Elżbieta Świętochowska

Blood serum levels of vascular cell adhesion molecule (sVCAM-1), intercellular adhesion molecule (sICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) in diabetic retinopathy

BackgroundInteraction between cells via intimate cell-cell contact is facilitated by a cell surface molecules, termed adhesion molecules. The aim of the study was to evaluate the blood serum concentration of soluble forms of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) in patients with type 1 diabetes mellitus without and with diabetic retinopathy.Materials and methodsThe study was performed in 75 patients with type 1 diabetes mellitus, 35 without retinopathy (group 1) and 40 with retinopathy (group 2). Soluble forms of VCAM-1, ICAM-1 and ELAM-1 were determined by enzyme-linked immunosorbent assay (ELISA).ResultsThe serum concentration of sICAM-1 and sELAM-1 were significantly elevated and the concentration sVCAM-1 was elevated but not significantly in diabetic patients when compared with control subjects. There was a significant difference in VCAM-1 concentrations between the control group and group 2 (965.9 ± 229.0 vs. 1283.7 ± 387.6 ng/ml, p < 0.05) and between group 1 and group 2 (1115.0 ± 285.5 vs. 1283.7 ± 387.6 ng/ml, p < 0.05). There were significant differences in sICAM-1 concentrations between the control group and group 1 (p < 0.05) and between the control group and group 2 (p < 0.05). Where was no significant difference in sICAM-1 concentration between group 1 and 2 (405.2 ± 135.9 vs. 443.1 ± 112.7 ng/ml, p = 0.08). ELAM-1 concentration was significantly elevated in group 2 (120.5 ± 49.3 ng/ml) when compared with the control group (51.7 ± 18.1 ng/ml, p < 0.005) and with group 1 (81.2 ± 27.7 ng/ml, p < 0.05).ConclusionsThe correlations found between sVCAM-1, sICAM-1 and sELAM-1 and the presence of retinopathy suggest that cellular adhesion and neovascularization may be linked processes.

Therapeutic effect of aripiprazole in chronic schizophrenia is accompanied by anti-inflammatory activity

BACKGROUND Weight gain and metabolic abnormalities occur in chronic schizophrenia patients treated with atypical antipsychotics. The purpose of the study was to evaluate changes in serum levels of C-reactive protein (CRP), insulin and cytokines (IL-6, TNF-α, IL-1β, IFN-γ, sTNF-R1, IL-12, IL-23, IL-1Ra, TGF-β1, IL-4, and IL-10) after switching to aripiprazole. METHODS Cytokine, hsCRP and insulin measurements were performed in patients (n=17) on day 0 and day 28 of the study using standard ELISA assays. The psychopathological status was assessed using PANSS. WC and BMI were measured and calculated, respectively. RESULTS We observed high clinical efficacy in aripiprazole linked to a 2.7% weight loss. There were statistically significant reductions in PANSS scores and body parameters (p<0.001). After 28 days we detected a significant reduction in hsCRP (p<0.001), insulin (p<0.001), IL-1β, IL-6, TNF-α, sTNF-R1, IL-12, IL-23, IL-1Ra, TGF-β1, IL-4 (p<0.001), IFN-γ (p<0.05) and a significant elevation of IL-10 (p<0.001). There was a significant negative correlation between IL-10 levels and PANSS positive, negative and total scores after the study (p=0.022, p=0.003, p=0.008, respectively). CONCLUSIONS Aripiprazole limits inflammatory processes by enhancing anti-inflammatory signaling. Aripiprazole also reduces the risk of metabolic abnormalities.

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.

Association between chemotherapy and plasma adipokines in patients with colorectal cancer.

