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Jessica D Macdougall,1,2,* Kevin O Thomas,1,2,* Onyinye I Iweala1,2 1Department of Medicine, Thurston Arthritis Research Center, Division of Rheumatology, Allergy, and Immunology, Chapel Hill, NC, 27599, USA; 2Department of Pediatrics, University of North Carolina Food Allergy Initiative, Division of Allergy and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA*These authors contributed equally to this workCorrespondence: Onyinye I Iweala, Department of Medicine, University of North Carolina at Chapel Hill, 3300 Thurston Building, CB#7280, Chapel Hill, NC, 27599-7280, USA, Tel +1-984-974-2645, Fax +1-984-974-2660, Email onyinye.iweala@med.unc.eduAbstract: Alpha-gal syndrome is an unconventional food allergy, characterized by IgE-mediated hypersensitivity responses to the glycan galactose-alpha-1,3-galactose (alpha-gal) and not to a food-protein. In this review, we discuss how alpha-gal syndrome reframes our current conception of the mechanisms of pathogenesis of food allergy. The development of alpha-gal IgE is associated with tick bites though the possibility of other parasites promoting sensitization to alpha-gal remains. We review the immune cell populations involved in the sensitization and effector phases of alpha-gal syndrome and describe the current understanding of why allergic responses to ingested alpha-gal can be delayed by several hours. We review the foundation of management in alpha-gal syndrome, namely avoidance, but also discuss the use of antihistamines, mast cell stabilizers, and the emerging role of complementary and alternative therapies, biological products, and oral immunotherapy in the management of this condition. Alpha-gal syndrome influences the safety and tolerability of medications and medical devices containing or derived from mammalian products and impacts quality of life well beyond food choices.Keywords: mammalian meat, red meat allergy, galactose-alpha-1, 3-galactose, tick

Jessica D Macdougall,1 A Wesley Burks,1 Edwin H Kim2 1Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC, USA; 2Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USACorrespondence: Edwin H KimDepartment of Medicine, University of North Carolina School of Medicine, 3004 Mary Ellen Jones Building, 116 Manning Dr, CB 8035, Chapel Hill, NC 27599, USATel +1 919 537 3193Fax +1 919 962 5478Email edwinkim@email.unc.eduAbstract: In the last decade, there has been increasing research dedicated to food immunotherapy to induce clinical desensitization and provide protection by increasing clinical reaction thresholds. Results from recent food immunotherapy studies with differing routes of administration (oral, sublingual, and epicutaneous) suggest that food immunotherapy can induce clinical desensitization with varying levels of safety, however lasting tolerance has not been demonstrated. Furthermore, treatment side effects and dosing logistics may make the therapies difficult for some supporting the need for alternative treatment approaches. Peptide immunotherapy and DNA vaccine approaches should in theory allow for safer administration by decreasing allergenicity but proof of their clinical efficacy and immunogenicity remains to be proven. Biologic agents may allow for increased safety and rapid up-dosing of immunotherapy with the added benefit of treating multiple allergens simultaneously.Keywords: food allergy, oral immunotherapy, sublingual immunotherapy, epicutaneous immunotherapy, omalizumab, dupilumab

Food allergy impacts up to 10 % of the population and can result in life-threatening anaphylactic reactions. The pathogenesis of food allergy is not entirely understood but the disruption in naturally occurring oral tolerance is presumed to be involved. Research has been directed not only toward prevention of food allergy but on the restoration of oral tolerance by various means including immunotherapy (oral, sublingual, and epicutaneous), as well as adjunctive therapies including biologicals and probiotics. This review paper briefly discusses the involvement of oral tolerance in the pathogenesis of food allergy and how food allergy might be prevented; however, the main focus is on the potential for restoration of oral tolerance with various treatment modalities (oral immunotherapy with and without adjunctive therapies)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: To examine the effect of fibre type on potentiation and fatigue., Methods: Young men (n = 4 per group) with a predominance of type I [61.4 +/- 6.9% (SD), group I (GI)] or type II [71.8 +/- 9.2%, group II (GII)] fibres in vastus lateralis, performed a fatigue protocol of sixteen 5-s maximal voluntary isometric contractions (MVCs) of the right knee extensors. Maximal twitches and corresponding muscle action potentials (M-waves) were evoked before the first MVC, during the 3-s rest period after each MVC and at intervals during the 5-min recovery period after the last MVC., Results: Group II [49.3 +/- 2.6% (SE)] had a greater decrease in MVC force than GI (22.8 +/- 6.2%) during the fatigue protocol. Group II (126.4 +/- 13.6%) showed greater twitch force potentiation early in the fatigue protocol than GI (38.2 +/- 2.3%), but greater depression at the end (33.7 +/- 13.7% vs.17.4 +/- 3.4%). Twitch time-to-peak torque (TPT) and half relaxation time (HRT) initially decreased but then increased as the fatigue protocol progressed; GII had a greater increase in HRT. During a 5-min recovery period twitch force increased above the prefatigue level and remained so until the end of the recovery period; the pattern was similar in GI and GII. Twitch TPT and HRT remained elevated during recovery. M-wave area increased throughout the fatigue protocol and the first part of recovery before returning to baseline values in GII, whereas there were no significant changes in GI. The interaction between potentiation and fatigue was amplified in GII early in the fatigue protocol with concurrently greater twitch and M-wave potentiation, and greater MVC force decrease and HRT increase. Late in the protocol, GII had a greater decrease in twitch and MVC force combined with greater M-wave potentiation., Conclusion: It is concluded that fibre type distribution influences potentiation and fatigue of the twitch, and potentiation of the M-wave during fatiguing exercise.

