Expression of smooth muscle and extracellular matrix proteins in relation to airway function in asthma

Background: Smooth muscle content is increased within the airway wall in patients with asthma and is likely to play a role in airway hyperresponsiveness. However, smooth muscle cells express several contractile and structural proteins, and each of these proteins may influence airway function distinctly. Objective: We examined the expression of contractile and structural proteins of smooth muscle cells, as well as extracellular matrix proteins, in bronchial biopsies of patients with asthma, and related these to lung function, airway hyperresponsiveness, and responses to deep inspiration. Methods: Thirteen patients with asthma (mild persistent, atopic, nonsmoking) participated in this cross-sectional study. FEV1 % predicted, PC20 methacholine, and resistance of the respiratory system by the forced oscillation technique during tidal breathing and deep breath were measured. Within 1 week, a bronchoscopy was performed to obtain 6 bronchial biopsies that were immunuhistochemically stained for alpha-SM-actin, desmin, myosin light chain kinase (MLCK), myosin, calponin, vimentin, elastin, type III collagen, and fibronectin. The level of expression was determined by automated densitometry. Results: PC20 methacholine was inversely related to the expression of alpha-smooth muscle actin (r = -0.62), desmin (r = -0.56), and elastin (r = -0.78). In addition, FEV1% predicted was positively related and deep inspiration-induced bronchodilation inversely related to desmin (r = -0.60), MLCK (r = -0.60), and calponin (r = -0.54) expression. Conclusion: Airway hyperresponsiveness, FEV1% predicted, and airway responses to deep inspiration are associated with selective expression of airway smooth muscle proteins and components of the extracellular matrix.

Airway smooth muscle thickness in asthma is related to severity but not duration of asthma

Asthma is characterised by an increased airway smooth muscle (ASM) area (ASMarea) within the airway wall. The present study examined the relationship of factors including severity and duration of asthma to ASMarea. The perimeter of the basement membrane (PBM) and ASMarea were measured on transverse sections of large and small airways from post mortem cases of fatal (n=107) and nonfatal asthma (n=37) and from control subjects (n=69). The thickness of ASM (ASMarea/PBM) was compared between asthma groups using multivariate linear regression. When all airways were considered together, ASMarea/PBM (in millimetres) was increased in nonfatal (median 0.04; interquartile range 0.013-0.051; p=0.034) and fatal cases of asthma (0.048; 0.025-0.078; p<0.001) compared with controls (0.036; 0.024-0.042). Compared with cases of nonfatal asthma, ASMarea/PBM was greater in cases of fatal asthma in large (p<0.001) and medium (p<0.001), but not small, airways. ASMarea/PBM was not related to duration of asthma, age of onset of asthma, sex or smoking. No effect due to study centre, other than that due to sampling strategy, was found. The thickness of the ASM layer is increased in asthma and is related to the severity of asthma but not its duration.

Postural Control in Elderly Persons with Osteoporosis: Efficacy of an Intervention Program to Improve Balance and Muscle Strength A Randomized Controlled Trial

Burke TN, Franc, a FJR, de Meneses SRF, Cardoso VI, Marques AP: Postural control in elderly persons with osteoporosis: Efficacy of an intervention program to improve balance and muscle strength: A randomized controlled trial. Am J Phys Med Rehabil 2010; 89: 549-556. Objective: To assess the efficacy of an exercise program aiming to improve balance and muscular strength, for postural control and muscular strength of women with osteoporosis. Design: Sample consisted of 33 women with osteoporosis, randomized into one of two groups: intervention group, in which exercises for balance and improvement of muscular strength of the inferior members were performed for 8 wks (n = 17, age 72.8 +/- 3.6 yrs); control group, which was women not practicing exercises (n = 16, age 74.4 +/- 3.7 yrs). At baseline and after 8 wks of treatment, postural control was assessed using a force plate (Balance Master, Neurocom), and muscular strength during ankle dorsiflexion, knee extension, and flexion was assessed by dynamometry. Results: Adherence to the program was 82%. When compared with the control group, individuals in the intervention group significantly improved the center of pressure velocity (P = 0.02) in the modified clinical test of sensory interaction for balance test, center of pressure velocity (P < 0.01), and directional control (P < 0.01) in limits of stability test, isometric force during ankle dorsiflexion (P = 0.01), knee extension (P < 0.01), and knee flexion (P < 0.01). Conclusions: Balance and strength exercises are effective in improving postural control and lower-limb strength in elderly women with osteoporosis.

Protein disulfide isomerase overexpression in vascular smooth muscle cells induces spontaneous preemptive NADPH oxidase activation and Nox1 mRNA expression: Effects of nitrosothiol exposure

Mechanisms regulating NADPH oxidase remain open and include the redox chaperone protein disulfide isomerase (PDI). Here, we further investigated PDI effects on vascular NADPH oxidase. VSMC transfected with wild-type PDI (wt-PDI) OF PDI mutated in all four redox cysteines (mut-PDI) enhanced (2.5-fold) basal cellular ROS production and membrane NADPH oxidase activity, with 3-fold increase in Nox1, but not Nox4 mRNA. However, further ROS production, NADPH oxidase activity and Nox1 mRNA increase triggered by angiotensin-II (AngII) were totally lost with PDI overexpression, suggesting preemptive Nox1 activation in such cells. PDI overexpression increased Nox4 mRNA after AngII stimulus, although without parallel ROS increase. We also show that Nox inhibition by the nitric oxide donor GSNO is independent of PDI. PDI silencing decreased specifically Nox1 mRNA and protein, confirming that PDI may regulate Nox1 at transcriptional level in VSMC. Such data further strengthen the role of PDI as novel NADPH oxidase regulator. (C) 2009 Elsevier Inc. All rights reserved.

