Serum concentrations of HGF and IL-8 in patients with active Graves' orbitopathy before and after methylprednisolone therapy.

INTRODUCTION: Graves' disease is the most common cause of hyperthyroidism, and orbitopathy is the most frequent extrathyroidal manifestation of Graves' disease. The aims of this study were as follows: (1) to evaluate the serum concentration of HGF and IL-8 in the blood of newly diagnosed Graves' disease patients with the first episode of active GO and healthy controls; (2) to estimate the influence of the thyroid function (euthyreosis vs. hyperthyreosis) on HGF and IL-8 blood levels in patients with active GO; (3) to evaluate the influence of intravenous (i.v.) methylprednisolone (MP) pulse therapy and additional oral MP treatment on HGF and IL-8 blood levels in patients with active GO. PATIENTS AND METHODS: Thirty-nine Graves' disease patients with the first episode of clinically active GO (Group A) were enrolled in the study. To estimate the influence of the thyroid function on serum concentrations of the studied proangiogenic factors, Group A was divided into Group A I (n = 18) in euthyroid and Group A II (n = 21) in hyperthyroid stage of Graves' disease in moderate-to-severe stage of GO. The control group consisted of 20 healthy volunteers age- and sex-matched to the GO group. Concentrations of the studied proangiogenic factors in serum samples were measured by an enzyme-linked immunosorbent assay before (Group A) and after (Group A1) intensive pulse i.v.MP treatment and 1 month after the end of additional oral MP treatment (Group A2). RESULTS: We found a significant increase in serum concentrations of studied factors in the GO group before immunosuppressive therapy when compared with the control group and decrease after i.v.MP treatment. One month after the end of additional oral MP treatment (Group A2), serum concentrations of HGF and IL-8 still decreased and no significant difference was observed in HGF and IL-8 concentrations when compared with the control group. We did not find the difference in serum concentration of the studied proangiogenic factors between patients in euthyroid and hyperthyroid stage of Graves' disease before MP therapy. CONCLUSIONS: Serum HGF and IL-8 concentrations are elevated in Graves' disease patients with active Graves' orbitopathy as compared to the healthy control group. Successful management of active Graves' orbitopathy with glucocorticoids is associated with a decrease in HGF and IL-8 serum concentrations.

Serum concentration of VEGF and PDGF-AA in patients with active thyroid orbitopathy before and after immunosuppressive therapy.

INTRODUCTION: Thyroid orbitopathy (TO) is the most frequent extrathyroid manifestation of Graves' disease. The aim of this study was to evaluate the serum concentration of Vascular Endothelial Growth Factor (VEGF), Plated-Derived Growth Factor-AA (PDGF-AA) in the blood of patients with active OT before and after immunosuppressive therapy. PATIENTS AND METHODS: The study was performed in group of 39 patients with clinically active TO (Group A) in euthyroid (n=18, Group A I) and hyperthyroid (n=21, Group A II) stage of Graves' disease in moderate or severe stage of TO. Control group consist of 20 healthy age-matched control subjects. Concentration of studied proangiogenic factors in serum samples were measured by an enzyme linked immunosorbent assay (ELISA) before (group A) and after (group A1) intensive pulse methylprednisolone treatment and one month after the end of additional oral methylprednisolone treatment (Group A2). RESULTS: We have found significant increased serum levels of VEGF in patients with TO (reg-ardless to treatment) when compared with control group (542.4±328.1 pg/ml vs. 94.6±55.3 pg/ml, p=0.0002) and increased serum levels of -PDGF-AA in patients before treatment (3 173.6±1 480.3 pg/ml) in comparison with controls (1 768.9±520.0 pg/ml) and patients after intensive pulse methyloprednisolone treatment (2 325.9±1 456.8 pg/ml). One month after the end of additional oral methylprednisolone treatment (Group A2) concentration of PDGF-AA still decreased and were was not significant difference with value in control group (1 853.1±795.4 vs. 1 769.9±520.0 pg/ml, p=0.99). Serum concentration of VEGF was still significantly higher compared with control. We have not observed difference in serum concentration of studied proangiogenic factors between patients in euthyroid or hyperthyroid stage of Graves' disease. CONCLUSIONS: RESULTS of the present study confirm the fact that angiogenesis could play a role in pathogenesis of thyroid orbitopathy.

