Search

Objective: To investigate the effects of single-session premotor and primary motor tDCS in chronic stroke patients with relation to possible inter-hemispheric interactions., Methods: Anodal tDCS of either M1 or premotor cortex of the side contralateral to the paretic hand, cathodal tDCS of the premotor cortex of the side ipsilateral to the paretic hand and sham stimulation were performed in 12 chronic stroke patients with mild hand paresis in a balanced cross-over design. The Jebsen-Taylor Hand Function test, evaluating the time required for performance of everyday motor tasks, was employed., Results: The repeated-measure ANOVA with Greenhouse-Geisser correction showed significant influence of the stimulation type (factor SESSION; F(2.6, 28.4) = 47.3, p < 0.001), the test performance time relative to stimulation (during or after tDCS; factor TIME, F(1.0, 11.0) = 234.5, p < 0.001) with higher effect after the stimulation and the interaction SESSION*TIME (F(1.7, 1.2) = 30.5, p < 0.001). All active conditions were effective for the modulation of JTT performance, though the highest effect was observed after anodal tDCS of M1, followed by effects after anodal stimulation of the premotor cortex contralateral to the paretic hand. Based on the correlation patterns, the inhibitory input to M1 from premotor cortex of another hemisphere and an excitatory input from the ipsilesional premotor cortex were suggested., Conclusion: The premotor cortex is a promising candidate area for transcranial non-invasive stimulation of chronic stroke patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In this study we compared the effects of transcranial direct current stimulation (tDCS) in the subacute and chronic stages of post-stroke recovery. Anodal/sham tDCS was applied to the primary motor cortex of stroke patients in these stages of recovery in a cross-over design. The Jebsen-Taylor hand function test was employed. The repeated-measure ANOVA showed significant influence of the stimulation type and test performance time (during/after tDCS) with no overall influence of recovery stage. The interaction TYPE*TIME*STAGE was significant. The effect after anodal tDCS in the subacute stage was significantly higher compared to the effects in all relevant conditions including the chronic stage. Therefore, tDCS treatment in the subacute stage of recovery can be superior, at least for some patients, to treatment in the chronic stage.

Background: Transcranial direct current stimulation (tDCS) can be an effective treatment for depression, however, the duration of the stimulation session, among other parameters, needs to be optimized., Methods: 69 mild to moderately depressed patients (age 37.6±10.5years, 19 men) were randomized into three groups - 30-, 20-minute or sham tDCS. 10 daily sessions of anodal/sham tDCS of the left DLPFC (0.5mA; electrode 3,5×7cm) combined with 50mg/day of sertraline were performed. Mood, cognition and BDNF level were assessed before and after the treatment., Results: A significant difference between groups was observed in the percent change of the Hamilton Depression Rating Scale (F(2, 66)=10.1; p<0.001). Sham group (43.4%±18.1) had a smaller improvement compared to the 30-minute (63.8%±13.4; 95% CI: 11.23-29.44; p=0.00003) and 20-minute group (53.2%±15.3; 95% CI: 0.21-19.26; p=0.045). 30-minute group had significantly greater percent improvement than 20-minute group (95% CI: 1.74-19.46; p=0.02). Responders constituted 89%, 68%, and 50% and remitters - 70%, 27%, and 35% in the 30-, 20-minute and sham groups, respectively. A significant difference in the number of responders was observed between 30-minute vs. sham group (odds ratio=8; 95% CI, 2.59-24.69; p=0.001), in remission rate - between 30-minute vs. sham (odds ratio=4.40; 95% CI, 2.02-9.57; p=0.02) and vs. 20-minute (odds ratio=6.33; 95% CI, 2.85-14.10; p=0.003) groups. Two hypomania cases and one case of blood pressure elevation were detected in the 20-minute group. Among neuropsychological tests, only the change in Digit Span Backwards test showed a significant interaction between groups (TIME*GROUP; F(2, 65)=6,6, p=0.002); a greater improvement was observed in both active groups compared to sham (p<0.05). The change in BDNF level after the treatment did not show the significant difference between groups., Conclusions: tDCS of 20- or 30-minutes combined with sertraline are efficient for the treatment of mild and moderate depression; the effect of 30min stimulation exceeds the one obtained from 20min., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A series of 4-(1H-benzo[d]imidazol-2-yl)-furazan-3-amines (BIFAs) were prepared in good yields (60-90% for each reaction step) via a novel procedure from aminofurazanyl hydroximoyl chlorides and o-diaminobenzenes. The synthetic sequence was run under mild reaction conditions, it was robust and did not require extensive purification of intermediates or final products. Furthermore, there was no need for protection of reactive moieties allowing for the parallel synthesis of diverse BIFA derivatives. Subsequent biological evaluation of the resulting compounds revealed their anti-proliferative effects in the sea urchin embryo model and in cultured human cancer cell lines. The most active compounds showed 0.2-2 μM activities in both assay systems. The unsubstituted benzene ring of the benzoimidazole template as well as the unsubstituted amino group in the furazan ring were essential prerequisites for the antimitotic activity of BIFAs. Compound 57 bearing the 2-chlorophenyl acetamide substituent at the nitrogen atom of the imidazole ring was the most active molecule in the examined set., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