Influence of visual feedback on pelvic floor muscle strength

Objective: The objective of this study is to evaluate the visual feedback influence on pelvic floor muscle contraction. Study design: Seventeen nulliparous, urinary-continent women participated in this study. Pelvic floor muscle strength with and without the use of visual feedback was measured with a dynamometric speculum in two directions (anteroposterior and left-right). To compare the mean strength values with and without the use of visual feedback, the t test was applied. Results: There was no significant difference between the pelvic floor muscle anteroposterior strength values with and without the use of visual feedback (p = 0.30), and no significant difference for the left-right strength (p = 0.37). Conclusion: There was no difference between the pelvic floor muscle strength values with and without the use of visual feedback. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Stretch Injuries of Skeletal Muscles: Experimental Study in Rats` Soleus Muscle

The study aimed to verify the physiological injury behavior by stretching the soleus muscle of rats, using a noninvasive experimental model. Twenty-four rats were used and divided into three groups of eight animals: control group (A), group that performed tetanus followed by electrical stimulation and a sudden dorsiflexion of the left paw performed by a device equipped with a mechanism of muscle soleus rapid stretching (B); and a group that only received the tetanus (C). Three days later, the animals were killed, and the soleus muscle was resected and divided into three segments. Morphological changes indicative of muscle damage appeared in all three segments of group B. In a lesser degree, similar changes were also detected in muscles subjected to only tetanus. This model was effective; reproducing an injury similar to what occurs in human sports injuries.

Changes in postnatal skeletal muscle development induced by alternative immobilization model in female rat

The objective of this study was to adapt a model of hind limb immobilization to newly weaned female rats and to determine the morphology of shortened soleus and plantaris muscles. Female Wistar rats were divided into three groups: control zero (n = 3) and control and free (n = 8), animals aged 21 and 31 days, respectively, submitted to no intervention, and immobilized (n = 25), animals aged 21 days submitted to immobilization for 10 days and sacrificed at 31 days of age. The device used for immobilization had advantages such as easy connection, good fit, and low cost. The immobilized rats showed a reduction in muscle fiber area and in connective tissue. The adaptation of this immobilization model originally used for adult rats was an excellent alternative for newly weaned rats and was also efficient in inducing significant hind limb disuse.

Electrical Stimulation During Gait Promotes Increase of Muscle Cross-sectional Area in Quadriplegics: A Preliminary Study

Increases in muscular cross-sectional area (CSA) occur in quadriplegics after training, but the effects of neuromuscular electrical stimulation (NMES) along with training are unknown. Thus, we addressed two questions: (1) Does NMES during treadmill gait training increase the quadriceps CSA in complete quadriplegics?; and (2) Is treadmill gait training alone enough to observe an increase in CSA? Fifteen quadriplegics were divided into gait (n = 8) and control (n = 7) groups. The gait group performed training with NMES for 6 months twice a week for 20 minutes each time. After 6 months of traditional therapy, the control group received the same gait training protocol but without NMES for an additional 6 months. Axial images of the thigh were acquired at the beginning of the study, at 6 months (for both groups), and at 12 months for the control group to determine the average quadriceps CSA. After 6 months, there was an increase of CSA in the gait group (from 49.8 +/- A 9.4 cm(2) to 57.3 +/- A 10.3 cm(2)), but not in the control group (from 43.6 +/- A 7.6 cm(2) to 41.8 +/- A 8.4 cm(2)). After another 6 months of gait without NMES in the control group, the CSA did not change (from 41.8 +/- A 8.4 cm(2) to 41.7 +/- A 7.9 cm(2)). The increase in quadriceps CSA after gait training in patients with chronic complete quadriplegia appears associated with NMES.

Biomechanical effects of immobilization and rehabilitation on the skeletal muscle of trained and sedentary rats

Because of the scarcity of information about the comparison of training to sedentarism beforehand immobilization and rehabilitation through muscle mechanical properties, the present work investigates this theme. Seventy rats were divided into 7 groups: 1-control (C); 2-trained (T); 3-sedentary (S); 4-trained and immobilized (TI); 5-sedentary and immobilized (SI); 6-trained, immobilized and rehabilitated (TIR); 7-sedentary, immobilized and rehabilitated (SIR). Interventions: Swimming training; Sedentarism (reduced size cages); Cast immobilization (pelvic limb) and water rehabilitation. Load at the limit of proportionality (LLP), maximum limit load (MLL) and stiffness (St) were the mechanical properties determined after a mechanical test of traction of the gastrocnemius. The training improved all mechanical properties when compared to sedentarism. After immobilization, LLP and MLL were reduced in TI and SI. However, there was no difference in St between C and TI. Additionally, TI showed improved MLL when compared to SI. The comparison of TI and TIR showed significant melioration in all properties after remobilization. SIR showed an improvement only in MLL when compared to SI. Significant melioration in LLP and St was observed in TIR compared to SIR. We demonstrated that the training before immobilization and rehabilitation had a positive effect on the muscle mechanical behavior compared to sedentarism. This analysis is of fundamental importance because it helps characterize the muscle tissue under different functional demands.