Relationship between Serum Sirtuin 1 and Growth Hormone/Insulin-like Growth Factor 1 Concentrations in Children with Growth Hormone Deficiency and Idiopathic Short Stature.

Sirtuin 1 (SIRT1) inhibits growth hormone (GH) intracellular signaling for the insulin-like growth factor 1 (IGF-1) synthesis via the janus kinase (JAK)/signal transducer and activator of transcription proteins (STATs) pathway. The aim of this study was to compare SIRT1 concentrations in children with GH deficiency (GHD) and so-called idiopathic short stature (ISS, non-GH deficient), in order to determine the possible impact of changes in serum SIRT1 concentrations on the GH-IGF-1 axis. The study group included 100 short-stature children: 38 with GHD and 62 with ISS (maxGH in two stimulation tests <10 and ≥10 ng/mL, respectively). The control group consisted of 47 healthy, normal-height children. For each child, the concentrations of SIRT1, IGF-1 and insulin-like growth factor-binding protein 3 (IGFBP-3) were determined and the IGF-1/IGFBP-3 molar ratio was calculated. The level of SIRT1 was significantly higher in both groups of short children than in the controls (p < 0.0001), but there were no differences between GHD and ISS (mean ± SD: 0.89 ± 0.45 for ISS; 1.24 ± 0, 86 for GHD; and 0.29 ± 0.21 for controls). A significant negative correlation was found between SIRT1 and height standard deviation score (SDS), IGF-1 and IGF-1/IGFBP-3, but not between SIRT1 and maxGH. Elevated SIRT1 levels may serve as one of the mechanisms through which the secretion of IGF-1 is reduced in children with short stature; however, further research is required to confirm this issue.

First trimester maternal sex steroids and the digit ratios of mothers and children.

BACKGROUND: It is thought that digit ratios (2D:4D) are a correlate of 1st trimester maternal and foetal sex steroids. Here we consider the relationship of 2D:4D to the former. METHOD: Digit lengths were directly measured with a calliper at infant age 13 months. Measures of T and E were obtained from mother's blood at 6-8 weeks, 10-11 weeks and 1st trimester means were calculated. RESULTS: There were 69 mother-infant pairs (33 boys). Sex differences in 2D:4D (boysboys) were found. For mothers of girls: there were negative relationships between 2D:4D and T at 6-8 weeks, 10-11 weeks and 1st trimester means. For infants: girls showed more correlations between 2D:4D and hormones than boys. For boys, there was one positive association between 2D:4D and E and two positive associations for E/T. For girls, 2D:4D was negatively related to T (four correlations) and positively related to E/T (four correlations). Considering associations in the total sample and controlling for sex, at 6-8 weeks right and left 2D:4D were positively related to E. At 10-11 weeks, right and left 2D:4D were negatively related to T. For 1st trimester means, 2D:4D's were positively related to E (right and left) and negatively related to T (right). CONCLUSION: Infant 2D:4D was correlated with first trimester maternal sex steroids, particularly at 10-11 weeks. The correlations were negative for T, and positive for E and E/T with weaker effects for male infants. The latter pattern may arise because in boys T produced by foetal testes masks the effect of maternal T.

The use of CA125, human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA), risk of malignancy index (RMI) and subjective assessment (SA) in preoperative diagnosing of ovarian tumors.

OBJECTIVES: To compare utility of CA125, human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA), risk of malignancy index (RMI) and subjective assessment (SA) in preoperative diagnosis of ovarian tumors. MATERIAL AND METHODS: Research was conducted among 456 patients qualified for surgery due to ovarian tumor. Preoperatively, CA125 and HE4 serum levels were estimated, and transvaginal ultrasound was performed. ROMA and RMI values and SA qualifications were obtained. Results were compared with pathomorphological findings. RESULTS: Receiver Operating Characteristic (ROC)-Area Under Curve (AUC) values for CA125, HE4, ROMA, RMI and SA in preoperative diagnosis of malignant lesions were 0.819, 0.909, 0.911, 0.895 and 0.895, respectively. Combinations of biochemical and sonographic methods increased sensitivity in diagnosis of ovarian tumors. Combinations utilizing serum HE4 concentrations were most useful. CONCLUSIONS: CA125, HE4, ROMA, RMI and SA proved to be useful in preoperative diagnosis of ovarian tumors. HE4 and ROMA occurred to be the most useful. Ultrasonographic methods are considerably useful in diagnosis of ovarian tumors. RMI and SA present similar overall diagnostic value.

