Assessing the usefulness of acute physiological responses following resistance exercise: sensitivity, magnitude of change, and time course of measures.

A variety of strategies exist to modulate the acute physiological responses following resistance exercise aimed at enhancing recovery and/or adaptation processes. To assess the true impact of these strategies, it is important to know the ability of different measures to detect meaningful change. We investigated the sensitivity of measures used to quantify acute physiological responses to resistance exercise and constructed a physiological profile to characterise the magnitude of change and the time course of these responses. Eight males accustomed to regular resistance exercise performed experimental sessions during a "control week", void of an exercise stimulus. The following week, termed the "exercise week", participants repeated this sequence of experimental sessions, and they also performed a bout of lower-limb resistance exercise following the baseline assessments. Assessments were conducted at baseline and at 2, 6, 24, 48, 72, and 96 h after the intervention. On the basis of the signal-to-noise ratio, the most sensitive measures were maximal voluntary isometric contraction, 20-m sprint, countermovement jump peak force, rate of force development (100-200 ms), muscle soreness, Daily Analysis Of Life Demands For Athletes part B, limb girth, matrix metalloproteinase-9, interleukin-6, creatine kinase, and high-sensitivity C-reactive protein with ratios >1.5. Clear changes in these measures following resistance exercise were determined via magnitude-based inferences. These findings highlight measures that can detect real changes in acute physiological responses following resistance exercise in trained individuals. Researchers investigating strategies to manipulate acute physiological responses for recovery and/or adaptation can use these measures, as well as the recommended sampling points, to be confident that their interventions are making a worthwhile impact.

Adolescent Distal Humerus Fractures: ORIF Versus CRPP.

BACKGROUND: Although supracondylar humerus fractures are common in young children, the incidence in adolescents is much lower. As a result, there is a paucity of literature to guide treatment. The purpose of this study was to review the treatment and outcomes for a consecutive series of distal humerus fractures in adolescents and to compare outcomes between patients treated with percutaneous skeletal fixation and those treated with open reduction and fixation. METHODS: A retrospective review of patients 10 to 17 years of age who underwent surgical treatment for a distal humerus fracture from 2005 to 2014 was performed. Patients with medial epicondyle fractures and those with insufficient follow-up to document union or return of motion were excluded. Medical records were reviewed to collect demographic data as well as operative approach and method of fixation. Clinical outcomes included range of motion, time to maximum motion, and complications [nerve dysfunction, heterotopic ossification (HO), need for secondary surgery]. Radiographs were reviewed to determine time to union as well as coronal and sagittal alignment. RESULTS: One hundred eighteen adolescents with displaced distal humerus fractures were identified. Eighty-one met inclusion criteria. Forty-four of these were classified as extra-articular [Orthopaedic Trauma Association (OTA) 13-A], and 37 were intra-articular fractures (10 OTA 13-B and 27 OTA 13-C).Although not statistically significant, closed treatment with percutaneous fixation of extra-articular fractures resulted in greater flexion-extension arc of motion at final follow-up (128 vs. 119 degrees, P=0.17) and demonstrated more rapid return of motion (2.8 vs. 3.9 mo, P=0.05) when compared with open treatment despite a longer duration of immobilization and less formal physical therapy. Complications such as HO (P=0.05), nerve dysfunction (P=0.02), and secondary surgery (P=0.001) were more common in the open treatment group.Closed treatment with percutaneous fixation of intra-articular fractures was performed in younger patients of similar size (12.8 vs. 14.4 y, P<0.01; 154 vs. 142 lbs, P=0.5). There were no significant differences between groups in regard to outcomes or complications. There were trends toward increased frequency of HO, nerve dysfunction, and secondary surgery in the open treatment group.Patients with intra-articular fractures were older (14.2 vs. 11.5 y, P<0.001) and heavier (144 vs. 94 lbs, P<0.001) than patients with extra-articular fractures and were more likely to be treated open (74% vs. 11%, P<0.001). Extra-articular fractures demonstrated a greater total arc of motion (126 vs. 118 degrees, P=0.04) at final follow-up despite longer duration of immobilization (23 vs. 15 d, P=0.002), and less physical therapy (27% vs. 73%, P<0.001). Radiographic carrying angle (16.6 vs. 22.3 degrees, P=0.08) and anterior humeral line (95% vs. 81%, P=0.07) trended toward more anatomic alignment in the extra-articular group. Secondary surgery was more common after intra-articular fracture (24% vs. 7%, P=0.03). CONCLUSIONS: Closed reduction and pinning of extra-articular distal humerus fractures in adolescents resulted in predictable clinical and radiographic outcomes and allowed for earlier return of motion and fewer complications when compared with open treatment. Intra-articular distal humerus fractures occur more frequently in older adolescents and are more likely to require open reduction and internal fixation to obtain joint congruity. Patients with intra-articular injuries should be cautioned that regaining full elbow motion may be more difficult, and there is an increased risk for complications and need for additional surgery. Closed reduction and percutaneous fixation of intra-articular injuries appears to be a reasonable option in select patients. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

