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Background/Aim. Multiple sclerosis (MS) is an immunemediated disease of the nervous system in which the myelin sheath is destroyed during the process of neurodegeneration. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS in which preservation of myelin and remyelination of axons can improve neuron survival. The aim of the study was to evaluate the activation capacity of neuronal tissue by autoimmune inflammation and treatment with intermittent (i) theta burst stimulation (TBS)-iTBS or continuous TBS (cTBS) based on the expression profiles of nestin in astrocytes, oligodendrocytes, and neurons. Methods. Two forms of TBS - iTBS and cTBS - were used to extend the period during which axons can be remyelinated. It was investigated how iTBS or cTBS protocols affect the expression profiles of nestin with glial fibrillary acidic protein, myelin basic protein (MBP), and neuronal nuclear protein in rat spinal cord. Changes at the molecular level were monitored using the immunofluorescence method. Results. The obtained results showed that both protocols (iTBS and cTBS) increased the expression of nestin and MBP and reduced astrogliosis in the spinal cord of EAE rats. Conclusion. The therapeutic potential of TBS in EAE contributes to the improvement of the intrinsic ability to recover from spinal cord injury. [ABSTRACT FROM AUTHOR]

Copyright of Serbian Dental Journal / Stomatološki Glasnik Srbije is the property of National Library of Serbia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background/Aim. Cell proliferation and the regulation of protein expression play an important role in gastritis, but in chronic superficial gastritis (CSG), they are rarely reported. The aim of this study was to determine the relationship between the expression of nuclear factor kappa B (NF- ϰ B) and regulatory proteins and the rat CSG. Methods. The CSG rat model was established artificially, by chemical agents and irregular diet. The expression of epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) in the gastric mucosa of CSG rats was measured by immunohistochemistry, while mRNA expression levels of NF- ϰ B p65 were detected by in situ hybridization. Results. There was more obvious infiltration of inflammatory cells in the gastric mucosa of CSG rats than in that of control rats, and the inflammation score was significantly increased. The expression levels of PCNA, EGFR, and NF- ϰ B p65 mRNA in the gastric mucosal cells of CSG model rats increased significantly. Correlation analysis showed that the inflammation score was positively correlated with the expression levels of NF- ϰ B p65 mRNA and EGFR, while it presented no significant correlation with the expression level of PCNA. In addition, there was a significant positive correlation between NF- ϰ B p65 mRNA and EGFR levels. Conclusion. High expression of NF- ϰ B and EGFR plays an important role in the occurrence and progression of CSG, and it is significantly positively correlated with the degree of inflammation in the gastric mucosa. Therefore, changes in NF- ϰ B and EGFR expression may be used as important indicators for the assessment of CSG; changes in their expression levels are helpful to assess the degree of gastric mucosal lesions and progression of CSG. [ABSTRACT FROM AUTHOR]

Background/Aim. The reaction of an organism to radiation depends on the level of irradiation and the sensitivity of the affected tissue cells. The biological effects on the cells and tissues are proportional to the absorbed radiation energy. The aim of our study was to examine the effects of hypofunction of the pituitary gland, previously irradiated with x-rays, on the growth of rat's craniofacial and stomatognathic system as well as rat's tibia. Methods. A total dose of x-rays of 27.92 Gy was applied in eight sessions in the period from 8 to 63 days of animal age on their heads and the effects of irradiation-induced hypofunction of the pituitary gland on the growth of rat's craniofacial and stomatognathic system and tibia were examined. In order to differentiate the effects of the irradiated pituitary gland from the direct effects of x-rays on the head, the experiment was set as a double study. One group of animals had the pituitary gland protected with a lead plate set beneath the projection of the gland, while the second group was irradiated with the same dose, but without the protection. The control group of animals were non-irradiated. Results. Growth measurements of numerous parameters of the craniofacial and stomatognathic system as well as tibia in rats with the entire locally irradiated head showed a statistically significant delay, compared to both the nonirradiated control group and the group with the protected pituitary gland. Conclusion. The damage of the stomatognathic and craniofacial system was greater in animals with irradiated head without pituitary gland protection compared to those with the gland protection whereby the growth of the craniofacial system was most affected. Irraduition-induced pituitary gland hypofunction and irradiation itself showed a stronger effect on the lower jaw growth rate impairment compared to the upper jaw. Similarly, the delay in tibia growth was more pronounced in animals without pituitary gland protection during irradiation of their heads compared to non-protected ones. [ABSTRACT FROM AUTHOR]

Background/Aim. Organophosphate pesticides (OPs) are used extensively worldwide in agriculture and forestry, and their application represents a major health problem for humans and animals. The aim of this study was to investigate the possibility of the adaptation of an organism to the prolonged administration of a low dose of diazinon. Methods. The study was conducted on a total of 60 male Wistar rats. The f irst 3 0 r ats were divided into four equal diazinon groups (n = 6) and the control one (corn oil). Diazinon was orally administered once at doses: 200, 400, 600, 800 mg/kg (one dose - one group). The concentration of glucose, the activity of α -amylase and the relative activity of LDH1- LDH5 isoenzymes in the blood were measured 24 hours after the application. The remaining 30 rats were divided into two equal diazinon groups (n = 10) and the control one (corn oil). The first group was treated during 7 days, and the second during 14 days with 55 mg/kg of diazinon (1/10 of previously determined LD50 value). The histopathology of the pancreas and the liver, as well as the relative activities of LDH isoenzymes in the blood, were determined after the completion of both time periods. Results. Single administration of increasing doses of diazinon resulted in a significant increase in the concentrations of glucose, activity of α-amylase and LDH isoenzymes. Subacute application of a low diazinon dose induced histopathological changes in the pancreas manifested by acinar cell necrosis, and in the liver in the form of portal hepatitis and multifocal necrosis. The cumulative doses resulted in statistically significantly lower activities of LDH isoenzymes compared with the single administration of these doses, indicating a lower degree of the cells damage after the subacute diazinon administration. Conclusion. Subacute administration of a low dose of diazinon leads to a different adaptation degree of organs and organ systems to toxic effects caused by this organophosphate. [ABSTRACT FROM AUTHOR]

