Acute Effect of Popular High-Intensity Functional Training Exercise on Physiologic Markers of Growth.

ABSTRACT: Kliszczewicz, B, Markert, CD, Bechke, E, Williamson, C, Clemons, KN, Snarr, RL, and McKenzie, MJ. Acute effect of popular high-intensity functional training exercise on physiologic markers of growth. J Strength Cond Res 35(6): 1677-1684, 2021-Constantly evolving, high-intensity functional training (HIFT) exercise consists of various modalities, orders, weights, and repetition schemes. High-intensity functional training has gained popularity among the general population, but lacks empirical evidence regarding acute adaptive responses. The purpose of this study was to describe the acute effects of 2 representative bouts of HIFT on physiologic markers of growth. For convenience, the bouts are designated "short" (<5 minutes) and "long" (∼15 minutes), although duration was not the only difference between bouts. Ten apparently healthy men (28.1 ± 5 years) performed 2 HIFT bouts in a randomized crossover design. Blood was collected at 5 time points (Pre, Post, 1, 3, and 6 hours) to examine growth hormone (GH), insulin-like growth factor (IGF-1), insulin-like growth factor binding proteins 1 and 2 (IGFBP-1 and IGFBP-2), and vascular endothelial growth factor (VEGF). Blood lactate concentration ([La]) was analyzed at the Pre and Post time points. A repeated-measures analysis of variance (ANOVA) revealed no trial differences among the markers (IGF-1, IGFBP-1, IGFBP-2, and VEGF) except GH at Post, where the long bout produced a greater effect (p = 0.005). Mean GH levels (pg·ml-1) in the short bout increased from 68.4 to 106.5, and in the long bout, mean GH levels increased from 38.5 to 286.4. The repeated-measures ANOVA revealed a main time effect in GH (p = 0.037), while a post hoc t-test demonstrated elevated GH at 1 hour (p = 0.018) when compared with Pre. No time-dependent change (p > 0.05) was observed in IGF-1, IGFBP-1, IGFBP-2, or VEGF. Mean blood [lactate] increased more than tenfold in both bouts. The findings of this descriptive study suggest that, other than GH, there are no acute differences in markers of skeletal muscle or vascular growth between these 2 specific HIFT bouts.

Synthesis and Activity of a Novel Autotaxin Inhibitor-Icodextrin Conjugate.

Autotaxin is an extracellular phospholipase D that catalyzes the hydrolysis of lysophosphatidyl choline (LPC) to generate the bioactive lipid lysophosphatidic acid (LPA). Autotaxin has been implicated in many pathological processes relevant to cancer. Intraperitoneal administration of an autotaxin inhibitor may benefit patients with ovarian cancer; however, low molecular mass compounds are known to be rapidly cleared from the peritoneal cavity. Icodextrin is a polymer that is already in clinical use because it is slowly eliminated from the peritoneal cavity. Herein we report conjugation of the autotaxin inhibitor HA155 to icodextrin. The conjugate inhibits autotaxin activity (IC50 = 0.86 ± 0.13 µg mL-1) and reduces cell migration. Conjugation of the inhibitor increased its solubility, decreased its membrane permeability, and improved its intraperitoneal retention in mice. These observations demonstrate the first application of icodextrin as a covalently-bonded drug delivery platform with potential use in the treatment of ovarian cancer.

Toward ß-Secretase-1 Inhibitors with Improved Isoform Selectivity.

BACE1 is responsible for the first step in APP proteolysis, leading to toxic Aß production, and has been indicated to play a key role in the pathogenesis of Alzheimer's disease. The related isoform BACE2 is thought to be involved in processing of the pigment cell-specific melanocyte protein. To avoid potential effects on pigmentation, we investigated the feasibility for developing isoform-selective BACE1 inhibitors. Cocrystal structures of 47 compounds were analyzed and clustered according to their selectivity profiles. Selective BACE1 inhibitors were found to exhibit two distinct conformational features proximal to the flap and the S3 subpocket. Several new molecules were designed and tested to make use of this observation. The combination of a pyrimidinyl C-ring and a methylcyclohexyl element resulted in lead molecule 28, which exhibited ∼50-fold selectivity. Compared to a nonselective BACE1/2 inhibitor, 28 showed significantly less inhibition of PMEL processing in human melanocytes, indicating good functional selectivity of this inhibitor class.

