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Muscle Tone (muscle + tone)
Kinds of Muscle Tone Selected AbstractsPosture, muscular tone and visual attention in 5 month-old infantsINFANT AND CHILD DEVELOPMENT, Issue 4 2002Carole Lefèvre Abstract The present paper aims at studying the relationships between posture, muscle tone and visual attention in 5 month-old infants. To this end, a specially designed seating arrangement made it possible to vary posture while keeping constant the spatial relationship between eyes and stimuli. Five month-olds were placed in the reclining position (30°) or in a more erect position (60°). The more erect the posture, the more difficult it should be for the infant to maintain a straight body axis. Muscle tone was evaluated, and infants distinguished in terms of whether they were hypertonic or hypotonic. It was hypothesised that in a more erect position hypotonic children, who experience more difficulties in maintaining posture, should organise their visual exploration in ways different from those considered to be hypertonic. To test it, pairs of three-dimensional stimuli were presented in the distal visual field for one group (N=48) and in the proximal visual field in another group (N=32) for 2 min in each posture. The dynamical organisation of attention was evaluated through the number and duration of fixations on each target, the number of shifts from one target to the other (alternations) and the number of repetitions (back to the previous target). Results showed that visual behaviour was significantly affected by the distance at which stimuli were presented. Infants spent more time in visual exploration when the object was within reach than when it was out of reach. Although posture was shown to play a role in the organisation of visual exploration, no link with muscle tone was found, a surprising result which is discussed. Copyright © 2002 John Wiley & Sons, Ltd. [source] Tonic Potentiation And Attenuation Produced By Membrane Depolarization In Guinea-Pig TrachealisCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2000Kenichi Yamaki SUMMARY 1. We studied how membrane depolarization directly affected intracellular Ca2+ signalling when voltage-operated Ca2+ channels (VOCC) were not available in guinea-pig tracheal smooth muscle. To block VOCC, we used 3 ,mol/L verapamil, which completely abolished high K+ (20,60 mmol/L)-induced contraction, and elevation of fura-2 signal. 2. Muscle tone was generated by adding Ca2+ to the extracellular Ca2+ -free solution containing prostaglandin (PG)E2 (100 nmol/L) after abolishing basal tone with indomethacin (1 ,mol/L). 3. In the absence of verapamil, high K+ (20,60 mmol/L) solution potentiated 2.4 mmol/L Ca2+ -induced sustained contractions. Even in the presence of 3 ,mol/L verapamil, replacement with 20 and 40 mmol/L K+ solution induced tonic potentiation, which was changed to attenuation with a higher K+ solution (60 mmol/L), lower extracellular Ca2+ concentration ([Ca2+]o) and pretreatment with cyclopiazonic acid (10 ,mol/L), a Ca2+ sequestration inhibitor. 4. These results indicate that the balance between depolarization-dependent Ca2+ release and receptor-operated cation channel inhibition may determine whether tonic potentiation or attenuation is manifested, depending on the availability of VOCC, the magnitude of the depolarization, [Ca2+]o and Ca2+ content in the sarcoplasmic reticulum. [source] Calcium handling in afferent arteriolesACTA PHYSIOLOGICA, Issue 4 2004M. Salomonsson Abstract The cytosolic intracellular calcium concentration ([Ca2+]i) is a major determining factor in the vascular smooth muscle tone. In the afferent arteriole it has been shown that agonists utilizing G-protein coupled receptors recruit Ca2+ via release from intracellular stores and entry via pathways in the plasma membrane. The relative importances of entry vs. mobilization seem to differ between different agonists, species and preparations. The entry pathway might include different types of voltage sensitive Ca2+ channels located in the plasmalemma such as dihydropyridine sensitive L-type channels, T-type channels and P/Q channels. A role for non-voltage sensitive entry pathways has also been suggested. The importance of voltage sensitive Ca2+ channels in the control of the tone of the afferent arteriole (and thus in the control of renal function and whole body control of extracellular fluid volume and blood pressure) sheds light on the control of the membrane potential of afferent arteriolar smooth muscle cells. Thus, K+ and Cl, channels are of importance in their role as major determinants of membrane potential. Some studies suggest a role for calcium-activated chloride (ClCa) channels in the renal vasoconstriction elicited by agonists. Other investigators have found evidence for several types of K+ channels in the regulation of the afferent arteriolar tone. The available literature in this field regarding afferent arterioles is, however, relatively sparse and not conclusive. This review is an attempt to summarize the results obtained by others and ourselves in the field of agonist induced afferent arteriolar Ca2+ recruitment, with special emphasis on the control of voltage sensitive Ca2+ entry. Outline of the Manuscript: This manuscript is structured as follows: it begins with an introduction where the general role for [Ca2+]i as a key factor in the regulation of the tone of vascular smooth muscles (VSMC) is detailed. In this section there is an emphasis is on observations that could be attributed to afferent arteriolar function. We then investigate the literature and describe our results regarding the relative roles for Ca2+ entry and intracellular release in afferent arterioles in response to vasoactive agents, with the focus on noradrenalin (NA) and angiotensin II (Ang II). Finally, we examine the role of ion channels (i.e. K+ and Cl, channels) for the membrane potential, and thus activation of voltage sensitive Ca2+ channels. [source] Decreased Tear Expression with an Abnormal Schirmer's Test Following Botulinum Toxin Type A for the Treatment of Lateral Canthal RhytidesDERMATOLOGIC SURGERY, Issue 2 2002Seth L. Matarasso MD background. Inactivation of muscles of facial expression by chemodenervation with botulinum toxin remains an off-label indication. Nevertheless, it continues to be a safe and effective technique to improve dynamic rhytides and is the treatment of choice for the hypertrophic lateral fibers of the orbicularis oculi muscle that can cause the superimposed crow's feet. objective. Although infrequent and self-limiting, the complication of unexpected muscle weakness from toxin diffusion or erroneous placement is documented. methods. However, injection into the pretarsal portion of the orbicularis oculi muscle resulting in unilateral ocular irritation and diminished tear expression as evidenced by a dry eye and an abnormal Schirmer's test has rarely been reported. Direct injection into the pretarsal fibers of the muscle as opposed to diffusion of the toxin into the muscle fibers or the lacrimal gland was consistent with the onset of action of the toxin and the prolonged duration of the ocular symptoms. results. Treatment consisted of ocular lubrication until the effects of the toxin dissipated and muscle tone returned. Subsequent treatment did not result in a result in a recurrence of adverse sequelae. conclusions. Facial muscles are small, not isolated, and often have fibers that interdigitate. An important factor in the administration of botulinum toxin is the identification of the muscles responsible for the corresponding rhytide. Precise knowledge of muscular anatomy and function will aid in minimizing this and other potential complications. [source] Intrathecal baclofen use in adults with cerebral palsyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2009LINDA E KRACH MD Intrathecal baclofen (ITB) is an effective treatment for both spasticity and dystonia in people with cerebral palsy (CP). Its use is becoming increasingly common. ITB is typically associated with fewer side effects than the oral form of the product, but there are risks related to the hardware needed for intrathecal delivery. Much of what has been reported in the literature about ITB is based on experience with children or groups of children and adults; few reports exclusively address its use in adults with CP. These reports indicate that muscle tone is consistently reduced, but there is some variability in functional outcomes. Few well-controlled studies have been done. Controversies remain concerning ITB, including whether a trial is needed before pump implantation, proper catheter tip placement, and programming options, as well as whether it contributes to the development or progression of scoliosis. These and other unanswered questions should be addressed in a systematic way. [source] Long-term effects of botulinum toxin A in children with cerebral palsyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2 2009KRISTINA TEDROFF MD The long-term effects of botulinum toxin A (BoNT-A) treatment in children with cerebral palsy (CP) are still elusive. We studied a prospective clinical cohort of 94 children with different subtypes (50% spastic diplegic CP, 22% hemiplegic CP, 25% tetraplegic CP, 3% dyskinetic CP), sex (55% male, 45% female), severity according to Gross Motor Function Classification System (29% Level I, 15% Level II, 16% Level III, 17% Level IV, 23% Level V), and age (median 5y 4mo, range 11mo,17y 8mo). The longest follow-up time was 3 years 7 months (median 1y 6mo) and included a maximum of eight injections per muscle (median two injections to a specific muscle). Outcome measurements were muscle tone (Modified Ashworth Scale) and joint range of motion (ROM). Assessments were made at a minimum before and 3 months after each injection. Ninety-five per cent confidence intervals for differences from baseline were used to identify significant changes. BoNT-A injections induced reduction of long-term spasticity in all muscle-groups examined: the gastrocnemius, hamstring, and adductor muscles. The reduction in tone was most distinct in the gastrocnemius muscle, and each repeated injection produced an immediate reduction in muscle tone. However, improvement in ROM was brief and measured only after the first injections, whereupon the ROM declined. Thus, the results suggest that BoNT-A can be effective in reducing muscle tone over a longer period, but not in preventing development of contractures in spastic muscles. The dissociation between the effects on muscle tone and ROM indicates that development of contractures is not coupled to increased muscle tone only, but might be caused by other mechanisms. [source] GluR3 subunit regulates sleep, breathing and seizure generationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2008Hendrik W. Steenland Abstract The functional role of GluR3 AMPA (,-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor subunits has remained elusive. In vitro studies of genetic knockout mice have not yielded significant alterations in synaptic communication. However, behavioural approaches utilizing knockout mice have shown that the subunit may be involved in exploration and motor coordination, suggesting that in vivo methodologies may be more forthcoming. We tested the hypothesis that GluR3 subunits are involved in the modulation of neural network activity. We used a freely behaving mouse model to examine the effect of GluR3,/, on field potential recordings of electroencephalogram, vital functions (i.e. breathing and heart rate) and muscle tone across natural sleep and wakefulness states. We found that GluR3,/, mice virtually lack electroencephalographic signatures of NREM sleep (n = 9) as demonstrated by reduction in electroencephalogram power in the low-frequency bands (,1, ,2 and ,). In addition, three of nine GluR3,/, mice expressed seizure activity during wakefulness and sleep, suggesting that