Background/Aim. Experimental autoimmune encephalomyelitis (EAE) is a model of multiple sclerosis (MS), in which we investigated the neuroprotective effect of agmatine (AGM), known as a primary amine produced via the decarboxylation of L-arginine. Methods. Dark Agouti rats were divided into groups: control (C), Complete Freund's Adjuvant (CFA), EAE rats decapitated on the 13th day post immunization (dpi) (EAE13) and on the 20th dpi (EAE20), EAE animals given three (EAE+AGM13) and 10 (EAE+AGM20) doses of AGM, and healthy animals administered three/10 doses of AGM (AGM). Thiobarbituric acid-reacting substances (TBARS), SH groups (SH), total glutathione (GSH), glutathione peroxidase activity (GPx), superoxide dismutase activities (tSOD, MnSOD, CuZnSOD) and nitrite/nitrate concentration (NO2+NO3) were assessed in plasma and brain structures [whole encephalitic mass (WEM) and brainstem (BS)]. Results. The obtained results showed that AGM treatment successfully attenuated severe clinical deficits in EAE. Applications of AGM in EAE rats induced normalized TBARS, SH, GSH, GPx and NO in WEM. In BS, AGM expressed less prominent effects, inducing normalized TBARS, GPx and NO, but no effect on SH and GSH. In both brain structures, tSOD activity lowered and normalized at the peak and in the remission phase of the disease, post-AGM treatment. The effect of AGM on the MnSOD in EAE was expressed in WEM/BS only in the remission phase as a reduced activity. Conclusion. Milder clinical form of developed EAE in rats indicates promising therapeutic effect of AGM in MS. The activated antioxidant system a nd s uppressed o xidative/nitrosative stress development may denote a successful blockade of neuroinflammation initiated by EAE immunization. The study implies the capability of AGM to attenuate oxidative/nitrosative damage at the peak of EAE by modulating antioxidative defense capacity during the time-course of the disease. Thus, AGM may be considered as an agent with a beneficial effect on neuroinflammation in EAE. [ABSTRACT FROM AUTHOR]

Background/Aim. Dysfunctions at the cellular, tissue, and organ level, which can result in death, are caused by metabolic changes and affection on the regulation of gene transcription and micro- and macrocirculation. The aim of the present study was to assess the impact of hyperbaric oxygenation (HBO) on isolated heart as well as on the oxidative status of rats with sepsis. Methods. The investigation included male Wistar albino rats classified into three groups: the first group was a control group (CTRL); the second group included animals exposed only to the induction of sepsis without HBO treatment (the Sepsis group), while the third group included animals treated with HBO after the induction of sepsis (the Sepsis + HBO group). For the induction of sepsis, fecal peritonitis model was used (3 mL/kg of fecal suspension administered intraperitoneally). After the induction of sepsis, the rats were exposed twice a day (on 12 hours) to H BO treatment at 2.8 atmospheres absolute (ATA) for 90 minutes over a period of 3 days. 72 h after the confirmation of sepsis, the animals were sacrificed and the hearts were retrogradely perfused on the Langendorff apparatus at a gradually increased coronary perfusion pressure (CPP = 40-120 cm H2O). The following parameters of heart function were continuously recorded: maximum and minimum rate of left ventricular pressure development (dp/dt max, dp/dt min); systolic and diastolic left ventricular pressure (SLVP and DLVP); heart rate (HR). Coronary flow (CF) was measured flowmetrically. Following oxidative stress markers were measured: nitrites (NO2-), superoxide anion radical (O2-), hydrogen peroxide (H2O2), index of lipid peroxidation (TBARS), activity of superoxide dismutase (SOD) and catalase (CAT) and the level of reduced glutathione (GSH). Results. There were no significant differences in dp/dt max, dp/dt min, SLVP and HR between the groups. CF was statistically significantly higher (p < 0.01) in the sepsis group. The values of all cardiac oxidative markers were lower in the sepsis + HBO group (p < 0.05), while systemic pro-oxidative and antioxidative parameters were unchanged. Conclusion. Our results showed that HBO treatment was not associated with improved cardiac function and coronary perfusion, while expressed promising beneficial effects on cardiac oxidative stress. [ABSTRACT FROM AUTHOR]

Background/Aim. Exposure of living organisms to γ-radiation results in the overproduction of free radicals. The aim of the study was to test if the subacute administration of micronized zeolite (MZC) accomplishes radioprotective role based on the evaluation of the status of oxidative stress (OS) in the brain and 8-hydroxyguanosine (8-OH-dG) in the plasma of the rats exposed to the single γ-ray irradiation of 2 and/or 10 Gray (Gy). Methods. Wistar rats were on a four-week normal or 5% MZC supplemented diet and afterward exposed to the single γ-ray irradiation of 2 a nd 1 0 Gy. Groups of rats were: a) on a normal diet (the control group, and 2Gy and 10Gy groups); b) on 5% MZC supplemented diet (the control group - MZC, MZC + 2Gy, and MZC + 10Gy groups). We measured malondialdehyde (MDA), glutathione (GSH) total, and activity of total superoxide dismutase (tSOD) and manganese superoxide dismutase (MnSOD) in vulnerable brain regions (cerebellum, hippocampus, and cerebral cortex) and 8-OH-dG in plasma. Results. Lower MDA was found in the MZC+2Gy and MZC+10Gy groups compared to the 2Gy and 10Gy groups. Activity od total SOD was higher in the MZC+10Gy group than in the 10Gy one. G SH was the highest in the 10Gy group. Compared to the control group, 8-OH-dG was extremely higher in groups radiated with 10 Gy regardless of a diet, but slightly lower in the MZC+2Gy and 2Gy groups. Conclusion. Subacute MZC pretreatment accomplished partial radioprotective effect in irradiated rats compared to non-irradiated rats, based on suppressed SOD activity at 2 Gy, and reduced brain MDA when exposed to 2 Gy and 10 Gy. [ABSTRACT FROM AUTHOR]

Background/Aim. Methotrexate (MTX) plays a significant role in the treatment of various diseases, but the toxicity remains the main issue of its use, especially when administered in high doses. Considering altered pharmacokinetics of MTX as a factor strongly implicated in the large interpatient variability and unexpected toxicity in certain patients, the accurate description of MTX pharmacokinetic behaviour of both low and high doses is of the utmost importance. Therefore, the objective of this study was to determine the pharmacokinetics of MTX after intravenous (iv) administration in ascending doses of 5, 40, 80 and 160 mg/kg in rats and to select the appropriate mathematical model describing MTX pharmacokinetics. Methods. Plasma concentrations of MTX were measured using the liquid chromatography - mass spectrometry (LC/MS) method. Pharmacokinetic parameters were calculated by noncompartmental and two-compartmental integer-order analyses. Results. MTX showed linear pharmacokinetics following iv administration up to the dose of 80 mg/kg. The administration of a high dose of MTX (160 mg/kg) resulted in the similar pharmacokinetic behaviour as when applied in the twice lower dose (80 mg/kg), which can be explained by dose-dependent changes in the expression of solute carrier (SLC) and ATP binding cassette (ABC) transport proteins and intracellular metabolism. Furthermore, the classical two-compartment model could not explain the pharmacokinetics of MTX in a small percentage of experimental animals, which opens up new strategies for the use of fractional order pharmacokinetic models in MTX therapy optimisation. Conclusion. These results of pharmacokinetic analyses may be helpful in adjusting the dosage regimen of MTX, but the application of novel pharmacokinetic models, such as those based on fractional calculus, is still needed in the process of MTX therapy optimisation. [ABSTRACT FROM AUTHOR]