Empty sella syndrome in thyroid cancer survivor.

Empty sella syndrome is a consequence of the herniation of the subarachnoid space within the sella associated with flattering of the pituitary gland. In this paper, we describe the atypical clinical manifestation of this condition in a 27-year-old survivor of thyroid cancer. We associate the development of empty sella syndrome in this subject with normalization of levothyroxine treatment in conditions of long-lasting and inaccurately managed thyroid ablation-induced hypothyroidism. Administration of hydrocortisone and implementation of hypogonadism treatment together with the appropriate management of hypothyroidism led to a significant improvement in the patient's condition.

Sleep apnea syndrome and snoring in patients with hypothyroidism with relation to overweight.

The relation between snoring and obstructive sleep apnea as well as hypothyroidism is the object of interest of many authors. The respiratory disturbances during sleep are often observed in patients suffering from hypothyroidism. The relation of snoring to overweight in those patients has not been taken into account. The aim of the study was to evaluate the relations between hypothyroidism and quantitative and qualitative respiratory disturbances during sleep. Additional aim was to establish the relations of sleep apnea syndrome, snoring, hypothyroidism and overweight. The subjects included 15 patients (11 females and 4 males) aged from 28 to 73 (mean 50.3) suffering from hypothyroidism. All of them underwent thyroid testing before and after the hormonal treatment. TSH and fT4 concentrations were determined. At the same time the sleep assessment (PolyMESAM) was performed twice. Data were obtained from sleep studies and questionnaires (Epworth sleepiness scale). After the thyroid hormones stabilization significant decrease of snoring severity was observed. On the contrary, the respiratory disturbance index (RDI), desaturation index (DI), the lowest saturation (LSAT) did not change significantly, however, the Epworth scale score showed significant improvement. The correlations showed the strong relation between loud snoring and TSH (r=0.73, p<0.01) and fT4 (r=-0.66, p<0.003) concentrations before the treatment. The analysis showed no correlation between body mass (BMI) and snoring. The hormonal stabilization in patients suffering from hypothyroidism causes improvement in snoring severity. Based on our investigation the relationship between hypothyroidism and severity of snoring and excessive daytime somnolence was confirmed. It indicates a possible connection between hypothyroidism and upper airway resistance syndrome.

Homocysteine, vitamin B12, and folic acid in age-related macular degeneration.

PURPOSE: Hyperhomocysteinemia is considered an independent risk factor for atherosclerosis and thrombosis. The purpose of this study was to evaluate plasma homocysteine, red blood cell folate, plasma folate, and plasma vitamin B12 concentration in patients with exudative age-related macular degeneration (ARMD). METHODS: The participants of this study included 30 patients aged 60 to 71 years (mean age 66.2+/-3.6) with exudative ARMD. Plasma homocysteine levels were determined by high performance liquid chromatography (HPLC). Red blood cell folate, plasma folate, and plasma vitamin B12 concentration were determined using a standard kit (Dualcount Solid Phase No Boill radioassay kit for B12/folic acid, DPC Diagnostic, USA) by radioassay method. RESULTS: The plasma concentration of Hcy (14.88+/-6.23 micromol/L) in ARMD patients was significantly increased (p<0.0001) compared with the control group (8.72+/-3.34 micromol/L). We found not a significant decrease of the plasma vitamin B12 concentration in the ARMD group (476.88+/-220.91 pg/mL) compared with the control group (527.08+/-208.97 pg/mL). Red blood cell folate (158.44+/-56.30 ng/mL) and plasma folate (6.5+/-3.4 ng/mL) in ARMD patients were also not significantly decreased when compared with the control group (183.86+/-59.33 ng/mL and 7.93+/-5.05 ng/mL). CONCLUSIONS: Hyperhomocysteinemia might be one of the risk factors for the exudative form of ARMD.

TGF-beta1 mRNA expression in liver biopsy specimens and TGF-beta1 serum levels in patients with chronic hepatitis C before and after antiviral therapy.

