Browsing by Author "Ugrešić, Nenad (6602152735)"

Background/Aim. Colorectal carcinoma (CRC) is one the most frequent malignant disease with early liver metastasis. It requires the timely use of anticancer drugs. Current treatment of metastatic CRC consists of conventional anticancer drugs use, but they cause liver damage which is manifested by disorder in biochemical liver function parameters. The addition of one of monoclonal antibodies, e.g. bevacizumab improves their therapeutic effect, but its influence on caused biochemical disturbances is not completely known. Therefore the aim of this study was to compare the level of liver function test parameters in patients treated with conventional anticancer drugs with parameters in patients additionally treated with bevacizumab. Methods. The study was performed on the two groups of adult patients with liver metastatic CRC assigned according to the treatment protocol. One group of the patients (n = 44) was treated with FOLFOX4 (the group 1), and the other one (n = 52) with bevacizumab added to FOLFOX4 treatment protocol (the group 2). Depending on the response of patients, the duration of treatment varied from 2 to 6 months. Standard liver function tests were performed before and after the completion of the treatment. Results. Initial values of some biochemical function test parameters [alkaline phosphatase (ALP) in the group 1 of patients, gamma-glutamyl transferase (GGT) and lactate dehydrogenase (LDH) in both groups] were increased in relation to the normal reference values, with some intergroup differences (p = 0.001). Biochemical disturbances of liver function tests in the group of patients treated with conventional anticancer drugs were due to not only their metastases but also due to the hepatotoxic effect of drugs used. After the treatment, significant differences in biochemical liver tests parameters were found in aspartate aminotransferase (AST), alanine aminotransferase (ALP), GGT and LDH, being lower in the group 2 (patients additionally treated by bevacizumab) (p values were: 0.002 for AST; 0.001 for ALP and GGT; 0.000 for LDH). The levels of the other studied parameters, alanine aminotransferase (ALT) bilirubin, and proteins did not differ significantly between groups both preor post-treatment. Conclusion. Both, metastatic CRC and treatment with the conventional anticancer drugs induce significant disturbances of several liver function parameters. The addition of bevacizumab to the conventional anticancer drugs did not affect these disturbances. © 2017, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved.

The antinociceptive effects of carbamazepine and oxcarbazepine, and the influence of caffeine, were examined in a paw pressure test in rats. Carbamazepine (10-40 mg/kg; intraperitoneal, i.p.) and oxcarbazepine (40-160 mg/kg; i.p.) caused a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by concanavalin A (Con A), intraplantarly (i.p1.). A comparable pattern of antinociceptive effect of carbamazepine and oxcarbazepine was observed; the only difference is their potency, in that carbamazepine was about three times more potent than oxcarbazepine. Caffeine (5-20 mg/kg; i.p.), a non-selective adenosine receptor antagonist, significantly depressed the antinociceptive effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Also, a significant depression of the antinociceptive effects of carbamazepine and oxcarbazepine was observed by pretreatment with 1,3-dipropyl-8-cyclopentylxantine (DPCPX, 0.4 and 0.8 mg/kg; i.p.), an adenosine A1 receptor antagonist. These findings indicate that, in a paw inflammatory hyperalgesia in rats, the antinociceptive effects of both drugs are, at least partially, mediated by adenosine A1 receptors. In conclusion, the present study suggests the potential clinical importance of carbamazepine and oxcarbazepine in the treatment of inflammatory pain. In addition, caffeine consumption could possibly depress the analgesic effects of both anticonvulsive drugs. © 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

The antinociceptive effects of carbamazepine and oxcarbazepine, and the influence of caffeine, were examined in a paw pressure test in rats. Carbamazepine (10-40 mg/kg; intraperitoneal, i.p.) and oxcarbazepine (40-160 mg/kg; i.p.) caused a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by concanavalin A (Con A), intraplantarly (i.p1.). A comparable pattern of antinociceptive effect of carbamazepine and oxcarbazepine was observed; the only difference is their potency, in that carbamazepine was about three times more potent than oxcarbazepine. Caffeine (5-20 mg/kg; i.p.), a non-selective adenosine receptor antagonist, significantly depressed the antinociceptive effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Also, a significant depression of the antinociceptive effects of carbamazepine and oxcarbazepine was observed by pretreatment with 1,3-dipropyl-8-cyclopentylxantine (DPCPX, 0.4 and 0.8 mg/kg; i.p.), an adenosine A1 receptor antagonist. These findings indicate that, in a paw inflammatory hyperalgesia in rats, the antinociceptive effects of both drugs are, at least partially, mediated by adenosine A1 receptors. In conclusion, the present study suggests the potential clinical importance of carbamazepine and oxcarbazepine in the treatment of inflammatory pain. In addition, caffeine consumption could possibly depress the analgesic effects of both anticonvulsive drugs. © 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

In this study, the effects of yohimbine (α 2 -adrenoceptor antagonist) and clonidine (α 2 -adrenoceptor agonist) on anti-hyperalgesia induced by carbamazepine and oxcarbazepine in a rat model of inflammatory pain were investigated. Carbamazepine (10-40 mg/kg; i.p.) and oxcarbazepine (40-160 mg/kg; i.p.) caused a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by concanavalin A (Con A, intraplantarly) in a paw pressure test in rats. Yohimbine (1-3 mg/kg; i.p.) significantly depressed the anti-hyperalgesic effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Both drug mixtures (carbamazepine-clonidine and oxcarbazepine-clonidine) administered in fixed-dose fractions of the ED 50 (1/2, 1/4 and 1/8) caused significant and dose-dependent reduction of the hyperalgesia induced by Con A. Isobolographic analysis revealed a significant synergistic (supra-additive) anti-hyperalgesic effect of both combinations tested. These results indicate that anti-hyperalgesic effects of carbamazepine and oxcarbazepine are, at least partially, mediated by activation of adrenergic α 2 -receptors. In addition, synergistic interaction for anti-hyperalgesia between carbamazepine and clonidine, as well as oxcarbazepine and clonidine in a model of inflammatory hyperalgesia, was demonstrated. © 2006 International Association for the Study of Pain.

In this study, the effects of yohimbine (α 2 -adrenoceptor antagonist) and clonidine (α 2 -adrenoceptor agonist) on anti-hyperalgesia induced by carbamazepine and oxcarbazepine in a rat model of inflammatory pain were investigated. Carbamazepine (10-40 mg/kg; i.p.) and oxcarbazepine (40-160 mg/kg; i.p.) caused a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by concanavalin A (Con A, intraplantarly) in a paw pressure test in rats. Yohimbine (1-3 mg/kg; i.p.) significantly depressed the anti-hyperalgesic effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Both drug mixtures (carbamazepine-clonidine and oxcarbazepine-clonidine) administered in fixed-dose fractions of the ED 50 (1/2, 1/4 and 1/8) caused significant and dose-dependent reduction of the hyperalgesia induced by Con A. Isobolographic analysis revealed a significant synergistic (supra-additive) anti-hyperalgesic effect of both combinations tested. These results indicate that anti-hyperalgesic effects of carbamazepine and oxcarbazepine are, at least partially, mediated by activation of adrenergic α 2 -receptors. In addition, synergistic interaction for anti-hyperalgesia between carbamazepine and clonidine, as well as oxcarbazepine and clonidine in a model of inflammatory hyperalgesia, was demonstrated. © 2006 International Association for the Study of Pain.