Functional architectonics of neuronal antinociceptive mechanisms during the electroacupuncture method of reflex action

The peculiarities of neurone bioelectric activity of sensory thalamic nuclei under electroacupuncture (EAP) stimulation have been studied in acute experiments on cats. EAP stimulation has been established to change spontaneous and evoked activity of neurones of sensory thalamic nuclei, that testifies to the development of a new functional state. The functional state of the cortex, in particular the second somatosensory region has been shown to determine the nature of neurone activation of sensory thalamic nuclei during the EAP stimulation. Schemes of possible organization of functional pools realizing the mechanisms of inhibition of nociceptive signals on central neurones during EAP way of reflex stimulation are suggested.     

Muscle enhancement using closed-loop electrical stimulation: volitional versus induced torque.

In cases of partial deficiency of muscle activation capacity, force augmentation can be achieved by hybrid activation, i.e., by combining electrical stimulation (ES) with volitional activation. In this activation modality the shares of the volitional and induced torques within the overall hybrid torque are unknown. The purpose of this study was to suggest a computational approach to parcel out the volitional and stimulation induced components of joint torque generated during combined voluntary and electrical activation of the Tibialis Anterior muscle (TA). For this purpose, isometric contraction of the TA was studied on 5 healthy subjects, using an activation protocol involving ES alone, volitional activation alone and hybrid activation. Ankle torque and TA EMG were measured. A computational algorithm was developed to dissociate the volitional from the overall torque, based on EMG filtering and on pre-measured calibration curves of volitional torque versus EMG. The results indicated that for a certain hybrid torque there is a linear decaying relationship between the induced torque and the volitional torque shares. Moreover, based on a defined enhancement ratio, the results indicate that within the range of stimulation intensities, there exist regions of increased facilitation, in which the stimulation efficiency is higher under combined compared to isolated conditions.     

Changes in somatosensory evoked potentials in patients with vertebrogenic pain syndromes treated by electroacupuncture

Application of electroacupuncture (EAP) of the segmental points to patients with vertebrogenic algesic syndromes decreased amplitude of N150 and P240 waves recorded from vertex to painful electrocutaneous stimulation in the region innervated by an affected root. As distinct from EAP of segmental point auricular EAP not only decreased the amplitude of late components of evoked potentials (EP), but also increased it, direction of EP changes depending on the character of sensitivity disorders. It is suggested that effect of EAP-evoked EP changes in patients with hypalgesia is determined by two oppositively acting factors: by a decrease of nociceptive afferent impulsation intensity as a result of the antinociceptive system activation and by an increase of the afferent impulsation intensity due to recovery of function of central terminals in primary sensory neurons.     

Cross-regulation of VPAC2 receptor internalization by m2 receptors via c-Src-mediated phosphorylation of GRK2

The aim of the study was to examine the mechanisms by which ACh, acting via m2 receptors, regulates GRK2-mediated VPAC(2) receptor desensitization in gastric smooth muscle cells. VIP induced VPAC(2) receptor phosphorylation and internalization in freshly dispersed smooth muscle cells. Co-stimulation with acetylcholine (ACh), in the presence of m3 receptor antagonist, 4-DAMP, augmented VPAC(2) receptor phosphorylation and internalization. The m2 receptor antagonist methoctramine or the c-Src inhibitor PP2 blocked the effect of ACh, suggesting that the augmentation was mediated by c-Src, derived from m2 receptor activation. ACh induced activation of c-Src and phosphorylation of GRK2 and the effects of ACh were blocked by methoctramine, PP2, or by uncoupling of m2 receptors from G(i3) with pertussis toxin. In conclusion, we identified a novel mechanism of cross-regulation of GRK2-mediated phosphorylation and internalization of G(s)-coupled VPAC(2) receptors by G(i)-coupled m2 receptors via tyrosine phosphorylation of GRK2 and stimulation of GRK2 activity.     

