Descrição morfológica do diafragma do sagui-de-tufo-branco (Callithrix jacchus)

O músculo diafragma, encontrado apenas nos mamíferos, é o principal músculo no processo respiratório, servindo de fronteira entre as cavidades torácica e abdominal. Sua importância também ganha destaque em pesquisas realizadas no âmbito dos enxertos, empregando-se diversos tipos de membranas biológicas para o reparo de defeitos diafragmáticos, os quais podem gerar hérnias diafragmáticas. Apesar de muitos estudos já conduzidos para com os primatas não humanos, especialmente no que tange a espécie do novo mundo Callithrix jacchus (Sagui-de-tufo-branco), oriundo do nordeste brasileiro, as pesquisas envolvendo o uso do diafragma em tal espécie é inexistente. Deste modo objetivou-se caracterizar a morfologia e a biometria do diafragma na espécie Callithrix jacchus de ambos os sexos, analisando possíveis divergências estruturais entre machos e fêmeas. Para tal foram utilizados quatros animais, 2 machos e 2 fêmeas, adultos, que vieram a óbito por causas naturais, provenientes de um criadouro comercial. Após fixação em solução de formaldeído 10% os animais foram devidamente dissecados para fotodocumentação e em seguida o diafragma coletado para efetuação da biometria (comprimento e largura) com o uso de um paquímetro e para o processamento histológico por meio da coloração de hematoxilina-eosina e tricrômio de masson, da porção muscular. As mensurações feitas permitiram concluir que não houve diferenças signifcativas entre machos e femeas. A topografia e a presença de três aberturas (forame da veia cava caudal, hiato aórtico e esofágico) na extensão do diafragma corroboram com descrições na literatura classica para outros mamíferos. A presença de um centro tendíneo em "V" difere do encontrado para animais como o peixe-boi e porquinho-da-india, mas é similar ao encontrado para o gambá-de-orelhas-brancas e rato albino. No que diz respeito aos achados histológicos conclui-se que as fibras musculares estão dispostas de forma organizada, apresentam diâmetro grande e núcleos basais, tendo, portanto, características similares do músculo estriado esquelético tanto nos animais machos como nas fêmeas.

Combined effect of AMPK/PPAR agonists and exercise training in mdx mice functional performance

The present investigation was undertaken to test whether exercise training (ET) associated with AMPK/PPAR agonists (EM) would improve skeletal muscle function in mdx mice. These drugs have the potential to improve oxidative metabolism. This is of particular interest because oxidative muscle fibers are less affected in the course of the disease than glycolitic counterparts. Therefore, a cohort of 34 male congenic C57Bl/10J mdx mice included in this study was randomly assigned into four groups: vehicle solution (V), EM [AICAR (AMPK agonist, 50 mg/Kg-1.day-1, ip) and GW 1516 (PPAR delta agonist, 2.5 mg/Kg-1.day-1, gavage)], ET (voluntary running on activity wheel) and EM+ET. Functional performance (grip meter and rotarod), aerobic capacity (running test), muscle histopathology, serum creatine kinase (CK), levels of ubiquitined proteins, oxidative metabolism protein expression (AMPK, PPAR, myoglobin and SCD) and intracellular calcium handling (DHPR, SERCA and NCX) protein expression were analyzed. Treatments started when the animals were two months old and were maintained for one month. A significant functional improvement (p<0.05) was observed in animals submitted to the combination of ET and EM. CK levels were decreased and the expression of proteins related to oxidative metabolism was increased in this group. There were no differences among the groups in the intracellular calcium handling protein expression. To our knowledge, this is the first study that tested the association of ET with EM in an experimental model of muscular dystrophy. Our results suggest that the association of ET and EM should be further tested as a potential therapeutic approach in muscular dystrophies.

Muscle Atrophy and Functional Deficits of Knee Extensors and Flexors in People With Chronic Stroke