Background/Aim. Energy drinks (EDs) are widely used by athletes as ergogenic agents and Red Bull® is one of the most consumed EDs among them. The aim of this study was to determine the acute and chronic effects of Red Bull® on cardiodynamics and parameters of oxidative stress in physically trained rats. Methods. Rats were subjected to a swimming practice (1h a day, 5 days a week, for 4 weeks). They were divided into 4 groups: rats that did not consume ED either before swimming or prior to sacrificing; rats that did not consume ED before swimming but did consume ED 30 min prior to sacrificing; rats that consumed ED 30 min before every swimming training but did not consume ED prior to sacrificing; rats that consumed ED 30 min before every swimming training and 30 min before sacrificing. After sacrificing, the hearts of the rats were isolated and perfused according to the Langendorff technique. The parameters of cardiac function were recorded, and also the levels of prooxidants were measured in the coronary effluent during coronary autoregulation. Results. Acute administration of the ED had a positive inotropic effect (manifested as a significantly higher level of the maximum and minimum rate of pressure development in the left ventricle), while chronic administration affected the isolated increase in systolic left ventricular pressure. The prooxidative effect of the ED was observed, which was more pronounced in chronic consumption. Conclusion. The main conclusion of our study is that chronic consumption of ED changes the cardiovascular response and redox status in acute consumption ED. [ABSTRACT FROM AUTHOR]

Background/Aim. Recently, there has been an increased interest in novel dietary antioxidants, including omega-3 fatty acids and bioactive proteins present in milk. The aim of this study was to examine potential antioxidant effects of four-weeks long fish-based and milk-based diets in female Wistar rats. Methods. Four-months old rats were divided into three groups receiving either: control diet, diet enriched with fish meal, or diet enriched with milk. The activities of antioxidant enzymes: glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), and concentration of thiobarbituric acid reactive substances (TBARS) were determined in liver homogenates obtained at the end of the treatment period. Results. Statistically significant higher activities of GPx (3.52 ± 0.73 U/mg) and CAT (147.25 ± 15.93 U/mg) were detected in rats fed with fishbased meal in comparison with both the control (GPx: 1.93 ± 0.11 U/mg; CAT: 99.37 ± 10.03 U/mg) and the group fed with milk-based diet (GPx: 1.72 ± 0.52 U/mg; CAT: 104.18 ± 37.49 U/mg). Despite somewhat lower concentration of TBARS in the milk-treated group (0.88 ± 0.23 nmoL/mg), no significant differences were detected in comparison with other groups (the control group: 1.00 ± 0.08 nmoL/mg; the fish-based diet group: 1.13 ± 0.15 nmoL/mg). Conclusion. Diet enriched with fish could improve one's oxidative status by enhancing activities of antioxidant enzymes in the liver tissue. On the contrary, we failed to obtain results suggesting that milk could serve as a source of dietary antioxidants. [ABSTRACT FROM AUTHOR]

Background/Aim. Chronically induced hypermethioninemia leads to hyperhomocysteinemia which causes oxidative stress, atherogenesis, neurodegeneration and cancer. However, little is known about the acute and subchronic effects of DL-methionine (Met). The aim of study was to assess the effects of acutely and subchronically applied Met on oxidative stress parameters in rat plasma [enzymes: catalase (CAT), glutathione peroxidise (GPx), superoxide dismutase (SOD) and index of lipid peroxidation, malondialdehyde (MDA)], and acetylcholinesterase (AChE) activity in rat cardiac tissue. Methods. The enzymes activities, as well as MDA concentration were evaluated following acute (n = 8) and subchronic (n = 10) application of Met [i.p. 0.8 mmoL/kg body weight (b.w.) in a single dose in the acute overload or daily during three weeks in the subchronic overload]. The same was done in the control groups following application of physiological solution [i.p. 1 mL 0.9% NaCl (n = 8) in the acute overload and 0.1-0.2 mL 0.9% NaCl, daily during three weeks (n =10) in the subchronic overload]. Tested parameters were evaluated 60 minutes after application in acute experiments and after three weeks of treatment in subchronic experiments. Results. There were no difference in homocysteine values between the groups treated with Met for three weeks and the control group. Met administration significantly increased the activity of CAT and GPx after 1 h compared to the control group (p = 0.008 for both enzymes), whereas the activity of SOD and MDA concentrations were unchanged. Subchronically applied Met did not affect activity of antioxidant enzymes and MDA level. AChE activity did not show any change in rat cardiac tissue after 1 h, but it was significantly decreased after the subchronic treatment (p = 0.041). Conclusion. Results of present research indicate that Met differently affects estimated parameters during acute and subchronic application. In the acute treatment Met mobilizes the most part of antioxidant enzymes while during the subchronic treatment these changes seems to be lost. On the contrary, the acute Met overload was not sufficient to influence on the AChE activity, while longer duration of Met loading diminished function of the enzyme. These findings point out that methionine can interfere with antioxidant defense system and cholinergic control of the heart function. [ABSTRACT FROM AUTHOR]

The aim of the present study was to examine, evaluate and compare the effects of administered dipeptidyl peptidase-4 (DPP4) inhibitors saxagliptin and sitagliptin on lipid status parameters and blood pressure in rats with streptozotocine induced diabetes mellitus type 2. Forty-eight Wistar albino rats were divided randomly into 4 groups: 1. group I: control healthy group; 2. group II: rats with diabetes mellitus type 2; 3. group III: rats with diabetes mellitus type 2+ treated with 0.6 mg/kg of sitagliptin; 4. group IV: rats with diabetes mellitus type 2 treated with 0.45 mg/kg of saxagliptin. The rats from experimental groups were fed with a high-fat diet for 4 weeks and after 6–8 h of starvation received one dose of streptozotocin (STZ) intraperitoneally (25 mg/kg body weight) to induce type 2 diabetes mellitus (T2DM). Animals with fasting glucose above 7 mmol/L and insulin over 6 mmol/L were included in the study as rats with T2DM. Upon completion of the experiments, the blood was collected from the anesthetized animals and serum triglyceride (TG), total cholesterol (TCH), high density lipoprotein (HDL), and low density lipoprotein (LDL) were measured using spectrophotometry and commercial kits. At the beginning of the study and the day before sacrificing animals, the blood pressure and heart rate were measured by a tail-cuff noninvasive method. DPP4 inhibitors, as glucagon-like peptide-1 (GLP-1) agonists, were associated with modest reductions in DBP, LDL-C, TCH, and TGL and significant improvement in HDL, SBP and HR. [ABSTRACT FROM AUTHOR]