Prospective analysis of the outcome of subpectoral breast augmentation: sensory changes, muscle function, and body image

This study is a prospective analysis of the outcome of subpectoral breast augmentation. Forty-seven patients undergoing breast augmentation were studied. They were assessed for pectoralis muscle function, breast sensation, and body image before and after subpectoral breast augmentation with saline implants. The patients were evaluated as follows: Pectoralis function was determined by measuring maximal voluntary isometric force. Sensation was evaluated by two means: vibration and pressure. The patient's body image was assessed using the Multidimensional Body-Self Relations Questionnaire. Results indicated a significant change in breast sensation at 3 months postoperatively but not at 6 months. Pectoralis muscle function did not significantly change during the study period. Body image was significantly improved at both postoperative measuring periods. The authors conclude that breast augmentation results in improved body image with negligible effect on muscle or nerve function.     

Participation of the primary motor cortex in programming of muscle activity during catching of falling object

Object fell into the cup that sitting subject held between thumb and index fingers. Transcranial magnetic stimulation (TMS) of the primary motor cortex was performed early before and during anticipatory grip force increasing. Comparison of current EMG activity of adductor pollicis brevis and first dorsal interosseous muscles and responses of these muscles on TMS showed that responses were increased before the raising of muscle activity. From the other side only slight augmentation of responses was observed during subsequent strong muscle activation. It is assumed that the increasing of the TMS responses that occurred before the initiation of muscle activity reflects the enhancement ofthe motor cortex excitability associated to specific processes related to the motor cortex participation in programming of the muscles activities.     

Effects of blood pressure on force production in cat and human muscle

In anesthetized cats reducing local arterial pressure from 125 to 75 Torr decreased blood flow (53 +/- 5%) and force production (57 +/- 7%) in soleus and medial gastrocnemius. Force was produced in these muscles by aerobic, slowly fatiguing fibers. Similar reductions in arterial pressure did not affect force production in caudofemoralis, which contains mainly fast-fatiguing fibers. In human subjects the electromyogram produced by the ankle extensors during rhythmic constant-force contractions increased as the contracting muscles were raised above the heart during legs-up tilt. This suggests that force production of active muscle fibers at a given level of activation fell with muscle perfusion pressure, thus requiring augmentation of muscle activity to sustain the standard contractions. Because aerobic fibers contributed to these contractions, it appears that force production of human muscle fibers is sensitive to small changes in perfusion pressure and, presumably, blood flow. The critical dependence of developed muscular force on blood pressure is of importance to motor control and may also play a significant role in cardiovascular control during exercise.     

Involvement of p42/44 MAPK and RhoA protein in augmentation of ACh-induced bronchial smooth muscle contraction by TNF-alpha in rats.

Bronchial asthma is characterized by chronic inflammation of airway tissues and nonspecific airway hyperresponsiveness (AHR), but the underlying mechanisms of AHR have yet to be elucidated. Recently, tumor necrosis factor-alpha (TNF-alpha) has been identified as a proinflammatory cytokine that might be important in the hyperresponsiveness of airway tissue. We have investigated the effects of SB-203580 (a p38 MAPK inhibitor), U-0126 (an inhibitor of p42/44 MAPK activation), and cycloheximide (an inhibitor of protein synthesis) on TNF-alpha-augmented ACh-induced bronchial smooth muscle contraction. We have also investigated the phosphorylation of p42/44 MAPK and upregulation of RhoA protein by TNF-alpha. Treatment of rat bronchial smooth muscles with TNF-alpha (300 and 1,000 ng/ml for 24 h) resulted in a significant upward shift in the concentration-response curve to ACh, but not to high K(+), compared with control tissues. The effect of TNF-alpha was completely blocked by pretreatment with U-0126 or cycloheximide, but not with SB-203580. Immunoblotting demonstrated that p42/44 MAPK was phosphorylated and RhoA protein was increased in bronchial tissue by TNF-alpha. Furthermore, the TNF-alpha-induced upregulation of RhoA protein was abolished by U-0126 pretreatment. In conclusion, we suggest that TNF-alpha might be one of the important mediators involved in the pathogenesis of augmented bronchial smooth muscle contractility in AHR. For the first time, we have demonstrated that augmentation of ACh-induced contractile response evoked by TNF-alpha was mediated by synthesis of protein, such as RhoA, through activation of p42/44, but not p38 MAPK, in rat bronchial smooth muscle.     

