Increased short interval intracortical inhibition in participants with previous hamstring strain injury.

PURPOSE: Cortical mechanisms may contribute to weakness in participants with previous hamstring strain injury. This study aims to examine intra-cortical inhibition (SICI) and corticospinal excitability in previously injured participants. METHODS: In this cross-sectional study, TMS was used to examine SICI, silent period, silent period: MEP ratios and area under the stimulus response curve in the biceps femoris and medial hamstrings. Comparisons were made between participants with (n = 10) and without (n = 10) previous hamstring strain injury. Motor threshold and isometric knee flexor strength were also compared between participants and the relationship between strength and SICI in control and previously injured participants was examined. RESULTS: Isometric knee flexor strength was lower in previously injured limbs compared with control limbs (mean difference = - 41 Nm (- 26%) [95% CI = - 80 to - 2 Nm], p = 0.04, Cohen's d = - 1.27) and contralateral uninjured limbs (mean difference = - 23 Nm (- 17%), [95% CI = - 40 to - 6 Nm], p = 0.01, Cohen's d = - 0.57). Previously injured limbs exhibited smaller responses to paired pulse stimulation (i.e. greater levels of SICI) in the biceps femoris compared with control limbs (mean difference = - 19%, [95% CI = - 34 to - 5%], p = 0.007, Cohen's d = - 1.33). Isometric knee flexor strength was associated with the level of SICI recorded in the biceps femoris in previously injured participants (coefficient = 23 Nm [95% CI = 7-40 Nm], adjusted R2 = 0.31, p = 0.01). There were no differences in markers of corticospinal excitability between previously injured and control limbs (all p > 0.24, all Cohen's d < 0.40). CONCLUSION: Athletes with previous injury in the biceps femoris exhibit increased SICI in this muscle compared with control participants. Increased SICI is related to lower levels of hamstring strength, and rehabilitation programs targeting the removal of intra-cortical inhibition should be considered.

Muscle activation patterns in the Nordic hamstring exercise: Impact of prior strain injury.

This study aimed to determine: (a) the spatial patterns of hamstring activation during the Nordic hamstring exercise (NHE); (b) whether previously injured hamstrings display activation deficits during the NHE; and (c) whether previously injured hamstrings exhibit altered cross-sectional area (CSA). Ten healthy, recreationally active men with a history of unilateral hamstring strain injury underwent functional magnetic resonance imaging of their thighs before and after six sets of 10 repetitions of the NHE. Transverse (T2) relaxation times of all hamstring muscles [biceps femoris long head (BFlh); biceps femoris short head (BFsh); semitendinosus (ST); semimembranosus (SM)] were measured at rest and immediately after the NHE and CSA was measured at rest. For the uninjured limb, the ST's percentage increase in T2 with exercise was 16.8%, 15.8%, and 20.2% greater than the increases exhibited by the BFlh, BFsh, and SM, respectively (P < 0.002 for all). Previously injured hamstring muscles (n = 10) displayed significantly smaller increases in T2 post-exercise than the homonymous muscles in the uninjured contralateral limb (mean difference -7.2%, P = 0.001). No muscles displayed significant between-limb differences in CSA. During the NHE, the ST is preferentially activated and previously injured hamstring muscles display chronic activation deficits compared with uninjured contralateral muscles.

Reduced biceps femoris myoelectrical activity influences eccentric knee flexor weakness after repeat sprint running.

The aim of this study was to determine whether declines in knee flexor strength following overground repeat sprints were related to changes in hamstrings myoelectrical activity. Seventeen recreationally active men completed maximal isokinetic concentric and eccentric knee flexor strength assessments at 180°/s before and after repeat sprint running. Myoelectrical activity of the biceps femoris (BF) and medial hamstrings (MHs) was measured during all isokinetic contractions. Repeated measures mixed model [fixed factors = time (pre- and post-repeat sprint) and leg (dominant and nondominant), random factor = participants] design was fitted with the restricted maximal likelihood method. Repeat sprint running resulted in significant declines in eccentric, and concentric, knee flexor strength (eccentric = 26 ± 4 Nm, 15% P < 0.001; concentric 11 ± 2 Nm, 10% P < 0.001). Eccentric BF myoelectrical activity was significantly reduced (10%; P = 0.035). Concentric BF and all MH myoelectrical activity were not altered. The declines in maximal eccentric torque were associated with the change in eccentric BF myoelectrical activity (P = 0.013). Following repeat sprint running, there were preferential declines in the myoelectrical activity of the BF, which explained declines in eccentric knee flexor strength.

The Acute Effects of Eccentrically-Biased Versus Conventional Weight Training in Older Adults: A Randomised Controlled Cross-Over Study.

BACKGROUND: Whilst resistance training has been proven to convey considerable benefits to older people; immediately post-exercise there may be elevated transient risks for cardiac events and falls. Objectives and Measurements: We assessed the acute effects of eccentrically-biased (EB) and conventional (CONV) resistance exercise on: platelet number, activation and granule exocytsosis; and mean velocity of centre of pressure displacement (Vm). DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: Ten older adults (7 males, 3 females; 69 ± 4 years) participated in this randomised controlled cross-over study in which they performed EB and CONV training sessions that were matched for total work and a control condition. RESULTS: Immediately post-exercise there was a statistically significant difference in platelet count between the control condition, in which it had declined (pre 224 ± 35 109/L; post 211 ± 30 109/L: P < 0.05) and CONV in which it had increased (pre 236 ± 55 109/L; post 242 ± 51 109/L: P > 0.05). There was no change in platelet activation and granule exocytsosis or Vm following EB and CONV. CONCLUSIONS: Overall, while minor differences between regimens were observed, no major adverse effect on parameters of platelet function or centre of pressure displacement were observed acutely following either regimen. Eccentrically-biased and conventional resistance exercise training regimens do not appear to present an elevated acute risk in the context of changes to platelet function contributing to a cardiac event or postural stability increasing falls risk for apparently healthy older adults.

