Search

Alzheimer’s Disease (AD) is a neurodegenerative condition characterized both by the presence of tau protein neurofibrillary tangles and amyloid beta (Aβ) containing extracellular “plaques”. The cleavage of amyloid precursor protein (APP) yields several Aβ peptides. Although Aβ toxicity to neurons has been described extensively, its effects on other components of the neurovasculature such as vascular smooth muscle cells have been less well characterized. AD is now also recognized as a neurovascular disease characterized by cerebral microbleeds and disturbances in autoregulation. AD is also a neuroinflammatory condition in which several proinflammatory cytokines are elevated and may contribute to the intensification of AD severity. Cerebral autoregulation (the mechanism by which brain blood flow is maintained despite changes in perfusion pressure) is extremely tightly controlled in the brain and shows disturbances in AD. The failure of autoregulation in AD may make the brain susceptible to cerebral microbleeds through a reduced capacity to limit blood flow when pressure is increased. Conversely, reduced vasodilation during low flow might could also exacerbate tissue hypoxia. Currently, whether and how Aβ peptides and inflammatory cytokines depress brain smooth muscle cell tonic contraction is not known, but could reveal important targets in the preservation of autoregulation which is disturbed in AD. We used a collagen gel contractility assay to evaluate the influence of Aβ25-35, Aβ1-40 and Aβ1-42 peptides and inflammatory cytokines on the tonic contractility of human brain vascular smooth muscle cells (HBVSMC) as an in vitro model of cerebral autoregulation. We found that 5 and 10 μM Aβ1-42 significantly depressed HBVSM contractility, while Aβ1-40 5–20 μM had no effect on contractility. Conversely, Aβ25-35 (1–50 μM) increased contractility. Interestingly, the inflammatory cytokines TNF-α (20 ng/mL), IL-1β (20 ng/mL) and IFN-γ (1000 U/mL) also depressed HBVSM tonic contractility alone and in combination. These data suggest that both the inflammatory milieu in AD as well as the abundance of Aβ peptides may promote autoregulatory failure and increase brain susceptibility to dysregulated perfusion and microbleeds which are an important and devastating characteristic of AD.

Background: Trismus is a restricted mouth opening due to the tonic contraction of muscles of mastication. It may occur mostly in HNF cancer patients undergoing radiation therapy treatment. This study was undertaken with the purpose of finding out the prevalence of trismus in patients undergoing radiation therapy. Method: 89 patients with HNF cancer patients receiving radiation therapy were included in the study. Inter incisal distance was measured using sliding digital vernier calliper. Patients with ≥ 35mm mouth opening were considered as trismus cases. Result: Out of 89 patients included 72 were diagnosed as trismus; hence the prevalence was 81%. Conclusion: Prevalence of Trismus is very high ( 81 %) in patients undergoing radiotherapy secondary to HNF cancer. Early diagnosis of trismus in these patients can help in time management and also planning of preventive strategies.

We have previously shown that supraspinal excitability is higher during arm cycling than a position- and intensity-matched tonic contraction. The present study sought to determine if short-interval intracortical inhibition (SICI) was present during arm cycling and if so, if the amount of SICI was different from an intensity-matched tonic contraction. SICI was assessed using conditioning stimuli (CS) of 70 and 90% of active motor threshold (AMT) and a test stimulus (TS) of 120% AMT at an interstimulus interval (ISI) of 2.5 ms. SICI was elicited in all participants; on average (i.e., cycling and tonic contraction grouped) test MEP amplitudes were reduced by 64.2% (p

The future of awake bruxism assessment will incorporate physiological data, possibly electromyography (EMG) of the temporal muscles. But up to now, temporal muscle contraction patterns in awake bruxism have not been characterized to demonstrate clinical utility. The present study aimed to perform surface EMG evaluations of people assessed for awake bruxism to identify possible different subtypes. A 2-year active search for people with awake bruxism in three regions of the country resulted in a total of 303 participants (223 women, 38 ± 13 years, mean and SD). Their inclusion was confirmed through non-instrumental approaches for awake bruxism: self-reported questionnaire and clinical exam, performed by three experienced and calibrated dentists (Kappa = 0.75). Also, 77 age- and sex-matched healthy controls were recruited (49 women, 36 ± 14 years). Temporalis surface EMG was performed with a portable device (Myobox; NeuroUp, Brazil). EMG signals were sent to a computer via Bluetooth 4.0 at a sampling rate of 1,000 Hz. Digital signal processing was performed using the commercial neuroUP software, transformed in RMS and then normalized for peak detection (EMG peaks/min), in a 10 min session. Cluster analysis revealed three distinct subtypes of awake bruxism: phasic, tonic, and intermediate. Individuals with a predominance of EMG peaks/min were classified as the “phasic” subtype (16.8%). Those with the highest EMG rest power were classified as the “tonic” subtype (32.3%). There was also an “intermediate” subtype (50.8%), when both variables remained low. Characterization of awake bruxism physiology is important for future establishment of instrumental assessment protocols and treatment strategies.

Crawling gastropods are unique models for studying the functioning of smooth muscles and ciliated epithelia, since they cover the foot sole and are involved in locomotion, allowing for direct investigation. Two types of crawling are known: creeping by muscular waves in terrestrial gastropods such as Helix and сiliary gliding in aquatic gastropods such as Lymnaea. It was found that the smooth muscles that underlie the ciliated epithelium in Lymnaea are involved in gliding and contribute significantly to fast crawling. Thus, the locomotor apparatus is fundamentally the same in both snails and the difference between crawling reflects an adaptation to a habitat. The control of crawling speed is also the same. Tonic contraction, relaxation, and rhythmic contractions are involved in this control. During a locomotor episode, the sole length and crawling speed spontaneously change and directly correlate with each other via the contraction force of the muscle cells in the locomotory waves. Dopamine, unlike ergometrine, decreases the sole length and crawling speed. Serotonin stimulates, increases crawling and determines the number of muscle cells involved in the locomotory waves for each locomotor episode. This control (taking into account heterogeneity) apparently might exist in any other phasic smooth muscle, including vertebrates.

