Soluble angiogenesis markers in gastric tumor patients.

Gastric cancer is the second commonest cause of cancer-associated death in the world. Its molecular markers can be useful not only for diagnostic, but also prognostic purposes. The aim of the study was to assess the usefulness of soluble angiogenesis markers such as endoglin and VEGFR2 in gastric cancer patients and to compare these results with those of VEGF levels. As a secondary objective, we compared the concentrations of all three soluble markers in plasma and serum. The study was performed on 26 patients with gastric cancer (17 intestinal-type and 9 diffuse-type), and additionally in 2 patients with B cell lymphoma and 2 with gastro-intestinal stromal tumor. In summary, we showed increases in circulating VEGF-A in patients with both types of gastric cancer. The levels of VEGFR2 did not change significantly in patients with gastric cancer as compared to healthy subjects. Interestingly, after the operation greater levels of VEGFR2 were observed in patients without metastases. Both VEGF and VEGFR2 circulating levels were greater in patients with lymphoma, when compared to both gastric cancer patients and the control group. However, because of small number of patients, this requires further studies. Presented data suggests that endoglin does not seem to be a valuable tool in the assessment of gastric cancer invasion and spread

Role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice.

Postmenopausal women frequently develop hypothyroidism. Estrogen depletion is accompanied by an increase of IL-6, accelerating bone turnover. The influence of hypothyroidism on bone metabolism in postmenopausal women is poorly understood. The aim of the study was an attempt to clarify the role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice. The study was performed on 56, 12-13 weeks old, female mice: C57BL/6J (wild-type; WT) and C57BL/6JIL6-/-Kopf (IL-6 knock-out; IL6KO). The mice were randomly divided into 8 groups with 7 mice in each one: 1/ WT controls, 2/ IL6KO controls, 3/ WT hypothyroid mice, 4/ IL6KO hypothyroid mice, 5/ WT ovariectomized, 6/ IL6KO ovariectomized, 7/ WT ovariectomized hypothyroid mice and 8/ IL6KO ovariectomized hypothyroid mice. Experimental model of menopause was produced by bilateral ovariectomy carried out in 8-9 weeks old mice. Experimental model of hypothyroidism was induced by propylthiouracyl administration in driking water. The serum levels of TRACP 5b, osteocalcin, OPG and RANKL were determined by ELISA. Serum RANKL concentrations were elevated significantly in all groups of ovariectomized mice as compared to respective controls, but in a minor degree in IL6KO hypothyroid mice as compared to wild-type animals. Moreover sRANKL values were significantly lower in IL6KO as compared to WT controls and IL6KO PTU injected mice. Osteoprotegerin serum levels were decreased in all IL-6 deficient mice and in a highest degree in sham-operated hypothyroid mice. To sum up, the results of the present study suggest that estrogens deficit is a strong stimulus for RANKL-RANK/OPG pathway that breaks an inhibitory influence of hypothyroidism even in IL-6 deficient mice

Interleukin-6 is not essential for bone turnover in hypothyroid mice.

Interleukin-6 (IL-6) has been shown to be involved in the pathogenesis of several bone diseases characterized by an imbalance between bone resorption and formation. The aim of the study was to estimate serum markers of bone turnover: osteoclast-derived tartrate-resistant acid phosphatase form 5a (TRACP 5b) and osteocalcin in IL-6-deficient mice to assess the role of IL-6 in bone metabolism in hypothyroidism in mice. C57BL/6J (wild-type; WT) and C57BL/6J(IL6-/-Kopf) (IL-6 knock-out; IL6KO) mice randomly divided into 4 groups with 10 in each one: 1/ WT mice in hypothyroidism (WT-ht), 2/ WT controls, 3/ IL6KO mice with hypothyroidism (IL6KO-ht) and 4/ IL6KO controls. Experimental model of hypothyroidism was induced by intraperitoneal injection of propylthiouracyl. The serum levels of TRACP 5b and osteocalcin were determined by ELISA. Serum concentrations of TRACP 5b (median and interquartile ranges) were significantly decreased in both groups of mice with hypothyroidism: WT (3.2 (2.5-4.7) U/l) and IL6KO (2.6 (1.8-3.5) U/l) as compared to the respective controls. Similarly, serum osteocalcin levels were significantly reduced in both groups of mice in experimental hypothyroidism: WT (25.8 (23.0-28.2) ng/ml) and IL6KO (21.5(19.0-24.6) ng/ml) in comparison to the respective controls. There were no significant differences in bone turnover markers between IL6KO and WT mice both in hypothyroid and control animals. The results of the present study suggest that IL-6 does not play an important role in bone turnover in both euthyroid and hypothyroid mice

The association of thyroid-stimulating hormone (TSH) and free thyroxine (fT4) concentration levels with carbohydrate and lipid metabolism in obese and overweight teenagers.

Introduction: Obesity has increased rapidly among children and adolescents during the last 30 years. Paediatric patients with a BMI above the 85th centile are more often diagnosed with increased TSH levels than are children with proper body weight. Material and methods: The data of 961 overweight and obese children, aged 13 years, recruited in four cities in Poland as part of PoZdro!, a two-year prophylactic program, were analysed to observe the relationship between serum TSH and fT4 concentration and carbohydrate and lipid metabolism parameters, as well as anthropometric parameters.Results: TSH concentration in the study group was positively correlated, whereas fT4 concentration was negatively correlated with WHR and WHtR values, fasting serum glucose concentrations and one-hour glucose concentration, fasting serum insulin concentrations, one-hour and two-hour insulin concentration, ALT serum activity, as well as total cholesterol, LDL cholesterol, and triglyceride serum concentrations. An increased risk of metabolic syndrome was diagnosed previously in patients with TSH concentrations > 2.5 mUI/L. Conclusions: TSH concentration in the upper half of the current reference range (> 2.50 mIU/L) is associated with an increased risk of lipid and carbohydrate metabolism disorders and therefore increased chances of developing metabolic syndrome. It seems advisable to regularly monitor thyroid function in overweight and obese paediatric patients

Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD