Wojciech Kostowski, Andrzej Bidziński, Paweł Krzaścik, Janusz Szyndler, Paulina Rok, Paulina Kołomańska, Aleksandra Wisłowska, Małgorzata Lehner, Adam Płaźnik
{"title":"Age-dependent effects of 5,7-dihydroxytryptamine on serotonin transporter in different brain areas in the rat.","authors":"Wojciech Kostowski, Andrzej Bidziński, Paweł Krzaścik, Janusz Szyndler, Paulina Rok, Paulina Kołomańska, Aleksandra Wisłowska, Małgorzata Lehner, Adam Płaźnik","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the present study, we investigated the [(3)H]citalopram binding using a quantitative autoradiography following intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) in neonatal and adult male Wistar rats. One group of animals was injected with 5,7-DHT at 3 days after birth while the second group received the neurotoxin at 3 months after birth. Control group was injected with saline. Afterwards, all rats were examined at 4(th) months after birth to determine the serotonin (5-HT) and catecholamines concentrations using the liquid chromatography with electrochemical detection HPLC system and distribution and density of [(3)H]citalopram binding sites in the brain using the quantitative autoradiography. A marked depletion of brain 5-HT was observed in rats lesioned either in postnatal or adult period of life. Rats lesioned in their adult period of life showed dramatic reduction of 5-HT transporter in all investigated brain areas (i.e.the frontal cortex, entorhinal cortex, hippocampus, caudate-putamen, nucleus accumbens and ventral tegmental area). On the other hand, administration of 5,7-DHT to newborn rats failed to reduce 5-HT transporter sites in the ventral tegmental area, and produced only slight or moderate reduction in the nucleus accumbens. Thus, it appears that the mesolimbic ventral tegmental area-nucleus accumbens systems are relatively more resistant to 5,7-DHT neurotoxicity in the early postnatal period.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 4","pages":"383-9"},"PeriodicalIF":0.0,"publicationDate":"2004-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24792580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrzej Wróbel, Gabriel Nowak, Grazyna Ossowska, Zofia Danilczuk, Iwona Zebrowska-Łupina, Marian Wielosz
{"title":"Effect of chronic treatment with dexamethasone on brain dopamine receptors in mice.","authors":"Andrzej Wróbel, Gabriel Nowak, Grazyna Ossowska, Zofia Danilczuk, Iwona Zebrowska-Łupina, Marian Wielosz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Glucocorticoids are expressed in the central nervous system. Radioligand binding studies have shown their presence in the neurons of the limbic system, a structure involved in mood control and subtle regulation of hypothalamic-pituitary-adrenal (HPA) axis. Structures of the limbic system are also rich in dopaminergic innervation. It has been hypothesized that glucocorticoids may be important in causing and perpetuating depression. Our previous study has demonstrated that dexamethasone decreases the locomotor activity of mice and counteracts the hyperactivity induced by agonists of dopamine receptors. The aim of the present study was to find the possible mechanism responsible for these behavioral effects of dexamethasone. So we sought to examine the influence of chronic dexamethasone treatment on selective radioligand binding to dopamine D(1) ([(3)H]SCH 23390) and D(2) ([(3)H]spiperone) receptors in the brain of mice. The male Albino Swiss mice received dexamethasone (4, 8 or 16 mg/kg/day) for 14 days. The striatum and limbic system structures were isolated and the binding procedure was performed 3.5 or 48 h after the last injection. It was shown that 3.5 h after the last dose of dexamethasone (4 mg/kg/day), specific D(2) receptor binding was statistically significantly increased (by 64%) in the limbic system. On the contrary, the tendency to the reduction of specific D(2) receptor binding was observed in the striatum. Dexamethasone treatment did not influence the specific binding to D(1) receptors in any structure of the brain.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 4","pages":"399-405"},"PeriodicalIF":0.0,"publicationDate":"2004-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24792583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kinga K Borowicz, Jarogniew J Łuszczki, Stanisław J Czuczwar