Background/Aim. The wearing of acrylic dentures is the cause of the inflammatory reaction of the oral mucosa. The aim of this study was to investigate the response of rat tissues to subcutaneous and intramuscular implantation of different acrylic samples, by histopathological analysis of the tissue. Methods. The study included two samples of hard and three samples of soft acrylic resins (heat and cold polymerized), that were subcutaneously and intramuscularly implanted in rats tissues. Implantation tests were designed to test the biological response of the surrounding tissue to the tested materials after their application for the period of two weeks and the period of four months. Results. After two weeks, regardless of the type of implantation, histopathological analysis showed an acute inflammatory response. There was an intense hyperplasia of inflammatory cells, multiplication of connective tissue as well as formation of many new blood vessels. The highest level of inflammatory changes was observed after the application of cold-polymerized resins. A lower intensity of inflammation in the case of heat polymerised resin was the result of its more complete polymerization. After the second observation period, fibrotic capsules were formed around the implanted samples indicating a chronic course of the inflammatory process. Less visible signs of inflammation and chronicity of the processes indicate that with time, i.e. with the length of the observation period, reduces inflammation. Conclusion. The subcutaneous and intramuscular implantation of acrylic resins material samples led to inflammatory response whose intensity was decreased over time. Heat polymerized resin was a biologically more acceptable in comparison to the cold polymerized acrylates. [ABSTRACT FROM AUTHOR]

Background/Aim. Duodenogastric reflux occurs after gastroenteroanastomosis, with or without resection of the stomach (Billroth I, Billroth II), after vagotomy and pyloroplasty, gastroduodenostomy as well as in conservatively treated patients. The aim of this study was to analyse the effect of carcinogenic N-nitroso compounds (MNNG) influence in conjunction with duodenogastric reflux, in the function of time for precancerous lesions development in gastric mucosa. A particular purpose of the study has been to suggest some effective surgical procedures, which could prevent the harmful effects of duodenogastric reflux on gastric mucosa, as a potential activator of carcinogenesis. Methods. The research included 90 experimental, male Wistar rats, divided into 3 groups. The two experimental groups were subjected to two surgical procedures: Billroth II gastric resection (group B2), and the Roux-en-Y reconstruction (group RY), respectively. The control group (group C) animals did not receive any surgical treatment. All groups were administered per os chemical cancerogen MNNG. All anastomoses were performed by extra mucosal suture with monofilament polypropilene 7-0, and 8-0. The animals were sacrificed consecutively, and subjected to total gastrectomy after 8, 16 and 24 weeks. Results. Pathohistological analysis was performed on defined regions of the rat stomach in three time period. The B2 group, at the end of our experiment, showed predominant incidence of severe lesions: hyperplasia (0%), gastritis (0%), metaplasia (6.7%), dysplasia (46.7%), early carcinoma (20%) and carcinoma (26.7%). At the end of our experiment, the RY and C groups showed the similarities of the obtained results related to time with predominant incidence of mild lesions: hyperplasia (13.3% vs 0%, respectively), gastritis (13.3% vs 13.3%, respectively), metaplasia (6.7% vs 13.3%, respectively), dysplasia (66.7% vs 66.7%, respectively), with an extremely low incidence of early carcinoma (0% vs 6.7%, respectively) and no incidence of carcinoma (0% vs 0%, respectively). Conclusion. Without the presence of duodenogastric reflux, MNNG causes a low degree of precancerous gastric lesions. However, direct contacts of MNNG with gastric mucosa, including the presence of duodenogastric reflux, induce precancerous lesions and carcinoma. The percentage of reversible changes decreases with time, while the percentage of irreversible lesions and carcinoma increases. A lack of distinction in the findings between the RY and C groups confirms a gastroprotective role of the Roux-en-Y procedure. [ABSTRACT FROM AUTHOR]

Background/Aim. The fennel (Foeniculum vulgare Miller, Apiaceae) has a long history of use as traditional herb medicine due to its carminative properties. The study was aimed to investigate the effects of aqueous and methanol fennel stem extracts on intestinal activity. Methods. Relaxant activity of aqueous and methanol fennel stem extracts was evaluated in vitro in three experimental models: spontaneous contraction, acetylcholine and potassium chloride (KCl)-induced contraction of an isolated rat ileum. The composition of aqueous and methanol fennel stem extracts was qualitatively analyzed using the high performance liquid chromatographic (HPLC) analysis. Results. In the presence of an aqueous fennel stem extract at a concentration of 3 mg/mL, the inhibition of the spontaneous contractions of isolated rat ileum was 35.05% ± 3.57%. In presence of a methanol fennel stem extract at the same concentration, the maximum reduction of the spontaneous contractions was 48.91% ± 6.31%. The extracts in a concentration- dependent manner significantly inhibited the acetylcholine and KCl induced contractions of the isolated rat ileum (p < 0.01). The following components were identified in fennel methanol stem extract: 3-caffeoylquinic acid, chlorogenic acid, 4-caffeoylquinic acid, 1,3-dicaffeoylquinic acid, rutin, miquelianin, quercetin heterosides, 1,5-dicaffeoylquinic acid, 1,4-dicaffeoylquinic acid, apigenin and rosmarinic acid. In an aqueous extract, their presence is found in trace amounts. Conclusion. The results of this study showed that the aqueous and methanol fennel stem extracts have spasmolytic effects on the intestinal smooth muscle and may be used for the control of intestinal motility. [ABSTRACT FROM AUTHOR]

