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Biomedical subjects

A Stavljenić

Publications and source records attributed to A Stavljenić.

At least 19 recordsLinked to original sources

The role of tumor necrosis factor-alpha in the generation of acute phase response and bone loss in rats and talc granulomatosis.

BACKGROUND: Trabecular bone loss is the part of acute-phase response (APR) in rats with subcutaneous granulomatous inflammation induced by talc. EXPERIMENTAL DESIGN: We investigated the possible involvement of inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of bone loss and other aspects of APR. Intraperitoneal administration of specific neutralizing antibodies to TNF-alpha or of recombinant cytokine indicated that TNF-alpha was the primary mediator of bone changes, evidence as slower bone elongation rate, bone marrow hyperplasia, and decreased trabecular bone volume and osteoblast number in tibial metaphysis. RESULTS: Moreover, direct intraosseal administration of anti-TNF-alpha antibody neutralized the effect of inflammation on bone. On the other hand, the serum indices of the APR (decreased zinc and iron concentrations, ACTH and C-reactive protein concentration) were not greatly affected after the administration of anti-TNF antibody, except for the normalization of the hypercupremia and weight loss. CONCLUSIONS: The data presented in this report demonstrated direct involvement of TNF-alpha in the generation of bone alterations during the development of APR in rats with talc granulomatosis.

Acute-Phase Reaction

Role of 1,25-dihydroxyvitamin D3 in the generation of the acute-phase response in rats with talc-induced granulomatosis.

Subcutaneous injection of nonspecific irritants such as magnesium silicate (talc) provokes granulomatous inflammation in the rat. Part of the acute phase response (APR) in these animals is the loss of trabecular bone at sites distant from the site of inflammation. To assess the possible involvement of vitamin D in the bone loss, we studied the development of the acute phase response in vitamin D-deprived rats. The serum APR provoked by subcutaneous inflammation in rachitic rats consisted of hypozincemia, hypercupremia, increased alkaline phosphatase activity and adrenocorticotropic hormone (ACTH) concentration, and was similar to that in control animals except for the absence of hypoferremia. Control rats with talc-induced subcutaneous inflammation also had splenomegaly and decreased total and mononuclear peripheral blood cell counts, while subcutaneous inflammation did not induce spleen changes in rachitic rats. Subcutaneous inflammation induced the loss of trabecular bone and decreased the osteoblastic cell count in tibial metaphyses in control animals. Rachitic rats had abundant osteoid on trabecular surfaces, and the number of osteoblasts and osteoclasts was comparable to that of the controls. Subcutaneous inflammation did not affect any of the bone parameters in rachitic rats. These results indicate that vitamin D plays an important role in the generation of the acute phase response during inflammation, particularly in the induction of spleen and bone cell changes. The discrepancy of the blood on one hand and bone and spleen indices of the APR on the other, indicate that they may be divergent pathways in the generation of the inflammatory response, some of which may be dependent on vitamin D.

Acute-Phase Reaction

Urinary glycosaminoglycans in different phases of Balkan endemic nephropathy.

The relationship between glycosaminoglycans and beta 2-microglobulin, glycosaminoglycans and N-acetyl-beta-D-glucosaminidase as well as the relationship between the chondroitin sulfate/heparan sulfate ratio and SDS electrophoresis in the urine of subjects from the endemic area of Balkan nephropathy was studied in order to establish a method for early detection of this disease. The results show an unquestionable increase in urinary excretion of total glycosaminoglycans in subjects with or suspected of having Balkan endemic nephropathy while the chondroitin sulfate/heparan sulfate ratio was not statistically different between the groups studied. Thus, the chondroitin sulfate/heparan sulfate ratio cannot be used as a cheap and quick semiquantitative method for the diagnosis of early tubular damage in Balkan endemic nephropathy. However, the determination of total glycosaminoglycans in the urine of subjects from endemic areas proved to be valuable additional information helping with the diagnosis of Balkan endemic nephropathy.

Acetylglucosaminidase

Polymorphism of apolipoprotein E, lipoprotein(a), and other lipoproteins in children with type I diabetes.