deletion of the GluR3 gene may predispose to seizure. GluR3 gene knockout also produced state-dependent respiratory modulation, with a selective reduction in breathing rate during behavioural inactivity. These findings show that GluR3 subunits have diverse neurophysiological impact, modulating oscillatory networks for sleep, breathing and seizure generation. Finally, this is the first study to demonstrate the feasibility of direct diaphragm electromyogram recordings in freely behaving mice. [source] Posture, muscular tone and visual attention in 5 month-old infantsINFANT AND CHILD DEVELOPMENT, Issue 4 2002Carole Lefèvre Abstract The present paper aims at studying the relationships between posture, muscle tone and visual attention in 5 month-old infants. To this end, a specially designed seating arrangement made it possible to vary posture while keeping constant the spatial relationship between eyes and stimuli. Five month-olds were placed in the reclining position (30°) or in a more erect position (60°). The more erect the posture, the more difficult it should be for the infant to maintain a straight body axis. Muscle tone was evaluated, and infants distinguished in terms of whether they were hypertonic or hypotonic. It was hypothesised that in a more erect position hypotonic children, who experience more difficulties in maintaining posture, should organise their visual exploration in ways different from those considered to be hypertonic. To test it, pairs of three-dimensional stimuli were presented in the distal visual field for one group (N=48) and in the proximal visual field in another group (N=32) for 2 min in each posture. The dynamical organisation of attention was evaluated through the number and duration of fixations on each target, the number of shifts from one target to the other (alternations) and the number of repetitions (back to the previous target). Results showed that visual behaviour was significantly affected by the distance at which stimuli were presented. Infants spent more time in visual exploration when the object was within reach than when it was out of reach. Although posture was shown to play a role in the organisation of visual exploration, no link with muscle tone was found, a surprising result which is discussed. Copyright © 2002 John Wiley & Sons, Ltd. [source] A review of nutrition in Duchenne muscular dystrophyJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 5 2009Z. E. Davidson Abstract Duchenne muscular dystrophy (DMD) is a recessive X linked genetic disorder characterised by progressive muscle weakness and reduced muscle tone. Affecting only boys, it limits life expectancy to approximately 20 years. A literature review was conducted using MEDLINE and the Cochrane Library, employing the term ,Duchenne muscular dystrophy'. A total of 1491 articles in English were recovered. These papers were searched thematically under the headings: body composition (n = 10), energy expenditure (n = 10), nutrition (n = 6), corticosteroid therapy (n = 55) and gene therapy (n = 199). Key dietetic practice points were identified relevant to nutritional management. Papers supporting these key themes were assigned a level of evidence and grade of recommendation. There is limited high-quality evidence to guide the nutritional management of boys with DMD. Currently, the majority of evidence is based on expert opinion and clinical expertise. Delayed growth, short stature, muscle wasting and increased fat mass are characteristics of DMD and impact on nutritional status and energy requirements. The early introduction of steroids has altered the natural history of the disease, but can exacerbate weight gain in a population already susceptible to obesity. Prior to commencing steroids, anticipatory guidance for weight management should be provided. Malnutrition is a feature of end stage disease requiring a multidisciplinary approach, such as texture modification and supplemental feeding. Micronutrient requirements are yet to be determined but, as a result of corticosteroid treatment, vitamin D and calcium should be supplemented. Some evidence exists supporting supplementation with creatine monohydrate to improve muscle strength. More research is needed to provide a higher quality of evidence for dietitians working within this area. [source] Management of Low Compliant Bladder in Spinal Cord Injured PatientsLUTS, Issue 2 2010Won Hee PARK Low bladder compliance means an abnormal volume and pressure relationship, and an incremental rise in bladder pressure during the bladder filling. It is well known that at the time bladder capacity decreases, intravesical pressure increases, and the risk of upper deterioration increases. Hypocompliance is usually thought to be the range from 1.0 to 20.0 mL/cmH2O. Though the exact cause of hypocompliance is not known, it may be caused by changes in the elastic and viscoelastic properties of the bladder, changes in detrusor muscle tone, or combinations of the two. Management aims at increasing bladder capacity with low intravesical pressure. The main is a medical therapy with antimuscarinics combined with clean intermittent catheterization. The results are sometimes unsatisfactory. Various drugs or agents through the mouth or the bladder, including oxybutynin, new antimuscarinics, capsaicin and resiniferatoxin were tried. Among them botulinum toxin-A is promising. Some patients eventually required surgical intervention in spite of the aggressive medical therapy. Finally most patients undergo the surgical treatment including autoaugmentation, diversion, and augmentation cystoplasty. Among them augmentation cystoplasty still seems the only clearly verified treatment method. [source] Cellular Physiology of Retinal and Choroidal Arteriolar Smooth Muscle CellsMICROCIRCULATION, Issue 1 2007C. N. SCHOLFIELD ABSTRACT Control of ocular blood flow occurs predominantly at the level of the retinal and choroidal arterioles. The present article provides an overview of the