Mónika Horváth

One session of whole body vibration increases voluntary muscle strength transiently in patients with stroke

Objective: To determine the effect of whole body vibration on isometric and eccentric torque and electromyography (EMG) variables of knee extensors on the affected side of stroke patients. Design: A randomized controlled study. Setting: A rehabilitation centre. Subjects: Sixteen patients (age 58.2 ± 9.4 years) were enrolled in an inpatient rehabilitation programme 27.2 ± 10.4 days after a stroke. Interventions: Eight patients were randomly assigned to the vibration group and received 20 Hz vibration (5 mm amplitude) while standing on a vibration platform for 1 minute six times in one session. Patients in the control group also stood on the platform but did not receive vibration. Main measures: Maximum isometric and eccentric torque, rate of torque development, root-mean-squared EMG, median frequency of vastus lateralis, and co-activation of knee flexors. Results: Isometric and eccentric knee extension torque increased 36.6% and 22.2%, respectively, after vibration (P < 0.05) and 8.4% and 5.3% in the control group. Vibration increased EMG amplitude 44.9% and the median frequency in the vastus lateralis by 13.1% (all P < 0.05) without changes in the control group (10.6% and 3.9%). Vibration improved the ability to generate mechanical work during eccentric contraction (17.5%). Vibration reduced biceps femoris co-activation during isometric (8.4%, ns) and eccentric (22.5%, P < 0.05) contraction. Conclusion: These results suggest that one bout of whole body vibration can transiently increase voluntary force and muscle activation of the quadriceps muscle affected by a stroke.

Effect of silibinin and vitamin E on restoration of cellular immune response after partial hepatectomy

Our aim was to study the antioxidant and immunomodulatory effect of silibinin and vitamin E on the early postoperative course in rats that had undergone a partial hepatectomy (PHX). Male Wistar rats that were treated with silibinin (50 mg/b.w.kg i.p.) and/or vitamin E (500 mg/b.w.kg p.o.) were randomised to undergo 70% PHX. At 72 h after operation, Concanavalin A (Con-A) induced lymphocyte proliferation, and lipopolysaccharide (LPS) induced interleukin-1 (IL-1) mitogenicity and tumour necrosis factor-alpha (TNF-alpha) cytotoxicity were measured in the spleen. In addition, total free radical scavenger capacity of the liver was analysed. In PHX animals, Con-A induced lymphocyte proliferation was significantly decreased, and both LPS induced IL-1 and TNF-alpha activity were significantly increased as compared to Sham treated animals. Treatment with silibinin and vitamin E synergistically restored both lymphocyte proliferation (P<0.01) and cytokine activity (P<0.001) in PHX animals. In addition, silibinin and vitamin E synergistically (P<0.001) restored total hepatic free radical scavenger capacity as well as serum levels of AST and gammaGT, that were all markedly decreased in PHX animals. Our results suggest that preoperative treatment with silibinin and/or vitamin E modulates the cellular immunoresponse and restores impaired liver function following PHX, presumably through their antioxidant capacity. This may explain their beneficial effects on the postoperative course of liver repair.

Dopamine receptor D1 and postsynaptic density gene variants associate with opiate abuse and striatal expression levels

Opioid drugs are highly addictive and their abuse has a strong genetic load. Dopamine–glutamate interactions are hypothesized to be important for regulating neural systems central for addiction vulnerability. Balanced dopamine–glutamate interaction is mediated through several functional associations, including a physical link between discs, large homolog 4 (Drosophila) (DLG4, PSD-95) and dopamine receptor 1 (DRD1) within the postsynaptic density to regulate DRD1 trafficking. To address whether genetic associations with heroin abuse exist in relation to dopamine and glutamate and their potential interactions, we evaluated single-nucleotide polymorphisms of key genes within these systems in three populations of opiate abusers and controls, totaling 489 individuals from Europe and the United States. Despite significant differences in racial makeup of the separate samples, polymorphisms of DRD1 and DLG4 were found to be associated with opiate abuse. In addition, a strong gene–gene interaction between homer 1 homolog (Drosophila) (HOMER1) and DRD1 was predicted to occur in Caucasian subjects. This interaction was further analyzed by evaluating DRD1 genotype in relation to HOMER1b/c protein expression in postmortem tissue from a subset of Caucasian subjects. DRD1 rs265973 genotype correlated with HOMER1b/c levels in the striatum, but not cortex or amygdala; the correlation was inversed in opiate abusers as compared with controls. Cumulatively, these results support the hypothesis that there may be significant, genetically influenced interactions between glutamatergic and dopaminergic pathways in opiate abusers.

