Assessment of the relationship between melatonin, hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes, and osteoprotegerin and its ligand sRANKL in girls with anorexia nervosa.

BACKGROUND: It has been suggested that disturbances in melatonin (MEL) secretion might play a role in osteoporosis development in females with anorexia nervosa (AN). It might be hypothesized that changes in the levels of hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes might mediate the potential relationship between MEL and bone tissue. AIM: We investigated whether a relationship existed between MEL and LH, FSH-E2, TSH-FT3, FT4 and ACTH-cortisol axes in girls with AN. We also aimed to establish whether such a relationship might adversely affect the balance of the OPG/sRANKL system. MATERIAL/METHODS: Eighty-six girls with AN and 21 healthy subjects aged 12.6 to 18.2 years participated in the study. The serum levels of hormones as well as OPG and sRANKL were determined by radioimmunoassay (RIA), immunoradiometric assay (IRMA) or enzyme-linked immunosorbent assay (ELISA) methods. DISCUSSION: Our study participants with AN showed a significant reduction in body mass and body mass index (BMI), a decrease in LH, E2 and FT3 concentrations, increased MEL concentration at 02.00 hours and increased amplitude between its nocturnal and morning levels (Δ MEL2.00/9.00) as well as an increase in cortisol concentration. These changes were associated with a significant increase of OPG and sRANKL levels and a decrease in the OPG/sRANKL ratio. BMI values correlated positively with LH, FSH, E2, FT3 and the OPG/sRANKL ratio while the correlation between BMI and cortisol was negative. Δ MEL2.00/9.00 correlated positively with cortisol and negatively with LH, FSH, E2, FT3 concentrations and the OPG/sRANKL ratio. A positive correlation was observed between LH, E2 and the OPG/sRANKL ratio as well as between cortisol and sRANKL while the correlation between LH and OPG as well as between cortisol and the OPG/sRANKL ratio was negative. E2 and LH were shown to be significant and independent predictors of Δ MEL2.00/9.00. LH turned out to be a significant and independent predictor of OPG, cortisol and FT3 were significant and independent predictors of sRANKL, while LH, E2, Δ MEL2.00/9.00 and FT3 were significant predictors of the OPG/sRANKL ratio. CONCLUSIONS: Alterations in OPG and sRANKL levels observed in girls with AN are associated with changes in nocturnal MEL secretion, the circadian rhythm of MEL, and LH, E2, FT3 and cortisol levels. Dysregulation of the relationships between MEL and LH, E2, FT3 and cortisol found in girls with AN might affect the balance of the OPG/sRANKL system. Low values of the OPG/sRANKL ratio associated with high OPG and sRANKL levels suggest some defect in the mechanism compensating for bone remodeling disturbances.

Melatonin, the RANKL/RANK/OPG system, and bone metabolism in girls with anorexia nervosa.

INTRODUCTION: Young women and girls with anorexia nervosa (AN) suffer from abnormalities in melatonin (MEL) secretion, especially in the nocturnal phase. This is paralleled by a considerable bone mass loss and abnormalities of bone metabolism. As melatonin has been implicated in playing a role in inducing osteoporosis and that the effect could be mediated by the RANKL/RANK/OPG system, we decided to investigate the potential associations between MEL and bone status in girls with AN. AIM: To evaluate the relationship between MEL, bone metabolism (as assessed by serum levels of bone turnover markers [OC and CTx]), and OPG and sRANKL in girls with AN. MATERIAL AND METHODS: A total of 57 girls with AN and 13 healthy girls, between 13 and 18 years of age, were enrolled in the study, and we evaluated BMI, fasting levels of OC, CTx, OPG and sRANKL, and levels of MEL (fasting levels and the levels at 2 a.m., at which time the secretion of the hormone peaks). RESULTS: We found a significantly increased mean serum level of MEL at 2 a.m. and an increased amplitude between nocturnal and morning levels of the hormone in girls with AN. We also showed a considerable suppression of the mean OC and CTx levels and an increase in serum OPG and RANKL levels paralleled by a significantly reduced OPG/sRANKL ratio. The changes in the MEL levels at 2 a.m. showed a statistically significant negative correlation with levels of the bone markers and a positive correlation with sRANKL. The changes in the amplitude between the nocturnal and morning levels of MEL showed a negative correlation with CTx levels and the OPG/sRANKL ratio. CONCLUSIONS: Our results indicate that the abnormalities of bone metabolism in girls with AN are associated with changes in the nocturnal levels of MEL with RANKL appearing to play an important role in this mechanism. The increased amplitude between the nocturnal and morning levels of MEL may adversely affect the bone tissue in girls with AN with the effect most likely resulting from influences on the OPG/RANKL balance. (Pol J Endocrinol 2010; 61 (1): 117-123).