We assessed the effect of particular apolipoprotein (apo) E phenotypes, lipoprotein(a) [Lp(a)], and other lipoproteins on the development of dyslipoproteinemia in 450 patients with type I diabetes, ages 13-14 years. The control group consisted of 450 healthy school children of both sexes, ages 13-14 years. Both groups were found to be normolipidemic, but the concentration of Lp(a) was significantly (P < 0.05) higher in the diabetic children than in the control group. Apo E 3/2 and apo E 4/4 phenotypes were more frequent in the group of diabetics. Diabetics with the apo E 3/3 phenotype had higher concentrations of very-low-density lipoprotein (VLDL) and Lp(a), and lower concentrations of low-density lipoprotein (LDL) than the apo E 3/3 nondiabetics. For apo E 3/2 phenotypes, total cholesterol, LDL cholesterol, LDL, apo A-I, and Lp(a) concentrations were higher in the diabetic children than in the control group; for apo E 4/3 phenotypes, this was true for triglycerides and VLDL cholesterol. The distribution of Lp(a) lipoprotein concentrations between 0.01 and > 0.5 g/L indicated a more frequent occurrence of higher Lp(a) values in diabetic children than in the control group. Results of this study indicate that an increased concentration of Lp(a) lipoprotein and apo E 3/2 and apo E 4/3 phenotypes contribute to the expression of dyslipoproteinemia in type I diabetes in childhood.

Adolescent

Distribution of structural and trace elements in human temporal bone.

This study was undertaken to evaluate a systematic analysis of mineral and trace elements of individual functionally determined parts of adult temporal bone. Marked differences were observed in basic structural elements (Ca, P, Mg, and Zn) among different bone regions. The more so, molar Ca/P ratio was significantly different in various regions, being highest in the hammer and vestibular regions. Taxonomic analysis revealed specific differences in the mineral ratio between the two petrous bone regions believed to develop from various embryonal bases. According to results, the observed differences in mineral trace element composition of particular regions of human temporal bone might be explained by their developmental specificities and functional adaptation.

Adult

Acute zinc deficiency and trabecular bone loss in rats with talc granulomatosis.

Subcutaneous inflammation induced by magnesium silicate (talc) leads to the suppression of bone elongation, osteoblast insufficiency, and subsequent bone loss in rats. Since bone and immunological changes in talc granulomatosis are similar to those observed in zinc deficiency, we investigated the kinetics of zinc tissue distribution and the effects of zinc supplementation on the development of bone loss in rats with talc-induced inflammation. Decrease in serum zinc concentration was observed between 5 and 15 h in rats with talc granulomatosis. It was paralleled by the accumulation of zinc in the liver and rapid disappearance of osteoblasts from the trabecular bone surfaces. However, talc-injected rats supplemented parenterally and orally with zinc sulfate exhibited a decrease in osteoblast trabecular surface comparable to that of unsupplemented rats bearing granulomas despite normalized serum zinc concentrations. Zinc supplementation slightly increased osteoblast trabecular surface in all supplemented groups, but this effect was not significant. We conclude that zinc is the earliest indicator of the acute-phase response in rats with talc granulomatosis. Although zinc appears to be important for the normal function of bone cells, there is no causative relationship between acute zinc deficiency and decreased osteoblast number and activity in rats with talc granulomatosis.

Acute-Phase Reaction

[Serum acute phase proteins for determining disease activity of ulcerative colitis and Crohn disease].

We studied the activity assessment of ulcerative colitis and Crohn's disease by 5 acute phase reactants: C-reactive protein (CRP), alpha 1-acid glycoprotein, alpha 1 antitrypsin, haptoglobin and fibrinogen. From a large register of patients with inflammatory bowel disease (IBD) we chose randomly 91 patients: 61 with ulcerative colitis and 30 with Crohn's disease. As a reference point in the disease activity assessment we used standard clinical indices. Statistical analysis was performed by non-parametric methods: the Kruskal-Wallis and Fisher's exact test. The disease activity assessment in patients with ulcerative colitis by the index according to Powell-Tuck indicated that the patients with active disease (N = 19) had significantly higher levels of all acute phase proteins mentioned above except fibrinogen (alpha less than 0.05 to 0.001) than patients in remission (N = 42). Analysis of the same data by Fisher's exact test indicated that there had been a probability for all the proteins measured to be higher than the normal values, particullary CRP (p less than 10(-8) and the other somewhat less. In patients with Crohn's disease, the disease activity assessment was performed by 2 indices. According to "The Crohn's Disease Activity Index" (CDAI), only alpha-1 acid glycoprotein and haptoglobin (alpha less than 0.05) were higher in patients with active disease (N = 4) than in patients with remission (N = 26).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins

Lecithin:cholesterol acyltransferase activity in patients with acute myocardial infarction and coronary heart disease.