BACKGROUND AND OBJECTIVE: Transforming growth factor (TGF)-beta1 is the best-characterized profibrogenic cytokine. TGF-beta1 increases the production of extracellular matrix proteins and their receptors and inhibits the synthesis of matrix degrading proteolytic enzymes. We undertook this study to simultaneously evaluate the effect of interferon alpha 2b plus ribavirin therapy on TGF-beta1 daily serum levels and on mRNA TGF-beta1 expression in liver biopsy specimens from 60 patients with chronic hepatitis C. METHODS: Serum levels of TGF-beta1 were measured by ELISA. The levels of the RNAs in liver biopsy specimens were measured by quantitative reverse transcriptase polymerase chain reaction. After treatment, patients were divided into two groups: 34 responders [undetectable hepatitis C virus (HCV)-RNA, normal ALT levels, decrease in histology activity index compared with pretreatment liver biopsy] and 26 non-responders (detectable HCV-RNA, elevated ALT levels, no decrease in the histology activity index). RESULTS AND DISCUSSION: In patients with hepatitis C, the 'responders' to the antiviral treatment showed significant decreases in both mean daily serum TGF-beta1 levels and mRNA TGF-beta1 expression in the liver biopsy specimens. The 'non-responders' serum TGF-beta1 concentrations did not change significantly, but the mRNA TGF-beta1 expression did. CONCLUSION: Both serum TGF-beta1 concentration and mRNA TGF-beta1 expression in liver biopsy specimens may be useful as prognostic markers in patients with hepatitis C undergoing antiviral therapy.

Changes in lipid metabolism in women with age-related macular degeneration.

Age-related macular degeneration (AMD) is one of the leading causes of visual loss among people aged 65 and older. At present the origin of AMD still remains unknown. The objective was to evaluate the chosen lipid and lipoprotein concentrations in blood of patients with AMD. Sixty women aged 55-71 (mean age 65.1+/-5.7) were treated in the outpatient ophthalmological clinic for more than two years because of AMD. We evaluated total serum cholesterol (TCH), triglycerides (TG), HDL-cholesterol (HDL), LDL-cholesterol (LDL), lipoprotein (a) (Lp(a)), apolipoprotein AI (Apo AI) and apolipoprotein B (Apo B) by direct spectrophotometry (Human and Randox standard kits, USA). We found a significant increase of TCH, LDL and TG (224.36+/-41.67 mg/dl, 159.02+/-39.66 mg/dl and 120.92+/-42.64 mg/dl), and a significant decrease of HDL (38.68+/-6.36 mg/dl) in the AMD patients when compared with the control group. We have not found a significant difference in the average TG level between the studied groups. The concentration of Apo B was markedly increased (164.66+/-46.46 mg/dl) and Apo AI concentration was markedly decreased (128.9+/-17.01 mg/dl) in the AMD patients when compared with the control group. There was no significant difference in the concentration of the Lp(a) between the two groups. The results of our present study could point to the fact that changes in the lipid metabolism could be one of the very important risk factors involved in the pathogenesis of AMD.

Homocysteine, vitamin B12, and folic acid in age-related macular degeneration.

PURPOSE: Hyperhomocysteinemia is considered an independent risk factor for atherosclerosis and thrombosis. The purpose of this study was to evaluate plasma homocysteine, red blood cell folate, plasma folate, and plasma vitamin B12 concentration in patients with exudative age-related macular degeneration (ARMD). METHODS: The participants of this study included 30 patients aged 60 to 71years (mean age 66.23.6) with exudative ARMD. Plasma homocysteine levels were determined by high performance liquid chromatography (HPLC). Red blood cell folate, plasma folate, and plasma vitamin B12 concentration were determined using a standard kit (Dualcount Solid Phase No Boill radioassay kit for B12/folic acid, DPC Diagnostic, USA) by radioassay method. RESULTS: The plasma concentration of Hcy (14.886.23 micronmol/L) in ARMD patients was significantly increased (p<0.0001) compared with the control group (8,.723,.34 micronmol/L). We found not a significant decrease of the plasma vitamin B12 concentration in the ARMD group (476.88220.91 pg/mL) compared with the control group (527.08208.97 pg/mL). Red blood cell folate (158.4456.30 ng/mL) and plasma folate (6.53.4 ng/mL) in ARMD patients were also not significantly decreased when compared with the control group (183.8659.33 ng/mL and 7.935.05 ng/mL). CONCLUSIONS: Hyperhomocysteinemia might be one of the risk factors for the exudative form of ARMD.

