Identification of new enterosynes using prebiotics: roles of bioactive lipids and mu-opioid receptor signalling in humans and mice.

OBJECTIVE: The enteric nervous system (ENS) plays a key role in controlling the gut-brain axis under normal and pathological conditions, such as type 2 diabetes. The discovery of intestinal actors, such as enterosynes, able to modulate the ENS-induced duodenal contraction is considered an innovative approach. Among all the intestinal factors, the understanding of the role of gut microbes in controlling glycaemia is still developed. We studied whether the modulation of gut microbiota by prebiotics could permit the identification of novel enterosynes. DESIGN: We measured the effects of prebiotics on the production of bioactive lipids in the intestine and tested the identified lipid on ENS-induced contraction and glucose metabolism. Then, we studied the signalling pathways involved and compared the results obtained in mice to human. RESULTS: We found that modulating the gut microbiota with prebiotics modifies the actions of enteric neurons, thereby controlling duodenal contraction and subsequently attenuating hyperglycaemia in diabetic mice. We discovered that the signalling pathway involved in these effects depends on the synthesis of a bioactive lipid 12-hydroxyeicosatetraenoic acid (12-HETE) and the presence of mu-opioid receptors (MOR) on enteric neurons. Using pharmacological approaches, we demonstrated the key role of the MOR receptors and proliferator-activated receptor γ for the effects of 12-HETE. These findings are supported by human data showing a decreased expression of the proenkephalin and MOR messanger RNAs in the duodenum of patients with diabetic. CONCLUSIONS: Using a prebiotic approach, we identified enkephalin and 12-HETE as new enterosynes with potential real beneficial and safety impact in diabetic human.

The effect of alpha-lipoic acid supplementation and electrical isotonic contraction on anthropometric parameters, body composition and angiogenesis factor, sirtunin-1 and peroxisome proliferator-activated receptor-γ coactivator-1α in obese people under a weight loss regime: A study protocol for a randomized controlled clinical trial.

BACKGROUND: Obesity is defined as a chronic disease, and is known as a public health problem in developed and developing countries. Several studies have shown the effects of anti-obesity of α-lactalbumin. AIM: This study was designed to investigate the effect of alpha-lipoic acid supplementation and electrical isotonic contraction on anthropometric parameters, body composition and angiogenesis factor, sirtunin-1 and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) in obese people under a weight loss regime. METHODS: Obese people who meet the inclusion criteria are included. Participants are randomly divided into four groups (alpha-lipoic (1200 mg) +weight loss regime group; Faradic (three 1 hour sessions) + weight loss regime group; alpha-lipoic (1200 mg) + Faradic (three 1 hour sessions) + weight loss regime group; control group (1200 mg placebo) for 2 months. At the beginning and the end of the study, demographic information, dietary intake, anthropometric parameters, body composition and serum levels of the angiogenesis factor (sirtunin-1, PGC1α and nitric oxide) are measured. CONCLUSION: Recent studies reported the anti-obesity effects of alpha-lipoic acid. This study is novel, since a similar study has not yet been carried out. This study evaluates the effect of 600 mg of alpha-lipoic acid supplementation or having three sessions of 1 hour per week electrical isotonic contraction induced by Faradic for 2 months alone or in combination in obese people that are undergoing a weight loss regime. TRIAL REGISTRATION: Iran Clinical Trials Registry, ID: IRCT20131117015424N2. Registered 2018-04-02.

Beta-alanine supplementation improves isometric, but not isotonic or isokinetic strength endurance in recreationally strength-trained young men.

ß-Alanine (BA) supplementation may be ergogenic during high-intensity exercise, primarily due to the buffering of hydrogen cations, although the effects of beta-alanine supplementation on strength endurance are equivocal. The aim of the study was to determine the effects of 4 weeks of beta-alanine supplementation on skeletal muscle endurance using a battery of performance tests. This study employed a parallel group, repeated measures, randomised, double-blinded and placebo-controlled design. Twenty recreationally strength-trained healthy males completed tests of isotonic strength endurance (repeated bench and leg press), along with tests of isometric and isokinetic endurance conducted using an isokinetic dynamometer. Tests were performed before and after a 4 week intervention, comprising an intake of 6.4 g day-1 of BA (n = 9) or placebo (maltodextrin, n = 11). Time-to-exhaustion during the isometric endurance test improved by ~ 17% in the BA group (p < 0.01), while PL remained unchanged. No significant within-group differences (p > 0.1) were shown for any of the performance variables in the isokinetic test (peak torque, fatigue index, total work) nor for the total number of repetitions performed in the isotonic endurance tests (leg or bench press). Four weeks of BA supplementation (6.4 g day-1) improved isometric, but not isokinetic or isotonic endurance performance.