Effects of high-intensity interval training on cardiometabolic risk in overweight and obese African-American women: a pilot study.

OBJECTIVE: Little is known about high-intensity interval training (HIIT) in African-American (AA) women. The purpose of this pilot study was to evaluate the effects of HIIT and steady-state (SS) exercise on cardiometabolic risk factors in young AA women. DESIGN: A 16-week exercise intervention was conducted 3x/week. Twenty-seven AA women were randomized to SS (n = 11; 32 continuous minutes of treadmill walking at 60-70% of maximum heart rate (HRmax)), or HIIT (n = 16; 32 min of treadmill HIIT alternating 3 min at 60-70% of HRmax with 1 min at 80-90% of HRmax). Two-way repeated measures ANOVA with intention-to-treat analysis was used to identify changes between groups. Significance was accepted at P ≤ 0.05. RESULTS: Of the 27 women who entered the study (age: 30.5 ± 6.8 years; BMI: 35.1 ± 5.1 kg/m2; 5274 ± 1646 baseline steps/day), 14 completed the intervention. HIIT significantly decreased waist circumference (107.0 ± 11.3 to 105.1 ± 11.9 cm) compared to SS, which showed no change. There was a significant time effect for steps where HIIT increased steps/day (5334 ± 1586 to 7604 ± 1817 steps/day), and SS had no change. There were no significant changes in either group for any other measurements. CONCLUSION: HIIT was more effective at reducing waist circumference and increasing daily steps/day than SS treadmill exercise over 16 weeks. Further research in a larger sample is indicated to evaluate the effects of each protocol on cardiometabolic risk factors.

Body Composition, Fitness Status, and Health Behaviors Upon Entering College: An Examination of Female College Students From Diverse Populations.

Although poor health-related behaviors that impact development of chronic diseases begin much earlier than when actual disease is evident, few studies have examined health behaviors in college students, who may be at an important transitional period where early intervention could prevent development of chronic diseases. The purpose of this study was to examine health-related factors in female college students (N = 61) by race/ethnicity and weight status. We found significant differences in health profiles between non-Hispanic White (White) and African American students, including greater physical fitness and healthier diets among White students. Overweight/obese students had worse health profiles than healthy BMI students. Furthermore, weight status was significantly associated with cardiovascular fitness. This supports a focus on PA promotion for interventions in the period of emerging adulthood, alongside the other healthy behaviors, to elicit improvements in weight status and potential reduction of chronic disease risks.

New biphenyl iminium salt catalysts for highly enantioselective asymmetric epoxidation: role of additional substitution and dihedral angle.

New biaryl iminium salt catalysts for enantioselective alkene epoxidation containing additional substitution in the heterocyclic ring are reported. The effects upon conformation and enantioselectivity of this additional substitution, and the influence of dihedral angle in these systems, has been investigated using a synthetic approach supported by density functional theory. Enantioselectivities of up to 97% ee were observed.

Kinetic resolution in asymmetric epoxidation using iminium salt catalysis.

The first reported examples of kinetic resolution in epoxidation reactions using iminium salt catalysis are described, providing up to 99% ee in the epoxidation of racemic cis-chromenes.

Enantioselective total synthesis of (+)-scuteflorin A using organocatalytic asymmetric epoxidation.

We report the first enantioselective total synthesis of (+)-scuteflorin A in 14% overall yield, employing a chiral iminium salt to effect an organocatalytic asymmetric epoxidation of xanthyletin in >99% ee as the key step.