Plasma concentration of soluble intercellular adhesion molecule-1 in women with polycystic ovary syndrome.

Soluble intercellular adhesion molecule-1 (sICAM-1) is ranked as one of the endothelial dysfunction markers and factors predicting diseases of the cardiovascular system. The main objective of this study was to assess the serum concentration of sICAM-1 in women with polycystic ovary syndrome (PCOS) and to verify correlations between serum sICAM-1 levels and selected anthropometric, metabolic and hormonal indices. The study assessed 57 women with PCOS (mean age 28.2 +/- 6.4 years). That group was further divided into two subgroups: the first with body mass index (BMI) < or =25 kg/m2 (21 women of mean age 27.4 +/- 7.0 years) and the second with BMI >25 kg/m2 (36 women of mean age 28.6 +/- 6.0 years). In the control group there were 22 healthy women (mean age of 31.6 +/- 8.5 years). That group again was divided accordingly to BMI into two subgroups: the first with BMI <25 kg/m2 (ten women, mean age 30.2 +/- 8.4 years) and the second with BMI > 25 kg/m2 (12 women, mean age 31.7 +/- 8.7 years). The results demonstrated statistically significantly higher mean concentrations of sICAM-1 in women with PCOS as compared to healthy individuals from the whole control group and also from the control subgroup of women with BMI >25 kg/m2. There was no statistically significant difference in sICAM-1 concentration between the PCOS group and the control subgroup with BMI < or =25 kg/m2 In conclusion, higher concentrations of sICAM-1 in women with PCOS may confirm the presence of a higher risk for cardiovascular diseases in this group. Further studies are therefore necessary to identify both the factors that are responsible for the increase in sICAM-1 concentration and the clinical usefulness of routine sICAM-1 measurement in females with PCOS.

Circadian rhythm of androstendione and free testosterone in asthmatic women with postmenopausal hormone therapy.

OBJECTIVE: of this study was to assess daily rhythm of androstendione (delta4alpha) and free testosterone (FT) levels in postmenopausal asthmatic women before and after hormonal replacement therapy and the influence of inhaled glucocorticosteroids (GC). METHODS: 54 asthmatic and 20 healthy postmenopausal women (aged 48-59) before and after 6 months of estrogen plus progestin therapy (EPT) were studied. Hormone concentrations in serum (delta4alpha and FT) were assessed with the use of RIA method. Statistical analysis of the circadian rhythm was performed with the use of cosinor test according to Halberg et al RESULTS: Cosinor analysis of delta4alpha and FT secretion during the day showed existence of daily rhythm in three studied groups before as well as after postmenopausal hormone therapy (HT). A statistically significant decrease of circadian concentrations of delta4alpha and FT in groups of patients treated with GC was observed. Changes in amplitude of delta4alpha and FT rhythm between studied groups were not observed. However, displacement of rhythm acrophase of studied hormones in asthmatic women in comparison to control group before and after HT was shown. No significant differences in circadian values of delta4alpha and FT concentrations before HT use compared to values after HT were shown. CONCLUSIONS: Postmenopausal asthmatic women show diminished circadian concentrations of androstendione and free testosterone in serum caused among other things by inhalative GC. Postmenopausal hormone therapy did not influence any changes in function of studied endocrine organs.

Serum adiponectin in women with polycystic ovarian syndrome and its relation to clinical, metabolic and endocrine parameters.