BACKGROUND A link between chemotherapy, the serum level of selected adipokines and clinical outcome in colorectal patients was investigated. METHODS Leptin, adiponectin, resistin, visfatin and insulin were measured by ELISA in colorectal cancer patients before and 3 months after the administration of cancer therapy. From August 2012 to August 2013, 34 patients with pathologically documented advanced colorectal cancer (T3/T4 with metastases or nodal status up to N3) and measurable metastatic disease, who required palliative chemotherapy based on the combination of 5-fluorouracil, oxaliplatin and irinotecan, were prospectively recruited in this study. Patients previously underwent curative surgical tumour resection, but the disease was disseminated (metastases in the liver and/or lungs) at the time of admission to the hospital. RESULTS Of the 34 patients in this study, 5 accomplished a chemotherapy course with partial response (PR), 23 with SD (stabilisation) and 6 with progression (PD). For further study, only patients with good prognostic outcomes (i.e., PR and SD patients) were included. The mean level of leptin before chemotherapy was 26.39 ± 9.53 ng/ml. After six courses of cancer treatment, the leptin level increased by 118-57.44 ± 27.72 ng/ml (p<0.001). Additionally, the adiponectin level increased considerably (47%) from 9.89 ± 3.96 ng/ml to 14.51 ± 7.79 ng/ml (p<0.001). In contrast to leptin and adiponectin, the resistin and visfatin levels decreased significantly from 7.24 ± 1.17 and 1.98 ± 0.44 to 6.36 ± 1.36 and 1.48 ± 0.34 ng/ml (p<0.001), respectively. Insulin also declined remarkably from 16.20 ± 1.96 to 12.87 ± 1.80 (p<0.001). There were no significant differences the between male and female patients regarding age, BMI, and leptin, adiponectin, resistin, visfatin and insulin serum levels. CONCLUSIONS The results of the present study are relevant because we found that chemotherapy in colorectal cancer patients, in addition to its beneficial clinical impact on the course of disease, positively affects cytokine production and release (increases the anti-inflammatory adiponectin and decreases visfatin and resistin, which are proangiogenic and promote cancer cell proliferation). The restoration of adequate adipose tissue function is essential for patients to achieve a good survival prognosis.

Is positive correlation between cortisol and met-enkephalin concentration in blood of women with breast cancer a reaction to stress before chemotherapy administration?

The role of stress in the course of neoplastic diseases has been emphasised over the past few years. Organism defence in form of increased release of hormones, corticosteroids and endogenous opioids should be assessed as a particular form of adaptation. Interactions between stress hormones and others which may influence the growth of breast cancer cells are possible. In this study, the concentration of cortisol and met-enkephalin vis-à-vis growth hormone, insulin-like growth factor-I, prolactin, estradiol, progesterone and melatonin in blood of women with breast cancer before the first cycle of supplementary chemotherapy was compared to that of healthy women. In a group of patients with breast cancer, before the first cycle of chemotherapy, high hypercortisolemia and positive correlation between cortisol and met-enkephalin was observed which may be a result of stress at the beginning of such treatment. A negative correlation between prolactin and met-enkephalin in this group can indirectly testify to essential participation of endogenous opioids in hormonal regulation and can be a response to stress caused by beginning chemotherapy.

Association between omentin-1, bone metabolism markers, and cytokines of the RANKL/RANK/OPG system in girls with anorexia nervosa

INTRODUCTION Omentin-1, secreted by visceral adipose tissue, has been indicated in the regulation of bone metabolism in girls with anorexia nervosa (AN). The aim of the study was to evaluate the relationship between omentin-1 and bone metabolism in girls with AN as well as the potential involvement of OPG and RANKL in this relationship. MATERIAL AND METHODS Serum omentin-1, OC, CTx, OPG, and sRANKL were determined by ELISA in 49 girls with AN and in 30 healthy controls, aged 13 to 17 years. RESULTS Girls with AN exhibited significant reduction in body weight, BMI, and Cole index as well as a significant increase in serum omentin-1 levels, compared to healthy participants. These changes were associated with a significant decrease in serum OC and CTx levels and a significant increase in OPG and sRANKL while the OC/CTx and OPG/sRANKL ratios were significantly decreased. BMI and the Cole index correlated negatively and significantly with omentin-1 levels, positively with CTx levels and the OC/CTx ratio in the control group (C), girls with AN, and all study participants (C + AN). Girls with AN showed a significant negative correlation between BMI, the Cole index, and OPG levels. The combined group (C + AN) showed a significant positive correlation between BMI, the Cole index, and the OPG/sRANKL ratio. Omentin-1 levels correlated negatively and significantly with OC and CTx levels as well as with the OC/CTx and OPG/sRANKL ratios in the C, AN, and C + AN groups. CONCLUSIONS The relationship between omentin-1, bone markers, and the OC/CTx and OPG/sRANKL ratios observed in girls with AN indicates the involvement of this adipokine in the regulation of dynamic balance between bone formation and resorption processes. Omentin-1 might exert a negative effect on bone remodelling in girls with AN by inhibiting both bone formation and resorption. The OPG/sRANKL system plays an important role in the latter.