Background. Further clarification is needed with regard to the degree of atrophy in individual muscle groups and its possible relationship to joint torque deficit poststroke. Objective. The purpose of this study was to investigate quadriceps and hamstring muscle volume and strength deficits of the knee extensors and flexors in people with chronic hemiparesis compared with a control group. Design. This was a cross-sectional study. Methods. Thirteen individuals with hemiparesis due to chronic stroke (hemiparetic group) and 13 individuals who were healthy (control group) participated in this study. Motor function, quadriceps and hamstring muscle volume, and maximal concentric and eccentric contractions of the knee extensors and flexors were assessed. Results. Only the quadriceps muscle of the paretic limb showed reduced muscle volume (24%) compared with the contralateral (nonparetic) limb. There were no differences in muscle volume between the hemiparetic and control groups. The peak torque of the paretic-limb knee extensors and flexors was reduced in both contraction modes and velocities compared with the nonparetic limb (36%-67%) and with the control group (49%-75%). The nonparetic limb also showed decreased extensor and flexor peak torque compared with the control group (17%-23%). Power showed similar deficits in strength (12%-78%). There were significant correlations between motor function and strength deficits (.54-.67). Limitations. Magnetic resonance imaging coil length did not allow measurement of the proximal region of the thigh. Conclusions. There were different responses between quadriceps and hamstring muscle volumes in the paretic limb that had quadriceps muscle atrophy only. However, both paretic and nonparetic limbs showed knee extensor and flexor torque and power reduction.

Mechanisms of blunted muscle vasodilation during peripheral chemoreceptor stimulation in heart failure patients

We described recently that systemic hypoxia provokes vasoconstriction in heart failure (HF) patients. We hypothesized that either the exaggerated muscle sympathetic nerve activity and/or endothelial dysfunction mediate the blunted vasodilatation during hypoxia in HF patients. Twenty-seven HF patients and 23 age-matched controls were studied. Muscle sympathetic nerve activity was assessed by microneurography and forearm blood flow (FBF) by venous occlusion plethysmography. Peripheral chemoreflex control was evaluated through the inhaling of a hypoxic gas mixture (10% O-2 and 90% N-2). Basal muscle sympathetic nerve activity was greater and basal FBF was lower in HF patients versus controls. During hypoxia, muscle sympathetic nerve activity responses were greater in HF patients, and forearm vasodilatation in HF was blunted versus controls. Phentolamine increased FBF responses in both groups, but the increase was lower in HF patients. Phentolamine and N-G-monomethyl-L-arginine infusion did not change FBF responses in HF but markedly blunted the vasodilatation in controls. FBF responses to hypoxia in the presence of vitamin C were unchanged and remained lower in HF patients versus controls. In conclusion, muscle vasoconstriction in response to hypoxia in HF patients is attributed to exaggerated reflex sympathetic nerve activation and blunted endothelial function (NO activity). We were unable to identify a role for oxidative stress in these studies. (Hypertension. 2012; 60: 669-676.) . Online Data Supplement

The beta 2-Adrenoceptor Agonist Formoterol Improves Structural and Functional Regenerative Capacity of Skeletal Muscles From Aged Rat at the Early Stages of Postinjury

Skeletal muscles from old rats fail to completely regenerate following injury. This study investigated whether pharmacological stimulation of beta 2-adrenoceptors in aged muscles following injury could improve their regenerative capacity, focusing on myofiber size recovery. Young and aged rats were treated with a subcutaneous injection of beta 2-adrenergic agonist formoterol (2 mu g/kg/d) up to 10 and 21 days after soleus muscle injury. Formoterol-treated muscles from old rats evaluated at 10 and 21 days postinjury showed reduced inflammation and connective tissue but a similar number of regenerating myofibers of greater caliber when compared with their injured controls. Formoterol minimized the decrease in tetanic force and increased protein synthesis and mammalian target of rapamycin phosphorylation in old muscles at 10 days postinjury. Our results suggest that formoterol improves structural and functional regenerative capacity of regenerating skeletal muscles from aged rats by increasing protein synthesis via mammalian target of rapamycin activation. Furthermore, formoterol may have therapeutic benefits in recovery following muscle damage in senescent individuals.

The Extracellular Matrix of the Lateral Pharyngeal Wall in Obstructive Sleep Apnea

Study Objectives: To compare the components of the extracellular matrix in the lateral pharyngeal muscular wall in patients with and without obstructive sleep apnea (OSA). This may help to explain the origin of the increased collapsibility of the pharynx in patients with OSA. Design: Specimens from the superior pharyngeal constrictor muscle, obtained during pharyngeal surgeries, were evaluated using histochemical and immunohistochemical analyses to determine the fractional area of collagen types I and II, elastic fibers, versican, fibronectin, and matrix metalloproteinases 1 and 2 in the endomysium. Setting: Academic tertiary center. Patiens: A total of 51 nonobese adult patients, divided into 38 patients with OSA and 13 nonsnoring control subjects without OSA. Interventions: Postintervention study performed on tissues from patients after elective surgery. Measurements and Results: Pharyngeal muscles of patients with OSA had significantly more collagen type I than pharyngeal muscles in control subjects. Collagen type I was correlated positively and independently with age. The other tested components of the extracellular matrix did not differ significantly between groups. In a logistic regression, an additive effect of both the increase of collagen type I and the increase in age with the presence of OSA was observed (odds ratio (OR), 2.06; 95% confidence interval (CI), 1.17-3.63), when compared with the effect of increased age alone (OR, 1.11; 95% CI, 1.03-1.20). Conclusion: Collagen type I in the superior pharyngeal constrictor muscle was more prevalent in patients with OSA and also increased with age. It was hypothesized that this increase could delay contractile-relaxant responses in the superior pharyngeal constrictor muscle at the expiratory-inspiratory phase transition, thus increasing pharyngeal collapsibility.

