Effect of neuromuscular electrical stimulation and isotonic exercises in flexor and extensor muscles of knee of hemiplegic patients

Aim. To verify the muscular force and resistance to the movement of the flexor and extensor muscles of the knee of patients with spasticity after treatment with neuromuscular electrical stimulation (NMES) and isotonic exercises. Patients and methods. The patients this study were divided into group I (NMES) and group 2 (isotonic exercises). Their muscular torque and resistance to the movement of the flexor and extensor knee muscles were measured by the isokinetic dynamometer and the degree of spasticity by the modified Ashworth scale before and after ten sessions. Results. Alterations in the scores of the modified Ashworth scale were not observed. An increase in the flexor torque in group 1 (p = 0.041) and in group 2 (p = 0.001) was verified. In the passive mode, group 1 presented a reduction of resistance to the flexion movement (p = 0.026), while in group 2, a reduction of resistance to both the flexion (p = 0,029) and extension movements (p = 0.019) was verified. Conclusions. The two therapeutical resources had their efficiency proven only for the increase of the force of the flexor muscles. The resistance to movement, the isotonic exercises were more effective because they promoted a reduction in the resistance of the flexor and extensor knee muscles.

Inexpensive footwear decreases joint loading in elderly women with knee osteoarthritis

Recent literature has highlighted that the flexibility of walking barefoot reduces overload in individuals with knee osteoarthritis (OA). As such, the aim of this study was to evaluate the effects of inexpensive, flexible, non-heeled footwear (Moleca (R)) as compared with a modern heeled shoes and walking barefoot on the knee adduction moment (KAM) during gait in elderly women with and without knee OA. The gait of 45 elderly women between 60 and 70 years of age was evaluated. Twenty-one had knee OR graded 2 or 3 according to Kellgren and Lawrence`s criteria, and 24 who had no OA comprised the control group (CG). The gait conditions were: barefoot, Moleca (R), and modern heeled shoes. Three-dimensional kinematics and ground reaction forces were measured to calculate KAM by inverse dynamics. For both groups, the Moleca (R) provided peak KAM and KAM impulse similar to barefoot walking. For the OA group, the Moleca (R) reduced KAM even more as compared to the barefoot condition during midstance. On the other hand, the modern heeled shoes increased this variable in both groups. Inexpensive, flexible, and non-heeled footwear provided loading on the knee joint similar to a barefoot gait and significant overload decreases in elderly women with and without knee OA, compared to modern heeled shoes. During midstance, the Moleca (R) also allowed greater reduction in the knee joint loads as compared to barefoot gait in elderly women with knee OA, with the further advantage of providing external foot protection during gait. (C) 2011 Elsevier B.V. All rights reserved.

Differing effects of exogenous and endogenous hydrogen sulphide in carrageenan-induced knee joint synovitis in the rat

Background and purpose: Recent findings suggest that the noxious gas H(2)S is produced endogenously, and that physiological concentrations of H(2)S are able to modulate pain and inflammation in rodents. This study was undertaken to evaluate the ability of endogenous and exogenous H(2)S to modulate carrageenan-induced synovitis in the rat knee. Experimental approach: Synovitis was induced in Wistar rats by intra-articular injection of carrageenan into the knee joint. Sixty minutes prior to carrageenan injection, the rats were pretreated with indomethacin, an inhibitor of H(2)S formation (dl-propargylglycine) or an H(2)S donor [Lawesson`s reagent (LR)]. Key results: Injection of carrageenan evoked knee inflammation, pain as characterized by impaired gait, secondary tactile allodynia of the ipsilateral hindpaw, joint swelling, histological changes, inflammatory cell infiltration, increased synovial myeloperoxidase, protein nitrotyrosine residues, inducible NOS (iNOS) activity and NO production. Pretreatment with LR or indomethacin significantly attenuated the pain responses, and all the inflammatory and biochemical changes, except for the increased iNOS activity, NO production and 3-NT. Propargylglycine pretreatment potentiated synovial iNOS activity (and NO production), and enhanced macrophage infiltration, but had no effect on other inflammatory parameters. Conclusions and implications: Whereas exogenous H(2)S delivered to the knee joint can produce a significant anti-inflammatory and anti-nociceptive effect, locally produced H(2)S exerts little immunomodulatory effect. These data further support the development and use of H(2)S donors as potential alternatives (or complementary therapies) to the available anti-inflammatory compounds used for treatment of joint inflammation or relief of its symptoms.

