Biomechanical factors associated with shoe/pedal interfaces. Implications for injury.

The principal demand on the body during cycling is on the lower extremities as they are responsible for producing a majority of the energy imparted to the bike. As a result the legs, due to high reactive forces between the foot and pedal, experience high loads on the joints. These loads may adversely affect joint tissues and contribute to overuse injuries, e.g. knee pain. The mechanical link between the leg and the bike is the shoe/pedal interface. This transmission site, by design, can either create smooth transfer of energy or abnormally high repetitive loads which are potentially injurious to the body. Incidence of lower extremity injury in cycling is high, and historically biomechanical analyses of this activity have focused their attention on either the rider or the bike, but not the link between the two. Recently, pedal designs have changed in response to complaints of sore knees with the development of pedals allowing varying degrees of float. This form of transmission is intended to enhance power transfer from rider to bike as well as minimise trauma to the legs by permitting the foot to rotate during the pedalling cycle in a toe-in/heel-out or heel-in/toe-out movement pattern. Recent evidence suggests this type of pedal design does reduce trauma and maintains power output. This article reviews common lower extremity overuse injuries and biomechanical factors during the pedalling cycle with the primary focus on the shoe/pedal interface. We will summarise information available on lower extremity kinematics and kinetics as well as recent data specifically related to shoe/pedal interface kinetics, evaluation of different pedal types-specifically comparison between clipless 'fixed' and clipless 'float' systems-and discuss their resultant effect on lower extremity dynamics and their implications for injury.

The influence of head restraint and occupant factors on peak head/neck kinematics in low-speed rear-end collisions.

Prior two-way analyses of variance showed that the peak kinematic response of the head and neck of subjects exposed to low-speed rear-end collisions was related to speed change and gender, however potential reasons for this gender dependence were not determined. Using multiple linear regression, this study further examined these response data to determine the relative influence of specific factors, including subject anthropometry, neck strength, cervical range of motion, seated posture and head restraint position, which may have been responsible for the previously-observed gender dependence. The results of this analysis showed that vehicle speed change and relative head restraint position explained the largest proportion of the observed variation in peak occupant kinematic response. Seated posture measures also explained some of the variation in kinematic response. The current analysis prioritizes which variables to explore more thoroughly in future research and which variables should be carefully controlled in future studies.

The relationship between clinical and kinematic responses from human subject testing in rear-end automobile collisions.

Recent experiments have produced a linked data set of clinical and kinematic responses for human subjects exposed to controlled low-speed rear-end collisions. The purpose of this paper was to examine this paired data set and determine whether the presence or absence of clinical symptoms could be predicted from the peak linear and angular kinematic response of the head and neck. The data were generated using 42 male and female human subjects seated normally in the front passenger seat of a stationary vehicle struck from behind to produce vehicle speed changes of 4 and 8 km/h. Pre- and post-test clinical examinations documented the presence, severity and duration of whiplash-associated disorders (WAD). Logistic regression and backward elimination of independent variables were used to develop the prediction model. The analysis yielded a 16 parameter model that was significantly related (odds ratio = 21.2; P = 0.0069) to the presence or absence of transient whiplash symptoms. The model correctly predicted symptom presence in 13 of 23 tests (sensitivity 57%) and symptom absence in 49 of 52 tests (specificity 94%) in a population of 75 with a symptom prevalence of 31%. The model's positive predictive value was 81% and its negative predictive value was 83%. Despite statistical significance, the model did not discriminate between the presence and absence of symptoms in all tests, and indicated that factors other than the selected peak kinematic responses influenced symptom production.

Cervical muscle response during whiplash: evidence of a lengthening muscle contraction.