A series of polyalkoxy substituted 7-hydroxy- and 7-methoxy-4-aryl-4H-chromenes were evaluated using the sea urchin embryo model to yield several compounds exhibiting potent antimitotic microtubule destabilizing activity. Data obtained by the assay were further confirmed in the NCI60 human cancer cell screen. The replacement of methylenedioxy ring A and lactone ring D in podophyllotoxin analogues by 7-methoxy, 2-NH2, and 3-CN groups in 4-aryl-4H-chromenes resulted in potent antimitotic microtubule destabilizing agents. Feasible synthesis and high yields render 7-methoxy-4H-chromenes to be a promising series for further anticancer drug development., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A regioselective synthesis of both 5-amino- and 3-aminodiarylisoxazoles substituted with polyalkoxyaryl pharmacophores has been validated. Starting materials for the synthetic scheme were easily available from plant extracts. The targeted molecules were further tested in the phenotypic sea urchin embryo assay to identify compounds with antimitotic microtubule destabilizing activity. Structure-activity relationship studies suggested that the structural features essential for potent antiproliferative activity include: 1) 5-aminoisoxazole bridge linking biaryl substituents (rings A and B); 2) unsubstituted 5-amino group; 3) 3,4,5-methoxy substituted benzene and 4-methoxy benzene pharmacophores as rings A and B, respectively. The most potent compounds also showed strong in vitro cytotoxicity in NCI60 anticancer drug screen against a panel of 60 human cancer cell lines, including multi-drug resistant cells., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

A series of novel 4-oxa-podophyllotoxin derivatives 7 featuring the intact lactone ring D and various substituents in rings B and E has been synthesized and evaluated in a phenotypic sea urchin embryo assay along with the representative 4-aza-analogs 5 for their antimitotic and microtubule destabilizing activity. The most active compounds exhibited myristicin-derived or a 3',5'-dimethoxy substitution pattern in the ring E and a 6-methoxy moiety replacing the methylenedioxy ring A. Compounds 5xb, 5xe, 5yb, 7xa, 7xb, and 7xc showed potent antiproliferative effects in the NCI60 cytotoxicity screen. Notably, growth of the multi-drug resistant NCI/ADR-RES cells was more affected by these agents than the parent OVCAR-8 cell line. Although generally 4-oxa-podophyllotoxins were less potent than the respective 4-aza-derivatives in these assays, stability of the former series towards oxidation may prove to be of interest for the development of anticancer agents with in vivo activity., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A series of 4-azapodophyllotoxin derivatives with modified rings B and E have been synthesized using allylpolyalkoxybenzenes from parsley seed oil. The targeted molecules were evaluated in vivo in a phenotypic sea urchin embryo assay for antimitotic and tubulin destabilizing activity. The most active compounds identified by the in vivo sea urchin embryo assay featured myristicin-derived ring E. These molecules were determined to be more potent than podophyllotoxin. Cytotoxic effects of selected molecules were further confirmed and evaluated by conventional assays with A549 and Jurkat human leukemic T-cell lines including cell growth inhibition, cell cycle arrest, cellular microtubule disruption, and induction of apoptosis. The ring B modification yielded 6-OMe substituted molecule as the most active compound. Finally, in Jurkat cells, compound induced caspase-dependent apoptosis mediated by the apical caspases-2 and -9 and not caspase-8, implying the involvement of the intrinsic caspase-9-dependent apoptotic pathway.

The modern classifications of headaches include primary headaches, e.g., migraines and headaches of tension (HAT), and secondary psychogenic headaches of tension (PHT). Forty-one patients with chronic variants of HAT and PHT were studied. In the first step, 12 patients with HAT and 11 patients with PHT were compared by clinical and psychometric scores on the following scales (the VAS, the McGill Pain Questionnaire, the MMPI). In the second step, 11 patients with HAT and 7 with PHT were treated with venlafaxine XR (velaxin) in dose 75 mg/d during 2 months. It has been shown that PHT differs from HAT by pain intensity and relationship with functional-neurologic symptoms as well as by personality deviations measured with MMPI and correlations between the pain intensity and MMPI peaks. The 2 month treatment with velaxin has improved significantly the state of patients. The significant decrease of pain severity, amount of analgesics and pain-associated symptoms as well as the normalization of functions of antinociceptive systems (the increase in nociceptive flexor reflex threshold) were noted in both groups. It has been concluded that venlafaxine is an effective drug in the treatment of both HAT and PHT.