Gene response of the gastrocnemius and soleus muscles to an acute aerobic run in rats.

Genes can be activated or inhibited by signals within the tissues in response to an acute bout of exercise. It is unclear how a particular aerobic exercise bout may influence two muscles with similar actions to the activity. Therefore, the purposes of this investigation was to determine the gene response of selected genes involved in the "stress" response of the gastrocnemius (fast-twitch) and soleus (slow-twitch) muscles to a single two hour aerobic exercise bout in female Sprague-Dawley Rats at the 1 hour time point after the exercise. Exercised rats were run (n=8) for 2 hours at 20 m.min(-1) and one hour after the completion of the bout had their soleus (S) and gastrocnemius (G) muscles removed. Age and timed matched sedentary control rats had both S and G muscles removed also. RNA was isolated from all muscles. Real-time PCR analysis was performed on the following genes: NFκB, TNFα, and Atf3. GAPDH was used as the housekeeping gene for both muscles. S muscle showed more genes altered (n = 52) vs G (n = 26). NFκB gene expression was 0.83 ± 0.14 in the exercised S but was + 1.36 ± 0.58 in the exercised G and was not significantly different between the muscles. TNFα was altered 1.30 ± 0. 34 in the exercised S and 1.36 ± 0.71 in the exercised G and was not significantly different between the muscles. The gene Atf3 was significantly altered at 4.97 ± 1.01 in the exercised S, while it was not significantly altered in the exercised G (0.70 ± 0.55). This study demonstrates that an acute bout of aerobic exercise can alter gene expression to a different extent in both the S and G muscles. It is highly likely that muscle recruitment was a factor which influenced the gene expression in theses muscles. It is interesting to note that some genes were similarly activated in these two muscles but other genes may demonstrate a varied response to the same exercise bout depending on the type of muscle. Key pointsThe soleus (primarily slow twitch) and the gastrocnemius (primarily fast type) do not respond the same to a given exercise bout.There are gene transcription differences in stress genes between the 2 muscles.The results of exercise studies should be carefully viewed as the muscle used in measurements may not provide an adequate representation of all skeletal muscles.

Highly enantioselective total synthesis of (-)-(3'S)-Lomatin and (+)-(3'S,4'R)-trans-khellactone.

Concise highly enantioselective three-step syntheses are described for (-)-(3'S)-lomatin and (+)-(3'S,4'R)-trans-khellactone from 7-hydroxycoumarin in 97% ee and in 57% and 58% overall yields, respectively, using nonaqueous enantioselective epoxidation by an iminium salt as the key step.

Hemiparetic stroke alters vastus lateralis myosin heavy chain profiles between the paretic and nonparetic muscles.

Skeletal muscle phenotype alterations following hemiparetic stroke contribute to disabilities associated with stroke. The phenotypic response following stroke is undefined. This investigation examined the myosin heavy chain (MHC) composition of the vastus lateralis (VL) of stroke survivors in paretic (P) and nonparetic (NP) muscle. Protein obtained from VL of 10 stroke survivors was isolated and purified, and MHC gel electrophoresis was performed. The MHC bands were quantified, and a paired sample two-tailed T test with significance set at p < or = 0.05 was performed. MHC I expression was significantly less in P versus NP VL (.93 vs. 1.00 arbitrary units [AU]). Significantly more IIx MHC was found in the P versus NP VL (1.33 vs. 1.0). No significant differences in type IIa MHC (1.07 P vs. 1.00 NP) were found. These changes in MHC composition suggest an alteration in muscle function due to stroke or the altered activity patterns of muscle following stroke.

Reduced skeletal muscle capillarization and glucose intolerance.

