Joanna Oświęcimska

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.

Assessment of Serum Apelin Levels in Girls with Anorexia Nervosa

CONTEXT Pilot studies in rats have suggested that apelin (APE) is involved in the control of appetite and food intake. APE is secreted in the organs involved in the control of hunger and satiety: the stomach, hypothalamus, and fat tissue. Anorexia nervosa (AN) is an eating disorder that represents a good biological model of chronic fat tissue atrophy in humans. To date, there are no reports of APE expression in the fat tissue and its circulating concentrations in patients with AN. OBJECTIVE Our objective was to assess serum APE concentrations in girls with AN. DESIGN, PARTICIPANTS, AND SETTING APE-36 and APE-12 serum concentrations were evaluated in 87 Polish girls with restrictive AN, in 61 healthy (H) controls, 17 girls with no otherwise specified eating disorders (NOS), and 30 girls with simple obesity (OB). RESULTS Mean serum APE-36 and APE-12 concentrations in patients with AN and NOS were significantly lower than in the H and OB groups. However, no differences between AN, H, and NOS groups were observed when APE concentrations were calculated per body mass index (BMI). In participants with normal BMI, serum APE-36 (r = 0.35) and APE-12 (r = 0.37) concentrations correlated positively with BMI. CONCLUSIONS We conclude that compared with H controls, serum APE-36 and APE-12 concentrations decreased as a result of fat tissue depletion in patients with AN. Conversely, obese adolescents had elevated APE-36 and APE-12 due to excessive fat mass as well as increased APE production in adipose tissue.

New insights into the pathogenesis and treatment of irritable bowel syndrome

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders (FGID), characterized by abdominal pain and a change in stool form that cannot be explained by structural abnormalities. Its prevalence ranges from 9 to 23% of the worldwide population. The pathophysiology of IBS is diverse and not well understood. Biopsychosocial concept assumes that the disease is a product of psychosocial factors and altered at multiple levels of gut physiology interactions. Some aetiological factors have been identified, yet. One of the most important is the disruption of brain-gut mutual communication that leads to visceral hypersensitivity. Also genetic and epigenetic factors are involved. Chronic stress may predispose to IBS as well as exacerbate its symptoms. Both quantitative and qualitative disorders of the gut microbiota are observed. There is also a relationship between the IBS symptoms and the intake of a specific type of food products. In the diarrhoea type of IBS the role of previous gastrointestinal infection is demonstrated. Recent studies have suggested that visceral hypersensitivity in patients with IBS may be secondary to the activation of the immune cells and low-grade inflammation. Clinical symptoms of IBS include abdominal pain and change in bowel habits as well as somatic and psychiatric comorbidities. IBS is diagnosed on the basis of Rome Diagnostic Criteria. Recently, their newest version (Rome IV) has been presented. The aim of this review is to summarize the past decade progress in IBS diagnosis, main pathophysiological aspects and therapeutic management strategy.

Dehydroepiandrosterone sulfate, osteoprotegerin and its soluble ligand sRANKL and bone metabolism in girls with anorexia nervosa.

BACKGROUND Only scarce data exist concerning the relationship between dehydroepiandrosterone (DHEA) and/or its sulfate form DHEAS and bone status in adolescents with anorexia nervosa (AN). AIM We investigated whether a relationship existed between DHEAS and bone metabolism (as assessed based on serum osteocalcin [OC], and collagen type I cross-linked carboxy-terminal telopeptide [CTx]). We also aimed to establish whether the above mentioned relationship might be affected by osteoprotegerin (OPG) and its soluble ligand sRANKL. MATERIAL/METHODS Fifty-six female patients with AN and 21 healthy female subjects aged 13 to 16 years participated in the study. Serum DHEAS, OC, CTx, OPG and sRANKL were measured by ELISA. RESULTS Our female patients with AN demonstrated significant suppression of DHEAS and bone markers, an increase in OPG and sRANKL levels, and a reduction of the OPG/sRANKL ratio. DHEAS, CTx and the OPG/sRANKL ratio correlated positively with BMI. A significant positive correlation was also observed between DHEAS and the OPG/sRANKL ratio, OC and the OPG/sRANKL ratio, and CTx and sRANKL. The correlation was negative in the case of DHEAS and CTx, DHEAS and sRANKL, CTx and the OPG/sRANKL ratio, and sRANKL and the OPG/sRANKL ratio. DISCUSSION/CONCLUSIONS DHEAS suppression in girls with anorexia nervosa was associated with a decrease in the levels of bone markers, an increase in OPG and sRANKL concentrations and a significant decrease in the OPG/sRANKL ratio. DHEAS suppression in girls with anorexia nervosa might have a harmful effect on their bone tissue, probably via a shift in the OPG/RANKL ratio toward a functional excess of sRANKL.

