Cardiorespiratory fitness mediates cortisol and lactate responses to winter and summer marches.

Background: The influence of homeostatically regulated physiological processes, including cardiorespiratory fitness (VO2max), on the response to physical stressors such as acclimatisation and marching, remains understudied. We aimed to investigate the effects of summer and winter acclimatisation and marching on cortisol levels and blood lactate, to gain insight into the role of these physiological processes in the stress response. Methods: Two groups of young Europeans, classified as poor (PCF; n=9) and good physical condition (GCF; n=21), based on a VO2MAX threshold of 40 mL O2/ kg/min, underwent 2-h March (6-7 km/h) in winter (5˚C) and summer (32˚C). Commercial tests, UniCel DxI Access Cortisol assay and EKF Biosen Clinic/GP assay were used for cortisol and lactate blood measurements (morning samples and those taken immediately after marches), respectively.

Influence of dental filling material type on the concentration of interleukin 9 in the samples of gingival crevicular fluid.

Background/Aim: Several cytokines and lymphokines (IL1ß, ENA78, IL6, TNFα, IL8 and S100A8) are expressed during dental pulp inflammation. Analysis of gingival crevicu-lar fluid (GCF) offers a non-invasive means of studying gen-eral host response in oral cavity. Although GCF levels of various mediators could reflect the state of inflammation both in dental pulp and gingiva adjacent to a tooth, GCF samples of those without significant gingivitis could be inter-preted as reflection of pulpal process. The aim of this study was to investigate IL9 GCF values in patients with dental car-ies and to assess possible influence of various dental fillings materials on local IL9 production. Methods: The study group included 90 patients, aged 18­70, with inclusion and exclusion criteria in the prospective clinical study. Of the 6 types of material used for the restoration of prepared cavities, 3 were intended for temporary and 3 for definitive restora-tion. According to dental fillings weight, all the participants were divided into 3 groups: those with fillings lighter than 0.50 g, those with 0.50­1.00 g, and those with fillings heavier than 1.00 g. Samples were taken from gingival sulcus using the filter paper technique. Clinical parameters were deter-mined by bleeding index, plaque index (Silness-Lou, 0­3), gingival index (0­3), and gingival sulcus depth. Cytokine con-centrations were assessed using commercially available cy-tomix. Results: According to the weight of dental fillings, there was a clear decreament trend of IL9 values meaning that dental defects greater than 1.00 g of dental filling were associated with lower GCF IL9 concentration. The IL9 val-ues correlated with the degree of gingival index and depth of gingival sulcus, being higher with more advanced gingivitis and more pronounced anatomical changes in the tooth edge. Different filling materials exerted various local IL9 responses. Zink polycarbonate cement and amalgam fillings induced a significant and long-lasting local IL9 decrement, while the use of Tetric EvoCeram and GMA-BISK significantly increased IL9 levels. Conclusion: The obtained results indicate that IL9 GCF could be regarded as a measure of odontoblasts' re-sponse to the extensity of dental caries. The type of material used for dental fillings could profoundly alter biological func-tion of gingival and pulpal cells. Also, the results obtained in this study suggest that some materials could even enhance wound repair by modulating macrophage activation.

Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma.

Background/Aim: Survivin is a multifunctional protein abundantly expressed in tumors of various types, including melanoma. There are still sparse data regarding relationship of melanoma cell survivin expression with accepted histopathological characteristics as well as serum concentration. The aim of this study was to investigate the association of local tumor survivin expression (primary tumor and metastatic lesions) and serum concentration with clinical and histopathological parameters in melanoma patients. Methods: The level of survivin expression was determined immunocytochemically in tumor tissue and with ELISA test in the serum of 84 melanoma patients diagnosed from 2009 to 2013 at the Institute for Pathology and Forensic Medicine and Institute for Medical Research at Military Medical Academy, Belgrade, Serbia. Results: The intensity of survivin expression was significantly higher in the patients whose tumor had ulceration, higher mitotic index, higher Clark and Breslow stage, that made vascular invasion or spread through lymphatic vessels in primary tumor, and was significantly higher in the patients with metastatic disease. Survivin expression and the number of survivin positive cells in metastatic lesions were significantly associated with the duration of disease free interval (DFI). The patients with high expression score had almost double shorter DFI comparing to those with weak local survivin expression and a small number of survivin+cells (9 ± 7 vs 19 ± 13 months, respectively). The degree of tumor infiltrating lymphocytes presence in tumor tissue was significantly associated with serum survivin concentration, with lowest average level detected in samples of patients with the highest degree of infiltration. Serum survivin concentrations were highest in samples of melanoma patients with IA American Joint Commission on Cancer (AJCC) clinical stage, pT1a histological stage, patients whose tumors were still in horizontal growth phase, without signs of lympho-hematological disease spreading, with the highest number of mitoses and the smallest Clark index. Conclusion: Survivin expression in tumor tissue and its serum concetration significantly correlate with clinical and histopathological parameters. Serum levels could be important in initial follow-up as indicators of those patients that would have aggressive local tumor growth and spreading. Survivin determination in tumor tissue is of great significance in estimation of DFI.

