Osteoprotegerin, RANKL, and bone turnover in primary hyperparathyroidism: the effect of parathyroidectomy and treatment with alendronate.

Receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and its decoy receptor osteoprotegerin (OPG) play key roles in regulating bone turnover. The OPG/RANKL/RANK system is regulated by many hormones and cytokines, among which parathormone (PTH) seems to be one of the most important. Primary hyperparathyroidism (PHPT) with chronic excess of PTH and enhanced bone resorption provides an opportunity to observe the relationships between PTH, OPG and RANKL. From a group of 63 patients with PHPT, 29 underwent effective parathyroidectomy (PTX) and 33 were treated with alendronate. After one year, bone mineral density (BMD) improved in both groups, but the biochemical disturbances and PTH returned to normal only after PTX. The baseline serum concentrations of OPG and RANKL were higher in PHPT patients than in healthy controls, whilst the OPG/RANKL-F ratio was lower. The mean OPG concentration did not change after PTX, and slightly increased after alendronate treatment despite the unchanged PTH. Twelve months after treatment, RANKL slightly declined in both groups and the ratio of OPG/RANKL consistently increased. Serum OPG and RANKL did not correlate with PTH before or after PTX or alendronate treatment. In conclusion, bone resorption in PHPT is accompanied by a high serum concentration of OPG and RANKL as well as a low OPG/RANKL ratio. Both parathyroidectomy and treatment with alendronate diminish bone resorption, and correct the OPG/RANKL ratio in favor of OPG, although the mechanisms of their actions are different. Serum OPG concentration does not depend directly on PTH.

Vitamin D and selected cytokine concentrations in postmenopausal women in relation to metabolic disorders and physical activity.

Obesity and metabolic disturbances constitute significant health problems in elderly women. Due to the multifactorial background of these disorders, assessing the interaction between risk factors remains a significant part of prevention and health promotion. Studies have illustrated a relationship between low physical activity and vitamin D deficiency with obesity and its complications. Furthermore, vitamin D affects the production of adipokines and the inflammatory response in adipose tissue. The aim of our study was to determine the association between selected adipokines, vitamin D concentrations, physical activity (PA), and visceral adiposity index (VAI) in postmenopausal women. The study sample consisted of 318 ethnically homogenous postmenopausal women aged 50-60. Both anthropometric measurements (BMI, WC, WHR) and biochemical measurements (TC, HDL, LDL, TG, AIP, glucose, insulin, IL-6, TNF-α, adiponectin, leptin) were made, and PA by IPAQ were recorded. Body mass index (BMI), waist-to-hip ratio (WHR), HOMA, atherogenic index of plasma (AIP), and VAI were calculated using the standard formulas. We observed a negative correlation between BMI, WC, insulin, HOMA, and PA. We determined that there is a negative association between leptin and vitamin 25(OH)D concentrations (P = 0.007) and a positive association with adiponectin (P = 0.014). The results of the multiple linear regression analysis indicate that vitamin D and HOMA are independent factors that significantly affect leptin and adiponectin levels, contrary to VAI.

[Importance of prolactin level indication in detection of Sheehan syndrome]. / Znaczenie oznaczania poziomu prolaktyny w rozpoznaniu zespolu Sheehana.

Prolactin (PRL) levels were studied in 5 women with Sheehan syndrome before and after metoclopramide (MCP, 10 mg i.v.) and domperidone (MOT, 10 mg i.v.) stimulation. The levels of PRL were measured by RIA method. The obtained results were compared with control group (10 female volunteers). Decreased serum level of PRL was found in 3 women before stimulation in comparison with control group. The highest serum concentration of PRL was found 30 min after MOT and MCP injection. In group of women with Sheehan syndrome the level of PRL was not significantly increased in MCP-test. In MOT-test the level of this hormone did not change. The findings of the present investigation suggest that measurement of PRL serum levels in MOT-test could be of value in early diagnosis of Sheehan syndrome.

[Effect of oestro-feminal on lipid metabolism in postmenopausal women]. / Wplyw oestro-feminalu na gospodarke lipidowa u kobiet postmenopauzalnych.

The cessation of hormonal function of ovaries after menopause leads, among others, to changes of concentration of serum lipids and lipoproteins which may cause an increased risk for atherosclerosis. The purpose of the study was an evaluation of the effect of three- and six-month use of conjugated oestrogens on lipid metabolism in women after surgically induced menopause. Both after three and six months of treatment a reduction of intensity or abolition was found of the climacteric syndrome symptoms. After six months of substitutive therapy beneficial changes were observed in lipid metabolism (decrease of total and LDL-cholesterol levels, and increase of HDL-cholesterol level). Hormonal therapy may play a protective role and prevent the development of atherosclerosis in women after menopause.