{"title":"SIB 1893, a selective mGluR5 receptor antagonist, potentiates the anticonvulsant activity of oxcarbazepine against amygdala-kindled convulsions in rats.","authors":"Kinga K Borowicz, Jarogniew J Łuszczki, Stanisław J Czuczwar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>SIB 1893 (a non-competitive antagonist of group I metabotropic glutamate receptors), given at 40 mg/kg (but not at 20-30 mg/kg), shortened the afterdischarge duration in amygdala-kindled rats, being ineffective on other seizure parameters - seizure severity, seizure duration, and afterdischarge threshold. Oxcarbazepine (at 7.5 mg/kg, but not at 5 mg/kg), a newer antiepileptic drug, reduced seizure severity, seizure and afterdischarge durations. When combined at ineffective doses in amygdala kindling, SIB 1893 at 20 or 30 mg/kg and oxcarbazepine at 5 mg/kg, significantly reduced seizure and afterdischarge durations. The results indicate that combinations of oxcarbazepine with antagonists of group I metabotropic glutamate receptors may offer a novel therapeutic approach in cases of drug-resistant epilepsy.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 4","pages":"459-64"},"PeriodicalIF":0.0,"publicationDate":"2004-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24792472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna K Wójtowicz, Ewa L Gregoraszczuk, Anna Ptak, Jerzy Falandysz
{"title":"Effect of single and repeated in vitro exposure of ovarian follicles to o,p'-DDT and p,p'-DDT and their metabolites.","authors":"Anna K Wójtowicz, Ewa L Gregoraszczuk, Anna Ptak, Jerzy Falandysz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The aim of the presented study was to compare the effect of o,p'-DDT [1,1-dichloro-2,2-bis-(p,p'-chlorophenyl)-ethylene] and p,p'-DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)-ethane] and their metabolites DDE and DDD on estradiol secretion by ovarian follicles, the target organs of environmental estrogens. Theca interna (Tc) and granulosa cells (Gc) were collected from medium size porcine follicles and cultured as a monolayer. The cells were initially cultured for 24 h to allow attachment to the plates and then media were changed for the new ones and o,p'-DDT and p,p'-DDT and their metabolites: o,p'-DDE, p,p'-DDE and o,p'-DDD were added at doses of 4, 40, 400 ng and 4 microg/ml medium to investigate dose-dependent effects. Media were collected after 24 h and frozen for estradiol content determination. When the effect of single and repeated exposure was investigated, the lowest dose of 4 ng/ml and the highest one of 4 microg/ml were chosen on the basis of the results of Experiment 1. o,p'-DDT exerted antiestrogenic action at all doses used while its metabolites and p,p'-DDT and its metabolites decreased estradiol secretion only when present in the medium at a dose of 4 ng/ml. The highest doses caused the increase in estradiol secretion. Parent o,p'-DDT and its metabolites showed antiestrogenic action after single exposure to 4 ng/ml while parent p,p'-DDT and its metabolites caused estrogenic action. All investigated compounds, except o,p'-DDT, increased estradiol secretion after single exposure to the dose of 4 microg/ml. Repeated exposure resulted in a massive antiestrogenic action of all investigated chemicals. In conclusion, our study points to time-dependent effect of DDT and its metabolites on ovarian follicles with the strongest estrogenic properties observed after single exposure and antiestrogenic action caused by repeated exposure. Given the duration of folliculogenesis, one can imagine many different potential mechanisms by which DDT could influence steroidogenesis.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 4","pages":"465-72"},"PeriodicalIF":0.0,"publicationDate":"2004-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24792473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Agnieszka Dejda, Hanna Gendek-Kubiak, Jerzy Z Nowak
{"title":"Effect of different forms of vasoactive intestinal peptide on cAMP formation in the mammalian cerebral cortex.","authors":"Agnieszka Dejda, Hanna Gendek-Kubiak, Jerzy Z Nowak","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Chicken, guinea pig and mammalian (human/porcine/rat) vasoactive intestinal peptides (VIP; 0.001-3 microM) were compared with respect to their ability to stimulate adenosine 3', 5'-cyclic monophosphate (cAMP) formation in the cerebral cortical slices of rat and guinea pig. Of the tested peptides, i.e. chicken VIP (cVIP), guinea pig VIP (gpVIP) and human/rat/porcine (mammalian) VIP (mVIP), the strongest stimulator of cAMP synthesis was cVIP, and the weakest one - the gpVIP. Pituitary adenylate cyclase-activating polypeptide (PACAP) used as a reference drug at 0.1 microM concentration strongly stimulated cAMP formation in the cerebrum of both species, being, however, significantly more potent in the guinea pig model. The obtained data demonstrate significant differences in biological activity between cVIP and two distinct mammalian VIPs in the cerebral cortex of rat and guinea pig.