ImGo: A Novel Tool for Behavioral Impulsivity Assessment Based on Go/NoGo Tasks.

This manuscript aims to present a novel behavioral impulsivity test ImGo, which is suitable for impulsivity assessment in the general population. A series of three studies was conducted to validate its psychometric qualities. In Study 1 we describe the principles of ImGo and verify its test-retest and split-half reliability and its convergent validity with an impulsivity self-report scale and Stop Signal test. In Study 2 we re-analyze the convergent validity of ImGo with a Stop Signal test and examine the potential relationship between ImGo and oculomotor inhibition measured by an Anti-Saccades test. In Study 3 we present a robust research with a large sample size and investigate the discriminant validity of ImGo with tests of other related cognitive and executive processes. Backed by our findings from these studies we can safely claim ImGo is a powerful tool with a good level of reliability (both test-retest and split-half) and validity (convergent and discriminant). Its potential lies in its use in diagnostic and research practice of experts from various countries as the test has already been translated to 9 languages so far. The open-source Hypothesis platform, on which the ImGo test is running, provides the option of both individual and group testing in laboratory conditions as well as remotely through an internet browser.

Pharmacogenomic association between a variant in SLC47A1 gene and therapeutic response to metformin in type 2 diabetes.

Pharmacogenetic studies revealed that variants in genes related to the pharmacokinetics of metformin were associated with glucose-lowering effect of metformin. The aim of this study was to investigate possible associations of the variants in genes encoding organic cationic transporters-solute carrier family 22, members A1, A2 (SLC22A1, SLC22A2) and solute carrier family 47, member A1 (SLC47A1) with response to metformin in type 2 diabetes. One hundred forty-eight drug-naive patients with type 2 diabetes were included in the study. Genotyping for SLC22A1 rs622342, SLC22A2 rs316019 and SLC47A1 rs2289669 variants was performed using real-time PCR with subsequent melting-curve analysis. SLC47A1 rs2289669 genotype was significantly associated with the reduction in haemoglobin A1c (HbA1c) after 6 months. Twenty percentage of patients with diabetes that are homozygous for A-allele of SLC47A1 had twofold reduction in HbA1c in comparison with the patients carrying G-allele (GG + GA: 0.55 ± 0.09% vs. AA: 1.10 ± 0.18%, p = 0.018). In conclusion, the results of this study might have in future practical implication in personalised treatment of patients with type 2 diabetes.

Variation in CDKAL1 gene is associated with therapeutic response to sulphonylureas.

The aim of the present pilot pharmacogenetic study was to analyse quantitative effects of sulphonylurea treatment in addition to metformin on parameters of glycemic control with respect to CDKAL1 genotypes in patients with type 2 diabetes. Effect of 6-month sulphonylurea therapy on glycemic control according to CDKAL1 genotypes was evaluated in 101 patients with type 2 diabetes who failed to achieve glycemic control on metformin monotherapy. CDKAL1 rs7756992 polymorphism was determined by melting curve analysis of small amplicon following real-time PCR. After sulphonylurea treatment fasting plasma glucose (FPG) levels were significantly different (p=0.045) among three CDKAL1 genotype groups (AA: n=49; AG: n=36; GG: n=16). In a dominant genetic model, carriers of the G-allele (AG+GG, n=52) achieved significantly lower FPG levels in comparison with patients with the AA genotype (6.90±1.08 vs. 7.48±1.12 mmol/l, p=0.013). Consequently, adjusted ΔFPG was significantly higher in the AG+GG compared to the AA group (1.48±1.51 vs. 1.02±1.33 mmol/l, p=0.022). Similar trend was observed for HbA(1c) levels, but the difference between the genotype groups did not reach the level of statistical significance. Relatively small number of included patients is a limitation of the present study. In conclusion, our results suggest that the magnitude of FPG reduction after 6-month sulphonylurea treatment in patients with type 2 diabetes is related to the variation in CDKAL1.

Effect of propentofylline on [3H]-leucine incorporation into protein of postischemic rat brain.

The effect of propentofylline on regional [3H]-leucine incorporation into brain proteins was investigated during early reperfusion following permanent occlusion of vertebral arteries and reversible occlusion of the common carotid arteries of awake rats. In rats subjected to 5 min ischemia/50 min reperfusion the total brain radioactivity and TCA-precipitable radioactivity were reduced in the cerebellum, medulla oblongata, hypothalamus, cortex, striatum and hippocampus and the fractional protein radioactivity was decreased in the cortex, striatum and hippocampus. Propentofylline pretreatment at a dose of 25 mg/kg p.o. daily for 14 days completely reversed the reduction in total radioactivity and partially reversed the reduction in TCA-precipitable radioactivity in all brain regions studied and decreased the reduction in fractional protein radioactivity in the hippocampus. The results suggest that the protective effect of propentofylline on transient ischemia-induced brain damage may be related to improvement of [3H]-leucine incorporation into brain proteins.

Effect of a combination of pentoxifylline and nimodipine on lipid peroxidation in postischemic rat brain.

The authors studied the effects of a combination of pentoxifylline and nimodipine on cerebral lipid peroxidation in postischemic rat brain. Pentoxifylline (40 mg/kg) and nimodipine (3 mg/kg) were administered per os 30 min before 5 min of ischemia (four-vessel occlusion model of transient ischemia). The extent of peroxidation in brain tissue (cerebral cortex, hippocampus, striatum) was then estimated by assay of thiobarbituric acid reactive substances (TBARS). The concentration of TBARS was significantly lower in the cerebral cortex and hippocampus of the group treated with the combination of drugs than in untreated ischemic rats. However, this concentration was not significantly different from that found in the cerebral cortex and hippocampus of other groups premedicated with nimodipine or pentoxifylline alone. The tested drugs had no effect on TBARS in the striatum. The hypothesis that the combination of drugs would have a synergistic effect on postischemic lipid peroxidation was therefore not confirmed.