[Atypical course of histiocytosis X]. / Nietypowy przebieg histiocytozy X.

A 48-year-old female patient was admitted because of increasing in size xanthomas of the eyelids lasting since 9 years (despite surgical treatment) and narrowing considerably the palpebral fissures. Five years earlier the diagnosis of type II b hyperlipoproteinaemia was made. Presently, besides palpebral lesions, a painless plum-sized tumour was found in the right frontoparietal area and two hard tumours of similar size were situated bilaterally in the submandibular area. In the biopsy specimens of all these tumours histological examination demonstrated lymphoid cells with numerous germinative centres. The diagnosis of histiocytosis X was followed by treatment with prednisone which resulted in a decrease in the size of palpebral xanthomas and improvement of the general condition of the patient.

Lipid disturbances in women with polycystic ovary syndrome.

Small but detectable disturbances concerning blood lipid levels manifested by somewhat higher concentrations of LDL-cholesterol and triglycerides as well as higher values of atherogenic indices expressing the ratio of cholesterol present in atherogenic lipoprotein fractions to that present in atheroprotective HDL fraction have been shown to exist in 36 women with polycystic ovary syndrome. HDL-cholesterol concentration was lower in women with polycystic ovary syndrome than in healthy women. The disturbances described above were more pronounced in obese patients. No correlation was found between the disturbances in lipid levels and hormonal disturbances particularly hyperandrogenemia.

[Results of treatment for acromegaly with long-acting bromocriptine (Parlodel LAR)]. / Wyniki leczenia akromegalii bromokryptyna o przedluzonym dzialaniu (Parlodel LAR).

Long-acting bromocriptine (Parlodel LAR) was used for treatment of 25 patients with acromegaly during the period of 3 to 24 months. Even after the first intramuscular injection of 50 milligrams of the drug a decrease in growth hormone (GH) concentration by at least 50% of the initial values was observed in 28% of patients and an improvement in a sense of well-being in 44%. After 6 months of administration of 100 mg of Parlodel LAR at intervals of 28 days a decrease in GH level by at least 50% was observed in a larger percentage of patients (36.8%), and in 10.5% of them there was a fall of GH concentration to below 10 microU/ml. Side effects, like nausea, vomiting and orthostatic hypotony, appeared within several hours after the injection of Parlodel and lasted in most cases up to 24 hours. After consecutive injections of the drug the side effects were of lesser intensity or completely disappeared. The results obtained allow to conclude that Parlodel LAR is an effective drug in some cases of acromegaly. In most patients the therapeutic effect can be seen after the first injection, but in some cases it appears only after several months of treatment.

The efficacy, tolerability and safety of Parlodel LAR versus Parlodel in hyperprolactinemia.

A double blind, double dummy study on the efficacy, tolerability and safety of Parlodel LAR versus oral Parlodel was carried out in 13 hyperprolactinemic women. Six patients received active from of Parlodel LAR (1 intramuscular injection at a dose of 50 mg) and placebo for oral Parlodel simultaneously. Seven other patients received active form of Parlodel orally (up to 7.5 mg daily) and placebo for Parlodel LAR injection. In all patients the marked reduction in serum prolactin level was observed. In normalization of prolactinemia was achieved in 8 patients (2 LAR, 6 oral). Galactorrhea disappeared in 7 of 8 patients (4 LAR, 3 oral), menstrual bleeding occurred in 5 of 10 amenorrheic patients (3 LAR, 2 oral). Tumor shrinkage was shown in 1 case (oral therapy). The improvement of slightly narrowed visual field was documented in 3 cases (2 LAR, 1 oral). The adverse effect during the therapy were mild and transient. We conclude that both froms of bromocriptine are very useful for treatment of hyperprolactinemia but Parlodel LAR is better tolerated and more convenient in application because of its prolonged activity.

Therapeutic effect of gevilon in patients with hyperlipoproteinaemia.