Copyright of Medical Journal / Medicinski Časopis is the property of Serbian Medical Society, Section Kragujevac and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The aim of this study was to evaluate the impact of increased homocysteine levels induced by methionine nutritional overload (twice as standard) and deficiency of the vitamins folate, pyridoxine and cobalamine, which plays an important role in homocysteine metabolism in anxiety-related behaviour, expressed by means of exploratory activity in rats. Twenty-three male Wistar albino rats (4 weeks old, 100±15 g body weight) were divided into three groups: control (n=8), methionine-enriched (Meth+, 7.7 g of methionine/kg chow, n=7) and methionine-enriched vitamin-deficient (Meth+Vit-, 7.7 g of methionine/kg chow, deficient in folate, pyridoxine and cobalamine - 0.08, 0.01 and 0.01 mg/kg, n=8). All animals had free access to food and water for 30 days. Behavioural testing was performed using the elevated plus maze (EPM) test. Standard parameters for vertical exploratory activity, the number of rearings and the number of head-dippings, as well as the total exploratory activity (summarizing overall exploratory activity in the EPM) were significantly reduced following 30 days of methionine nutritional overload (p<0.05, p<0.05 and p<0.01, respectively). A methionine-enriched diet coupled with a reduction in some B vitamins resulted in a more pronounced decline in exploratory drive observed in the EPM test compared to the control (p<0.01). The decline in total exploratory activity associated with vitamin deficiency was significant compared to the Meth+ group (p<0.05). The results of this study highlight the important role of homocysteine in the modulation of exploratory activity in rats. Decreased exploratory drive induced by both a methionine-enriched and vitamin-deficient diet could be attributed to an anxiogenic effect of hyperhomocysteinemia. [ABSTRACT FROM AUTHOR]

Since the early 1940s, a significant amount of research has been conducted to describe the impact of the high-G acceleration on the cardiovascular system. The objective of the present study was to examine the role of the antioxidant enzyme system under biodynamic stress in the liver, heart and gastric mucosa in response to high-magnitude +Gz exposure in a rat model. Twenty adult male Wistar albino rats (10 rats per group; 9-11 weeks old, 200-250 g b.w.) were divided into the following two groups: control and G (exposed to a biodynamic stress model under positive (+7 Gz) acceleration for 40 s). The influence of acute biodynamic stress on pro-oxidative parameters in the rat liver (xanthine oxidase (XOD), catalase (CAT), peroxidase (Px), glutathione peroxidase (GSH-Px), total content of glutathione (GSH), lipid peroxidation (LPx)) and on histopathological alterations in the liver, cardiac muscle and gastric mucosa was examined. Biodynamic stress resulting from positive (+7 Gz) acceleration resulted in a highly statistically significant increase of CAT GSH-Px activity compared to the control group. The LPx levels were significantly decreased, but the GSH contents and the activities of other enzymes were not significantly changed. Significant microscopic changes in the liver, heart and gastric mucosa were observed in the G group. These results clearly indicate that +Gz acceleration alters biochemical systems. These alterations in cellular processes may be mediated by influences of hypoxia or ischaemia via changes in the antioxidant capacity. [ABSTRACT FROM AUTHOR]

Introduction. In performed experiments, the parietal electrocortical activity of the cerebral cortex and the activity of the cerebellar cortex were simultaneously recorded. The main purpose was to compare their spontaneous activity, as the recording was conducted during anesthesia. Material and Methods. We used 2-3 months old rats weighing 200 - 350 g. Two groups of rats with same characteristics were made. The first group of 15 rats (control group) was recorded under anesthesia and there was a change in spectral power in accordance with frequency ranges. The second group of 30 rats was recorded under the same experimental conditions, but the rats were treated intraperitoneally by aluminium chloride hexahydrate solution or with 1.5% solution of aluminium chloride hexahydrate per os. Discussion. Changes in spontaneous activity of the cerebellum during aluminium intoxication were compared with control values. It was shown that lesion and neurotoxicity during stable anesthesia led to desynchronization of the cerebellar activity. This is described by the change in fractal dimension of cerebellar electrocortical activity. The assumption is that the inhibition caused by anesthetic is compensated during aluminium intoxication. Conclusion. The cerebellum plays a role in compensation through changes in spontaneous activity. This response involves an increase in the value of fractal dimension of cerebellar electrocortical activity which is reduced in neurotoxicity. [ABSTRACT FROM AUTHOR]

Backgroung/Aim. Since combining conventional drugs with herbal medicinal products is in current research focus and possible of great interest as therapy improvement way, the aim of this study was to determine the effects of wellestablished antiatherosclerotic drug atorvastatin (CAS number 134523-00-5) and commercially available artichoke leaf tincture (ALTINC), used as combined therapy, as well as to compare effects of these two treatments separately. Methods. Experimental animals were divided into five groups: the group I (the control group of rats fed with standard diet during 11 weeks), and the remaining 4 groups of rats (II, III, IV and V) fed with standard diet during the first week and then with hypercholesterolemic diet during the next 10 weeks. The group II of rats were left without treatment, while in the groups III, IV and V were rats treated per os with atorvastatin (1.15 mg/kg body wright - b.w.), ALTINC (0.1 mL/kg b.w.) and their combination in same doses, respectively, for the last six weeks. Results. The cholesterol rich diet led to pronounced hyperlipidemia which could not be overcame with the therapy. However, the therapy showed positive effects on abdominal aorta wall thickness and parameters of oxidative stress (malondialdehyde - MDA, proxidative-antioxidative balance - PAB) and antioxidative protection (reduced glutathione - GSH, paraoxanase 1 - PON1, superoxide dismutase - SODA SH groups), especially ALTINC was successful in oxidative status improvement. Conclusion. Separate treatments comparison showed that artichoke leaf tincture is very potent antioxidant with beneficial effects in early stages of atherosclerosis. Since atorvastatin and constituents of ALTINC probably have different mechanisms of action, simultaneous use of both therapies could be beneficial but should be further investigated since our results showed that ALTINC is less effective when used in combination with atorvastatin. [ABSTRACT FROM AUTHOR]

The aim of this experimental study was to assess the effects of the acute administration of L-arginine alone and in combination with L-NAME (a non-selective NO synthase inhibitor) on the coronary flow and oxidative stress markers in isolated rat hearts. The experimental study was performed on hearts isolated from Wistar albino rats (n=12, male, 8 weeks old, body mass of 180-200 g). Retrograde perfusion of the isolated preparations was performed using a modified method according to the Langendorff technique with a gradual increase in the perfusion pressure (40-120 cmH2O). The following values were measured in the collected coronary effluents: coronary flow, released nitrites (NO production marker), superoxide anion radical and the index of lipid peroxidation (measured as thiobarbiturate reactive substances). The experimental protocol was performed under controlled conditions, followed by the administration of L-arginine alone (1 mmol) and L-arginine (1 mmol) + L-NAME (30 μmol). The results indicated that L-arginine did not significantly increase the coronary flow or the release of NO, TBARS and the superoxide anion radical. These effects were partially blocked by the joint administration of L-arginine + L-NAME, which indicated their competitive effect. Hence, the results of our study do not demonstrate significant effects of L-arginine administration on the coronary flow and oxidative stress markers in isolated rat hearts. [ABSTRACT FROM AUTHOR]

