Effects of the herbal preparation STW 5-II on in vitro muscle activity in the guinea pig stomach.

BACKGROUND: STW 5 is a combination of nine medicinal herbal extracts and used to treat functional gastrointestinal disorders including functional dyspepsia. It has a region-specific effect by relaxing the proximal and contracting the distal stomach. The research combination STW 5-II (Iberogast® Advance) lacks three herbal extracts but seems clinically as effective as STW 5. However, the action of STW 5-II on gastric motility is unknown. METHODS: In vitro circular and longitudinal muscle tone and contractility were recorded from guinea pig gastric fundus and antrum with isometric force transducers. KEY RESULTS: STW 5-II decreased concentration-dependently (64-512 µg/ml) the tone of circular and longitudinal muscle strips from the fundus. In contrast, STW 5-II increased concentration-dependently contraction amplitude in antral circular and longitudinal muscle. The effects were region-dependent but comparable in the two muscle layers. Application of 512 µg STW 5 or STW 5-II revealed comparable effects in the fundus and antrum circular and longitudinal muscle strips. CONCLUSIONS AND INTERFERENCES: STW 5-II had a region-specific effect and relaxed the proximal stomach but increased the contractility in the antrum. It was as effective as STW 5 which may explain its comparable clinical effects in treating functional dyspepsia. Impaired accommodation may be normalized through relaxation of the fundus, while the motility-promoting effects leading to an increase in antral motility may activate the gastric pump.

Exploration of the establishment of manganese poisoning rat model and analysis of discriminant methods.

OBJECTIVE: We explored methods to establish an animal model of manganese poisoning and evaluate the feasibility of the determination method. METHODS: Twenty-four specific pathogen-free male rats were randomly divided into four groups: control, low-dose (15.0 mg/kg), middle-dose (25.0 mg/kg), and high-dose (50.0 mg/kg). Intraperitoneal injection of MnCl2·H2O was administered every 48 h for three months. Rats were tested for behavior, muscle tension, and with a balance beam experiment at the end of each month. Three months later, the rats were sacrificed and brain tyrosine hydroxylase (TH) expression levels were measured. RESULTS: Rats in each group exhibited changes in behavior, muscle tone, and balance after exposure to manganese, and the scores of each test for the high-dose and middle-dose groups were statistically different from the low-dose and control groups. Finally, a rat model of manganese poisoning was identified with the TH expression less than 30% of the normal value. We find that the modeling success rate of the middle-dose and high-dose groups were 66.67% and 100%, respectively. In addition, there were negative correlations between the three assessment methods such as behavioral tests and TH expression levels. CONCLUSIONS: Intraperitoneal injection of MnCl2·H2O (25 mg/kg) can successfully establish a manganese poisoning rat model with low mortality rate. Muscle tension, balance beam, and behavioral tests can be used as preliminary determination methods for modeling.

The effect of topical thiocolchicoside in preventing and reducing the increase of muscle tone, stiffness, and soreness: A real-life study on top-level road cyclists during stage competition.

In professional road cyclists, the majority of overuse injuries affect the lower limbs and are mostly represented by contractures or muscle shortening, characterized by an increase of tone and stiffness and a variation of elasticity. Treatment and prevention of these specific conditions may include physical, supplementary, and pharmacologic support. The aim of this real-life study was to determine: first, the alterations of tone, stiffness, elasticity, and soreness of rectus femoris (RF) and biceps femoris (BF) in top class cyclists engaged in 3 multistage races, and second, whether any variable in the management of the athletes may affect the prevention and/or reduction of such alterations.Twenty-three professional cyclists competing in 3 international, cycling stage races were assessed. Athletes could receive, upon the approval of the medical staff, physical, dietary, and/or pharmacological management which could include treatments with topical over-the-counter myorelaxants to prevent and/or reduce muscle contractures. MyotonPro was used to daily measure tone, stiffness, and elasticity in RF and BF in relaxed and contracted state after every stage. In parallel, BF and RF soreness was also assessed with a Likert scale.All athletes received the same general massage management; none of them received dietary supplements; some of the athletes were treated with a topical myorelaxant thiocolchicoside (TCC 0.25%) foam 3 times daily. TCC was identified as the only variable able to affect these muscle parameters in the cyclists. Tone, stiffness (regardless of the state), and soreness significantly increased over time either in BF or RF in all athletes. In the group of athletes that used TCC (n = 11; TCC+) the increase in tone, stiffness, and soreness was significantly lower than in the group not receiving TCC (n = 12; No-TCC). Elasticity varied coherently with tone and stiffness.A very intense and protracted sport activity increases muscular tone, stiffness, and soreness over time. Topical TCC foam significantly attenuates these alterations and might represent an efficient strategy both to prevent and manage contractures and their consequences in professional cyclists as well in athletes from other disciplines involving similar workloads.