UNLABELLED: Several studies have demonstrated that low levels of serum adiponectin are present in obesity, insulin resistance, hypertension and hyperlipidemias. The aim of our study was to determine whether serum adiponectin level is different between patients with polycystic ovarian syndrome (PCOS) and control subjects. We also investigated relationships between various cardiovascular risk factors, levels of serum adiponectin and other hormones, such as androstendione, testosterone, estradiol, DHEAS, sex hormone binding globulin (SHBG), and leptin. We also analysed the correlation between serum adiponectin and free androgen index. Ninety-one women with clinical diagnosed PCOS and 53 healthy control subjects, carefully matched by body mass index (BMI) and age, were enrolled in the study. The fasting blood samples were obtained and all participants underwent an oral 75 g glucose tolerance test. The prevalences of impaired glucose tolerance (IGT), hypertension and hypertriglyceridemia were higher in the PCOS group. PCOS women had increased androgen concentrations and higher free androgen index and decreased level of serum SHBG. Lower serum adiponectin concentrations were observed among cases than in controls (median 13.7 microg/ml vs 17.8 microg/ml, p<0.001) despite being matched by BMI. In the PCOS group adiponectin levels correlated significantly with: BMI (r=-0.32, p=0.002), waist circumference (r=-0.32, p=0.003), waist-to-hip ratio (WHR, r=-0.38, p=0.001), triglycerides (r=-0.31, p=0.007), SHBG (r=0.30, p=0.003) and free androgen index (r=-0.29, p=0.02). In contrast, the adiponectin level does not appear to be related to total testosterone, DHEAS and leptin levels. The adiponectin and SHBG levels were found to be decreased in PCOS women with IGT compared to PCOS women with normal glucose tolerance, but after adjustment by BMI or WHR, the differences were no longer statistically significant. To exclude a possible confounding effect due to a higher prevalence of IGT in the PCOS group, this comparison was repeated for the subgroup of 58 PCOS women and 48 control women after excluding those with IGT. Neither adiponectin nor SHBG were significantly different between those subgroups. Multiple regression analysis revealed that serum adiponectin concentrations were best predicted by WHR, free androgen index and presence of IGT when all patients were considered. In PCOS subjects, the only independent predictor of adiponectin concentrations was glucose tolerance status. CONCLUSIONS: Lower adiponectin levels were observed in PCOS group than in control women, and these differences were probably due to higher prevalence of IGT in these cases.

Adrenal cortex function in asthmatic patients following the discontinuation of chronic therapy with systemic glucocorticosteroids.

OBJECTIVE: To estimate the time it takes for adrenal cortex function in asthmatic patients to return to normal after discontinuation of chronic therapy with systemic glucocorticosteroids (GCs) and to assess the relationship between the duration of the disease, chronic therapy, and the return of the normal adrenal cortex functioning. MATERIALS AND METHODS: The study involved 58 asthmatic patients and 31 healthy volunteers (aged 20-69 years). Adrenal cortex function was evaluated with the Synacthen short test, and determining serum and urinary free cortisol levels after 1, 3, 6, 12, 18, and 21 months following the discontinuation of systemic therapy with GCs. RESULTS: A decreased adrenal reserve was observed 1 month after withdrawal of GCs in 50% of the chronically treated patients. Adrenal cortex function returned to normal in 55% of patients within 6 months, in 24% within 12 months, and in 14% within 15 months of discontinuation of systemic GCs administration. A significant positive correlation between the time taken for return to normal adrenal cortex function and duration of the disease and of GCs therapy was found. CONCLUSIONS: Symptoms of adrenal failure may develop in about 50% of asthmatic patients. In the majority of patients treated long term with systemic GCs, adrenal cortex function returns to normal within 6 months following discontinuation of GCs. The time of such return depends on the duration of the disease and of therapy with systemic GCs.

Influence of lighting conditions on daily rhythm of bone metabolism in rats and possible involvement of melatonin and other hormones in this process.

OBJECTIVE: To evaluate the influence of lighting conditions on daily fluctuations of biochemical markers of bone and mineral metabolism such as the activity of serum alkaline phosphatase (ALP), the concentration of carboxyterminal propeptide of type I procollagen (PICP), cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and inorganic phosphorus (iP) as well as urinary excretion of hydroxyproline (HYP) and calcium (Ca). In addition, possible involvement of daily secretion of melatonin (MEL), GH/IGF-I axis activity and parathyroid, thyroid, adrenocortical and gonadal function in this process. METHODS: Three series of 48 adult male Wistar rats weighing 180 +/- 10 g were conditioned to different lighting conditions for 4 weeks: 1. control group (LD 12:12 h, light on from 7.00 to 19.00); 2. short-day group (LD 0.5:23.5 h, light on from 7.00 to 7.30); 3. long-day group (LD 23.5:0.5 h, light on from 19.30 to 19.00). The blood was obtained by decapitation. Material for studies was collected every 3 hours during a day. The concentration of hormones, PICP and ICTP was determined with the use of RIA method, whereas ALP, iP, HYP and Ca levels were estimated spectrophotometrically. RESULTS: A significant influence of different lighting conditions on the daily profile of investigated markers of bone metabolism in rats was confirmed. Thus a short day was found to have an inducing effect upon the level of these markers, while a long day showed a suppressing effect. Furthermore, substantial changes in the values of amplitude and phase of their daily rhythms were found. Also some distinct anomalies in daily oscillations of ALP, PICP, ICTP, HYP and Ca were found which were dependent on the time of the day and showed a negative correlation with the changes in endogenous MEL concentrations. Moreover, ICTP, HYP and Ca concentrations correlated positively with daily fluctuations of IGF-I and triiodothyronine. CONCLUSIONS: Lighting conditions can influence daily fluctuations of studied bone metabolism markers in rats, and in the mechanism of this dependence the changes in endogenous MEL concentrations seem to play an important role. Secondary changes in daily IGF-I and triiodothyronine oscillations, caused by short- and long-day conditions, result in altered daily bone resorption rhythmicity.