The Effects of Montmorency Tart Cherry Concentrate Supplementation on Recovery Following Prolonged, Intermittent Exercise.

This study investigated Montmorency tart cherry concentrate (MC) supplementation on markers of recovery following prolonged, intermittent sprint activity. Sixteen semi-professional, male soccer players, who had dietary restrictions imposed for the duration of the study, were divided into two equal groups and consumed either MC or placebo (PLA) supplementation for eight consecutive days (30 mL twice per day). On day 5, participants completed an adapted version of the Loughborough Intermittent Shuttle Test (LISTADAPT). Maximal voluntary isometric contraction (MVIC), 20 m Sprint, counter movement jump (CMJ), agility and muscle soreness (DOMS) were assessed at baseline, and 24, 48 and 72 h post-exercise. Measures of inflammation (IL-1-ß, IL-6, IL-8, TNF-α, hsCRP), muscle damage (CK) and oxidative stress (LOOH) were analysed at baseline and 1, 3, 5, 24, 48 and 72 h post-exercise. Performance indices (MVIC, CMJ and agility) recovered faster and muscle soreness (DOMS) ratings were lower in the MC group (p < 0.05). Additionally, the acute inflammatory response (IL-6) was attenuated in the MC group. There were no effects for LOOH and CK. These findings suggest MC is efficacious in accelerating recovery following prolonged, repeat sprint activity, such as soccer and rugby, and lends further evidence that polyphenol-rich foods like MC are effective in accelerating recovery following various types of strenuous exercise.

Phytochemical uptake following human consumption of Montmorency tart cherry (L. Prunus cerasus) and influence of phenolic acids on vascular smooth muscle cells in vitro.

PURPOSE: To investigate the phytochemical uptake following human consumption of Montmorency tart cherry (L. Prunus cerasus) and influence of selected phenolic acids on vascular smooth muscle cells in vitro. METHODS: In a randomised, double-blinded, crossover design, 12 healthy males consumed either 30 or 60 mL of Montmorency tart cherry concentrate. Following analysis of the juice composition, venous blood samples were taken before and 1, 2, 3, 5 and 8 h post-consumption of the beverage. In addition to examining some aspects of the concentrate contents, plasma concentrations of protocatechuic acid (PCA), vanillic acid (VA) and chlorogenic (CHL) acid were analysed by reversed-phase high-performance liquid chromatography (HPLC) with diode array for quantitation and mass spectrometry detection (LCMS) for qualitative purposes. Vascular smooth muscle cell migration and proliferation were also assessed in vitro. RESULTS: Both the 30 and 60 mL doses of Montmorency cherry concentrate contained high amounts of total phenolics (71.37 ± 0.11; 142.73 ± 0.22 mg/L) and total anthocyanins (62.47 ± 0.31; 31.24 ± 0.16 mg/L), as well as large quantities of CHL (0.205 ± 0.24; 0.410 ± 0.48 mg/L) and VA (0.253 ± 0.84; 0.506 ± 1.68 mg/L). HPLC/LCMS identified two dihydroxybenzoic acids (PCA and VA) in plasma following MC concentrate consumption. Both compounds were most abundant 1-2 h post-initial ingestion with traces detectable at 8 h post-ingestion. Cell migration was significantly influenced by the combination of PCA and VA, but not in isolation. There was no effect of the compounds on cell proliferation. CONCLUSIONS: These data show new information that phenolic compounds thought to exert vasoactive properties are bioavailable in vivo following MC consumption and subsequently can influence cell behaviour. These data may be useful for the design and interpretation of intervention studies investigating the health effects of Montmorency cherries.