Human catechol O-methyltransferase genetic variation: gene resequencing and functional characterization of variant allozymes.

Catechol O-methyltransferase (COMT) plays an important role in the metabolism of catecholamines, catecholestrogens and catechol drugs. A common COMT G472A genetic polymorphism (Val108/158Met) that was identified previously is associated with decreased levels of enzyme activity and has been implicated as a possible risk factor for neuropsychiatric disease. We set out to 'resequence' the human COMT gene using DNA samples from 60 African-American and 60 Caucasian-American subjects. A total of 23 single nucleotide polymorphisms (SNPs), including a novel nonsynonymous cSNP present only in DNA from African-American subjects, and one insertion/deletion were observed. The wild type (WT) and two variant allozymes, Thr52 and Met108, were transiently expressed in COS-1 and HEK293 cells. There was no significant change in level of COMT activity for the Thr52 variant allozyme, but there was a 40% decrease in the level of activity in cells transfected with the Met108 construct. Apparent K(m) values of the WT and variant allozymes for the two reaction cosubstrates differed slightly, but significantly, for 3,4-dihydroxybenzoic acid but not for S-adenosyl-L-methionine. The Met108 allozyme displayed a 70-90% decrease in immunoreactive protein when compared with WT, but there was no significant change in the level of immunoreactive protein for Thr52. A significant decrease in the level of immunoreactive protein was also observed in hepatic biopsy samples from patients homozygous for the allele encoding Met108. These observations represent steps toward an understanding of molecular genetic mechanisms responsible for variation in COMT level and/or properties, variation that may contribute to the pathophysiology of neuropsychiatric disease.

Role of glutathione S-transferase mu (GSTM1) in styrene-7,8-oxide toxicity and mutagenicity.

In the human glutathione S-transferase (GST) mu gene family, homozygous deletion of GSTM1 is the null phenotype (frequency of approximately 50% in Caucasians). In the current study, GSTM1 status was determined in human cell lines using reverse transcriptase, polymerase chain reaction, and immunochemistry. Cell lines were challenged with a range of doses of styrene-7,8-oxide (SO) and then toxicity and genotoxicity were monitored. Toxicity was determined by growth in flasks and genotoxicity by cloning in microplates in the presence/absence of 6-thioguanine, to detect mutations at the hypoxanthine phosphoribosyltransferase (hprt) locus. A SO concentration-dependent decrease in survival was observed for all cell lines, with GSTM1-deficient lines being more sensitive. The IC(50)s of deficient and proficient cell lines were 0.45 and 0.55 mM SO, respectively. The difference between survival of GSTM1-deficient and -proficient cell lines approached statistical significance. The background mutation frequency of GSTM1-deficient cell lines was 2 x 10(-5), and that of GSTM1-proficient cell lines was 3 x 10(-6). GSTM1-deficient cell lines were significantly more sensitive than GSTM1-proficient cell lines to mutation induction for concentrations up to 2.5 mM SO (P < 0.001, regression analysis). These results suggest that cell lines containing metabolically competent GSTM1 are able to efficiently use GSTM1 to conjugate SO and reduce its hazard. This supports the epidemiological evidence that GSTM1 influences sensitivity to chemical carcinogenesis and subsequent risk of cancer induction.

Mutagenic damage to mammalian cells by therapeutic alkylating agents.

Cytotoxic alkylating agents used as therapeutics include nitrogen mustards, ethyleneimines, alkyl sulfonates, nitrosoureas and triazenes. Their reactivity with DNA, RNA and proteins can cause cell death. Side-effects of treatment include tissue toxicity and secondary malignancies, likely due to the genetic damage induced. The full mutagenic potential of alkylating agents may only be realised after they undergo metabolic activation, principally by cytochromes P450. Mutagenicity is related to the ability of alkylating agents to form crosslinks and/or transfer an alkyl group to form monoadducts in DNA. The most frequent location of adducts in the DNA is at guanines. Expressed mutations involve different base substitutions, including all types of transitions and transversions. The mutational spectra of alkylating agents on mammalian cells is distinct from that induced in bacterial cells, reflecting the different codon usage by bacteria and differences in DNA repair and replication enzymes. Mutations are induced by busulfan, chlorambucil (CAB), cyclophosphamide (CP, or its metabolite), dacarbazine, mechlorethamine, melphalan, mitomycin-C (MMC), nitrosoureas and thiotepa. Although dose-dependent, the relationship is not always linear. The molarities at which alkylating agents induce cell killing and mutations vary over three orders of magnitude. The mutagenic efficiency, of alkylating agents also varies, with some agents inducing three times more mutations for equivalent cell killing. The induction of micronuclei, sister chromatid exchanges, or chromosome aberrations is variable, but has been observed for CP, CAB, MMC, melphalan and triethylenemelamine. There is insufficient information to determine whether any synergistic effects of alkylating agents used in combination will influence the cytotoxic and mutagenic damage equally. Understanding the potential synergy of alkylating agents at the cellular and molecular level should allow improvement of the therapeutic efficacy of alkylating agents without increasing the unwanted mutation induction.