The relationship between bone metabolism, melatonin and other hormones in sham-operated and pinealectomized rats.

OBJECTIVE: The influence of pinealectomy and long-term melatonin (MEL) administration on circadian oscillations of selected biochemical markers of bone metabolism [serum alkaline phosphatase (ALP) activity, carboxyterminal propeptide type I procollagen (PICP) and carboxyterminal telopeptide type I collagen (ICTP) concentrations as well as urinary excretion of hydroxyproline (HYP) and Ca] and possible involvement of circadian secretion of IGF-I, parathyroid, thyroid, adrenal cortex and gonads function in this mechanism was evaluated. METHODS: Studies were performed in 192 adult male Wistar rats weighing 145 +/- 9 g which were subjected to pinealectomy or sham operation. In half of the animals from each group MEL (Sigma, USA) in a dose of 50 mg/100 g b.w. was administered intraperitonealy (daily between 17.00 and 18.00 h for a 4-week period). Material for studies (blood and urine) was collected every 3 hours during a day. Hormones, PICP and ICTP concentrations were determined with the use of RIA methods. whereas ALP, HYP and Ca values - spectrophotormetrically. RESULTS: The study has shown that pinealectomy had an inducing, while exogenous MEL a suppressing effect upon the level of investigated biochemical markers of bone metabolism. Furthermore, substantial changes in the values of amplitude and phase of their circadian oscillations were shown. Distinct, dependent on the time of day disturbances in circadian fluctuations of PICP, ICTP, HYP and Ca showing generally negative correlation with changes in endogenous MEL concentrations and positive with IGF-I and corticosterone (B) levels were found. In addition, changes in circadian oscillations of ALP and PICP correlated negatively with daily oscillations of calciotropic hormones and B. However, ICTP, HYP and Ca concentrations correlated positively with circadian fluctuations of B and FT3 (the latter only in sham operated rats receiving MEL). CONCLUSIONS: This study showed that both pinealectomy and long-term MEL administration influence the circadian rhythm of bone metabolism and that an important role in the mechanism of this dependence is played by the changes of endogenous MEL levels. Secondary changes in circadian oscillations of calciotropic hormones, IGF-I and corticosterone concentrations, caused by pinealectomy and long-term MEL administration result in altered bone metabolism rhythm.

Dynamic pattern of IGF-I and chosen biochemical markers of bone metabolism in a rat model of postmenopausal osteoporosis.