Influence of clove oil and eugenol on muscle contraction of silkworm (Bombyx mori).

Clove oil is used in fish anesthesia and expected to have a mechanism via glutamic receptor. The present study explores the activities of clove oil and its major compound, eugenol, in comparison with L-glutamic acid on glutamic receptor of silkworm muscle and fish anesthesia. It was found that clove oil and eugenol had similar effects to L-glutamic acid on inhibition of silkworm muscle contraction after treated with D-glutamic acid and kainic acid. Anesthetic activity of the test samples was investigated in goldfish. The results demonstrated that L-glutamic acid at 20 and 40 mM could induce the fish to stage 3 of anesthesia that the fish exhibited total loss of equilibrium and muscle tone, whereas clove oil and eugenol at 60 ppm could induce the fish to stage 4 of anesthesia that the reflex activity of the fish was lost. These results suggest that clove oil and eugenol have similar functional activities and mechanism to L-glutamic acid on muscle contraction and fish anesthesia.

Muscle-Nerve-Muscle Grafting for Facial Reanimation in Rats.

OBJECTIVE: Facial paralysis is a devastating condition leaving patients with a myriad of aesthetic and functional consequences. Muscle-nerve-muscle (MNM) neurotization is a reinnervation technique that involves implanting an autogenous nerve graft as a conduit between an innervated "donor" muscle and a denervated "recipient" muscle. We investigated the use of MNM reinnervation, alone or in combination with electrical stimulation (ES) and testosterone propionate (TP) in comparison to nerve reanastomosis (RE), on functional recovery following rat facial nerve injury. METHODS: Thirty-one male, Sprague-Dawley rats were assigned to groups: no graft (control), MNM grafting alone (MNM), MNM grafting with ES and TP (MNM+ES+TP), or RE. Harvested right facial nerve branches were used as the MNM graft. Functional recovery was assessed by behavioral observations and electromyographic recordings. RESULTS: The MNM grafting improved muscle tone and vibrissae movement. The ES+TP treatment further enhanced muscle tone as well as reduced recovery time for coordinated movement in a manner that is comparable to those of RE. Electromyographic recordings demonstrated electrical conductance across all MNM grafts. CONCLUSION: These data have important implications for patients with unilateral paralysis from facial or laryngeal nerve injury, particularly those who are not candidates for nerve reanastomosis.

Comparison of saddle, lumbar epidural and caudal blocks on anal sphincter tone: A prospective, randomized study.

Objective To compare the effects of saddle, lumbar epidural and caudal blocks on anal sphincter tone using anorectal manometry. Methods Patients undergoing elective anorectal surgery with regional anaesthesia were divided randomly into three groups and received a saddle (SD), lumbar epidural (LE), or caudal (CD) block. Anorectal manometry was performed before and 30 min after each regional block. The degree of motor blockade of the anal sphincter was compared using the maximal resting pressure (MRP) and the maximal squeezing pressure (MSP). Results The study analysis population consisted of 49 patients (SD group, n = 18; LE group, n = 16; CD group, n = 15). No significant differences were observed in the percentage inhibition of the MRP among the three regional anaesthetic groups. However, percentage inhibition of the MSP was significantly greater in the SD group (83.6 ± 13.7%) compared with the LE group (58.4 ± 19.8%) and the CD group (47.8 ± 16.9%). In all groups, MSP was reduced significantly more than MRP after each regional block. Conclusions Saddle block was more effective than lumbar epidural or caudal block for depressing anal sphincter tone. No differences were detected between lumbar epidural and caudal blocks.

