Cardiovascular Responses to Unilateral, Bilateral, Upper, and Lower Limbs Resistance Exercise.

The effects of different resistance exercises on cardiovascular responses remain elusive. Therefore, the present study aimed to investigate acute cardiovascular responses to unilateral and bilateral upper and lower limb resistance exercise. Young healthy males (n = 22; 26.9 ± 5.4 years, 170.0 ± 6.0 cm, 77.0 ± 10.8 kg) participated in the present study. Four experimental sessions were carried out, each consisting of one of the four exercises: unilateral and bilateral knee extension, unilateral and bilateral biceps curl. Cardiovascular responses (heart rate; HR, systolic blood pressure; SBP, and rate-pressure product; RPP) were measured at rest and after each of the three sets in each resistance exercise. All sets were performed until concentric muscle failure with a rest interval of two min. The HR, SBP, and RPP progressively increased during all sessions with uni- and bilateral exercises of the lower and upper limbs. Importantly, bilateral exercises, mainly of the lower limbs, induced greater increases in HR, and RPP than unilateral exercises of the upper and lower limbs. Regarding SBP, bilateral knee extension exercise induced greater increases than unilateral biceps curl. From a practical standpoint, exercise professionals may consider prescribing unilateral upper and lower limb exercises to alleviate cardiovascular stress, because even when performed until concentric muscle failure, this exercise mode seems to induce lower cardiovascular demand during the resistance training session.

Changes in Insulin Sensitivity and Lipid Profile Markers Following Initial and Secondary Bouts of Multiple Eccentric Exercises.

An acute bout of eccentric exercise affects insulin sensitivity and lipid profile, but how the magnitude of muscle damage affects them is not clear. We compared changes in blood insulin sensitivity and lipid markers after the first (EC1) and second (EC2) eccentric exercise bouts. Fifteen sedentary young men performed arm, leg and trunk muscle eccentric exercises, and repeated them 2 weeks later. Fasting blood samples were taken before, 2 h and 1-5 days after each exercise bout to analyze plasma creatine kinase (CK) activity, serum glucose (GLU), insulin, homeostasis model assessment (HOMA), triacylglycerols (TG), total (TC) and low- (LDLC) and high-density lipoprotein cholesterol (HDLC) concentrations as well as TC/HDLC ratio. Changes in these measures were compared between bouts and relationships to peak plasma CK activity were analyzed. Plasma CK activity increased (p < 0.05) after EC1 (peak: 101,668 ± 58,955 IU/L) but not after EC2. The magnitude of changes in GLU (peak after EC1: 26 ± 10% vs. EC2: 7 ± 6%), insulin (46 ± 27% vs. 15 ± 8%), HOMA (86 ± 48% vs. 24 ± 15%), TC (-20 ± 5% vs. -6 ± 4%), TG (-32 ± 11% vs. -6 ± 3%), LDHC (-47 ± 15% vs. -12 ± 9%), HDLC (35 ± 26% vs. 7 ± 4%), and TC/HDLC ratio (-139 ± 13% vs. -11 ± 7%) were significantly greater after EC1 than EC2. Peak plasma CK activity was significantly (p < 0.05) correlated with the peak changes in blood insulin sensitivity and lipid markers for the combined data of EC1 and EC2. These results suggest that the greater the magnitude of muscle damage, the greater the magnitude of changes in the insulin sensitivity to a negative direction and lipid markers to a positive direction.

Decreased running economy is not associated with decreased force production capacity following downhill running in untrained, young men.