OBJECTIVE: To assess the relationship between the dynamic pattern of IGF-I levels and chosen biochemical markers of bone metabolism in ovariectomized rats - a model of postmenopausal osteoporosis. METHODS: Six-month-old rats were randomized to sham operation (control group) or ovariectomy. Serum levels of insulin-like growth factor (IGF-I) and chosen biochemical markers of bone metabolism (alkaline phosphatase - ALP, carboxyterminal propeptide of type I procollagen - PICP, cross-linked carboxyterminal telopeptide of type I collagen - ICTP in serum as well as urinary excretion of hydroxyproline - HYP and total calcium - Ca) were measured before (group 0) and 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 and 28 weeks after the operation. RESULTS: In a model of experimental osteoporosis induced by ovariectomy in female rats a distinct tendency to decrease the IGF-I concentrations was shown. Differences were significant in relation to the control group in a period from 2 to 28 weeks after operation. Ovariectomy stimulated the values of studied markers of bone metabolism; it was more intensified in regard to resorption markers. Significant ICTP and HYP concentrations' changes, in relation to the control group, were shown in the some period and total calcium - from 2 to 16 weeks after ovariectomy. However, the values of studied markers of bone formation were generally changing to a slight degree. Significant differences of ALP activity, in relation to the control group, were observed only at 8 and 20 weeks, while those of PICP concentrations were found at in 4, 8 and 12 weeks after the operation. The alterations in the levels of IGF-I correlated significantly and negatively with the changes in ALP activity as well as in PICP, ICTP, HYP and Ca concentrations both in ovariectomized and control rats. This relation was more expressed in the ovariectomized group. CONCLUSIONS: Our findings suggest that secondary changes in IGF-I concentration, due to the deficiency of sex hormones, results in altered bone metabolism in ovariectomized rats.

Effects of hormone replacement therapy on endocrine and spirometric parameters in asthmatic postmenopausal women.

The aim of the study was to see if there are any correlations between changes in the endocrine system and clinical condition of asthmatic patients, in particular their lung function, caused by hormone replacement therapy (HRT). Fifty-five asthmatic and 20 healthy postmenopausal women (aged 48-60) were studied before HRT and after 6 months of cyclical transdermal 17 beta-estradiol and medroxyprogesterone acetate treatment. Serum estradiol, cortisol and dehydroepiandrosterone sulfate (DHEAS) concentrations were assessed with the use of RIA, and spirometry parameters were measured. Statistically significant diminution of asthma exacerbations, reduced consumption of inhaled glucocorticosteroids and improvement in all investigated spirometry parameters was shown in patients treated with glucocorticosteroids during HRT. A reduction in mean 24-hour serum estradiol levels in asthmatic women was noted, whereas cortisol and DHEAS serum concentrations were decreased in asthmatic patients treated with glucocorticosteroids compared with the control group, before HRT. HRT produced increases in the concentrations of estradiol, cortisol and DHEAS in serum. Significant positive correlations were noted between estradiol concentrations and small and medium bronchi tests. In conclusion, HRT in postmenopausal asthmatic women has a favorable influence on the course of asthma, reduces daily use of glucocorticosteroids and frequency of asthma exacerbations and normalizes serum concentrations of estradiol, cortisol and DHEAS, which were decreased before HRT.

Influence of pinealectomy and long-term melatonin administration on GH-IGF-I axis function in male rats.

BACKGROUND: A relationship between circadian GH-IGF-I axis activity and pineal gland function in rats is not sufficiently elucidated, particularly in the aspect of melatonin (MEL) participation with relation to a possible mechanism of these dependencies. OBJECTIVE: Influence of pinealectomy and long-term MEL administration on circadian GH-IGF-I axis function in male rats was evaluated. An attempt was also made to determine whether the effect of exogenous MEL is dependent on the pineal gland presence. METHODS: Studies were performed in 192 sexually mature male Wistar rats, which were subjected to pinealectomy or sham operation. In half of the animals from each group MEL (Sigma, USA) in dose of 50 microg/ 100g b.m. was administrated intraperitoneally (daily between 5 and 6 pm during a 4-week period). Blood for RIA assays of MEL, GH and IGF-I concentrations was collected every 3 hours during a day-beginning at 8 am (rats killed by decapitation). RESULTS: Significant influence of pinealectomy and exogenous MEL on a daily profile of endogenous MEL in rats was confirmed. Distinct, dependent on the time of the day anomalies in circadian oscillations of GH and IGF-I showing positive correlation with changes in endogenous MEL concentrations were also shown. GH rhythm was suppressed in a group of rats with removed pineal gland; after pinealectomy distinct decrease and after MEL use - distinct increase of GH and IGF-I concentrations during the day were observed. It had influenced mean daily concentrations and values of amplitude of circadian GH and IGF-I oscillations in all studied groups of animals. In rats with preserved pineal gland the effect of exogenous MEL action was more intensified. CONCLUSIONS: Pineal gland can influence circadian function of GH-IGF-I axis, and in mechanism of this dependence, changes in endogenous MEL concentrations seem to play an important role. Administration of MEL in rats after pinealectomy only partly prevents changes of GH-IGF-I axis function caused by gland removal, which can indicate participation of other pineal gland substances in generating disturbances. Influence of exogenous MEL on GH-IGF-I axis function during the day is dependent on the presence of pineal gland, which can be connected with indirect and/or direct influence of administrated hormone on this gland.