Background/Aim. Based on numerous studies in animals, the most prominent toxic effects of decabrominated diphenyl ether (BDE-209) are observed in the liver, thyroid hormone homeostasis, reproductive and nervous systems. BDE-209 exhibits its toxic effects partly through the aryl hydrocarbon (Ah) receptor and consequent induction of hepatic microsomal enzymes. The aim of this study was to assess the hepatotoxic effect vs target tissue dose of BDE- 209 in the subacutely orally exposed Wistar rats. Methods. Effects were examined on male Wistar rats, weighing 200-240 g, exposed to doses of 1,000, 2,000 or 4,000 mg BDE-209/kg body weight (bw)/day by gavage during 28 days. Animals were treated according to the decision of the Ethics Committee of the Military Medical Academy, No 9667-1/2011. Evaluation of the hepatotoxic effect was based on: relative liver weight water and food intake, biochemical parameters of liver function [aspartate amino transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gama glutamyl transferase (γ-GT)], and oxidative stress parameters in liver homogenates [malondialde-hiyde (MDA), superoxide dismutase (SOD), -SH] and morphological and pathohistological changes in the liver. For the assessment of internal dose -- response relationship, lower confidence limit of Benchmark dose (BMDL) of 5% or 10% i.e. BMDL5 or BMDL10, were calculated using PROAST software. Results. After the application of 1,000, 2,000 or 4,000 mg BDE-209/kg bw/day, the concentrations of BDE-209 measured in liver were 0.269, 0.569 and 0.859 mg/kg of liver wet weight, (ww) respectively. Internal doses correlated with external (r = 0.972; p < 0.05) according to equation: internal dose (mg BDE-209/kg of liver ww) = 0.0002 ? external dose (mg/kg bw/day) + 0.0622. Hepatotoxicity was demonstrated based on significant increase in AST and γ-GT activities and the degree of histopathological changes. The lowest BMDL5 of 0.07228 mg BDE-209/kg of liver ww, correlating to external dose of 39 mg/kg/day, indicated the increase of AST activity as the most sensitive biomarker of BDE-209 hepatotoxicity in subacutely exposed rats. Conclusion. The results of the present work add up to the issue of BDE-209 toxicity profile with a focus on relationship between internal dose and hepatotoxicity. Critical internal dose for the effect on AST of 0.07 mg/kg of liver ww, corresponding to external dose of 39 mg/kg/day, is the lowest dose ever observed among the studies on BDE-209 hepatotoxicity. For the persistent sub- stances with low absorption rate such as BDE-209, critical effect based on internal dose in majority of cases is considered as more precisely defined than the effect established based on external dose, particularly. [ABSTRACT FROM AUTHOR]

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Introduction. By examining the production of c-Fos protein, we analyzed the response to the ischemic attack in different brain tissue, two of which are regions of the limbic system: the anterior amygdaloid area and nc. accumbens. Material and Methods. We used the model of rat brain ischemia--four-vessel occlusion, and Pulsinelli's method. The rats were treated in two ways, according to which they were divided into two groups: a total ischemia (ligation of four blood vessels, i.e. electrocauterization of the vertebral artery with bilateral ligation of the carotid artery--the so-called R-group rats), and transient ischemic attack (ligation of four blood vessels, i.e. electrocauterization of the vertebral artery, with mutual re-ligation of the carotid arteries in the form of transient ischemia--the so-called T-group rats, which can also be called "pre-conditioned group"). Both groups had their own control group. Conclusion. We have concluded that parts of the brain with an important role for the survival have a strong expression of c-fos gene. [ABSTRACT FROM AUTHOR]

Background/Aim. The cell line C6 is a continuous cell line of rat glioma and, as a transplantable line, is frequently used for induction into in vivo model of primary brain tumor. It is believed that, pursuant to its histological traits and biological behavior, this experimental tumor corresponds to human anaplastic astrocytoma of grade II/III, which is characterized by proliferative and invasive potency, and marked cell differentiation. The aim of this study was to determine macroscopic analysis of rat brain with implanted tumor during tumorigenesis, histological features of tumor cells of induced brain tumor and markers of proliferation (proliferation cell nuclear antigen - PCNA, cytokeratin - CK 19) and differentiation (glial fibrillary acidic protein -GFAP) in rat brain with implanted tumor. Methods. To determine histological structure of the brain with implanted C6 cells, we used brain sections stained for hematoxylin-eosin or kresyl violet, whereas other sections were immunohistochemically stained for GFAP, CK 19 and PCNA. Results. A statistically significant difference in weights of the left and right brain hemispheres with implanted tumors during tumorigenesis in as soon as 7 days from the day of inducing tumors was revealed. The tumor was of cellular type, with distinct pleomorphism of cells and frequent hyperchromasia of the nucleus. Immunohistochemical staining for PCNA revealed a significant number of positive cells on the days 7, 14 and 21 day following the implantation of C6 cells. CK 19 positive cells were present in both brain hemispheres, and numerous GFAP positive astrocytes were found around the puncture lesion. Conclusions. Within the experimental conditions of the present research, C6 glioma did not demonstrate any relevant deviations concerning development, clinical symptomatology and macroscopic anatomy relative to those already described in the literature. [ABSTRACT FROM AUTHOR]

Background/Aim. Stevioside is a glycoside that supposedly possesses a number of pharmacodynamic effects such as anti-infective, hypoglycemic, along with the beneficial influence on the cardiovascular system. The aim of this study was to determine the effect of rats pretreatment with aqueous solution of stevioside on pharmacological actions of adrenaline, metoprolol and verapamil. Methods. Rats were administered (intraperitoneally 200 mg/kg/day) stevioside as aqueous solution or physiological saline in the course of 5 days, then anaesthetized with urethane and the first ECG recording was made. The prepared jugular vein was connected to an infusion pump with adrenaline (0.1 mg/mL), verapamil (2.5 mg/mL) or metoprolol (1 mg/mL). Control animals, pretreated with saline, in addition to the mentioned drugs, were also infused with the solution of stevioside (200 mg/mL) in the course of recording ECG. Results. The infusion of stevioside produced no significant changes in ECG, even at a dose exceeding 1,600 mg/kg. In the control group, a dose of adrenaline of 0.07 ± 0.02 mg/kg decreased the heart rate, whereas in the stevioside-pretreated rats this occurred at a significantly higher dose (0.13 ± 0.03 mg/kg). In stevioside-pretreated rats, the amount of verapamil needed to produce the decrease in heart rate was significantly lower compared to the control. The pretreatment with stevioside caused no significant changes in the parameters registered on ECG during infusion of metoprolol. Conclusion. The results suggest that pretreatment with stevioside may change the effect of adrenaline and verapamile on the heart rate. [ABSTRACT FROM AUTHOR]