TGF-β1, bone metabolism, osteoprotegerin, and soluble receptor activator of nuclear factor-kB ligand in girls with anorexia nervosa

INTRODUCTION Numerous investigations, and especially in vitro studies, indicate that TGF-β1 may act as an important regulator of bone remodelling. Thus, it could be expected that disturbances of this cytokine production observed by several researchers might play a role in the mechanism leading to the development of osteoporosis in girls with anorexia nervosa (AN). The aim of the study was to determine whether 1) girls with AN exhibited a relationship between TGF-β1 and bone metabolism (as assessed based on serum OC and CTx concentrations) and 2) whether OPG and sRANKL might modify the possible relationship between TGF-β1 and bone metabolism. MATERIAL AND METHODS Serum concentrations of TGF-β, OC, CTx, OPG, and its soluble ligand sRANKL were determined by ELISA in 60 girls with AN and in 20 healthy controls (C). All study participants were aged 13 to 17 years. RESULTS Body weight, BMI, BMI-SDS and the Cole index, serum TGF-β1, OC, CTx, and the OPG/sRANKL ratio were significantly reduced, while OPG and sRANKL levels were significantly increased, in girls with AN compared to healthy participants. BMI and the Cole index correlated negatively and significantly with serum CTx and OPG (AN group) or CTx only (groups C and C + AN). Girls with AN showed a positive and significant correlation between the Cole index and serum TGF-β1. The combination group (C + AN) showed a positive and significant correlation between BMI, the Cole index, and the OPG/sRANKL ratio and TGF-β1 concentration, while TGF-β1 correlated positively and significantly with OC concentrations and the OPG/sRANKL ratio. The Cole index and BMI were identified to be significant and independent predictors of CTx (C, AN, and C+AN groups) and OPG (AN group); the Cole index, BMI, and TGF-β1 independently predicted the OPG/sRANKL ratio (C, AN, and C + AN groups); TGF-β1 was found to be an independent predictor of OC (C + AN group). CONCLUSIONS Changes in bone markers, OPG, and/or OPG/sRANKL ratio observed in girls with AN are associated with changes in serum TGF-β1 concentrations. TGF-β1 suppression in girls with AN might lead to disturbances in the relationship between bone metabolism and the OPG/sRANKL system, which, in turn, might compromise the mechanism compensating for bone remodelling disturbances. (Endokrynol Pol 2016; 67 (5): 493-500).

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.

Role of omentin and chemerin in metabolic syndrome and tumor diseases.

For the past few years adipokines have been a center of appreciation and interest. They are biologically active molecules causing pleiotropic effects. They assist in angiogenesis, adipose tissue metabolism and inflammation, and modulate tissue sensitivity for insulin. Adipokines are produced in adipose tissue, so an abnormal quantity of this tissue leads to impaired levels of these factors. Because of their different concentrations in various conditions, it would be plausible to use them as markers for individual conditions, such as obesity, type 2 diabetes mellitus, pancreatitis, gastric cancer, lung cancer or colon cancer. Such adipokines as leptin, resistin, visfatin, adiponectin, and apelin are subjects of research. In our study we focused on the function and significance of chemerin and omentin in metabolic syndrome and cancers. In type 2 diabetes mellitus, both chemerin and omentin enhance the body sensitivity to insulin, which results in increased glucose uptake. However, in diabetic patients, serum concentration of omentin decreases, while that of chemerin increases. A similar trend was observed in obese patients. As a cancer marker, chemerin turned out to be helpful in diagnosis of gastric cancer, mesothelioma, and polycystic ovary syndrome, which can lead to endometrial cancer. An elevated concentration of omentin was noted in colon cancer, and increased expression of the omentin gene was reported in nasal polyps and mesothelioma.

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.