Influence of adjuvant chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil on plasma melatonin and chosen hormones in breast cancer premenopausal patients.

OBJECTIVE: To investigate the effect of chemotherapy on levels of melatonin in patients with breast cancer. BACKGROUND: In light of reports on the possible oncostatic role of melatonin in breast cancer patients, it is essential to know the influence of adjuvant chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) on plasma melatonin concentration as well as on its contributing factors, e.g. current hormonal state of the organism. The combination therapy is one of the oldest, safest and most commonly prescribed adjuvant treatments. METHOD: Twenty-four breast cancer patients on CMF chemotherapy were studied along with a control group of 16 healthy pre-menopausal women. RESULTS: Plasma melatonin concentration (determined by RIA method) in breast cancer patients prior to treatment did not differ significantly from that of healthy women, but it was significantly increased after the initial cycle of CMF, and significantly increased as compared to a group of healthy women. We did not notice any significant interactions between plasma melatonin and growth hormone, prolactin, estradiol, progesterone, cortisol and met-enkephalin concentrations in all studied groups. CONCLUSION: The possible oncostatic action of melatonin warrants further investigation to elucidate whether the induced increase of blood melatonin concentration is essential to successful CMF chemotherapy.

[Function of the growth hormone axis--insulin-like growth factors--insulin-like growth factor binding proteins in patients with chronic liver diseases]. / Czynnosc osi hormon wzrostu--insulinopodobne czynniki wzrostowe--bialka wiazace insulinopodobne czynniki wzrostowe u chorych z przewleklym uszkodzeniem czynnosci watroby.

Up to date have demonstrated that more and more young people are affected by chronic liver diseased. There is a close relationship between the liver and endocrine system as far as hormone inactivation, synthesis of growth factors, proteins binding hormones and proteins binding growth factors in the liver are related. Impairment of the hepatocyte function may lead to disturbed homeostasis of the endocrine system. Current opinions on growth hormone (GH)--insulin-like growth factors (IGFs)--insulin-like growth factors binding proteins (IGFBPs) axis activity in men with chronic liver diseases are presented.

Assessment of the relationship between dynamic pattern of nighttime levels of melatonin and chosen biochemical markers of bone metabolism in a rat model of postmenopausal osteoporosis.

BACKGROUND: Lately, there have been suggestions that bone mass changes occurring in postmenopausal women may remain related to melatonin. OBJECTIVE: To assess the relationship between the dynamic pattern of nighttime levels of melatonin and chosen biochemical markers of bone metabolism in ovariectomized rats--a model of postmenopausal osteoporosis. METHODS: Mature Wistar female rats were either ovariectomozed or underwent a sham operation. Following this they were killed at 02:00AM at weekly intervals for 8 weeks after surgery. Serum levels of MEL at death related to the chosen biochemical markers of bone formation (alkaline phosphatase--ALP; carboxyterminal propeptide of type I procollagen--PICP, both in serum) and resorption (cross-linked carboxyterminal telopeptide of type I collagen--ICTP in serum; hydroxyproline--HYP and total calcium--Ca, both excreted in urine). RESULTS: In all ovariectomized rats changes of examined indices of bone tissue metabolism were found to be dynamic and statistically significant relative to the control group; however the changes were more pronounced regarding resorption markers. Following ovariectomy, the increase in ALP and PICP values was found to begin at the 4th and the 1st week, while that in ICTP, HYP and Ca at the 2nd, the 1st and the 1st week, respectively. The ALP and PICP values remained at a similar level until the end of observation, whereas ICTP, HYP and Ca gradually decreased. MEL levels were decreased during the 2nd week following surgery and slightly increased 2 weeks later. The serum MEL levels in the ovariectomized group were significantly and negatively correlated with serum ICTP and both urinary HYP and Ca levels. CONCLUSION: Our findings in rats seem to corroborate the concept of secondary changes in MEL levels co-participating in the development of bone mass changes characteristic for postmenopausal osteoporosis.