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Comparative Study 2016; 37(1): 65-69 PubMed PMID: 26994388 Citation  Keywords:  Adolescent, Adult, Aged, Case-Control Studies, Child, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Membrane Transport Proteins:genetics, Middle Aged, Protein Tyrosine Phosphatase, Non-Receptor Type 22:genetics, Receptors, Immunologic.   

BACKGROUND: Numerous genetic studies revealed several susceptibility genes of autoimmune thyroid diseases (AITD), including CTLA4, PTPN22 and FCRL3. These immune-modulating genes are involved in genetic background of AITD among children and adult patients. However, possible age-related differences in overexpression of these genes remain unclear.

PURPOSE: The goal of this single centre cohort study was evaluation of expression levels of three (3) genes CTLA4, PTPN22 and FCRL3 in adult patients and children with autoimmune thyroiditis.

METHODS: A total of 47 patients--24 adults (mean age--47.7 years) and 23 children (mean age--12.4 years) with autoimmune thyroiditis were assessed for the level of expression of CTLA4, PTPN22 and FCRL3 genes, utilizing ABI PRISM' 7500 Sequence Detection System (Applied Biosystem, Foster City, CA, USA).

RESULTS: The overexpression of PTPN22 (mean RQ = 2.988) and FCRL3 (mean RQ = 2.544) genes were confirmed in adult patients with autoimmune thyroiditis, at the same time the expression level of CTLA4 gene was significantly decreased (mean RQ = 0.899) (p < 0.05). Similar discrepancies were not observed in children with autoimmune thyroiditis in whom overexpression of all three genes--CTLA4, PTPN22 and FCRL3--was observed. Differences in CTLA4 and FCRL3 genes expression levels in patients with autoimmune thyroiditis were found depending on the age, with increased expression levels of CTLA4 (mean RQ = 3.45 1) and FCRL3 (mean RQ = 7.410) in children when compared to adults (p < 0.05) (Mann-Whitney's U-test). There were moderate negative linear correlations between two genes in question (CTLA4 and FCRL3) expression level and patients' age [correlation coefficient (r) = -0.529 (p < 0.0002) and -0.423 (p < 0.0032), respectively; Spearman's rank correlation test].

CONCLUSION: Our results are consistent with the hypothesis that there are few age-dependent genetic differences as regards autoimmune thyroiditis in adults and children. Accordingly, CTLA4 and FCRL3 genes overexpression may play an important role in children suffering from autoimmune thyroiditis....

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Journal Article 2015; 36(Suppl 1): 79-87 PubMed PMID: 26757128 Citation  Keywords:  Animals, Anti-Bacterial Agents:toxicity, Body Size:drug effects, Carps:embryology, Embryo, Nonmammalian:drug effects, Fluoroquinolones:toxicity, Glutathione Peroxidase:drug effects, Glutathione Reductase:drug effects, Glutathione Transferase:drug effects,.   

OBJECTIVES: The aim of this study was to assess the effect of the subchronic exposure of early stages of common carp (Cyprinus carpio L.) to norfloxacin using morphometric data and oxidative stress parameters.

METHODS: A subchronic toxicity test was performed on fertilized embryos of common carp according to the OECD Guidelines No. 210. Embryos were exposed to norfloxacin concentrations of 0.0001 (environmental), 0.1, 1.0, 5.0, and 10.0 mg.L(-1) for 34 days.

RESULTS: At the end of the test (day 34), significant (p<0.05) stimulation of development was observed in all experimental groups, in contrast to the control. Significantly greater (p<0.01) total body length was also observed in the group exposed to 10.0 mg.L(-1) of norfloxacin compared to the control. A significant increase in the activity of glutathione S-transferase in all carp exposed to norfloxacin concentrations of 0.1 and 1.0 mg.L(-1) (p<0.01), and 5.0 mg.L(-1) (p<0.05) compared to control group was revealed. The activity of glutathione peroxidase was significantly lower (p<0.01) in experimental carp exposed to a norfloxacin concentration of 10.0 mg.L(-1). In experimental carp exposed to a norfloxacin concentration of 0.0001 mg.L(-1), a significant increase (p<0.05) in glutathione reductase activity was found. Significant (p<0.01) decreases in the content of thiobarbituric acid reactive substances in the groups exposed to norfloxacin concentrations of 1.0, 5.0, and 10.0 mg.L(-1) were revealed.