Contractility of Right Ventricular Myocardium in Male and Female Rats during Physiological and Pathological Hypertrophy.

Sex differences in the morphogenesis and adaptation of the mechanisms controlling myocardium contractility during physiological and pathological hypertrophy of the right ventricle were demonstrated in mature rats. The study revealed sex-dependent effects of physiological and pathological cardiac hypertrophy on the coefficient of variation of the cardiomyocyte diameter, length-dependent control of the contractile force, and the maximum velocity of isotonic shortening.

Combined Inhibition of Histamine H1 Receptors and Leukotrienes Reduces Compound 48/80-Induced Contraction of the Human Bronchus in vitro.

BACKGROUND/AIMS: Bronchial asthma continues to be a big challenge to therapy. Mast cells play an important role in allergic asthma. Histamine and leukotrienes are established mast cell mediators, but antihistamines currently play no role in asthma therapy. METHODS: Human bronchial strips were exposed to the mast cell activator compound 48/80 (200 µg/ml) in isolated organ experiments. RESULTS: The contractile response was not inhibited by the H1 receptor antagonist antihistamine chloropyramine (0.3 µmol/l), the leukotriene cys-LT1 receptor antagonist MK 571 (3 µmol/l), the 5-lipoxygenase inhibitor MK 886 (5 µmol/l), the cyclo-oxygenase inhibitor indomethacin (5 µmol/l), tetrodotoxin, or atropine. Chloropyramine, combined with either MK 571 or MK 886 significantly reduced the response. CONCLUSION: A supra-additive effect is proposed for the antihistamine and the anti-leukotrienes, which might have relevance to human asthma therapy as well; such a combination deserves a large-scale clinical study. These data also indicate that substances like compound 48/80 should be denoted as mast cell activators rather than 'histamine liberators'.

[Effect of acute hypoxia on the mechanical and electrical properties of the isolated skeletal muscles in the last third of chick embryogenesis].

The age-related changes of the contractile and electrical responses of the fast (m. tibialis anterior) and slow (m. soleus) isolated skeletal muscles and their changes under acute hypoxia were estimated during the 16-20 days of the chick embryogenesis. For the first time, the contractile and electrical characteristics of these muscles were described in the specified period of embryogenesis. It was shown that the normalized values of the strength of single and tetanic contractile responses m. tibialis anterior significantly exceed these values for m. soleus. It is shown that the normalized values for the strength of the single and tetanic contractile responses in m. tibialis anterior significantly exceed the values for m. soleus. Using the extracellular microelectrodes (loose patch method) on incubation days 16-17, the slow decaying oscillatory excitation waves were registered in the muscle fibers of m. soleus and m. tibialis anterior, and the extracellular action potentials (APs) were registered in 20% of the investigated muscle fibers in m. tibialis anterior. On the developmental day 20 in fast muscles, the amount of muscle fibers, which were able to generate conductive AP, was about 100%, at the same time, it was about 50% in slow fibers. No significant differences in the amplitude-time characteristics of AP between m. soleus and m. tibialis anterior not observed. Under the results obtained, it is assumed that the muscles fast type principally involve in the chicken embryonic motility in normal and during acute hypoxia in the period of incubation from days 16 to 20. To study the mechanisms of change of muscle contractile responses in hypoxia, the influence of caffeine, insulin and ouabain was investigated. Hypoxia caused the decrease of the force of the muscles contractile responses on all studied stages of embryonic development (16-20 days), but did not impact the value of the contracture response caused by caffeine. Proceeding from this, we can conclude that in our conditions, hypoxia does not affect the functional state of the ryanodine receptors. Muscle treated with insulin and ouabain, significantly reduced sensitivity of the contractile responses to the action of hypoxia. It is assumed that membrane Na+, K(+)-ATPase actively particinates in the hypoxic effects.

Maximum shortening velocity of lymphatic muscle approaches that of striated muscle.

