Changes of Hippocampal Noradrenergic Capacity in Stress Condition.

This study aimed to investigate the effects of chronic restraint stress (CRS) on the protein levels of dopamine-ß-hydroxylase (DBH), noradrenaline transporter (NET), vesicular monoamine transporter 2 (VMAT2) and brain-derived neurotrophic factor (BDNF), as well as the concentration of noradrenaline (NA) in the rat hippocampus. The investigated parameters were quantified by Western blot analyses and ELISA kits. We found that CRS increased the protein levels of DBH by 30 %, VMAT2 by 11 %, BDNF by 11 % and the concentration of NA by 104 %, but decreased the protein levels of NET by 16 % in the hippocampus of chronically stressed rats. The molecular mechanisms by which CRS increased the hippocampal NA level are an important adaptive phenomenon of the noradrenergic system in the stress condition.

Antioxidant status and sex hormones in women with complex endometrial hyperplasia.

Endometrial tissue is under a strong influence of sex hormones. These hormones are considered as developmental factors of endometrial hyperplasia and endometrial cancer. We examined the influence of gonadotropins (follicle-stimulating and luteinizing hormone) and sex hormones (estradiol, progesterone) on oxidant/antioxidant parameters in blood and endometrial tissue of women with complex endometrial hyperplasia. In blood, superoxide dismutase activity was significantly higher in luteal phase and postmenopause compared to the follicular phase. A significant phase-related difference of glutathione peroxidase and glutathione reductase activity was recorded in the endometrium. Both enzymes had lower activity in luteal phase and postmenopause compared to the follicular phase. The linear regression analysis of individual hormonal variables against antioxidant parameters showed negative correlation between glutathione peroxidase activity and gonadotropin concentrations in the endometrium. The regression of hyperplastic to normal endometrium is the purpose of conservative treatment based on administration of progestogens or gonadotropin-releasing hormone analogues. Our findings indicate that gonadotropins influence the antioxidant enzymes activity in women with complex endometrial hyperplasia, which may affect disease development. Further studies are needed to clarify the molecular basis of hormone action on antioxidant system that may potentially initiate a development of treatments based on redox-dependent mechanism.

Antioxidant status in blood of gynaecological patients: influence of diagnosis and reproductive factors.

Cancer of the reproductive tract is an important cause of morbidity and mortality among women worldwide. In this study we evaluated the influence of diagnostic categories, age and reproductive factors on antioxidant enzymes and lipid hydroperoxides in the blood of gynaecological patients diagnosed with endometrial polyp, myoma, hyperplasia simplex, hyperplasia complex and endometrial adenocarcinoma. Multivariate regression analysis was used to assess the association of diagnosis, age, parity, abortions and abnormal uterine bleeding with the examined parameters. Diagnosis provided the best predictive model for superoxide dismutase, catalase and glutathione peroxidase activities, and also for the lipid hydroperoxide level. Abortions fitted the best predictive model for superoxide dismutase activity. A significant correlation was also found between the predictor variables themselves. This study showed that reproductive and other factors may be associated, at least partially, with antioxidant capacity and ability to defend against the oxidative damage in gynaecological patients with various diagnoses.

Our first experience with extended proximal femoral osteotomy for revision hip surgery.

INTRODUCTION: The extended proximal femoral osteotomy (EPFO) is a demanding but useful technique for revision of both cemented or noncemented femoral components. MATERIALS AND METHODS: Between 2000 and 2004 we performed extended proximal femoral osteotomy (EPFO) in 25 cases during revision hip surgery. The main indication for doing revision surgery was aseptic loosening of both total hip arthroplasty (THA) components (18 patients), whilst in the remaining 7 patients the indications were: aseptic loosening of acetabular component in three patients, septic loosening of THA in two patients, recurrent dislocation of the THA because of incorrectly positioned femoral component in one patient and aseptic loosening of cemented hip hemiarthroplasty in one patient. RESULTS: There were 14 women and 11 men. The mean follow-up was 22 months. The average time to revision was 8.3 years. The mean age at the time of revision was 70.3 years (range 55 to 81). At the time of the last control examination all osteotomy sites had healed with signs of remodelling. The mean time to union ranged from 11 weeks to 6 months, shown by the bridging callous formation in both radiographic projections. Bone remodelling occurred in all patients by 12 months and no complications such as nonunion, excessive fragment migration or wire breakage were found. CONCLUSION: In our experience, the extended proximal femoral osteotomy when properly indicated represents an efficient and reliable technique in revision hip surgery.

Regional differences in antioxidative response of rat brain after cranial irradiation.

In order to examine if differences in activity and inducibility of antioxidative enzymes in rat cerebral cortex and hippocampus are underlying their different sensitivity to radiation, we exposed four-day-old female Wistar rats to cranial radiation of 3 Gy of gamma-rays. After isolation of hippocampus and cortex 1 h or 24 h following exposure, activities of copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD) and catalase (CAT) were measured and compared to unirradiated controls. MnSOD protein levels were determined by SDS-PAGE electrophoresis and Western blot analysis. Our results showed that CuZnSOD activity in hippocampus and cortex was significantly decreased 1 h and 24 h after irradiation with 3 Gy of gamma-rays. MnSOD activity in both brain regions was also decreased 1 h after irradiation. 24 h following exposure, manganese SOD activity in hippocampus almost achieved control values, while in cortex it significantly exceeded the activity of the relevant controls. CAT activity in hippocampus and cortex remained stable 1 h, as well as 24 h after irradiation with 3 Gy of gamma-rays. MnSOD protein level in hippocampus and cortex decreased 1 h after irradiation with 3 Gy of gamma-rays. 24 h after exposure, MnSOD protein level in cortex was similar to control values, while in hippocampus it was still significantly decreased. We have concluded that regional differences in MnSOD radioinducibility are regulated at the level of protein synthesis, and that they represent one of the main reasons for region-specific radiosensitivity of the brain.