Chemokine expression in patients with ovarian cancer or benign ovarian tumors.

Introduction: Chemokines play a crucial role in tumor growth and progression according to proangiogenic and immunosuppressive action. The aim of this study was to investigate the serum levels of selected chemokines in patients with ovarian cancer or benign ovarian tumors to assess their role in tumorigenesis and their potential use in preoperative diagnosis of an adnexal mass. Material and methods: The study group consisted of 59 women with ovarian cancer: 17 epithelial ovarian cancer (EOC) patients and 42 women with benign ovarian tumors. We measured in sera obtained preoperatively the level of CA125 and a panel of 5 chemokines - CX3CL1/fractalkine, CXCL1/GRO-α, CXCL12/SDF-1, CCL20/MIP-3α and IL-17F - using the chemiluminescence method with multiplexed bead based immunoassay. Results: CX3CL1 was significantly elevated in sera of advanced ovarian cancer patients compared to women with benign ovarian tumors. The significant elevation of CXCL1 was also observed (both early and advanced stages). A similar pattern was present with the standard ovarian cancer marker CA125. In our patients with endometriotic cysts CA125 levels were significantly higher than in women with other benign tumors, whereas all analyzed chemokines had similar serum titers in patients with endometriotic vs. other benign ovarian cysts. Conclusions: CX3CL1 and CXCL1 are elevated in sera of EOC patients, which indicates their role in cancer development. Moreover, they might be useful in preoperative differential diagnosis of ovarian tumors, especially as they were not elevated in cases of endometriosis.

Ceftazidime/Avibactam and Other Commonly Used Antibiotics Activity Against Enterobacterales and Pseudomonas aeruginosa Isolated in Poland in 2015-2019.

Purpose: Infections caused by resistant Gram-negative bacteria are becoming increasingly common and now pose a serious public health threat worldwide, because they are difficult to treat due to few treatment options and they are associated with high morbidity and mortality. The combination of ceftazidime with the beta-lactamase inhibitor avibactam - seems to be the right choice in this situation. The aim of the study was to evaluate the activity of ceftazidime/avibactam and other commonly used antibiotics against Enterobacterales and Pseudomonas aeruginosa strains isolated within last years in Poland. Patients and Methods: This study analyzed the antibiotic susceptibility of 1607 Enterobacterales isolates and 543 nonfermenting P. aeruginosa strains collected between 2015 and 2019 in 4 medical laboratories participating in the ATLAS (Antimicrobial Testing Leadership And Surveillance) program in Poland. Unduplicated clinically significant Enterobacterales and P. aeruginosa strains were collected from patients with respiratory, skin and musculoskeletal, genitourinary, abdominal, bloodstream or other infections (ear, eye). Results: The ceftazidime/avibactam combination demonstrates the highest activity against Enterobacterales (98.9%), in both adults and children, including strains presenting MDR (multidrug-resistant) (97.5%) and ESBL (extended spectrum ß-lactamase) (96.3%) phenotypes. The activity of ceftazidime/avibactam increased to 100% when only MBL (metallo-ß-lactamase)-negative subset of Enterobacterales was considered. This combination also achieved the second highest activity result (89.3%) after colistin in P. aeruginosa, including isolates of MDR (65.9%) and carbapenem-resistant (CR) phenotypes (54.8%). When MBL-positive isolates were excluded, susceptibility rate of P. aeruginosa increased to 94.7%. It is worth to note that susceptibility of the examined P. aeruginosa strains to ceftazidime/avibactam was very high in children (93.3%), especially in a pediatric intensive care unit (94.2%). Conclusion: Enterobacterales and P. aeruginosa included in this analysis presented high susceptibility rates to ceftazidime/avibactam. Ceftazidime/avibactam showed the highest activity against Enterobacterales strains among all antibiotics studied, both for the total population as well as for MDR phenotype and ESBL phenotype. Ceftazidime/avibactam also achieved the second highest activity result against P. aeruginosa strains (including MDR and CR phenotypes). These results are much higher when excluding MBL-positive isolates that exhibit intrinsic resistance to ceftazidime/avibactam.