Lymphatic muscle (LM) is widely considered to be a type of vascular smooth muscle, even though LM cells uniquely express contractile proteins from both smooth muscle and cardiac muscle. We tested the hypothesis that LM exhibits an unloaded maximum shortening velocity (Vmax) intermediate between that of smooth muscle and cardiac muscle. Single lymphatic vessels were dissected from the rat mesentery, mounted in a servo-controlled wire myograph, and subjected to isotonic quick release protocols during spontaneous or agonist-evoked contractions. After maximal activation, isotonic quick releases were performed at both the peak and plateau phases of contraction. Vmax was 0.48 ± 0.04 lengths (L)/s at the peak: 2.3 times higher than that of mesenteric arteries and 11.4 times higher than mesenteric veins. In cannulated, pressurized lymphatic vessels, shortening velocity was determined from the maximal rate of constriction [rate of change in internal diameter (-dD/dt)] during spontaneous contractions at optimal preload and minimal afterload; peak -dD/dt exceeded that obtained during any of the isotonic quick release protocols (2.14 ± 0.30 L/s). Peak -dD/dt declined with pressure elevation or activation using substance P. Thus, isotonic methods yielded Vmax values for LM in the mid to high end (0.48 L/s) of those the recorded for phasic smooth muscle (0.05-0.5 L/s), whereas isobaric measurements yielded values (>2.0 L/s) that overlapped the midrange of values for cardiac muscle (0.6-3.3 L/s). Our results challenge the dogma that LM is classical vascular smooth muscle, and its unusually high Vmax is consistent with the expression of cardiac muscle contractile proteins in the lymphatic vessel wall.

[Modulation of the effects of dexamethasone in rat skeletal muscle by testosterone].

In experiments on young females white rats by means of methods of electromyography and ergography we investigated the efficiency of a testosterone-propionate for smoothing of negative effects of dexamethasone on skeletal muscle. It has been established that the chronic injection of dexamethasone causes the decreasing of amplitude of contraction of forward tibial muscle on 29.7-59.3% (after 5-25 injections) and the lengthening of the latent period of muscle's excitation on 18.5-16.5% (after 15-25 injections), whereas the complex application of testosterone and dexamethasone prevents the changing of these parameters. At the same time testosterone didn't provide the smoothing of negative influence of dexamethasone on muscle's resistance to fatigue development.

Nitric oxide modulates bladder afferent nerve activity in the in vitro urinary bladder-pelvic nerve preparation from rats with cyclophosphamide induced cystitis.

Effects of a nitric oxide (NO) donor (SNAP), NO substrate (l-arginine), and NO synthase inhibitor (l-NAME) on bladder afferent nerve (BAN) activity were studied in an in vitro bladder-pelvic nerve preparation from untreated or cyclophosphamide (CYP) treated rats. Distension of the bladder induced phasic bladder contractions (PBC) that were accompanied by multiunit afferent firing. Intravesical administration of SNAP (2mM) which did not change the amplitude of PBC significantly decreased peak afferent firing from 79 ± 15 spikes/s to 44 ± 8 spikes/s in CYP pretreated but not untreated preparations. In CYP treated preparations SNAP also decreased by 33-55% BAN firing induced by isotonic distension of the bladder at 10-40 cmH(2)O pressures. Electrical stimulation on the surface of the bladder elicited action potentials (AP) in BAN. SNAP significantly increased the voltage threshold by 75% (p<0.05) and decreased by 45% (p<0.05) the area of the AP evoked at submaximal stimulus intensity. Bath application of SNAP (2mM) or l-arginine (50mM) elicited similar inhibitory effects on the distension evoked BAN firing. The effects of l-arginine were blocked by bath application of l-NAME (20mM). l-NAME alone did not alter BAN firing. In preparations from normal rats SNAP or l-arginine did not alter BAN activity. These results suggest that exogenous as well as endogenously generated NO depresses the excitability of sensitized but not normal BAN and that NO may have an antinociceptive function and modulate bladder hyperactivity induced by pathological conditions.

Children with heavy prenatal alcohol exposure experience reduced control of isotonic force.