Low-level laser therapy (808 nm) reduces inflammatory response and oxidative stress in rat tibialis anterior muscle after cryolesion

Background and Objective Muscle regeneration is a complex phenomenon, involving coordinated activation of several cellular responses. During this process, oxidative stress and consequent tissue damage occur with a severity that may depend on the intensity and duration of the inflammatory response. Among the therapeutic approaches to attenuate inflammation and increase tissue repair, low-level laser therapy (LLLT) may be a safe and effective clinical procedure. The aim of this study was to evaluate the effects of LLLT on oxidative/nitrative stress and inflammatory mediators produced during a cryolesion of the tibialis anterior (TA) muscle in rats. Material and Methods Sixty Wistar rats were randomly divided into three groups (n?=?20): control (BC), injured TA muscle without LLLT (IC), injured TA muscle submitted to LLLT (IRI). The injured region was irradiated daily for 4 consecutive days, starting immediately after the lesion using a AlGaAs laser (continuous wave, 808?nm, tip area of 0.00785?cm2, power 30?mW, application time 47?seconds, fluence 180?J/cm2; 3.8?mW/cm2; and total energy 1.4?J). The animals were sacrificed on the fourth day after injury. Results LLLT reduced oxidative and nitrative stress in injured muscle, decreased lipid peroxidation, nitrotyrosine formation and NO production, probably due to reduction in iNOS protein expression. Moreover, LLLT increased SOD gene expression, and decreased the inflammatory response as measured by gene expression of NF-k beta and COX-2 and by TNF-a and IL-1 beta concentration. Conclusion These results suggest that LLLT could be an effective therapeutic approach to modulate oxidative and nitrative stress and to reduce inflammation in injured muscle. Lasers Surg. Med. 44: 726735, 2012. (c) 2012 Wiley Periodicals, Inc.

Potential therapeutic effects of branched-chain amino acids supplementation on resistance exercise-based muscle damage in humans

Branched-chain amino acids (BCAA) supplementation has been considered an interesting nutritional strategy to improve skeletal muscle protein turnover in several conditions. In this context, there is evidence that resistance exercise (RE)-derived biochemical markers of muscle soreness (creatine kinase (CK), aldolase, myoglobin), soreness, and functional strength may be modulated by BCAA supplementation in order to favor of muscle adaptation. However, few studies have investigated such effects in well-controlled conditions in humans. Therefore, the aim of this short report is to describe the potential therapeutic effects of BCAA supplementation on RE-based muscle damage in humans. The main point is that BCAA supplementation may decrease some biochemical markers related with muscle soreness but this does not necessarily reflect on muscle functionality.

Mechanical alterations in airway smooth muscle after interaction with indoor pollutant - A mathematical model