In this study, we employed single-leg submaximal cycle training, conducted over a 10-wk period, to investigate adaptations in sarcoplasmic reticulum (SR) Ca(2+)-regulatory proteins and processes of the vastus lateralis. During the final weeks, the untrained volunteers (age 21.4 +/- 0.3 yr; means +/- SE, n = 10) were exercising 5 times/wk and for 60 min/session. Analyses were performed on tissue extracted by needle biopsy approximately 4 days after the last training session. Compared with the control leg, the trained leg displayed a 19% reduction (P < 0.05) in homogenate maximal Ca(2+)-ATPase activity (192 +/- 11 vs. 156 +/- 18 micromol. g protein(-1). min(-1)), a 4.3% increase (P < 0.05) in pCa(50), defined as the Ca(2+) concentration at half-maximal activity (6.01 +/- 0.05 vs. 6.26 +/- 0.07), and no change in the Hill coefficient (1.75 +/- 0.15 vs. 1.76 +/- 0.21). Western blot analysis using monoclonal antibodies (7E6 and A52) revealed a 13% lower (P < 0.05) sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) 1 in trained vs. control in the absence of differences in SERCA2a. Training also resulted in an 18% lower (P < 0.05) SR Ca(2+) uptake and a 26% lower (P < 0.05) Ca(2+) release. It is concluded that a downregulation in SR Ca(2+) cycling in vastus lateralis occurs with aerobic-based training, which at least in the case of Ca(2+) uptake can be explained by reduction in Ca(2+)-ATPase activity and SERCA1 protein levels.

Recent evidence from our laboratory and others have suggested that the mechanism for a decrease in resting blood pressure after an acute bout of exercise is a centrally mediated decrease in total peripheral resistance. This study examined the effect of the central serotonergic system on post exercise hypotension (PEH) in 11 borderline hypertensive individuals (nine male, two female) aged 24.5 +/- 5.1 years. Each subject completed two, 30-min cycling bouts at 70% of VO2peak while under placebo or a selective serotonin re-uptake inhibitor (SSRI) treatment. Blood pressure was recorded directly from the radial artery, and treatments were randomised, double blinded and separated by at least 14 days. Baseline blood pressure was 145/72 mm Hg for systolic (SBP) and diastolic (DBP) respectively. Peripheral measures of serotonin (5-HT) were lower under SSRI treatment, whereas the major 5-HT metabolite, 5-hydroxyindoleacetic acid, was not significantly changed, indicating elevated central 5-HT levels. There was no difference in any of the haemodynamic variables between trials. Despite an increased heart rate for the initial 75 min post exercise, SBP was decreased as much as 23 mm Hg during the initial 60 min post exercise, after which it had returned to normal. DBP was unchanged after exercise. Circulating adrenaline (0.60 +/- 0.14 ng/mL to 1.3 +/- 1.6 ng/ml) and noradrenaline (0.27 +/- 0.31 ng/ml to 4.5 +/- 2.1 ng/ml) were significantly elevated during exercise. Both returned to pre-exercise levels within 15 min post exercise. Unexpectedly, oxygen uptake was slightly (5%), but significantly increased over the entire duration of the SSRI trial. We conclude that the central serotonergic system is not responsible for PEH in our borderline hypertensive population.

The purpose of this study was to assess strength performance after an acute bout of maximally tolerable passive stretch (PS(max)) in human subjects. Ten young adults (6 men and 4 women) underwent 30 min of cyclical PS(max) (13 stretches of 135 s each over 33 min) and a similar control period (Con) of no stretch of the ankle plantarflexors. Measures of isometric strength (maximal voluntary contraction), with twitch interpolation and electromyography, and twitch characteristics were assessed before (Pre), immediately after (Post), and at 5, 15, 30, 45, and 60 min after PS(max) or Con. Compared with Pre, maximal voluntary contraction was decreased at Post (28%) and at 5 (21%), 15 (13%), 30 (12%), 45 (10%), and 60 (9%) min after PS(max) (P < 0.05). Motor unit activation and electromyogram were significantly depressed after PS(max) but had recovered by 15 min. An additional testing trial confirmed that the torque-joint angle relation may have been temporarily altered, but at Post only. These data indicate that prolonged stretching of a single muscle decreases voluntary strength for up to 1 h after the stretch as a result of impaired activation and contractile force in the early phase of deficit and by impaired contractile force throughout the entire period of deficit.

We have previously quantified the extent of myofibrillar disruption which occurs following an acute bout of resistance exercise in untrained men, however the response of well-trained subjects is not known. We therefore recruited six strength-trained men, who ceased training for 5 days and then performed 8 sets of 8 uni-lateral repetitions, using a load equivalent to 80% of their concentric (Con) 1-repetition maximum. One arm performed only Con actions by lifting the weight and the other arm performed only eccentric actions (Ecc) by lowering it. Needle biopsy samples were obtained from biceps brachii of each arm approximately 21 h following exercise, and at baseline (i.e., after 5 days without training), and subsequently analyzed using electron microscopy to quantify myofibrillar disruption. A greater (P < or = 0.05) proportion of disrupted fibres was found in the Ecc arm (45 +/- 11%) compared with baseline values (4 +/- 2%), whereas fibre disruption in the Con arm (27 +/- 4%) was not different (P > 0.05) from baseline values. The proportion of disrupted fibres and the magnitude of disruption (quantified by sarcomere counting) was considerably less severe than previously observed in untrained subjects after an identical exercise bout. Mixed muscle protein synthesis, assessed from approximately 21-29 h post-exercise, was not different between the Con- and Ecc-exercised arms. We conclude that the Ecc phase of resistance exercise is most disruptive to skeletal muscle and that training attenuates the severity of this effect. Moreover, it appears that fibre disruption induced by habitual weightlifting exercise is essentially repaired after 5 days of inactivity in trained men.

In small mammals, muscles with shorter twitch contraction times and a predominance of fast-twitch, type II fibers exhibit greater posttetanic twitch force potentiation than muscles with longer twitch contraction times and a predominance of slow-twitch, type I fibers. In humans, the correlation between potentiation and fiber-type distribution has not been found consistently. In the present study, postactivation potentiation (PAP) was induced in the knee extensors of 20 young men by a 10-s maximum voluntary isometric contraction (MVC). Maximal twitch contractions of the knee extensors were evoked before and after the MVC. A negative correlation (r = -0. 73, P < 0.001) was found between PAP and pre-MVC twitch time to peak torque (TPT). The four men with the highest (HPAP, 104 +/- 11%) and lowest (LPAP, 43 +/- 7%) PAP values (P < 0.0001) underwent needle biopsies of vastus lateralis. HPAP had a greater percentage of type II fibers (72 +/- 9 vs. 39 +/- 7%, P < 0.001) and shorter pre-MVC twitch TPT (61 +/- 12 vs. 86 +/- 7 ms, P < 0.05) than LPAP. These data indicate that, similar to the muscles of small mammals, human muscles with shorter twitch contraction times and a higher percentage of type II fibers exhibit greater PAP.

