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1.
BackgroundExcessive consumption of ethanol is known to activate the mTORC1 pathway and to enhance the Collapsin Response Mediator Protein-2 (CRMP-2) levels in the limbic region of brain. The latter helps in forming microtubule assembly that is linked to drug taking or addiction-like behavior in rodents. Therefore, in this study, we investigated the effect of lacosamide, an antiepileptic drug and a known CRMP-2 inhibitor, which binds to CRMP-2 and inhibits the formation of microtubule assembly, on ethanol-induced conditioned place preference (CPP) in mice.MethodsThe behavior of mice following ethanol addiction and withdrawal was assessed by performing different behavioral paradigms. Mice underwent ethanol-induced CPP training with alternate dose of ethanol (2 g/kg, po) and saline (10 ml/kg, po). The effect of lacosamide on the expression of ethanol-induced CPP and on ethanol withdrawal associated anxiety and depression-like behavior was evaluated. The effect of drug on locomotor activity was also assessed and hippocampal CRMP-2 levels were measured.ResultsEthanol-induced CPP was associated with enhanced CRMP-2 levels in the hippocampus. Lacosamide significantly reduced the expression of ethanol-induced CPP and alleviated the levels of hippocampal CRMP-2 but aggravated withdrawal-associated anxiety and depression in mice.ConclusionThe present study demonstrated the beneficial effect of lacosamide in attenuation of expression of ethanol induced conditioned place preference via reduction of hippocampal CRMP-2 level. These findings suggest that lacosamide may be investigated further for ethanol addiction but not for managing withdrawal. 相似文献
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B. C. Beaudette-Zlatanova B. Whalen D. Zipris H. Yagita J. Rozing H. Groen C. D. Benjamin T. Hunig H. A. Drexhage M. J. Ansari J. Leif J. P. Mordes D. L. Greiner M. H. Sayegh A. A. Rossini 《American journal of transplantation》2006,6(5P1):894-902
Costimulatory signals regulate T-cell activation. To investigate the role of costimulation in autoimmunity and transplantation, we studied the BB rat model of type 1 diabetes. Diabetes-prone BB (BBDP) rats spontaneously develop disease when 55–120 days of age. We observed that two anti-CD28 monoclonal antibodies (mAb) with different functional activities completely prevented diabetes in BBDP rats. Anti-CD154 mAb delayed diabetes, whereas treatment with CTLA4-Ig or anti-CD80 mAb accelerated disease. Anti-CD86 or anti-CD134L mAbs had no effect. Diabetes resistant BB (BBDR) rats are disease-free, but >95% of them develop diabetes after treatment with polyinosinic-polycytidylic acid and an mAb that depletes Treg cells. In the induced BBDR model, anti-CD154 mAb delayed onset of diabetes, whereas CTLA4-Ig, anti-CD134L or either of the anti-CD28 mAbs had little or no effect. In contrast, blockade of the CD134-CD134L pathway was highly effective for preventing autoimmune recurrence against syngeneic islet grafts in diabetic BBDR hosts. Blockade of the CD40-CD154 pathway was also effective, but less so. These data suggest that the effectiveness of costimulation blockade in the treatment of type 1 diabetes is dependent on both the costimulatory pathway targeted and the mechanism of induction, stage, intensity and duration of the pathogenic process. 相似文献
4.
Forty-seven patients with oesophageal carcinoma were managed in 6 years' time. Average duration of illness was 5.5 months. History of chronic smoking and/or tobacco chewing was present in 80.85% of patients. Carcinoma included squamous cell variety (80.85%) and adenocarcinoma (19.15%). Thirty-one patients were in stage III while 16 patients were in stage II. Surgery included oesophagogastrectomy/oesophagogastrostomy (16 patients), feeding gastrostomy (11 patients), Mousseau-Barbin tube insertion (10 patients), only 10 patients were subjected to palliative radiotherapy. All patients after palliative treatment died within one year whereas 3-year and 5-year survivals after oesophagogastrectomy/oesophagogastrostomy were 68.75% and 31.25% respectively. Local lymph node metastasis adversely affected the 5-year survival rate. 相似文献
5.
Mohammed T Ansari Mohammad T Mahmood Johan P E Karlberg 《Blood coagulation & fibrinolysis》2006,17(5):335-341
This is the first study to examine the hypothesis that prolonged sitting is associated with procoagulant changes in the local lower-limb venous system. A comparison was made with upper-limb venous changes. Changes in markers of thrombin generation, fibrinolysis, endothelial perturbation and haemoconcentration were analysed as 10 healthy adult male participants sat for 8 h. The change in foot volume was estimated. Subjective venous thromboembolism assessment was undertaken hourly, along with 2-week and 4-week safety follow-up for clinical events.Expected increases in median prothrombin fragments 1 and 2, thrombin-antithrombin complex and D-dimer were not observed in either limb. An increase greater than 45% in the median tissue plasminogen activator and plasminogen activator-1 molar ratio (t-PA/PAI-1), and a decrease greater than 15% in median soluble thrombomodulin were noted in both limbs. Median haematocrit decreased minimally (1%) in the lower limbs, while the foot volume increased by 4%. Subjects experienced vague symptoms after 6 h of sitting, but none developed symptomatic venous thromboembolism. Upper and lower-limb changes in biomarkers did not correlate, except those in t-PA/PAI-1 ratio and plasminogen activator-1. Significant correlation was found between changes in the lower-limb t-PA/PAI-1 ratio and right foot volume.This study originally reveals that even in the lower limbs, prolonged daytime cramped sitting is not associated with significant procoagulant changes in healthy adult male volunteers, and confirms a previous observation that local lower-limb venous changes are not identically reflected in the upper limbs. 相似文献
6.
