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Journal Article 2009; 30(Suppl 1): 46-51 PubMed PMID: 20027144 Citation  Keywords:  Animals, Anisoles:metabolism, Chromatography, High Pressure Liquid:methods, Cytochrome P-450 Enzyme Inhibitors, Cytochrome P-450 Enzyme System:metabolism, Humans, Inhibitory Concentration 50, Kinetics, Microsomes, Liver:enzymology, Nitrophenols:metabolism.   

OBJECTIVES: 2-Nitrophenol (2-NP) is the major detoxification metabolite of an important industrial pollutant and a potent carcinogen, 2-nitroanisole (2-NA). Characterization of the products of 2-NP metabolism by rat hepatic microsomes containing cytochromes P450 (CYPs) and identification of the major CYP enzymes participating in this process are aims of this study.

METHODS: HPLC with UV detection was employed for the separation and characterization of 2-NP metabolites. Inducers and inhibitors of CYPs and rat recombinant CYPs were used to characterize the enzymes participating in 2-NP oxidation.

RESULTS: Rat hepatic microsomes oxidize 2-NP to its hydroxylated metabolite, 2,5-dihydroxynitrobenzene (2,5-DNB). No nitroreductive metabolism leading to the formation of o-aminophenol was evident when using rat hepatic microsomes. Selective CYP inhibitors and hepatic microsomes of rats pre-treated with specific CYP inducers were used to characterize CYPs oxidizing 2-NP in rat livers. Based on these studies, we attribute most of 2-NP oxidation in rat liver to CYP2E1 and 3A, followed by CYP2D and 2C. Among recombinant rat CYP enzymes tested in this study, CYP2E1 and 2C11 were the most effective enzymes oxidizing 2-NP. Oxidation of 2-NP by rat CYP2E1 exhibits the Michaelis-Menten kinetics, having the Km value of 0.35 mM.

CONCLUSION: The results found in this study, the first report on the metabolism of 2-NP by rat hepatic microsomes and rat CYP enzymes, demonstrate that CYP2E1 is the major enzyme oxidizing this compound in rat liver....

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Journal Article 2009; 30(Suppl 1): 22-24 PubMed PMID: 20027138 Citation  Keywords:  Administration, Oral, Animals, Antioxidants:metabolism, Aorta:physiopathology, Arthritis, Experimental:chemically induced, Edema:chemically induced, Freund's Adjuvant, Hexosaminidases:metabolism, Immunologic Factors:administration & dosage, Male, Mycobact.   

OBJECTIVES: The goal of this study was to evaluate the effect of sesame oil on functional damage induced by adjuvant arthritis (AA) and on changes of selected biochemical parameters reflecting oxidative tissue injury.

DESIGN: Mycobacterium butyricum in incomplete Freund's adjuvans was intradermally administered to Lewis male rats. Hind paw edema and endothelium-dependent relaxation of the aorta were determined on day 28. Further, plasmatic levels of TBARS, gamma-glutamyltransferase (GGT) activity in the joint and spleen tissues, level of protein carbonyls and total antioxidant capacity (TAC) in plasma, as well as activity of the lysosomal enzyme N-acetyl-glucosaminidase (NAGA) in serum were assessed. The effect of sesame oil (SO, 1ml/kg, daily oral administration) was evaluated on day 28.

RESULTS: The beneficial effect of sesame oil on markers of oxidative stress accompanying AA was demonstrated by decrease of plasma TBARS and decrease of GGT activity in the joint and spleen tissues. Level of protein carbonyls, TAC in plasma and activity of NAGA in serum and in the kidney were improved, yet not significantly. In the hind paw edema the maximal increase was found on day 28 of AA, and in the same time we observed a significant decrease of aortic endothelium-dependent relaxation. Administration of SO resulted in mild, non-significant decrease of hind paw swelling and in significantly increased acetylcholine-evoked relaxation.