The Effect of Recombinant Human TSH on Sclerostin and Other Selected Bone Markers in Patients after Total Thyroidectomy for Differentiated Thyroid Cancer.

The direct effect of TSH on bone metabolism in vivo is difficult to capture as the changes of its concentrations are followed by respective alterations of thyroid hormone levels. We evaluated the effect of recombinant human TSH (rhTSH) on sclerostin and other bone markers in 29 patients after total thyroidectomy for differentiated thyroid cancer (DTC), without any signs of disease recurrence, who received L-thyroxine, most at non-suppressive doses. For two consecutive days, the patients were administered a standard dose of 0.9 mg rhTSH, i.m. Concentrations of sclerostin, osteocalcin, ß-CrossLaps, PTH, and some other parameters, were measured before and five days after the first rhTSH administration. The greater the increase in TSH concentration (∆TSH), the greater the decrease in: ∆sclerostin (r = -0.672; p < 0.001), ∆ß-CrossLaps (r = -0.580; p < 0.001) and ∆osteocalcin (r = -0.405; p = 0.029) levels, were recorded. The degree of TSH increase depended on the baseline PTH (r = 0.651; p < 0.001), age, and creatinine concentrations. rhTSH strongly inhibited bone turnover, thus, TSH-independently of thyroid hormones-exerted a direct protective effect on bone metabolism. Baseline PTH affected the magnitude of TSH increase and the degree of lowering in sclerostin and ß-CrossLaps that suggest factors affecting PTH may play a role in the effect of TSH on the bone.

Ghrelin, Obestatin and Their Receptors As Well As Metabotropic Glutamate Receptor Assessment in Chronic Functional Constipation in Children.

OBJECTIVES: The aim of this study was to examine the role of ghrelin, obestatin, and glutamate and their receptors in the pathogenesis of children functional constipation. METHODS: Children ages 4-17 were the subject of the study: 121 children with constipation (55 boys and 66 girls), 36 patients of the same age (26 boys and 10 girls) were the controls. Expression of ghrelin, obestatin, and glutamate receptors on gastric and colon specimens taken by endoscopy were assessed. The concentration of the above agents was estimated in serum by the enzyme-linked immunosorbent assay test. RESULTS: The lower median serum concentrations of ghrelin, in the constipated children than in controls were confirmed (1.9 ng/mL vs 2.6 ng/mL, P < 0.05). The expression of the metabotropic receptor 7 for glutamate (mGlu7) RNA was higher in the stomach (32.49 vs 31.47, P < 0.05), and was lower in the rectum in constipated patients compared to the control group (31.76 vs 32.62, P < 0.05). A negative correlation between the concentration of ghrelin in serum and colonic transient time (P = 0.01, rho = -0.23) was shown in the study group.Higher median expression of obestatin receptor G protein-coupled receptor39 in rectal mucosae was found in a constipated group than in the controls (29.9 vs 26.9, P < 0.05). CONCLUSION: Ghrelin, and receptors for ghrelin, obestatin, and glutamate in gastrointestinal mucosa play a role in the pathogenesis of functional constipation in children.

Is serum anti-Müllerian hormone (AMH) assay a satisfactory measure for ovarian reserve estimation? A comparison of serum and peritoneal fluid AMH levels.

