Effects of serotonin (5-HT)(1B) receptor ligands,microinjected into accumbens subregions,on cocaine discrimination in rats

Recent data indicate a significant input of serotonin (5-HT) on mesoaccumbens dopamine-dependent behavioral effects of cocaine in rats. The present study investigated the role of 5-HT(1B) receptors in nucleus accumbens subregions (the shell and the core) and the effect of stimulation of those receptors in the discriminative stimulus effects of cocaine in rats. Male Wistar rats were trained to discriminate cocaine (10 mg/kg, i.p.) from saline (i.p.) in a two-choice, water-reinforced fixed-ratio 20 procedure. After reaching the cocaine-saline discrimination criterion, rats were stereotaxically implanted with bilateral cannulae in the accumbens shell or core, and then were microinjected with selective 5-HT(1B) receptor ligands. In substitution studies, microinjections of the 5-HT(1B) receptor antagonist GR 55562 (0.1-10 microg/side) or the 5-HT(1B) receptor agonist CP 93129 (0.1-10 microg/side) into accumbens subregions did not evoke cocaine-lever responding. Pretreatment with the 5-HT(1B) receptor antagonist GR 55562 (0.1-10 microg/side) in the accumbens shell or core failed to modulate the discriminative stimulus effects of cocaine (5 mg/kg). Combination tests using a fixed dose of CP 93129 (1-10 microg/side) into the accumbens shell prior to cocaine administration (0.6-5.0 mg/kg) did not affect cocaine discrimination. CP 93129 (1 microg/side, but not 0.1 microg/side) microinjected in the accumbens core, and low doses of systemic cocaine (0.6-2.5 mg/kg) produced a leftward shift in the cocaine dose-response curve and a decrease in its ED(50) value. GR 55562 (1 microg/side) significantly attenuated the enhancement of cocaine discrimination evoked by a combination of CP 93129 (1 microg/side) and cocaine (1.25 mg/kg or 2.5 mg/kg). These results seem to exclude a major role for the accumbens shell and core 5-HT(1B) receptors in controlling the discriminative stimulus effects of cocaine. However, they do suggest that the stimulation of 5-HT(1B) receptors in the accumbens core, but not in the shell, enhances cocaine discrimination in rats.     

Effect of intra-tegmental microinjections of 5-HT1B receptor ligands on the amphetamine-induced locomotor hyperactivity in rats

Previous research demonstrated that the mesoaccumbens dopamine (DA) pathway played a critical role in the behavioral effects of amphetamine in rodents. Nonetheless, recent findings have also indicated involvement of 5-hydroxytryptamine (5-HT, serotonin) transmission in these effects. In the present study, we investigated the role of 5-HT1B receptors located in the ventral tegmental area (VTA) in the amphetamine-induced locomotor hyperactivity in rats. Male Wistar rats, implanted bilaterally with cannulae in the VTA were infused with saline (0.2 microl/side), GR 55562 (an antagonist of 5-HT1B receptors; 0.1-1 microg/side) or CP 93129 (an agonist of 5-HT1B receptors; 0.003-0.03 microg/side) immediately prior to the injection of saline (1 ml/kg, ip) or amphetamine (0.5 mg/kg, ip). The monitoring of locomotor activity in photobeam chambers began at once and proceeded for 60 min. Neither GR 55562 nor CP 93129 affected basal locomotor activity. Pretreatment with GR 55562 (0.1-1 microg/side) did not affect the locomotor hyperactivity evoked by amphetamine. On the other hand, microinjections of CP 93129 (0.01-0.03 microg/side) enhanced the amphetamine-induced hyperlocomotor activity. GR 55562 (1 microg/side) markedly reduced the enhancing effects of CP 93129 (0.01 microg/side) on the amphetamine-induced hyperactivity. These findings indicate that 5-HT1B receptors located in the VTA do not play a major role in the hyperlocomotion elicited by amphetamine, whereas their activation may modulate the behavioral response to the psychostimulant.     