CONCLUSION: We conclude that SO has beneficial effects on oxidative stress induced biochemical changes occurring in AA, moreover it improves endothelium-dependent relaxation of the aorta and tends to decrease hind paw edema....

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Journal Article 2009; 30(Suppl 1): 13-16 PubMed PMID: 20027136 Citation  Keywords:  Animals, Bacterial Toxins:toxicity, Cyanobacteria:metabolism, Fishes:immunology, Liver:drug effects, Microcystins:toxicity, Neurosecretory Systems:drug effects, Peptides, Cyclic:toxicity, Uracil:analogs & derivatives,.   

: Cyanotoxins are the metabolites of cyanobacteria, belonging to different chemical groups and of diverse mechanisms of toxicity. Generally, they are divided into hepatotoxins, neurotoxins and dermatotoxins/irritant toxins. There is a growing evidence, that besides the above mentioned toxicity, exposure to cyanotoxins may also induce other effects, among others the disruption of neuroendocrine and immune systems. The purpose of that paper is to sum up the current information obtained from the literature and from our own studies about the influence of cyanohepatotoxins on neuroendocrine and immune systems of fish. From the presented data it appears, that microcystins, nodularin and cylindrospermopsin, except for their hepatotoxic activity, are potent to exert such effects as HPI axis activation resulting in physiological and behavioural changes, disturbances in thyroid hormones release/metabolism, as well as impairment of immune responses in fish. However the studies in that area are still incomplete and many questions remain to be answered, especially what consequences for fish population health status it brings....

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Journal Article 2009; 30(4): 491-495 PubMed PMID: 20010507 Citation  Keywords:  Adult, Autonomic Nervous System:physiology, Baroreflex:physiology, Blood Pressure:physiology, Diabetes Mellitus, Type 1:physiopathology, Diabetic Neuropathies:physiopathology, Female, Humans, Hyperglycemia:physiopathology, Linear Models, Male,.   

OBJECTIVES: To date, the clinical usefulness of measuring baroreflex sensitivity (BRS) to detect impairment of the autonomic nervous system in patients with diabetes mellitus (DM) type I has not been evaluated sufficiently (Mlcáková et al. 2008). The aim of the current study was the determination and statistical comparison of the mean values of BRS in our DM type I patients cohort and in a control group of healthy volunteers as well as the determination of BRS value dependency on the duration of diabetes and the level of glycemic control in DM I patients. We also aimed to determine the inter-individual and intra-individual variability of BRS in our patients.

MATERIAL AND METHODS: We examined 100 patients with type I diabetes mellitus (37 women and 63 men, mean age 30 years, duration of the disease >or= 10 years) and 40 healthy, age- and sex-matched, subjects. Data from the patient cohort were subsequently analysed for duration of the diabetes and the level of glycemic control as assessed by glycated haemoglobin (HbA1c). We used a simple proportional test to compare the occurrence of impaired BRS in the patient cohort and the control group, and a simple linear regression to assess associations between BRS and duration of the diabetes and the levels of glycemic control.

RESULTS: The mean BRS value in our group of diabetic patients and the control group were 10.15 ms/mmHg and 13.35 ms/mmHg, respectively. II. Statistically significant association between BRS impairment and the duration of the disease or level of glycemic control was not confirmed in our patient cohort. III. We observed an increased inter-individual variability and a relatively low intra-individual variability of BRS in patients with DM type I.

CONCLUSIONS: We found a statistically highly significant difference between the proportions of impaired BRS in the group of diabetics vs. control. However, BRS did not correlate with the duration of the disease or with the level of glycemic control significantly. Albeit not reaching statistical significance, trends could be observed, which we consider clinically interesting....

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Journal Article 2009; 30(4): 470-476 PubMed PMID: 20010505 Citation  Keywords:  Adult, Autonomic Nervous System:physiology, Cognition Disorders:metabolism, Coronary Artery Disease:mortality, Fatigue Syndrome, Chronic:metabolism, Female, Heart Failure:metabolism, Humans, Male, Middle Aged, Oxidative Stress:physiology, Risk Factors, Ub.   