Effective treatment of spasticity using dronabinol in pediatric palliative care.

BACKGROUND: Cannabis extracts have a wide therapeutic potential but in many countries they have not been approved for treatment in children so far. OBJECTIVE: We conducted an open, uncontrolled, retrospective study on the administration of dronabinol to determine the value, efficacy, and safety of cannabis-based medicines in the treatment of refractory spasticity in pediatric palliative care. DESIGN AND PARTICIPANTS: Sixteen children, adolescents and young adults having complex neurological conditions with spasticity (aged 1.3-26.6 years, median 12.7 years) were treated with dronabinol by our specialized pediatric palliative care team between 01.12.2010 and 30.04.2015 in a home-care setting. Therapeutic efficacy and side effects were closely monitored. RESULTS: Drops of the 2.5% oily tetrahydrocannabinol solution (dronabinol) were administered. A promising therapeutic effect was seen, mostly due to abolishment or marked improvement of severe, treatment resistant spasticity (n = 12). In two cases the effect could not be determined, two patients did not benefit. The median duration of treatment was 181 days (range 23-1429 days). Dosages to obtain a therapeutic effect varied from 0.08 to 1.0 mg/kg/d with a median of 0.33 mg/kg/d in patients with a documented therapeutic effect. When administered as an escalating dosage scheme, side effects were rare and only consisted in vomiting and restlessness (one patient each). No serious and enduring side effects occurred even in young children and/or over a longer period of time. CONCLUSIONS: In the majority of pediatric palliative patients the treatment with dronabinol showed promising effects in treatment resistant spasticity.

Inhaled Umeclidinium in COPD Patients: A Review and Meta-Analysis.

A number of new agents for the management of chronic obstructive pulmonary disease (COPD) are at different stages of development, including several inhaled long-acting antimuscarinics (LAMA). Long-acting bronchodilators are considered to be central to the management of COPD due to the evidence supporting their efficacy and safety. Umeclidinium, a LAMA, has recently been approved for the maintenance treatment of moderate to very severe COPD in a number of countries. This comprehensive review and pooled meta-analysis provides detailed information about the efficacy and safety of this agent. The pharmacokinetics and pharmacodynamics of umeclidinium observed in phase I and II studies support its once-daily administration. Umeclidinium is rapidly cleared from blood, and renal or hepatic impairment do not lead to significant changes in drug disposition. A pooled analysis of phase III and comparative studies of umeclidinium in patients with moderate to very severe COPD showed significant improvement in lung function measures, including trough forced expiratory volume in 1 s (FEV1), as well as in acute exacerbations of COPD, dyspnea, and quality of life. Adverse effects, including known anticholinergic effects, were uncommon with umeclidinium. Limited data suggest the efficacy of umeclidinium is similar to that of tiotropium. Umeclidinium is administered as a dry powder inhaler, provides adequate lung delivery in patients with moderate to very severe airflow obstruction, and appears to be easily used by patients. Umeclidinium provides a safe and effective option as an inhaled LAMA for the management of COPD.

Combining Sprague-Dawley rat uterus cell membrane chromatography with HPLC/MS to screen active components from Leonurus artemisia.