Recovery facilitation with Montmorency cherries following high-intensity, metabolically challenging exercise.

The impact of Montmorency tart cherry (Prunus cerasus L.) concentrate (MC) on physiological indices and functional performance was examined following a bout of high-intensity stochastic cycling. Trained cyclists (n = 16) were equally divided into 2 groups (MC or isoenergetic placebo (PLA)) and consumed 30 mL of supplement, twice per day for 8 consecutive days. On the fifth day of supplementation, participants completed a 109-min cycling trial designed to replicate road race demands. Functional performance (maximum voluntary isometric contraction (MVIC), cycling efficiency, 6-s peak cycling power) and delayed onset muscle soreness were assessed at baseline, 24, 48, and 72 h post-trial. Blood samples collected at baseline, immediately pre- and post-trial, and at 1, 3, 5, 24, 48, and 72 h post-trial were analysed for indices of inflammation (interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor alpha, high-sensitivity C-reactive protein (hsCRP)), oxidative stress (lipid hydroperoxides), and muscle damage (creatine kinase). MVIC (P < 0.05) did not decline in the MC group (vs. PLA) across the 72-h post-trial period and economy (P < 0.05) was improved in the MC group at 24 h. IL-6 (P < 0.001) and hsCRP (P < 0.05) responses to the trial were attenuated with MC (vs. PLA). No other blood markers were significantly different between MC and PLA groups. The results of the study suggest that Montmorency cherry concentrate can be an efficacious functional food for accelerating recovery and reducing exercise-induced inflammation following strenuous cycling exercise.

Effects of seated and standing cold water immersion on recovery from repeated sprinting.

This study investigated the effects of two different hydrostatic pressures (seated or standing) during cold water immersion at attenuating the deleterious effects of strenuous exercise on indices of damage and recovery. Twenty four male well-trained games players (age 23 ± 3 years; body mass 81.4 ± 8.7 kg: [Formula: see text]O2max 57.5 ± 4.9 ml∙kg(-1)∙min(-1)) completed the Loughborough Intermittent Shuttle Test (LIST) and were randomly assigned to either a control, seated cold water immersion or a standing cold water immersion (14 min at 14°C). Maximal isometric voluntary contraction, counter-movement jump, creatine kinase, C-reactive protein, interleukin-6 and delayed onset muscle soreness (DOMS) were measured before and up to 72 h following the LIST. All dependent variables showed main effects for time (P < 0.05) following the LIST, indicating physiological stress and muscle damage following the exercise. There were no significant group differences between control and either of the cold water immersion interventions. Seated cold water immersion was associated with lower DOMS than standing cold water immersion (effect size = 1.86; P = 0.001). These data suggest that increasing hydrostatic pressure by standing in cold water does not provide an additional recovery benefit over seated cold water immersion, and that both seated and standing immersions have no benefit in promoting recovery following intermittent sprint exercise.

Montmorency cherries reduce the oxidative stress and inflammatory responses to repeated days high-intensity stochastic cycling.

This investigation examined the impact of Montmorency tart cherry concentrate (MC) on physiological indices of oxidative stress, inflammation and muscle damage across 3 days simulated road cycle racing. Trained cyclists (n = 16) were divided into equal groups and consumed 30 mL of MC or placebo (PLA), twice per day for seven consecutive days. A simulated, high-intensity, stochastic road cycling trial, lasting 109 min, was completed on days 5, 6 and 7. Oxidative stress and inflammation were measured from blood samples collected at baseline and immediately pre- and post-trial on days 5, 6 and 7. Analyses for lipid hydroperoxides (LOOH), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), interleukin-1-beta (IL-1-ß), high-sensitivity C-reactive protein (hsCRP) and creatine kinase (CK) were conducted. LOOH (p < 0.01), IL-6 (p < 0.05) and hsCRP (p < 0.05) responses to trials were lower in the MC group versus PLA. No group or interaction effects were found for the other markers. The attenuated oxidative and inflammatory responses suggest MC may be efficacious in combating post-exercise oxidative and inflammatory cascades that can contribute to cellular disruption. Additionally, we demonstrate direct application for MC in repeated days cycling and conceivably other sporting scenario's where back-to-back performances are required.