Assessment of serum visfatin levels in girls with anorexia nervosa.

Objective  Visfatin (VISF) is a recently described peptide regulating the process of adipocyte differentiation. Only one pilot study of VISF expression in the fat tissue and its circulating concentrations in a small group of patients with anorexia nervosa (AN) have been published, yet.

Bone metabolism, osteoprotegerin, receptor activator of nuclear factor-kB ligand and selected adipose tissue hormones in girls with anorexia nervosa

INTRODUCTION The aim of this study was to determine whether girls with anorexia nervosa (AN) exhibited any relationships between serum levels of LP, ADIPO, RES, VISF, APE-36, APE-12, and bone markers, OPG and sRANKL. MATERIAL AND METHODS Serum levels of selected adipose tissue hormones, OC, CTx, OPG and sRANKL were assessed using ELISA in 86 study participants suffering from AN and 21 healthy controls, all aged 13 to 18 years. RESULTS Girls with AN showed a significant reduction in body mass, BMI, serum concentrations of LP, RES, VISF, APE-36, APE-12, OC, CTx and increased ADIPO concentration. These changes were associated with significant increases in OPG and sRANKL and a decrease in the OPG/sRANKL ratio. Significant positive correlations were revealed between BMI and LP, APE-36, CTx, OPG/sRANKL ratio; OC and VISF; OPG and ADIPO; OPG/sRANKL ratio and LP, APE-36, APE-12. Significant negative correlations were revealed between CTx, sRANKL and RES, APE-36; OPG and APE-36, APE-12; OPG/sRANKL ratio and ADIPO. VISF was shown to be an independent predictor of OC. APE-36 and RES turned out to be independent predictors of CTx, and sRANKL, APE-36 and ADIPO were independent predictors of OPG while APE-36, LP and ADIPO were independent predictors of the OPG/sRANKL ratio. CONCLUSIONS Changes in bone markers, OPG, sRANKL and/or the OPG/sRANKL ratio exhibited by girls with AN have been found to be associated with changes in the levels of the selected adipose tissue hormones. Abnormal relationships between bone metabolism and LP, ADIPO, RES, VISF and APE might adversely affect the balance of the OPG/sRANKL system and thus potentially compromise the mechanism which compensates for bone remodelling disturbances.

The effect of central noradrenergic system lesion on dopamine (DA) and serotonin (5-HT) synthesis rate following administration of 5-HT3 receptor ligands in chosen parts of the rat brain.

INTRODUCTION Since little has been known about the effect of the central noradrenergic system on the reactivity of serotonin 5-HT3 receptors, the aim of the current study was to find out whether this reactivity could be altered by chemical damage to the system in adult rats in early developmental stage. MATERIALS AND METHODS Adult male Wistar rats with central noradrenergic lesion induced by DSP-4 on day 1 and 3 of life were injected with analgesic model substance - morphine, serotoninergic 5-HT3 receptor agonist (1-phenylbiguanide, PBG), 5-HT3 receptor antagonist (ondansetron) or both compounds jointly followed by decarboxylase inhibitor of aromatic amino acids (NSD-1050). After 30 min following NSD-1050 injection, the animals were decapitated using a guillotine. Chosen cerebral structures were dissected, and the contents of 5-hydroxytryptofan (5-HTP) and l-dihydroxyphenylalanine (l-DOPA) were determined using high-pressure liquid chromatography with electrochemical detection (HPLC/ED). RESULTS Neither PBG nor morphine affected l-DOPA contents in the hippocampus in control rats; however, DSP-4 lesion caused a significant decrease in the synthesis rate of DA in this structure. Hippocampal contents of 5-HTP increased after morphine or PBG administration, and central noradrenergic lesion attenuated this effect. Morphine or PBG decreased cerebellar DA synthesis rate in control rats and DSP-4 lesion did not modify it. Cerebellar levels of 5-HTP increased after morphine or PBG challenge in control rats. DSP-4 lesion intensified the effect of morphine and attenuated that of PBG. Ondansetron abolished the effects mediated by PBG. We did not observe any impact of PBG or ondansetron on DA and 5-HT synthesis in the striatum. CONCLUSION Damage to the central noradrenergic system in rat newborns, through altered reactivity of central 5-HT3 receptors, results in permanent disorders in serotoninergic transmission in hippocampus and cerebellum as well as dopaminergic transmission in hippocampus, which may attenuate the activity of the descending pathways that derive from these structures.