CONTEXT: Leonurus artemisia (Lour.) S.Y.Hu (Lamiaceae) (YiMuCao in Chinese) is a traditional Chinese medicine. Leonurus artemisia has been shown to have many pharmacological effects such as increasing uterine contraction amplitude, and tension, but the active components are still unknown. OBJECTIVE: The objective of this study is to determine active components of L. Artemisia that are responsible for the biological activity using HPLC and cell membrane-based system. MATERIALS AND METHODS: The whole L. artemisia ethanol extract and its eight fractions were screened using Sprague-Dawley rat uterus cell membrane chromatography (CMC) combined with the HPLC/MS system. Oxytocin was used to investigate the activity of CMC column. The effect of active components screened from L. artemisia was studied by tension measurement of isolated rat uterine strips in vitro at a dose of 10(-7)-10(-4 )mol/L with oxytocin as a control. RESULTS: The acetone extract showed obvious activity when compared with the eight extracts of L. artemisia. From the acetone extract, in the negative ionization mode, the active compound was identified as genkwanin, with a molecular weight of 283. In vitro pharmacological experiments proved that genkwanin promoted uterine contractions at a dose from 10(-7) to 10(-4 )mol/L. The EC50 value was 4.86 ± 4.21 µmol/L for genkwanin and 4.30 ± 3.65 µmol/L for oxytocin on the contractile amplitude of uterine strips isolated from rats. DISCUSSION AND CONCLUSION: Genkwanin was identified as the active compound in L. artemisia by this method. In vitro pharmacological experiments proved that genkwanin promoted uterine contractions. Genkwanin may be used to uterine inertia and may have an effect on postpartum hemorrhage.

Relaxant effects of a hydroalcoholic extract of Ruta graveolens on isolated rat tracheal rings.

BACKGROUND: Ruta graveolens L. (R. graveolens) is a medicinal plant employed in non-traditional medicines that has various therapeutic properties, including anthelmintic, and vasodilatory actions, among others. We evaluated the trachea-relaxant effects of hydroalcoholic extract of R. graveolens against potassium chloride (KCl)- and carbachol-induced contraction of rat tracheal rings in an isolated organ bath. RESULTS: The results showed that the airway smooth muscle contraction induced by the depolarizing agent (KCl) and cholinergic agonist (carbachol) was markedly reduced by R. graveolens in a concentration-dependent manner, with maximum values of 109 ± 7.9 % and 118 ± 2.6 %, respectively (changes in tension expressed as positive percentages of change in proportion to maximum contraction), at the concentration of 45 µg/mL (half-maximal inhibitory concentration IC50: 35.5 µg/mL and 27.8 µg/mL for KCl- and carbachol-induced contraction, respectively). Additionally, the presence of R. graveolens produced rightward parallel displacement of carbachol dose-response curves and reduced over 35 % of the maximum smooth muscle contraction. CONCLUSIONS: The hydroalcoholic extract of R. graveolens exhibited relaxant activity on rat tracheal rings. The results suggest that the trachea-relaxant effect is mediated by a non-competitive antagonistic mechanism. More detailed studies are needed to identify the target of the inhibition, and to determine more precisely the pharmacological mechanisms involved in the observed biological effects.

Cutaneous Application of Silicone Wafers Containing Carbon Microcoils: Efficacy in Relieving Chronic Muscle Tension and Pain.

BACKGROUND: Chronic musculoskeletal pain is highly prevalent worldwide. PRIMARY STUDY OBJECTIVE: The aim of this study was to evaluate the efficacy of Helical(®) microcoils, a new, noninvasive treatment for chronic musculoskeletal pain. DESIGN: This was a prospective, observational study. SETTING: The study was conducted at the main author's private clinic, in São Paulo, Brazil. PARTICIPANTS: We evaluated 20 physicians, from 2 different hospitals, who suffered from chronic musculoskeletal pain and volunteered to participate in the study. INTERVENTION: The Helical(®) microcoils were applied to the skin over the affected areas. Before and after the intervention, the physician-patients completed questionnaires and a visual analog scale. PRIMARY OUTCOME MEASURES: We quantified postintervention improvement or worsening of pain and muscle tension. RESULTS: Significant improvements in pain and muscle tension were observed in 95% of the physician-patients evaluated. The only side effect reported was mild pruritus at the application site, which occurred in 5 of the 20 cases. CONCLUSION: The use of Helical microcoils was found to be safe and efficacious in relieving muscle tension and pain.