CONCLUSION: From the results, we can conclude that norfloxacin has a negative impact on selected biochemical processes related to the production of reactive oxygen species in early-life stages of common carp....

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Journal Article 2015; 36(Suppl 1): 133-140 PubMed PMID: 26757116 Citation  Keywords:  Animals, Carps:blood, Catalase:drug effects, Gills:drug effects, Glutathione Reductase:drug effects, Hematocrit, Hemoglobins:drug effects, Insecticides:toxicity, Kidney:drug effects, Liver:drug effects, Nitriles:toxicity, Oxidative Stress:drug effects, Py.   

OBJECTIVES: The aim of this study is to evaluate effects of the insecticide Decis Mega (DM; active substance deltamethrin 50 g.L(-1)) on common carp on the basis of haematological profile, oxidative stress, antioxidant enzymes and histopathology.

DESIGN: Fish were exposed two concentrations of DM 6.56 μg.L(-1) (1DM) and 65.6 μg.L(-1) (2DM) for 96 h. Then the remaining fish were transferred into DM-free water for depuration for another period of 96 h.

RESULTS: Exposure to 1DM and 2DM proved effect on enzymatic activity of superoxide dismutase, catalase, glutathione reductase and on oxidative damage of cells in gills, liver and kidney (p<0.05, p<0.01). Exposure to 1DM showed differences (p<0.05, p<0.01) in hematocrit and hemoglobin in blood. Histopathological changes were observed after acute exposure to DM as well as to DM-free water in gills, liver and kidney.

CONCLUSION: This study concludes that deltamethrin has influence on the haematological parameters, activity of antioxidant enzymes and caused oxidative damage, and histopathological changes in the fish. However, antioxidant balance in the body was restored after placing the fish in clean water for 4 days, however, this time was not sufficient complete regeneration....

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Comparative Study 2015; 36(Suppl 1): 141-146 PubMed PMID: 26757110 Citation  Keywords:  Aminobenzoates:pharmacology, Anesthetics:pharmacology, Animals, Clove Oil:pharmacology, Cyprinidae, Ethylene Glycols:pharmacology, Etomidate:pharmacology, Gills:drug effects, Glutathione Reductase:drug effects, Liver:drug effects, Muscle, Skeletal:drug ef.   

OBJECTIVES: Currently, many questions regarding the effect of anaesthetics to fish remain unresolved. Fish species may differ widely in their response to an anaesthetic, the screening of dosages is often necessary. The aim of this study was to compare the effect of tricaine methane sulphonate (MS 222), clove oil, 2-phenoxyethanol and Propiscin on haematological profiles, oxidative stress biomarkers and antioxidant enzymes in barbel (Barbus barbus).

DESIGN: The haematological profiles, oxidative stress biomarkers and antioxidant enzymes of barbel were evaluated immediately after a 10 min anaesthesia (MS 222--100 mg.L(-1), clove oil--33 mg.L(-1), 2-phenoxyethanol--0.4 mg.L(-1), Propiscin--1.0 mg.L(-1)), and 24 h after anaesthesia.

RESULTS: The 10 min exposure in the recommended concentrations of tested anaesthetics have no significant effect on haematological profiles, levels of thiobarbituric acid reactive substances, and activity of glutathione reductase of barbel. The activity of superoxide dismutase (SOD) was significantly decreased (p<0.01) in the muscle in all experimental groups. The activity of SOD showed a significant decrease (p<0.01) in the liver 24 h after all anaesthetics; however in the gill the activity of SOD was significantly increased (p<0.01) in Propiscin (10 min). The activity of catalase (CAT) was significantly increased (p<0.05) in the muscle 24 h after all anaesthetics.