BACKGROUND: Clinical cases have been reported with women who got pregnant with confirmed low serum anti-Müllerian hormone (AMH) concentrations, thus demonstrating that low serum AMH concentration cut-points could be fairly specific for poor ovarian response (POR) to gonadotrophin stimulation, but not for pregnancy. That observation prompted the question whether serum AMH concentration accurately corresponded to the whole amount of AMH secreted by granulosa cells. OBJECTIVES: To measure AMH levels in peritoneal fluid and their correlations with serum AMH concentrations. MATERIAL AND METHODS: The reported study involved 48 female patients, aged 18-40 years, diagnosed with benign ovarian cysts and qualified for a laparoscopic cystectomy. Prior to surgery, the ovarian reserve was assessed using serum AMH concentration assay. The peritoneal fluid was also collected during the laparoscopy and AMH concentrations in peritoneal fluid were measured. RESULTS: The AMH present in the peritoneal fluid strongly correlated with AMH levels in blood serum (r = 0.54; p < 0.001) and higher serum AMH concentrations corresponded to higher AMH concentrations in the peritoneal fluid. There was also a significant correlation between AMH levels in serum and in peritoneal fluid, collected from patients with endometrioma and other benign cysts (r = 0.61; p = 0.001 vs r = 0.43; p = 0.03). CONCLUSIONS: The AMH is present in the peritoneal fluid and its concentrations significantly correlate with AMH levels in serum. The assessment of AMH concentration in the peritoneal fluid may be a valuable complement to the evaluation of ovarian reserve and the diagnosis of infertility after adnexal surgery.

Bone Metabolism in Patients Treated for Depression.

BACKGROUND: Depression and osteoporosis are severe public health problems. There are conflicting findings regarding the influence of depression on bone metabolism. The aim of the presented study was to compare bone turnover markers and vitamin D levels between patients treated for depression and healthy controls. PATIENTS AND METHODS: We determined a concentration of osteocalcin, carboxy-terminal telopeptide of type I collagen (ß-CTX), 25-hydroxyvitamin D (25OHD) and 1,25(OH)2D3 in 99 patients, aged 46.9 ± 11 years, treated for depression, as well as in 45 healthy subjects. Depressive status was determined with the Hamilton Depression Scale (HDRS). RESULTS: In patients treated for depression, we demonstrated significantly lower osteocalcin concentrations (p < 0.03) and higher concentration of ß-CTX (result on the border of significance; p = 0.08). Those relationship were stronger in women. The level of 25OHD and 1,25(OH)2D3 did not differ significantly between the examined groups. We observed a negative correlation between the 25OHD and HDRS score after treatment in all patients treated for depression and in subgroups of women and subjects with recurrent depression. CONCLUSIONS: Our results indicate that depression is related to disturbances in bone metabolism, especially in women and patients with recurrent depression, suggesting its role in context of osteoporosis development.

Klotho and fibroblast growth factors 19 and 21 serum concentrations in children and adolescents with normal body weight and obesity and their associations with metabolic parameters.

BACKGROUND: Fibroblast growth factor 19 (FGF19), fibroblast growth factor 21 (FGF21) and Klotho are regulators of energy homeostasis. However, in the pediatric population, the relationships between obesity, metabolic disorders and the aforementioned factors have not been clearly investigated. We analyzed the role of FGF19, FGF21 and Klotho protein in children with normal body weight as well as in overweight and obese subjects and explored their associations with insulin resistance (IR) and metabolic syndrome (MS) and its components. METHODS: This was a cross-sectional study conducted in a group of hospitalized children and adolescents. Laboratory investigations included serum analysis of FGF19, FGF21, and Klotho with ELISA kits as well as the analysis of the lipid profile and ALT serum concentrations. Moreover, each subject underwent an oral glucose tolerance test (OGTT) with fasting insulinemia measurement to detect glucose tolerance abnormalities and calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. Furthermore, the clinical analysis included blood pressure measurement, body fat percentage estimation and assessment of the prevalence of MS and its components. RESULTS: The study was conducted with 174 children/adolescents aged 6-17 years with normal body weight (N = 48), obesity (N = 92) and overweight (N = 34). Klotho concentration was significantly higher in the obese children [median 168.6 pg/ml (90.2 to 375.9)]) than in the overweight [131.3 pg/ml (78.0 to 313.0)] and normal-body-weight subjects [116.6 pg/ml (38.5 to 163.9)] (p = 0.0334) and was also significantly higher in insulin-resistant children than in insulin-sensitive children [185.3 pg/ml (102.1 to 398.2) vs 132.6 pg/ml (63.9 to 275.6), p = 0.0283]. FGF21 was elevated in patients with MS compared to the FGF21 levels in other subjects [136.2 pg/ml (86.5 to 239.9) vs 82.6 pg/ml (41.8 to 152.4), p = 0.0286]. The multivariable model showed that FGF19 was an independent predictor of IR after adjusting for pubertal stage and BMI Z-score. CONCLUSIONS: Klotho levels were associated with body weight status in children and adolescents. Moreover, Klotho, FGF19 and FGF21 concentrations correlated with IR status and/or components of MS.