Histological and functional renal alterations caused by Bothrops alternatus snake venom: Expression and activity of Na(+)/K(+)-ATPase

Background: Acute renal failure is a serious complication of human envenoming by Bothrops snakes. The ion pump Na(+)/K(+)-ATPase has an important role in renal tubule function, where it modulates sodium reabsorption and homeostasis of the extracellular compartment. Here, we investigated the morphological and functional renal alterations and changes in Na(+)/K(+)-ATPase expression and activity in rats injected with Bothrops alternatus snake venom. Methods: Male Wistar rats were injected with venom (0.8 mg/kg, iv.) and renal function was assessed 6.24, 48 and 72 h and 7 days post-venom. The rats were then killed and renal Na(+)/K(+)-ATPase activity was assayed based on phosphate release from ATP; gene and protein expressions were assessed by real time PCR and immunofluorescence microscopy, respectively. Results: Venom caused lobulation of the capillary tufts, dilation of Bowman`s capsular space. F-actin disruption in Bowman`s capsule and renal tubule brush border, and deposition of collagen around glomeruli and proximal tubules that persisted seven days after envenoming. Enhanced sodium and potassium excretion, reduced proximal sodium reabsorption, and proteinuria were observed 6 h post-venom, followed by a transient decrease in the glomerular filtration rate. Gene and protein expressions of the Na(+)/K(+)-ATPase alpha(1) subunit were increased 6 h post-venom, whereas Na(+)/K(+)-ATPase activity increased 6 h and 24 h post-venom. Conclusions: Bothrops alternatus venom caused marked morphological and functional renal alterations with enhanced Na(+)/K(+)-ATPase expression and activity in the early phase of renal damage. General significance: Enhanced Na(+)/K(+)-ATPase activity in the early hours after envenoming may attenuate the renal dysfunction associated with venom-induced damage. (C) 2011 Elsevier B.V. All rights reserved.

Chronic supplementation of beta-hydroxy-beta methylbutyrate (HM beta) increases the activity of the GH/IGF-I axis and induces hyperinsulinemia in rats

Objective: Beta-hydroxy-beta-methylbutyrate (HM beta) is a metabolite of leucine widely used for improving sports performance. Although limp is recognized to promote anabolic or anti-catabolic effects on protein metabolism, the impact of its long-term use on skeletal muscle and/or genes that control the skeletal protein balance is not fully known. This study aimed to investigate whether chronic HM beta treatment affects the activity of GH/IGF-I axis and skeletal muscle IGF-I and myostatin mRNA expression. Design: Rats were treated with HK beta (320 mg/kg BW) or vehicle, by gavage, for 4 weeks, and killed by decapitation. Blood was collected for evaluation of serum insulin, glucose and IGF-I concentrations. Samples of pituitary, liver, extensor digitorum longus (EDL) and soleus muscles were collected for total RNA or protein extraction to evaluate the expression of pituitary growth hormone (GH) gene (mRNA and protein), hepatic insulin-like growth factor I (IGF-I) mRNA, skeletal muscle IGF-I and myostatin mRNA by Northern blotting/real time-PCR, or Western blotting. Results: Chronic HM beta treatment increased the content of pituitary GH mRNA and GH, hepatic IGF-I mRNA and serum IGF-I concentration. No changes were detected on skeletal muscle IGF-I and myostatin mRNA expression. However, the HIM-treated rats although normoglycemic, exhibited hyperinsulinemia. Conclusions: The data presented herein extend the body of evidence on the potential role of HM beta-treatment in stimulating GH/IGF-I axis activity. In spite of this effect, HM beta supplementation also induces an apparent insulin resistance state which might limit the beneficial aspects of the former results, at least in rats under normal nutritional status and health conditions. (C) 2010 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved.