The viscoelasticity of mammalian lung is determined by the mechanical properties and structural regulation of the airway smooth muscle (ASM). The exposure to polluted air may deteriorate these properties with harmful consequences to individual health. Formaldehyde (FA) is an important indoor pollutant found among volatile organic compounds. This pollutant permeates through the smooth muscle tissue forming covalent bonds between proteins in the extracellular matrix and intracellular protein structure changing mechanical properties of ASM and inducing asthma symptoms, such as airway hyperresponsiveness, even at low concentrations. In the experimental scenario, the mechanical effect of FA is the stiffening of the tissue, but the mechanism behind this effect is not fully w1derstood. Thus, the aim of this study is to reproduce the mechanical behavior of the ASM, such as contraction and stretching, under FA action or not. For this, it was created a two-dimensional viscoelastic network model based on Voronoi tessellation solved using Runge-Kutta method of fourth order. The equilibrium configuration was reached when the forces in different parts of the network were equal. This model simulates the mechanical behavior of ASM through of a network of dashpots and springs. This dashpot-spring mechanical coupling mimics the composition of the actomyosin machinery of ASM through the contraction of springs to a minimum length. We hypothesized that formation of covalent bonds, due to the FA action, can be represented in the model by a simple change in the elastic constant of the springs, while the action of methacholinc (MCh) reduce the equilibrium length of the spring. A sigmoid curve of tension as a function of MCh doses was obtained, showing increased tension when the muscle strip was exposed to FA. Our simulations suggest that FA, at a concentration of 0.1 ppm, can affect the elastic properties of the smooth muscle fibers by a factor of 120%. We also analyze the dynamic mechanical properties, observing the viscous and elastic behavior of the network. Finally, the proposed model, although simple, ir1corporates the phenomenology of both MCh and FA and reproduces experirnental results observed with ir1 vitro exposure of smooth muscle to .FA. Thus, this new mechanical approach incorporates several well know features of the contractile system of the cells ir1 a tissue level model. The model can also be used in different biological scales.

Effects of ATP-induced leg vasodilation on VO2 peak and leg O2 extraction during maximal exercise in humans

[EN] During maximal whole body exercise VO2 peak is limited by O2 delivery. In turn, it is though that blood flow at near-maximal exercise must be restrained by the sympathetic nervous system to maintain mean arterial pressure. To determine whether enhancing vasodilation across the leg results in higher O2 delivery and leg VO2 during near-maximal and maximal exercise in humans, seven men performed two maximal incremental exercise tests on the cycle ergometer. In random order, one test was performed with and one without (control exercise) infusion of ATP (8 mg in 1 ml of isotonic saline solution) into the right femoral artery at a rate of 80 microg.kg body mass-1.min-1. During near-maximal exercise (92% of VO2 peak), the infusion of ATP increased leg vascular conductance (+43%, P<0.05), leg blood flow (+20%, 1.7 l/min, P<0.05), and leg O2 delivery (+20%, 0.3 l/min, P<0.05). No effects were observed on leg or systemic VO2. Leg O2 fractional extraction was decreased from 85+/-3 (control) to 78+/-4% (ATP) in the infused leg (P<0.05), while it remained unchanged in the left leg (84+/-2 and 83+/-2%; control and ATP; n=3). ATP infusion at maximal exercise increased leg vascular conductance by 17% (P<0.05), while leg blood flow tended to be elevated by 0.8 l/min (P=0.08). However, neither systemic nor leg peak VO2 values where enhanced due to a reduction of O2 extraction from 84+/-4 to 76+/-4%, in the control and ATP conditions, respectively (P<0.05). In summary, the VO2 of the skeletal muscles of the lower extremities is not enhanced by limb vasodilation at near-maximal or maximal exercise in humans. The fact that ATP infusion resulted in a reduction of O2 extraction across the exercising leg suggests a vasodilating effect of ATP on less-active muscle fibers and other noncontracting tissues and that under normal conditions these regions are under high vasoconstrictor influence to ensure the most efficient flow distribution of the available cardiac output to the most active muscle fibers of the exercising limb.

Human muscle net K(+) release during exercise is unaffected by elevated anaerobic metabolism, but reduced after prolonged acclimatization to 4,100 m

[EN] It was investigated whether skeletal muscle K(+) release is linked to the degree of anaerobic energy production. Six subjects performed an incremental bicycle exercise test in normoxic and hypoxic conditions prior to and after 2 and 8 wk of acclimatization to 4,100 m. The highest workload completed by all subjects in all trials was 260 W. With acute hypoxic exposure prior to acclimatization, venous plasma [K(+)] was lower (P < 0.05) in normoxia (4.9 +/- 0.1 mM) than hypoxia (5.2 +/- 0.2 mM) at 260 W, but similar at exhaustion, which occurred at 400 +/- 9 W and 307 +/- 7 W (P < 0.05), respectively. At the same absolute exercise intensity, leg net K(+) release was unaffected by hypoxic exposure independent of acclimatization. After 8 wk of acclimatization, no difference existed in venous plasma [K(+)] between the normoxic and hypoxic trial, either at submaximal intensities or at exhaustion (360 +/- 14 W vs. 313 +/- 8 W; P < 0.05). At the same absolute exercise intensity, leg net K(+) release was less (P < 0.001) than prior to acclimatization and reached negative values in both hypoxic and normoxic conditions after acclimatization. Moreover, the reduction in plasma volume during exercise relative to rest was less (P < 0.01) in normoxic than hypoxic conditions, irrespective of the degree of acclimatization (at 260 W prior to acclimatization: -4.9 +/- 0.8% in normoxia and -10.0 +/- 0.4% in hypoxia). It is concluded that leg net K(+) release is unrelated to anaerobic energy production and that acclimatization reduces leg net K(+) release during exercise.