The administration of Fructus Schisandrae attenuates dexamethasone-induced muscle atrophy in mice.

In the present study, we aimed to determine whether ethanol extracts of Fructus Schisandrae (FS), the dried fruit of Schizandra chinensis Baillon, mitigates the development of dexamethasone-induced muscle atrophy. Adult SPF/VAT outbred CrljOri:CD1 (ICR) mice were either treated with dexamethasone to induce muscle atrophy. Some mice were treated with various concentrations of FS or oxymetholone, a 17α-alkylated anabolic-androgenic steroid. Muscle thickness and weight, calf muscle strength, and serum creatine and creatine kinase (CK) levels were then measured. The administration of FS attenuated the decrease in calf thickness, gastrocnemius muscle thickness, muscle strength and weight, fiber diameter and serum lactate dehydrogenase levels in the gastrocnemius muscle bundles which was induced by dexamethasone in a dose-dependent manner. Treatment with FS also prevented the dexamethasone-induced increase in serum creatine and creatine kinase levels, histopathological muscle fiber microvacuolation and fibrosis, and the immunoreactivity of muscle fibers for nitrotyrosine, 4-hydroxynonenal, inducible nitric oxide synthase and myostatin. In addition, the destruction of the gastrocnemius antioxidant defense system was also inhibited by the administration of FS in a dose-dependent manner. FS downregulated the mRNA expression of atrogin-1 and muscle ring-finger protein-1 (involved in muscle protein degradation), myostatin (a potent negative regulator of muscle growth) and sirtuin 1 (a representative inhibitor of muscle regeneration), but upregulated the mRNA expression of phosphatidylinositol 3-kinase, Akt1, adenosine A1 receptor and transient receptor potential cation channel subfamily V member 4, involved in muscle growth and the activation of protein synthesis. The overall effects of treatment with 500 mg/kg FS were comparable to those observed following treatment with 50 mg/kg oxymetholone. The results from the present study support the hypothesis that FS has a favorable ameliorating effect on muscle atrophy induced by dexamethasone, by exerting anti-inflammatory and antioxidant effects on muscle fibers, which may be due to an increase in protein synthesis and a decrease in protein degradation.

Bufei Jianpi granules improve skeletal muscle and mitochondrial dysfunction in rats with chronic obstructive pulmonary disease.

BACKGROUND: Bufei Jianpi granules has been confirmed effective in improving pulmonary function, alleviating acute exacerbations, improving six-minute walk distance and quality of life, and benefited in 12-month follow-up in chronic obstructive pulmonary disease (COPD) patients with syndrome of lung-spleen qi deficiency. Skeletal muscle dysfunction (SMD), an important extrapulmonary complication, occurs in the very initiation of COPD and is closely related to morbidity and mortality. To evaluate the efficacy of Bufei Jianpi granules on SMD, we observed skeletal muscular function and histomorphology, mitochondrial morphormetry and proteins in COPD rats induced by cigarette-smoke and Klebsiella pneumoniae. METHODS: Seventy-two Sprague-Dawley rats were randomized into Control + Saline, Control + Bufei Jianpi, Control + Aminophylline, COPD + Saline, COPD + Bufei Jianpi and COPD + Aminophylline groups. From week 9 to 20, rats were administrated intragastricly by normal saline, Bufei Jianpi granules and aminophylline, respectively. Muscular tension and fatigue index of intercostal muscle, quadriceps, biceps and soleus were detected by using electrophysiological technology. Pathological and ultrastructural changes and expressions of mitochondrial Bcl-2 nineteen-kilodalton interacting protein 3 (Bnip3) and cytoplasm cytochrome C (Cyto C) in the four skeletal muscles were observed by using optical and electron microscope and western blotting. RESULTS: There was no statistical difference among the control rats treated with saline, Bufei Jianpi granules or aminophylline in above-mentioned parameters. Muscular tension, mitochondria volume density (Vv) and compared membrane surface (δm) of the four muscles were significantly lower in COPD + Saline group compared to Control + Saline group, while fatigue index, mitochondria surface area (δ), Bnip3 and Cyto C were higher (P < 0.05). COPD rats showed more morphological changes in muscle tissues than controls, such as atrophy, degeneration, necrosis and matrix hyperplasia. Utrastructurally, mitochondria populations decreased significantly in the four muscles, and were shrunken and even cavitation changed. The up-mentioned parameters were improved in Bufei Jianpi group (P < 0.05) in the four muscles. CONCLUSIONS: Bufei Jianpi granules can improve skeletal muscle function via improving mitochondria population and function, reducing apoptotic factors such as Bnip3 and Cyto C, and is more effective than aminophylline.

