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71.
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Ze-Jun Wang Boris Tabakoff Simon R Levinson Thomas Heinbockel 《Acta pharmacologica Sinica》2015,36(7):791-799
Aim:
Methyl eugenol is a major active component extracted from the Chinese herb Asari Radix et Rhizoma, which has been used to treat toothache and other pain. Previous in vivo studies have shown that methyl eugenol has anesthetic and antinociceptive effects. The aim of this study was to determine the possible mechanism underlying its effect on nervous system disorders.Methods:
The direct interaction of methyl eugenol with Na+ channels was explored and characterized using electrophysiological recordings from Nav1.7-transfected CHO cells.Results:
In whole-cell patch clamp mode, methyl eugenol tonically inhibited peripheral nerve Nav1.7 currents in a concentration- and voltage-dependent manner, with an IC50 of 295 μmol/L at a −100 mV holding potential. Functionally, methyl eugenol preferentially bound to Nav1.7 channels in the inactivated and/or open state, with weaker binding to channels in the resting state. Thus, in the presence of methyl eugenol, Nav1.7 channels exhibited reduced availability for activation in a steady-state inactivation protocol, strong use-dependent inhibition, enhanced binding kinetics, and slow recovery from inactivation compared to untreated channels. An estimation of the affinity of methyl eugenol for the resting and inactivated states of the channel also demonstrated that methyl eugenol preferentially binds to inactivated channels, with a 6.4 times greater affinity compared to channels in the resting state. The failure of inactivated channels to completely recover to control levels at higher concentrations of methyl eugenol implies that the drug may drive more drug-bound, fast-inactivated channels into drug-bound, slow-inactivated channels.Conclusion:
Methyl eugenol is a potential candidate as an effective local anesthetic and analgesic. The antinociceptive and anesthetic effects of methyl eugenol result from the inhibitory action of methyl eugenol on peripheral Na+ channels. 相似文献74.
75.
High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis 总被引:1,自引:0,他引:1
Shevchenko YL Novik AA Kuznetsov AN Afanasiev BV Lisukov IA Kozlov VA Rykavicin OA Ionova TI Melnichenko VY Fedorenko DA Kulagin AD Shamanski SV Ivanov RA Gorodokin G 《Experimental hematology》2008,36(8):922-928
High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (auto-HSCT) is a new and promising approach to the treatment of multiple sclerosis (MS) patients because currently there are no effective treatment methods for this disease. In this article, we present results of a prospective clinical study of efficacy of HDIT + auto-HSCT in MS patients. The following treatment strategies were employed in the study: "early," "conventional," and "salvage/late" transplantation. Fifty patients with various types of MS were included in this study. No toxic deaths were reported among 50 MS patients; transplantation procedure was well-tolerated by the patients. The efficacy analysis was performed in 45 patients. Twenty-eight patients achieved an objective improvement of neurological symptoms, defined as at least 0.5-point decrease in the Expanded Disability Status Scale (EDSS) score as compared to the baseline and confirmed during 6 months, and 17 patients had disease stabilization (steady EDSS level as compared to the baseline and confirmed during 6 months). The progression-free survival at 6 years after HDIT + auto-HSCT was 72%. Magnetic resonance imaging data were available in 37 patients before transplantation showing disease activity in 43.3%. No active, new, or enlarging lesions were registered in patients without disease progression. In conclusion, HDIT + auto-HSCT suggests positive results in management of patients with different types of MS. Identification of treatment strategies based on the level of disability, namely "early," "conventional," and "salvage/late" transplantation, appears to be feasible to improve treatment outcomes. 相似文献
76.
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Michael M Havranek Matthias Vonmoos Christian P Müller Jessica R Büetiger Eve Tasiudi Lea M Hulka Katrin H Preller Rainald M?ssner Edna Grünblatt Erich Seifritz Boris B Quednow 《Neuropsychopharmacology》2015,40(13):2929-2937
Cocaine users consistently develop working memory (WM) impairments but the mediating molecular mechanisms are unknown so far. Recent evidence suggests that the serotonin (5-HT) system is altered by chronic cocaine use, while also being involved in WM processing. Thus, we investigated the effects of genetic variations impacting 5-HT activity and of peripheral 5-HT transporter (5-HTT) mRNA expression on WM performance in cocaine users and stimulant naive controls. Two hundred twenty participants (126 cocaine users, 94 controls) were assessed with visuospatial, spatial, and verbal WM tasks, genotyped for the length polymorphism in the promoter region of the 5-HTT (5-HTTLPR), the variable number of tandem repeats in the second intron of the 5-HTT (VNTR In2), two single-nucleotide polymorphisms (rs4570625 and rs1386497) in the tryptophan hydroxylase-2 (TPH2) gene and quantified for peripheral 5-HTT mRNA expression in whole-blood samples. Several significant gene × environment interactions between 5-HT genotypes and cocaine use on WM emerged: in cocaine users, the long/long (5-HTTLPR), 9+10/9+10 (VNTR In2) and C/C (TPH2 rs1386497) genotypes were risk alleles for WM impairments, whereas in healthy controls these polymorphisms were associated with improved WM performance. Analogously, high 5-HTT mRNA levels were associated with worse executive WM performance in cocaine users but with increased performance in controls. These gene × environment interactions suggest that the 5-HT system has an important role in the development of cognitive deficits in chronic cocaine users. Hence, pharmacological compounds targeting 5-HT neurotransmission might be promising for the treatment of cognitive deficits in cocaine dependence. 相似文献
78.
79.
Boris Gramatikov Kristina Irsch Marie Müllenbroich Nicole Frindt Yinhong Qu Ron Gutmark Yi-Kai Wu David Guyton 《Annals of biomedical engineering》2013,41(9):1968-1978
A device for continuous monitoring of central fixation utilizes birefringence, the property of the Henle fibers surrounding the human fovea, to change the polarization state of light. A circular scan of retinal birefringence, where the scanning circle encompasses the fovea, allows identification of true central fixation—an assessment much needed in various applications in ophthalmology, psychology, and psychiatry. The device allows continuous monitoring for central fixation over an extended period of time in the presence of fixation targets and distracting stimuli, which may be helpful in detecting attention deficit hyperactivity disorder, autism spectrum disorders, and other disorders characterized by changes in the subject’s ability to maintain fixation. A proof-of-concept has been obtained in a small study of ADHD patients and normal control subjects. 相似文献
80.
Céline Ramdani Laurence Carbonnell Arnaud Rabat Cédric Meckler Boris Burle Thierry Hasbroucq Franck Vidal 《Biological psychology》2013
We studied the impact of sleep deprivation on action monitoring. Each participant performed a Simon task after a normal night of sleep and after 26 h of awakening. Reaction time (RT) distributions were analyzed and the sensitivity of the error negativity (Ne/Ne like) to response correctness was examined. 相似文献