OBJECTIVE: Reduced capillarization in hemiparetic skeletal muscle of chronic stroke patients can limit insulin, glucose, and oxygen supply to muscle, thereby contributing to impaired glucose metabolism and cardiovascular deconditioning. We hypothesized that compared to sedentary controls, stroke subjects have reduced skeletal muscle capillarization that is associated with glucose intolerance and reduced peak oxygen consumption (Vo(2peak)). METHODS: Twelve chronic stroke subjects (ages, 62.1+/-2.8 years), and matched sedentary controls with impaired (n=12) or normal (n=12) glucose tolerance underwent oral glucose tolerance tests, exercise tests, and vastus lateralis biopsies. RESULTS: Stroke subjects had lower capillarization in hemiparetic muscle than in nonparetic muscle and normal glucose tolerant controls ( approximately 22 and approximately 28%, respectively; P<0.05) and had similar bilateral capillarization, compared to controls with impaired glucose tolerance. Capillary density in hemiparetic muscle inversely correlated with 120-minute glucose (r=-0.70, P<0.01) and glucose area under the curve (r=-0.78, P<0.01). Vo(2peak) was approximately 40% lower in stroke subjects, compared to controls (P<0.001), but did not correlate with capillarization (P=n.s.). CONCLUSIONS: Hemiparetic muscle capillarization is reduced after stroke, and reduced capillarization is associated with glucose intolerance in stroke and control subjects. Interventions to increase skeletal muscle capillarization may prove beneficial for improving glucose metabolism in chronic stroke patients.

Human genome comparison of paretic and nonparetic vastus lateralis muscle in patients with hemiparetic stroke.

Hemiparetic stroke leads to major skeletal muscle abnormalities, as illustrated by paretic leg atrophy, weakness, and spasticity. Furthermore, the hemiparetic limb muscle shifts to a fast-twitch muscle fiber phenotype with anaerobic metabolism. This study investigated whether skeletal muscle genes were altered in chronic hemiparetic stroke. The nonparetic leg muscle served as an internal control. We used Affymetrix microarray analysis to survey gene expression differences between paretic and nonparetic vastus lateralis muscle punch biopsies from 10 subjects with chronic hemiparetic stroke. Stroke latency was greater than 6 months. We found that 116 genes were significantly altered between the paretic and non paretic vastus lateralis muscles. These gene differences were consistent with reported differences after stroke in areas such as injury and inflammation markers, the myosin heavy chain profile, and high prevalence of impaired glucose tolerance and type 2 diabetes. Furthermore, while many other families of genes were altered, the gene families with the most genes altered included inflammation, cell cycle regulation, signal transduction, metabolism, and muscle contractile protein genes. This study is an early step toward identification of specific gene regulatory pathways that might lead to these differences, propagate disability, and increase vascular disease risk.

Gender comparisons of exercise-induced oxidative stress: influence of antioxidant supplementation.

The purpose of this study was to determine the influence of gender and antioxidant supplementation on exercise-induced oxidative stress. Twenty-five men and 23 women ran for 30 min at 80% VO2 max, once before and once after 2 weeks of supplementation, and again after a 1-week wash-out period. Subjects were randomly assigned to either placebo (P), antioxidant (A: 400 IU vitamin E+1 g vitamin C), or a fruit and vegetable powder (FV) treatment. Blood was obtained at rest and immediately after exercise. Before supplementation, women had higher resting reduced glutathione, total glutathione, and plasma vitamin E compared with men. With both A and FV supplementations, plasma vitamin E gender differences disappeared. Protein carbonyls, oxidized glutathione, and malondialdehyde all increased similarly for both genders in response to exercise. Both A and FV attenuated the reduced glutathione decrease and the oxidized glutathione and protein carbonyls increase compared with P, with no gender differences. 8-hydroxydeoxyguanosine was lower with treatment A compared with FV and P only for men. Plasma vitamin C increased 39% (A) and 21% (FV) compared with P. These data indicate that women have higher resting antioxidant levels than men. Markers of oxidative stress increased similarly in both genders in response to exercise of similar intensity and duration. Two weeks of antioxidant supplementation can attenuate exercise-induced oxidative stress equally in both genders.