The purpose of this study was to elucidate whether the long-term practice of isolated finger movements reduces the enslaved response of the little finger abductor to the index finger abduction. The right-handed participants tonically or phasically abducted the index finger, while they maintained at rest or tonic abduction of the little finger. The enslaved response of the tonically contracting little finger abductor to the tonic abduction of the index finger was greater than the response of the same muscle at rest in the nonpianists. This indicates that the tonic contraction of the little finger abductor enhances the enslaving drive from the tonically contracting index finger abductor to the little finger abductor. The enslaved response of the tonically contracting little finger abductor to the tonic abduction of the index finger in the pianists was significantly smaller than that in the nonpianists, but such a significant group difference was absent when the little finger abductor was at rest. This indicates that the inhibitory process on the enslaving drive from the tonically contracting index finger abductor to the tonically active little finger abductor is unmasked through the long-term practice.

In the current study, the potential contributions of ryanodine receptors (RyRs) to intrinsic pumping and responsiveness to substance P (SP) were investigated in isolated rat mesenteric collecting lymphatic vessels. Responses to SP were characterized in lymphatic vessels in the absence or presence of pretreatment with nifedipine to block L-type Ca2+ channels, caffeine to block normal release and uptake of Ca2+ from the sarcoplasmic reticulum, ryanodine to block all RyR isoforms, or dantrolene to more selectively block RyR1 and RyR3. RyR expression and localization in lymphatics was also assessed by quantitative PCR and immunofluorescence confocal microscopy. The results show that SP normally elicits a significant increase in contraction frequency and a decrease in end-diastolic diameter. In the presence of nifedipine, phasic contractions stop, yet subsequent SP treatment still elicits a strong tonic contraction. Caffeine treatment gradually relaxes lymphatics, causing a loss of phasic contractions, and prevents subsequent SP-induced tonic contraction. Ryanodine also gradually diminishes phasic contractions but without causing vessel relaxation and significantly inhibits the SP-induced tonic contraction. Dantrolene treatment did not significantly impair lymphatic contractions nor the response to SP. The mRNA for all RyR isoforms is detectable in isolated lymphatics. RyR2 and RyR3 proteins are found predominantly in the collecting lymphatic smooth muscle layer. Collectively, the data suggest that SP-induced tonic contraction requires both extracellular Ca2+ plus Ca2+ release from internal stores and that RyRs play a role in the normal contractions and responsiveness to SP of rat mesenteric collecting lymphatics. NEW & NOTEWORTHY The mechanisms that govern contractions of lymphatic vessels remain unclear. Tonic contraction of lymphatic vessels caused by substance P was blocked by caffeine, which prevents normal uptake and release of Ca2+ from internal stores, but not nifedipine, which blocks L-type channel-mediated Ca2+ entry. Ryanodine, which also disrupts normal sarcoplasmic reticulum Ca2+ release and reuptake, significantly inhibited substance P-induced tonic contraction. Ryanodine receptors 2 and 3 were detected within the smooth muscle layer of collecting lymphatic vessels.

Diarrhea is a gastrointestinal symptom associated with systemic anaphylaxis and could be induced by increased colonic motility. We determined colonic motility and expulsion by measuring the intracolonic pressure (ICP) and expelled fluid weight in anesthetized rats during anaphylactic hypotension. Substantial systemic hypotension occurred in every sensitized rat after antigen injection. One min after antigen injection, ICP began to increase and remained elevated for 5 min, which was revealed to represent tonic contraction by the video-recording procedure, and was accompanied by increased colonic fluid expulsion. Parasympathectomy composed of subdiaphragmatic vagotomy combined with pelvic nerve transection reduced the duration of the tonic contraction, but not expelled colonic fluid. Furthermore, denervation of afferent parasympathetic nerves produced essentially the same effect as parasympathectomy. Sympathectomy did not significantly change any parameters. In conclusion, the colonic motility during anaphylactic hypotension is characterized by 5-min lasting tonic contraction which is associated with increased colonic fluid expulsion and is involved by parasympathetic nerves, especially their afferents, but not sympathetic nerves, in anesthetized rats.

It is generally thought, although probably not scientifically proven, that convulsive ictal apnea is secondary to diaphragm tonic contraction in conjunction with tonic limb muscular contraction.

The purpose of the present study was to examine corticospinal excitability to the biceps and triceps brachii during arm cycling and an intensity-matched tonic contraction using stimulus response curves (SRCs) elicited via transcranial magnetic stimulation (TMS). Corticospinal excitability was assessed using TMS elicited motor-evoked potentials (MEPs) at eight different stimulation intensities (85-190% of MEP threshold). MEPs were recorded during arm cycling at two different positions, mid-elbow flexion (6 o'clock relative to a clock face) and mid-elbow extension (12 o'clock relative to a clock face), in addition to an intensity-matched (12 o'clock) tonic contraction. At the 12 o'clock position, the slope of the SRC was significantly lower during arm cycling than the tonic contraction for the biceps brachii (Cycling: 0.64 ± 0.47, Tonic: 1.02 ± 0.38, P0.05) but was not different for the triceps brachii (Cycling: 1.33 ± 0.49, Tonic: 1.48 ± 0.43, P = 0.42). Within arm cycling, the SRC slope was significantly greater at the 6 o'clock position than 12 o'clock position for the biceps brachii (6 o'clock: 1.37 ± 0.24, 12 o'clock: 0.64 ± 0.47, P0.05) but was not different for the triceps brachii (6 o'clock: 1.11 ± 0.28, 12 o'clock: 1.33 ± 0.49, P = 0.34). These findings demonstrate that corticospinal excitability to the biceps brachii is task-dependent during the extension phase of arm cycling. Neither position nor task influenced corticospinal excitability to the triceps brachii, providing further support that the motor control of locomotor outputs is muscle-specific.