Authors examined 46 patients with hyperlipoproteinaemia divided according to hyperlipoproteinaemia type II A, II B, IV. After one month of isocaloric diet the patients were given a single night gevilon dose of 900 mg for a period of 3 months. After therapy we examined lipid metabolism, liver and kidney function, carbohydrate metabolism, hematopoietic system and water--electrolyte balance. In all groups increased levels of cholesterol, beta-lipoproteins and triglycerides were significantly reduced after 3 months of gevilon treatment. In all patients the HDL/LDL ratio increased close to normal values. No impairment of kidney or liver function hematopoietic system and electrolyte balance after 3 months of treatment were noted. Because gevilon is easy to apply and has a limited number of side effects, it is very readily taken by the patients who have lipid balance disorders.

The influence of DHEA on serum lipids, insulin and sex hormone levels in rabbits with induced hypercholesterolemia.

The authors estimated the influence of dehydroepiandrosterone (DHEA) administration, a potential antiatherogenic agent, on serum lipids, sex hormones and insulin levels in male rabbits fed on an atherogenic diet. They concluded that (1) DHEA administration has an unfavorable impact on the serum lipid profile; (2) an atherogenic diet causes insulin resistance; (3) the glucose and insulin levels are not related to DHEA in normally fed rabbits and in rabbits with hyperlipoproteinemia; (4) an atherogenic diet causes a slight increase of estradiol concentration; (5) DHEA treatment has no significant effect on testosterone and estradiol concentrations in both normally fed rabbits and those on an atherogenic diet; (6) DHEA administration has an anti-obesity effect.

The influence of dehydroepiandrosterone on histology of selected organs in rabbits on an atherogenic diet.

The influence of dehydroepiandrosterone (DHEA) in fodder on the histology of selected organs in rabbits with induced hypercholesterolemia and in healthy rabbits was studied. Rabbits were randomly assigned into four groups: (1) control; (2) atherogenic diet; (3) atherogenic diet with addition of DHEA; (4) normal diet with addition of DHEA. After 12 weeks, the rabbits were bled. Tissue samples were collected, fixed in a 0.4% solution of buffered formalin, dehydrated and embedded in paraffin. Fragments of 5-7 microns were stained with hematoxylin and eosin as well as according to the van Gieson method. Histological analysis showed features of steatosis and intense degenerative changes in analyzed organs of animals from group 2, i.e. liver, kidneys, adrenal glands, lungs and bone. The degenerative changes in the group which in addition to a fat-rich diet received DHEA, were similar to group 2, but much less intense. Histological pictures of organs of the rabbits which received DHEA and normal diet did not differ significantly from the control group. In animals with experimental hyperlipidemia, DHEA acts protectively, decreasing degenerative changes in internal organs caused by an atherogenic diet. DHEA does not change the histological picture of organs in healthy animals.

[Treatment of hyperandrogenic manifestations in polycystic ovary syndrome]. / Leczenie objawów hiperandrogenizmu w zespole wielotorbielowatych jajników.

Etiopathogenesis of the polycystic ovarian disease is not clarified. Therefore, optimum therapy of hyperandrogenic syndromes, menstrual and fertility disorders pose a difficult problem. Sequential therapy with estrogens and progestagens is of value in young women, who are not planning to conceive in order to reduce hirsutism and regulate menses. A reduction of hirsutism, acne and seborrhea is produced within 3 months. However, cessation of the treatment produces the symptoms of excessive androgen production. Another method is therapy with antiandrogens, especially cyproterone acetate. This drug inhibits androgens biosynthesis and has also peripheral activity. Spironolactone is another antiandrogen frequently used, but it is known as a primarily diuretic agent. It acts primarily at the androgen receptor sites. Other antiandrogens such as ketoconazole and flutamide are used less frequently. It has been shown, that cimetidine--known H2 receptor inhibitor--also decreases the symptoms of hyperandrogenism. However, cimetidine has not been used for the treatment of polycystic ovarian disease. In cases of enzymatic defects in adrenocortical steroido-synthesis glucocorticoids are used, mainly low doses of triamcinolone and dexamethasone. Other therapies are preferred in case of polycystic ovarian disease in women, who want to conceive. Clomiphene citrate and gonadotropins, mainly FSH, are used to induce ovulation. If pharmacotherapy does not produce ovulation, wedge resection of the ovaries must be performed.

Serum lipid peroxides and total antioxidant status in postmenopausal women on hormone replacement therapy.