INTRODUCTION: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a medical illness characterized by disorders in inflammatory and oxidative and nitrosative (IO&NS) pathways.

METHODS: This paper examines the role of Coenzyme Q10 (CoQ10), a mitochondrial nutrient which acts as an essential cofactor for the production of ATP in mitochondria and which displays significant antioxidant activities. Plasma CoQ10 has been assayed in 58 patients with ME/CFS and in 22 normal controls; the relationships between CoQ10 and the severity of ME/CFS as measured by means of the FibroFatigue (FF) scale were measured.

RESULTS: Plasma CoQ10 was significantly (p=0.00001) lower in ME/CFS patients than in normal controls. Up to 44.8% of patients with ME/CFS had values beneath the lowest plasma CoQ10 value detected in the normal controls, i.e. 490 microg/L. In ME/CFS, there were significant and inverse relationships between CoQ10 and the total score on the FF scale, fatigue and autonomic symptoms. Patients with very low CoQ10 (<390 microg/L) suffered significantly more from concentration and memory disturbances.

DISCUSSION: The results show that lowered levels of CoQ10 play a role in the pathophysiology of ME/CFS and that symptoms, such as fatigue, and autonomic and neurocognitive symptoms may be caused by CoQ10 depletion. Our results suggest that patients with ME/CFS would benefit from CoQ10 supplementation in order to normalize the low CoQ10 syndrome and the IO&NS disorders. The findings that lower CoQ10 is an independent predictor of chronic heart failure (CHF) and mortality due to CHF may explain previous reports that the mean age of ME/CFS patients dying from CHF is 25 years younger than the age of those dying from CHF in the general population. Since statins significantly decrease plasma CoQ10, ME/CFS should be regarded as a relative contraindication for treatment with statins without CoQ10 supplementation....

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Journal Article 2009; 30(4): 477-481 PubMed PMID: 20010504 Citation  Keywords:  Adenoma:metabolism, Adult, Aged, Apoptosis:physiology, Biomarkers, Tumor:metabolism, Cell Division:physiology, Female, Humans, Immunohistochemistry, Inhibitor of Apoptosis Proteins, Male, Microtubule-Associated Proteins:metabolism, Middle Aged, Pituitary .   

OBJECTIVES: The survivin is the protein involved in regulation of basic and cycle-specific functions of cells both in normal and cancer tissue. Recent studies present survivin as a factor having the leading role in the regulation of apoptosis and mitosis as well as a target of anticancer therapy. The employing of survivin in this therapy is based on its high expression level in most human cancers, as well as its association with the disease's progression. The aim of our study was to evaluate the expression and localization of survivin's gene product on the protein level in different types of pituitary tumors and normal pituitary. The coexpression of survivin and proliferating cell nuclear antigen - PCNA in pituitary was also examined.

DESIGN AND METHODS: The study was conducted on the postoperative pituitary tumors tissue taken during standard neurosurgical removal of tumor from 43 patients. The group of patients consists of 23 women and 20 men, aged from 27 to 71 years. As a control of the study three normal pituitary tissues obtained at the autopsy were used. Evaluation of survivin and PCNA expression was performed using immunohistochemical staining.

RESULTS: The study demonstrated the presence of survivin in all analyzed by us pituitary tumors. Survivin was present also in normal pituitary tissue. The protein was localized mainly in cell's nuclei, however the less intense immunostaining was observed also in the cytoplasm of pituitary tumors cells. Furthermore survivin was found in normal pituitary, but the positive immunostaining was limited to a single cells. The analysis of pituitary tumor cells proliferation index based on PCNA reactivity showed that survivin is coexpressed with PCNA, especially in invasive tumors.