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 4","pages":"421-5"},"PeriodicalIF":0.0,"publicationDate":"2004-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24792585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pharmacokinetic interaction after joint administration of zinc and imipramine in forced swim test in mice.","authors":"Elzbieta Wyska, Joanna Szymura-Oleksiak, Włodzimierz Opoka, Bogusław Baś, Ewa Niewiara, Lucyna Pomierny, Małgorzata Dybała, Gabriel Nowak","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Recent preclinical and clinical data indicate beneficial role of zinc in the antidepressant treatment. To evaluate the mechanism of interaction between zinc and antidepressants, in the present study we examined the brain zinc, imipramine and desipramine concentrations in mice treated with combinations of zinc and imipramine and subjected to the forced swim test. We have chosen doses of zinc (10 mg/kg) and imipramine (15 mg/kg) which we have previously found to be ineffective in the forced swim test when given alone. However, when administered jointly, a significant reduction in the immobility time in this test was demonstrated. In the present study, we demonstrated a significant ca. 60% reduction in the brain desipramine and non-significant reduction (ca. 40%) in brain imipramine concentrations in the group of animals treated with zinc plus imipramine compared with animals treated with imipramine alone. The brain zinc concentration in the zinc plus imipramine group was reduced when compared with the group treated with zinc or imipramine alone. Since there was no increase in brain imipramine/desipramine or zinc brain concentration after combined zinc and imipramine treatment, the data suggest that pharmacodynamic rather than pharmacokinetic interaction between zinc and imipramine is responsible for behavioral effect in the forced swim test.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 4","pages":"479-84"},"PeriodicalIF":0.0,"publicationDate":"2004-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24793537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ewa Herba, Dorota Pojda-Wilczek, Agata R Plech, Stefan M Pojda, Ryszard Szkilnik
{"title":"Influence of dopamine on flash visual evoked potentials (FVEP) in prenatally mercury intoxicated rats.","authors":"Ewa Herba, Dorota Pojda-Wilczek, Agata R Plech, Stefan M Pojda, Ryszard Szkilnik","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The female adult white Wistar rats were given tap water (control) or 50 ppm of methylmercury chloride (MMC) ad libitum throughout their pregnancies. Newborn rats drank mother's milk during the first 21 days after delivery and then only tap water. The study was carried out on three-month old offsprings of white Wistar rats. The flash visual evoked potentials (FVEP) were recorded before and after injecting of 10 microl 0.9% saline, 50 or 100 nmols of dopamine (DA) into the lateral brain ventricle by method used before in our laboratory. The amplitude of the first deep negative (N(1)) peak significantly increased to 109-114% after both doses of DA in the control group and to 138-139% in mercury-treated animals. The amplitude of the next positive (P(1)) wave decreased to 94% and 86% in the control group after 50 and 100 nmols of DA, respectively. In Hg-treated group after 50 nmols of DA, the value dropped down to 91%, but increased to 109% after 100 nmols of DA. The increasing of DeltaN(1)P(1) was observed in the control group to 112% after 50 nmols and to 109% after 100 nmols of DA and in Hg-exposed rats, respectively, to 127% and to 129%. The described changes were statistically significant (p < 0.05). The N(1) and P(1) latencies were prolonged in the control group after both doses of DA. In Hg-treated group, the prolongation of N(1) latency was recorded, while the P(1) latency was not changed. We concluded that prenatal Hg intoxication disturbed the effect of DA on FVEP.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 4","pages":"415-9"},"PeriodicalIF":0.0,"publicationDate":"2004-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24792584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Dmoszyńska, Monika Podhorecka, Jacek Roliński, Maria Soroka-Wojtaszko