Selected pro-inflammatory cytokines, bone metabolism, osteoprotegerin, and receptor activator of nuclear factor-kB ligand in girls with anorexia nervosa

INTRODUCTION It has been indicated that disturbances in the production of certain pro-inflammatory cytokines might contribute to the development of osteoporosis in girls with anorexia nervosa (AN). The aim of the study was to determine whether girls with AN exhibited a relationship between IL-1β, IL-6, TNF-α, bone turnover markers (OC and CTx), OPG, sRANKL, and the OPG/sRANKL ratio. MATERIAL AND METHODS Serum IL-1β, IL-6, TNF-α, OC, CTx, OPG, and sRANKL were determined by ELISA in 59 girls with AN and in 17 healthy counterparts, aged 13 to 17 years. RESULTS Girls with AN showed significant reduction in body weight, BMI, BMI-SDS, and Cole index compared to the controls. These changes were associated with a significant increase in IL-1β, IL-6, TNF-α, OPG, and sRANKL concentrations and a decrease in bone markers and the OPG/sRANKL ratio. Significant negative correlations were found between BMI, the Cole index and CTx, OPG (girls with AN); between BMI and OC, CTx as well as the Cole index and CTx (the control group - C); between BMI, the Cole index and IL-β1, IL-6, TNF-α, CTx in all study participants (group AN+C). The combined group AN+C also exhibited positive correlation between BMI, the Cole index, and the OPG/sRANKL ratio. Girls with AN showed positive correlations between IL-1β, IL-6, and CTx as well as between TNF-α and sRANKL whereas the correlation between TNF-α and the OPG/sRANKL ratio was negative (IL-6 and IL-1β were identified to be independent predictors of CTx, TNF-α and IL-6 independently predicted sRANKL while TNF-α, IL-6, and IL-1β were independent predictors of the OPG/sRANKL ratio). The control participants exhibited negative correlations between IL-1β and OPG and positive correlations between IL-1β and sRANKL (IL-1β was found to be an independent predictor of OPG and sRANKL). In the AN+C group, IL-1β correlated negatively with OC and OPG and positively with sRANKL, while IL-6 and TNF-α positively correlated with CTx (IL-6 and TNF-α turned out to be independent predictors of CTx, IL-1β of OPG while IL-6, TNF-α, and IL-1β were independent predictors of sRANKL and the OPG/sRANKL ratio). CONCLUSIONS The relationship between the nutritional status and IL-1β, IL-6, and TNF-α concentrations as well as bone status indicators seems to indicate that abnormalities observed regarding the concentrations of pro-inflammatory cytokines and bone remodelling in girls with AN might result from malnutrition. Correlations between IL-1β, IL-6, TNF-α, bone markers, OPG, its ligand sRANKL, and/or the OPG/sRANKL ratio suggest potential involvement of these cytokines in the mechanism underlying the lack of the expected bone mineral density increase in adolescent girls.

Serum vaspin concentrations in girls with anorexia nervosa.

Abstract Background: Vaspin (VASP) is a protein detected in pre- and mature adipocytes, the production and secretion of which may be conditioned by nutrition status. VASP may also play a role in the regulation of food intake. Since to date, there are no available studies on serum vaspin concentrations in patients with anorexia nervosa (AN), the aim of our study is to assess serum vaspin concentrations in girls with AN in comparison to healthy subjects and determine its relationship with body weight, body masss index (BMI) and insulin. Methods: In this cross-sectional study vaspin serum concentrations were evaluated using a commercially available ELISA kit in 47 Polish girls hospitalized due to restrictive AN and 39 healthy controls (H). Results: The mean serum concentration of VASP in girls with AN was significantly higher than in the H group. These differences were also noted after adjustment for body masss index-standard deviation score (BMI-SDS), the homeostatic model assessment-insulin resistance (HOMA-IR) index and insulin levels. There were no statistically significant correlations between the serum concentrations of VASP and body mass, BMI, BMI-SDS, insulin and HOMA-IR in the AN or healthy group. Conclusions: Serum vaspin levels in lean subjects are regulated in different mechanisms than previously reported in obesity. It should be established if elevated serum vaspin levels in girls with AN may contribute to low food intake in these patients.

Elevated levels of exhaled nitric oxide in patients with anorexia nervosa

BackgroundNitric oxide (NO) is involved in eating behavior and inflammatory response. Moreover, there is evidence that NO production is altered in patients with anorexia nervosa (AN).AimTo assess whether the overproduction of NO in AN can affect NO level in exhaled air.Materials and methodsExhaled NO level was studied in 23 girls with AN and compared with that of healthy age- and gender-matched nonatopic controls.ResultsExhaled NO levels were significantly higher in girls with AN compared with healthy age-matched controls.ConclusionsIt appears that anorexia nervosa was accompanied by a higher level of exhaled NO, likely resulting from a systemic increase in NO production because of the severe catabolic state.