Progranulin and chemerin plasma level in obese patients with type 2 diabetes treated with a long-acting insulin analogue and premixed insulin analogue.

Diabetes, referred to as the first non-infectious epidemic, covers a heterogenous group of metabolic diseases marked by hyperglycemia resulting from a defect of insulin secretion and/or insulin resistance. Highly endocrine active adipocytes, particularly those located in white adipose tissue, constitute a source of cytokines, growth factors and complement component as well as adipocytokines including chemerin and progranulin could be the key molecules in the pathomechanism of hypertension, dyslipidemia, metabolic disorders or diabetes type 2. In this study, it was decided to verify the existence of possible relationships between the plasma concentration of progranulin and chemerin and the values of intermediate indices of insulin sensitivity and insulin resistance in patients, both before and after the 6-month insulin therapy by long-acting insulin analogue and premixed insulin analogue. The level of laboratory parameters in blood plasma collected from the control group and from obese individuals with type 2 diabetes mellitus was estimated with the test kits using enzyme-linked immunosorbent assay (ELISA): the test of Mediagnost E103 GmbH GmbH, Reutlingen, Germany for progranulin; the test of BioVendor R&D, Brno, Czech Republic for chemerin. The aim of this study was to assess the progranulin and chemerin plasma level in obese individuals with type 2 diabetes, before and after 6 months of pharmacological treatment with a long-acting analogue human insulin or premixed insulin. In the blood plasma of untreated diabetics - in contrary to progranulin plasma concentration in diabetic patients after management implementation - progranulin was found to occur in a significantly higher concentration in relation to the level of this protein in the blood plasma of control group individuals. Despite the fact that 6-month therapy, both with the insulin mixture and with the long-acting analogue in people with diabetes, does not significantly affect the plasma chemerin concentration, the high, negative correlation between the progranulin and chemerin levels in the blood of individuals of the control group, and a positive one between the levels of progranulin and chemerin in people with diabetes before and after treatment was found. The conducted studies indicated the modified, in the course of diabetes type 2, mutual quantitative relations between progranulin and chemerin - the biological mediators of systemic metabolism, reflecting their active participation in the pathogenetic changes underlying type 2 diabetes. The obtained study results indicate a modification of mutual relationships of the adipocytokines assessed in the paper - progranulin and chemerin, associated with the development of the systemic inflammatory response occurring in the course of obesity which, by inducing insulin resistance, may consequently lead to type 2 diabetes. Taking into consideration the fact that the plasma progranulin and chemerin concentrations in obese patients with type 2 diabetes subjected to pharmacotherapy have not been assessed so far, it is possible that the obtained study results may cast light on the potential influence of the applied treatment on the systemic changes of the both adipocytokines involved in the pathomechanism of the mentioned disorder and thus create the possibility of implementing new therapeutic strategies in the management of patients with diabetes, which is an increasingly common, fast-spreading metabolic disease considered as a non-infectious epidemic of the 21st century.

The expression profile of genes encoding tumor necrosis factor-alpha, interleukin-6 and their receptor in benign adrenal tumors.

In the process of neoplasia, during which benign adrenal tumors are formed, stimulators of new blood vessel growth as well as growth of tumor cells are cytokines, especially tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). We analyzed the expression profile of genes coding: TNF-α, tumor necrosis factor receptor 1 (TNF-R1), TNF-R2, IL-6, interleukin 6 receptor (IL-6R) in sections of adrenocortical tumor tissue, rated on the Weiss point scale, in patients with clinically diagnosed Conn's and Cushing's syndrome, and the usefulness of determining the examined genes as markers differentiating individual clinical units. There was no correlation between the expression of the examined genes and clinical parameters such as age, BMI or blood pressure, both in the entire study group and in individual subgroups. Elevated expression of the genes coding TNF-α, TNF-R2 and IL-6R was observed, whereas genes encoding TNF-R1 and IL-6 showed relatively low expression. The highest statistically significant differences in the expression of the examined genes were observed between IL-6 and IL-6R. High positive correlation was found in the subgroup of patients with Conn's clinical syndrome, between genes encoding both types of receptors for TNF-α, IL-6 and TNF-R2, TNF-α and IL-6 receptor, and between TNF-R2 and IL6-R receptors, which may suggest the mutual influence of these cytokines and their receptors on their own expression.

Clinical significance of urinary glycosaminoglycan excretion in inflammatory bowel disease patients.

The research focused on the diagnostic usefulness of urinary glycosaminoglycans excretion as new markers related to the ECM remodeling in the intestine. Their possible suitability in the diagnosis, differential diagnosis and treatment monitoring in the course of the two most common forms of inflammatory bowel diseases (IBD), i.e. ulcerative colitis (UC) and Crohn's disease (CD) were assessed in this study. Urinary excretion of total sulfated glycosaminoglycans (TGAG) and fraction of chondroitin sulfates (CS) were analysed in 47 patiens with IBD, including 31 patients with UC and 16 patients with CD at baseline and after one year of therapy. Sulfated GAGs excreted in urine were quantitated using standardized dye-binding method. A several-fold increase in urinary excretion of total GAG and CS fraction in both UC and CD patients compared to healthy subjects indicates the potential usefulness of quantitative urinary GAG analysis in the diagnosis of IBD. No differences were found in the amount of GAG excreted in the urine in patients with UC and CD. Adalimumab resulted in a decrease in the activity of the inflammatory process and the activity of the disease expressed in the Mayo scale, which was accompanied by an increase in the amount of CS excreted in the urine of UC patients. Moreover, significant correlation was found between Mayo scale and urinary total GAG and CS excretion in UC patients. The quantitative assessment of total glycosaminoglycans and chondroitin sulfates fraction in urine may be a marker helpful in the early diagnosis of IBD.