A new asymmetric synthesis of the anti-tumor alkaloid (R)-(+)-crispine A.

We report a novel, facile, and asymmetric approach for the synthesis of the anti-tumor alkaloid (+)-crispine A via a highly diastereoselective N-acyliminium cyclization reaction as a key synthetic step.

Aerobic exercise bout effects on gene transcription in the rat soleus.

PURPOSE: This study was designed to identify changes in gene transcription that occur in the soleus muscle of untrained, 10-wk-old rats after a single aerobic exercise bout, and to identify which families of genes are most likely affected. METHODS: Rats were either run for 2 h and killed 1 h after exercise, or they remained sedentary and were killed at a matched time. Soleus muscles from each animal were examined using DNA microarrays, four genes related to RONS were analyzed by PCR, and two proteins were checked by Western blot analysis. RESULTS: The microarray identified 52 genes significantly altered by the exercise. The major gene families altered were metabolism, apoptosis, muscle contraction, transcription/cell signaling, tissue generation, and inflammation. Real-time PCR was performed on four genes (NFkappaB, TNFalpha, Atf3, and Mgst1), and the results from PCR analysis agreed with the microarray results. NFkappaB and TNFalpha were unaltered, whereas Atf3 was upregulated and Mgst1 was downregulated in the exercised soleus muscles. NFkappaB protein level was not different between the two groups, whereas Atf3 protein level was elevated in the exercise group according to Western blot analysis. CONCLUSIONS: These data suggest that 1 h after a 2-h run at approximately 65% of VO2max, the soleus muscle undergoes significant gene-transcript changes. Also, the genes examined with the real-time PCR matched the microarray results and the measured protein concentration concentrations agreed with gene-transcript data at the 1-h postexercise time point.

Oxidative stress response to aerobic exercise: comparison of antioxidant supplements.

PURPOSE: To compare the effects of two antioxidant formulas on biomarkers of oxidative stress before and after aerobic exercise. METHODS: Aerobically trained men (N=25) and women (N=23) were assigned to one of three treatments: 400 IU of vitamin E+1 g of vitamin C (V; N=15), a fruit and vegetable juice powder concentrate (FV; N=16), or a placebo (P; N=17). Subjects ran for 30 min at 80% VO(2 max) before, after 2 wk of supplementation, and after a 1-wk washout period. Blood samples were taken before and immediately after exercise and analyzed for protein carbonyls (PC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and vitamins C and E. RESULTS: The V treatment increased plasma vitamin C and E after 2 wk (P

Effects of acute aerobic and anaerobic exercise on blood markers of oxidative stress.

The purpose of this study was to compare oxidative modification of blood proteins, lipids, DNA, and glutathione in the 24 hours following aerobic and anaerobic exercise using similar muscle groups. Ten cross-trained men (24.3 +/- 3.8 years, [mean +/- SEM]) performed in random order 30 minutes of continuous cycling at 70% of Vo(2)max and intermittent dumbbell squatting at 70% of 1 repetition maximum (1RM), separated by 1-2 weeks, in a crossover design. Blood samples taken before, and immediately, 1, 6, and 24 hours postexercise were analyzed for plasma protein carbonyls (PC), plasma malondialdehyde (MDA), and whole-blood total (TGSH), oxidized (GSSG), and reduced (GSH) glutathione. Blood samples taken before and 24 hours postexercise were analyzed for serum 8-hydroxy-2'-deoxyguanosine (8-OHdG). PC values were greater at 6 and 24 hours postexercise compared with pre-exercise for squatting, with greater PC values at 24 hours postexercise for squatting compared with cycling (0.634 +/- 0.053 vs. 0.359 +/- 0.018 nM.mg protein(-1)). There was no significant interaction or main effects for MDA or 8-OHdG. GSSG experienced a short-lived increase and GSH a transient decrease immediately following both exercise modes. These data suggest that 30 minutes of aerobic and anaerobic exercise performed by young, cross-trained men (a) can increase certain biomarkers of oxidative stress in blood, (b) differentially affect oxidative stress biomarkers, and (c) result in a different magnitude of oxidation based on the macromolecule studied. Practical applications: While protein and glutathione oxidation was increased following acute exercise as performed in this study, future research may investigate methods of reducing macromolecule oxidation, possibly through the use of antioxidant therapy.