Altered pH(i) regulation and Na(+)/HCO3(-) transporter activity in choroid plexus of cilia-defective Tg737(orpk) mutant mouse.

Tg737(orpk) mice have defects in cilia assembly and develop hydrocephalus in the perinatal period of life. Hydrocephalus is progressive and is thought to be initiated by abnormal ion and water transport across the choroid plexus epithelium. The pathology is further aggravated by the slow and disorganized beating of motile cilia on ependymal cells that contribute to decreased cerebrospinal fluid movement through the ventricles. Previously, we demonstrated that the hydrocephalus phenotype is associated with a marked increase in intracellular cAMP levels in choroid plexus epithelium, which is known to have regulatory effects on ion and fluid movement in many secretory epithelia. To evaluate whether the hydrocephalus in Tg737(orpk) mutants is associated with defects in ion transport, we compared the steady-state pH(i) and Na(+)-dependent transport activities of isolated choroid plexus epithelium tissue from Tg737(orpk) mutant and wild-type mice. The data indicate that Tg737(orpk) mutant choroid plexus epithelium have lower pH(i) and higher Na(+)-dependent HCO(3)(-) transport activity compared with wild-type choroid plexus epithelium. In addition, wild-type choroid plexus epithelium could be converted to a mutant phenotype with regard to the activity of Na(+)-dependent HCO(3)(-) transport by addition of dibutyryl-cAMP and mutant choroid plexus epithelium toward the wild-type phenotype by inhibiting PKA activity with H-89. Together, these data suggest that cilia have an important role in regulating normal physiology of choroid plexus epithelium and that ciliary dysfunction in Tg737(orpk) mutants disrupts a signaling pathway leading to elevated intracellular cAMP levels and aberrant regulation of pH(i) and ion transport activity.

Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus.

Cilia are complex organelles involved in sensory perception and fluid or cell movement. They are constructed through a highly conserved process called intraflagellar transport (IFT). Mutations in IFT genes, such as Tg737, result in severe developmental defects and disease. In the case of the Tg737orpk mutants, these pathological alterations include cystic kidney disease, biliary and pancreatic duct abnormalities, skeletal patterning defects, and hydrocephalus. Here, we explore the connection between cilia dysfunction and the development of hydrocephalus by using the Tg737orpk mutants. Our analysis indicates that cilia on cells of the brain ventricles of Tg737orpk mutant mice are severely malformed. On the ependymal cells, these defects lead to disorganized beating and impaired cerebrospinal fluid (CSF) movement. However, the loss of the cilia beat and CSF flow is not the initiating factor, as the pathology is present prior to the development of motile cilia on these cells and CSF flow is not impaired at early stages of the disease. Rather, our results suggest that loss of cilia leads to altered function of the choroid plexus epithelium, as evidenced by elevated intracellular cAMP levels and increased chloride concentration in the CSF. These data suggest that cilia function is necessary for regulating ion transport and CSF production, as well as for CSF flow through the ventricles.

Amyloid beta peptide 1-40 stimulates the Na+/Ca2+ exchange activity of SNCX.