Ca2 + handling mechanisms and plasmalemmal ion channels involved in the regulation of retinal and choroidal arteriolar smooth muscle tone. Increases in global intracellular free Ca2 + ([Ca2 +]i) involve multiple mechanisms, including agonist-dependent release of Ca2 + from intracellular stores through activation of the inositol trisphosphate (IP3) pathway. Ca2 + enters by voltage-dependent L-type Ca2 + channels and novel dihydropyridine-sensitive store-operated nonselective cation channels. Ca2 + extrusion is mediated by plasmalemmal Ca2 + -ATPases and through Na+/Ca2+ exchange. Local Ca2 + transients (Ca2 + sparks) play an important excitatory role, acting as the building blocks for more global Ca2 + signals that can initiate vasoconstriction. K+ and Cl, channels may also affect cell function by modulating membrane potential. The precise contribution of each of these mechanisms to the regulation of retinal and choroidal perfusion in vivo warrants future investigation. [source] Recent advances in enteric neurobiology: mechanosensitive interneuronsNEUROGASTROENTEROLOGY & MOTILITY, Issue 11 2007T. K. Smith Abstract, Until recently, it was generally assumed that the only intrinsic sensory neuron, or primary afferent neuron, in the gut was the after-hyperpolarizing AH/Type II neuron. AH neurons excited by local chemical and mechanical stimulation of the mucosa appear to be necessary for activating the peristaltic reflex (oral excitation and anal inhibition of the muscle layers) and anally propagating ring like contractions (peristaltic waves) that depend upon smooth muscle tone. However, our recent findings in the guinea-pig distal colon suggest that different neurochemical classes of interneuron in the colon are also mechanosensitive in that they respond directly to changes in muscle length, rather than muscle tone or tension. These interneurons have electrophysiological properties consistent with myenteric S-neurons. Ascending and descending interneurons respond directly to circumferential stretch by generating an ongoing polarized peristaltic reflex activity (oral excitatory and anal inhibitory junction potentials) in the muscle for as long as the stimulus is maintained. Some descending (nitric oxide synthase +ve) interneurons, on the other hand, appear to respond directly to longitudinal stretch and are involved in accommodation and slow transit of faecal pellets down the colon. This review will present recent evidence that suggests some myenteric S interneurons, in addition to AH neurons, behave as intrinsic sensory neurons. [source] Do ,1 -adrenoceptor antagonists improve lower urinary tract symptoms by reducing bladder outlet resistance?,NEUROUROLOGY AND URODYNAMICS, Issue 3 2008Maurits M. Barendrecht Abstract Aims To test the hypothesis that improvements of lower urinary tract symptoms (IPSS) upon treatment with an ,-blocker are due to reduction of bladder outlet obstruction (assessed as the bladder outlet obstruction index, BOOI); relationships of either with free flow Qmax were also explored. Methods The database of a large placebo-controlled, randomized, double-blind study with the ,-blocker tamsulosin was analyzed retrospectively. Patients were stratified into lower and upper halves according to baseline IPSS, Qmax or BOOI and treatment-associated alterations thereof. In these strata differences between values for the other two parameters were analyzed, for example, improvement of IPSS and Qmax were compared in patients with below and above median improvement of BOOI. Results Patients with below and above median baseline for one parameter, for example, IPSS had rather similar values for the other two parameters, for example, Qmax and BOOI. Likewise, patients based upon baseline strata for one parameter had rather similar improvements of the other two parameters. Most importantly, patients with below and above median treatment-associated improvements of one parameter, for example, BOOI exhibited only small if any difference for alterations of the other two parameters, for example, IPPS and Qmax. Conclusions We conclude that IPSS, free flow Qmax and BOOI are only loosely related at baseline. More importantly, treatment-induced improvements of these parameters are also only loosely related. These data do question the hypothesis that ,-blockers largely improve lower urinary tract symptoms by reducing bladder outlet obstruction and suggest that they may also act independent of prostatic smooth muscle tone. Neurourol. Urodynam. 27:226,230, 2008. © 2007 Wiley-Liss, Inc. [source] Improvement of bladder storage function by ,1-blocker depends on the suppression of C-fiber afferent activity in rats,NEUROUROLOGY AND URODYNAMICS, Issue 5 2006Osamu Yokoyama Abstract Aims ,1-blockers improve voiding symptoms through the reduction of prostatic and urethral smooth muscle tone; however, the underlying mechanism of improvement of storage symptoms is not known. Using a rat model of detrusor overactivity caused by cerebral infarction (CI), we undertook the present study to determine whether the effect of an ,1-blocker, naftopidil, is dependent on the suppression of C-fiber afferents. Methods To induce desensitization of C-fiber bladder afferents, we injected resiniferatoxin (0.3 mg/kg, RTX) sub-cutaneously to female Sprague-Dawley rats 2 days prior to left middle cerebral artery occlusion (MCAO) (RTX-CI rats). As controls we used rats without RTX treatment (CI rats). MCAO and insertion of a polyethylene catheter through the bladder dome were performed under halothane anesthesia. We investigated the effects on cystometrography (CMG) of intravenous (i.v.), intracerebroventricular (i.c.v.), or intrathecal (i.t.) administration of naftopidil in conscious CI rats. Results Bladder capacity (BC) was markedly reduced after MCAO in both RTX-CI and CI rats. I.v. administration of naftopidil significantly increased BC in CI rats without an increase in residual volume, but it had no effects on BC in RTX-CI rats. I.t. administration of naftopidil significantly increased BC in CI but not in RTX-CI rats. Conclusions These results suggest that naftopidil has an inhibitory effect on C-fiber afferents in the lumbosacral spinal cord, improving BC during the storage phase. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc. [source] Predicting motor recovery of the upper limb after stroke rehabilitation: value of a clinical examinationPHYSIOTHERAPY RESEARCH INTERNATIONAL, Issue 1 2000Hilde Feys Abstract Background and Purpose Only a few studies have been conducted to predict motor recovery of the arm after stroke. The aims of this study were to identify which clinical variables, assessed at different points in time, were predictive of motor recovery, and to construct useful regression equations. Method One hundred consecutive stroke patients who had an obvious motor deficit of the upper limb were evaluated on entry to the study (two to five weeks post-stroke) and at two, six and 12 months after stroke. The Brunnström,Fugl-Meyer test was used as the outcome measure. Predictors included demographic data, overall disability, clinical neurological features, neuropsychological factors and secondary shoulder complications. Results In multiple regression analyses, motor performance was invariably retained as the predictive factor with the highest R-square. Other significant predictive variables were overall disability, muscle tone, proprioception and hemi-inattention. Between 53% and 89% of the total amount of variance was accounted for in all selected models. The accuracy of prediction from clinical measurement in the acute phase diminished as the time span of measurement of outcome increased. Similarly, assessment of the variables at two and six months, rather than in the acute stage, resulted in a considerable improvement in the percentage variance explained at 12 months. The highest accuracy was obtained when predictions were made step-by-step in time. Conclusions It is possible to predict motor recovery of the upper limb accurately through the use of a few clinical measures. Predictive equations are proposed, the use of which are practicable in both clinical practice and research. Copyright © 2000 Whurr Publishers Ltd. [source] Characterization of Phosphodiesterase Type 5 Expression and Functional Activity in the Human Male Lower Urinary TractTHE JOURNAL OF SEXUAL MEDICINE, Issue 1pt1 2010Benedetta Fibbi MD ABSTRACT Introduction., Phosphodiesterase type 5 (PDE5) inhibitors ameliorate low urinary tract (LUT) symptoms in men with ED and symptomatic benign prostatic hyperplasia (BPH). PDE5 is highly expressed in rat and human bladder, where it regulates cyclic guanosine monophosphate (cGMP) degradation, muscle tone, and proliferation. Aim., To investigate PDE5 tissue distribution and activity in human LUT tissues (urethra, prostate, and bladder). Main Outcome Measures., PDE5 expression and activity were analyzed and compared within the same BPH patient in LUT tissues and in smooth muscle cells (SMCs) cultured from urethra, prostate, and bladder. Methods., In LUT tissues, PDE5 was localized by immunohistochemistry and mRNA expression by quantitative real-time polymerase chain reaction. Proliferation assay was used as readout of PDE5 activity, evaluated as ability of vardenafil to increase the antiproliferative effect of different nitric oxide (NO)/cGMP pathway activators [the PDE5-resistant cGMP analog Sp-8-Br-PET-cGMPS, the NO donor sodium nitroprusside (SNP), and the soluble guanylate cyclase (sGC) stimulator BAY 41-8543]. Results., In all the LUT tissues, PDE5 was immunolocalized in blood vessels and in muscular fibres, but not in epithelium. PDE5 mRNA expression was higher in urethra and bladder than in prostate SMC. The antiproliferative effect of Sp-8-Br-PET-cGMPS was similar in all LUT SMC. In prostatic SMC, SNP and BAY 41-8543 show a dose-dependent antiproliferative effect that resulted marginally enhanced by vardenafil. Conversely, in urethra and bladder SMC the antiproliferative effect of SNP and BAY 41-8543 was lower than in prostatic SMC, but it was significantly enhanced by vardenafil. In urethral and bladder cells vardenafil half-maximal response inhibiting concentration was in the subnanomolar range, whereas in prostate cells it resulted significantly higher. Conclusions., The highest expression and biological activity of PDE5 was found in bladder. However, a consistent PDE5 expression and activity was also found in prostatic urethra. In contrast, the prostate gland showed the lowest PDE5 abundance and cultures derived from this tissue were less sensitive to vardenafil. Fibbi B, Morelli A, Vignozzi L, Filippi S, Chavalmane A, De Vita G, Marini M, Gacci M, Vannelli GB, Sandner P, and Maggi M. Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. J Sex Med 2010;7:59,69. [source] Expression and Activity of Heme Oxygenase-1 in Artificially Induced Low-Flow Priapism in Rat Penile TissuesTHE JOURNAL OF SEXUAL MEDICINE, Issue 8 2008Yong Chun Jin ABSTRACT Introduction., The inducible isoform of heme oxygenase (HO)-1 regulates the vascular smooth muscle tone and responds to hypoxia. Aim., To investigate the role of HO-1 in a low-flow priapism. Materials and Methods., Sixty male Sprague-Dawley rats were divided into five groups of six rats each. Each group of rats was sacrificed at 0 hour (group 1, control), 4 hours (group 2), 8 hours (group 3), 12 hours (group 4), and 24 hours (group 5) after inducing an artificial veno-occlusive priapism. The changes of the expression and activity of HO-1, and the expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), and levels of cyclic guanosine monophosphate in the penis were examined in a low-flow priapism. In addition, the HO-1 expression level in the aortas from each group was simultaneously measured to determine whether the changes in HO-1 were systemic. Main Outcome Measures., The expression and activity of HO-1 was examined in artificially induced veno-occlusive priapism