Role of dopamine D3 receptors in controlling the expression of cocaine sensitization in rats

It is established that dopamine (DA) is an important brain mediator of the behavioral (i.e. sensitizing) effects of cocaine in rodents. Among DA receptors, recent findings point to engagement of DA D3 receptors in cocaine addictive actions. In the present study, we attempted to determine the role of DA D3 receptors in the expression phase of sensitization to cocaine in rats, using the selective ligands 7-OH-PIPAT (an agonist) and nafadotride (an antagonist) of these receptors. Repeated administration (1-5 days) of cocaine (10 mg/kg, ip) to male Wistar rats significantly enhanced the locomotor activation induced by its challenge dose given after 5-day withdrawal (on day 10). 7-OH-PIPAT (1 mg/kg, but not 0.01-0.1 mg/kg, sc) administered together with a challenge dose of cocaine significantly decreased the response to cocaine in rats treated repeatedly with cocaine. On the other hand, the expression of cocaine sensitization was increased when that drug was combined with nafadotride (0.4 mg/kg, ip) on day 10. The results indicate a role of DA D3 receptors in controlling the expression of cocaine sensitization in rats, and may suggest an importance of DA D3 receptor agonists in the therapy of cocaine abuse.     

Reovirus oncolysis as a novel purging strategy for autologous stem cell transplantation

Hematologic stem cell rescue after high-dose cytotoxic therapy is extensively used for the treatment of many hematopoietic and solid cancers. Gene marking studies suggest that occult tumor cells within the autograft may contribute to clinical relapse. To date purging of autografts contaminated with cancer cells has been unsuccessful. The selective oncolytic property of reovirus against myriad malignant histologies in in vitro, in vivo, and ex vivo systems has been previously demonstrated. In the present study we have shown that reovirus can successfully purge cancer cells within autografts. Human monocytic and myeloma cell lines as well as enriched ex vivo lymphoma, myeloma, and Waldenstr?m macroglobulinemia patient tumor specimens were used in an experimental purging model. Viability of the cell lines or purified ex vivo tumor cells of diffuse large B-cell lymphoma, chronic lymphocytic leukemia, Waldenstr?m macroglobulinemia, and small lymphocytic lymphoma was significantly reduced after reovirus treatment. Further, [35S]-methionine labeling and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of cellular proteins demonstrated reovirus protein synthesis and disruption of host cell protein synthesis as early as 24 hours. Admixtures of apheresis product with the abovementioned tumor cells and cell lines treated with reovirus showed complete purging of disease. In contrast, reovirus purging of enriched ex vivo multiple myeloma, Burkitt lymphoma, and follicular lymphoma was incomplete. The oncolytic action of reovirus did not affect CD34+ stem cells or their long-term colony-forming assays even after granulocyte colony-stimulating factor (G-CSF) stimulation. Our results indicate the ex vivo use of an unattenuated oncolytic virus as an attractive purging strategy for autologous stem cell transplantations.     

Aims of neurorehabilitation

The aim of this article is to present basic problems of new neuro-rehabilitation, its purposes and methods. This paper shows the newest methods of kinezytherapy and drugs used in improving the rehabilitation process. Authors present interdisciplinary rehabilitation teams dealing with neurologically disabled patients. They also show short programs of rehabilitation in multiple sclerosis and in stroke patients. That diseases are very popular in main population and are one of the main cause of disability in adult people.     

Analysis of epileptic pregnant women delivering between 1992-1998 in obstetric departments of the University Medical School in Lublin

Pregnancy in woman with epilepsy arouses several serious medical problems and always belongs to the group of high obstetric risks. The aim of the present clinical study was the evaluation of the antiepileptic treatment efficiency during pregnancy, including risk factor, effects on pregnancy and delivery in epileptic patients. The study group consisted of 84 epileptic pregnant women which delivered between 1992-1998 in Obstetric Departments of University Medical School of Lublin. A randomised group 80 healthy pregnant women constituted the control group. The mean age of the analysed patients was 25 years. 51 epileptic patients were pregnant for the first time, 23 patients for the second time and 10 patients for the third time or more. The mean duration time of the disease was 8.6 years. In our study group: 45 (53.8%) patients experienced primary generalized tonic-clonic seizures and 39 (46.6%) patients experienced partial seizures. 26 patients were treated with monotherapy and the rest with polytherapy methods. The estimation of the seizure frequency during pregnancy in 52 (61.9%) patients did not change, in 13 (15.4%) patients increased. Among obstetric complications: urinary tract infections, hypertonia (EPH-gestosis) were observed. In 4 newborn congenital defects have been noted. Mothers of three of them were treated with Phenydantin (heart lesion, developmental anomaly of fingers). The fourth mother used Convulex (meningoarachnided hernia, hydrocephalus).     