The Na+/Ca2+ exchangers, RNCX and SNCX, were cloned from mesangial cells of salt sensitive and salt resistant Dahl/Rapp rats, respectively, and differ at amino acid 218 (RNCXi/SNCXf) and in the exons expressed at the alternative splice site (RNCXB, D/SNCXB, D, F). These isoforms are also expressed in myocytes, neurons, and astrocytes where they maintain cytosolic calcium homeostasis. We demonstrated that cells expressing SNCX were more susceptible to oxidative stress than cells expressing RNCX. Others demonstrated that amyloid beta peptide (Abeta) augments the adverse effects of oxidative stress on calcium homeostasis. Therefore, we sought to assess the effect of Abeta 1-40 on the abilities of OK-PTH cells stably expressing RNCX and SNCX and human glioma cells, SKMG1, to regulate cytosolic calcium homeostasis. Our studies showed that Abeta 1-40 (1 microM) did not affect RNCX activity, as assessed by changes in [Ca2+]i (Delta[Ca2+]i, 260+/-10 nM to 267+/-8 nM), while stimulating exchange activity 2.4 and 3 fold in cells expressing SNCX (100+/-8 to 244+/-12 nM) and in SKMG1 cells (90+/-11 nM to 270+/-18 nM), respectively. Our results also showed that Abeta 1-40, while not affecting the rate of Mn2+ influx in cells expressing RNCX, stimulated the rate of Mn2+ influx 2.8 and 2.9 fold in cells expressing SNCX and in SKMG1 cells. Thus, our studies demonstrate that Abeta-induced cytosolic calcium increase is mediated through certain isoforms of the Na+/Ca2+ exchanger and reveals a possible mechanism by which Abeta 1-40 can alter cytosolic calcium homeostasis.

Macula densa basolateral ATP release is regulated by luminal [NaCl] and dietary salt intake.

One component of the macula densa (MD) tubuloglomerular feedback (TGF) signaling pathway may involve basolateral release of ATP through a maxi-anion channel. Release of ATP has previously been studied during a maximal luminal NaCl concentration ([NaCl](L)) stimulus (20-150 mmol/l). Whether MD ATP release occurs during changes in [NaCl](L) within the physiological range (20-60 mmol/l) has not been examined. Also, because TGF is known to be enhanced by low dietary salt intake, we examined the pattern of MD ATP release from salt-restricted rabbits. Fluorescence microscopy, with fura 2-loaded cultured mouse mesangial cells as biosensors, was used to assess ATP release from the isolated, perfused thick ascending limb containing the MD segment. The mesangial biosensor cells, which contain purinergic receptors and elevate intracellular Ca(2+) concentration ([Ca(2+)](i)) on ATP binding, were placed adjacent to the MD basolateral membrane. Elevations in [NaCl](L) between 0 and 80 mmol/l, in 20-mmol/l increments, caused stepwise increases in [Ca(2+)](i), with the highest increase at [NaCl](L) of approximately 60 mmol/l. Luminal furosemide at 10(-4) mol/l blocked ATP release, which suggests that the efflux of ATP required MD Na-2Cl-K cotransport. A low-salt diet for 1 wk increased the magnitude of [NaCl](L)-dependent elevations in biosensor [Ca(2+)](i) by twofold, whereas high-salt intake had no effect. In summary, ATP release occurs over the same range of [NaCl](L) (20-60 mmol/l) previously reported for TGF responses, and, similar to TGF, ATP release was enhanced by dietary salt restriction. Thus these two findings are consistent with the role of MD ATP release as a signaling component of the TGF pathway.

Macula densa cell signaling involves ATP release through a maxi anion channel.

Macula densa cells are unique renal biosensor cells that detect changes in luminal NaCl concentration ([NaCl](L)) and transmit signals to the mesangial cellafferent arteriolar complex. They are the critical link between renal salt and water excretion and glomerular hemodynamics, thus playing a key role in regulation of body fluid volume. Since identification of these cells in the early 1900s, the nature of the signaling process from macula densa cells to the glomerular contractile elements has remained unknown. In patch-clamp studies of macula densa cells, we identified an [NaCl](L)-sensitive ATP-permeable large-conductance (380 pS) anion channel. Also, we directly demonstrated the release of ATP (up to 10 microM) at the basolateral membrane of macula densa cells, in a manner dependent on [NaCl](L), by using an ATP bioassay technique. Furthermore, we found that glomerular mesangial cells respond with elevations in cytosolic Ca(2+) concentration to extracellular application of ATP (EC(50) 0.8 microM). Importantly, we also found increases in cytosolic Ca(2+) concentration with elevations in [NaCl](L), when fura-2-loaded mesangial cells were placed close to the basolateral membrane of macula densa cells. Thus, cell-to-cell communication between macula densa cells and mesangial cells, which express P2Y(2) receptors, involves the release of ATP from macula densa cells via maxi anion channels at the basolateral membrane. This mechanism may represent a new paradigm in cell-to-cell signal transduction mediated by ATP.