administration of the compound, the dipropionate esters of anordrin were rapidly hydrolyzed to the dihydroxy parent compound, anordiol. After i.v. administration, anordrin had a mean residence time (MRT) of 5.0 +/- 1.3 (SE) min. [14C]Anordiol formed from [14C]anordrin had an MRT of 139 +/- 27 (SE) min. The metabolic clearance rates (MCR) of anordrin and anordiol were 55 and 34 mL/min.kg, respectively. The apparent volume of distribution at steady state (Vss) for anordrin was 276 mL/kg, 7.5% of body weight of the animals; anordrol had a much larger Vss of 4460 mL/kg. The MRT of anordiol after i.m. administration of 1.0 mg/kg of [14C]anordrin was 26.3 days. An average of 44% of the dose appeared in urine regardless of the route of administration or dose. The MRT values of total radioactivity were the same when calculated from serum or urine after an i.v. dose, but after i.m. administration, values from urine were approximately 60% of that calculated from serum, indicating that products appearing in urine had a shorter MRT than products appearing primarily in feces. A separate group of monkeys was given anordrin i.m. in doses ranging from 0.1 to 0.4 mg/kg on the first day of menses. The regression of length of menstrual cycle on dose was significant (P = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

[Histologic examination of slow epiphyseal distraction in the femur of rabbits].

Slow, symmetric epiphyseal distraction of the distal femur has been performed in 30 immature rabbits aged 10 weeks (group 1) and 16 weeks (group 2). Histological examination has been carried out after 2, 4, 12 and 24 weeks of distraction in both groups. In all animals hyperplasia and hypertrophy of the distracted epiphysis and regular remodeling of the bony growth zone were found after 4 weeks of follow-up. No premature closure of the physis has been noted compared to the controls. Histological differences observed were attributed to various, age related biological potential and they resulted from physiological involution.

Animals↗

PubMed1993

The impact of subchronic hypercortisolemia on progesterone metabolism and the luteinizing hormone-progesterone axis in the cynomolgus monkey.

The purpose of the study was to assess the impact of subchronic hypercortisolemia on progesterone (P) metabolism and production and on peripheral LH levels in a nonhuman primate using a repeated measures experimental design. Osmotic pumps that released hydrocortisone phosphate (HP) at a dose of 15 mg/day were implanted sc in seven cynomolgus monkeys for two menstrual cycles. The pumps were filled with saline for the two control cycles, which either preceded (three animals) or followed (four animals) HP infusion. P metabolism, P production, and episodic secretion of LH were determined 8 +/- 1 days after the serum estradiol peak in the second control cycle and in the second cycle of HP infusion in each monkey, after iv bolus administration of 50 microCi [3H]P, followed by a 6-h blood sampling period. HP infusion elevated serum cortisol levels 1.6-fold. Serum P levels were decreased throughout the luteal phase by 58% (P < 0.01). The MCR of P and the volume of distribution at steady state of P were increased by 200% during HP infusion (both P < 0.005). The production rate of P was increased by HP treatment in five of seven monkeys. HP infusion increased the ratio of 20 alpha-[3H]dihydroprogesterone to [3H]P in serum from 0.5 to 1.0 (P < 0.05) while decreasing the fraction of [3H]P and its metabolites excreted in urine from 20% to 11% (P < 0.05). Serum LH levels, determined over a 5.25-h period in the luteal phase, were elevated by 200% during HP treatment (P < 0.05). Episodic secretion of LH during treatment was characterized by a 660% increase in the pulse amplitude (P < 0.05) and an apparent decrease in the pulse frequency. The results of this study provide evidence that moderate elevation of serum cortisol levels for two menstrual cycles in primates 1) increases the MCR of P, which may be the cause of the observed decrease in serum P levels; and 2) elevates serum LH levels by amplifying its pulse amplitude, which may result in a compensatory rise in the production rate of P.

Animals↗

PubMed1992

Peripheral and not central suppression of ovarian function during osmotic pump infusion of adrenocorticotropin-(1-24) for one menstrual cycle in the cynomolgus monkey and its partial compensation by a transitory elevation of sex hormone-binding globulin levels.