Overview of endogenous and synthetic melanocortin peptides.

The melanocortin system consists of five seven-transmembrane spanning G-protein coupled (GPCRs) receptors (MC1R-MC5R), the endogenous agonists a-, B- and melanocyte stimulating hormone (MSH), adrenocorticotropic hormone (ACTH), and the endogenous antagonists Agouti and Agouti-related protein (AGRP). Melanocortin agonists are involved in the regulation of feeding behavior and weight omeostasis in mammals. Structure-activity relationships (SAR) have been performed on the endogenous melanocortin receptor agonists and antagonists that have identified ligand amino acid residues implicated as important for receptor binding and stimulation. Knowledge of putative ligand-receptor interactions may help to design molecules as therapeutic agents for the treatment of physiological diseases.

[Functional and radiographic results in partial unipolar hip joint arthroplasty after 6-15 years].

Due to extreme conditions during civil war in early 1990's we were forced to deviate from accepted guidelines in treatment of intracapsular fractures of the femoral neck. Therefore, majority of patients were treated non-operatively. In those that were subjected to surgery, unipolar hemiarthroplasty was treatment of choice, since conditions permitted us to attempt osteofixation in very few, youngest of our patients. As a result of this practice born of necessity, we can now look back and learn from this unique experience.

Synthesis and activity of the melanocortin Xaa-d-Phe-Arg-Trp-NH tetrapeptides with amide bond modifications.

The melanocortin receptor (MCR) pathway has been identified as participating in several physiologically important pathways including pigmentation, energy homeostasis, inflammation, obesity, hypertension, and sexual function. All the endogenous MCR agonists contain a core His-Phe-Arg-Trp sequence identified as important for receptor molecular recognition and stimulation. Several structure-activity studies using the Ac-His-d-Phe-Arg-Trp-NH2 tetrapeptide template have been performed in the context of modifying N-terminal 'capping' groups and amino acid constituents. Herein, we report the synthesis and pharmacologic characterization of modified Xaa-d-Phe-Arg-Trp-NH2 (Xaa = His or Phe) melanocortin tetrapeptides (N-site selective methylation, permethylation, or amide bond reduction) at the mouse MC1, MC3, MC4 and MC5 receptors. The modified peptides generated in this study resulted in equipotent or reduced MCR potency when compared with control ligands. The reduced amide bond analog of the Phe-d-Phe-Arg-Trp-NH2 peptide converted its agonist activity into an antagonistic at the central mMC3 and mMC4 receptors involved in the regulation of energy homeostasis, while retaining full agonist activity at the peripheral MC1 and MC5 receptors.

The melanocortin pathway: effects of voluntary exercise on the melanocortin-4 receptor knockout mice and ACTH(1-24) ligand structure activity relationships at the melanocortin-2 receptor.

The melanocortin pathway consists of endogenous agonists, antagonists, G-protein coupled receptors, and ancillary proteins that mediate the function of the endogenous antagonists. The melanocortin-4 receptor (MC4R) is involved in the regulation of obesity and the melanocortin-2 receptor (MC2R) is involved in the regulation of steroidogenesis. Herein, we present the effects of voluntary exercise on the MC4R knockout mice in terms of bypassing the morbid obesity and hyperphagia phenotypes associated with this genetic obesity model. Additionally, a systematic truncation study of the adrenocorticotropin hormone (ACTH 1-24) has been performed and characterized at the cloned MC2R.

[Study of Co-Cr-Mo alloys in metal-ceramics]. / Ispitivanje Co-Cr-Mo legura u metal-keramici.

The new interest of dental workers in Co-Cr-Mo alloys has increased because of the potential risk of nickel-related allergic responses and berylium-related toxic effects. The aim of the present study was to assess the transverse bond strength, rigidity modulus and compatibility of ceramics in four selected Co-Cr-Mo alloys. The obtained results indicate that oxide formation was not easily controlled and that additional sand-blasting was necessary after oxidation of the metal. The bond strength and rigidity modulus were the highest in the alloy containing titanium. Thermal shock tests confirmed the results of mechanical testing.

[Bond strength and rigidity modulus of non-precious alloys]. / Jacina metalo-keramickog meduspoja i modul krutosti neplemenitih legura.

The use of non-precious alloys in construction of metalceramic restorations has been increasing since 1979. This was the reason to study the bond strength and rigidity modulus of four selected base metal alloys developed for use with bonding porcelain. Three point loading design test was performed to evaluate the bond strength. The specimens made of Co-Cr-Mo alloys showed porcelain fracture at bond failure in a high percentage. Ni-Cr-Mo alloys showed mainly lamelar failure of the bond. The highest bond strength and rigidity modulus were found, in alloy containing titanium. It was noticed that ceramic can increase the rigidity of modulus metal by almost ten times. All studied alloys are technically very sensitive and manufacturer's instruction must be closely followed.