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1

Effects of high sucrose diet, gemfibrozil, and their combination of plasma paraoxonase 1 activity and lipid levels in rats

100%
Macan M., Vrkic N., Vrdoljak L. A., Radic B., Bradamante V.
Acta Biochimica Polonica
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2010
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tom 57
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nr 3
 We investigated the influence of high sucrose diet (HSD) after 3 or 5 weeks of administration on paraoxonase 1 (PON1) activity in plasma of normolipidemic rats and the relationship between serum PON1 activity, triacylglycerides (TGs), HDL and total cholesterol vs. the control group of rats fed normal, control diet (CD). Because the data about the influence of gemfibrozil (GEM) on PON1 activity are controversial, we also investigated its effects (administration in the 4th and 5th week in rats on HSD and CD) on plasma PON1 activity and lipid levels in normolipidemic rats, and in rats with hypertriglyceridemia caused by HSD. Our results obtained in rats on HSD show a significant increase of plasma TGs levels by 47 % (P < 0.05) after 5 weeks of treatment, and PON1 activity by 32 % and 23 % (P < 0.05) after 3 and 5 weeks, but without change in lipid levels vs. rats on CD. In the rats on CD and HSD, GEM caused a significant decrease of PON1 activity by 44 % and 33 %, while a significant decrease of TGs level by 38 % (P < 0.05) was measured only in rats on CD. The effects of GEM on total cholesterol, HDL and LDL in both groups of rats were typical for its action on lipoprotein metabolism. Because GEM in the rat liver stimulates proliferation of peroxisomes, β oxidation, and production of H2O2, it is possible that the oxidative stress induced by GEM damages hepatocytes and lowers the synthesis of PON1.
2

Evaluation of HI-6 oxime: potential use in protection of human acetylcholinesterase inhibited by antineoplastic drug irinotecan and its cyto-genotoxicity in vitro

86%
Radic B., Vrdoljak A. L., Zeljezic D., Fuchs N., Berend S., Kopjar N.
Acta Biochimica Polonica
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2007
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tom 54
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nr 3
The function of acetylcholinesterase (AChE) is the rapid hydrolysis of the neurotransmitter acetylcholine (ACh), which is involved in the numerous cholinergic pathways in both the central and the peripheral nervous system. Therefore, AChE measurement is of high value for therapy management, especially during the course of intoxication with different chemicals or drugs that inhibit the enzyme. Pyridinium or bispyridinium aldoximes (oximes) are able to recover the activity of the inhibited enzyme. Since their adverse effects are not well elucidated, in this study the efficiency of HI-6 oxime in protection and/or reactivation of human erythrocyte AChE inhibited by the antineoplastic drug irinotecan as well as its cyto/genotoxicity in vitro were investigated. HI-6 was effective in protection of AChE and increased its activity up to 30%; the residual activity after irinotecan inhibition was 7%. Also, it reactivated the enzyme previously inhibited by 50% irinotecan (4.6 µg/ml) applied at ¼ of the IC50 value. The tested concentrations of HI-6 exhibited acceptable genotoxicity towards white blood cells, as estimated by the alkaline comet assay, DNA diffusion assay and cytogenetic endpoints (structural chromosome aberrations and cytokinesis-block micronucleus assay). The results obtained warrant the further investigation of HI-6 in vivo, as well as its development for possible application in chemotherapy.
3

Tenocyclidine treatment in soman-poisoned rats - intriguing results on genotoxicity versus protection