We examined the effect of an isolated bout of maximal tolerated passive stretch on fractional muscle protein synthetic rate in human soleus muscle. Eight healthy males performed two separate trials with the same leg: one session of passive stretch and one of intermittent active isometric contraction at a force equivalent to that which occurred during the passive stretch trial. This force was approximately 40% of maximum voluntary contraction force and produced volitional fatigue in approximately 27 min. Intermittent passive stretch, for the same duration, elicited a 6.1 degrees increase in joint angle (P<.0005) with silent electromyography. Fractional protein synthetic rate from experimental and control soleus in each trial was assessed from biopsy samples over the period 10-22 hr postexercise by the incorporation rate of L-[1-13C] leucine into muscle. Protein synthesis was elevated in the soleus of the exercised leg following the active contraction trial by 49% (P<.05) but not following the passive stretch trial. Results indicate that a single bout of maximal passive stretch does not significantly elevate fractional muscle protein synthetic rate in humans and thus suggests that muscle stretch per se is not the stimulus for the muscle hypertrophy that occurs with resistance training.

We examined the effects of androstenedione supplementation on the hormonal profile of 10 males and its interaction with resistance exercise. Baseline testosterone, luteinizing hormone, estradiol, and androstenedione concentrations were established by venous sampling at 3 hr intervals over 24 hr. Subjects ingested 200 mg of androstenedione daily for 2 days, with second and third day blood samples. Two weeks later, they ingested androstenedione or a placebo for 2 days, in a double-blind, cross-over design. On day 2, they performed heavy resistance exercise with blood sampled before, after, and 90 min post. The supplement elevated plasma androstenedione 2--3-fold and luteinizing hormone approximately 70% but did not alter testosterone concentration. Exercise elevated testosterone, with no difference between conditions. Exercise in the supplemented condition significantly elevated plasma estradiol by approximately 83% for 90 min. Androstenedione supplementation, thus, is unlikely to provide male athletes with any anabolic benefit and, with heavy resistance exercise, elevates estrogen.

Biopsies (biceps) were examined in 8 bodybuilders across a typical arm-curl training session (80% 1-RM). [PCr] and [glycogen] decreased 62 and 12% after 1 set (n = 4), and 50 and 24% after 3 sets (n = 4). [Lactate] was 91 and 118 mmol &times kg-1, respectively, after 1 and 3 sets. Fatigue was probably partially caused by decreased [PCr] and increased [H+] (first set) and by decreased [H+] in subsequent sets.

Our purposes were (1) to examine resting arterial blood pressure following an acute bout of resistance exercise and submaximal dynamic exercise, (2) to examine the effects of these exercises on the plasma concentrations of atrial natriuretic peptide ([ANP]), and (3) to evaluate the potential relationship between [ANP] and post-exercise blood pressure. Thirteen males [24.3+/-(2.4) years] performed 15 min of unilateral leg press exercise (65% of their one-repetition maximum) and, I week later, approximately 15 min of cycle ergometry (at 65% of their maximum oxygen consumption). Intra-arterial pressure was monitored during exercise and for 1 h post-exercise. Arterial blood was drawn at rest, during exercise and at intervals up to 60 min post-exercise for analysis of haematocrit and [alphaANP]. No differences occurred in blood pressure between trials, but significant decrements occurred following exercise in both trials. Systolic pressure was approximately 20 mmHg lower than before exercise after 10 min, and mean pressure was approximately 7 mmHg lower from 30 min onwards. Only slight (non-significant) elevations in [alphaANP] were detected immediately following exercise, with the concentrations declining to pre-exercise values by 5 min post-exercise. We conclude that post-exercise hypotension occurs following acute bouts of either resistance or submaximal dynamic exercise and, in this investigation, that this decreased blood pressure was not directly related to the release of alphaANP.

Our purpose was to examine the effects of sprint interval training on muscle glycolytic and oxidative enzyme activity and exercise performance. Twelve healthy men (22 +/- 2 yr of age) underwent intense interval training on a cycle ergometer for 7 wk. Training consisted of 30-s maximum sprint efforts (Wingate protocol) interspersed by 2-4 min of recovery, performed three times per week. The program began with four intervals with 4 min of recovery per session in week 1 and progressed to 10 intervals with 2.5 min of recovery per session by week 7. Peak power output and total work over repeated maximal 30-s efforts and maximal oxygen consumption (VO2 max) were measured before and after the training program. Needle biopsies were taken from vastus lateralis of nine subjects before and after the program and assayed for the maximal activity of hexokinase, total glycogen phosphorylase, phosphofructokinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase, malate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase. The training program resulted in significant increases in peak power output, total work over 30 s, and VO2 max. Maximal enzyme activity of hexokinase, phosphofructokinase, citrate synthase, succinate dehydrogenase, and malate dehydrogenase was also significantly (P < 0.05) higher after training. It was concluded that relatively brief but intense sprint training can result in an increase in both glycolytic and oxidative enzyme activity, maximum short-term power output, and VO2 max.

Six male subjects made maximal isometric plantar flexions unilaterally (UL) and bilaterally (BL), with the knee joint angle positioned at 90 degrees and 0 degrees (full extension) and the ankle joint kept at 90 degrees. Plantar flexion torque and electromyogram (EMG) of the lateral gastrocnemius (LG) and the soleus (Sol) muscles were recorded. There was a deficit in torque in BL compared to UL (P<0.05), and the deficit was greater when the knee was extended than when bent to 90 degrees (13.9% vs 6.6%). The integrated EMG (iEMG) of UL and BL did not differ when the knee was at 90 degrees. On the other hand, when the knee was extended iEMG of LG was smaller for BL than for UL, suggesting that the larger bilateral deficit when the knee was extended was due to a reduced activity of the LG motor units. In addition, the H-reflex recorded from Sol when the contralateral leg was performing a maximal unilateral plantarflexion was reduced. This would indicate that the force deficit was associated with a reduction of motoneuron excitability.