Lymphocytes in peripheral blood and thyroid tissue in children with Graves’ disease

Background  This study was undertaken to analyze subsets of lymphocytes in peripheral blood in the early phase and in the thyroid tissue in the late phase of Graves’ disease (GD) in children. Methods  The study included 30 children with GD and 30 healthy children. Monoclonal antibodies were used to define peripheral blood lymphocyte subsets and they were analyzed using the flow cytometer Ortho Diagnostic System. After thyroidectomy, T cells were detected by CD3, CD4, CD8 antibodies, B cells by CD79α antibodies, and the antigen presenting dendritic cells (APCs) by CD1α antibodies (DakoCytomation) in the thyroid tissue. Results  Before the treatment, an increased percentage of CD4+ T helper cells and B cells and decreased CD8+ T suppressor/cytotoxic cells were observed in peripheral blood in all the GD children. The number of lymphocytes and dendritic cells in the thyroid tissue increased in the children with GD in comparison to the control group, especially T cells subsets CD4+ and CD8+ and CD79α+ B cells. The percentage of T cells in the thyroid tissue was lower and that of B cells was higher than in peripheral blood. In their structure, thyrocytes can have components similar to α-chains connected with β-microglobulins, which were characteristic for APCs. Conclusions  The primary defect of immunoregulation in children with GD is probably dependent on a large number and the activity of T helper cells and on a small number and hypofunction of T suppressor cells. The amount of lymphocytes decreased proportionally to the duration of methimazole treatment. The thyrocytes probably can present antigens.     

Effect of lamivudine treatment on plasma levels of transforming growth factor β1, tissue inhibitor of metalloproteinases-1 and metalloproteinase-t in patients with chronic hepatitis B

AIM: Transforming growth factor (TGF)-β1, metalloproteinase(MMP)-1 and its tissue inhibitor (TIMP)-1 are consideredpredictive biomarkers of chronic hepatitis activity and fibrosis. The aim of this study was to evaluate the effect of lamivudine treatment on the plasma levels of these peptides in patients with chronic hepatitis B.METHODS: TGF-β1, MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 40 patients treated with lamivudine for 48 wk. Elimination of HBV-DNAand HBV antigens was evaluated 24 wk after treatment completion.RESULTS: Baseline TGF-β1 (29.6±2.2 ng/mL) and TIMP-1(1 578±93 ng/mL) significantly exceeded normal values(18.3±1.6 ng/mL and 1 102±67 ng/mL respectively). Lamivudine treatment resulted in a significant decrease of TGF-β1 andTIMP-1 during treatment with an increase after 24 wk oftreatment. Pretreatment MMP-1 levels (6.7±0.7 ng/mL) weresignificantly lower than normal values (11.9±0.9 ng/mL) and increased during treatment and follow-up. A significant correlation was noted between TGF-β1 or TIMP-1 and aminotransferases as well as fibrosis scored in liver biopsy specimens. There were no statistically significant differences of TGF-β1, TIMP-1 and MMP-1 between four groups atbaseline, 24 and 48 wk of treatment. TGF-β1 and TIMP-1 levels increased significantly in non-responders and normalized in responders at wk 72. MMP-1 also normalized in responders and decreased to values significantly lower than normal innon-responders.CONCLUSION: These findings support the role of TGF-β1,TIMP-1 and MMP-1 in the pathogenesis of chronic hepatitis B.Because of their association with hepatic injury and antiviral treatment efficacy, determination of these peptides may be useful in disease management.