Background/Aim. There is a lack of data on the effects of prolactin on calcium metabolism and bone turnover in hyperprolactinemia of various origins. The aim of this study was to compare the influence of medicamentous and physiological hyperprolactinemia on bone turnover in female rats. Methods. Experimental animals (18 weeks old, Wistar female rats) were divided as follows: the group P -9 rats, 3 weeks pregnant; the group M3-10 rats that were intramuscularly administrated sulpirid (10 mg/kg) twice daily for 3 weeks, the group M6 - 10 rats that were intramuscularly administrated with sulpirid (10 mg/kg) twice daily for 6 weeks, and age matched nulliparous rats as the control group: 10 rats, 18-week-old (C1) and 7 rats, 24 weeks old (C2). Laboratory investigations included serum ionized calcium and phosphorus, urinary calcium and phosphorous excretion, osteocalcin and serum procollagen type 1 N-terminal propeptide (P1NP). Results. Experimental animals in the group P compared to the control group, displayed lower mean serum ionized calcium (0.5 ± 0.2 vs 1.12 ± 0.04 mmol/L;p < 0.001); higher mean serum phosphorus (2.42 ± 0.46 vs 2.05 ± 0.2 mmol/L; p < 0.05); increased urinary calcium (3.90 ± 0.46 vs 3.05 ± 0.58; p < 0.01) and significantly increased P1NP (489,22 ± 46,77 vs 361.9 ± 53,01 pg/mL; p < 0.001). Experimental animals in the group M3 had significantly decreased P1NP, compared to the contol group. Prolongated medicamentous hyperprolactinemia (the group M6) induced increased serum ionized calcium (1.21 ± 0.03 vs 1.15 ± 0.02 mmol/L; p < 0.001); decreased serum phosphorus (1.70 ± 0.13 vs 1.89 ± 0.32 mmol/L; p < 0.001); decreased osteocalcin and P1NP. Conclusions. Physiological hyperprolactinemia does not have such harmful effect on bone metabolism as medicamentous hyperprolactinemia. Chronic medicamentous hyperprolactinemia produces lower serum levels of bone formation markers. Assessment of bone turnover markers in prolongated medicamentous hyperprolactinemia provides an opportunity for earlier diagnosis of bone metabolism disturbances and should be considered as mandatory. [ABSTRACT FROM AUTHOR]

Background/Aim. Autogenous bone grafting has been the gold standard in clinical cases when bone grafts are required for bone defects in dentistry. The study was undertaken to evaluate multilevel designed carbonated hydroxyapatite (CHA) obtained by hydrothermal method, as a bone substitute in healing bone defects with or without corticosteroid treatment in rats as assessed by histo-pathologic methods. Methods. Bone defects were created in the alveolar bone by teeth extraction in 12 rats. The animals were initially divided into two groups. The experimental group was pretreated with corticosteroids: methylprednisolone and dexamethasone, intramuscularly, while the control group was without therapy. Posterior teeth extraction had been performed after the corticosteroid therapy. The extraction defects were fulfilled with hydroxyapatite with bimodal particle sizes in the range of 50250 µm and the sample from postextocactional defect of the alveolar bone was analyzed pathohystologically. Results. The histopatological investigations confirmed the biologic properties of the applied material. The evident growth of new bone in the alveolar ridge was clearly noticed in both groups of rats. Carbonated HA obtained by hydrothermal method promoted bone formation in the preformed defects, confirming its efficacy for usage in bone defects. Complete resorption of the material's particles took place after 25 weeks. Conclusion. Hydroxyapatite completely meets the clinical requirements for a bone substitute material. Due to its microstructure, complete resorption took place during the observation period of the study. Corticosteroid treatment did not significantly affect new bone formation in the region of postextractional defects. [ABSTRACT FROM AUTHOR]

Introduction. Candidiasis has become a human disease of increasing importance in the last decades. The aim of the study is to establish pathomorphological alterations caused by the blastospores of the Candida albicans as well as morphometric alterations. Material and Methods. The experiment was carried out on 2.5-month-old rats, weighting 110-130 g. The study sample was divided into the animals infected by a submucous inoculation in the periodontal region and the controls. The gingival specimens were taken, preparations were done and stained by the hematoxylin-eosin and Periodic acid Schiff methods. Results. The following alterations were found out by the stereological analysis: an average volume of nuclei of the gingival epithelial cells was 111.82 µm³ (SD=25.34) on the first day. A statistically significant increase in the volume of nuclei in the experimental group began to occur from the fourth day (202.97 µm³; SD=31.16, p<0.05) and the highest value of the nuclei volume was found out on the eight day of the experiment (316.83 µm³; SD=40.15). Conclusion. Blastospores of Candida albicans are pathogenic for the gingival tissue where they cause degenerative necrotic alterations of the granulomatous character and after the fourth day from the inoculation, the development of the pseudohyphae was observed. The obtained values of stereologic measurement show the acute increase in the volume of nuclei. [ABSTRACT FROM AUTHOR]

Introduction. This study used the immunohistochemical method to follow the expression of cytoplasmatic protein somatostanin in the course of ischemia of rat brain. The aim of the study was to define all the areas of expression of somatostain and to show the protein distribution on the map. Material and Methods. All the sections of telencephalon, diencephalon and midbrain were studied in resistant, and transitory ischemia, which enabled us to observe the reaction of neurons to an ischemic attack or to repeated attacks. Results and Discussion. The results of this study show that there is a difference in the reaction between the resistant and transitory ischemia groups of rats, especially in the parietofrontal cortex, area amygdaloidea anterior, clastrum, nc. reuniens and nc. suprachiasmaticus. The mapping shows the reaction in the structures of motor, sensitive and sensory cortex, mostly in the laminae II/III and V/VI, hippocampus -- gyrus dentatus and CA1, CA2, CA3, endopiriform nucleus, paraventricular and periventricular nucleus of hypothalamus, corpus amygdaloideum, claustrum and caudoputamen. The more primitive sections of the brain - rhinencephalon, also showed a reaction, which led us to conclude that both newer and older brain structures reacted immunohistochemically. Histological data showed that small neurons are most commonly found while the second most common are big pyramidal cells of multipolar and bipolar type, with the different body shape. Conclusion. Our findings have confirmed the results of rare studies that dealt with these issues, and offered a precise and detailed map of cells expressing somatostanin in the rat brain following ischemic attack. [ABSTRACT FROM AUTHOR]