CONCLUSIONS: The observed effects on barbel antioxidant systems may be a defence against oxidative damage. The results of this study suggest that the antioxidant systems of barbel are altered by Propiscin anaesthesia, but are slightly affected by MS 222, clove oil, and 2-phenoxyethanol anaesthesia....

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Case Reports 2015; 36(5): 414-416 PubMed PMID: 26707039 Citation  Keywords:  Aged, Amyotrophic Lateral Sclerosis:genetics, Diabetes Mellitus:genetics, Female, Humans, Mutation, Superoxide Dismutase:genetics, Superoxide Dismutase-1,.   

: Familial amyotrophic lateral sclerosis (ALS) are caused by the mutations in the copper (Cu) / zinc (Zn) superoxide dismutase 1 (SOD1) gene. SOD1 has been reported to play a critical role in glucose metabolism in yeast and cell models, and mice. However, effects of SOD1 for glucose metabolism in humans remain unknown. A 72-year-old woman was admitted to our hospital due to hyperglycemia. She showed severe muscle atrophy and visceral fat accumulation due to ALS. Her serum free fatty acids levels elevated and serum Cu and Zn levels decreased. Her two younger brothers and aunt were also diagnosed as having ALS, and DNA sequence analysis revealed the presence of the I113T SOD1 mutation. She may have developed diabetes due to SOD1 dysfunction by the I113T SOD1 mutation, and severe insulin resistance induced by ALS. The I113T SOD1 mutation may be the causative factor for diabetes as well as familial ALS....

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Journal Article 2015; 36(2): 178-182 PubMed PMID: 26071589 Citation  Keywords:  Animals, Animals, Newborn, Aromatase:genetics, Brain:metabolism, Estrogen Receptor alpha:genetics, Female, Fetus, Hypothalamus:metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, RNA, Messenger:metabolism,.   

OBJECTIVES: Local estrogen production in the brain regulates critical functions including neuronal development, gonadotropin secretion and sexual behavior. In the mouse brain, a 36 kb distal promoter (l.f) regulates the Cyp19a1 gene that encodes aromatase, the key enzyme for estrogen biosynthesis. In vitro, promoter l.f interacts with estrogen receptor alpha (Esr1) to mediate Cyp19a1 mRNA expression and enzyme activity in mouse hypothalamic neuronal cell lines. The in vivo mechanisms that control mammalian brain aromatase expression during fetal and adult development, however, are not thoroughly understood. Our aim was to elucidate the basis of the in vivo connection between Esr1 and Cyp19a1.

METHODS: Pregnant mice were sacrificed at gestational days 9, 11, 13, 15, 16, 19, 21 and the brain tissues of the fetuses were harvested along with five newborns at the age of postnatal day 2. Esr1KO (female) were also sacrificed and their hypothalamus were excised out. Then both fetuses and adults RNA were isolated, reverse transcribed and amplified employing primers specific for Esr1 and Cyp19a1 with Real time PCR.

RESULTS: In the fetal mouse brain, Cyp19a1 mRNA levels are inversely correlated with estrogen receptor alpha (Esr1) mRNA levels in a temporal manner. Moreover, Cyp19a1 mRNA levels increased in the hypothalamus of estrogen receptor-alpha knockout female mice (Esr1KO).

CONCLUSION: Taken together, our findings might indicate that Esr1 has crucial roles in the in vivo regulation of aromatase expression in the brain during fetal and adult life....