Human studies have not assessed corticospinal excitability of an upper-limb prime mover during arm cycling. The purpose of the present study was to determine whether supraspinal and/or spinal motoneuron excitability of the biceps brachii was different between arm cycling and an intensity-matched tonic contraction. We hypothesized that spinal motoneuron excitability would be higher during arm cycling than an intensity-matched tonic contraction. Supraspinal and spinal motoneuron excitability were assessed using transcranial magnetic stimulation (TMS) of the motor cortex and transmastoid electrical stimulation (TMES) of the corticospinal tract, respectively. TMS-induced motor-evoked potentials (MEPs) and TMES-induced cervicomedullary-evoked potentials (CMEPs) were assessed at three separate positions (3, 6, and 12 o'clock relative to a clock face) during arm cycling and an intensity-matched tonic contraction. MEP amplitudes were 7.2 and 8.8% maximum amplitude of the compound muscle action potential (Mmax) larger during arm cycling compared with a tonic contraction at the 3 ( P < 0.001) and 6 o'clock ( P < 0.001) positions, respectively. There was no difference between tasks during elbow extension (12 o'clock). CMEP amplitudes were 5.2% Mmax larger during arm cycling compared with a tonic contraction at the 3 o'clock position ( P < 0.001) with no differences seen at midflexion (6 o'clock) or extension (12 o'clock). The data indicate an increase in the excitability of corticospinal neurons, which ultimately project to biceps brachii during the elbow flexion portion of arm cycling, and increased spinal motoneuron excitability at the onset of elbow flexion during arm cycling. We conclude that supraspinal and spinal motoneuron excitability are phase- and task-dependent.

To study the efficacy and short-term sequelae of modified shoelace repair for midline incisional hernias. A prospective non-randomized study of 30 cases of midline incisional hernias was carried out at a public hospital from May 2009 to Oct 2012. Patients underwent modified shoelace repair which comprises reconstruction of linea alba along with the use of polypropylene mesh to reinforce the facial layer. A proforma was maintained for each patient documenting patient details, nature of previous surgery and complications if any, postoperative course, and complications postincisional hernia repair. Thirty patients underwent this repair with no complications and no recurrence for minimum follow-up period of 12 months. Our technique is a simple extra-peritoneal procedure with no extensive tissue dissection and avoids the potential complications of bowel injury and adhesions with the mesh. The principle involved is that during straining, the recti shorten by tonic contraction and approximate toward the midline. An incisional hernia weakens the midline and causes the recti to move laterally with contraction as medial pull is lost. By reforming a strong new linea alba, there is restoration of medial pull on recti. This is further buttressed by the mesh. Modified shoelace repair is a simple and safe extra-peritoneal procedure and can be used for all midline incisional hernias.

An epileptic seizure is a transient symptom of excessive or synchronous neuronal activity in the brain, which can be observed by electroencephalography (EEG). The epileptic seizure which characterized by abrupt loss of consciousness followed by tonic contraction of the muscles often impact depressive disorder. Although dhikr has been widely used to reduce depressive disorder, only a little research is known about the impact to epileptic seizure. This research aims to determine influence of dhikr on epileptiform activity in a teenager with depression disorder. The method used in this research was quasi experimental study using the Single Subject Randomized Time Series Design in a teenager with high depression disorder. Dhikr were conducted routinely in 4 weeks. This study's result showed there's a reduction to zero on artefact signs of seizure in EEG record of the subject even under stressful conditions. There's also an enhancement of epileptic fuze resistance. Dhikr succeeded to reduce epileptiform activity in the subject. This can be considered in other epileptic teenager with depression disorder.

Theta-burst stimulation (TBS) is a technique that elicits long-lasting changes in the excitability of human primary motor cortex (M1). Tonic contraction of the target muscle modifies the aftereffects of TBS, whereas interactions between phasic muscle contraction and the aftereffects of TBS are unknown. In this paper, we investigated whether phasic voluntary movements influence TBS-induced changes in M1 excitability. We examined whether a brief sequence of phasic finger movements performed by healthy humans before both intermittent TBS (iTBS) and continuous TBS (cTBS) influences TBS-induced aftereffects. Ten healthy subjects underwent iTBS and cTBS. To evaluate the TBS-induced aftereffects on M1 excitability, single TMS pulses were given over the FDI motor area before (T0) and 5 (T1), 15 (T2), and 30 min (T3) after TBS. To find out whether finger movements influenced the TBS-induced aftereffects, we tested motor-evoked potentials (MEPs) size by single TMS pulses at T0, immediately after movements, and at T1–T3. We also measured the kinematic variables mean amplitude and mean peak velocity of the movements. When no phasic voluntary movements preceded TBS, iTBS elicited facilitatory and cTBS elicited inhibitory aftereffects on MEP size. Conversely, movements performed before TBS elicited significant changes in the direction of the TBS-induced aftereffects. iTBS produced inhibitory instead of facilitatory aftereffects and cTBS produced facilitatory instead of inhibitory aftereffects. Finger movements alone had no effects on MEPs size tested with single-pulse TMS. Peripheral electrical stimulation had no effect on iTBS-induced aftereffects. Repeated phasic finger movements interfere with TBS-induced aftereffects probably by modulating mechanisms of brain metaplasticity.

Background and purpose Contraction of the muscles of the unaffected hand is associated with enhanced activation of lesioned motor cortex (ie, crossed facilitation) in some individuals after stroke. However, the association between crossed facilitation and motor function status remains unclear. We investigated whether existence of crossed facilitation corresponds to motor status of the affected upper limb after stroke. Methods Data were collected from 58 participants with unilateral stroke. The Fugl-Meyer assessment of upper extremity (FMA-UE) was used to evaluate motor status. Motor-evoked potentials (MEPs) were elicited from the abductor pollicis brevis (ABP) of the affected side under 3 conditions: rest, tonic contraction of the ABP of the unaffected side, or tonic contraction of the tibialis anterior of the unaffected side. Results In 28 of the 58 participants, MEPs could be elicited from the affected ABP at rest; these participants also exhibited crossed facilitation during contraction on the unaffected side. Participants with MEPs at rest exhibited higher FMA-UE scores (53.04 ± 2.59) compared with participants with absent MEP (19.83 ± 1.60; Z = -6.21). Seven participants with no MEPs at rest had MEPs with crossed facilitation; their FMA-UE scores were higher compared with the 23 who had no ABP MEP under any condition (Z = -2.66). FMA-UE scores were positively correlated with the amount of crossed facilitation during the APB task (r = 0.68) and the tibialis anterior task (r = 0.54). Discussion and conclusions In some participants, MEPs in the affected hand muscle were enhanced by tonic contraction of the muscles on the unaffected side even if no MEP could be evoked at rest. The degree of crossed facilitation in the affected hand muscle was correlated with the level of motor function of the affected upper limb, and the FMA-UE score could classify the presence/absence of crossed facilitation.Video abstract available for more insights from the authors (Supplemental Digital Content 1, http://links.lww.com/JNPT/A117).