Palmitate increases superoxide production through mitochondrial electron transport chain and NADPH oxidase activity in skeletal muscle cells

The effect of unbound palmitic acid (PA) at plasma physiological concentration range on reactive oxygen species (ROS) production by cultured rat skeletal muscle cells was investigated. The participation of the main sites of ROS production was also examined. Production of ROS was evaluated by cytochrome c reduction and dihydroethidium oxidation assays. PA increased ROS production after 1 h incubation. A xanthine oxidase inhibitor did not change PA-induced ROS production. However, the treatment with a mitochondrial uncoupler and mitochondrial complex III inhibitor decreased superoxide production induced by PA. The importance of mitochondria was also evaluated in 1 h incubated rat soleus and extensor digitorum longus (EDL) muscles. Soleus muscle, which has a greater number of mitochondria than EDL, showed a higher superoxide production induced by PA. These results indicate that mitochondrial electron transport chain is an important contributor for superoxide formation induced by PA in skeletal muscle. Results obtained with etomoxir and bromopalmitate treatment indicate that PA has to be oxidized to raise ROS production. A partial inhibition of superoxide formation induced by PA was observed by treatment with diphenylene iodonium, an inhibitor of NADPH oxidase. The participation of this enzyme complex was confirmed through an increase of p47(phox) phosphorylation after treatment with PA.

beta-ADRENERGIC ACTIVITY PRESERVES GLUT4 PROTEIN IN GLYCOLYTIC FIBERS IN FASTING

Glucose transporter 4 (GLUT4) expression in adipose tissue decreases during fasting. In skeletal muscle, we hypothesized that GLUT4 expression might be maintained in a beta-adrenergic-dependent way to ensure energy disposal for contractile function. Herein we investigate beta-blockade or beta-stimulation effects on GLUT4 expression in oxidative (soleus) and glycolytic [extensor digitorum longus (EDL)] muscles of fasted rats. Fasting increased GLUT4 mRNA in soleus (24%) and EDL (40%) but the protein content increased only in soleus (30%). beta 1-beta 2-, and beta 1-beta 2-beta 3-blockade decreased (20-30%) GLUT4 mRNA content in both muscles, although GLUT4 protein decreased only in EDL. When mRNA and GLUT4 protein regulations were discrepant, changes in the mRNA poly(A) tail length were detected, indicating a posttranscriptional modulation of gene expression. These results show that beta-adrenergic activity regulates GLUT4 gene expression in skeletal muscle during fasting, highlighting its participation in preservation of GLUT4 protein in glycolytic muscle. Muscle Nerve 40: 847-854, 2009

Acute exhaustive exercise regulates IL-2, IL-4 and MyoD in skeletal muscle but not adipose tissue in rats

Background: The purpose of this study was to evaluate the effect of exhaustive exercise on proteins associated with muscle damage and regeneration, including IL-2, IL-4 and MyoD, in extensor digitorum longus (EDL) and soleus muscles and mesenteric (MEAT) and retroperitoneal adipose tissues (RPAT). Methods: Rats were killed by decapitation immediately (E0 group, n = 6), 2 (E2 group, n = 6) or 6 (E6 group, n = 6) hours after the exhaustion protocol, which consisted of running on a treadmill at approximately 70% of VO(2max) for fifty minutes and then at an elevated rate that increased at one m/min every minute, until exhaustion. Results: The control group (C group, n = 6) was not subjected to exercise. IL-2 protein expression increased at E0 in the soleus and EDL; at E2, this cytokine returned to control levels in both tissues. In the soleus, IL-2 protein expression was lower than that in the control at E6. IL-4 protein levels increased in EDL at E6, but the opposite result was observed in the soleus. MyoD expression increased at E6 in EDL. Conclusion: Exhaustive exercise was unable to modify IL-2 and IL-4 levels in MEAT and RPAT. The results show that exhaustive exercise has different effects depending on which muscle is analysed.