OBJECTIVE: To assess the potential for cervical muscle injury from a rear-end automobile collision. DESIGN: Experimental design in which human subjects were exposed to low-speed rear-end collisions. The influence of independent variable (gender, speed change, muscle group, and motion phase) on dependent variables (kinematic response, muscle onset and muscle activation level) was examined using repeated-measures analysis of variance. BACKGROUND: Injuries to various tissues of the cervical spine have been proposed, yet little attention has been focused on the cervical muscles as a site of injury. METHODS: 42 subjects (21 males, 20-40 yr) were exposed to collisions of 4 and 8 km/h speed change while measuring kinematic response of the head and torso and electromyography of the sternocleidomastoid and cervical paraspinal muscles. RESULTS: Muscle activation occurred earlier in females and in the 8 km/h speed change. Sternocleidomastoid onset preceded paraspinal onset. Muscle activation level varied significantly with speed change, motion phase and muscle group. Initial rearward retraction of the head relative to the torso resulted in lengthening of the activated sternocleidomastoid, consistent with a contraction-induced muscle injury. CONCLUSIONS: The cervical muscles contract rapidly in response to impact and the potential exists for muscle injury due to lengthening contractions. RELEVANCE: The clinician should recognize the role of cervical retraction in the mechanism of whiplash injury and avoid aggressive motion in that plane during diagnosis and treatment. An understanding of whiplash injury mechanisms should improve patient education and preventative measures.

Purification and characterization of a rat liver bile acid coenzyme A ligase from rat liver microsomes.

In the present study, using the C24 bile acid chenodeoxycholic acid as substrate, rat liver bile acid CoA ligase activity (rBAL) was purified 200-fold from detergent-solubilized microsomes using a combination of Q-Sepharose anion exchange, hydroxyapatite, and CM-Sepharose chromatography. Purified rBAL had a molecular weight of 65 kDa by SDS-PAGE analysis. Gel filtration of purified rBAL indicated that rBAL activity forms a complex with other proteins with an apparent aggregate molecular weight of 243 kDa. A monoclonal antibody raised against the 65-kDa protein and covalently coupled to 6B-Sepharose completely absorbed rBAL activity from a semipurified preparation of rat liver microsomes. Western blot analysis confirmed the elution of the 65-kDa protein from the affinity phase at low pH. Optimum rBAL activity was found at pH 8.5, and activity was dependent on the divalent cation Mg2+. In the presence of 50 microM CoA and 2.5 mM MgCl2, kinetic analysis revealed that the apparent K(m)s of ATP and chenodeoxycholic acid of the purified enzyme were 548 +/- 247 and 18.0 +/- 6.2 microM, respectively, and the apparent Vmax was 9.53 +/- 2.0 nmol min-1 mg protein-1. The formation of chenodeoxycholyl-CoA by rBAL was strongly inhibited by hydrophobic bile acids (the C24 monohydroxy bile acid lithocholic acid and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid, the C27 homolog of cholic acid), but only weakly by cholic acid. Chenodeoxycholyl-CoA and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-27-oyl-CoA were confirmed as reaction products of purified rBAL by HPLC-electrospray ionization mass spectrometry.

Conjugation of haloalkanes by bacterial and mammalian glutathione transferases: mono- and vicinal dihaloethanes.

Glutathione (GSH) transferases are generally involved in the detoxication of xenobiotic chemicals. However, conjugation can also activate compounds and result in DNA modification. Activation of 1,2-dihaloethanes (BrCH(2)CH(2)Br, BrCH(2)CH(2)Cl, and ClCH(2)CH(2)Cl) was investigated using two mammalian theta class GSH transferases (rat GST 5-5 and human GST T1) and a bacterial dichloromethane dehalogenase (DM11). Although the literature suggests that the bacterial dehalogenase does not catalyze reactions with CH(3)Cl, ClCH(2)CH(2)Cl, or CH(3)CHCl(2), we found a higher enzyme efficiency for DM11 than for the mammalian GSH transferases in conjugating CH(3)Cl, CH(3)CH(2)Cl, and CH(3)CH(2)Br. Enzymatic rates of activation of 1,2-dihaloethanes were determined in vitro by measuring S,S-ethylene-bis-GSH, the major product trapped by nonenzymatic reaction with the substrate GSH. Salmonella typhimurium TA 1535 systems expressing each of these GSH transferases were used to determine mutagenicity. Rates of formation of S,S-ethylene-bis-GSH by the GSH transferases correlated with the mutagenicity determined in the reversion assays for the three 1,2-dihaloethanes, consistent with the view that half-mustards are the mutagenic products of the GSH transferase reactions. Half-mustards [S-(2-haloethyl)GSH] containing either F, Cl, or Br (as the leaving group) were tested for their abilities to induce revertants in S. typhimurium, and rates of hydrolysis were also determined. GSH transferases do not appear to be involved in the breakdown of the half-mustard intermediates. A halide order (Br > Cl) was observed for both GSH transferase-catalyzed mutagenicity and S,S-ethylene-bis-GSH formation from 1,2-dihaloethanes, with the single exception (both assays) of BrCH(2)CH(2)Cl reaction with DM11, which was unexpectedly high. The lack of substrate saturation seen for conjugation of dihalomethanes with GSTs 5-5 and T1 was also observed with the mono- and 1,2-dihaloethanes [Wheeler, J. B., Stourman, N. V., Thier, R., Dommermuth, A., Vuilleumier, S., Rose, J. A., Armstrong, R. N., and Guengerich, F. P. (2001) Chem. Res. Toxicol. 14, 1118-1127], indicative of an inherent difference in the catalytic mechanisms of the bacterial and mammalian GSH transferases.