Effect of electroacupuncture on the nature of changes in the activity of neurons in the 2d somatosensory region of the cerebral cortex

Effects of electroacupuncture (EAP) on the character of spontaneous and evoked neuronal impulse activity changes in the second somatosensory area (S2) of the brain cortex by nociceptive and non-nociceptive stimulation were studied in acute experiments on cats. It was demonstrated that EAP changed the character of S2 neurons activity and formed their new functional state. After EAP activity of non-nociceptive neurons were not changed, evoked activity of nociceptive neurons were inhibited. It is suggested, that EAP preferential blocking the protopathic components of the acute pain.     

Tissue length modulates "stimulated actin polymerization," force augmentation, and the rate of swine carotid arterial contraction

"Stimulated actin polymerization" has been proposed to be involved in force augmentation, in which prior submaximal activation of vascular smooth muscle increases the force of a subsequent maximal contraction by ～15%. In this study, we altered stimulated actin polymerization by adjusting tissue length and then measured the effect on force augmentation. At optimal tissue length (1.0 L(o)), force augmentation was observed and was associated with increased prior stimulated actin polymerization, as evidenced by increased prior Y118 paxillin phosphorylation without changes in prior S3 cofilin or cross-bridge phosphorylation. Tissue length, per se, regulated Y118 paxillin, but not S3 cofilin, phosphorylation. At short tissue length (0.6 L(o)), force augmentation was observed and was associated with increased prior stimulated actin polymerization, as evidenced by reduced prior S3 cofilin phosphorylation without changes in Y118 paxillin or cross-bridge phosphorylation. At long tissue length (1.4 L(o)), force augmentation was not observed, and there were no prior changes in Y118 paxillin, S3 cofilin, or cross-bridge phosphorylation. There were no significant differences in the cross-bridge phosphorylation transients before and after the force augmentation protocol at all three lengths tested. Tissues contracted faster at longer tissue lengths; contractile rate correlated with prior Y118 paxillin phosphorylation. Total stress, per se, predicted Y118 paxillin phosphorylation. These data suggest that force augmentation is regulated by stimulated actin polymerization and that stimulated actin polymerization is regulated by total arterial stress. We suggest that K(+) depolarization first leads to cross-bridge phosphorylation and contraction, and the contraction-induced increase in mechanical strain increases Y118 paxillin phosphorylation, leading to stimulated actin polymerization, which further increases force, i.e., force augmentation and, possibly, latch.     

Electric acupuncture stimulates non-parietal cell secretion of the stomach in dog

Effects of acupuncture and electroacupuncture (EAP) on gastric secretion were studied in the interdigestive state of five conscious dogs prepared with esophagostomy and gastric cannulas. Both EAP and acupuncture without electrical stimulation produced significant increases in gastric secretion of bicarbonate and sodium. At the same time, a marked decrease in gastric secretion of acid was noted. EAP clearly demonstrated a greater effect on gastric secretion within these three parameters than did simple acupuncture. The fact that the effects of EAP and acupuncture on gastric secretion of bicarbonate and sodium were completely blocked by either a local anesthetic agent or anticholinergic agent indicates that gastric secretion involves a somatic afferent-visceral reflex mechanism in which a cholinergic nerve plays a role.     

Regulation of PDGF production and ERK activation by estrogen is associated with TSC2 gene expression

Mechanisms that regulate the growth response to estrogen (17beta-estradiol, E2) are poorly understood. Recently, loss of function of the tuberous sclerosis complex 2 (TSC2) gene has been associated with E2-related conditions that are characterized by benign cellular proliferation. We examined the growth response to E2 in vascular smooth muscle cells (VSMCs) that possess wild-type TSC2 and compared them with ELT-3 smooth muscle cells that do not express TSC2. In TSC2-expressing VSMCs, growth inhibition in response to E2 was associated with downregulation of platelet-derived growth factor (PDGF), PDGF receptor (PDGFR), and limited activation of extracellular signal-regulated kinase (ERK). In contrast, the growth-promoting effect of E2 in TSC2-null ELT-3 cells was associated with induction of PDGF, robust phosphorylation of PDGFR, and sustained activation of ERK. Furthermore, in ELT-3 cells, cellular growth and ERK activation by E2 were inhibited by the PDGFR inhibitor tyrphostin AG 17 and by PDGF-neutralizing antibody. These results demonstrate that autocrine production of PDGF and augmentation of the ERK pathway leads to estrogen-induced cellular proliferation in TSC2-null cells, a pathway that was downregulated in cells that express TSC2. Understanding the mechanisms that regulate the diverse responses to the steroid hormone estrogen could lead to novel approaches to the treatment of estrogen-related diseases that are characterized by aberrant cell proliferation.     