Combined antioxidant treatment effects on blood oxidative stress after eccentric exercise.

PURPOSE: This study was designed to ascertain the effects of a combination antioxidant therapy on plasma protein carbonyls (PC), malondialdehyde (MDA), and whole blood total (TGSH), oxidized (GSSG), and reduced (GSH) glutathione in non-resistance trained females after eccentric resistance exercise. METHODS: Eighteen women (aged 19-31 yr) were randomized in a double-blind manner to either an antioxidant supplement (N = 9; 400 IU vitamin E, 1 g vitamin C, and 90 mug selenium per day) or a lactose placebo (N = 9) for 14 d before and for 2 d after eccentric elbow flexor exercise. Blood samples taken before and immediately, 2, 6, 24, and 48 h postexercise were analyzed for PC, MDA, TGSH, and GSSG. RESULTS: No treatment by time interaction was noted for any variable, with all blood markers experiencing a change after the exercise in both conditions. Time main effects were observed for PC, MDA, and GSSG, with values elevated above preexercise after the eccentric exercise, whereas GSH concentration decreased after the eccentric exercise. Antioxidant supplementation resulted in a condition main effect for PC and MDA, with lower values compared with placebo. The antioxidant treatment attenuated the rise in both PC (75%) and MDA (100%). CONCLUSION: These data suggest that eccentric resistance exercise can increase blood biomarkers of oxidative stress in non-resistance trained females, and this vitamin E, C, and selenium supplementation can attenuate the rise in PC and MDA.

Oxidative stress response in normal and antioxidant supplemented rats to a downhill run: changes in blood and skeletal muscles.

The purpose of this study was to determine if changes in oxidative stress biomarkers in blood and skeletal muscles are similar in normal and antioxidant supplemented rats after a downhill run. Sixty-six male Sprague-Dawley rats were pretreated with a normal rat diet or diet + antioxidants (2,000 mg vitamin C + 1,000 IU vitamin E/kg diet) for 2 weeks. Exercised rats ran 90 min on a rodent treadmill at a speed of 16 m/min at -16 degrees grade. Rats were sacrificed either at rest, immediately, 2 hrs, or 48 hrs postexercise. Malondialdehyde (MDA) and protein carbonyl (PC) concentrations and glutathione status in blood, vastus lateralis (white fast-twitch), vastus intermedius (red fast-twitch), and soleus (slow-twitch) muscles were determined. A significant increase from rest in PC occurred in plasma, vastus intermedius and soleus muscle 2 hrs after the downhill run (p < 0.05), with no changes observed at any other times postexercise. Antioxidant supplementation significantly decreased PC concentrations in both vastus intermedius and soleus muscles at all times combined (p < 0.05). MDA and glutathione status in blood and muscles were unaffected by either the downhill run or antioxidant treatment. For PC and MDA, the concentrations were lower in blood as compared to skeletal muscle, with the opposite finding for oxidized glutathione; however, the pattern of response postexercise was similar. These data indicate that (a) PC, but not MDA or oxidized glutathione, is elevated transiently following downhill running in male rats; (b) the elevation in PC postexercise occurs in plasma, vastus intermedius, and soleus muscles; (c) antioxidant therapy can attenuate PC in vastus intermedius, and soleus muscles; and (d) while the concentrations of oxidative stress biomarkers differ between blood and the various skeletal muscles, the pattern of response postexercise is similar.