The effect of inhibition of nitric oxide synthase on aluminium-induced toxicity in the rat brain.

The goal of the present study was to examine the effectiveness of a non-specific nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME) to modulate the toxicity of aluminium chloride (AlCl3). Rats were killed at 3 h and at 30 days after treatments and the striatum was removed. Nitrite, superoxide, superoxide dismutase activity, malondialdehyde and reduced glutathione were determined. AlCl3 exposure promoted oxidative stress in the striatum. The biochemical changes observed in neuronal tissues show that aluminium acts as pro-oxidant, while the NOS inhibitor exerts antioxidant action in AlCl3-treated rats. We conclude that L-NAME can efficiently protect neuronal tissue from AlCl3-induced toxicity.

Nitric oxide synthase inhibitors partially inhibit oxidative stress development in the rat brain during sepsis provoked by cecal ligation and puncture.

IOxidative stress development in different brain structures and the influence of nitric oxide (NO) overproduction during sepsis was investigated using male Wistar rats. Rats were subjected to cecal ligation and puncture (CLP) or were sham-operated. To evaluate the source of NO production, 30 min before the operation septic and control animals were treated with single intraperitoneal doses of NO synthase (NOS) inhibitors: L-NAME and aminoguanidine (AG) (10, 30 or 90 mg/kg) and 7-nitroindazole (7-NI) (30 mg/kg). The concentration of GSH in the cortex, brain stem, cerebellum, striatum and hippocampus significantly decreased post CLP at both early and late stage sepsis. Lipid peroxidation also occurred in the cortex and cerebellum in late stage sepsis. Pre-treatment with a non-selective NOS inhibitor (L-NAME) and with selective inducible and neuronal NOS inhibitors (AG and 7-NI) revealed benefit effects on the GSH concentrations. Unexpectedly, NOS inhibition resulted in diverse effects on TBARS concentrations, suggesting the importance of specific quantities of NO in specific brain structures during sepsis.

Oxidative stress in rat kidneys due to 3,4-methylenedioxymetamphetamine (ecstasy) toxicity.

AIM: The mechanism of MDMA (3,4-methylenedioxymethamphetamine)-induced toxicity is believed to be, in part, due to enhanced oxidative stress. As MDMA is eliminated via the kidney, the aim of this study was to investigate whether MDMA created conditions of oxidative stress within rat kidney. METHODS: Adult male Wistar rats were divided into three groups, control treatment (water), acute MDMA administration (single oral dose: 5, 10, 20 or 40 mg/kg body weight) and subacute MDMA administration (5, 10, or 20 mg/kg body weight per day during 14 days). Animals were sacrificed 8 h after the single oral MDMA administration in the acute MDMA administration group and after the last MDMA administration in the subacute MDMA administration group. Rectal temperature measurements, oxidative stress status parameters and histological examinations were performed. RESULTS: In all MDMA-administered rats, rectal temperature markedly increased peaking approximately 1 h after MDMA ingestion. Superoxide dismutase activity and thiobarbituric acid reactive substances increased after MDMA administration. Histological examinations of the kidney revealed dose-dependent disruption of tissue structure in subacute MDMA-administered rats. The latter was not observed in acute MDMA-administered rats.