Relative contribution of pre- and post-synaptic effects to the neostigmine-induced recovery of neuromuscular transmission blocked by vecuronium

The relative contribution of the pre- and post-synaptic effects to the neostigmine-induced recovery of neuromuscular transmission blocked by vecuronium was studied. A conjunction of myographical and electrophysiological techniques was employed. The preparation was the sciatic nerve-extensor digitorum longus muscle of the rat, in vitro. The physiological variables recorded were nerve-evoked twitches (generated at 0.1 Hz), tetanic contractions (generated at 50 Hz) and end-plate potentials (epps), generated in trains of 50 Hz. The epps were analyzed in: amplitude of first epp in the train; mean amplitude of the 30th to the 59th epp in the train (epps-plateau); half-decay time of the epp; early tetanic rundown of epps in the train; plateau tetanic rundown of epps in the train; quantal content of the epps and quantal size. In myographical experiments, a concentration of vecuronium was found (0.8 mu m) that affected both twitches and tetanic contractions and a concentration of neostigmine was found (0.048 mu m) that completely restored the twitch affected by vecuronium. The cellular effects of vecuronium and neostigmine, studied alone or in association, in the above-mentioned concentrations, were scrutinized by means of electrophysiological techniques. These showed that vecuronium alone decreased the peak amplitude, the quantal content of epps and the quantal size and reinforced the tetanic rundown of epps. Neostigmine alone increased the peak amplitude, the quantal content and the half-decay time of the epps. When employed in the presence of vecuronium, neostigmine increased both the quantal content of the epps (via a presynaptic effect) and the half-decay time of the epps (via a postsynaptic effect). Seeing the pre- and the post-synaptic effects of neostigmine were of similar magnitude, they permit to conclude that both these effects contributed significantly to the restoration by neostigmine of the neuromuscular transmission blocked by vecuronium.

Differential effects of neuromuscular blockers on twitches and tetani in the isolated rat muscle: a multiple comparison study using simultaneous confidence intervals

In the present work a comparative quantitative evaluation of the differential effects of neuromuscular blockers on twitches and tetani was performed, encompassing: atracurium, cisatracurium, mivacurium, pancuronium, rocuronium and vecuronium. The sciatic nerve-extensor digitorum longus muscle of the rat was used, in vitro. Twitches were evoked at 0.1 Hz and tetani at 50 Hz. The differential effects of the studied compounds on twitches and tetani were statistically compared using simultaneous confidence intervals for the ratios between mean IC(50) for the block of twitches and mean IC(50) for the block of tetani. The results of ratios of mean IC(50) together with their corresponding 95% simultaneous confidence intervals were: vecuronium: 2.5 (1.8-3.5); mivacurium: 3.8 (3.0-4.9); pancuronium: 3.9 (2.0-7.6); rocuronium: 6.1 (3.8-9.9); atracurium: 9.0 (6.4-12.6); cisatracurium: 13.1 (6.0-28.4). Using the criteria that neuromuscular blockers displaying disjunct confidence intervals for the ratios of mean IC(50) differ statistically with regard to differential effects on twitches and tetani, significant differences in ratios of IC(50) were detected in the following cases: vecuronium vs. rocuronium, vs. atracurium and vs. cisatracurium and mivacurium vs: cisatracurium and vs. atracurium. The results show that the magnitude of the differential effects of neuromuscular blockers on twitches and tetani, as evaluated in the present work in the form of ratios of mean IC(50), does not depend on the chemical structure (comparing steroidal and isoquinolinic compounds), but seems to depend on differential pre- and post-synaptic effects of the compounds. It is also suggested that the greater the ability of a compound to block twitches and tetani in a differential manner, the safer is the compound from the clinical anesthesiology viewpoint.