The association between insulin-like growth factor 1 (IGF-1), IGF-binding proteins (IGFBPs), and the carboxyterminal propeptide of type I procollagen (PICP) in pre- and postmenopausal women with rheumatoid arthritis.

OBJECTIVES: To assess the association between plasma levels of the insulin-like growth factor (IGF) system including IGF-1, IGF-binding proteins (IGFBPs) including IGFBP-1, total (t-)IGFBP-3 and functional (f-)IGFBP-3, and the carboxyterminal propeptide of type I procollagen (PICP) in pre- and postmenopausal women with rheumatoid arthritis (RA). METHOD: Plasma concentrations of IGF-1, IGFBP-1, t-IGFBP-3, f-IGFBP-3, and PICP were measured by immunoassay. RESULTS: No significant difference was observed in plasma IGF-1 levels between pre- and postmenopausal subjects. Plasma levels of IGFBP-1 were elevated in RA. PICP and f-IGFBP-3 were greatly affected by menopausal status. Of the three IGFBPs tested, only f-IGFBP-3 plasma levels in RA women correlated negatively with age and disease duration. A positive correlation was demonstrated between PICP and erythrocyte sedimentation rate (ESR) in RA. Moreover, there was no correlation between PICP and IGF-1 and any of the IGFBPs in RA women. CONCLUSIONS: Considerable disruption of the IGF system in RA was found to be related to disease activity and duration. Changes in the IGF-IGFBP axis and PICP levels were different in pre- and postmenopausal women with RA. Elevated plasma PICP concentrations may indicate an increased rate of bone formation in postmenopausal RA women. Additionally, the observed changes in the IGF/IGFBP system did not affect bone formation during RA.

Serum matrix-degrading enzymes in rats intoxicated with selenium.

The effect of poisoning doses of selenium on serum matrix-degrading enzymes activity was investigated in rats intoxicated with selenium. Fifteen animals were receiving orally sodium selenite in a daily dose of 300 microg/kg body weight. Intoxication with selenium was carried out for 10 weeks. The present study revealed significant increase in activities of enzymes involved in the connective tissue matrix metabolism i.e. beta-glucuronidase, N-acetyl-beta-glucosaminidase, elastase and collagen peptidase. There was no change in the cathepsin activity. The relative enzyme activities calculated over protein level resulted in higher values than those found in direct measurements. Serum enzyme activity was increased most for elastase (about 31%) and N-acetyl-beta-glucosaminidase (about 33%) based on activity per gram of protein. The current data indicate that lysosomes are target organelles for selenium toxicity. Generalized increase in lysosomal enzymes activity contributes to the altered metabolism of the connective tissue in selenium-intoxicated animals. The mechanisms that lead to the increase of lysosomal enzymes activity in rats receiving poisoning doses of selenium could be related to biochemical disturbances caused by selenium toxicity.

Free radical activity and antioxidant defense mechanisms in patients with hyperthyroidism due to Graves' disease during therapy.

Free radical-mediated oxidative stress has been implicated in the etiopathogenesis of several autoimmune disorders. We investigated the prooxidant-antioxidant status in order to evaluate the possible deleterious role of oxidative phenomena in patients with Graves' disease. Thirty patients with hyperthyroidism due to Graves' disease were investigated. Thirty age-matched healthy subjects were studied as a control group. Free radical activity indices, antioxidant defense systems, and thyroid and pituitary hormone levels were measured in fasting blood samples. Blood samples were taken before initiation of therapy and after attainment of euthyroid state. A significant increase in lipid peroxidation activity indices, i.e., conjugated dienes and thiobarbituric acid-reacting substances, was found in blood serum of the patients with untreated Graves' disease. These changes were accompanied by a decrease in plasma thiol and erythrocyte lysate thiol groups concentrations. Hyperthyroidism resulted in a marked increase in intracellular antioxidant enzymes, i.e., superoxide dismutase, catalase and glutathione peroxidase activities as compared to the controls. Extracellular anti-free radical scavenging systems potential, measured by glutathione reductase activity and total antioxidant status level, was found to be significantly decreased in untreated Graves' patients. Treatment with thiamazole resulted in normalization of the free radical and antioxidant activity indices. The obtained results indicate an enhanced generation of reactive oxygen species and impairment of cellular and extracellular antioxidant systems potential in patients with Graves' disease. The attainment of euthyroid state led to an improvement in oxidative stress indices and antioxidant potential parameters.

[Free radical concepts in the etiopathogenesis of Graves-Basedow disease]. / Wolnorodnikowa koncepcja etiopatogenezy choroby Gravesa i Basedowa.

Increased metabolism due to hyperthyroidism leads to the dysfunction of the mitochondria respiratory chain, resulting in elevated formation of the reactive oxygen species in the course of Graves-Basedow disease. It has also been reported that excessive thyroid hormone level may induce oxidative tissue injury. Furthermore, Graves-Basedow disease is frequently associated with changes of the antioxidant defence system activity. The disturbed balance between oxidative and antioxidative processes may be of significant importance in the pathogenesis of Graves-Basedow disease.