The influence of pinealectomy and melatonin administration on the dynamic pattern of biochemical markers of bone metabolism in experimental osteoporosis in the rat.

BACKGROUND AND OBJECTIVES: There have been suggestions in literature that characteristic changes of bone mass in osteoporosis may be related to the melatonin (Mel): The aim of this study was to demonstrate whether pinealectomy and Mel administration can affect postmenopausal osteoporosis processes induced in female rats by way of ovariectomy. METHODS: The study included 198 animals; 6 remained intact (0), 96 were ovariectomized (Ox), and the remaining ones underwent a sham operation (SOx). Two weeks after surgery, the rats were divided into eight groups: 1) SOx + SPx, 2) SOx + SPx + Mel, 3) Ox + SPx, 4) Ox + SPx + Mel, 5) SOx + Px, 6) SOx + Px + Mel, 7) Ox + Px, 8) Ox + Px + Mel. Animals from the 5th, 6th, 7th and 8th groups were pinealectomized (Px) while the remaining ones underwent a sham operation (SPx). Two weeks after surgery Mel (50microg/100g of bm) were administered intraperitoneally in rats in the 2nd, 4th, 6th and 8th groups while the remaining animals were administered with solvent only (5% solution of ethyl alcohol in physiological saline). Rats were administered the Mel solution or the solvent daily between 5 and 6 pm during a 4-week period. At the appropriate time, i.e. prior to surgery (group 0) and after 6, 12, 18 and 24 weeks from Px or SPx (time subgroups a, b, c and d) the animals were placed separately in metabolic cages (from 6.30 until 9.30 am) in order to collect urine aliquots for HYP and Ca determinations. The blood for the assay of ALP, PICP and ICTP was collected within the next 24 hours at 8 am (rats killed by decapitation). RESULTS: The study has shown that pinealectomy had inducing, while exogenous Mel suppressing effect upon the level of investigated markers of bone metabolism; these changes were more pronounced in ovariectomized rats. Administration of Mel only partially levelled changes of bone metabolism caused by pinealectomy. In rats with preserved pineal gland effect of Mel on bone turnover markers was less pronounced. After discontinuing administration of Mel distinct tendency to increase studied biochemical markers of bone metabolism was shown. CONCLUSION: Our findings suggest that Mel is an important modulator of experimental osteoporosis processes induced in female rats by way of ovariectomy.

[Influence of dithranol therapy on clinical status and serum calcitonin concentrations in patients with common psoriasis]. / Wplyw leczenia cignolina na obraz kliniczny i wartosci stezenia kalcytoniny w surowicy u chorych na luszczyce.

The aim of this work was to study the effects of external dithranol therapy of psoriatic patients on the clinical status and serum calcitonin concentrations. This was done on 19 patients with common psoriasis using Cignoderm in the short contact therapy. Calcitonin concentration in serum samples was determined before and after a 14-day therapy. Results obtained before were compared with concentrations after dithranol treatment and with results in control group. Serum TSH was also measured in serum samples from both groups at the very beginning time. The determinations showed statistically significant lower serum TSH level in psoriatic patients before therapy vs. control and significant, negative correlation with calcitonin concentration in those patients. After a 14-day dithranol therapy a significant calcitonin concentration decrease as well as clinical effects were observed in the investigated group.

[Circadian rhythm of melatonin in patients with hypertension]. / Rytm dobowy melatoniny u chorych z nadcisnieniem samoistnym.

Few reports, especially experimental ones indicate cause-effect connection between melatonin (Mel) and blood pressure. The aim of the study was to assess connection between a daily profile of Mel concentration in saliva and 24-hour cycle of blood pressure in 22 patients with moderate hypertension (12 men, 10 women), 20 patients with severe hypertension (9 men, 11 women) and 25 healthy subjects with normal blood pressure (13 men, 12 women). The age of studied subjects oscillated between 37 and 46 years. Concentrations of Mel were assessed in saliva collected during the day with intervals of 3 hours with the use of RIA method. Blood pressure assessment was done at the same time. A significant decrease of mesor's value and amplitude of Mel rhythm without essential changes in acrophase's value were observed in men and women with severe hypertension. Mean concentrations of Mel in saliva were significantly decreased from 8 pm to 5 am. Significant, negative correlation between nighttime Mel concentrations in saliva and both systolic and diastolic blood pressure was shown in patients with moderate and severe hypertension. Correlation coefficients values were in general higher in patients with severe hypertension. Results of our studies seem to confirm the conception that decreased Mel secretion can be one of the causes of hypertension.

[Blood concentration of homocysteine, vitamin B (12), and folic acid in patients with exudative age related macular degeneration]. / Stezenie homocysteiny, witaminy B12 oraz kwasu foliowego w surowicy krwi chorych z wysiekowa postacia zwyrodnienia siatkówki zwiazanego z wiekiem.

PURPOSE: Recent studies have shown a relationship between elevated levels of Hcy and vascular disease including cerebrovascular accidents and myocardial infarctions. Elevated Hcy plasma is considered as an independent risk factor for atherosclerosis and trombosis. MATERIAL AND METHODS: This study included 30 patients with diagnosed exudative form of AMD. We evaluated plasma homocysteine levels, by high performance liquid chromatography and red blood cell folic acid, plasma folic acid and plasma vitamin B12 concentration by radioassay method. RESULTS: The plasma concentration of Hcy in AMD patients had significantly increased when compared with control group. We found not significant decrease of the plasma vitamin B12, red blood cell folic acid and plasma folic acid concentration in AMD group, when compared with the control group.

[The apolipoprotein E polymorphism in age related macular degeneration]. / Polimorfizm apolipoproteiny E u chorych ze zwyrodnieniem siatkówek zwiazanym z wiekiem

PURPOSE: The aim of the study was to evaluate association of apo E polymorphism with AMD. MATERIAL AND METHODS: The included participants of this study were: 45 patients aged 60 to 71 (mean age 66.2 +/- 3.6), treated because of AMD. Genomic DNA was extracted from peripheral blood leukocytes, and the subsequent analysis of apo E genotypes was performed by polymerase chain reaction (PCR). RESULTS: In our study the allele frequencies in control group of patients weresimilar to the apo E allele distribution presented by other authors in Caucasian populations. We have not found significant differences between AMD and control group patients for apo (E) genotype or allele frequency. Compared with control group (epsilon4 -13.6%, epsilon2 -2.27%), the frequency of epsilon4 allele was not significantly decreased (11.11%) and epsilon2 allele frequency (7.77%) increased in AMD patients. CONCLUSIONS: The results of our present study have not indicate a significant association between AMD development and apo E allele frequency, in our studied population of AMD patients.

RANKL/RANK/OPG system and bone status in females with anorexia nervosa.

Minimal data exist concerning the relationship between osteokines of the RANKL/RANK/OPG system, especially RANKL, and bone status in females with anorexia nervosa (AN). For this reason we investigated the relationship between bone metabolism (as assessed based on serum levels of OC and CTx), and OPG and sRANKL concentrations in females with AN. Ninety-one female patients with AN and 29 healthy female subjects aged 13 to 18 years of age participated in the study. Serum OC, CTx, OPG and sRANKL were measured by ELISA. The female patients with AN demonstrated an essential suppression of OC and CTx, increased OPG and sRANKL levels, and a reduced OPG/sRANKL ratio. OC, CTx and the OPG/sRANKL ratio correlated positively with body mass and BMI in these patients, whereas in the case of OPG and sRANKL the relationship was negative. A significant positive correlation was observed between OPG and sRANKL and also between bone markers and the OPG/sRANKL ratio, and negative between CTx and sRANKL. In female patients with AN, the OPG/RANKL ratio was a significant and independent predictor of osteocalcin, a bone formation marker - OC (R(2)=0.065, p=0.012) whereas the OPG/sRANKL ratio and BMI were significant and independent predictors of a bone resorption marker - CTx (R(2)=0.095; p=0.012). In conclusion, the body mass, BMI values, and bone markers suppression observed in female patients with AN might be associated with an increase in OPG and sRANKL levels and a significant decrease of the OPG/sRANKL ratio. Although higher OPG levels may compensate for excessive bone resorption in female patients with AN, the lower OPG/sRANKL ratio seems to indicate that some inadequacies exist regarding this compensation effect, which might contribute to low bone density in these patients. The OPG/sRANKL ratio might prove a more relevant marker to predict bone metabolism in female patients with AN than sRANKL and/or OPG alone.