Low resonance frequency vibration affects strength of paretic and non-paretic leg differently in patients with stroke

The objective of the study was to investigate the chronic effect of low frequency whole body vibration (WBV) on isometric and eccentric strength of knee extensors with different force exertion capacity. It was hypothesized that (1) four-week WBV intervention with the low frequency domain would enhance muscle strength and (2) the improvement would be more pronounced in the weaker muscle. To test our hypothesis twenty patients with acute stroke were recruited. Ten patients were randomly assigned to vibration and the remaining ten patients served for control.The patients in the vibration group received WBV with 20 Hz frequency three times per week standing on a vibration platform in half squat position meanwhile flexing and extending the joints and placing the weight from one leg to the other. Knee extensor strength was determined under isometric and eccentric contraction before and after WBV intervention. Myoelectrical activity (EMG) of the vastus lateralis muscle was also measured.Significant improvement was revealed in the vibration group only. The maximum isometric torque and EMG activity increased significantly for both paretic and non-paretic leg, but the improvement was threefold greater in the vibration group. No significant alteration was found in rate of torque development. Maximum eccentric torque and EMG increased significantly for the paretic leg only. Mechanical work enhanced significantly in the paretic side only.The results of our study indicate that the selection of the effective vibration frequency depends upon the physical condition of neuromuscular system. Low vibration frequency intervention can increase the strength in weak muscles due to neuromuscular impairment and restricted physical activity.

Adaptation to altered balance conditions in unilateral amputees due to atherosclerosis: a randomized controlled study

BackgroundAmputation impairs the ability to balance. We examined adaptation strategies in balance following dysvascularity-induced unilateral tibial amputation in skilled prosthetic users (SPU) and first fitted amputees (FFA) (N = 28).MethodsExcursions of center of pressure (COP) were determined during 20 s quiet standing using a stabilometry system with eyes-open on both legs or on the non-affected leg(s). Main measures: COP trajectories and time functions; distribution of reaction forces between the two legs; inclination angles obtained through second order regression analysis using stabilogram data.ResultsFFA vs SPU demonstrated 27.8% greater postural sway in bilateral stance (p = 0.0004). Postural sway area was smaller in FFA standing on the non-affected leg compared with SPU (p = 0.028). The slope of the regression line indicating postural stability was nearly identical in FFA and SPU and the direction of regression line was opposite for the left and right leg amputees.ConclusionOf the two adaptation strategies in balance, the first appears before amputation due to pain and fatigue in the affected leg. This strategy appears in the form of reduced postural sway while standing on the non-affected leg. The second adaptation occurs during rehabilitation and regular use of the prosthesis resulting in normal weightbearing associated with reduced postural sway on two legs and return to the normal postural stability on one leg.

ELK1 Transcription Factor Linked to Dysregulated Striatal Mu Opioid Receptor Signaling Network and OPRM1 Polymorphism in Human Heroin Abusers

BACKGROUND Abuse of heroin and prescription opiate medications has grown to disturbing levels. Opioids mediate their effects through mu opioid receptors (MOR), but minimal information exists regarding MOR-related striatal signaling relevant to the human condition. The striatum is a structure central to reward and habitual behavior and neurobiological changes in this region are thought to underlie the pathophysiology of addiction disorders. METHODS We examined molecular mechanisms related to MOR in postmortem human brain striatal specimens from a homogenous European Caucasian population of heroin abusers and control subjects and in an animal model of heroin self-administration. Expression of ets-like kinase 1 (ELK1) was examined in relation to polymorphism of the MOR gene OPRM1 and drug history. RESULTS A characteristic feature of heroin abusers was decreased expression of MOR and extracellular regulated kinase signaling networks, concomitant with dysregulation of the downstream transcription factor ELK1. Striatal ELK1 in heroin abusers associated with the polymorphism rs2075572 in OPRM1 in a genotype dose-dependent manner and correlated with documented history of heroin use, an effect reproduced in an animal model that emphasizes a direct relationship between repeated heroin exposure and ELK1 dysregulation. A central role of ELK1 was evidenced by an unbiased whole transcriptome microarray that revealed ~20% of downregulated genes in human heroin abusers are ELK1 targets. Using chromatin immune precipitation, we confirmed decreased ELK1 promoter occupancy of the target gene Use1. CONCLUSIONS ELK1 is a potential key transcriptional regulatory factor in striatal disturbances associated with heroin abuse and relevant to genetic mutation of OPRM1.

Vitamin E protects against iron-hexachlorobenzene induced porphyria and formation of 8-hydroxydeoxyguanosine in the liver of C57BL/10ScSn mice.