Motor representations express some degree of somatotopy in human primary motor hand area (M1HAND), but within-M1HAND corticomotor somatotopy has been difficult to study with transcranial magnetic stimulation (TMS). Here we introduce a "linear" TMS mapping approach based on the individual shape of the central sulcus to obtain mediolateral corticomotor excitability profiles of the abductor digiti minimi (ADM) and first dorsal interosseus (FDI) muscles. In thirteen young volunteers, we used stereotactic neuronavigation to stimulate the right M1HAND with a small eight-shaped coil at 120% of FDI resting motor threshold. We pseudorandomly stimulated six targets located on a straight mediolateral line corresponding to the overall orientation of the central sulcus with a fixed coil orientation of 45° to the mid-sagittal line (STRAIGHT-450FIX) or seven targets in the posterior part of the crown of the central sulcus following the bending of the central sulcus (CURVED). CURVED mapping employed a fixed (CURVED-450FIX) or flexible coil orientation producing always a current perpendicular to the sulcal wall (CURVED-900FLEX). During relaxation, CURVED but not STRAIGHT mapping revealed distinct corticomotor excitability peaks in M1HAND with the excitability maximum of ADM located medially to the FDI maximum. This mediolateral somatotopy was still present during tonic contraction of the ADM or FDI. During ADM contraction, cross-correlation between the spatial excitability profiles of ADM and FDI was lowest for CURVED-900FLEX. Together, the results show that within-M1HAND somatotopy can be readily probed with linear TMS mapping aligned to the sulcal shape. Sulcus-aligned linear mapping will benefit non-invasive studies of representational plasticity in human M1HAND.

Stimulation of the tracheal muscle bundle by acetylcholine (ACh) results in the generation of asynchronous repetitive Ca2+ waves (ACW) in intact tracheal smooth muscle (TSM) cells. We showed previously that ACW underlie cholinergic excitation-contraction coupling in porcine TSM and that Ca2+ entry through the L-type voltage-gated Ca2+ channel (VGCC) contributes partially to maintenance of the ACW. However, the mechanism of the ACW remains undefined. In this study, we pharmacologically characterized the mechanism of ACh-induced ACW in the intact porcine tracheal muscle bundle. We found that inhibition of receptor-operated channels/store-operated channels (ROC/SOC) by SKF-96365 completely abolished the nifedipine-insensitive component of ACh-mediated ACW and tonic contraction. Blockade of Na+/Ca2+ exchange with KB-R7943 or 2′,4′-dichlorobenzamil or removal of extracellular Na+ resulted in nearly complete inhibition of the nifedipine-insensitive component of ACh-mediated ACW and tonic contraction. Inhibition of the sarco(endo)plasmic reticulum Ca2+-ATPase by cyclopiazonic acid abolished the ongoing ACW. Application of 2-aminoethoxydiphenyl borate (2-APB) or xestospongin C to inhibit the inositol 1,4,5-trisphosphate-sensitive sarcoplasmic reticulum (SR) Ca2+ release channels produced no effect on ACh-mediated ACW and tonic contraction. However, pretreatment with caffeine or ryanodine inhibited ACh-induced ACW. Furthermore, application of procaine or tetracaine prevented the generation and abolished the ongoing ACh-mediated ACW and tonic contraction. Collectively, these results indicate that the ACh-stimulated ACW in porcine TSM are produced by repetitive cycles of Ca2+ release from SR through 2-APB- and xestospongin C-insensitive Ca2+ release channels, and plasmalemmal Ca2+ entry involving reverse-mode Na+/Ca2+ exchange, ROC/SOC, and L-type VGCC is required to refill the SR via SERCA to support the ongoing ACW.

SUMMARY The anterior byssal retractor muscle (ABRM) of the bivalve Mytilus edulis shows a prolonged tonic contraction, called the catch state. To investigate the catch mechanism, details of which still remain obscure, we studied the mechanical responses of ABRM fibres to quick increases in load applied during maximum active isometric force (P0)generation and during the catch state. The mechanical response consisted of three components: (1) initial extension of the series elastic component (SEC),(2) early isotonic fibre lengthening with decreasing velocity, and (3) late steady isotonic fibre lengthening. The ABRM fibres could bear extremely large loads up to 10–15P0 for more than 30–60 s,while being lengthened extremely slowly. If, on the other hand, quick increases in load were applied during the early isometric force development,the ABRM fibres were lengthened rapidly (`give') under loads of 1.5–2P0. These findings might possibly be explained by two independent systems acting in parallel with each other; one is the actomyosin system producing active shortening and active force generation,while the other is the load-bearing system responsible for the extremely marked load-bearing ability as well as the maintenance of the catch state.

Summary 1. Caffeine has wide-ranging activities on smooth muscles, including contractile and relaxant effects. The aim of the present study was to examine the activity of caffeine on rabbit corpus cavernosum (RCC). 2. The effects of caffeine (0.5–4.0 mmol/L) on the response of RCC to high K+ solution, noradrenaline (NA) and transmural electrical stimulation (EFS) were studied in a tissue bath system. 3. Caffeine did not contract the RCC. However, 0.5–4.0 mmol/L caffeine caused concentration-dependent relaxation of tension development in high-K+ (120 mmol/L) solution in contrast with the solvent control. At 4.0 mmol/L caffeine, high-K+ solution-induced tone of the RCC was reduced by 73.4 ± 7.3%. Caffeine (0.5–4.0 mmol/L) also concentration-dependently relaxed NA (12.5 µmol/L)-induced tonic contraction of the RCC. At 4.0 mmol/L caffeine, NA-induced tone of the RCC was reduced by 41.1 ± 7.0%. Incubation of RCC in 2.0 mmol/L caffeine for 30 min prior to EFS (1–40 Hz) caused a marked rightward shift in the frequency–response curve. 4. The results of the present study suggest that caffeine exhibits relaxant activity on rabbit cavernosal smooth muscle and the mechanism of this activity possibly involves inhibition of Ca2+ signalling.