in rat penile tissues. Results., The expression of the HO-1 protein and the HO-1 enzyme activities in the penile tissues were gradually increased as time increased from 0 to 24 hours (P < 0.01). HO-1 immunoreactivities were localized in the endothelial layer of the cavernosal sinusoids. The expression of iNOS were also increased at 12 and 24 hours. The cyclic guanosine monophosphate level was also significantly increased at 24 hours (P < 0.05). However, the expression of the eNOS protein showed no statistically significant change with time, and the expression of the HO-1 protein in the aorta also showed no significant change with time. Conclusions., A higher induction of HO-1 with time was observed in artificially induced veno-occlusive priapism, which might play a protective role against hypoxic injury. However, this may also play an important role in the vicious circle observed in a low-flow priapism. Jin YC, Gam SC, Jung JH, Hyun JS, Chang KC, and Hyun JS. Expression and activity of heme oxygenase-1 in artificially induced low-flow priapism in rat penile tissues. J Sex Med 2008;5:1876,1882. [source] cGMP-enhancing- and ,1A/,1D -adrenoceptor blockade-derived inhibition of Rho-kinase by KMUP-1 provides optimal prostate relaxation and epithelial cell anti-proliferation efficacyTHE PROSTATE, Issue 13 2007Chi-Ming Liu Abstract Background Soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) and Rho kinase (ROCK2) pathways are important in the regulation of prostate smooth muscle tone. This study is aimed to examine the relaxation activities of a sGC activator and PDE5A/ROCK2 inhibitor KMUP-1 in rat prostate and associated anti-proliferation activity in human prostatic epithelial cells. Methods The action characteristics of KMUP-1 were identified by isometric tension measurement, receptor binding assay, Western blotting and radioimmunoassay in rat prostate. Anti-proliferation activity of KMUP-1 in human prostatic epithelial PZ-HPV-7 cells was identified using flow cytometry and real time QRT-PCR. Results KMUP-1 inhibited phenylephrine-induced contractility in a concentration-dependent manner. KMUP-1 possessed potent ,1A/,1D -adrenoceptor binding inhibition activity, increased cAMP/cGMP levels and increased the expression of sGC, PKG, and PKA protein in rat prostate. Moreover, KMUP-1 inhibited phenylephrine-induced ROCK2 expression. KMUP-1 inhibited cell growth, arrested the cell cycle at G0/G1 phase and increased the expression of p21 in PZ-HPV-7 cells. Conclusions These results broaden our knowledge of sGC/cGMP/PKG and ROCK2 regulation on the relaxation and proliferation of prostate, which may help in the design of benign prostate hyperplasia (BPH) therapies that target these signaling pathways. KMUP-1 possesses the potential benefit in the treatment of BPH by its ,1A/,1D -adrenoceptor blockade, sGC activation, inhibition of PDE5A and ROCK2 and p21 protein enhancement, leading to attenuation of the smooth muscle tone and the proliferation of epithelial PZ-HPV-7 cells. The synergistic contribution of these pathways by KMUP-1 may benefit BPH patients with lower urinary tract symptoms. Prostate 67: 1397,1410, 2007. © 2007 Wiley-Liss, Inc. [source] Mild-onset presentation of Canavan's disease associated with novel G212A point mutation in aspartoacylase geneANNALS OF NEUROLOGY, Issue 2 2006Christopher G. Janson MD We describe two sisters with a mild-onset variant of Canavan's disease who presented at age 50 and 19 months with developmental delay but without macrocephaly, hypotonia, spasticity, or seizures. Remarkably, both patients had age-appropriate head control, gross motor development, and muscle tone. There were very mild deficits in fine motor skills, coordination, and gait. Both sisters had a history of strabismus, but otherwise vision was normal. The older child showed evidence of mild cognitive and social impairment, whereas language and behavior were normal for age in the infant. Both patients were found to be compound heterozygotes for C914A (A305E) and G212A (R71H) mutations in ASPA. Like all other known ASPA mutations, this previously unknown G212A mutation appears to have low absolute enzyme activity. Nevertheless, it is associated in these patients with an extremely benign phenotype that is highly atypical of Canavan's disease. Biochemical and clinical data were evaluated using a generalized linear mixed model generated from 25 other subjects with Canavan's disease. There were statistically significant differences in brain chemistry and clinical evaluations, supporting a distinct variant of Canavan's disease. Future studies of ASPA enzyme structure and gene regulation in these subjects could lead to a better understanding of Canavan's pathophysiology and improvements in ASPA gene therapy Ann Neurol 2006;59:428,431 [source] Brainstem pathology in DYT1 primary torsion dystoniaANNALS OF NEUROLOGY, Issue 4 2004Kevin St. P. McNaught PhD DYT1 dystonia is a severe form of young-onset dystonia caused by a mutation in the gene that encodes for the protein torsinA, which is thought to play a role in protein transport and degradation. We describe, for the first time to our knowledge, perinuclear inclusion bodies in the midbrain reticular formation and periaqueductal gray in four clinically documented and genetically confirmed DYT1 patients but not in controls. The inclusions were located within cholinergic and other neurons in the pedunculopontine nucleus, cuneiform nucleus, and griseum centrale mesencephali and stained positively for ubiquitin, torsinA, and the nuclear envelope protein lamin A/C. No evidence of inclusion body formation was detected in the substantia nigra pars compacta, striatum, hippocampus, or selected regions of the cerebral cortex. We also noted tau/ubiquitin-immunoreactive aggregates in pigmented neurons of the substantia nigra pars compacta and locus coeruleus in all four DYT1 dystonia cases, but not in controls. This study supports the notion that DYT1 dystonia is associated