Background: To establish the contribution of eight founder alleles in three DNA damage repair genes ( BRCA1 , CHEK2 and NBS1 ) to prostate cancer in Poland, and to measure the impact of these variants on survival among patients. Methods: Three thousand seven hundred fifty men with prostate cancer and 3956 cancer-free controls were genotyped for three founder alleles in BRCA1 ( 5382insC , 4153delA, C61G ), four alleles in CHEK2 ( 1100delC , IVS2+1G>A, del5395, I157T ), and one allele in NBS1 (657del5) . Results: The NBS1 mutation was detected in 53 of 3750 unselected cases compared with 23 of 3956 (0.6%) controls (odds ratio (OR)=2.5; P =0.0003). A CHEK2 mutation was seen in 383 (10.2%) unselected cases and in 228 (5.8%) controls (OR=1.9; P <0.0001). Mutation of BRCA1 (three mutations combined) was not associated with the risk of prostate cancer (OR=0.9; P =0.8). In a subgroup analysis, the 4153delA mutation was associated with early-onset (age ⩽60 years) prostate cancer (OR=20.3, P =0.004). The mean follow-up was 54 months. Mortality was significantly worse for carriers of a NBS1 mutation than for non-carriers (HR=1.85; P =0.008). The 5-year survival for men with an NBS1 mutation was 49%, compared with 72% for mutation-negative cases. Conclusion: A mutation in NBS1 predisposes to aggressive prostate cancer. These data are relevant to the prospect of adapting personalised medicine to prostate cancer prevention and treatment.

II Department of Anaesthesiology and Intensive Care, F. Skubiszewski Medical University in Lublin, Poland, Lublin, Poland

II Department of Anaesthesiology and Intensive Care, F. Skubiszewski Medical University in Lublin, Poland, Lublin, Poland Background and Goal of Study: The aim of study was to assess antiallodynic and anti-hyperalgesic activity of vigabatrin (VGB), and its effect on the duration of mechanical allodynia and thermal hyperlgesia in Seltzer model of chronic neuropathic pain in the rat. Materials and Methods: Experiments were performed on male Wistar rats, initially weighing 250–300 g. The experimental groups consisted of 14 animals at the beginning of experiment. VGB were administered intraperitoneally once a day at doses of 50, 100, and 200 mg/kg, starting from the second day after the operation, one hour prior to behavioral tests. Mechanical allodynia and thermal-hyperalgesia, were assessed every second day after surgery, with the use of von Frey filaments and hot plate test, respectively. Results and Discussion: Nerve injury resulted in exhibited foot withdrawal responses to von Frey hair and decreased latency to noxious thermal stimuli 2–16 days after surgery. The anti-allodynic activity of VGB was significant at 200 mg/kg, however, no effect on the duration of mechanical allodynia was observed. VGB at doses of 100 and 200 mg/kg significantly elevated the nociceptive thresholds in hot plate test. In no case, there was a complete reversal of thermal hyperalgesia in the VGB-treated group. Conclusion: VGB proved to be more efficient in relieving thermal hyperalgesia than mechanical allodynia in the Seltzer model of chronic neuropathic pain.

Allopurinol, an inhibitor of xanthine oxidase, is indicated in the management of patients with elevated serum and urinary uric acid levels. It was also reported to be beneficial in patients with epilepsy when added to traditional antiepileptic drug. Here, we investigated the effect of allopurinol upon the electrical seizure threshold and its effect on the protective efficacy of common antiepileptic drugs, carbamazepine (CBZ) and valproate (VPA) against maximal electroshock (MES)-induced convulsions in mice. We found that allopurinol administered at doses of 5, 15 or 45 mg/kg, did not affect electrical seizure threshold. When administered acutely or for a prolonged period of time (5 times every 24 h), it did not affect anticonvulsant activity of CBZ and VPAin MES. Free plasma concentration of both anticonvulsants was not affected by allopurinol given at a dose of 45 mg/kg for 5 days. Thus, our results did not support suggestions that allopurinol can be beneficial as add-on drug in the management of epilepsy at least in patients treated with CBZ or VPA.

Summary: Purpose: The study investigated the types of interactions between lamotrigine (LTG) and first‐generation antiepileptic drugs (AEDs) or topiramate (TPM) with isobolographic analysis. Methods: Anticonvulsant and adverse‐effect profiles of combinations of LTG with other AEDs, at fixed ratios of 1:3, 1:1, and 3:1, were evaluated in the maximal electroshock (MES)‐induced seizures and the chimney test (motor performance) in mice, which allowed the determination of benefit indices (BIs) for individual combinations. Results: Combinations of LTG with TPM or valproate (VPA), at fixed ratios of 1:1, were significantly supraadditive (synergistic) in the MES test and, simultaneously, subadditive (antagonistic) in the chimney test, showing the best profile for AED combinations. In contrast, combinations between LTG and carbamazepine (CBZ), in terms of antiseizure protection against MES, were subadditive (antagonistic) and additive in the chimney test, resulting in unfavorable AED combinations. Moreover, the combination of LTG with phenobarbital (PB), at a fixed ratio of 1:1, despite synergy in the MES test, also was synergistic in the chimney test, resulting in a modest BI for AED combination. LTG combined with phenytoin was additive in both the MES and chimney tests in mice. The remaining combinations, at fixed ratios not mentioned earlier, also showed an average BI for AED combinations. Furthermore, LTG combined with all studied AEDs did not affect long‐term memory in mice. None of the AEDs influenced the free plasma level of LTG, whereas LTG slightly reduced the free plasma concentration of PB. Conclusions: Interactions between LTG and TPM or LTG and VPA at a fixed ratio of 1:1 might be profitable from a preclinical point of view, displaying the most optimal BI.

Nicotine administered acutely at subconvulsive dose of 4 mg/kg, significantly decreased the protective activity of valproate, carbamazepine, diphenylhydantoin, phenobarbital, topiramate and lamotrigine against maximal electroshock-induced tonic convulsions in mice. The obtained data may suggest that interaction between nicotine and antiepileptic drugs should be carefully considered as a cause of the therapeutic failure in epileptic patients.

Gabapentin and baclofen at doses not affecting motor performance, produced dose-dependent inhibition of both phases in the formalin test in mice. Isobolographic analysis revealed an additive interaction between the studied drugs in the second phase of the formalin test. Gabapentin given at doses effective in both phases of the formalin test significantly potentiated baclofen-induced motor impairment.

Kynurenic acid, an antagonist of glutamatergic ionotropic receptors and alpha7 nicotinic cholinergic receptors failed to affect nicotine-induced convulsions in mice which may indicate that alpha7 nicotinic receptor-mediated events play no role in seizure activity produced by nicotine.

Valproate and baclofen dose-dependently inhibited both phases of the formalin test. Combination of valproate and baclofen exerted the additive antinociceptive effect on both phases of the formalin test.

The problem of glueball mass spectra using the relativistic Dirac equation is studied. Also the Breit-Fermi approach is used to obtain hyperfine splitting in glueballs. Our approach is based on the assumption that the nature and the forces between two gluons are short-range. We were able to calculate the glueball masses in both models with screened potential.