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Journal Article 2015; 36(2): 165-170 PubMed PMID: 26071586 Citation  Keywords:  Adult, Aged, Ether-A-Go-Go Potassium Channels:metabolism, Growth Hormone-Secreting Pituitary Adenoma:metabolism, Humans, Ki-67 Antigen:metabolism, Male, Middle Aged, Pilot Projects, Young Adult,.   

OBJECTIVE: To determine immunohistochemical expression of Eag1 in pituitary adenomas of patients with acromegaly and to assess the correlation between Eag1 expression with cavernous sinus invasion, tumoral Ki-67 labeling index (LI), age and gender of the patients.

METHODS: The paraffin embedded pituitary adenoma tissue sections of 28 patients with acromegaly who were diagnosed as monohormonal growth hormone (GH) secreting adenomas were immunostained for Eag1 using the avidin-biotin-peroxidase complex method. Eag1 immunoreactivity was scored according to the extensity of the cytoplasm and cell membrane immunoreactivity for Eag1 (score 1 = <10%, score 2 = 10-25%, score 3 = 25-50% and score 4 = >50% of the adenoma cells showed immunoreactivity for Eag1, respectively).

RESULTS: Overall, GH secreting pituitary adenomas displayed diverse levels of Eag1 immunoreactivity, however, 64% of the adenomas displayed a strong Eag1 immunoreactivity (score 3 and 4). Five of the tumors displayed Eag1 immunoreactivity score 1, 5 displayed score 2, 10 displayed score 3 and 8 displayed score 4, respectively. No correlation was found between Eag1 immunoreactivity with cavernous sinus invasion, Ki-67 LI, age and gender of the patients.

CONCLUSIONS: Our results suggest Eag1 is strongly expressed in the majority of GH secreting pituitary adenomas. However, we could not find any correlation between immunoreactivity of Eag1 with cavernous sinus invasion, Ki-67 LI, age and gender of the patients. Further studies with larger sample sizes are required to demonstrate the role of Eag1 on tumorigenesis, angiogenesis, invasion and response to the treatment in GH secreting pituitary adenomas....

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Journal Article 2014; 35(Suppl 2): 123-132 PubMed PMID: 25638376 Citation  Keywords:  Animals, Aristolochic Acids:metabolism, Dicumarol:pharmacology, Enzyme Inhibitors:pharmacology, Humans, Quinone Reductases:metabolism, Rats,.   

OBJECTIVES: Dicoumarol is known to act as an inhibitor of

NAD(P)H: quinone oxidoreductase (NQO1). This cytosolic reductase significantly contributes to the genotoxicity of the nephrotoxic and carcinogenic alkaloid aristolochic acid I (AAI). Aristolochic acid causes aristolochic acid nephropathy (AAN), and Balkan endemic nephropathy (BEN), as well as associated urothelial malignancies. NQO1 is the most efficient enzyme responsible for the reductive bioactivation of AAI to species forming covalent AAI-DNA adducts. However, it is still not known how dicoumarol influences the NQO1-mediated reductive bioactivation of AAI.

METHODS: AAI-DNA adduct formation was determined by 32P-postlabeling. Expression of NQO1 mRNA and NQO1 protein was determined by real-time polymerase chain reaction and Western blotting, respectively.

RESULTS: In this study, dicoumarol inhibited AAI bioactivation to form AAI-DNA adducts mediated by rat and human NQO1 in vitro as expected. We however, demonstrated that dicoumarol acts as an inducer of NQO1 in kidney and lung of rats treated with this NQO1 inhibitor in vivo, both at protein and activity levels. This NQO1 induction increased the potency of kidney cytosol to bioactivate AAI and elevated AAI-DNA adduct levels were found in ex-vivo incubations of AAI with renal cytosols and DNA. NQO1 mRNA levels were induced in liver only by dicoumarol.

CONCLUSION: Our results indicate a dual role of dicoumarol in NQO1-mediated genotoxicty of AAI. It acts both as an NQO1 inhibitor mainly in vitro and as an NQO1 inducer if administered to rats.

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