Relaxant effects of a hydroalcoholic extract of Ruta graveolens on isolated rat tracheal rings

BACKGROUND: Ruta graveolens L. (R. graveolens) is a medicinal plant employed in non-traditional medicines that has various therapeutic properties, including anthelmintic, and vasodilatory actions, among others. We evaluated the trachea-relaxant effects of hydroalcoholic extract of R. graveolens against potassium chloride (KCl)- and carbachol-induced contraction of rat tracheal rings in an isolated organ bath. RESULTS: The results showed that the airway smooth muscle contraction induced by the depolarizing agent (KCl) and cholinergic agonist (carbachol) was markedly reduced by R. graveolens in a concentration-dependent manner, with maximum values of 109 ± 7.9 % and 118 ± 2.6 %, respectively (changes in tension expressed as positive percentages of change in proportion to maximum contraction), at the concentration of 45 µg/mL (half-maximal inhibitory concentration IC50: 35.5 µg/mL and 27.8 µg/mL for KCl- and carbachol-induced contraction, respectively). Additionally, the presence of R. graveolens produced rightward parallel displacement of carbachol dose-response curves and reduced over 35 % of the maximum smooth muscle contraction. CONCLUSIONS: The hydroalcoholic extract of R. graveolens exhibited relaxant activity on rat tracheal rings. The results suggest that the trachea-relaxant effect is mediated by a non-competitive antagonistic mechanism. More detailed studies are needed to identify the target of the inhibition, and to determine more precisely the pharmacological mechanisms involved in the observed biological effects.

[Comparison of paravertebral soft tissue tension changes in patients with chronic lower back pain treated by sliver needle and traditional Chinese medicine fumigation].

OBJECTIVE: To evaluate clinical significance of waist soft tissue tension detection in treating chronic nonspecific low back pain. METHODS: From August 2011 to March 2012,60 patients with chronic nonspecific low back pain were divided into two groups (sliver needle group and TCM fumigation group) according to propotion of 1:1. In sliver needle group, there were 17 males and 13 females aged from 28 to 55 years old with an average age of (45.70 +/- 4.15), treated with sliver needle; In TCM fumigation group,there were 19 males and 11 females aged from 27 to 55 years old with an average age of (43.03 +/- 5.86), treated with TCM fumigation. Changes of force-displacement distance (FDD), specific absorption rate (S) of two groups were observed before treatment, 1 week and 3 months after treatment respectively, VAS scoring and Roland-Morris disability questionnaire (RMDQ) were used to access clinical effects. RESULTS: (1) VAS score of silver needle group was 4.77 +/- 0.78, 1.99 +/- 1.08 and 2.55 +/- 0.94, respectively before treatment, at 1 week and 3 months after treatment,while VAS score in TCM fumigation group were 4.43 +/- 0.61, 2.48 +/- 0.71 and 3.05 +/- 0.86, respectively. VAS score of two groups after treatment were sigificant decrease than that of before treatment (P < 0.05). There was no sigificant differences between two groups before treatment, but sliver needle group performed well in analgesia than TCM fumigation group, and had obvious differences (P < 0.05). RMDQ score of silver needle group was 13.63 +/- 1.96, 5.87 +/- 2.33 and 6.53 +/- 2.89, respectively before treatment, at 1 week and 3 months after treatment, while RMDQ score in TCM fumigation group were 13.40 +/- 2.01, 6.90 +/- 2.31, 9.23 +/- 2.87, respectively. There was no significant differences between two groups before treatment and 1 week after treatment (P > 0.05), and had obvious differences between two groups at 3 months after treatment (P < 0.01). Both groups could obvious improve dysfunction caused by chronic low back pain, and curative effect of sliver needle groups was more endurable. (2) Following-up at 3 months after treatment, FDD of multifidus, erector spinae of effected side and multifidus of healthy in sliver needle group were obvious increased (P < 0.05); In TCM fumigation group, FDD of multifidus and erector spinae on both side were increased at 1 week after treatment (P < 0.05), but had no significant meaning at 3 months after treatment on health side (P>0.05). There was no significant meaning before treatment (P > 0.05), FDD of multifidus, erector spinae of effected side in sliver needle group were obvious increased at 1 week after treatment (P < 0.05); but no obvious meaning on health side. FDD of both side in sliver needle group were obvious increased at 3 months after treatment. (3) There was correlation among differences of FDD in multifidus and erector spinae, VAS score and differences of RMDQ, and Spearman correlation coefficient R was 0.517, 0.811, 0.746 and 0.625; There was correlation between items of soft tissue tension and sympotoms, function and life quality. Conclusion:Soft tissue tension detection can effectively manifest degree of pain and dysfunction of low back, and improve objectivity of therapeutic evaluation for chronic low back pain.