One-year follow-up of ovarian reserve by three methods in women after laparoscopic cystectomy for endometrioma and benign ovarian cysts.

OBJECTIVE: To determine the long-term impact of laparoscopic cystectomy for endometriomas and benign cysts on ovarian reserve and selection of the most effective method of assessment. METHODS: The present study was carried out between November 2013 and December 2016. Participants were assigned to laparoscopic cystectomy for diagnosed unilateral benign ovarian cysts and divided into groups: the endometrioma group (EG) (n=35) and the other benign ovarian tumor group (OG) (n=35). Before and at 3 and 12 months after the procedure, transvaginal ultrasonography was performed to assess antral follicle count (AFC) and ovarian volume (OvVol); laboratory tests were ordered for anti-Mullerian hormone (AMH) serum concentration assays. Pregnancy rates were counted in a 12-month follow-up. Statistica12 software was used for analysis. RESULTS: The present study included 70 women aged 18-40 years. AMH serum concentration decreased significantly 3 months after laparoscopic cystectomy (4.89 ± 3.66 ng/mL to 3.45 ± 3.37 ng/mL; P<0.001). A greater decrease of AMH concentrations was observed in the EG (45.39% vs 14.87%; P=0.021). Twelve months of observation revealed a suppression in the drop of the AMH concentration, while AFC and OvVol remained unaffected. The likelihood of spontaneous pregnancy was three times higher in the OG (hazard ratio [HR] 3.57, 95% confidence interval [CI] 1.08-12.5). CONCLUSION: There was a significant decline in AMH levels in the EG 3 months after cystectomy. No further fall in AMH concentration was observed in the 12-month follow-up. The serum AMH concentration could be considered a valuable marker for ovarian reserve assessment after laparoscopic cystectomy.

Serum concentrations of soluble (s)L- and (s)P-selectins in women with ovarian cancer.

INTRODUCTION: The aim of the study was to compare serum concentration of soluble L- and P-selectins in women with ovarian cancer (OC) and healthy controls, and to investigate sL- and sP-selectin levels with regard to clinical and pathological parameters. Correlation analysis was used to measure the following: sL- and sP-selectin concentration and Ca125; sP-selectin and platelet concentrations; and sL-selectin and serum leukocyte levels in women with OC. MATERIAL AND METHODS: The study included 29 patients with OC and 23 healthy controls. Serum concentrations of sL- and sP-selectins were measured in all subjects. Routine diagnostic tests: CBC and USG (both groups) and Ca125 (study group) were performed. RESULTS: Significantly higher serum concentrations of sL- and sP-selectins were found in the study group as compared to controls. Lower levels of serum sL-selectin were observed in women with poorly-differentiated OC (G3) and advanced stages of the disease (FIGO III, IV), but the results were statistically insignificant. No statistically significant relationship was detected between sP-selectin serum concentration in women with OC and tumour differentiation, histological type, and stage of the disease. No significant correlation was found between sL- and sP-selectins and Ca125 levels. A weak correlation was found between serum concentration of sP-selectin in women with OC and platelet count. No statistically significant correlation was observed between sL-selectin concentration and serum leukocyte levels in women with OC. CONCLUSIONS: The analysis of sL- and sP-selectin concentrations may be a useful tool in the diagnosis of OC. The levels of sL-selectin decrease with disease progression.

