Cutting edge: guinea pigs with a natural C3a-receptor defect exhibit decreased bronchoconstriction in allergic airway disease: evidence for an involvement of the C3a anaphylatoxin in the pathogenesis of asthma.

Asthma is a major cause of morbidity worldwide with prevalence and severity still increasing at an alarming pace. Hallmarks of this disease include early-phase bronchoconstriction with subsequent eosinophil infiltration, symptoms that may be mimicked in vivo by the complement-derived C3a anaphylatoxin, following its interaction with the single-copy C3aR. We analyzed the pathophysiological role of the C3a anaphylatoxin in a model of experimental OVA-induced allergic asthma, using an inbred guinea pig strain phenotypically unresponsive to C3a. Molecular analysis of this defect revealed a point mutation within the coding region of the C3aR that creates a stop codon, thereby effectively inactivating gene function. When challenged by OVA inhalation, sensitized animals of this strain exhibited a bronchoconstriction decreased by approximately 30% in comparison to the corresponding wild-type strain. These data suggest an important role of C3a in the pathogenesis of asthma and define a novel target for drug intervention strategies.

Support for a linear length-tension relation of the torso extensor muscles: an investigation of the length and velocity EMG-force relationships.

This study investigated the hypothesis that the length-tension relation of the torso erectors would be linear, mirroring the observed linear increase in extension strength capability toward full flexion. The effect of torso extension velocity on the tension capability of these muscles was also investigated for common motion speeds. A myoelectric-based approach was used wherein a dynamic biomechanical model incorporating active and passive tissue characteristics provided muscle kinematic estimates during controlled sagittal plane extension motions. A double linear optimization formulation from the literature provided muscle tension estimates. The data of five male subjects supported the hypothesis of a linear length-tension relation toward full flexion for both the erector spinae and latissimus muscles. Velocity trends agreed with the predicted by Hill's exponential relation, although linear trends were found to fit the data almost as well. The results have implications for muscle tension estimation in biomechanical torso modeling, and suggest a possible low back pain injury mechanism through tissue strain while lifting in fully flexed postures.

Distributed moment histogram: a neurophysiology based method of agonist and antagonist trunk muscle activity prediction.

A neurocortical-based technique of muscle recruitment is presented to solve the muscle indeterminacy problem for lumbar torso modeling. Cortical recordings from behaving primates have established motor cortex cells that respond to a wide range of task directions, but are tuned to a preferred direction. A characteristic activity pattern of these neurons seems to be associated with effort direction. It was hypothesized that a model which recruits muscles based on a similar distribution would predict antagonistic muscle activity with greater realism than a widely referenced optimization formulation. The predictions of the Distributed Moment Histogram (DMH) method were evaluated under common speed (< 30 degrees s-1) sagittal plane lifting conditions using five subjects. The predicted forces showed high correspondence with agonist and antagonist myoelectric patterns. The mean coefficient of determination for the erector spinae was r2 = 0.91, and 0.41 for the latissimus. For the antagonistic muscles, the rectus abdominus was found to be electrically silent (< 3% MVC) and no activity was predicted by the method. The external oblique muscle was observed to be minimally active (< 16% MVC), and the DMH method predicted its mostly constant activity with a mean standard error of 1.6% MVC. The realistic antagonistic predictions supported the hypothesis and justify this cortical based technique as an alternative for muscle tension estimation in biomechanical torso modeling. A primary advantage of this method is its computational simplicity and direct physiologic analog.

Trunk and hip muscle recruitment in response to external anterior lumbosacral shear and moment loads.

The response of select lumbar torso and pelvic muscles to loads applied at the lumbar spine and across the pelvis was investigated to help identify the sources of antagonistic lower torso muscle recruitment. Five subjects in the neutral upright posture were loaded with L(4-5) moment and anterior shear forces under constrained and free pelvic rotation conditions. The activity states of the erector spinae, latissimus dorsi, external oblique, rectus abdominis, gluteus maximus, and rectus femoris muscles were monitored using surface electromyography. Regression analysis was used to test if (1) lumbar shear loads influence the activity of the torso muscles, and (2) moments about the pelvis significantly influence the torso muscle activities. The pelvic muscles (gluteus maximus and rectus femoris) were monitored for their role in stabilizing pelvic rotation. The statistical analysis did not support the hypothesis that torso muscles are recruited in response to shear loading. Also, the data did not provide conclusive evidence that moments about the pelvis relative to the lumbar spine significantly influence torso muscle recruitment. For the subjects that exhibited elevated antagonistic muscle activity, no explanation of this recruitment strategy could be statistically related to lumbar shear or pelvic moments. RELEVANCE:--Omission of pelvic moments in biomechanical modelling of the lumbar torso does not seem to be introducing significant error in the prediction of torso muscle activity. The results of this study indicate that the source of lumbar torso muscle antagonistic activity under sagittal plane flexion loading seems to be a result of yet unidentified factors.