Erectile dysfunction (ED) reduces the quality of life. It is estimated that 52% of men have some degree of ED, which is associated with ageing. While it is clear that there are a variety of current treatment options for ED, each of these has drawbacks and contraindications. A better understanding of the physiological mechanisms involved in penile erection will provide new ways to treat ED. This review not only focuses on the vasoconstrictors and vasodilators that control the state of contraction and relaxation of the corpora cavernosa smooth muscle, but also presents a novel Ca(2+)-sensitising pathway that contributes to maintaining the penis in the non-erect state. Studies have shown that inhibition of the RhoA/Rho-kinase signalling pathway induces penile erection. Further understanding of this RhoA/Rho-kinase pathway may provide a novel alternative treatment for ED.

The purpose of this study was to determine if supraspinal and/or spinal motoneuron excitability of the biceps brachii were differentially modulated before: 1) arm cycling and 2) an intensity-matched tonic contraction. Surface EMG recordings of motor evoked potentials (MEPs) and cervicomedullary motor evoked potentials (CMEPs) were used to assess supraspinal and spinal motoneuron excitability, respectively. MEP amplitudes were larger and onset latencies shorter, before arm cycling and tonic contraction when compared with rest with no intent to move, but with no difference between motor outputs. CMEP amplitudes and onset latencies remained unchanged before cycling and tonic contraction compared with rest. Premovement enhancement of corticospinal excitability was due to an increase in supraspinal excitability that was not task-dependent. This suggests that a common neural drive is used to initiate both motor outputs with task-dependent changes in neural excitability only being evident once the motor outputs have begun.

Dilated cardiomyopathy (DCM) inevitably afflicts patients with Duchenne muscular dystrophy (DMD). Understanding of the molecular pathophysiology of DCM in DMD has advanced, but correlation of these advances with clinical disease is lacking. We sought to identify echocardiographic changes that occur

We evaluated the effects of the nonselective beta-adrenoceptor agonist isoproterenol and the nonselective muscarinic antagonist butylscopolamine on ureteral wall tension, namely friction between an artificial stone and the intraureteral wall, in anesthetized rabbits.The relaxing effect of the drugs on the KCl induced tonic contraction was examined in isolated rabbit ureters. The effect of the drugs on the applied force needed for the artificial stone to pass at a constant speed through the ureter, called sliding force, was evaluated in anesthetized rabbits.In a concentration dependent manner isoproterenol but not butylscopolamine reduced the KCl induced contraction in isolated ureter (mean pD2 7.35 +/- 0.06). Intravenous administration of 1 and 10 microg./kg. isoproterenol significantly decreased the friction between the artificial stone and intraureteral wall in anesthetized rabbits with sliding force at 15 minutes after drug administration decreased by 54.5% and 63.6%, respectively. In contrast, 100 and 1,000 microg./kg. butylscopolamine intravenously had no evident effect on ureteral wall tension.Our results strongly suggest that ureteral smooth muscle relaxation by beta-adrenergic stimulation reduces ureteral wall tension, thereby, diminishing mechanical effects impeding the movement of a ureteral stone down the ureter.

Background: Studies in laboratory animals suggest that repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive shock (ECS) increase seizure inhibition acutely. This study was designed to explore whether chronic rTMS would also have seizure inhibition properties. Methods: To this purpose we administered rTMS (Magstim Rapid) and sham rTMS twice daily (2.5 T, 4-sec train duration, 20 Hz) to two groups of 10 rats for 16 days. The rTMS coil was a 50-mm figure-8 coil held directly over the rat’s head. Raters were blind to experimental groups. On days 11, 17, and 21 (5 days after the last rTMS) ECS was administered with a Siemens convulsator using three electrical charge levels. Variables examined were the presence or absence of seizures and seizure length (measured from the initiation of the tonic contraction until the end of the limb movement). Results: At day 11 rTMS had no effect on seizures, and both rTMS and sham rTMS animals convulsed equally. At day 17, however, rTMS-treated animals convulsed significantly less (both at presence/absence of seizures, and at seizure length) than sham rTMS animals. At day 21 the effects of rTMS had disappeared. Conclusions: These findings suggest that rTMS administered chronically leads to changes in seizure threshold similar to those reported for ECS and ECT; however, these effects were short-lived.

During the first months of life, children can present with unusual movements, which need to be differentiated from epileptic seizures. Some occur spontaneously, others are induced by various external stimuli. In 2001, we described a new clinical entity, which we called tonic reflex seizures of early infancy [1]. The condition occurs in otherwise normal children, mainly boys, and usually during the second or more rarely the third month of life. In all cases described the preganancy and delivery was normal. The attacks consist of tonic contractions predominantly of the limbs provoked by shaking, tactile stimulation or sudden postural changes, whether involving forward, upward or downward movements obviously, such stimuli occur during normal childcare. Upright rhythmical movements appear to be particularly likely to provoke attacks and some mothers are aware of the likely occurrence of the attacks if they descend stairs while holding their child in a vertical position. The attacks themselves consist of a sudden sustained diffuse tonic contraction with extension and abduction of all four limbs,although most noticeable in the upper limbs. This is accompanied by apnea and cyanosis but no impairment of consciousness. Attacks usually last between 3 to 10 sec and are usually followed by a brief cry. They may be repeated if the stimulus is repeated the phenomenon

The pelvic floor and urethral sphincters play an important part in maintaining continence after childbirth. The pelvic floor consists of the levator ani muscles and supports the external urinary and anal sphincters. The special feature of the sphincters is that they are in a continuous slight tonic contraction (Gowers, 1877; Floyd and Walls, 1953) which aids continence.

The gradient of permeability along the capillaries of voluntary muscle and the capillaries and venules of skin exists independently of the hydrostatic conditions, though influenced by them. Its presence cannot be explained by a graded tonic contraction of the capillaries. The evidence,—like that of previous papers,—points to local differences in the barrier offered by the wall of these vessels as responsible for the gradient.