1. This study investigated the effects of 7 weeks of sprint training on gas exchange across the lungs and active skeletal muscle during and following maximal cycling exercise in eight healthy males. 2. Pulmonary oxygen uptake (VO2) and carbon dioxide output (VCO2) were measured before and after training during incremental exercise (n = 8) and during and in recovery from a maximal 30 s sprint exercise bout by breath-by-breath analysis (n = 6). To determine gas exchange by the exercising leg muscles, brachial arterial and femoral venous blood O2 and CO2 contents and lactate concentration were measured at rest, during the final 10 s of exercise and during 10 min of recovery. 3. Training increased (P < 0.05) the maximal incremental exercise values of ventilation (VE, by 15.7 +/- 7.1%), VCO2 (by 9.3 +/- 2.1%) and VO2 (by 15.0 +/- 4.2%). Sprint exercise peak power (3.9 +/- 1.0% increase) and cumulative 30 s work (11.7 +/- 2.8% increase) were increased and fatigue index was reduced (by -9.2 +/- 1.5%) after training (P < 0.05). The highest VE, VCO2 and VO2 values attained during sprint exercise were not significantly changed after training, but a significant (P < 0.05) training effect indicated increased VE (by 19.2 +/- 7.9%), VCO2 (by 9.3 +/- 2.1%) and VO2 (by 12.7 +/- 6.5%), primarily reflecting elevated post-exercise values after training. 4. Arterial O2 and CO2 contents were lower after training, by respective mean differences of 3.4 and 21.9 ml l-1 (P < 0.05), whereas the arteriovenous O2 and CO2 content differences and the respiratory exchange ratio across the leg were unchanged by training. 5. Arterial whole blood lactate concentration and the net lactate release by exercising muscle were unchanged by training. 6. The greater peak pulmonary VO2 and VCO2 with sprint exercise, the increased maximal incremental values, unchanged arterial blood lactate concentration and greater sprint performance all point strongly towards enhanced gas exchange across the lungs and in active muscles after sprint training. Enhanced aerobic metabolism after sprint training may contribute to reduced fatigability during maximal exercise, whilst greater pulmonary CO2 output may improve acid-base control after training.

1. This study investigated the effects of 7 weeks of sprint training on changes in electrolyte concentrations and acid-base status in arterial and femoral venous blood, during and following maximal exercise for 30 s on an isokinetic cycle ergometer. 2. Six healthy males performed maximal exercise, before and after training. Blood samples were drawn simultaneously from brachial arterial and femoral venous catheters, at rest, during the final 10 s of exercise and during 10 min of recovery, and analysed for whole blood and plasma ions and acid-base variables. 3. Maximal exercise performance was enhanced after training, with a 13% increase in total work output and a 14% less decline in power output during maximal cycling. 4. The acute changes in plasma volume, ions and acid-base variables during maximal exercise were similar to previous observations. Sprint training did not influence the decline in plasma volume during or following maximal exercise. After training, maximal exercise was accompanied by lower arterial and femoral venous plasma [K+] and [Na+] across all measurement times (P < 0.05). Arterial plasma lactate concentration ([Lac-]) was greater (P < 0.05), but femoral venous plasma [Lac-] was unchanged by training. 5. Net release into, or uptake of ions from plasma passing through the exercising muscle was assessed by arteriovenous concentration differences, corrected for fluid movements. K+ release into plasma during exercise, and a small net K+ uptake from plasma 1 min post-exercise (P < 0.05), were unchanged by training. A net Na+ loss from plasma during exercise (P < 0.05) tended to be reduced after training (P < 0.06). Release of Lac- into plasma during and after exercise (P < 0.05) was unchanged by training. 6. Arterial and venous plasma strong ion difference ([SID]; [SID] = [Na+] + [K+] - [Lac-] - [Cl-]) were lower after training (mean differences) by 2.7 and 1.8 mmol l-1, respectively (P < 0.05). Arterial and femoral venous CO2 tensions and arterial plasma [HCO3-] were lower after training (mean differences) by 1.7 mmHg, 4.5 mmHg and 1.2 mmol l-1, respectively (P < 0.05), with arterial plasma [H+] being greater after training by 2.2 nmol l-1 (P < 0.05). 7. The acute changes in whole blood volume and ion concentrations during maximal exercise were similar to previous observations: Arterial and femoral whole blood [K+] and [Cl-] were increased, whilst [Na+] was lower, across all observation times after training (P < 0.05). 8. Net uptake or release of ions by exercising muscle was assessed by arteriovenous whole blood concentration differences, corrected for fluid movements. A net K+ uptake by muscle occurred at all times, including exercise, but this was not significantly different after training. An increased net Na+ uptake by muscle occurred during exercise (P < 0.05) with greater Na+ uptake after training (P < 0.05). Net muscle Lac- release and Cl- uptake occurred at all times (P < 0.05) and were unchanged by training. 9. Sprint training improved muscle ion regulation, associated with increased intense exercise performance, at the expense of a greater systemic acidosis. Increased muscle Na+ and K+ uptake by muscle during the final seconds of exercise after training are consistent with a greater activation of the muscle Na(+) - K+ pump, reduced cellular K+ loss and the observed lesser rate of fatigue. The greater plasma acidosis found after sprint training was caused by a lower arterial plasma [SID] due to lower plasma [K+] and [Na+], and higher plasma [Lac-].