{"title":"Influence of lovastatin on BCL-2 and BAX expression by plasma cells and T lymphocytes in short-term cultures of multiple myeloma bone marrow mononuclear cells.","authors":"Anna Dmoszyńska, Monika Podhorecka, Jacek Roliński, Maria Soroka-Wojtaszko","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Lovastatin (LOV), until now largely used for the treatment of hypercholesterolemia is a new promising drug in multiple myeloma (MM), however, the precise mechanism of its antitumor activity is not clear yet. It is probable that this effect is mediated by down-regulation of BCL-2 expression. In this study, we analyzed BCL-2 and BAX expression in cells of MM patients exposed to LOV in short-term culture. The obtained results indicate an increase in susceptibility to apoptosis both in CD138+ malignant cells and CD8+ T lymphocytes. Interestingly, such a tendency was confirmed in vivo in MM patient subjected to 3 cycles of LOV therapy.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 4","pages":"485-9"},"PeriodicalIF":0.0,"publicationDate":"2004-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24793540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Preparation of cardiovascular disease-related genes microarray and its application in exploring ligustrazine-induced changes in endothelial gene expression.","authors":"Zesong Li, Deliang Li, Jian Huang, Wen Zhang, Yu Ding, Shengqi Wang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>To study the molecular mechanism of action of ligustrazine, a low-density oligonucleotide microarray for cardiovascular disease-related genes, was constructed, and the preparation and hybridization protocols were optimized. Under the optimized conditions, the molecular mechanism of action of ligustrazine was analyzed with human umbilical vein endothelial cells. After 4 h of treatment with 100 microg/ml of ligustrazine, calcium-ATPase gene, sodium channel gene, P450c11 gene in human umbilical vein endothelial cells were up-regulated while apolipoprotein C-III gene was down-regulated. The results were shown to be reproducible. RT-PCR confirmed the results from microarray. These results suggest that ligustrazine may act on the function of human umbilical vein endothelial cells via modulating the expressions of cardiovascular disease-related genes. This also demonstrates the use of oligonucleotide microarray technology as an approach to studying targets of active components of Traditional Chinese Medicine.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 4","pages":"427-33"},"PeriodicalIF":0.0,"publicationDate":"2004-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24792469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Basem M William, Ahmed M Abdel-tawab, Essam A Hassan, Omar Fathy Mohamed
{"title":"Acetylator phenotyping in patients with malignant lymphomas, using caffeine as the metabolic probe.","authors":"Basem M William, Ahmed M Abdel-tawab, Essam A Hassan, Omar Fathy Mohamed","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>The study was designed to answer the question whether a particular (slow/fast) acetylator phenotype is a risk for malignant lymphoma patients. Differences in acetylator phenotypes were previously described in urinary bladder and colorectal carcinoma patients compared to controls. Addressing this issue may help understanding the possible role of xenobiotics' metabolism in the pathogenesis of malignant lymphomas. Caffeine is currently preferred as a metabolic probe due to its noninvasiveness.</p><p><strong>Design: </strong>Case-control study.</p><p><strong>Setting: </strong>Hematology/oncology inpatient unit and outpatient clinic, Ain Shams University Hospitals, Cairo, Egypt: a tertiary care academic medical institution.</p><p><strong>Participants: </strong>Urine samples were collected 4 h after the oral administration of a caffeine-containing beverage to 83 patients with malignant lymphomas and 92 control subjects. Diagnosis of lymphoma was ascertained histopathologically. Controls were matched in terms of age, sex and residence (urban/rural).</p><p><strong>Measurements: </strong>To define the acetylation phenotype, the nanomolar ratio of the urinary concentrations of the caffeine metabolites: acetylamino-6-amino-3-methyluracil and 1-methylxanthine (AAMU/1X) was calculated for every study subject.</p><p><strong>Results: </strong>An excess of fast acetylators was shown in the malignant lymphoma group compared to the control. The odds ratio for malignant lymphoma associated with fast acetylation was 1.304 (95% CI, 0.709-2.398; p = 0.439). Paradoxically, an excess of the slow acetylator phenotype was observed in patients with low-grade non-Hodgkin lymphoma (n = 25) compared to other subjects of the lymphoma group. The odds ratio for low-grade lymphoma associated with slow acetylation was 4.00 (95% CI, 1.316-12.155; p = 0.014).</p><p><strong>Conclusions: </strong>Owing to the small sample size, the association between the acetylator phenotype and malignant lymphomas could not be excluded. However, the study suggests that, compared to other types of lymphoma, low-grade non-Hodgkin lymphoma would be associated with slow acetylator phenotype.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 4","pages":"445-9"},"PeriodicalIF":0.0,"publicationDate":"2004-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24792471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}