The contraction mechanisms of GI smooth muscle can be differentiated with the aid of blockers of the voltage-controlled calcium channel (e.g. nifedipine). On the one hand, nifedipine-sensitive processes produce predominantly phasic-rhythmical contractions which can merge to sustained tonic activation, called 'tetanic tone', and which are combined with spike discharges and calcium influx. On the other hand, nifedipine-resistant and electrically silent processes produce a 'specific tone'. The cooperation of both processes in one and the same cell leads to a great diversity of patterns of smooth muscle activity. 'Specific tone' dominates in regions with reservoir function and contributes significantly to the contractions of GI sphincters, with great differences between sphincter types, the various species, and, in man, also between individuals.

1. 31 P NMR spectra of anterior byssus retractor muscle (ABRM) of Mytilus edulis were recorded at rest and treated by acetylcholine (ACh), the neuromediator causing muscular contraction. 2. An acceleration of metabolic processes after addition of ACh was observed as reflected by the increase of the phosphoarginine hydrolysis rate. 3. The contracting agent significantly decreases the activation energy of this hydrolysis reaction and the lowering is attributed to the activation of enzymes involved in the metabolic process. 4. In isometric conditions, the contractile force developed by the muscles is correlated to the phosphoarginine consumption due to the contraction.

This study links the reduction in jaw physiological tremor around 8 Hz following periodontal mechanoreceptor (PMR) anaesthetisation to changes in coherence between masseteric motor unit discharges. We have recorded single motor unit activity from two separate sites in the right masseter muscle during a low level tonic contraction, both prior to and during anaesthetisation of the peri-incisal PMRs. Anaesthetisation of PMRs decreased coherent activity between motor units circa 8 Hz, and decreased synchrony between the same motor unit pairs. It is proposed that tremor-generating inputs that cause rhythmic synchronisation of masseteric motor units arise from, or are amplified by the PMRs.

The gallbladder (GB) maintains tonic contraction modulated by neurohormonal inputs but generated by myogenic mechanisms. The aim of these studies was to examine the role of prostaglandins in the genesis of GB myogenic tension. Muscle strips and cells were treated with prostaglandin agonists, antagonists, cyclooxygenase (COX) inhibitors, and small interference RNA (siRNA). The results show that PGE2, thromboxane A2(TxA2), and PGF2αcause a dose-dependent contraction of muscle strips and cells. However, only TxA2and PGE2(E prostanoid 1 receptor type) antagonists induced a dose-dependent decrease in tonic tension. A COX-1 inhibitor decreased partially the tonic contraction and TxB2(TxA2stable metabolite) levels; a COX-2 inhibitor lowered the tonic contraction partially and reduced PGE2levels. Both inhibitors and the nonselective COX inhibitor indomethacin abolished the tonic contraction. Transfection of human GB muscle strips with COX-1 siRNA partially lowered the tonic contraction and reduced COX-1 protein expression and TxB2levels; COX-2 siRNA also partially reduced the tonic contraction, the protein expression of COX-2, and PGE2. Stretching muscle strips by 1, 2, 3, and 4 g increased the active tension, TxB2, and PGE2levels; a COX-1 inhibitor prevented the increase in tension and TxB2; and a COX-2 inhibitor inhibited the expected rise in tonic contraction and PGE2. Indomethacin blocked the rise in tension and TxB2and PGE2levels. We conclude that PGE2generated by COX-2 and TxA2generated by COX-1 contributes to the maintenance of GB tonic contraction and that variations in tonic contraction are associated with concomitant changes in PGE2and TxA2levels.

A 6-year-old girl with a history of partial seizures had parietal spontaneous spikes, and high-voltage paroxysms, evoked by tapping of the hands and feet, in the parietal contralateral region during the electroencephalogram. The girl underwent a somatosensory evoked potential study, when she had a seizure, with tonic contraction rising of the right leg then followed by clonic jerks of the right leg, version of the head to the right, followed by a tonic contraction of the ipsilateral arm with flexion at the elbow. The seizure lasted 20–30 seconds. We believe this is the first description of a seizure during a somatosensory evoked potential procedure.

The anterior byssal retractor muscle (ABRM) of a bivalve mollusc Mytilus edulis is known to exhibit catch state, i.e. a prolonged tonic contraction maintained with very little energy expenditure. Two different hypotheses have been put forward concerning the catch state; one assumes actin-myosin linkages between the thick and thin filaments that dissociate extremely slowly (linkage hypothesis), while the other postulates a load-bearing structure other than actin-myosin linkages (parallel hypothesis). We explored the possible load-bearing structure responsible for the catch state by examining the arrangement of the thick and thin filaments within the ABRM fibers, using techniques of quick freezing and freeze substitution. No thick filament aggregation was observed in the cross-section of the fibers quickly frozen not only in the relaxed and actively contracting states but also in the catch state. The thick filaments were, however, occasionally interconnected with each other either directly or by distinct projections in all the three states studied. The proportion of the interconnected thick filaments relative to the total thick filaments in a given cross-sectional area was much larger in the catch state than in the relaxed and actively contracting states, providing evidence that the thick filament interconnection is responsible for the catch state.

In this study, we attempted to identify the interactions and mechanisms between veratrine and paeoniflorin on isolated mouse vas deferens. Paeoniflorin had no effect on isolated mouse vas deferens. Veratrine (1 x 10(-5) approximately 1 x 10(-3) g/ml) could directly induce contraction of isolated rat and mouse vas deferens. The concentration induced by veratrine (1 x 10(-5) g/ml) was completely inhibited by Ca2+-free solution and verapamil (1 x 10(-5) M), in both the epididymal and the prostatic portions of isolated mouse vas deferens. Naloxone (1 x 10(-5) M) did not alter the contraction induced by veratrine (1 x 10(-5) g/ml) in either the epididymal or the prostatic portions of isolated mouse vas deferens. Paeoniflorin (4.8 x 10(-5) g/ml) inhibited the contraction induced by veratrine (1 x 10(-5) g/ml) in both the epididymal and the prostatic portions of isolated mouse vas deferens. Paeoniflorin (4.8 x 10(-5) g/ml) potentiated norepinephrine (1 x 10(-5) M)-induced phasic contraction in the epididymal portion, but decreased contractions in the prostatic portion. Paeoniflorin (4.8 x 10(-5) g/ml) increased KCI (56 mM)-induced phasic contraction in the epididymal portion, but decreased the tonic contraction in either the epididymal or the prostatic portion. Veratrine (1 x 10(-5) g/ml)-induced contractions could be decreased by pretreatment with ryanodine (1 x 10(-5) M) in both the epididymal and the prostatic portions. Pretreatment with the combination of paeoniflorin (4.8 x 10(-5) g/ml) and ryanodine (1 x 10(-5) M) did not potentiate the inhibition of paeoniflorin in the veratrine-induced contraction in both the epididymal and the prostatic portions of isolated mouse vas deferens.

