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M Hadzija

Publications and source records attributed to M Hadzija.

24 records · Page 2Linked to original sources

Effect of the degree of hyperglycaemia on the catalytic activities of glycosidases in kidney and urine of diabetic rats.

The catalytic activities of N-acetyl-beta-D-glucosaminidase, beta-galactosidase and alpha-glucosidase in kidney and urine of diabetic rats were investigated in relation to the duration of diabetes, to the degree of constant hyperglycaemia and to the therapeutic control in the early stage of disease. The results suggest that the degree of constant hyperglycaemia and the duration of untreated diabetes are significant determining factors for the course of morphological changes. These changes are manifested as a decrease of the glycosidases in kidney (0.5 to 0.6 time the age-matched controls) and as moderate to severe enzymurias. Daily variation of blood glucose with inadequate insulin Lente therapy caused decreased N-acetyl-beta-D-glucosaminidase and beta-galactosidase activities in kidney as well as enzymuria. Since such changes can be correlated with histologically visible changes in the kidney, the measurement of these enzymes in urine is a simple way of monitoring the development of kidney damage in poorly controlled diabetes. When constant normoglycaemia was maintained for three weeks with insulin Ultralente in diabetic rats with a confirmed decrease of kidney glycosidases, the persisting morphological alteration of the organ was reflected by a urinary output of N-acetyl-beta-D-glucosaminidase.

Animals↗

[Separation of lymphocytes into classes from peripheral human blood using centrifugation on a discontinuous gradient].

Peripheral blood lymphocytes of 20 normal volunteers were separated on a discontinuous gradient of Ficoll. The ability of lymphocytes from the fractions to from sponteneous (E) and induced (EAC) rosettes and undergo transformation in the presence of phytohaemagglutinin (PHA) was tested. T-lymphocytes were concentrated in the density of 1,067 g/ml and B-lymphocytes in the density of 1,063 g/ml.

B-Lymphocytes↗

Tryptophan content in serum and brain of long-term insulin-treated diabetic rats.

The metabolism of tryptophan (TRP) was studied in diabetic and insulin-treated diabetic rats throughout a five-month period. In alloxan diabetic rats the serum and brain TRP levels were decreased (serum: 38 to 48 mmol/l, brain: 8.6 to 9.2 mmol/g) in comparison to the values of control rats (serum: 59 to 64 mmol/l, brain: 11.3 to 12.6 mmol/g). Daily long-term (for 45, 75, 90 or 135 days) treatment with intermediately acting insulin (4 IU/rat, s.c.) was not able to restore brain concentration of TRP. On the contrary, the serum TRP concentrations were totally or partially restored. The concentrations of branched chain amino acids (BCAA) were increased in serum (valine = 361.2 to 461.0 mumol/l or leucine + isoleucine = 431.0 to 520.3 mumol/l) throughout the entire five-month examination period. Insulin treatment did not return serum concentration of BCAA to normal level in the observation period either.

Amino Acids↗

Influence of antigen processing on thymic T-cell selection.

The design of a specific blocking peptide for the immunosuppressive therapy of an autoimmune disease requires the identification of peptides of an autoantigen that are physiologically processed in vivo and bind to MHC-encoded membrane glycoproteins. However, knowledge of how an antigen is physiologically processed by antigen-presenting cells (APC) in vivo, particularly in the thymus, is lacking. It is also unknown whether the processing of an antigen by different APC in the thymus can influence thymic T-cell selection. This is an important consideration for attempts to delete or inactivate autoreactive T cells that elicit autoimmune disease. To address these issues, we investigated the processing of biosynthetically labelled recombinant human insulin (rHI), a model autoantigen, injected into mice and characterized the insulin peptides associated with MHC class II molecules on thymic epithelial cells and dendritic cells. These APC were found to differ in the way they process insulin. The detection of MHC-class-II-bound insulin peptides on the surface of the epithelial cells but not the dendritic cells correlated with their capacity to either present or not present insulin to T cells, respectively. Thus, antigen processing may control the appearance of different peptide-MHC class II complexes on thymic APC that mediate positive and negative selection, and thereby influence the development of the T-cell repertoire. Our findings could have important bearing on the future design of synthetic blocking peptides that reduce or eliminate the onset of autoimmune disease.

Animals↗

Transfer to in vitro conditions influences expression and intracellular distribution of galectin-3 in murine peritoneal macrophages.

Galectin-3 is a beta-galactoside-binding lectin that has been implicated in numerous physiological processes, including mRNA splicing, cell differentiation, tumor metastasis and the stress response. We have studied effects of transfer of resident murine peritoneal macrophages to in vitro conditions on galectin-3 in different cell compartments. Galectin-3 was purified by immunoprecipitation with rat monoclonal antibody M3/38, and analyzed by immunoblotting using the same antibody. Transfer to in vitro conditions nearly doubled the total amount of galectin-3 in cells, and caused significant alterations in its intracellular distribution, indicating that galectin-3 is involved in the adaptation of peritoneal macrophages to in vitro conditions.

Animals↗

Concentration of sialic acid in alloxan diabetic rat islets of Langerhans.

A microanalytical procedure for the determination of total and surface sialic acid concentrations was employed to establish their changes in relation to the length of alloxan diabetes in rat islets of Langerhans. 14 and 60 days after alloxan administration (65 mg/kg), the number of Langerhans islets was significantly decreased (p < 0.001) compared to the control. According to their size, the distribution of islets displayed no significant difference in diabetic and control animals 14 days after alloxan administration, while after 60 days no large islets (dia > or = 128 microns) were found in diabetic animals. The surface sialic acid was significantly increased in the small islets (p < 0.001), whereas no change was found in the large islets 14 days after alloxan administration. After 60 days, the surface sialic acid of both small and large islets was significantly decreased (p < 0.001). These results demonstrate that chronic beta-cell destruction induces a decrease in the sialic acid content in the pancreatic islet cells, suggesting that sialic acid might play a role in insulin secretory regulation regarding chronic effects of alloxan beta-cytotoxicity.

Animals↗