BACKGROUND: Heavy prenatal alcohol exposure can result in diverse and extensive damage to the central nervous system, including the cerebellum, basal ganglia, and cerebral cortex. Given that these brain regions are involved in the generation and maintenance of motor force, we predicted that prenatal alcohol exposure would adversely affect this parameter of motor control. We previously reported that children with gestational alcohol exposure experience significant deficits in regulating isometric (i.e., constant) force. The purpose of this study was to determine whether these children exhibit similar deficits when producing isotonic (i.e., graded) force. METHODS: Children with heavy prenatal alcohol exposure and typically developing children completed a series of isotonic force contractions by exerting force on a load cell to match a criterion target force displayed on a computer monitor. Two levels of target force (5 or 20% of maximum voluntary force) were investigated in combination with varying levels of visual feedback. RESULTS: Compared with control children, children with heavy prenatal alcohol exposure generated isotonic force signals that were less accurate, more variable, and less complex in the time domain. Specifically, interactions were found between group and visual feedback for response accuracy and signal complexity, suggesting that these children have greater difficulty altering their motor output when visual feedback is low. CONCLUSIONS: These data suggest that prenatal alcohol exposure produces deficits in regulating isotonic force, which presumably result from alcohol-related damage to developing brain regions involved in motor control. These children will most likely experience difficulty performing basic motor skills and daily functional skills that require coordination of finely graded force. Therapeutic strategies designed to increase feedback and, consequently, facilitate visual-motor integration could improve isotonic force production in these children.

Time course of isotonic shortening and the underlying contraction mechanism in airway smooth muscle.

Although the structure of the contractile unit in smooth muscle is poorly understood, some of the mechanical properties of the muscle suggest that a sliding-filament mechanism, similar to that in striated muscle, is also operative in smooth muscle. To test the applicability of this mechanism to smooth muscle function, we have constructed a mathematical model based on a hypothetical structure of the smooth muscle contractile unit: a side-polar myosin filament sandwiched by actin filaments, each attached to the equivalent of a Z disk. Model prediction of isotonic shortening as a function of time was compared with data from experiments using ovine tracheal smooth muscle. After equilibration and establishment of in situ length, the muscle was stimulated with ACh (100 µM) until force reached a plateau. The muscle was then allowed to shorten isotonically against various loads. From the experimental records, length-force and force-velocity relationships were obtained. Integration of the hyperbolic force-velocity relationship and the linear length-force relationship yielded an exponential function that approximated the time course of isotonic shortening generated by the modeled sliding-filament mechanism. However, to obtain an accurate fit, it was necessary to incorporate a viscoelastic element in series with the sliding-filament mechanism. The results suggest that a large portion of the shortening is due to filament sliding associated with muscle activation and that a small portion is due to continued deformation associated with an element that shows viscoelastic or power-law creep after a step change in force.

Mode of action of peppermint oil and (-)-menthol with respect to 5-HT3 receptor subtypes: binding studies, cation uptake by receptor channels and contraction of isolated rat ileum.

Peppermint oil (Mentha × piperita L. (Lamiaceae) has been shown to exert potent antiemetic properties, but its mode of action has not yet been elucidated. Among its active constituents (-)-menthol is the most important. Three different in vitro models were used to investigate the effects on 5-HT(3) receptors (serotonin receptor subtype): [(14)C]guanidinium influx into N1E-115 cells which express 5-HT(3) receptors, isotonic contractions of the isolated rat ileum and equilibrium competition binding studies using a radioactively labelled 5-HT(3) receptor antagonist ([(3)H]GR65630) (3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone). Both peppermint oil and (-)-menthol inhibited [(14)C]guanidinium influx through 5-HT(3) receptor channels as well as contractions of the ileum induced by serotonin. Neither the peppermint oil nor (-)-menthol, however, was able to displace [(3)H]GR65630 from 5-HT(3) binding sites. It may be concluded that peppermint oil and (-)-menthol exert their antiemetic effect at least partly by acting on the 5-HT(3) receptor ion-channel complex, probably by binding to a modulatory site distinct from the serotonin binding site.

Urocortin-2 induces vasorelaxation of coronary arteries isolated from patients with heart failure.