CONCLUSIONS: The study documented the presence of survivin in different types of pituitary tumors as well as in normal pituitary. Additionally the coexpression of survivin and PCNA in tumor cells was shown. The expression of survivin in both normal and cancer pituitary cells suggests that it may play an important role in regulation of the gland's proliferation....

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Journal Article 2009; 30(4): 511-514 PubMed PMID: 20010499 Citation  Keywords:  Adrenocorticotropic Hormone:blood, Animals, Blood Glucose:drug effects, Cholinergic Fibers:drug effects, Cholinesterase Inhibitors:pharmacology, Hippocampus:cytology, Male, Microinjections, Motor Activity, Neostigmine:pharmacology, Neural Pathways, Rats, .   

OBJECTIVE: In our previous study, a lesion in the lateral bed nucleus of the stria terminalis (BNSTL) was found to significantly attenuate the elevation of adrenocorticotropic hormone (ACTH) in plasma during microinjectin of neostigmine, an inhibitor of acetylcholine esterase, into the rat hippocampus. The current study was designed to examine the role of the BNSTL in regulation of blood glucose elevation induced by hippocampal neostigmine injection.

MATERIALS AND METHODS: Ibotenic acid (15 microg/microl) was stereotaxically bilaterally injected into the BNSTL of rats. Two weeks after the injections, neostigmine methylsulfate (sigma, 5 x 10-8 mol) was microinjected into the rat hippocampus in a volume of 1 microl for 1 min using a CMA/100 microinjection pump. Plasma ACTH and glucose concentrations were examined using radioimmunoassay and immobilized enzyme casing/H2O2 method techniques, respectively.

RESULTS: Compared with sham-operated control rats, rats with BNSTL lesions produced by ibotenic acid showed significantly attenuated the elevations of plasma ACTH evoked by the microinjection of neostigmine into the hippocampus. However, no significant difference of blood glucose in response to the injection was observed between the BNSTL-lesioned rats and controls.

CONCLUSION: The results of the present study indicate that the BNSTL plays a role in ACTH regulation and not in blood glucose regulation when the hippocampal cholinergic system is activated....

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Journal Article 2009; 30(4): 515-524 PubMed PMID: 20010498 Citation  Keywords:  Androgens:pharmacology, Animals, Catalase:metabolism, Cell Division:drug effects, Cell Line, Transformed, Cell Survival:drug effects, Down-Regulation:drug effects, Drug Interactions, Glioma, Glucose:pharmacology, Mice, Microtubules:drug effects, Neuroblas.   

OBJECTIVES: Diabetic complications can often affect the central nervous system since the chronic exposure to hyperglycemia can result in the production of high concentration of reactive oxygen species with subsequent damage of several cell structures such as the cytoskeleton. In order to antagonize the oxidative status many substances have been tested as antioxidants. In the present work attention has been focused on the possible nitrosative effect of hyperglycemia on microtubular network of neuroblastoma and glioma mortalized cell lines, testing the possible neuroprotective effect of testosterone.

METHODS: Neuroblastoma (C1300) and glioma (C6) cell lines were cultured in the presence of 300 mM (C1300) or 310 mM (C6) D-glucose, with or without 50 nM testosterone. After 72 hrs, morphology, growth rate, cell viability and catalase activity were evaluated. In addition, with the aim to detect any changes in the amount of tubulin isoforms, Western blot analysis was performed.

RESULTS: In D-glucose-exposed cells, it was found a down-regulation of tubulin isoforms and an increase in 3-nitro-L-tyrosine and subsequent modifications in cell morphology, growth rate, viability and catalase activity. All these changes were more severe in neuroblastoma than in glioma cell line. When testosterone was added to the medium, all the parameters were very similar to controls. This neuroprotective action was well-detectable in C1300 cells, whereas testosterone was not able to recover significantly in C6 cells.

CONCLUSION: Our results displayed: i) a selective action of high glucose on microtubules; ii) a different sensitivity to oxidative stress in neuronal and glial cells; iii) a different neuroprotective action of testosterone on neuronal and glial cells....

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