J. Mikaeli M. Yaghoobi G. Montazeri R. Ansari F. Bishehsari R. Malekzadeh 《Diseases of the esophagus》2004,17(3):213-217
Graded pneumatic dilatation (PD) is an appropriate long-term therapy and botulinum toxin injection (BT) is a relatively short-term therapy in idiopathic achalasia. Their combination has not been previously scrutinized. This study aimed to evaluate the role of BT in enhancing the efficacy of PD with 30 mm balloons. Patients who underwent PD with 30 mm balloons after botulinum toxin injections and a group of age- and sex-matched controls who were treated only with PD were enrolled in the study. Symptom scores were taken before, 1 month after and then every 3 months after PD. There were no significant differences between the two groups in gender, duration or severity of symptoms. One of the 12 patients in the case group relapsed 30 months after PD but the others were in remission for an average of 25.6 months. In the control group, all the patients relapsed after a mean of 12.6 months and needed a 35-mm PD. The cumulative remission rate was significantly higher in the case group compared with the control group (P < 0.01). The mean symptom score decreased by 76% in the case group (P < 0.001) and 53% in the controls (P < 0.01) at the end of the first month. Neither age, sex, nor duration or severity of symptoms were predictive of patients' responses to treatment. It seems that BT may be a meaningful enhancing factor in long-term efficacy of PD. PD with a 30 mm balloon after a BT session may resolve the need for the future higher grade PD. 相似文献
7.
Dr. med. Dipl.-Soz. T. Krones E. Schlüter S. El Ansari T. Wissner R. Zoll G. Richter 《Gyn?kologische Endokrinologie》2004,2(4):245-250
Preimplantation genetic diagnosis (PGD) has been vigorously debated in Germany ever since the Bundesärztekammer (BÄK) published a draft of guidelines for PGD in March 2000. Many stakeholders such as churches, medical societies, and diverse associations have participated in the discussion. However, little is known about the attitudes of experts, directly affected patient groups, and the public in Germany. In several studies that are part of the German research program on ethical implications of the Human Genome Project, representative surveys were undertaken to assess the attitudes of the general population (n=1017), five relevant expert groups (n=879), and couples at high risk for genetic disorders(n=324) towards PGD and prenatal diagnosis (PD). All groups favor legislation for PGD. Differences exist in regard to the extent of their approval. For 17% of the high-risk couples with a persisting desire for a child, PGD performed in a neighboring country is the most probable reproductive option. These results should be carefully considered in the ongoing legislation process on human reproduction in our country. 相似文献
8.
T R Driscoll G Ansari J E Harrison M S Frommer E A Ruck 《Occupational and environmental medicine》1994,51(9):612-616
OBJECTIVES--To describe the types and circumstances of traumatic work related fatalities in Australian commercial fishermen. METHODS--Work related traumatic fishing fatalities were studied as part of a larger study of all work related traumatic fatalities in Australia from 1982 to 1984. Data on 47 cases were obtained from inspection of coroners' files. RESULTS--The incidence of fatality of 143/100,000 person-years was 18 times higher than the incidence of fatality for the entire workforce, and considerably higher than that of the mining and agricultural workforces. 68% of decedents drowned and 13% died from physical trauma. Rough weather, non-seaworthy vessels, inadequate use of personal flotation devices, and inexperience were associated with many of the fatal incidents. DISCUSSION--Improved vessel and equipment maintenance, better training of workers, greater use of personal flotation devices, and development of improved clothing and personal flotation devices are recommended. 相似文献
9.
Inhibition kinetics of human kidney aldose and aldehyde reductases by aldose reductase inhibitors 总被引:1,自引:0,他引:1
Kinetic patterns of inhibition of homogenous human kidney aldose reductase (AR, EC 1.1.1.21) and aldehyde reductase II (AR II, EC 1.1.1.19) by statil, ICI 105552 [1-(3,4-dichlorobenzyl)-3-methyl-1,2-dihydro-2-oxoquinol-4-yl acetic acid], tolrestat, alrestatin, chromone carboxylic acid (CCA), quercetin, phenobarbital and sorbinil were studied. On the basis of the kinetic nature of inhibition, the inhibitors were classified into four distinct categories. For aldose reductase, sorbinil and phenobarbital were noncompetitive (NC; category I) and CCA and alrestatin were uncompetitive (UC; category II) to both the aldehyde substrate and NADPH. Quercetin and ICI 105552 were NC to the aldehyde and UC to NADPH (category III) and tolrestat and statil were UC to the aldehyde and NC to NADPH (category IV). For AR II, sorbinil and alrestatin were category I inhibitors, ICI 105552 and statil belong to category II, phenobarbital, tolrestat and CCA to category III, and quercetin to category IV. To determine the specificity of inhibition, the ratios of the inhibition constants (Kii) for AR and AR II were calculated. A lower ratio indicates greater specificity. With aldehyde as the varied substrate the specificity ratios were: statil less than ICI 105552 less than alrestatin less than tolrestat less than quercetin less than CCA less than sorbinil less than phenobarbital, and with NADPH as the varied substrate, ICI 105552 less than statil less than alrestatin less than tolrestat less than quercetin less than CCA less than sorbinil less than phenobarbital. For AR, double-inhibition plots generated for one inhibitor from each kinetic category versus sorbinil showed that AR inhibitors of categories I-III bind to the same site on the protein molecule as sorbinil. However, tolrestat seemed to bind to a site different from the sorbinil binding site. For AR II, inhibitors from all the four categories appeared to bind to the same inhibitor binding site. 相似文献
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