Membrane currents in canine bronchial artery and their regulation by excitatory agonists

The bronchial vasculature plays an important role in airway physiology and pathophysiology. We investigated the ion currents in canine bronchial smooth muscle cells using patch-clamp techniques. Sustained outward K(+) current evoked by step depolarizations was significantly inhibited by tetraethylamonium (1 and 10 mM) or by charybdotoxin (10(-6) M) but was not significantly affected by 4-aminopyridine (1 or 5 mM), suggesting that it was primarily a Ca(2+)-activated K(+) current. Consistent with this, the K(+) current was markedly increased by raising external Ca(2+) to 4 mM but was decreased by nifedipine (10(-6) M) or by removing external Ca(2+). When K(+) currents were blocked (by Cs(+) in the pipette), step depolarizations evoked transient inward currents with characteristics of L-type Ca(2+) current as follows: 1) activation that was voltage dependent (threshold and maximal at -50 and -10 mV, respectively); 2) inactivation that was time dependent and voltage dependent (voltage causing 50% maximal inactivation of -26 +/- 22 mV); and 3) blockade by nifedipine (10(-6) M). The thromboxane mimetic U-46619 (10(-6) M) caused a marked augmentation of outward K(+) current (as did 10 mM caffeine) lasting only 10-20 s; this was followed by significant suppression of the K(+) current lasting several minutes. Phenylephrine (10(-4) M) also suppressed the K(+) current to a similar degree but did not cause the initial transient augmentation. None of these three agonists elicited inward current of any kind. We conclude that bronchial arterial smooth muscle expresses Ca(2+)-dependent K(+) channels and voltage-dependent Ca(2+) channels and that its excitation does not involve activation of Cl(-) channels.     

Involvement of the 2'-5' A pathway in the augmentation of natural killer activity

Pretreatment of human large granular lymphocytes (LGL) or unseparated peripheral blood mononuclear cells with interferon (IFN) resulted in a significant augmentation of natural killer (NK) activity. This increase was paralleled by an increase in the 2'-5'A synthetase activity. In order to investigate the possibility that IFN might be inducing augmentation of NK cells via the 2'-5'A pathway, we tested the effects of nonphosphorylated core material [(A2'p)2A] and of the triphosphorylated form of the 2'-5'A [ppp(A2'p)2A]. The core material had no detectable effect on NK activity. In contrast, when experiments were performed with the triphosphorylated form of 2'-5'A, NK activity was stimulated. In order to achieve activation, permeabilization of LGL with calcium chloride was necessary and, under these conditions, a dose-dependent augmentation of NK activity was seen. However, the calcium treatment had considerable toxic effects on basal levels of NK activity. Collectively, these results suggest that IFN may be inducing augmentation of NK activity via the 2'-5'A pathway. Further studies will be necessary to determine the effects of IFN and/or 2'-5'A on subsequent activation steps in the process leading to cytotoxicity by NK cells.     

Postfatigue potentiation of the paralyzed soleus muscle: evidence for adaptation with long-term electrical stimulation training.

Understanding the torque output behavior of paralyzed muscle has important implications for the use of functional neuromuscular electrical stimulation systems. Postfatigue potentiation is an augmentation of peak muscle torque during repetitive activation after a fatigue protocol. The purposes of this study were 1) to quantify postfatigue potentiation in the acutely and chronically paralyzed soleus and 2) to determine the effect of long-term soleus electrical stimulation training on the potentiation characteristics of recently paralyzed soleus muscle. Five subjects with chronic paralysis (>2 yr) demonstrated significant postfatigue potentiation during a repetitive soleus activation protocol that induced low-frequency fatigue. Ten subjects with acute paralysis (<6 mo) demonstrated no torque potentiation in response to repetitive stimulation. Seven of these acute subjects completed 2 yr of home-based isometric soleus electrical stimulation training of one limb (compliance = 83%; 8,300 contractions/wk). With the early implementation of electrically stimulated training, potentiation characteristics of trained soleus muscles were preserved as in the acute postinjury state. In contrast, untrained limbs showed marked postfatigue potentiation at 2 yr after spinal cord injury (SCI). A single acute SCI subject who was followed longitudinally developed potentiation characteristics very similar to the untrained limbs of the training subjects. The results of the present investigation support that postfatigue potentiation is a characteristic of fast-fatigable muscle and can be prevented by timely neuromuscular electrical stimulation training. Potentiation is an important consideration in the design of functional electrical stimulation control systems for people with SCI.     