Literature data suggest that identification of the conditions preventing lecithin:cholesterol acyltransferase (LCAT) to produce normal cholesterol esterification might be of utmost importance in the follow-up of atherosclerosis. Interrelationship between LCAT activity, and total cholesterol (TC), unesterified cholesterol (UC), esterified cholesterol (EC), low and high density lipoprotein cholesterol (LDL-C, HDL-C), triglycerides (TG), phospholipids (PL), free fatty acids (FFA), l-lactate (LAC), and electrolytes, i.e. zinc (Zn), calcium (Ca) and magnesium (Mg), was investigated in 60 patients with acute myocardial infarction (AMI), 30 patients with coronary heart disease (CHD) and 30 healthy control subjects. Results of the study revealed LCAT activity to be significantly decreased in atherosclerotic patients, with a significantly increased ratio of unesterified-esterified cholesterol (UC/EC), as compared to the control group of normal subjects. A decreased LCAT activity was accompanied by elevated values of phospholipids and LDL-C, a moderate increase in triglycerides, and a decreased quotient of HDL3/HDL2 cholesterol. Accordingly, a decreased activity of LCAT could with great certainty be considered a high-risk biochemical factor for atherosclerosis.

Adult

Haematological features of the population of the area of Croatia, Yugoslavia, endemic for Balkan nephropathy.

Normochromic, normocytic anaemia is a sign recognized as essential for the diagnosis of Balkan endemic nephropathy, although its relationship to the disease is still unclear. The aim of this study was to investigate whether a random sample of the population of a village endemic for nephropathy differed from the population of a village with no clinical case of nephropathy with respect to certain basic haematological parameters. During a screening campaign in 1984, 133 blood samples were collected from the endemic village and 40 from the nonendemic village and analysed for a number of haematological parameters; in 1991, 449 samples were collected in the endemic village and 156 in the nonendemic village and analysed for haemoglobin content and red blood cell count. Whereas in 1984 the haemoglobin content and red blood cell count were significantly lower in the endemic village (p less than 0.01), in 1991 the erythrocyte count was much lower in the nonendemic village and there was no difference in haemoglobin concentration. Several controversial explanations, all of them speculative, are offered.

Anemia

Epidemiological aspects of Balkan endemic nephropathy in a typical focus in Yugoslavia.

Balkan endemic nephropathy is a noninflammatory bilateral kidney lesion that affects rural populations in several circumscribed areas of the Balkans. Its etiology is still not understood, but recently it has been associated with exposure to nephrotoxic mycotoxins. It has been known to be present since the mid-1950s in 14 villages in an endemic area of Croatia, where approximately 10,000 people are at risk. Its prevalence fluctuates between 0.4 and 8.3%, showing a slight decline in recent years, but it has not disappeared from any of the endemic villages. The occurrence of the disease in several ethnic groups contradicts the hypothesis of a primary hereditary basis for Balkan endemic nephropathy. Recently, evidence has been found of an extremely high incidence of urinary tract tumours in the endemic area, and particularly of urothelial tumours of the pelvis and ureter. There may therefore be a common causative agent for these two rare diseases.

Adolescent

In vivo models in the study of osteopenias.

A better insight into bone pathophysiology is required for a full understanding of the mechanisms leading to bone loss in humans. Animal models of bone disease appear to be the most valuable for this purpose. Certain differences in bone metabolism exist between various species. Non-human primates are the most human-compatible animal species, whereas dogs appear to be most appropriate among small laboratory animals. However, the high cost of studies on primates and dogs restricts the number of animals examined. The rat is the most frequently used animal. Many similarities have been observed in bone metabolism of humans and rats. Like humans, rats also lose bone with aging, and in some parts of the rat skeleton bone remodelling occurs. However, bone metabolism in rat is mainly characterized by growth and modelling, which makes the rat model completely appropriate for studies of juvenile osteopenias. Characteristics of animal models of osteopenias should be comprehensively investigated in order to render the study results completely, or with known exceptions, comparable to the corresponding processes in humans.

Adrenal Cortex Hormones

Decreased osteoinductive potential of bone matrix from ovariectomized rats.