Glomerular filtration decrease after diagnostic cardiac catheterisation in children with congenital cardiac malformation - the role of serum creatinine, cystatin C, neutrophil gelatinase and urine output monitoring.

INTRODUCTION: Diagnosis of contrast induced-nephropathy (CIN) by a classic renal biomarker such as creatinine concentration can be delayed because of various factors that can influence this marker. Changes in new biomarkers such as neutrophil-gelatinase associated lipocalin (NGAL) and cystatin C are postulated to be more sensitive for recognizing patients prone to CIN-acute kidney injury (AKI). AIM: To investigate the role of NGAL and cystatin C as early biomarkers in the diagnosis of kidney injury after cardiac catheterisation. MATERIAL AND METHODS: The study group consisted of 50 patients with congenital heart malformation admitted for scheduled cardiac catheterisation. The biomarkers serum creatinine, serum NGAL and serum cystatin C were tested at 5 time-points sequentially from start to 48 h after the procedure. RESULTS: Significant changes were noted during the research in the serum creatinine concentration (p < 0.001) and serum NGAL concentration (p < 0.001). CIN-AKI, diagnosed by the modified Schwartz formula, occurred in 16 (32%) patients after 24 h and in 8 (16%) after 48 h. Subsequent analysis showed that serum creatinine significantly rose in the first 2 h of the study with simultaneous reduction in the eGFR. Maximum growth in serum NGAL occurred at 6 h after contrast administration and then returned to the baseline values at 24 h. Serum cystatin C level did not significantly change during the study. CONCLUSIONS: We observed a transient decrease in eGFR and a rise of serum NGAL after 2 h but NGAL was most pronounced at 6 h after the procedure. The potential role of cystatin C as a biomarker of CIN-AKI was not proved.

Analysis of preoperative blood platelet parameters in terms of diversity of epithelial ovarian cancer.

Smouldering inflammation, thrombocytosis, and platelet hyper-reactivity are linked to malignancy. The relationships between preoperative diagnostic blood morphology parameters and cancer have been the focus of much interest, because some of these parameters are correlated with advanced cancer stages and poor patient survival rates. This study aimed to perform an observational, retrospective analysis of the intradiversity of blood platelet parameters in patients with different International Federation of Gynaecology and Obstetrics (FIGO) stages and different histological types of epithelial ovarian carcinomas (EOC), and also an analysis of the overall survival rate.In all, 94 EOC patients were included in this analysis (23 mucinous, 33 serous, 20 undifferentiated, 14 endometrioid, and 4 clear cell carcinoma cases). Peripheral blood samples were collected and analyzed before drug or surgical treatment.The platelet-to-neutrophil ratio (PNR) was related to the histological type of EOC, particularly mucinous carcinoma. In patients with mucinous cancer, the PNR was significantly lower compared with patients with nonmucinous cancer, and this parameter distinguished between mucinous and nonmucinous groups of patients (area under receiver-operating characteristic [ROC] curve 0.721 ±â€Š.056; sensitivity 82.6%; specificity 61%; P < .001; ROC analysis), regardless of the FIGO stage. Moreover, elevated PNR values were correlated with lower survival rate of EOC patients.The reduced PNR, similar to the lower level of cancer antigen 125, is characteristic for mucinous ovarian carcinoma patients. Moreover, elevated PNR index might correlate with poor survival of patients.

Does IGF-1 play a role in the biology of ovarian cancer?

