Effects of therapeutic and toxic doses of levamisole on thyroid hormones and some biochemical parameters in sheep

This study was carried out to establish the effects of therapeutic and toxic doses of levamisole on thyroid hormone levels and some biochemical parameters in sheep. Twelve Akkaraman ewes were used. Levamisole was given orally at doses of 7.5 mg kg(-1) (group 1) and 40 mg kg(-1) (group 2) to the animals. Blood samples were taken from the jugular vein at 2, 4, 8, 24, 48, 96 and 144 h after the administrations. Serum thyroid hormones and some biochemical parameters were determined on these samples. When compared with the control levels, no significant changes were observed in triiodothyronine (T3) and thyroxin (T4) levels in group 1. Although levamisole was found to increase the levels of total T3, it decreased the levels of total T4 in group 2. On the other hand, free T3 and free T4 levels were not changed in either group. While serum alkaline phosphatase (ALP) activities were decreased, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatinine kinase (CK) activities were increased significantly by levamisole. However, it increased the serum albumin and cholesterol levels, but decreased the inorganic phosphate levels in groups 1 and 2. On the other hand, when compared with the control levels, no significant changes were detected in serum sodium, potassium and calcium levels. In conclusion, therapeutic and toxic doses of levamisole were determined to affect thyroid metabolism and some biochemical parameters in sheep.     

Serum free prostate-specific antigen and zinc levels in experimental acute pancreatitis

Serum free prostate-specific antigen (fPSA) is the most useful tumor marker for prostatic cancer screening. However, recently, fPSA has also been detected in sera from patients with pancreatic diseases. In addition, it has been shown that zinc (Zn) concentration might change in both serum and tissues in pancreatic disease. In the present study, we measured serum concentrations of fPSA and Zn as possible markers and prognostic factors in an experimental acute-pancreatitis model. Twenty-five female Wistar albino rats were divided into two groups: the control group (n=10) and the experimental group (n=15). Acute pancreatitis was induced by injection of ethyl alcohol into the common biliary duct. The animals were sacrificed 24 h later to detect the concentrations of serum fPSA and Zn. fPSA values were detected to be significantly higher in the experimental group p<0.001). There was also a significant decrease in the serum Zn level of the acute-pancreatitis group (p<0.001). In conclusion, these findings suggested that a combination of these parameters might represent a significant improvement on the diagnostic value of each of them separately and provide a powerful tool for differential diagnosis and prognosis in pancreatic diseases.     

Application of isotopic ratio mass spectrometry for the in vitro determination of demethylation activity in human liver microsomes using N-methyl-13C-labeled substrates

The reaction of demethylation mediated by cytochrome P450 (CYP) leads to the equimolar production of demethylated metabolite and formaldehyde. From a 13C-substrate labeled on a carbon of the methyl moiety, [13C]formaldehyde (H13CHO) is liberated. A highly sensitive and specific assay involving the oxidation of H13CHO to 13CO(2) by a double-enzymatic-step reaction is reported. The 13CO(2) was quantified by the method of reverse isotopic dilution based on gas chromatography-isotope ratio mass spectrometry analysis. The method first involves the limiting step of the CYP-dependent reaction, which is stopped with a mixture of zinc sulfate 5 mM and trichloroacetic acid 100 mM. Then, the transformation of H13CHO to 13CO(2) is performed with the formaldehyde (0.2 unit) and the formate (0.2 unit) dehydrogenase NAD-dependent enzymes. The recovery of 13CO(2) from the incubation mixture was equal to 91.4 +/- 3.0%. The accuracy and the precision of the present method were within 12 and 10%, respectively. The limit of quantification was set to 25 pmol. The performance of the assay was validated on human liver microsomes with five probes: [13C]erythromycin, [1-13C]caffeine, [3-13C]caffeine, [7-13C]caffeine, and [13C(2)]aminopyrine. This method is useful for the rapid determination of N-demethylase activity of human liver microsomes from methyl-13C-substrates.     

Cytotoxicity and apoptotic effects of nickel oxide nanoparticles in cultured HeLa cells

The aim of this study was to observe the cytotoxicity and apoptotic effects of nickel oxide nanoparticles on human cervix epithelioid carcinoma cell line (HeLa). Nickel oxide precursors were synthesized by an nickel sulphate-excess urea reaction in boiling aqueous solution. The synthesized NiO nanoparticles (<200 nm) were investigated by X-ray diffraction analysis and transmission electron microscopy techniques. For cytotoxicity experiments, HeLa cells were incubated in 50-500 μg/mL NiO for 2, 6, 12 and 16 hours. The viable cells were counted with a haemacytometer using light microscopy. The cytotoxicity was observed low in 50-200 μg/mL concentration for 16 h, but high in 400-500 μg/mL concentration for 2-6 h. HeLa cells' cytoplasm membrane was lysed and detached from the well surface in 400 μg/mL concentration NiO nanoparticles. Double staining and M30 immunostaining were performed to quantify the number of apoptotic cells in culture on the basis of apoptotic cell nuclei scores. The apoptotic effect was observed 20% for 16 h incubation.     

Gender related differential effects of Omega-3E treatment on diabetes-induced left ventricular dysfunction

The present study was designed to determine whether there are beneficial effects of intake of Ω-3E (containing 70% pure omega-3 and 2% natural vitamin E) in cardiac dysfunction of diabetic rats. We also examined whether there are gender-related differences in the responses to the intake of Ω-3E on the heart dysfunction. Experiments were performed by using Langendorff-perfused hearts from normal, diabetic (with 50 mg/kg streptozotocin), and Ω-3E (50 mg/kg body weight/day) treated diabetic 3-month-old Wistar rats. Ω-3E treatment of the diabetics caused small, but significant decrease (13% and 14% female versus male) in the blood glucose level. Ω-3E treatment of the diabetic female rats did not prevent diabetes-induced decrease in left ventricular developed pressure (LVDP) and increase in left ventricular end-diastolic pressure (LVEDP) with respect to the control female rats. On the other hand, the treatment of diabetic male rats caused significant recovery in depressed LVDP. Furthermore, such treatment of diabetic female and male rats caused significant recovery in depressed rates of changes of developed pressure. This effect was more significant in males. Besides, Ω-3E caused significant further lengthening in the diabetes-induced increased time to the peak of the developed pressure in females, while it normalized the lengthening in the relaxation of the developed pressure in diabetic males. In addition, Ω-3E treatment caused significant restorations in the diabetes-induced altered activities of antioxidant enzymes without any significant gender discrepancy. Present data show that there are gender related differences in diabetic heart dysfunction and the response to antioxidant treatment.