The effect of estrogen deficiency on matrix-induced bone formation was investigated. Female rats were ovariectomized and given demineralized bone matrix (DBM) intramuscularly 3 weeks before termination. The DBM was taken from previously ovariectomized and from sham-operated on rats. The animals were killed at various times after ovariectomy (6-27 weeks). Implants were processed undemineralized for histologic and biochemical studies. Normal DBM implanted in ovariectomized or normal rats induced extensive bone formation 6 weeks postovariectomy. The amount of newly formed bone decreased with the age of host rats. Bone matrix taken from ovariectomized rats was incompletely resorbed in both ovariectomized and normal hosts, therefore reducing the extent of osteogenesis and bone-marrow formation. Instead, chondrogenesis was intensive, but delayed. The calcium, magnesium, and zinc contents were decreased in implants taken from ovariectomized rats when compared with implants taken from normal animals. Normal osteoinduction with DBM taken from normal rats and implanted in ovariectomized rats and the absence of osteogenesis with DBM taken from ovariectomized rats indicate that an estrogen-deficient environment is not crucial for altered matrix-induced endochondral bone formation in ovariectomized rats. An altered composition of matrix from ovariectomized rats and a subsequent abnormality in the cell-matrix interaction should be considered responsible.

Animals

Holographic analysis of the human pelvis.

Twelve fresh human pelves with preserved lumbar spines, hip joints, and ligaments, were tested by double-exposure and sandwich-hologram interferometry. During physiologic loadings (50-300 N), the pelvis moved as a whole downward and backward. Iliac wings exhibited marked undulation, except for the central part, which showed minor deformations. The sacrum moved downward and rotated forward over an axis 5-9 cm below the promontorium. Removal of the sacroiliac interosseous ligaments eliminated all joint movements and caused a tighter contact between articular surfaces. Removal of the sacrotuberous and sacrospinous ligaments had no influence on the pelvic behavior. The magnitudes of deformations as well as their underlying mineral contents were unequally distributed between the two pelvic sides. These results indicate that the sacroiliac interosseous ligaments are the main determinant of sacral movement. Asymmetric load transmittance to the hip joints might be responsible for the mineral content differences between the pelvic sides.

Adult

Talc granulomatosis in the rat. Involvement of bone in the acute-phase response.

We investigated the dynamics of the acute-phase response (APR) and osteoblast trabecular surface in rats with subcutaneous inflammation provoked by magnesium silicate (talc). The first visible indicator of the APR was a rapid and profound hypozincemia, paralleled by a decrease in metaphyseal trabecular surfaces covered with osteoblasts in long bones. Both the intensity of serum APR and the decrease in osteoblast trabecular surface were directly proportional to the number of granulomas. Alterations in bone metabolism were specific for the inflammation, whereas mild hypozincemia and decrease in mononuclear and increase in polymorphonuclear peripheral white blood cell fractions developed in animals pair-fed with rats bearing two or four granulomas. Rats with talc granulomatosis had high serum ACTH and corticosterone levels, but neither adrenalectomy nor high doses of hydrocortisone could revert bone alterations in talc-injected animals. Glucocorticoids were necessary for the development of hypozincemia and hypercupremia seen in talc granulomatosis, as well as for normal bone metabolism. Inhibition of prostaglandin synthesis had no effect on bone alterations and serum APR in rats bearing talc-induced granulomas. We conclude that the decrease in bone formation constitutes an important aspect of the host acute-phase response in a rat model of talc granulomatosis.

Acute-Phase Reaction

Effects of pyridoxine and riboflavin supplementation on physical fitness in young adolescents.

The effects of pyridoxine and riboflavin supplementation on physical fitness was studied in a group of children with higher prevalence of subclinical, biochemically defined pyridoxine and riboflavin deficiencies. One hundred and thirteen children aged 12-14 years were allocated to three groups to receive daily (except Sundays) for two months either a placebo or a supplement of pyridoxine or riboflavin. The supplementation resulted in marked improvement of pyridoxine and riboflavin nutrition status and was followed by disappearance of respective biochemical deficiencies. The improvement in pyridoxine biochemical status was also accompanied by a slight and statistically significant increase in physical fitness (p less than 0.05) assessed by bicycle ergometer technique. The increase in physical fitness in the riboflavin supplemented group was statistically non-significant (p greater than 0.05). In both supplemented groups there was a significant increase in physical fitness in subjects with initially deficient biochemical vitamin status whereas supplementation had no effect on physical fitness in subjects with initially high biochemical values.

Adolescent