Introduction. The immunohistochemical method was used to follow the expression of neuropeptide Y in the course of pre ischemia of the rat brain. The aim of the study was to define all the areas of expression of this protein, show their localization, their map of distribution and histological types. Material and Methods. All the sections of telencephalon, diencephalon and midbrain were studied in resistant, and transitory ischemia, which enabled us to observe the reaction of neurons to an ischemic attack or to repeated attacks. The mapping was done for all three proteins by introducing our results into the maps of rat brain atlas, George Paxinos, Charles Watson. Photographing and protein expression was done using Analysis program. Results. The results of this research show that there is a differens in reaction between the resistant and transitory ischemia groups of rats, especially in the caudoputamen, gyrus dentatus, corpus amygdaloideum, particularly in the medial nucleus. The mapping shows the reaction in caudoputamen, gyrusdentatus, corpus amygdaloideum -- especially in the central nucleus, then in the sensitive and secondary auditory cortex, mostly in the laminae V/VI, but less in neuron groups CA1, CA2, CA3 of hippocampus. Discussion. The phylogenetically older parts of the brain-rhinencephalon, also showed reaction, which lead us to conclude that both newer and older brain structures reacted immunohistochemically. Histological data have shown that small neurons are most commonly found while the second most common ones are big pyramidal cells of multipolar and bipolar type, with a different body shape. Conclusion. Our findings have confirmed the results obtained in some rare studies dealing with this issue, and offered a precise and detailed map of cells expressing neuropeptide Y in the rat brain following ischemic attack. [ABSTRACT FROM AUTHOR]

Carcinogenic effects of cadmium on lungs, testicles and prostate are well known, so as cumulative and toxic effects on kidney, liver and bones; however, there have not been many published articles about the effects of cadmium on myocardium. The aim of this study was to estimate the morphological changes in rat myocardium chronically treated by cadmium. The study was carried out on male albino Wistar rats (n=30, age=35-37 days, body mass 120g +/- 10g). The animals were raised in controlled laboratory conditions and provided with standard laboratory rat food and tap water ad libitum. The rats were divided into two groups: ten animals composed the control group and did not undergo any treatment. The 20 experimental rats were exposed to 10mg of CdCl2 /L drinking water for 90 days. After 90 days, all animals were victimized and after the macroscopic inspection of the heart, myocardial tissue was routinely processed and embedded in paraffin. Sections 5 micrometers thick were stained by HE method and histochemical PAS-AB (pH 2, 5), Masson trichrome method for demonstrating collagen fibers and Toluidine blue for mast cells identification. Cross-striated banding pattern of cardiac cells was ruined. Noticeable atrophy and hydropic degeneration of subendocardial localized cardiac cells were found, with the focal presence of myocytolysis. Endothelial cell hyperplasia and edema of the intima were present on arteriolar type blood vessels causing the focal subocclusion. Fibrocytes, histiocytes and mast cells were numerous, perivascularly localized. Mast cells were polymorphic, larger than normal, oval and mostly degranulated. Instead of scanty endomysium, there is a noticeable interstitial fibrillar fibrosis with few fields of collagen in all myocardium layers between cardiac cells, which is particularly prominent around the larger blood vessels. Cadmium has pronounced vasculotropic properties causing morphological changes of cardiomyocytes, myocardial interstitial fibrillar collagen network and on the heart small blood vessels. [ABSTRACT FROM AUTHOR]

Background/Aim. Zinc is an essential element which has considerable interaction with gamma-aminobutyric acid A type receptors (GABAA) and glutamate receptors in the central nervous system (CNS). It is believed that zinc acts as a potent inhibitor of glutamate N-methyl-D-aspartate (NMDA) receptors, and binding to structurally specific site on the GABAA receptor leads to inhibition of GABA-dependent Clpass. The aim of our research was to test the anxiolytic and antidepressant effects of zinc after single application and its influence on general behavioural parameters after repeated administration. Methods. Male Wistar rats were treated with increasing doses of zinc histidine dehydrate (10, 20, 30 mg/kg, i.p.). To determine anxiolytic and antidepressant properties of zinc two models were used: elevated plus maze (EPM) and forced swim test (FST). Behavioural parameters (stillness and mobility) were, also, recorded after single and repeated administration of active substance. Results. Testing animals in the EPM showed a statistically significant difference as follows: dose of 20 mg/kg significantly increased the time animals spent in open arms, indicating an acute anxiolytic effect, while doses of 30 mg/kg significantly reduced the time in the open arms, indicating a potentially anxiogenic effect. Testing the animals by FST showed a statistically significant difference in immobility time of animals treated with the lowest applied (10 mg/kg) and highest applied (30 mg/kg) doses of zinc, compared to the control group. The first day of testing behavioral parameters showed the tendency to increase locomotor activity of the animals with the lowest dose of zinc (10 mg/kg), while the following day revealed a reduced activity with the highest dose applied (30 mg/kg). Conclusion. Zinc has important effects on the CNS: After single application, in all doses zinc showed antidepressant effects. The effects of zinc on anxiety and locomotor activity showed dose-dependent bidirectional effects. [ABSTRACT FROM AUTHOR]

The aim of this study was to estimate ovarian changes in 7,12 dimethylbenz (α) anthracene (DMBA) induced rat mammary carcinomas. The study was carried out on female virgin albino Wistar rats (n=35, age=35-37days, body mass 120-140g), divided into control (n=10) and experimental group (n=25). Anesthetised animals of experimental group were inoculated with 2 mg mixture (1 mg of DMBA and 1 mg of cholesterol-buffer) into the fifth left mammary gland. The animals were sacrificed 90 days after implantation, and ovaries and mammary glands were investigated. Mammary gland carcinomas (in situ and/or invasive) were pathohistologically verified in 19 experimental animals. Histological, histochemical, and immunohistochemical (cytokeratin AE1/AE3 and PCNA ) studies of ovaries were performed. Besides non-neoplastic changes, such as decrease in ovary's volume, reduction in the rate of follicular development and numerous corpora lutea formation were found in the vicinity of preneoplastic changes: papillomatous epithelial hyperplasia and inclusion cysts, microglandular formations with dysplasia and seromucinous microcystic formation. Intensive diffuse PCNA expression was present in the epithelium of glandlike structures, follicular and inclusion cysts. These morphological changes confirmed that DMBA is a pluripotent carcinogen capable to induce a wide spectrum of preneoplastic lesions in the ovaries. The present dilemma is whether the changes described are the consequence of the direct effects of DMBA or of hormonal activity of the induced breast carcinomas, or both. [ABSTRACT FROM AUTHOR]