We determined the effect of the timing of glucose supplementation on fractional muscle protein synthetic rate (FSR), urinary urea excretion, and whole body and myofibrillar protein degradation after resistance exercise. Eight healthy men performed unilateral knee extensor exercise (8 sets/approximately 10 repetitions/approximately 85% of 1 single maximal repetition). They received a carbohydrate (CHO) supplement (1 g/kg) or placebo (Pl) immediately (t = 0 h) and 1 h (t = +1 h) postexercise. FSR was determined for exercised (Ex) and control (Con) limbs by incremental L-[1-13C]leucine enrichment into the vastus lateralis over approximately 10 h postexercise. Insulin was greater (P < 0.01) at 0.5, 0.75, 1.25, 1.5, 1.75, and 2 h, and glucose was greater (P < 0.05) at 0.5 and 0.75 h for CHO compared with Pl condition. FSR was 36.1% greater in the CHO/Ex leg than in the CHO/Con leg (P = not significant) and 6.3% greater in the Pl/Ex leg than in the Pl/Con leg (P = not significant). 3-Methylhistidine excretion was lower in the CHO (110.43 +/- 3.62 mumol/g creatinine) than P1 condition (120.14 +/- 5.82, P < 0.05) as was urinary urea nitrogen (8.60 +/- 0.66 vs. 12.28 +/- 1.84 g/g creatinine, P < 0.05). This suggests that CHO supplementation (1 g/kg) immediately and 1 h after resistance exercise can decrease myofibrillar protein breakdown and urinary urea excretion, resulting in a more positive body protein balance.

Objective: To characterize the pattern of plasma beta-endorphin throughout the normal menstrual cycle and test the hypothesis that beta-endorphin concentrations are elevated in trained women with amenorrhea compared with trained and sedentary eumenorrheic women., Design: Cohort analytic study., Setting: Academic research environment., Participants: Healthy female volunteers: 10 eumenorrheic sedentary, 11 eumenorrheic trained, and 11 amenorrheic trained women., Interventions: Blood samples were collected three times per week for either one complete menstrual cycle (eumenorrheic sedentary and trained subjects) or for a 4-week period (amenorrheic trained subjects)., Main Outcome Measure: Plasma beta-endorphin concentrations., Results: beta-Endorphin levels varied considerably across the sampling period and were not associated with menstrual status, gonadotropin, or gonadal steroid concentrations. Average beta-endorphin levels were not different between the follicular and luteal phases for menstruating subjects, but were greater in the eumenorrheic athletes. Compared with eumenorrheic sedentary subjects, plasma beta-endorphin levels were higher in the athletic groups, regardless of menstrual status., Conclusion: There were no cycle-related beta-endorphin changes. Eumenorrheic and amenorrheic athletes have higher beta-endorphin concentrations that may reflect adaptations to intense training and not exercise-associated amenorrhea.

This study examined whether training under normobaric hypoxic conditions (simulating medium level altitude) would enhance physical performance and selected muscle adaptations over and above that which occurs with normoxic training. Ten healthy males (19-25 yr) underwent 8 wk of unilateral cycle ergometry training so that one leg was trained while breathing an inspirate of 13.5% O2 and the other while breathing normal ambient air. Pre- and post-training measurements included single leg VO2max and time to fatigue at 95% VO2max. Needle biopsies from quadriceps were assayed for oxidative and glycolytic enzyme activity and analyzed for capillary density, fiber area, % fiber type, and mitochondrial and lipid volume density. VO2max, time to fatigue, citrate synthase (CS), succinate dehydrogenase, and phosphofructokinase activity increased significantly (P > 0.05) in both legs following training. The increase in CS activity in the hypoxically trained leg was also significantly greater than that in the normoxically trained leg. It thus appears that training under moderate normobaric hypoxic conditions enhances muscle citrate synthase activity to a greater extent than training under normoxic conditions.

Objective: To examine the effect of energy restriction and wrestling on muscle glycogen content in highly-trained male wrestlers., Design: Randomized, unblinded intervention trial., Setting: McMaster University Nutrition and Metabolism Research Laboratory., Participants: Twelve highly trained male wrestlers volunteered as subjects and were randomly assigned to one of two groups (Group A, n = 6; Group B, n = 6) as defined below., Assessment of Risk Factors: All subjects were free of medical conditions that would preclude participation in the study and all had performed rapid weight loss at least three times/year with no medical complications., Interventions: Group A: simulated wrestling tournament, four 5-min wrestling bouts ( > 7 h) following a 5% body weight loss and 17 h repletion period; Group B: 5% weight loss through energy restriction (1,141 kcal/day), exercise, fluid restriction, and dehydration methods (sauna) > 72 h., Main Outcome Measures: Group A: muscle glycogen content before and after wrestling tournament and plasma lactate after each bout; Group B: muscle glycogen before and after weight loss., Results: Group A: no significant effect on muscle glycogen concentration, yet large increases were observed in blood lactate concentrations (up to 14.7 mmol/L); Group B: weight loss resulted in a 54% (p < 0.018) reduction in muscle glycogen concentration., Conclusions: The weight loss methods commonly performed by wrestlers resulted in large decreases in muscle glycogen concentration that were largely reversed during the 17-h repletion period between weigh-in and the start of the competition; participation in a wrestling tournament did not have a significant impact upon biceps brachii glycogen concentration when ad libitum feeding is allowed between matches.

It has been shown that muscle protein synthetic rate (MPS) is elevated in humans by 50% at 4 hrs following a bout of heavy resistance training, and by 109% at 24 hrs following training. This study further examined the time course for elevated muscle protein synthesis by examining its rate at 36 hrs following a training session. Six healthy young men performed 12 sets of 6- to 12-RM elbow flexion exercises with one arm while the opposite arm served as a control. MPS was calculated from the in vivo rate of incorporation of L-[1,2-13C2] leucine into biceps brachii of both arms using the primed constant infusion technique over 11 hrs. At an average time of 36 hrs postexercise, MPS in the exercised arm had returned to within 14% of the control arm value, the difference being nonsignificant. It is concluded that following a bout of heavy resistance training, MPS increases rapidly, is more than double at 24 hrs, and thereafter declines rapidly so that at 36 hrs it has almost returned to baseline.