The present study investigated the relationships between changes in running economy (RE) and indirect muscle damage markers following downhill running (DHR) to test the hypothesis that decreased RE after DHR would be associated with decreases in muscle function. Forty-five young men ran downhill (-15%) for 30 min at the velocity corresponding to 70% of their peak oxygen uptake (VO2peak). Oxygen uptake (VO2) and other parameters possibly associated with RE (blood lactate concentration, perceived exertion, stride length and frequency) were measured during 5-minute level running at the velocity corresponding to 80%VO2peak before, immediately after and 1-3 days after DHR. Knee extensor maximal voluntary contraction torque (MVC), rate of torque development, vertical jump performance, muscle soreness and serum creatine kinase activity were assessed at the same time points. The values of the dependent variables were compared among time points by one-way ANOVAs followed by Bonferroni post-hoc tests when appropriate. Pearson's correlation tests were used to examine relationships between changes in VO2 (RE parameter) and changes in muscle damage parameters. VO2 during the level run increased (p < 0.05) immediately after DHR (18.3 ± 4.6%) and sustained until 2 days post-DHR (11.7 ± 4.2%). MVC decreased (p < 0.05) immediately (-21.8 ± 6.1%) to 3 days (-13.6 ± 5.9%) post-DHR, and muscle soreness developed 1-3 days post-DHR. The magnitude of changes in VO2 did not significantly (p < 0.05) correlate with the changes in muscle damage makers (r = -0.02-0.13) nor stride length (r = -0.05) and frequency (r = -0.05). The absence of correlation between the changes in VO2 and MVC suggests that strength loss was not a key factor affecting RE.

Consumption of An Anthocyanin-Rich Antioxidant Juice Accelerates Recovery of Running Economy and Indirect Markers of Exercise-Induced Muscle Damage Following Downhill Running.

This study examined the effects of anthocyanin-rich antioxidant juice (AJ) on the recovery of exercise-induced muscle damage (EIMD) and the running economy (RE) following downhill running (DHR). Thirty healthy young men were randomly divided into two blinded groups and consumed either AJ or placebo (PLA) for nine days (240 mL twice-a-day). On day 5, the participants from both groups ran downhill (-15%) for 30 min at 70% of their maximal oxygen uptake (VO2max) speeds. The changes in RE (oxygen uptake (VO2) and perceived effort (PE) during 5-min runs at 80%VO2max) and EIMD (isometric peak torque (IPT), muscle soreness (SOR) and serum creatine kinase activity (CK)) were compared over time and between the groups on the 4 days following DHR. VO2 and PE increased (p < 0.05) immediately following DHR for both groups and remained elevated for PLA until 48h post-DHR while fully recovering 24 h post-DHR for AJ. SOR was greater (p < 0.05) for PLA throughout the study. CK increased for both groups and was greater (p < 0.05) for PLA at 96 h post-DHR. IPT decreased for both groups but recovered faster for AJ (72 h) compared to PLA (no full recovery). AJ accelerated recovery of RE and EIMD and should be used in specific contexts, but not chronically.

Isometric pre-conditioning blunts exercise-induced muscle damage but does not attenuate changes in running economy following downhill running.

Running economy (RE) is impaired following unaccustomed eccentric-biased exercises that induce muscle damage. It is also known that muscle damage is reduced when maximal voluntary isometric contractions (MVIC) are performed at a long muscle length 2-4 days prior to maximal eccentric exercise with the same muscle, a phenomenon that can be described as isometric pre-conditioning (IPC). We tested the hypothesis that IPC could attenuate muscle damage and changes in RE following downhill running. Thirty untrained men were randomly assigned into experimental or control groups and ran downhill on a treadmill (-15%) for 30 min. Participants in the experimental group completed 10 MVIC in a leg press machine two days prior to downhill running, while participants in the control group did not perform IPC. The magnitude of changes in muscle soreness determined 48 h after downhill running was greater for the control group (122 ±â€¯28 mm) than for the experimental group (92 ±â€¯38 mm). Isometric peak torque recovered faster in the experimental group compared with the control group (3 days vs. no full recovery, respectively). No significant effect of IPC was found for countermovement jump height, serum creatine kinase activity or any parameters associated with RE. These results supported the hypothesis that IPC attenuates changes in markers of muscle damage. The hypothesis that IPC attenuates changes in RE was not supported by our data. It appears that the mechanisms involved in changes in markers of muscle damage and parameters associated with RE following downhill running are not completely shared.

Attenuation of eccentric exercise-induced muscle damage conferred by maximal isometric contractions: a mini review.