Myorelaxant effect of bee venom topical skin application in patients with RDC/TMD Ia and RDC/TMD Ib: a randomized, double blinded study.

The aim of the study was the evaluation of myorelaxant action of bee venom (BV) ointment compared to placebo. Parallel group, randomized double blinded trial was performed. Experimental group patients were applying BV for 14 days, locally over masseter muscles, during 3-minute massage. Placebo group patients used vaseline for massage. Muscle tension was measured twice (TON1 and TON2) in rest muscle tonus (RMT) and maximal muscle contraction (MMC) on both sides, right and left, with Easy Train Myo EMG (Schwa-medico, Version 3.1). Reduction of muscle tonus was statistically relevant in BV group and irrelevant in placebo group. VAS scale reduction was statistically relevant in both groups: BV and placebo. Physiotherapy is an effective method for myofascial pain treatment, but 0,0005% BV ointment gets better relief in muscle tension reduction and analgesic effect. This trial is registered with Clinicaltrials.gov NCT02101632.

Soluble guanylyl cyclase (sGC) degradation and impairment of nitric oxide-mediated responses in urethra from obese mice: reversal by the sGC activator BAY 60-2770.

Obesity has emerged as a major contributing risk factor for overactive bladder (OAB), but no study examined urethral smooth muscle (USM) dysfunction as a predisposing factor to obesity-induced OAB. This study investigated the USM relaxant machinery in obese mice and whether soluble guanylyl cyclase (sGC) activation with BAY 60-2770 [acid 4-({(4-carboxybutyl) [2-(5-fluoro-2-{[4-(trifluoromethyl) biphenyl-4-yl] methoxy} phenyl) ethyl] amino} methyl) benzoic] rescues the urethral reactivity through improvement of sGC-cGMP (cyclic guanosine monophosphate) signaling. Male C57BL/6 mice were fed for 12 weeks with a high-fat diet to induce obesity. Separate groups of animals were treated with BAY 60-2770 (1 mg/kg per day for 2 weeks). Functional assays and measurements of cGMP, reactive-oxygen species (ROS), and sGC protein expression in USM were determined. USM relaxations induced by NO (acidified sodium nitrite), NO donors (S-nitrosoglutathione and glyceryl trinitrate), and BAY 41-2272 [5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-pyrimidin-4-ylamine] (sGC stimulator) were markedly reduced in obese compared with lean mice. In contrast, USM relaxations induced by BAY 60-2770 (sGC activator) were 43% greater in obese mice (P < 0.05), which was accompanied by increases in cGMP levels. Oxidation of sGC with ODQ [1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one] (10 µM) potentiated BAY 60-2770-induced USM responses in the lean group. Long-term oral BAY 60-2770 administration fully prevented the impairment of USM relaxations in obese mice. Reactive-oxygen species (ROS) production was enhanced, but protein expression of ß1 second guanylate cyclase subunit was reduced in USM from obese mice, both of which were restored by BAY 60-2770 treatment. In conclusion, impaired USM relaxation in obese mice is associated with ROS generation and down-regulation of sGC-cGMP signaling. Prevention of sGC degradation by BAY 60-2770 ameliorates the impairment of urethral relaxations in obese mice.