Estradiol (E2) has antioxidant properties. The role of progestins in antioxidant defense is still unknown. We have evaluated the influence of E2 and E2 plus medroxyprogesterone acetate (MPA) on serum lipid peroxide (LPO) levels, a marker of free radical reactions, and serum total antioxidant status (TAS) in postmenopausal women. Subjects consisted of 26 women with surgical menopause, before and after 4 months of estrogen replacement therapy (ERT; E2), and 54 women with natural menopause on hormone replacement therapy (HRT; E2 plus MPA). Forty premenopausal women served as a control group. Serum E2 was estimated by radioimmunoassay, follicle-stimulating hormone by IRMA methods, LPO and TAS by colorimetric methods. Before therapy, LPO levels in the postmenopausal women were significantly higher (p < 0.001) than in the control group. After both ERT and HRT, LPO decreased significantly and did not differ between both groups and the control group. TAS was significantly lower in postmenopausal women (p < 0.001) than in the control group before therapy. After both ERT and HRT, TAS increased significantly and did not differ between both groups and the control group. We conclude that oxidative stress is increased after menopause. ERT and HRT inhibit the generation of free radicals and raise antioxidant potential to the levels found in premenopausal women. MPA did not influence the antioxidant action of E2.

Serum lipid peroxide levels and erythrocyte glutathione peroxidase and superoxide dismutase activity in premenopausal and postmenopausal women.

Free radical reactions are involved in processes connected with aging. Estradiol acts as antioxidant and free radical scavenger, but the mechanism of this action remains unknown. Estradiol has a hydroxyphenolic structure and may donate hydrogen atoms to lipid peroxyradicals to terminate chain reactions. There are a few reports concerning the influence of estradiol on natural antioxidant enzyme activity, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). The aim of this study was to estimate the relationship between the levels of estradiol and lipid peroxide (LPO), a marker of membrane lipid peroxidation, and the correlation between estradiol and erythrocyte SOD and GSH-Px activity. The study included 13 premenopausal and 13 postmenopausal healthy women. Serum levels of estradiol, follicle-stimulating hormone (FSH) and LPO, and erythrocyte SOD and GSH-Px activity were estimated in all subjects. Premenopausal women revealed significantly higher estradiol levels and lower LPO concentrations, as well as significantly higher GSH-Px activity than the postmenopausal group. SOD activity did not differ between the two groups. There was a negative correlation between serum estradiol and LPO levels as well as a positive correlation between estradiol and GSH-Px activity. These results support the hypothesis that estradiol exerts its antioxidant action not only through its chemical structure but probably also through its influence on natural cellular antioxidant enzyme activity.

Influence of dehydroepiandrosterone on platelet aggregation, superoxide dismutase activity and serum lipid peroxide concentrations in rabbits with induced hypercholesterolemia.

UNLABELLED: Special interest in the role of DHEA dates back to the finding of a correlation between low serum DHEA concentrations and a higher morbidity and mortality rate due to coronary diseases in humans. Animal studies with experimental atherosclerosis confirmed the anti-sclerotic effect of DHEA. The mechanism of DHEA action remains unclear. We determined the influence of dehydroepiandrosterone (DHEA) administration, a potential anti-atherogenic agent, on platelet aggregation, platelet superoxide dismutase (SOD) activity and serum lipid peroxide (LPO) levels in male rabbits fed on a normal and atherogenic diet. 44 adult male New Zealand white rabbits were divided into 4 groups: 1--control group fed on standard rabbit food, 2--fed on an atherogenic diet, 3--fed on an atherogenic diet with DHEA, 4--fed on standard food with DHEA. We detected blood platelet aggregation following (ADP) and collagen activation by means of photometry. Platelet SOD activity was detected by means of fluorometry determining the inhibition of adrenaline auto-oxidation. The serum LPO concentration was measured by means of the colorimetric method. The serum DHEA-S concentration was measured by means of RIA methods, and serum lipid levels were measured by means of Biomérieux manufactured kits. Results demonstrate that (1) elevated LPO concentrations in rabbits with hyperlipidemia did not decrease following DHEA administration. (2) In rabbits fed on a normal diet, DHEA caused a decrease of LPO, which emphasizes the positive influence of this steroid on the oxidative stress in healthy animals. Such a result was not seen in the group with severe hyperlipidemia. (3) Rabbits with hyperlipidemia demonstrated a significantly decreased SOD activity. (4) In healthy animals as well as in those with hyperlipidemia, DHEA administration caused an increase of platelet SOD activity, the main enzyme of the antioxidant defence system, which protects the organism against free radical damage (5) (DHEA had no influence on platelets aggregation in both tested groups). IN CONCLUSION: DHEA administration improves platelet SOD activity, which protects cells against oxidative damage. The hypothesis that DHEA administration leads to an increase in antioxidant potency requires further investigations.