1. We characterized the mechanisms in vascular smooth muscle cells (VSMCs) that produce asynchronous, wave-like Ca(2+) oscillations in response to phenylephrine (PE). Confocal imaging was used to observe [Ca(2+)](i) in individual VSMCs of intact inferior vena cava (IVC) from rabbits. 2. It was found that the Ca(2+) waves were initiated by Ca(2+) release from the sarcoplasmic reticulum (SR) via inositol 1,4,5-trisphosphate-sensitive SR Ca(2+) release channels (IP(3)R channels) and that refilling of the SR Ca(2+) store through the sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase (SERCA) was required for maintained generation of the repetitive Ca(2+) waves. 3. Blockade of L-type voltage-gated Ca(2+) channels (L-type VGCCs) with nifedipine reduced the frequency of PE-stimulated [Ca(2+)](i) oscillations, while additional blockade of receptor-operated channels/store-operated channels (ROCs/SOCs) with SKF96365 abolished the remaining oscillations. Parallel force measurements showed that nifedipine inhibited PE-induced tonic contraction by 27 % while SKF96365 abolished it. This indicates that stimulated Ca(2+) entry refills the SR to support the recurrent waves of SR Ca(2+) release and that both L-type VGCCs and ROCs/SOCs contribute to this process. 4. Application of the Na(+)-Ca(2+) exchanger (NCX) inhibitors 2',4'-dichlorobenzamil (forward- and reverse-mode inhibitor) and KB-R7943 (reverse-mode inhibitor) completely abolished the nifedipine-resistant component of [Ca(2+)](i) oscillations and markedly reduced PE-induced tone. 5. Thus, we conclude that each Ca(2+) wave depends on initial SR Ca(2+) release via IP(3)R channels followed by SR Ca(2+) refilling through SERCA. Na(+) entry through ROCs/SOCs facilitates Ca(2+) entry through the NCX operating in the reverse mode, which refills the SR and maintains PE-induced [Ca(2+)](i) oscillations. In addition some Ca(2+) entry through L-type VGCCs and ROCs/SOCs serves to modulate the frequency of the oscillations and the magnitude of force development.

Mifepristone, a synthetic 19-norsteroid, relaxed the KCl-induced tonic contraction in isolated rat uterus in a concentration-dependent way and CaCl2 (0.1 to 10 mM) counteracted it. This effect was similar to other steroids although the mechanisms involved are unclear. Before adding the contracturant, tissue was incubated with actinomycin D (10 microM), cycloheximide (300 microM), TPCK (3 and 10 microM), Rp-cAMPS (30 microM), DDA (100 microM) and H-7 (1 microM). None of these modified the relaxing effect of mifepristone. Incubation with drugs that interfere with cGMP such as a nucleotide analogue DDG (100 microM), a soluble guanylyl cyclase inhibitor ODQ (1 microM) and an inhibitor of protein kinase G 8pCPTcGMPS (1 microM) significantly modified the effect of mifepristone, increasing its IC50.

The effect of temperature (5–35° C) on maximum force production was examined in intact and chemically skinned muscle fibre bundles (10–25 fibres) from the anterior byssus retractor muscle of Mytilus edulis. In intact fibre bundles, 10 μm acetylcholine induced a tonic contraction which had a magnitude of 65.4±4.0 N cm-2 (n=30) at 23° C. Activation by caffeine (20 mm) produced a force response which was 157.1±7.9% (n=16) of the acetylcholine response at 23° C and acetylcholine and caffeine together produced force which was not significantly different from the response to caffeine alone. At 5° C the acetylcholine and caffeine responses were decreased by 9.6±3.4% (n=6) and 14.6±2.8% (n=8) compared with the respective responses at 23° C. However, there was no significant reduction of the response induced by the combined action of acetylcholine and caffeine when the temperature was decreased from 23° C to 5° C. The 20–80% of peak force activation time increased by about one order of magnitude for all acetylcholine, caffeine and combined acetylcholine-caffeine-induced responses when the temperature was decreased from 23–5° C. Repeated exposure of the intact preparation to caffeine caused a marked decrease in the caffeine-induced response (complete abolition of force after the third exposure to caffeine), but the response to caffeine could be fully restored following one acetylcholine-induced activation. The maximum Ca2+-activated force after skinning the preparation with saponin was not significantly different from the caffeine or combined acetylcholine-caffeine-induced responses before skinning. In the saponin skinned fibre preparation a drop in temperature from 23° C to 15° C or 5° C decreased the maximum Ca2+-activated force by 13.2±1.4% (n=8) and 41.4±3.1% (n=5) respectively. The activation time between 20–80% of the peak Ca2+-activated force increased at 15° C and 5° C by a factor of 1.5±0.1 (n=5) and 6.8±1.1 (n=5) respectively when compared to corresponding values at 23° C. The relaxation half-time decreased by a factor of 1.7±0.2 (n=5) and 3.0±0.2 (n=5) at 15° C and 5° C respectively compared with that at 23° C. It was possible to distinguish between the temperature effects on the contractile apparatus per se and the Ca2+ regulatory system with the results indicating that the contractile apparatus was more sensitive to a change in temperature than the Ca2+-regulatory system. Increasing the temperature to 35° C irreversibly affected the ability to develop and maintain force in both intact and skinned muscle preparations. These results indicate that: (1) acetylcholine does not fully activate the intact ‘catch’ muscle at 23° C; (2) acetylcholine is able to replenish the internal stores after depletion by caffeine; (3) compensatory mechanisms which oppose the inhibitory effect of lower temperatures on the contractile apparatus and the Ca2+-regulatory system must be operating in the intact fibre preparations.