We used computer-assisted analysis of myofiber cross-sectional areas to measure skeletal muscle responses to injury and disease. We developed a simple, inexpensive method for measuring myofiber size in human muscle samples using Kodak photo compact discs (CDs) as the image source. The photo CD serves as a permanent image storage medium and provides a high-resolution image that can be used to detect small myofibers. The use of double labeling for dystrophin and desmin allowed positive identification of both degenerating and regenerating fibers in a single biopsy specimen.

Six women and 6 men trained the elbow flexors 3 days per week for 20 wks, one arm performing in each session 3-5 sets of 10 maximal concentric actions on an accommodating resistance device, the other arm 3-5 sets of 8-12 coupled eccentric/concentric actions on a weight training device. With results collapsed across the two training modes, the women made significantly (p < 0.05) greater relative increases than men in strength measured on the weight (116 vs. 46%) and accommodating (99 vs. 46%) resistance devices, and greater absolute (3.5 vs. -1.3 N.m) and relative (13.7 vs. -3.2%) increases in strength measured on an isokinetic dynamometer. Absolute (cm2) and relative (%) biceps, brachialis, and total elbow flexor cross-sectional area (from CT scans) increased significantly; however, the women's vs. men's respective relative and absolute increases did not differ significantly: biceps (13 vs. 7%, 0.9 vs. 1.0 cm2), brachialis (53 vs. 31%, 2.1 vs. 2.3 cm2), and total (26 vs. 15%, 3.1 vs. 3.3 cm2) flexor area. Biceps type I and II fiber area, and the II/I area ratio did not increase significantly. The data indicate that in response to the same short-term training program, muscle size increases similarly in women and men but women make greater relative increases in strength.

During endurance exercise at approximately 65% maximal O2 consumption, women oxidize more lipids, and therefore decrease carbohydrate and protein oxidation, compared with men (L.J. Tarnopolsky, M.A. Tarnopolsky, S.A. Atkinson, and J.D. MacDougall. J. Appl. Physiol. 68: 302-308, 1990; S.M. Phillips, S.A. Atkinson, M.A. Tarnopolsky, and J.D. MacDougall. J. Appl. Physiol. 75: 2134-2141, 1993). The main purpose of this study was to examine the ability of similarly trained male (n = 7) and female (n = 8) endurance athletes to increase muscle glycogen concentrations in response to an increase in dietary carbohydrate from 55-60 to 75% of energy intake for a period of 4 days (carbohydrate loading). In addition, we sought to examine whether gender differences existed in metabolism during submaximal endurance cycling at 75% peak O2 consumption (VO2 peak) for 60 min. The men increased muscle glycogen concentration by 41% in response to the dietary manipulation and had a corresponding increase in performance time during an 85% VO2 peak trial (45%), whereas the women did not increase glycogen concentration (0%) or performance time (5%). The women oxidized significantly more lipid and less carbohydrate and protein compared with the men during exercise at 75% VO2-peak. We conclude that women did not increase muscle glycogen in response to the 4-day regimen of carbohydrate loading described. In addition, these data support previous observations of greater lipid and lower carbohydrate and protein oxidation by women vs. men during submaximal endurance exercise.

Muscle ultrastructure and contractile properties were examined before and after a single bout of resistance exercise (8 sets of 8 repetitions at 80% of 1 repetition maximum). Eight untrained males performed the concentric (Con) phase of arm-curl exercise with one arm and the eccentric (Ecc) phase with the other arm. Needle biopsies were obtained from biceps brachii before exercise (Base), immediately postexercise from each arm (post-Con and post-Ecc), and 48 h postexercise from each arm (48 h-Con and 48 h-Ecc). Electron microscopy was used to quantify the presence of disrupted fibers in each sample. Analysis of variance revealed a greater (P < or = 0.05) proportion of disrupted fibers in post-Con, post-Ecc, 48 h-Con, and 48 h-Ecc samples compared with Base. Significantly more fibers were disrupted in post-Ecc (82%) and 48 h-Ecc (80%) samples compared with post-Con (33%) and 48 h-Con (37%), respectively. Voluntary and evoked strength measurements recovered to Base values within 24 h in the Con arm but remained depressed (P < or = 0.05) for 72-96 h in the Ecc arm. These data indicate that both the raising and lowering phases of weightlifting produced myofibrillar disruption, with the greatest disruption occurring during the lowering phase.

The optimum pre-competition taper procedure for "strength athletes" is not known. We examined voluntary strength and evoked contractile properties of the elbow flexors over a 10 day rest only (ROT) and a 10 day reduced volume taper (RVT) in 8 resistance trained males (23 +/- 2.1 years). Following 3 wks of standardized training of the elbow flexors, subjects were randomly assigned to one of the tapers. Upon completion, they resumed training for 3 wks and completed the other taper. No arm training was performed during the ROT, while high intensity, low volume training was done every second day during the RVT. Maximum isometric (MVC), low (0.52 rad.s-1; LV) and high velocity (3.14 rad.s-1; HV) concentric peak torque, and evoked isometric twitch contractile properties were measured before and after each training phase and every 48 h during each taper. ANOVA comparison of the tapers revealed that MVC increased (p < or = 0.05) over pre-taper values throughout the RVT (measurement days 2, 4, 6, 8 and 10), as did LV at 2, 4, 6, and 8 d. MVC did not change over the ROT but LV was significantly higher on day 2 and lower on days 8 and 10. LV was also greater on days 4, 6, 8 and 10 during the RVT compared to the ROT. The evoked contractile properties remained largely unchanged. The data indicate that resistance-trained athletes can improve low velocity concentric strength for at least 8 days by greatly reducing training volume, but maintaining training intensity.