The purpose of our study was to assess the impact of subchronic administration of ACTH-(1-24) on ovarian function in the primate using a repeated measures experimental design. Osmotic pumps that released ACTH-(1-24) at a dose of 67 micrograms/day were implanted sc in four cynomolgus monkeys for one menstrual cycle. The pumps were filled with saline for the two control cycles, one of which preceded and one of which followed peptide infusion. Administration of ACTH-(1-24) elevated cortisol levels in serum 1.6-fold and those in urine 2.2-fold, without affecting adrenal androgen concentrations. In the follicular phase (FP) of the menstrual cycle, infusion of ACTH-(1-24) did not alter serum levels of estradiol, FSH, or LH. However, immunoreactive estrone excretion in urine was decreased by 71% (P less than 0.05), and serum concentrations of sex hormone-binding globulin (SHBG) were increased by 100% (P less than 0.01). In the luteal phase (LP) of the menstrual cycle, infusion of ACTH-(1-24) suppressed levels of serum estradiol by 54% (P less than 0.001), urinary immunoreactive estrone by 72% (P less than 0.05), serum progesterone by 53% (P less than 0.001), and urinary immunoreactive pregnanediol by 71% (P less than 0.01). Serum FSH concentrations were increased during treatment by 100% (P less than 0.001) in LP, but LH concentrations were not altered. Also, serum levels of SHBG returned to control values in the LP. The lengths of menstrual cycles and the lengths of FP or LP were not affected during or after treatment. These data provide evidence that subchronic infusion of ACTH-(1-24) in primates: 1) suppresses estradiol production by the ovarian follicle as well as estradiol and progesterone production by the corpus luteum, 2) compromises ovarian function without concomitant suppression of serum gonadotropin levels, and 3) induces a transitory elevation of SHBG levels in the circulation, which may compensate for reduced estrogen output.

Animals↗

PubMed1992

Effects of subchronic infusion of dehydroepiandrosterone sulfate on serum gonadotropin levels and ovarian function in the cynomolgus monkey.

OBJECTIVE: To assess the impact of elevated adrenal androgen levels on ovarian function in a nonhuman primate using a repeated measures experimental design. DESIGN: Osmotic pumps that released dehydroepiandrosterone sulfate (DHEAS) were implanted subcutaneously in five cynomolgus monkeys (Macaca fascicularis) for one menstrual cycle. The pumps were filled with saline for the two control cycles, one preceding and the other following DHEAS infusion. RESULTS: Administration of DHEAS elevated its levels in serum fourfold and in urine sevenfold, which returned to pretreatment values in the next cycle. Serum concentrations of estradiol (E2) were reduced by 55% during DHEAS administration in both follicular and luteal phases and were still decreased in the following cycle by 69% in follicular phase and 48% in luteal phase (P less than 0.01). Luteal serum progesterone (P) levels were diminished by 52% during treatment and were accompanied by 56% reduction in immunoreactive pregnanediol excretion in urine (P less than 0.05). Serum luteinizing hormone (LH) levels were decreased during DHEAS infusion by 51% in follicular phase and 58% in luteal phase (P less than 0.01) but returned to baseline in the next cycle. Conversely, serum follicle-stimulating hormone (FSH) concentrations were increased during treatment by 70% in follicular phase and 101% in luteal phase and remained increased by 58% in follicular phase of the next cycle (P less than 0.05). Estrone excretion in urine was higher during DHEAS infusion (1.5-fold increase) but was below pretreatment values in the following cycle by 57% in follicular phase and 51% in luteal phase (P less than 0.001). Administration of DHEAS did not change significantly serum levels of sex hormone-binding globulin. The length of menstrual cycles was not affected by increased levels of adrenal androgens either. However, in the cycles that followed DHEAS infusion, follicular phase was prolonged by an average of 9 days, and luteal phase was shortened by an average of 5 days (P less than 0.01). CONCLUSIONS: These data document that subchronically elevated adrenal androgen levels in primates: (1) suppress E2 and P levels, which may affect fertility; (2) differentially affect gonadotropin secretion, decreasing LH and increasing FSH serum concentrations; and (3) result in disturbances of ovarian function that persist for at least one menstrual cycle after normalization of androgen levels.

Animals↗

PubMed1991

Sick absence in dockers.

The reasons for sick absence in dockers performing heavy loading jobs (stevedores) in the port of Gdynia, in 1986-1991, were identified and subjected to statistical analysis. The study group consisted of 603 people--73% of the whole population of dockers in the port. The prevailing reason were the diseases of the musculoskeletal system--on the average 5.6 days of sick leave per 1 docker per year--28.7% of the total sick absence in the occupational group studied. On the second place were traumas, mainly of the extremities and of the spine--4.7 days (24.9%). The proportion of the circulatory system diseases was a mere 1.9-0.4 days. The high sick absence caused by the first group of diseases calls for preventive interventions during pre-entry and periodic medical examinations of dockers.

Absenteeism↗

PubMed1989

[Current views on the treatment of endometriosis].

The authors present modern views on the therapy of endometriosis, paying much attention to pathophysiological aspects. They present both conventional methods, as hormonal therapy or surgery, and non-conventional methods as laser laparoscopy, microsurgery and fertilization in vitro. The authors stress the lack of casual treatment of endometriosis, which does not result in full effectiveness of the therapy and sometimes there is recurrence of the disease.

Danazol↗

PubMed1989

[Immunologic aspects of endometriosis].

The paper presents modern views on immunological conditioning of endometriosis. It seems that lowered cellular response, intensified humoral response and increased activation of peritoneal macrophages play an important role in the pathogenesis of endometriosis. Immunological research may lead to pharmacological causal treatment of endometriosis considering abnormal function of the immunological system. The paper also discusses the importance of the first biochemical marker of endometriosis--antigen CA-125--in the diagnostics and monitoring the disease.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1987