Clinical response of human subjects to rear-end automobile collisions.

OBJECTIVE: Forty-two persons were exposed to controlled low-speed rear-end automobile collisions to assess the relation between both gender and impact severity and the presence, severity, and duration of whiplash-associated disorders (WAD). Individual measures were also assessed for their potential to predict the onset of WAD. DESIGN: Experimental study subjecting individuals to a speed change of 4 km/h and 8 km/h and utilizing pretest and posttest physical examinations (immediately after and 24 hours after impact) to quantify subjects' clinical response. RESULTS: Approximately 29% and 38% of the subjects exposed to the 4 km/h and 8 km/h speed changes, respectively, experienced WAD symptoms, with cervical symptoms and headaches predominating. Objective clinical deficits consistent with WAD were measured in both men and women subjects at both 4 km/h and 8 km/h. At 4 km/h, the duration of symptoms experienced by women was significantly longer when compared with that in men (p < .05). There were no significant differences in the presence and severity of WAD between men and women at 4 km/h and 8 km/h or in the duration of WAD at 8 km/h. There was also no significant difference in the presence, severity, and duration of WAD between 4 km/h and 8 km/h. No preimpact measures were predictive of WAD. CONCLUSION: The empirical findings in this study contribute to establishing a causal relationship between rear-end collisions and clinical signs and symptoms.

Conjugation of haloalkanes by bacterial and mammalian glutathione transferases: mono- and dihalomethanes.

A primary route of metabolism of dihalomethanes occurs via glutathione (GSH) transferase-catalyzed conjugation. Mammalian theta class GSH transferases and a group of bacterial dichloromethane dehalogenases are able to catalyze the hydrolytic dehalogenation of dihalomethanes via GSH conjugation and subsequent formation of HCHO. Dihalomethanes have been shown to induce revertants in Salmonella typhimurium TA 1535 expressing theta class GSH transferases. Two mammalian theta class GSH transferases (rat GST 5-5 and human GST T1) and the bacterial dehalogenase DM11 were compared in the in vitro conjugation of CH(3)Cl and using in vitro assays (HCHO formation) and the S. typhimurium mutagenesis assay with the dihalomethanes CH(2)Cl(2), CH(2)Br(2), CH(2)BrCl, CH(2)ICl, CH(2)I(2), and CH(2)ClF. GSTs 5-5 and T1 had similar characteristics and exhibited first-order rather than Michaelis-Menten kinetics for HCHO formation over the range of dihalomethane concentrations tested. In contrast, the DM11 enzyme displayed typical hyperbolic Michaelis-Menten kinetics for all of the compounds tested. A similar pattern was observed for the conjugation of CH(3)Cl. The reversion tests with S. typhimurium expressing DM11 or GST 5-5 showed a concentration-dependent increase in revertants for most of the dihalomethanes, and DM11 produced revertants at dihalomethane concentrations lower than GST 5-5. Collectively, the results indicate that rates of conversion of dihalomethanes to HCHO are not correlated with mutagenicity and that GSH conjugates are genotoxic. The results are compared with the conjugation and genotoxicity of haloethanes in the preceding paper in this issue [Wheeler, J. B., Stourman, N. V., Armstrong, R. N., and Guengerich, F. P. (2001) Chem. Res. Toxicol. 14, 1107-1117]. The halide order appears most important in the dihalomethane conjugation reactions catalyzed by GST 5-5 and less so in GST T1 and DM11, probably due to changes in the rate-limiting steps.