Chronic exercise decreases cytokine production in healthy rat skeletal muscle

Skeletal muscle is the source of pro- and anti-inflammatory cytokines, and recently, it has been recognized as an important source of interleukin-6 (IL-6). Acute physical exercise is known to induce a pro-inflammatory cytokine profile in the plasma. However, the effect of chronic physical exercise in the production of pro- and anti-inflammatory cytokines by the skeletal muscle has never been examined. We assessed IL-6, TNF-alpha, IL-1 beta and IL-10 levels in the skeletal muscle of rats submitted to endurance training. Animals were randomly assigned to either a Sedentary group (S, n = 7) or an endurance exercise trained group (T, n = 8). Trained rats ran on a treadmill for 5 days week(-1) for 8 weeks (60% VO(2max)). Detection of IL-6, TNF-alpha, IL-1 beta and IL-10 protein expression was carried out by ELISA. We found decreased expression of IL-1 beta, IL-6, TNF-alpha and IL-10 (28%, 27%. 32% and 37%, respectively, p < 0.05) in the extensor digital longus (EDL) from T, when compared with S. In the soleus, IL-1 beta, TNF-alpha and IL-10 protein levels were similarly decreased (34%, 42% and 50%, respectively, p < 0.05) in T in relation to S, while IL-6 expression was not affected by the training protocol. In conclusion, exercise training induced decreased cytokine protein expression in the skeletal muscle. These data show that in healthy rats, 8-week moderate-intensity aerobic training down regulates skeletal muscle production of cytokines involved in the onset, maintenance and regulation of inflammation, and that the response is heterogeneous according to fibre composition. Copyright (C) 2009 John Wiley & Sons, Ltd.

Objective characterization of the course of the parasellar internal carotid artery using mathematical tools

Background Along the internal carotid artery (ICA), atherosclerotic plaques are often located in its cavernous sinus (parasellar) segments (pICA). Studies indicate that the incidence of pre-atherosclerotic lesions is linked with the complexity of the pICA; however, the pICA shape was never objectively characterized. Our study aims at providing objective mathematical characterizations of the pICA shape. Methods and results Three-dimensional (3D) computer models, reconstructed from contrast enhanced computed tomography (CT) data of 30 randomly selected patients (60 pICAs) were analyzed with modern visualization software and new mathematical algorithms. As objective measures for the pICA shape complexity, we provide calculations of curvature energy, torsion energy, and total complexity of 3D skeletons of the pICA lumen. We further measured the posterior knee of the so-called ""carotid siphon"" with a virtual goniometer and performed correlations between the objective mathematical calculations and the subjective angle measurements. Conclusions Firstly, our study provides mathematical characterizations of the pICA shape, which can serve as objective reference data for analyzing connections between pICA shape complexity and vascular diseases. Secondly, we provide an objective method for creating Such data. Thirdly, we evaluate the usefulness of subjective goniometric measurements of the angle of the posterior knee of the carotid siphon.

Active galactic nuclei: sources for ultra high energy cosmic rays

Ultra high energy cosmic ray events presently show a spectrum, which we interpret here as galactic cosmic rays due to a starburst, in the radio galaxy Cen A which is pushed up in energy by the shock of a relativistic jet. The knee feature and the particles with energy immediately higher in galactic cosmic rays then turn into the bulk of ultra high energy cosmic rays. This entails that all ultra high energy cosmic rays are heavy nuclei. This picture is viable if the majority of the observed ultra high energy events come from the radio galaxy Cen A, and are scattered by intergalactic magnetic fields across much of the sky.

Exercise-associated thermographic changes in young and elderly subjects

This study aimed at evaluating the thermographic changes associated with localized exercise in young and elderly subjects. An exercise protocol using 1 kg load was applied during 3 min to the knee flexors of 14 elderly (67 +/- 5 years) and 15 young (23 +/- 2 years) healthy subjects. The posterior thigh`s skin temperature of the exercised limb and contralateral limb were measured by infrared thermography on pre-exercise, immediately post-exercise, and during the 10-min period post-exercise. Difference (p < 0.01) between elderly and young subjects was observed on pre-exercise temperature. Although differences were not observed between pre-exercise and immediately post-exercise temperature in the exercised limb, thermographic profile displayed heat concentration in exercised areas for both groups. Temperature reduction was only observed for the young group on the 10-min post-exercise (p < 0.05) in the exercised limb (30.7 +/- 1.7 to 30.3 +/- 1.5 degrees C). In contrast, there was a temperature reduction post-exercise (p < 0.01) in the contralateral limb for both groups. These results present new evidences that elderly and young subjects display similar capacity of heat production; however, the elderly subjects presented a lower resting temperature and slower heat dissipation. This work contributes to improve the understanding about temperature changes in elderly subjects and may present implications to the sports and rehabilitation programs.