Die Funktion von Dystroglycan in der Entwicklung des zentralen Nervensystems

Die Funktion von Dystroglycan in der Entwicklung des zentralen Nervensystems Der DAG ist ein oligomerer Proteinkomplex, der in den Muskelfasern die extrazelluläre Matrix mit dem Zytoskelett verbindet und dadurch der Muskulatur die mechanische Stabilität bei der Kontraktion verleiht. Mutationen des DAG sind die genetische Grundlage für verschiedene Formen von muskulären Dystrophien. Muskuläre Dystrophien sind Krankheiten, die neben einer Degeneration der Muskulatur auch verschiedene ZNS-Defekte aufweisen. Die Funktion des DAG im ZNS ist bisher unbekannt. Um seine Funktion im ZNS zu analysieren, wurde Huhn-Dystroglycan, eine zentrale Komponente des DAG, kloniert. Dystroglycan besteht aus dem extrazellulären Matrixprotein alpha-Dystroglycan und dem transmembranen beta-Dystroglycan. Beide Proteine werden vom selben Gen codiert und posttranslational gespalten. Die Huhn-Dystroglycan-Sequenz ist sehr homolog zu anderen Spezies. Antikörper hergestellt gegen die Interaktionsdomänen von alpha- und beta-Dystroglycan, wurden verwendet um die Interaktion von Dystroglycan selektiv an der Grenzfläche zwischen Gliazellendfüßen und Basallamina in der Retina zu stören. Die Antikörper wurden in vivo intravitreal in Augen von Hühnerembryoanen der Stadien E6 bis E10 injiziert. Die Injektion der Antikörper und entsprechender Fab-Fragmente führten zu schweren Veränderungen in der Retina, unter anderem Hyperproliferation, Auflösung der radialen Struktur der neuroepithelialen Zellen und einer veränderten Schichtung. Diese Ergebnisse deuten darauf hin, daß der DAG am Kontakt der radiären Glizellen zur Basalmembran beteiligt sind.

Mitochondrial DNA rearrangements during human aging: a study on liver, muscle and adipose tissue

Aging is characterized by a chronic, low-grade inflammatory state called “inflammaging”. Mitochondria are the main source of reactive oxygen species (ROS), which trigger the production of pro-inflammatory molecules. We are interested in studying the age-related modifications of the mitochondrial DNA (mtDNA), which can be affected by the lifelong exposure to ROS and are responsible of mitochondrial dysfunction. Moreover, increasing evidences show that telomere shortening, naturally occurring with aging, is involved in mtDNA damage processes and thus in the pathogenesis of age-related disorders. Thus the primary aim of this thesis was the analysis of mtDNA copy number, deletion level and integrity in different-age human biopsies from liver, vastus lateralis skeletal muscle of healthy subjects and patients with limited mobility of lower limbs (LMLL), as well as adipose tissue. The telomere length and the expression of nuclear genes related to mitobiogenesis, fusion and fission, mitophagy, mitochondrial protein quality control system, hypoxia, production and protection from ROS were also evaluated. In liver the decrease in mtDNA integrity with age is accompanied with an increase in mtDNA copy number, suggesting the existence of a “compensatory mechanism” able to maintain the functionality of this organ. Different is the case of vastus lateralis muscle, where any “compensatory pathway” is activated and mtDNA integrity and copy number decrease with age, both in healthy subjects and in patients. Interestingly, mtDNA rearrangements do not incur in adipose tissue with advancing age. Finally, in all tissues a marked gender difference appears, suggesting that aging and also gender diversely affect mtDNA rearrangements and telomere length in the three human tissues considered, likely depending on their different metabolic needs and inflammatory status.

Velocity recovery cycles of human muscle action potentials in chronic renal failure

To test the hypothesis that muscle fibers are depolarized in patients with chronic renal failure, by measuring velocity recovery cycles of muscle action potentials as indicators of muscle membrane potential.

Muscle membrane dysfunction in critical illness myopathy assessed by velocity recovery cycles

To test the hypothesis that muscle fibers are depolarized in patients with critical illness myopathy by measuring velocity recovery cycles (VRCs) of muscle action potentials.