OBJECTIVES: The aim of the study was to investigate serum concentrations of the insulin-like growth factor-1 in women with ovarian cancer and healthy controls, and to compare free IGF-1 levels with selected clinical and pathological param-eters. Correlation analysis was used to measure the following: IGF-1 concentration and Ca125; IGF-1 level and the height of the OC patients. MATERIAL AND METHODS: The study included 70 patients with OC and 50 healthy controls. Serum concentrations of free IGF-1 were measured in all subjects. Routine diagnostic tests (CBC and USG and Ca125) were performed. RESULTS: Significantly higher serum concentrations of free IGF-1 were found in the study group as compared to controls. No statistically significant relationships between IGF-1 serum concentrations and tumor differentiation, histological type, and disease stage were detected. No statistically significant correlations between IGF-1 and Ca125 level or between IGF-1 and growth of OC patients were found. CONCLUSIONS: Serum IGF-1 participates in the etiopathogenesis of ovarian cancer in menstruating women, while local synthesis of this factor and other components of the autocrine loop of the IGF-1 system play a greater role in their post-menopausal peers.

Sub-optimal primary surgery leads to unfavorable immunological changes in ovarian cancer patients.

Primary cytoreduction, followed by chemotherapy, is a standard treatment of patients with epithelial ovarian cancer (EOC). However, the effectiveness of this treatment depend on various elements e.g. type of operation. It is accepted that optimal surgery correlates with longer survival of patients. The other element, an efficiency of immune system after surgical intervention although important is less elucidated. The aim of this study was to establish the impact of optimal and sub-optimal operation on immunological status of EOC patients regarding also their overall survival (OS). On the day of primary cytoreduction and 7days after, the selected serum immunological parameters were determined in 49 patients with confirmed EOC. We found that, the level of immunosuppressive (interleukin 10; transforming growth factor-ß - TGF-ß1) and pro-inflammatory (interleukin-6 and 8) cytokines was significantly higher in the group of patients with advanced stage of disease, compared to early stage. However, the number of circulating CD3+, CD4+ or CD8+ cells, CD19+ and NK cells was similar in both group of EOC patients. The overall survival of patients who underwent optimal cytoreduction was significantly higher than that in whom only sub-optimal surgery was performed. Sub-optimal cytoreduction only partially weakened the serum level of TGF-ß1 and IL-8 and what is more enhanced the number of circulating CD4+CD25+high cells in patients with advanced stage of disease. Sub-optimal surgery and high post-operative level of TGF-ß1 increased the hazard ratio for patients. Besides, we noticed that the high pre-operative concentration of TGF-ß1 could distinguish all EOC patients (independently of FIGO classification) for whom optimal or sub-optimal surgery would be applied. Sub-optimal debulking resulted in higher immunosuppression and lower OS of EOC patients.

The role of adhesion molecules in inflammatory bowel disease in children. Assessment of the possible risk of cardiovascular complications.

INTRODUCTION: Inflammatory bowel diseases (IBD) are chronic diseases that proceed with exacerbation and remission phases. Adhesion molecules play a significant role in inflammatory processes. The same adhesion molecules play an important role in atherogenesis. AIM: To assess the risk of atherosclerosis in IBD in children. MATERIAL AND METHODS: The study included 40 patients with IBD (25 with Crohn's disease - CD and 15 with ulcerative colitis - UC) aged 4-17 years. In the study group, concentrations of selected adhesion molecules (intracellular adhesion molecule - ICAM, vascular cell adhesion molecule - VCAM, E-selectin) and selected parameters of lipid metabolism in serum were assessed. RESULTS: No statistically significant differences between CD and UC patients and in the control group, in mean values of selected adhesins were obtained. Average variable VCAM was significantly lower in patients with CD than in patients with UC in the active stage of the diseases. Significantly higher average levels of triglycerides (TG) and high density lipoproteins (HDL) were found in the control group than in patients with CD. Significantly higher levels of total cholesterol (CHL) and HDL were noticed in the control group patients than in the patients with UC. The HDL/CHL was significantly higher in controls than in patients with UC. CONCLUSIONS: No increased risk of developing atherosclerosis was found in children with IBD. Decreased risk in patients during exacerbation of inflammatory bowel disease was revealed, which may result from malnutrition typical for acute disease phase.

The sL1CAM in sera of patients with endometrial and ovarian cancers.