86%
Petek M. J., Berend S., Kopjar N., Zeljezic D., Mladinic M., Radic B., Vrdoljak A. L.
Acta Biochimica Polonica
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2008
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tom 55
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nr 1
This study aimed to evaluate the antidotal potency of tenocyclidine (TCP) that probably might protect acetylcholinesterase (AChE) in the case of organophosphate poisoning. TCP was tested alone as a pretreatment or in combination with atropine as a therapy in rats poisoned with ¼ and ½ of LD50 of soman. Possible genotoxic effects of TCP in white blood cells and brain tissue were also studied. Results were compared with previous findings on the adamantyl tenocyclidine derivative TAMORF. TCP given alone as pretreatment, 5 min before soman, seems to be superior in the protection of cholinesterase (ChE) catalytic activity in the plasma than in brain, especially after administration of the lower dose of soman. Plasma activities of the enzyme after a joint treatment with TCP and soman were significantly increased at 30 min (P < 0.001) and 24 h (P = 0.0043), as compared to soman alone. TCP and atropine, given as therapy, were more effective than TCP administered alone as a pretreatment. The above therapy significantly increased activities of the enzyme at 30 min (P = 0.046) and 24 h (P < 0.001), as compared to controls treated with ¼ LD50 of soman alone. Using the alkaline comet assay, acceptable genotoxicity of TCP was observed. However, the controversial role of TCP in brain protection of soman-poisoned rats should be studied further.
4
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Gastric pentadecapeptide BPC 157 counteracts morphine-induced analgesia in mice

72%
Boban Blagaic A., Turcic P., Blagaic V., Dubovecak M., Jelovac N., Zemba M., Radic B., Becejac T., Stancic Rokotov D., Sikiric P.
Journal of Physiology and Pharmacology. Supplement
|
2009
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tom 60
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nr 7
5

A conjugate of pyridine-4-aldoxime and atropine as a potential antidote against organophosphorus compounds poisoning

72%
Lovric J., Berend S., Vrdoljak A. L., Radic B., Katalinic M., Kovarik Z., Zeljezic D., Kopjar N., Rast S., Mesic M.
Acta Biochimica Polonica
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2011
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tom 58
|
nr 2
A conjugate of pyridine-4-aldoxime and atropine (ATR-4-OX) was synthesized and its antidotal efficiency was tested in vitro on tabun- or paraoxon-inhibited acetylcholinesterase (AChE) of human erythrocytes as well as in vivo using soman-, tabun- or paraoxon-poisoned mice. Its genotoxic profile was assessed on human lymphocytes in vitro and was found acceptable for further research. ATR-4-OX showed very weak antidotal activity, inadequate for soman or tabun poisoning. Conversely, it was effective against paraoxon poisoning both in vitro and in vivo. All animals treated with 5 % or 25 % LD50 doses of the new oxime survived after administration of 10.0 or 16.0 LD50 doses of paraoxon, respectively. Based on the persistence of toxicity symptoms in mice, the atropine moiety had questionable effects in attenuating such symptoms. It appears that ATR-4-OX has a therapeutic effect related to the reactivation of phosphylated AChE, but not to receptor antagonization.
6

Deposol reclamation along a canal of the Danube-Tisza- -Danube hydro system

59%
Kadovic R., Belanovic S., Ristic R., Knezevic M., Kostadinov S., Beloica J., Radic B., Dragovic N., Milijic S., Miljanovic D., Braunovic S.
Polish Journal of Environmental Studies
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2014
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tom 23
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nr 4
After the excavation of the canals of the main canal network (MCN) of the Danube-Tisza-Danube (DTD) hydro system, specific technological schemes were used to form deposited materials. In 1958 an experiment with forest plantings was set up on the deposols of the Odžaci-Sombor Canal. Its purpose was the protection and reclamation of the newly-formed dikes. The main aim of this paper is to point to the speed of the process of reclamation and changes in soil properties in the course of a 54-year-long experiment, on the basis of a years-long study of the experimental area.
7
Content available remote

Stable gastric pentadecapeptide BPC 157 heals cysteamine-colitis and colon-colon-anastomosis and counteracts cuprizone brain injuries and motor disability

59%
Klicek R., Kolenc D., Suran J., Drmic D., Brcic L., Aralica G., Sever M., Holjevac J., Radic B., Turudic T., Kokot A., Patrij L., Rucman R., Seiwerth S., Sikiric P.
Journal of Physiology and Pharmacology
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2013
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tom 64
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nr 5
8
Content available remote

