Retinoic Acid and VEGF Delay Smooth Muscle Relative to Endothelial Differentiation to Coordinate Inner and Outer Coronary Vessel Wall Morphogenesis

Rationale: Major coronary vessels derive from the proepicardium, the cellular progenitor of the epicardium, coronary endothelium, and coronary smooth muscle cells (CoSMCs). CoSMCs are delayed in their differentiation relative to coronary endothelial cells (CoEs), such that CoSMCs mature only after CoEs have assembled into tubes. The mechanisms underlying this sequential CoE/CoSMC differentiation are unknown. Retinoic acid (RA) is crucial for vascular development and the main RA-synthesizing enzyme is progressively lost from epicardially derived cells as they differentiate into blood vessel types. In parallel, myocardial vascular endothelial growth factor (VEGF) expression also decreases along coronary vessel muscularization. Objective: We hypothesized that RA and VEGF act coordinately as physiological brakes to CoSMC differentiation. Methods and Results: In vitro assays (proepicardial cultures, cocultures, and RALDH2 [retinaldehyde dehydrogenase-2]/VEGF adenoviral overexpression) and in vivo inhibition of RA synthesis show that RA and VEGF act as repressors of CoSMC differentiation, whereas VEGF biases epicardially derived cell differentiation toward the endothelial phenotype. Conclusion: Experiments support a model in which early high levels of RA and VEGF prevent CoSMC differentiation from epicardially derived cells before RA and VEGF levels decline as an extensive endothelial network is established. We suggest this physiological delay guarantees the formation of a complex, hierarchical, tree of coronary vessels. (Circ Res. 2010;107:204-216.)

Effect of low-level laser therapy (GaAs 904 nm) in skeletal muscle fatigue and biochemical markers of muscle damage in rats

We wanted to test if pre-exercise muscle irradiation with 904 nm laser affects the development of fatigue, blood lactate levels and creatine kinase (CK) activity in a rat model with tetanic contractions. Thirty male Wistar rats were divided into five groups receiving either one of four different laser doses (0.1, 0.3, 1.0 and 3.0 J) or a no-treatment control group. Laser irradiation was performed immediately before the first contraction for treated groups. Electrical stimulation was used to induce six tetanic tibial anterior muscle contractions with 10 min intervals between them. Contractions were stopped when the muscle force fell to 50% of the peak value for each contraction; blood samples were taken before the first and immediately after the sixth contraction. The relative peak forces for the sixth contraction were significantly better (P < 0.05) in the two laser groups irradiated with highest doses [151.27% (SD +/- A 18.82) for 1.0 J, 144.84% (SD +/- A 34.47) for 3.0 J and 82.25% (SD +/- A 11.69) for the control group]. Similar significant (P < 0.05) increases in mean performed work during the sixth contraction for the 1.0 and 3.0 J groups were also observed. Blood lactate levels were significantly lower (P < 0.05) than the control group in all irradiated groups. All irradiated groups except the 3.0 J group had significantly lower post-exercise CK activity than the control group. We conclude that pre-exercise irradiation with a laser dose of 1.0 J and 904 nm wavelength significantly delays muscle fatigue and decreases post-exercise blood lactate and CK in this rat model.

Effect of Cluster Multi-Diode Light Emitting Diode Therapy (LEDT) on Exercise-Induced Skeletal Muscle Fatigue and Skeletal Muscle Recovery in Humans

Background and Objectives: There are some indications that low-level laser therapy (LLLT) may delay the development of skeletal muscle fatigue during high-intensity exercise. There have also been claims that LED cluster probes may be effective for this application however there are differences between LED and laser sources like spot size, spectral width, power output, etc. In this study we wanted to test if light emitting diode therapy (LEDT) can alter muscle performance, fatigue development and biochemical markers for skeletal muscle recovery in an experimental model of biceps humeri muscle contractions. Study Design/Materials and Methods: Ten male professional volleyball players (23.6 [SD +/- 5.6] years old) entered a randomized double-blinded placebo-controlled crossover trial. Active cluster LEDT (69 LEDs with wavelengths 660/850 nm, 10/30 mW, 30 seconds total irradiation time, 41.7J of total energy irradiated) or an identical placebo LEDT was delivered under double-blinded conditions to the middle of biceps humeri muscle immediately before exercise. All subjects performed voluntary biceps humeri contractions with a workload of 75% of their maximal voluntary contraction force (MVC) until exhaustion. Results: Active LEDT increased the number of biceps humeri contractions by 12.9% (38.60 [SD +/- 9.03] vs. 34.20 [SD +/- 8.68], P = 0.021) and extended the elapsed time to perform contractions by 11.6% (P = 0.036) versus placebo. In addition, post-exercise levels of biochemical markers decreased significantly with active LEDT: Blood Lactate (P = 0.042), Creatine Kinase (P = 0.035), and C-Reative Protein levels (P = 0.030), when compared to placebo LEDT. Conclusion: We conclude that this particular procedure and dose of LEDT immediately before exhaustive biceps humeri contractions, causes a slight delay in the development of skeletal muscle fatigue, decreases post-exercise blood lactate levels and inhibits the release of Creatine Kinase and C-Reative Protein. Lasers Surg. Med. 41:572-577, 2009. (C) 2009 Wiley-Liss, Inc.