The effect of vitamin E treatment on total porphyrin content, lipid peroxidation (LOOH) and 8-hydroxydeoxyguanosine (8-OHdG) was studied in the livers of C57BL/10ScSn mice following hexachlorobenzene (HCB) and iron treatment. HCB was administered i.p. (totalling 300 mg/kg) twice, with 1 week interval. Three days after the first HCB injection iron-dextran was given i.p. (500 mg Fe per kg). Vitamin E was administered weekly (20 mg/kg) by s.c. injection. Both total hepatic porphyrin and LOOH levels were significantly (P<0.001) increased in the HCB-iron treated group as compared with the control group. Mice treated additionally with vitamin E had significant (P<0.001) lower levels as compared with the HCB-iron group. Similarly, the levels of 8-OHdG were significantly (P<0.001) increased above controls after HCB-iron treatment and this increase was reduced after co-treatment with vitamin E (P<0.02). The data support the hypothesis that the mechanism of hepatic porphyrinogenicity of HCB with iron overload is an oxidative free radical process.

Comparison of proton channel, phagocyte oxidase, and respiratory burst levels between human eosinophil and neutrophil granulocytes

Abstract Robust production of reactive oxygen species (ROS) by phagocyte NADPH oxidase (phox) during the respiratory burst (RB) is a characteristic feature of eosinophil and neutrophil granulocytes. In these cells the voltage-gated proton channel (Hv1) is now considered as an ancillary subunit of the phox needed for intense ROS production. Multiple sources reported that the expression of phox subunits and RB is more intensive in eosinophils than in neutrophils. In most of these studies the eosinophils were not isolated from healthy individuals, and a comparative analysis of Hv1 expression had never been carried out. We performed a systematic comparison of the levels of essential phox subunits, Hv1 expression and ROS producing capacity between eosinophils and neutrophils of healthy individuals. The expression of phox components was similar, whereas the amount of Hv1 was ∼10-fold greater in eosinophils. Furthermore, Hv1 expression correlated with Nox2 expression only in eosinophils. Additionally, in confocal microscopy experiments co-accumulation of Hv1 and Nox2 at the cell periphery was observed in resting eosinophils but not in neutrophils. While phorbol-12-myristate-13-acetate-induced peak extracellular ROS release was ∼1.7-fold greater in eosinophils, oxygen consumption studies indicated that the maximal intensity of the RB is only ∼1.4-fold greater in eosinophils. Our data reinforce that eosinophils, unlike neutrophils, generate ROS predominantly extracellularly. In contrast to previous works we have found that the two granulocyte types display very similar phox subunit expression and RB capacity. The large difference in Hv1 expression suggests that its support to intense ROS production is more important at the cell surface.

The superoxide scavenging activity of dihydroquinoline type derivatives (CH402 and MTDQ-DA)

Electron paramagnetic resonance/spin trapping studies were applied, to verify the superoxide radical scavenging activity of two non-toxic, water soluble dihydroquinoline type antioxidants, CH402 (Na-2,2-dimethyl-1,2-dihydroquinoline-4-yl methane sulphonate and MTDQ-DA (6,6-methylene bis 2,2-dimethyl-4-methane sulphonic acid: Na-1,2-dihydroquinoline). Results were compared with other indirect methods such as the amperometric, spectrophotometric and luminometric methods, respectively. Both dihydroquinoline type antioxidants scavenged superoxide in vitro specifically. MTDQ-DA scavenged superoxide an order of magnitude faster than CH-402. Neither CH402 nor MTDQ-DA affected the hypoxanthine/xanthine oxidase superoxide generating system, nor did they inhibit xanthine oxidase directly.

An Approach to Consider Upper Limb Kinematics for the Improvement of Motion Control in a Two Arm Robotic Rehabilitation System

REHAROB is a robotic system for upper limb physiotherapy including two co-operating robotic arms. The original version of the system included two independent standalone outer-loop force controllers of the two robotic arms. During the manual walk-through programming of the robotic system it was entirely the task of the physiotherapist to consider the human anatomic movements of the upper limb, and ensure the synchronized movement of the two robotic arms. Among other tasks the operator had to contribute actively to overcoming the instabilities caused by the interference of the two separated controls. The authors have modified and upgraded the motion controller of REHAROB to administer the kinematical constraints of the human arm, to which the two robots are connected. This paper presents the new co-operative control method of REHAROB. The method requires no additional sensors or extensive calibration process. The new control concept was implemented and clinically tested. The approach is general and can be extended to any multiple arm lower or upper limb robotic exercising device.