We examined cardiac volumes (using echocardiography), intra-arterial blood pressure (BP), and intrathoracic pressure (ITP) in healthy males performing leg press exercise to failure at 95% of their maximum dynamic strength. Compared with preexercise, during the lifting phase of exercise, end-diastolic volume (EDV; 147 +/- 8 to 103 +/- 7 ml) and end-systolic volume (ESV; 54 +/- 5 to 27 +/- 4 ml) decreased (P < 0.05); heart rate (82 +/- 6 to 143 +/- 5 beats/min), systolic BP (160 +/- 6 to 270 +/- 21 Torr), diastolic BP (91 +/- 2 to 183 +/- 18 Torr), ITP (0.8 +/- 0.8 to 57.8 +/- 24 Torr), and peak systolic BP/ESV (SBP/ESV; 3.0 +/- 0.3 to 11.0 +/- 1.5 Torr/ml) increased (P < 0.05); and stroke volume decreased (94 +/- 3 to 77 +/- 4 ml; P > 0.05). Full knee extension was associated with most values returning to preexercise levels except for ESV (38 +/- 7 ml), heart rate (130 +/- 9 beats/min), and ITP (-12.5 +/- 2.1 Torr). During the lowering phase, significant decreases in EDV to 105 +/- 14 ml and ESV to 27 +/- 7 ml were observed with increases in systolic BP to 207 +/- 23 Torr, diastolic BP to 116 +/- 8 Torr, and SBP/ESV to 10.0 +/- 2.5 Torr/ml. Stroke volume decreased to 78 +/- 9 ml (P > 0.05). Thus rapid changes in cardiac volumes, contractility, and pressure occur during weight lifting that are related to different phases of the lift.

The current Canadian Recommended Nutrient Intake (RNI) for protein (0.86 g.kg-1.day-1) makes no allowance for an effect of habitual physical activity. In addition, Tarnopolsky et al. (J. Appl. Physiol. 68: 302-308, 1990) showed that males may catabolize more protein than females consequent to endurance exercise. We examined nitrogen (N) balance and leucine kinetics during submaximal endurance exercise to determine the adequacy of the current Canadian RNI for protein for male and female endurance athletes. Athletes were matched for equal training volume, competitive status, and conditioning and were fed diets isoenergetic with their habitual intake, containing protein at the Canadian RNI. Subjects were adapted to the diet for 10 days before completing a 3-day measurement of N balance. N balance showed that the RNI was inadequate for females (-15.9 +/- 6.0 mg.kg-1.day-1) and males (-26.3 +/- 11.0 mg.kg-1.day-1). Leucine kinetics during exercise were determined for each subject on day 3 of the N balance experiment by use of a primed continuous infusion of L-[1-13C]leucine and the reciprocal pool model. Exercise resulted in a significant (P < 0.01) increase in leucine oxidation for both groups. Males oxidized a greater amount of leucine during the infusion than females (P < 0.01). Leucine flux also increased significantly (P < 0.01) during exercise in both groups. We conclude that the current Canadian RNI for protein is inadequate for those who chronically engage in endurance exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

We examined the effects of 12 wk of dynamic strength training on the heart rate (HR) and blood pressure of older male subjects during 10 repetitions of single-arm curl and single- and double-leg press at 60 and 80% of both the pre- and posttraining maximum capacities and during single maximum lifts (1 RM). The circulatory responses were greater at 80% of 1 RM than at 60% and increased with active muscle mass. After training, the 1 RMs increased by 24 (legs) to 54% (arms) and there was a marked attenuation of HR and arterial pressure during exercise when subjects lifted the same absolute load. Greatest reductions in HR (108 +/- 4 to 94 +/- 2 beats/min), systolic blood pressure (BPs, 247 +/- 14 to 206 +/- 9 Torr), diastolic pressure (156 +/- 9 to 116 +/- 5 Torr), mean arterial pressure (143 +/- 6 to 131 +/- 5 Torr), and rate-pressure product (268 +/- 22 to 196 +/- 12 HR.BPs/100) occurred during double-leg press at 80% of the pretraining 1 RM. After training, during lifting at 60, 80, and 100% of the posttraining 1 RMs, the HRs and arterial pressures were the same as those during pretraining testing when the same relative, but lighter, absolute loads were used. These observations are consistent with a significant part of the circulatory response to weight lifting being mediated by a feedforward "central command" mechanism coupled to the relative intensity rather than to the absolute level of force.

The increase in blood pressure provided by the standard AGSM is caused by both the contraction of the muscles of the lower body and by an increased intrathoracic pressure due to a respiratory straining (Valsalva) maneuver. This study examined the relative effectiveness and fatigability of the two components at +1 Gz and during +Gz acceleration in a human centrifuge. Brachial arterial pressure was recorded from a pressure-tip transducer in six subjects performing isometric leg presses only and on a separate occasion while performing respiratory straining only. Measurements were made over a range of intensities for the leg press contractions and Valsalva maneuvers and were conducted at +1 Gz and during slow and rapid onset runs up to +5 Gz in a human centrifuge. Blood pressure was also recorded during pulsing or intermittent contractions of the legs. We found it difficult to completely separate the blood pressure response to the leg press component from that of the respiratory straining alone component, since a moderate respiratory straining maneuver usually accompanied forceful contractions of the legs. We conclude, however, that a major portion of the elevation in blood pressure caused by the AGSM can be attributed to contraction of the muscles of the lower body and that this component is less fatiguing than the respiratory straining component. At +1 Gz a pulsing isometric contraction of the legs was no more effective in elevating blood pressure than a constant isometric contraction over the same duration.

The influence of elbow joint angle on voluntary isometric elbow flexion strength was assessed in 15 young women (F), 18 young men (M) and 11 male bodybuilders (BB). Measurements were made at elbow joint angles of 1.31, 1.57, 1.83, 2.09, 2.36, 2.62 and 2.88 rad (3.14 rad = 180 degrees = full extension). The peak voluntary strength [mean (SE), N.m] in M [69.5 (4.3)] and BB [93.3 (4.8)] occurred at 2.09 rad (120 degrees), but occurred at 1.57 rad (90 degrees) in F [35.4 (2.4)]. Peak torque at 1.31 rad was 20% and 25% lower than at 2.09 rad in M and BB, respectively, but did not differ between these two angles in F. The larger elbow flexor muscle and fibre size in M and BB may have been responsible for their impaired torque production at joint angles corresponding to the shortest muscle lengths.