Involvement of Eukaryotic Translation Initiation Factor 5A (eIF5A) in Skeletal Muscle Stem Cell Differentiation

The eukaryotic translation initiation factor 5A (eIF5A) contains a special amino acid residue named hypusine that is required for its activity, being produced by a post-translational modification using spermidine as substrate. Stem cells from rat skeletal muscles (satellite cells) were submitted to differentiation and an increase of eIF5A gene expression was observed. Higher content of eIF5A protein was found in satellite cells on differentiation in comparison to non-differentiated satellite cells and skeletal muscle. The treatment with NI-guanyl- 1,7-diaminoheptane (GC7), a hypusination inhibitor, reversibly abolished the differentiation process. In association with the differentiation blockage, an increase of glucose consumption and lactate production and a decrease of glucose and palmitic acid oxidation were observed. A reduction in cell proliferation and protein synthesis was also observed. L-Arginine, a spermidine precursor and partial suppressor of muscle dystrophic phenotype, partially abolished the GC7 inhibitory effect on satellite cell differentiation. These results reveal a new physiological role for eIF5A and contribute to elucidate the molecular mechanisms involved in muscle regeneration.

Differences in muscle activity during hand dexterity tasks between women with arthritis and a healthy reference group

Background. Impaired hand function is common in patients with arthritis and it affects performance of daily activities; thus, hand exercises are recommended. There is little information on the extent to which the disease affects activation of the flexor and extensor muscles during these hand-dexterity tasks. The purpose of this study was to compare muscle activation during such tasks in subjects with arthritis and in a healthy reference group. Methods. Muscle activation was measured in m. extensor digitorium communis (EDC) and in m. flexor carpi radialis (FCR) with surface electromyography (EMG) in women with rheumatoid arthritis (RA, n = 20), hand osteoarthritis (HOA, n = 16) and in a healthy reference group (n = 20) during the performance of four daily activity tasks and four hand exercises. Maximal voluntary isometric contraction (MVIC) was measured to enable intermuscular comparisons, and muscle activation is presented as %MVIC. Results. The arthritis group used a higher %MVIC than the reference group in both FCR and EDC when cutting with a pair of scissors, pulling up a zipper and—for the EDC—also when writing with a pen and using a key (p < 0.02). The exercise “rolling dough with flat hands” required the lowest %MVIC and may be less effective in improving muscle strength. Conclusions. Women with arthritis tend to use higher levels of muscle activation in daily tasks than healthy women, and wrist extensors and flexors appear to be equally affected. It is important that hand training programs reflect real-life situations and focus also on extensor strength.

Relative development of tissues, commercial meat cuts and live weight components in Saanen goats

Objetivando avaliar o desenvolvimento relativo dos componentes do peso vivo (PV), dos cortes comerciais e dos tecidos da carcaça, utilizaram-se 40 cabritos Saanen. Os animais foram abatidos ao atingir 5,0; 12,5; 20,0; 27,5 e 35,0 kg de PV e a carcaça foi seccionada em paleta, pescoço, 1ª a 5ª costelas, 6ª a 13ª costelas, peito/fralda, lombo e perna. A perna foi dissecada em ossos, músculos e gordura. Utilizou-se a equação alométrica Y=aXb para estimar o desenvolvimento relativo. O crescimento do tecido ósseo foi precoce, o do tecido muscular intermediário e o da gordura crescimento tardio, uma vez que a gordura subcutânea é depositada mais tardiamente. Os cortes comerciais apresentaram coeficiente de alometria isogônico, com exceção do corte da 6ª a 13ª costelas e do peito/fralda. O desenvolvimento da carcaça e dos não-componentes da carcaça acompanhou o peso de corpo vazio. Cabritos com 35 kg de PV possuem proporção de músculos e relação músculo:osso adequadas, mas apresentam proporção de gordura maior que a observada nos animais abatidos com 20 kg de PV.