High hepatotoxic dose of paracetamol produces generalized convulsions and brain damage in rats. A counteraction with the stable gastric pentadecapeptide BPC 157 (PL 14736)

52%
Ilic S., Drmic D., Zarkovic K., Kolenc D., Coric M., Brcic L., Klicek R., Radic B., Sever M., Djuzel V., Ivica M., Boban Blagaic A., Zoricic Z., Anic T., Zoricic I., Djidic S., Romic Z., Seiwerth S., Sikiric P.
Journal of Physiology and Pharmacology
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2010
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tom 61
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nr 2
We focused on stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, an anti-ulcer peptide efficient in inflammatory bowel disease trials (PL 14736), no toxicity reported) because of its hepatoprotective effects. We investigate a particular aspect of the sudden onset of encephalopathy with extreme paracetamol overdose (5 g/kg intraperitoneally) so far not reported: rapidly induced progressive hepatic encephalopathy with generalized convulsions in rats. BPC 157 therapy (10 µg, 10 ng, 10 pg/kg, intraperitoneally or intragastrically) was effective (µg-ng range) against paracetamol toxicity, given in early (BPC 157 immediately after paracetamol, prophylactically) or advanced stage (BPC 157 at 3 hours after paracetamol, therapeutically). At 25 min post-paracetamol increased ALT, AST and ammonium serum values precede liver lesion while in several brain areas, significant damage became apparent, accompanied by generalized convulsions. Through the next 5 hour seizure period and thereafter, the brain damage, liver damage enzyme values and hyperammonemia increased, particularly throughout the 3-24 h post-paracetamol period. BPC 157 demonstrated clinical (no convulsions (prophylactic application) or convulsions rapidly disappeared (therapeutic effect within 25 min)), microscopical (markedly less liver and brain lesions) and biochemical (enzyme and ammonium serum levels decreased) counteraction. Both, the prophylactic and therapeutic benefits (intraperitoneally and intragastrically) clearly imply BPC 157 (µg-ng range) as a highly effective paracetamol antidote even against highly advanced damaging processes induced by an extreme paracetamol over-dose.
9
Content available remote

Duodenocutaneous fistula in rats as a model for "wound healing-therapy" in ulcer healing: the effect of pentadecapeptide BPC 157, L-nitro-arginine methyl ester and L-arginine

52%
Skorjanec S., Kokot A., Drmic D., Radic B., Sever M., Klicek R., Kolenc D., Zenko A., Lovric Bencic M., Belosic Halle Z., Situm A., Zivanovic Posilovic G., Masnec S., Suran J., Aralica G., Seiwerth S., Sikiric P.
Journal of Physiology and Pharmacology
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2015
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tom 66
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nr 4
10
Content available remote

BPC 157 therapy to detriment sphincters failure-esophagitis-pancreatitis in rat and acute pancreatitis patients low sphincters pressure

52%
Petrovic I., Dobric I., Drmic D., Sever M., Klicek R., Radic B., Brcic L., Kolenc D., Zlatar M., Kunjko K., Jurcic D., Martinac M., Rasic Z., Boban Blagaic A., Romic Z., Seiwerth S., Sikiric P.
Journal of Physiology and Pharmacology
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2011
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tom 62
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nr 5
11
Content available remote

Over-dose insulin and stable gastric pentadecapeptide BPC 157. Attenuated gastric ulcers, seizures, brain lesions, hepatomegaly, fatty liver, breakdown of liver glycogen, profound hypoglycemia and calcification in rats

52%
Ilic S., Brcic I., Mester M., Filipovic M., Sever M., Klicek R., Barisic I., Radic B., Zoricic Z., Bilic V., Berkopic L., Brcic L., Kolenc D., Romic Z., Pazanin L., Seiwerth S., Sikiric P., Seiwerth S., Sikiric P.
Journal of Physiology and Pharmacology. Supplement
|
2009
|
tom 60
|
nr 7
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