Additive effects of beta-alanine and sodium bicarbonate on upper-body intermittent performance.

We examined the isolated and combined effects of beta-alanine (BA) and sodium bicarbonate (SB) on high-intensity intermittent upper-body performance in judo and jiu-jitsu competitors. 37 athletes were assigned to one of four groups: (1) placebo (PL)+PL; (2) BA+PL; (3) PL+SB or (4) BA+SB. BA or dextrose (placebo) (6.4 g day⁻¹) was ingested for 4 weeks and 500 mg kg⁻¹ BM of SB or calcium carbonate (placebo) was ingested for 7 days during the 4th week. Before and after 4 weeks of supplementation, the athletes completed four 30-s upper-body Wingate tests, separated by 3 min. Blood lactate was determined at rest, immediately after and 5 min after the 4th exercise bout, with perceived exertion reported immediately after the 4th bout. BA and SB alone increased the total work done in +7 and 8 %, respectively. The co-ingestion resulted in an additive effect (+14 %, p < 0.05 vs. BA and SB alone). BA alone significantly improved mean power in the 2nd and 3rd bouts and tended to improve the 4th bout. SB alone significantly improved mean power in the 4th bout and tended to improve in the 2nd and 3rd bouts. BA+SB enhanced mean power in all four bouts. PL+PL did not elicit any alteration on mean and peak power. Post-exercise blood lactate increased with all treatments except with PL+PL. Only BA+SB resulted in lower ratings of perceived exertion (p = 0.05). Chronic BA and SB supplementation alone equally enhanced high-intensity intermittent upper-body performance in well-trained athletes. Combined BA and SB promoted a clear additive ergogenic effect.

Multiple sclerosis and extract of cannabis: results of the MUSEC trial.

OBJECTIVE: Multiple sclerosis (MS) is associated with chronic symptoms, including muscle stiffness, spasms, pain and insomnia. Here we report the results of the Multiple Sclerosis and Extract of Cannabis (MUSEC) study that aimed to substantiate the patient based findings of previous studies. PATIENTS AND METHODS: Patients with stable MS at 22 UK centres were randomised to oral cannabis extract (CE) (N=144) or placebo (N=135), stratified by centre, walking ability and use of antispastic medication. This double blind, placebo controlled, phase III study had a screening period, a 2 week dose titration phase from 5 mg to a maximum of 25 mg of tetrahydrocannabinol daily and a 10 week maintenance phase. The primary outcome measure was a category rating scale (CRS) measuring patient reported change in muscle stiffness from baseline. Further CRSs assessed body pain, spasms and sleep quality. Three validated MS specific patient reported outcome measures assessed aspects of spasticity, physical and psychological impact, and walking ability. RESULTS: The rate of relief from muscle stiffness after 12 weeks was almost twice as high with CE than with placebo (29.4% vs. 15.7%; OR 2.26; 95% CI 1.24 to 4.13; p=0.004, one sided). Similar results were found after 4 weeks and 8 weeks, and also for all further CRSs. Results from the MS scales supported these findings. CONCLUSION: The study met its primary objective to demonstrate the superiority of CE over placebo in the treatment of muscle stiffness in MS. This was supported by results for secondary efficacy variables. Adverse events in participants treated with CE were consistent with the known side effects of cannabinoids. No new safety concerns were observed. TRIAL REGISTRATION NUMBER: NCT00552604.