Mechanisms for consideration for intervention in the development of organophosphorus-induced delayed neuropathy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Development of a rabbit's urethral sphincter deficiency animal model for anatomical-functional evaluation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of incubation temperature on muscle morphology and growth in the pacu (Piaractus mesopotamicus)

This study describes the influence of incubation temperature during initial development phase on the morphology and muscle growth characteristics in the pacu (Piaractus mesopotamicus). Pacu eggs were incubated at 25, 27, and 29 degreesC until hatching. After day 5, fish from each temperature were transferred to 5001 tanks. At hatching and after 5, 25, and 60 days, muscle samples were collected, some were frozen in liquid nitrogen and others fixed in 4% paraformaldehyde or 2.5% glutaraldehyde. These samples were used for morphological, histochemical, immunohistochemical, and morphometric analysis. At hatching, we observed a superficial monolayer of small diameter fibers, lying just beneath the skin surrounding several round cells. From day 5, we observed two distinct populations of muscle fibers distributed in two layers: (1) red-in a superficial region with aerobic activity, and following acid preincubation, high mATPase activity, and 2) white-with anaerobic activity, and following alkaline preincubation, high mATPase activity. Twenty-five days after hatching, an intermediate layer and cell proliferating zones could be seen in the dorsal fin muscle region, with intermediate characteristics. Throughout the experimental period, there was an increase in muscle mass due to new fiber recruitment in the cell proliferating zones and between the more differentiated fibers in red, intermediate, and white muscles. This was more obvious from day 25, and at 29 degreesC than at 25 and 27 degreesC. Fiber hypertrophy occurred from hatching to 60 days and was more evident from 5 to 25 days. The number of proliferating nuclei (PCNA-labelling) increased from hatching to 60 days, and was more obvious in the 29 degreesC group at 60 days. Our results show that at incubation temperatures of 25, 27 and 29 degreesC, hypertrophy was predominantly from hatching to 25 days, after that muscle growth by hyperplastic mechanism increased. The interaction of muscle hypertrophic and hyperplastic growth processes in the 29 degreesC group produced the largest fish at the end of the experiment. (C) 2004 Elsevier B.V. All rights reserved.

Study About the Development of the Temporomandibular Joint in the Human Fetuses

The temporomandibular joint (TMJ) is a highly specialized articulation that differs from all the other synovial articulations for many reasons. In children, different from what we observe in adults, these articulations have rarely been studied under the morphofunctional aspect, mainly in the embryonary and fetal stages. In this study 10 fetuses with ages varying from 16 to 39 weeks of intrauterine life were used, and it could be observed that the fibers and thickness of the articular disc, as well as the articular capsule and the condylar process, suffer modifications according to age. It was also observed that the superior head of the lateral pterygoid muscle inserts itself in the articular disc and capsule in all the ages studied. Also, the maturation of the articular tissues, especially of the articular disc, as well as, the associated muscles, suggests that the TMJ was able to carry out mandibular movements since the 24(th) week of intrauterine life.

Differential expression of myogenic regulatory factor MyoD in pacu skeletal muscle (Piaractus mesopotamicus Holmberg 1887: Serrasalminae, Characidae, Teleostei) during juvenile and adult growth phases

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of Citrus aurantium l. essential oil on muscle regeneration in mdx mice

Duchenne muscular dystrophy (DMD) is a severe X-linked recessive disorder characterized by the progressive loss of muscular strength. Mdx mutant mice show a marked deficiency in dystrophin, which was related to muscle membrane stability. The aim of this study was to verify the possible protective anti-inflammatory effect of citrus oil on mdx muscle fibers. Thus, adult male and female mdx mice (014/06-CEEA) were divided into control and citrus-treated. After 60 days of treatment, one ml of blood was collected for creatine kinase (CK) test. Diaphragm, sternomastoideus, anterior tibial and gastrocnemius muscles were removed and processed according to histological routine methods. The observed alterations indicate a direct effect of citrus. Recent studies have improved the diagnosis of muscular diseases but with no definitions of efficient treatments. Intervention with several therapies is important to many patients presenting muscular dystrophy, which enables them to live longer and be more active, while there is no development of gene therapies.