with impaired protein handling and the nuclear envelope. The role of the pedunculopontine and cuneiform nuclei, and related brainstem other involved brainstem structures in mediating motor activity and muscle tone also suggest that alterations in these structures, in mediating motor activity and controlling muscle tone suggests that alterations in these structures could underlie the pathophysiology of DYT1 dystonia. Ann Neurol 2004 [source] The investigation of putative agents, using an in vitro model, to prevent cavernosal smooth muscle dysfunction during low-flow priapismBJU INTERNATIONAL, Issue 8 2008Asif Muneer OBJECTIVE To investigate the effect of putative agents for preventing irreversible smooth muscle dysfunction, using an in vitro model of low-flow priapism (a condition conventionally managed using a combination of corporal blood aspiration and instillation of ,-adrenergic agonists), as failure of detumescence results in a high incidence of erectile dysfunction. MATERIALS AND METHODS We investigated the effects of several agents (N-acetylcysteine, BayK 8644, glutathione, digoxin, calcium and N, -nitro- l -arginine methyl ester) on the recovery of smooth muscle tone after exposure to 4 h of a combination of hypoxia, glucopenia and acidosis in corpus cavernosum isolated from rabbit. RESULTS After 4 h of ischaemia, none of the agents were able to prevent irreversible smooth muscle dysfunction. CONCLUSION Prolonged low-flow priapism leads to smooth muscle dysfunction and fibrosis within the corpus cavernosum. When ,-adrenergic agents fail to reverse the condition, surgical intervention is required. We showed that the administration of novel agents, including antioxidants, does not prevent smooth muscle dysfunction. [source] Sustained beneficial effects of intraprostatic botulinum toxin type A on lower urinary tract symptoms and quality of life in men with benign prostatic hyperplasiaBJU INTERNATIONAL, Issue 5 2006Yao-Chi Chuang OBJECTIVE To present a comprehensive experience with intraprostatic botulinum toxin-type A (BoNT-A) injection in men with symptomatic benign prostatic hyperplasia (BPH) and to assess the efficacy on lower urinary tract symptoms (LUTS) and quality of life (QoL). PATIENTS AND METHODS In all, 41 men (mean age 69.1 years, sd 7.1 ) with an International Prostate Symptom Score of ,,8, peak flow rate of <12 mL/s, and who were refractory to medical treatment were injected with BoNT-A (Botox®, Allergan, Inc., CA, USA) at 100 U (21 men, for prostate volume <30 mL) or 200 U (20, for prostate volume >30 mL) into the prostate transperineally under transrectal ultrasonography guidance. Study exclusion criteria were confirmed or suspected malignancy, previous pelvic surgery or trauma and previous invasive treatment for BPH. The clinical effects were evaluated at baseline and at 1, 3 and 6 months after treatment. RESULTS There were no significant local or systemic side-effects in any men. LUTS and QoL indices improved by >30% in 31 of the 41 men (76%), and four of five men with urinary retention for >1 month could void spontaneously at 1 week to 1 month after the BoNT-A injection. In 12 of 41 men (29%) there was no change in prostate volume, yet seven of these men still had a >30% improvement in maximum flow rate, LUTS and QoL. The efficacy was sustained at 12 months. CONCLUSION BoNT-A injected into the prostate is safe and effective for men with symptomatic BPH. The mechanisms of relief of symptoms might not depend totally on the volume shrinkage; the inhibitory effect on the smooth muscle tone and aberrant sensory function might also be important. [source] Efficacy and safety of NT 201 for upper limb spasticity of various etiologies , a randomized parallel-group studyACTA NEUROLOGICA SCANDINAVICA, Issue 4 2010M. Barnes Barnes M, Schnitzler A, Medeiros L, Aguilar M, Lehnert-Batar A, Minnasch P. Efficacy and safety of NT 201 for upper limb spasticity of various etiologies , a randomized parallel-group study. Acta Neurol Scand: 2010: 122: 295,302. © 2010 John Wiley & Sons A/S. Objective,,, To assess efficacy and safety of two dilutions of botulinum neurotoxin type A NT 201 (Xeomin®) in patients with upper limb spasticity of diverse etiology. Methods,,, Changes in functional disability and muscle tone from baseline to week 4 after NT 201 treatment. Results,,, One hundred ninety-two patients with stroke, brain injury, multiple sclerosis, or cerebral palsy were randomized to either 50 or 20 U/ml NT 201 dilutions. The maximum total NT 201 dose was 495 units. Four weeks post-injection, a , 1-point reduction was observed on the Disability Assessment Scale in 57.1%, and on the Ashworth scale in , 62.2% of patients. The 20 U/ml NT 201 dilution was non-inferior to the 50 U/ml NT 201 dilution. Global improvement was rated high by patients (80.2%) and investigators (89.0%). Conclusions,,, NT 201 improved functional disability and muscle tone and was well tolerated in patients with upper limb spasticity of diverse etiology in both dilutions. [source] Botulinumtoxin A treatment in toddlers with cerebral palsyACTA PAEDIATRICA, Issue 8 2010K Tedroff Abstract Aims:, In this study the aim was to evaluate the effect of botulinum toxin A (BoNT-A) treatment on muscle tone, contracture development and gait pattern in young children with cerebral palsy (CP). Method:, Fifteen children with spastic CP (mean age = 16 months) were included in a randomized control study. All received a daily stretching programme and children in the BoNT-A group additionally received two injections, 6 months apart in the gastrocnemius muscle. Outcomes were assessed at baseline, and after 1 and 3.5 years. A 3D gait-analysis was performed at 5 years of age. Results:, Plantarflexor muscle tone in the BoNT-A group was significantly reduced after 3.5 years, while the muscle tone at the ankle and knee in the control group remained unchanged. The change-score in knee-flexion muscle tone between the groups was significantly different