Strength and muscle characteristics were examined in biceps brachii and vastus lateralis of eight men and eight women. Measurements included motor unit number, size and activation and voluntary strength of the elbow flexors and knee extensors. Fiber areas and type were determined from needle biopsies and muscle areas by computerized tomographical scanning. The women were approximately 52% and 66% as strong as the men in the upper and lower body respectively. The men were also stronger relative to lean body mass. A significant correlation was found between strength and muscle cross-sectional area (CSA; P < or = 0.05). The women had 45, 41, 30 and 25% smaller muscle CSAs for the biceps brachii, total elbow flexors, vastus lateralis and total knee extensors respectively. The men had significantly larger type I fiber areas (4597 vs 3483 microns2) and mean fiber areas (6632 vs 3963 microns2) than the women in biceps brachii and significantly larger type II fiber areas (7700 vs 4040 microns2) and mean fiber areas (7070 vs 4290 microns2) in vastus lateralis. No significant gender difference was found in the strength to CSA ratio for elbow flexion or knee extension, in biceps fiber number (180,620 in men vs 156,872 in women), muscle area to fiber area ratio in the vastus lateralis 451,468 vs 465,007) or any motor unit characteristics. Data suggest that the greater strength of the men was due primarily to larger fibers. The greater gender difference in upper body strength can probably be attributed to the fact that women tend to have a lower proportion of their lean tissue distributed in the upper body.(ABSTRACT TRUNCATED AT 250 WORDS)

Brachial arterial pressure, oesophageal pressure, and knee joint angle were monitored in eight untrained young men as they performed bilateral leg-press actions (simultaneous hip and knee extension and ankle plantarflexion) against resistance. Single maximal leg-press actions on an isokinetic device evoked mean peak arterial (systolic/diastolic) pressures of 35.4/26.2 and 34.0/23.4 kPa at lever arm velocities of 0.262 and 1.31 rad.s-1, respectively. The corresponding oesophageal pressures were 13.2 and 10.4 kPa, respectively. Although the peak force was 30% greater, and duration of the action 3-4 times longer at 0.262 than 1.31 rad.s-1, the arterial and oesophageal pressure responses did not differ. On a weight-lifting machine, a set of repetitions [mean (SEM): 11 (3)] to failure at 80-90% one repetition maximum evoked peak arterial pressures of 45.5/32.8 kPa; the corresponding oesophageal pressure was 15.7 kPa. The peak systolic and diastolic pressures observed during weight-lifting were significantly (P < 0.05) higher than during isokinetic actions at both velocities, whereas oesophageal pressure was more elevated only in relation to isokinetic actions at the higher velocity. These data indicate that resisted leg-press actions cause extreme elevations in arterial blood pressure. The degree of voluntary effort is the major determinant of the blood pressure response, rather than the resistance mode or the type (concentric, eccentric, isometric) of muscle action. Repetitive resistance exercise (e.g. a set of repetitions to failure in weight-lifting) tends to produce greater pressure elevations than isolated, single maximal effort actions.

The influence of elbow joint angle on elbow flexor isometric evoked twitch contractile properties was assessed in 15 young women (F), 18 young men (M) and 11 male bodybuilders (BB). Measurements were made at elbow joint angles of 1.31, 1.57, 1.83, 2.09, 2.36, 2.62 and 2.88 rad (3.14 rad = 180 degrees = full extension). The largest peak twitch torque values [mean (SE) N.m] in F [3.77 (0.20)], M [10.38 (0.68)] and BB [11.38 (1.05)] occurred at 2.88 rad. Peak torque was progressively smaller at smaller joint angles, but the decline from 2.88 to 1.31 rad was greater in M (68%) and BB (76%) than F (59%). Thus, the magnitude of intergroup differences in peak twitch torque (PT) was joint angle dependent. Twitch time to peak torque (TPT) was influenced in a complex way by joint angle in the three groups; BB had the lowest values at small joint angles but the highest values at the largest angles. Half-relaxation time (HRT) generally increased from the smallest to largest joint angles in a pattern that did not differ significantly among the three groups. Maximum rates of twitch torque development and relaxation showed the same pattern of results as PT, indicating that these time-related measures were more sensitive to joint angle effects on PT than on TPT or HRT. The results of this study indicate that careful consideration should be given to the selection of joint angles in the measurement of evoked twitch contractile properties for the purpose of making group comparisons or investigating the effects of interventions such as training.

Leucine kinetic and nitrogen balance (NBAL) methods were used to determine the dietary protein requirements of strength athletes (SA) compared with sedentary subjects (S). Individual subjects were randomly assigned to one of three protein intakes: low protein (LP) = 0.86 g protein.kg-1.day-1, moderate protein (MP) = 1.40 g protein.kg-1.day-1, or high protein (HP) = 2.40 g protein.kg-1.day-1 for 13 days for each dietary treatment. NBAL was measured and whole body protein synthesis (WBPS) and leucine oxidation were determined from L-[1-13C]leucine turnover. NBAL data were used to determine that the protein intake for zero NBAL for S was 0.69 g.kg-1.day-1 and for SA was 1.41 g.kg-1.day-1. A suggested recommended intake for S was 0.89 g.kg-1.day-1 and for SA was 1.76 g.kg-1.day-1. For SA, the LP diet did not provide adequate protein and resulted in an accommodated state (decreased WBPS vs. MP and HP), and the MP diet resulted in a state of adaptation [increase in WBPS (vs. LP) and no change in leucine oxidation (vs. LP)]. The HP diet did not result in increased WBPS compared with the MP diet, but leucine oxidation did increase significantly, indicating a nutrient overload. For S the LP diet provided adequate protein, and increasing protein intake did not increase WBPS. On the HP diet leucine oxidation increased for S. These results indicated that the MP and HP diets were nutrient overloads for S. There were no effects of varying protein intake on indexes of lean body mass (creatinine excretion, body density) for either group. In summary, protein requirements for athletes performing strength training are greater than for sedentary individuals and are above current Canadian and US recommended daily protein intake requirements for young healthy males.