Chemical composition,digestibility and in situ degradability of dried and ensiled apple pomace and maize silage

The nutritive value of the dried and ensiled apple pomace (DAP and EAP), taken from two processing factories in Urmia city, was compared with maize silage (MS). For EAP, 1 tonnes of AP was mixed with 100 kg of wheat straw and 5 kg of urea (on fresh weight basis). The chemical composition of all feedstuffs was determined by laboratory analysis. Additionally, pH and the concentration of ammonia-N and volatile fatty acids (VFA) were measured in the EAP and MS silages. An in vivo digestibility study was undertaken with three Gezel wether sheep to determine the digestible organic matter content in the dry matter (DOMD) and to estimate the metabolisable energy (ME) content. The dry matter (DM) and protein effective degradabilities (ED) of the feedstuffs were assessed using a nylon bag method. The mean values of the DM, OM, CP, acid detergent fibre (ADF), neutral detergent fibre (NDF), lignin and acid detergent insoluble nitrogen (ADIN) were, respectively, 749 g/kg fresh weight, 929, 64, 405, 473, 10 and 5.6 g/kg DM for DAP, 284 g/kg fresh weight, 925, 72, 460, 567, 20 and 6.5 g/kg DM for EAP and 429 g/kg fresh weight, 936, 260, 463, 44 and 4.4 g/kg DM for MS. No butyric acid was found in EAP and MS, which indicate good preservation for these silages. However, ammonia-N was higher in MS than EAP. The DOMD values were 690, 654 and 580 g/kg DM for DAP, MS and EAP, respectively. The DOMD and ME values for DAP and MS were significantly higher than those of EAP. The dry matter ED of EAP was significantly lower than that of DAP and MS and there was a significant difference among all feedstuffs in the protein ED where MS was the highest and EAP the lowest. The nutritive value of AP was reduced by the addition of wheat straw. However, ensiling apple with straw is a practical method to preserve such high moisture by-product.     

Effect of long-term hypergravitation on the skeletal-muscular tissue in rats

The space flight or simulated gravitational unloading lead to the muscle atrophy, slow-to-fast transformation of muscle fibers and myofibrillar damages both in humans and animals (1, 7, 13, 17). This process could be prevented by the exercise training during space flight (1), (partly) by periodic weight support during unloading (13). It has been demonstrated in these studies that there is some level of force production necessary for the maintenance of skeletal muscle properties. It is known that adaptation to the physical training frequently induces augmentation in cross-sectional area (CSA) of muscle fibers (MF), transformation of fibers, augmentation of mitochondrial volume density, and increase in absolute volume of myofibrillas. Numerous observations suggest importance of gravitational loading in regulating muscle mass. The centrifuging is believed to be useful for preventing muscle functional and structural losses under microgravity. But there are few studies designed to investigate effect of artificial gravity on the skeletal musculature (2, 7). Our objective was to investigate structural adaptation in slow-twitch soleus muscle (percentage of connective tissue and central nuclei, fiber size, myosin heavy chain isotope, myofibrillar proteins and mitochondria volume density) after 19 and 33 days of hypergravity.     