Recordings from awake behaving cats indicate that muscle spindle sensitivity is lower during walking than during postural tasks (Prochazka, 1989), due to a predominant static fusimotor drive. Thus, during walking the effectiveness of the stretch reflex should be relatively reduced by this static fusimotor drive. We investigated this possibility in acute locomoting spinal cats, where we could directly measure spindle sensitivity and reflex responsiveness. For comparison, measurements were also taken in the quiescent state (resting) and during tonic contractions. As tonic contractions are unusual in the spinal cat, we elicited them in the decerebrate cat prior to spinalisation.

We compared the morphology of the accommodative apparatus in myopic and control chicks using light microscopy and scanning and transmission electron microscopy. Results indicate no significant difference in ciliary muscle and ciliary fold structure between control chick eyes and eyes in which at least 10 D of myopia was induced by the application of a translucent goggle. Based on the assumption that sustained tonic contraction of the accommodative apparatus in the myopic eye would lead to morphological differences, we conclude that the myopic eye is not accommodating excessively during development. These results, in combination with previous findings concerning the role of accommodation in experimental myopia, strongly indicate that accommodation does not play a significant role in this type of experimental myopia in chicks.

The purpose of this investigation was to determine whether α1-adrenoceptor subtypes (co)exist in the rat portal vein and, if so, whether they could be functionally associated with the phasic and tonic types of contraction as a response to α1-adrenoceptor stimulation by phenylephrine. A low Ca2+concentration (0.9 mmol/l) in the Tyrode solution enabled us to quantify changes both in the phasic myogenic activity and in the basal tone of the rat portal vein preparation very precisely. We used both competitive and non-competitive α-adrenoceptor antagonists which have been employed successfully by other investigators to discriminate between α1-adrenoceptor subtypes in vascular and other tissues. Schild analysis showed that the competitive α-adrenoceptor antagonists prazosin, phentolamine, yohimbine, corynanthine, idazoxan, rauwolscine and 5-methyl-urapidil could not distinguish between the phasic and tonic responses to phenylephrine and/or different α1-adrenoceptor subtypes in the rat portal vein. However, when we compared our pA2values with those found to be representative indicators according to subclassifications based on the use of selective antagonists in different tissues, the α1-adrenoceptors in the rat portal vein appeared to belong to the α(1L)- or α(1a)-subtype. This subclassification was not in accordance with the data obtained with the irreversible α-adrenoceptor antagonist chloroethylclonidine. However, the validity of this alkylating agent as a tool for receptor classification was restricted, at least in the rat portal vein, by its effects on receptor reserve. In contrast to the competitive α-adrenoceptor antagonists, the irreversible α-adrenoceptor antagonists phenoxybenzamine and chloroethylclonidine could indeed discriminate between the phasic and tonic types of contraction in response to α1-adrenoceptor stimulation by phenylephrine, indicating two different receptor reserves for phenylephrine for the two types of responses. In conclusion, both the phasic and tonic types of contraction elicited by phenylephrine in the longitudinal smooth muscle of the rat portal vein appear to be mediated by one particular α1-adrenoceptor subtype as defined by Schild analysis with selective, competitive α-adrenoceptor antagonists. However, using the method of receptor alkylation with phenoxybenzamine, two different affinity constants for the two types of responses could be calculated for phenylephrine. This may reflect the involvement of two different subtypes of α1-adrenoceptors or, more probably, the existence of only one α1-adrenoceptor subtype, which is coupled with two different intrinsic efficacies to the effector pathways mediating the phasic and tonic responses, respectively.

Force development in muscle is thought to result from cyclic attachment and detachment of crossbridges extending from “thick” myosin-containing filaments to binding sites on “thin” actin-containing filaments. According to the crossbridge model formulated by Huxley (1957) and extended by Huxley and Simmons (1971), the rate constants for attachment and detachment are functions of the position of the crossbridge relative to the binding site on the actin filament, which also determines the force by the elastic extension of the crossbridge. Particularly, “negative” strain on the crossbridge, giving rise to a force tending to oppose shortening of the muscle, is associated with a high rate constant for crossbridge detachment.

Publisher Summary This chapter discusses measurement of noninactivating calcium current in smooth muscle cells. Elevation of extracellular K+ concentration (high K+) is often used as a convenient pharmacological tool to activate smooth muscle tissues by a mechanism not mediated by stimulation of particular receptor. In smooth muscle, tonic contraction induced by high-K+ solution is because of sustained Ca2+ influx through voltage-dependent Ca2+ channels (VDCCs). This chapter discusses a methodology that allows direct measurement of sustained Ca2+ influx through VDCC(s). This methodology is developed by combining some techniques with other drug application techniques to optimize quantitation of a noninactivating Ca2+ current [ICa(ni)]. The ICa(ni) is very sensitive to organic and inorganic Ca2+ antagonists and Ca2+ agonists, and depends strongly upon extracellular Ca2+ concentration. Therefore, current flowing through VDCCs can explain the sustained Ca2+ influx in smooth muscle during a prolonged depolarization, for example, in high-K+ solution. This methodology is useful for pharmacological quantitation of the effects of drugs on sustained Ca2+ influx through VDCC not only in smooth muscle but also in neuronal cells.

to the editor: In their recent paper, Cong et al. ([1][1]) argue that nitric oxide (NO) does not play a role in the relaxation of gallbladder muscle strips since a nitric oxide synthase inhibitor (NOSI) does not change gallbladder tonic contraction or block relaxation induced by electrical field

Supplementary motor seizures (SMS) are among the group of frontal lobe seizures that may often be misdiagnosed as pseudoseizures (PS). We designed this study to determine the value of clinical phenomena in distinguishing between the two. In a series of patients with SMS, we identified those with signs and symptoms mimicking PS and compared the clinical phenomena with those of clinically similar PS. We found that SMS are short in duration, stereotypic, tend to occur in sleep, and often present with a tonic contraction of the upper extremities in abduction. This sign was specific for SMS, particularly when occurring at the onset. Conversely, PS are long in duration, nonstereotypic, and occur in the awake state. We conclude that clinical phenomena may be useful in distinguishing PS from SMS, although the final diagnosis must be documented by neurophysiologic means.