after 3.5 years. The knee joint ROM was significantly increased at 1 year in the BoNT-A group but reduced at the knee and ankle joints in the control group after 3.5 years. No group differences were found for gait analysis, GMFM-66 or PEDI. Conclusion:, Early treatment of BoNT-A in children with spastic CP may decrease muscle tone and decelerate contracture development after 3.5 years. The effect on gait development remains inconclusive. [source] Variations of Apgar score of very low birth weight infants in different neonatal intensive care unitsACTA PAEDIATRICA, Issue 9 2009Mario Rüdiger Abstract Objective:, The Apgar score should be an objective method to assess the state of newborns; however, its applicability in preterm infants is hampered by large variations among different observers. The study tested whether physicians that give low scores to written case descriptions also apply lower scores to preterm infants. Patients and Methods:, Descriptions (BMJ 2004; 329: 143,4) were sent to 14 neonatal units. Physicians were asked to evaluate the Apgar (case score). From seven units Apgar scores of all very low birth weight infants (VLBW) born between January 2004 and December 2006 were obtained from charts (clinical score). Results:, In total, 121 physicians from 14 institutions (median 9, range 3,15) replied: 24 residents with <6-month and 28 with >6-month neonatal experience, and 69 consultants. The assessment of the case scores was very heterogeneous with large variations in respiration, muscle tone and reflexes. Clinical scores were obtained from 1000 VLBW infants. The score depended on the gestational age, with a median of 4 at 24 and 7 at 27 weeks. With one exception, centres that assigned low case scores had also low clinical scores. Conclusion:, There is considerable variation in assigning Apgar scores. Definitions are required to apply the Apgar score to infants under clinical conditions such as preterm delivery, resuscitation or artificial ventilation. [source] RALOXIFENE, TAMOXIFEN AND VASCULAR TONECLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2007Fung Ping Leung SUMMARY 1Oestrogen deficiency causes progressive reduction in endothelial function. Despite the benefits of hormone-replacement therapy (HRT) evident in earlier epidemiological studies, recent randomized trials of HRT for the prevention of heart disease found no overall benefit. Instead, HRT users had higher incidences of stroke and heart attack. Most women discontinue HRT because of its many side-effects and/or the increased risk of breast and uterine cancer. This has contributed to the development of selective oestrogen receptor modulators (SERMs), such as tamoxifen and raloxifene, as alternative oestrogenic agents. 2A SERM is a molecule that binds with high affinity to oestrogen receptors but has tissue-specific effects distinct from oestrogen, acting as an oestrogen agonist in some tissues and as an antagonist in others. Clinical and animal studies suggest multiple cardiovascular effects of SERMs. For example, raloxifene lowers serum levels of cholesterol and homocysteine, attenuates oxidation of low-density lipoprotein, inhibits endothelial,leucocyte interaction, improves endothelial function and reduces vascular smooth muscle tone. 3Available evidence suggests that raloxifene and tamoxifen are capable of acting directly on both endothelial cells and the underlying vascular smooth muscle cells and cause a multitude of favourable modifications of the vascular wall, which jointly contribute to improved local blood flow. The outcome of the Raloxifene Use for the Heart (RUTH) trial will determine whether raloxifene, currently approved for the treatment of post-menopausal osteoporosis, could substitute for HRT in alleviating cardiovascular symptoms in post-menopausal women. [source] RELAXANT EFFECT OF ADRENOMEDULLIN ON BOVINE ISOLATED IRIS SPHINCTER MUSCLE UNDER RESTING CONDITIONSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2005Y Uchikawa SUMMARY 1.,The mechanisms involved in the fine adjustment of iris sphincter muscle tone are largely unknown. The aim of the present study was to clarify the effects of adrenomedullin on the resting tension of the bovine isolated iris sphincter muscle. 2.,The motor activity of the bovine isolated iris sphincter muscle was measured isometrically. The effects of adrenomedullin on resting tension were analysed in the presence of indomethacin. The presence of adrenomedullin mRNA in the preparation was determined by reverse transcription,polymerase chain reaction. Immunolabelling for adrenomedullin was also performed. 3.,Adrenomedullin significantly decreased the resting tension of the muscle. The relaxant effect of adrenomedullin was significantly inhibited by adrenomedullin (22,52), a putative antagonist for the adrenomedullin receptor, or calcitonin gene-related peptide (CGRP) (8,37), a putative antagonist for the CGRP1 receptor. The relaxant effect was almost completely blocked by a combination of adrenomedullin (22,52) and CGRP (8,37). 4.,The relaxant effect of adrenomedullin was also significantly diminished by 2,,5,-dideoxyadenosine, an inhibitor of adenylate cyclase, NG -nitro- l -arginine, an inhibitor of nitric oxide synthesis, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase. 5.,Reverse transcription,polymerase chain reaction analysis showed that adrenomedullin mRNA was expressed in the muscle strip. Immunopositive staining for adrenomedullin was detected in blood vessel cells and in the iris sphincter muscle cells. 6.,These results suggest that adrenomedullin may be an autocrine and paracrine regulator of the resting tension of the iris sphincter muscle. Its biological effects may be due to the direct involvement of adrenomedullin receptors and also to the stimulation of CGRP1 receptors. The stimulation of these receptors by the peptide leads to the activation of adenylate cyclase and soluble guanylate cyclase and subsequent relaxation of the muscle strip. [source] |