1. Urocortin-2 (Ucn2) is a vasoactive peptide belonging to the corticotrophin-releasing factor (CRF) family that has potent cardiovascular actions. It has been suggested that Ucn2 participates in the pathophysiology of heart failure. However, little is known about the mechanisms underlying the action of Ucn2 in human coronary arteries. The aim of the present study was to assess the effects of Ucn2 on the vascular tone of human coronary arteries dissected from heart failure patients. 2. Human coronary arteries were dissected from the hearts of patients subjected to orthotopic heart transplantation. Coronary arteries were obtained from 17 patients with heart failure due to dilated cardiomyopathy of ischaemic origin in Stage III-IV of the New York Heart Association classification. Changes in tone were measured in arterial rings using force transducers. 3. Application of increasing concentrations of Ucn2 (5-20 nmol/L) to arterial rings precontracted with agonists induced dose-dependent relaxation of the coronary artery, which was independent of endothelial cell activation. Furthermore, the inhibition of the adenylyl cyclase by MDL-12 (100 nmol/L) and protein kinase A (PKA) by H89 (1 µmol/L) prevented Ucn2-mediated relaxation of coronary artery rings. 4. The results of the present study suggest that, in heart failure patients, Ucn2 could be useful in modulating coronary artery circulation independent of endothelial integrity through mechanisms that involve adenylyl cyclase activation and PKA stimulation. The findings warrant further investigation of the role of Ucn2 in circulatory regulation and its potential therapeutic application in heart disease.

Cardiovascular effects induced by Cymbopogon winterianus essential oil in rats: involvement of calcium channels and vagal pathway.

OBJECTIVES: This study has investigated the cardiovascular effects of the Cymbopogon winterianus essential oil (EOCW) in rats. C. winterianus is a plant used in folk medicine for the treatment of hypertension. METHODS: For the measurement of haemodynamic and ECG parameters, male Wistar rats under anaesthesia were cannulated in the abdominal aorta and lower vena cava and electrodes were subcutaneously implanted in their paws. For an in-vitro approach, the rats were killed and the superior mesenteric artery was removed and cut into rings (1-2 mm). These rings were then mounted in organ baths containing Tyrode's solution at 37 degrees C and gassed with carbogen. KEY FINDINGS: In rats, EOCW (1-20 mg/kg, i.v.) induced dose-dependent hypotension and tachycardia. These effects were not affected by L-NAME or indometacin, but were partially reduced after atropine administration. EOCW (20 mg/kg only) also induced bradycardia-associated sinoatrial blockade, junctional rhythm, and first-degree atrioventricular block, which was abolished after atropine administration or vagotomy. In arterial rings, EOCW (0.1-3000 microg/ml) induced relaxation of phenylephrine tonus that was not affected by removal of the endothelium. These relaxations were similar to those observed in rings without endothelium precontracted with KCl 80 mm. EOCW was able to antagonize the CaCl(2) (30-300 mum) induced contractions in depolarizing solution (KCl 60 mm). CONCLUSIONS: These results demonstrated that EOCW induced hypotension and vasorelaxation. These effects appeared to be mainly mediated by Ca(+2)-channel blocking. Furthermore, the higher dose of EOCW induced transient bradycardia and arrhythmias due to a cardiac muscarinic activation secondary to a vagal discharge.

Improvement of diaphragm and limb muscle isotonic contractile performance by K+ channel blockade.

The K+ channel blocking aminopyridines greatly improve skeletal muscle isometric contractile performance during low to intermediate stimulation frequencies, making them potentially useful as inotropic agents for functional neuromuscular stimulation applications. Most restorative applications involve muscle shortening; however, previous studies on the effects of aminopyridines have involved muscle being held at constant length. Isotonic contractions differ substantially from isometric contractions at a cellular level with regards to factors such as cross-bridge formation and energetic requirements. The present study tested effects of 3,4-diaminopyridine (DAP) on isotonic contractile performance of diaphragm, extensor digitorum longus (EDL) and soleus muscles from rats. During contractions elicited during 20 Hz stimulation, DAP improved work over a range of loads for all three muscles. In contrast, peak power was augmented for the diaphragm and EDL but not the soleus. Maintenance of increased work and peak power was tested during repetitive fatigue-inducing stimulation using a single load of 40% and a stimulation frequency of 20 Hz. Work and peak power of both diaphragm and EDL were augmented by DAP for considerable periods of time, whereas that of soleus muscle was not affected significantly. These results demonstrate that DAP greatly improves both work and peak power of the diaphragm and EDL muscle during isotonic contractions, which combined with previous data on isometric contractions indicates that this agent is suitable for enhancing muscle performance during a range of contractile modalities.

Acute motor response following a single IVIG treatment course in chronic inflammatory demyelinating polyneuropathy.

In chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), the acute motor response following withdrawal and reestablishment of intravenous immunoglobulin (IVIG) therapy was studied. In a prospectively designed case series 11 CIDP patients in IVIG maintenance therapy were assessed with isokinetic dynamometry, nerve conduction studies, and functional tests. After short-term withdrawal of IVIG, eight treatment-responsive patients had a 14.2% (8.6-20.0) loss of isokinetic strength of 12 muscle groups. Three patients remained stable without treatment and were excluded from further study. On days 5 and 10 after reinitiation of IVIG therapy isokinetic muscle strength increased by 5.5% (1.6-9.6) and 11.9% (7.5-16.5), respectively, but there was no further increase at day 15. Improvement of walking velocity and hand function coincided. The minimal F-wave latency shortened, whereas other electrophysiological parameters remained unchanged. In conclusion, isokinetic dynamometry is a sensitive and clinically relevant method for monitoring the acute response to IVIG treatment in CIDP.

Mechano-growth factor, an IGF-I splice variant, rescues motoneurons and improves muscle function in SOD1(G93A) mice.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motoneuron degeneration. Although viral delivery of IGF-I has shown therapeutic efficacy in the SOD1(G93A) mouse model of ALS, clinical trials of IGF-I in ALS patients have led to conflicting results. Here we examine the effects of an IGF-I splice variant, mechano-growth factor (MGF) which has previously been shown to have greater neuroprotective effects than IGF-I in a number of models of neurodegeneration. A mammalian expression plasmid containing either MGF or, for comparison, the IGF-I cDNA sequence was delivered to the hindlimb muscles of SOD1(G93A) mice at 70 days of age, at symptom onset. Treatment with either IGF-I or MGF resulted in a significant improvement in hindlimb muscle strength, and an increase in motor unit and motoneuron survival. Significantly more motoneurons survived in MGF treated mice.

Calcium dynamics and vasomotion in arteries subject to isometric, isobaric, and isotonic conditions.

In vitro, different techniques are used to study the smooth muscle cells' calcium dynamics and contraction/relaxation mechanisms on arteries. Most experimental studies use either an isometric or an isobaric setup. However, in vivo, a blood vessel is neither isobaric nor isometric nor isotonic, as it is continuously submitted to intraluminal pressure variations arising from heart beat. We use a theoretical model of the smooth muscle calcium and arterial radius dynamics to determine whether results may be considerably different depending on the experimental conditions (isometric, isobaric, isotonic, or cyclic pressure variations). We show that isobaric conditions appear to be more realistic than isometric or isotonic situations, as the calcium dynamics is similar under cyclic intraluminal pressure variations (in vivo-like situation) and under a constant pressure (isobaric situation). The arterial contraction is less pronounced in isotonic than in isobaric conditions, and the vasoconstrictor sensitivity higher in isometric than isobaric or isotonic conditions, in agreement with experimental observations. Interestingly, the model predicts that isometric conditions may generate artifacts like the coexistence of multiple stable states. We have verified this model prediction experimentally using rat mesenteric arteries mounted on a wire myograph and stimulated with phenylephrine.

The effects of 10 weeks of resistance training combined with beta-alanine supplementation on whole body strength, force production, muscular endurance and body composition.

Carnosine (Carn) occurs in high concentrations in skeletal muscle is a potent physico-chemical buffer of H+ over the physiological range. Recent research has demonstrated that 6.4 g x day(-1) of beta-alanine (beta-ala) can significantly increase skeletal muscle Carn concentrations (M-[Carn]) whilst the resultant change in buffering capacity has been shown to be paralleled by significant improvements in anaerobic and aerobic measures of exercise performance. Muscle carnosine increase has also been linked to increased work done during resistance training. Prior research has suggested that strength training may also increase M-[Carn] although this is disputed by other studies. The aim of this investigation is to assess the effect of 10 weeks resistance training on M-[Carn], and, secondly, to investigate if increased M-[Carn] brought about through beta-ala supplementation had a positive effect on training responses. Twenty-six Vietnamese sports science students completed the study. The subjects completed a 10-week resistance-training program whilst consuming 6.4 g x day(-1) of beta-ala (beta-ALG) or a matched dose of a placebo (PLG). Subjects were assessed prior to and after training for whole body strength, isokinetic force production, muscular endurance, body composition. beta-Alanine supplemented subjects increased M-[Carn] by 12.81 +/- 7.97 mmol x kg(-1) dry muscle whilst there was no change in PLG subjects. There was no significant effect of beta-ala supplementation on any of the exercise parameters measured, mass or % body fat. In conclusion, 10 weeks of resistance training alone did not change M-[Carn].