PURPOSE: L1CAM is a cell adhesion molecule suspected to play an important role in carcinogenesis. The objective of the study was to evaluate the level of soluble L1CAM in the sera of patients with endometrial and ovarian carcinomas and verify the feasibility of the sL1CAM as a marker of these carcinomas. METHODS: 35 endometrial and 18 ovarian cancer patients were enrolled in the study. 43 patients with benign gynecological conditions constituted a control group. The sL1CAM serum level was measured with ELISA test in each patient and it was referred to the data from the surgical staging of the cancers. RESULTS: The sL1CAM serum level was significantly lower in patients with endometrial cancer than in healthy women and slightly lower in the ovarian cancer group than in the control group. In the endometrial cancer group there was no correlation between sL1CAM concentration and cancer histopathology, stage or grade. sL1CAM concentration positively correlated with ovarian cancer stage and (not significantly) with grade. CONCLUSIONS: Despite the increasing data about the possible role of L1CAM as a strong prognostic factor of poor outcome in many cancers, we did not find evidence supporting the use of sL1CAM as a marker of endometrial or ovarian cancers.

Secretion of cytokines and heat shock protein (HspA1A) by ovarian cancer cells depending on the tumor type and stage of disease.

Epithelial ovarian cancer is a heterogeneous disease comprising several tumor types that each have multiple histopathological features and different biological behaviors. Recent morphologic and molecular genetic studies have allowed for the categorization of various types of ovarian cancer into two groups: type I and type II. Type I tumors are low-grade and are genetically more stable, while type II tumors are high-grade and genetically unstable. The determination of the type of ovarian cancer may have implications in terms of the appropriate therapeutic strategy because different prognoses and responses to chemotherapeutic agents are observed. Therefore, the current challenge is better recognition of the features of cancer cells, which may result in more individualized therapy. The aim of the current studies was to compare the ability of ovarian cancer cells isolated from tumors, which were classified as type I or type II ovarian cancer, to release pro-inflammatory and immunosuppressive cytokines and heat shock protein (HspA1A). These factors are known to facilitate tumor cell survival, invasion and metastasis. Our studies demonstrated that ovarian cancer cells isolated from patients with type II tumors released high levels of immunosuppressive cytokines (i.e., interleukin 10 and transforming growth factor ß) and HspA1A in vitro. Conversely, ovarian cancer cells obtained from of type I tumors were significantly less active. We did not observe any difference in the ability of the isolated cancer cells to secrete pro-inflammatory cytokines, regardless of the type of ovarian cancer. In this study, we found that cancer cells from patients with type II tumors demonstrated more intense activity in regards to survival and metastasis, which should be considered during therapy.

Folate status, regulatory T cells and MTHFR C677T polymorphism study in allergic children.

PURPOSE: This study aimed to investigate early-life folate serum concentrations in children with food, inhalant or mixed type allergy. The influence of folate levels on the FoxP3 expression in Treg (regulatory T) cells in the studied children, taking into account the MTHFR (5,10-methylenetetrahydrofolate reductase) genotypes was also analyzed. MATERIAL AND METHODS: The study was performed in 83 allergic children (study group) and 49 healthy children (control group), aged 2-72 months. Medical history of each child was obtained and laboratory tests (serum folic acid concentrations and MTHFR C677T polymorphism) were carried out. The percentage of Treg cells was evaluated in almost a half of the examined subjects (48.5%). RESULTS: Significantly higher serum folate levels in the group of children with food allergy than in those with inhalant allergy was confirmed (P=0.037). In the study group the TT homozygotes were characterized by significantly lower folate concentrations than CC homozygotes (P=0.045). A negative correlation was demonstrated between the FoxP3 expression in CD4+CD25highFoxP3+ peripheral blood lymphocytes and serum folic acid concentrations. The correlation was more pronounced in the group of allergic children and it was statistically significant (r=-0.339, P<0.05). CONCLUSIONS: The results of the study indicate a possibility of some effects of folate status on Treg cells, thus suggesting their potential role in the development and course of allergy in children.