Ca2+-independent synergistic augmentation of O2- production by FMLP and PMA in HL-60 cells

N-Formyl-Met-Leu-Phe (FMLP) and phorbol 12-myristate 13-acetate (PMA) caused a synergistic augmentation of superoxide anion (O2-) production in neutrophil-like HL-60 cells differentiated with dibutyryl cAMP. The present study was undertaken to investigate the mechanism of the synergistic augmentation of O2- production. FMLP increased intracellular free Ca2+ concentration ([Ca2+]i), which was slightly suppressed by PMA and completely inhibited by an intracellular Ca2+ chelating agent, O,O'-bis(2-aminophenyl)ethyleneglycol-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM). Although FMLP-induced O2- production was inhibited by BAPTA-AM, a major part of the synergistic augmentation of O2- production by FMLP and PMA remained after BAPTA-AM treatment, suggesting that a Ca2+-independent mechanism might be involved in the augmentation. FMLP and PMA caused an activation of phospholipase D (PLD) almost additively in a Ca2+-sensitive manner. The synergistic activation of mitogen-activated protein kinase (MAPK) was evoked by combined addition of PMA and FMLP in a BAPTA-AM resistant manner. However, PD98059, a MAPK kinase inhibitor, did not affect the synergistic augmentation of O2- production, although it potently inhibited the synergistic augmentation of tyrosine phosphorylation of MAPK. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, inhibited FMLP-induced O2- production, but it did not inhibit the synergistic augmentation of O2- production by PMA and FMLP. In contrast, staurosporine and GF109203X, protein kinase C inhibitors, reduced the synergistic augmentation induced by PMA and FMLP. In addition, pertussis toxin (PT) abolished the synergistic augmentation of O2- production. It is concluded that the synergistic augmentation of O2- production induced by PMA and FMLP is mediated through a PT-sensitive G protein and a protein kinase C in a Ca2+-independent manner.     

Fcgamma-receptor signaling augments the LPS-stimulated increase in serum tumor necrosis factor-alpha levels

The phagocytosis of IgG-coated erythrocytes (EIgG) has been shown to augment the bacterial lipopolysaccharide (LPS)-stimulated increase in serum tumor necrosis factor-alpha (TNF-alpha) levels. The present study evaluated the role of Fcgamma-receptor (FcgammaR) signaling and complement activation in the effect of EIgG on the TNF-alpha response to LPS. The role of FcgammaR was determined using FcR gamma-chain knockout mice that lack functional FcgammaRI and FcgammaRIII. In wild-type animals, EIgG caused a 16-fold augmentation of the serum TNF-alpha response to LPS, whereas there was no augmentation in the FcgammaR-deficient animals. Heat-damaged erythrocytes also augmented the TNF-alpha response to LPS. This effect was absent in FcgammaR-deficient animals. An IgG antibody against heated erythrocytes was detected in mouse serum. The complement activation caused by EIgG had little effect on the LPS-stimulated increase in serum TNF-alpha levels as indicated by activation of complement with cobra venom factor or IgM-coated erythrocytes as well as studies with C5-deficient mice. These results indicate that FcgammaR signaling primarily mediates the augmented serum TNF-alpha response to LPS caused by EIgG.     

Action potentials of the rabbit, guinea pig, dog and albino rat working ventricular myocardium under interpolated extrasystole conditions during postnatal ontogenesis

Experiments were carried out on the working myocardium of the right heart ventricle of newborn and adult rabbits, guinea-pigs, dogs and albino rats. In the dog, the guinea-pig and the rabbit, after ten action potentials (AP) elicited with 1 Hz frequency we always interpolated an extrasystole at an interval (TE) of 100-900 ms. In albino rats we used a basic frequency of 2 Hz and a TE of 30-370 ms from the last regular AP. Using glass microelectrodes, we recorded the extrasystolic AP (EAP) and the next subsequent AP (2AP). The results were evaluated by constructing graphs of the correlations of the duration of the plateau phase (D0) to TE and of the duration of repolarization to -60 mV level (D60) to the TE. In the myocardium of newborn rabbits, guinea-pigs and dogs, with short TE both D0 and D60 of the EAP are shorter than in the steady state (SS), while for the 2AP the same parameters are influenced only a little. As the TE lengthens, the EAP gradually acquire a length corresponding more to the SS. With TE longer than half the duration of the cycle in the steady state the EAP return to normal, while the 2AP become shorter. The effect of extrasystole on the rat EAP and 2AP diminished with advancing age. In the myocardium of adult rabbits and adult guinea-pigs, and slightly in the myocardium of adult dogs and newborn rats, we observed that the duration of the EAP, with certain TE, was greater than in the steady state.(ABSTRACT TRUNCATED AT 250 WORDS)