Mastoparan effects in skeletal muscle damage: An ultrastructural view until now concealed

Animal venoms have been valuable sources for development of new drugs and important tools to understand cellular functioning in health and disease. The venom of Polybia paulista, a neotropical social wasp belonging to the subfamily Polistinae, has been sampled by headspace solid phase microextraction and analyzed by gas chromatography-mass spectrometry. Recent study has shown that mastoparan, a major basic peptide isolated from the venom, reproduces the myotoxic effect of the whole venom. In this study, Polybia-MPII mastoparan was synthesized and studies using transmission electron microscopy were carried out in mice tibial anterior muscle to identify the subcellular targets of its myotoxic action. The effects were followed at 3 and 24 h, 3, 7, and 21 days after mastoparan (0.25 mu g/mu L) intramuscular injection. The peptide caused disruption of the sarcolemma and collapse of myofibril arrangement in myofibers. As a consequence, fibers presented heteromorphic amorphous masses of agglutinated myofilaments very often intermingled with denuded sarcoplasmic areas sometimes only surrounded by a persistent basal lamina. To a lesser extent, a number of fibers apparently did not present sarcolemma rupture but instead appeared with multiple small vacuoles. The results showed that sarcolemma, sarcoplasmic reticulum (SR), and mitochondria were the main targets for mastoparan. In addition, a number of fibers showed apoptotic-like nuclei suggesting that the peptide causes death both by necrosis and apoptosis. This study presents a hitherto unexplored view of the effects of mastoparan in skeletal muscle and contributes to discuss how the known pharmacology of the peptide is reflected in the sarcolemma, SR, mitochondria, and nucleus of muscle fibers, apparently its subcellular targets.

Relationship between lower-limb muscle strength and frailty among elderly people

CONTEXTO E OBJETIVO: A sarcopenia é o principal fator envolvido no desenvolvimento da síndrome de fragilidade. O objetivo foi investigar a relação entre força muscular de membros inferiores e as variáveis sexo, idade e critérios de fragilidade; comparar a força muscular de membros inferiores com cada critério de fragilidade e verificar seu poder de estimativa do risco para fragilidade em idosos ambulatoriais. TIPO DE ESTUDO E LOCAL: Estudo transversal no Ambulatório de Geriatria de um hospital universitário de Campinas. MÉTODO: Foi avaliada uma amostra de conveniência não-probabilística de 150 idosos de ambos os sexos em acompanhamento ambulatorial, com coleta de dados sócio-demográficos (sexo e idade) e de saúde física (critérios de fragilidade e teste de levantar e sentar da cadeira cinco vezes consecutivamente). Foram realizadas análises descritivas, de comparação e de regressão logística multivariada. RESULTADOS: A maioria dos idosos (77,3%) apresentou idade igual ou superior a 70 anos, com predomínio do sexo feminino (64,0%) e baixo escore no teste de levantar e sentar da cadeira cinco vezes consecutivas (81,4% escore 0 ou 1), 55,3% dos idosos apresentaram três ou mais critérios de fragilidade. Verificou-se associação significativa entre a força muscular de membros inferiores e as variáveis idade e número de critérios de fragilidade. CONCLUSÕES: Menores níveis de força muscular de membros inferiores estão associados a idade avançada e maior presença de sinais de fragilidade. Além disso, a força muscular de membros inferiores também está associada com os critérios redução da velocidade de marcha e da força de preensão palmar.

Spectral analysis of the electromyograph of the erector spinae muscle before and after a dynamic manual load-lifting test

The aim of the present study was to assess the spectral behavior of the erector spinae muscle during isometric contractions performed before and after a dynamic manual load-lifting test carried out by the trunk in order to determine the capacity of muscle to perform this task. Nine healthy female students participated in the experiment. Their average age, height, and body mass (± SD) were 20 ± 1 years, 1.6 ± 0.03 m, and 53 ± 4 kg, respectively. The development of muscle fatigue was assessed by spectral analysis (median frequency) and root mean square with time. The test consisted of repeated bending movements from the trunk, starting from a 45º angle of flexion, with the application of approximately 15, 25 and 50% of maximum individual load, to the stand up position. The protocol used proved to be more reliable with loads exceeding 50% of the maximum for the identification of muscle fatigue by electromyography as a function of time. Most of the volunteers showed an increase in root mean square versus time on both the right (N = 7) and the left (N = 6) side, indicating a tendency to become fatigued. With respect to the changes in median frequency of the electromyographic signal, the loads used in this study had no significant effect on either the right or the left side of the erector spinae muscle at this frequency, suggesting that a higher amount and percentage of loads would produce more substantial results in the study of isotonic contractions.