Although, beneficial in determined contexts, eccentric exercise-induced muscle damage (EIMD) might be unwanted during training regimens, competitions and daily activities. There are a vast number of studies investigating strategies to attenuate EIMD response after damaging exercise bouts. Many of them consist of performing exercises that induce EIMD, consuming supplements or using equipment that are not accessible for most people. It appears that performing maximal isometric contractions (ISOs) 2-4 days prior to damaging bouts promotes significant attenuation of EIMD symptoms that are not related to muscle function. It has been shown that the volume of ISOs, muscle length in which they are performed, and interval between them and the damaging bout influence the magnitude of this protection. In addition, it appears that this protection is not long-lived, lasting no longer than 4 days. Although no particular mechanisms for these adaptations were identified, professionals should consider applying this non-damaging stimulus before submitting their patients to unaccustomed exercised. However, it seems not to be the best option for athletes or relatively trained individuals. Future, studies should focus on establishing if ISOs protect other populations (i.e., trained individuals) or muscle groups (i.e., knee extensors) against EIMD, as well as investigate different mechanisms for ISO-induced protection.

Transcription Blockage Leads to New Beginnings.

Environmental agents are constantly challenging cells by damaging DNA, leading to the blockage of transcription elongation. How do cells deal with transcription-blockage and how is transcription restarted after the blocking lesions are removed? Here we review the processes responsible for the removal of transcription-blocking lesions, as well as mechanisms of transcription restart. We also discuss recent data suggesting that blocked RNA polymerases may not resume transcription from the site of the lesion following its removal but, rather, are forced to start over from the beginning of genes.

DNA repair and recovery of RNA synthesis following exposure to ultraviolet light are delayed in long genes.

The kinetics of DNA repair and RNA synthesis recovery in human cells following UV-irradiation were assessed using nascent RNA Bru-seq and quantitative long PCR. It was found that UV light inhibited transcription elongation and that recovery of RNA synthesis occurred as a wave in the 5'-3' direction with slow recovery and TC-NER at the 3' end of long genes. RNA synthesis resumed fully at the 3'-end of genes after a 24 h recovery in wild-type fibroblasts, but not in cells deficient in transcription-coupled nucleotide excision repair (TC-NER) or global genomic NER (GG-NER). Different transcription recovery profiles were found for individual genes but these differences did not fully correlate to differences in DNA repair of these genes. Our study gives the first genome-wide view of how UV-induced lesions affect transcription and how the recovery of RNA synthesis of large genes are particularly delayed by the apparent lack of resumption of transcription by arrested polymerases.

ATR suppresses apoptosis after UVB irradiation by controlling both translesion synthesis and alternative tolerance pathways.

Ultraviolet (UV) light can stall replication forks owing to the formation of bulky lesions in the DNA. Replication across these blocking lesions occurs through translesion DNA synthesis, and cells activate the ATR damage responses to UV. However, it remains unclear whether lesion bypass requires the replication checkpoint because ATR is not necessary for PCNA ubiquitylation. We observed that ATR knockdown by siRNA increased replication stress and promoted early induction of apoptosis following UVB irradiation in SV40-immortalized human cells, including cells from XP-V and XP-C patients. XP-V cells were further sensitized by the silencing, indicating that DNA polymerase η (Pol η) remains active despite ATR control. However, following UVB irradiation, ATR-depleted cells were unable to achieve mitosis, as would be expected after the loss of a DNA checkpoint control. Thus, ATR also regulates replication arrest recovery following UVB-induced damage, independently of Pol η, in SV40-immortalized cell lines. The ATR-mediated DNA damage response regulates replication and different tolerance pathways, and in these cells, ATR depletion induces replication catastrophe, which contributes to explain the potential of ATR inhibition to protect against UVB-induced carcinogenesis.

Long-term behavioral and cognitive outcomes following clipping for incidental unruptured intracranial aneurysms.

OBJECTIVE: Recent advances in neuroimaging techniques have resulted in more frequent detection of unruptured intracranial aneurysms. Regardless of the method employed, most interventions to treat lesions have low morbidity and mortality rates. Recently, some studies have suggested that changes in cognitive status are one complication of microsurgical treatments. However, no study to date has performed any behavioral analysis. Moreover, cognitive assessment beyond 12 months after surgical intervention is missing. The current study sought to evaluate the long-term impact of clipping on the behavioral and cognitive functions of patients with unruptured intracranial aneurysms. METHOD: A within-subjects prospective clinical trial was performed to evaluate 40 patients who underwent microsurgical clipping for incidental unruptured intracranial aneurysms. The participants underwent a full neuropsychological evaluation during the preoperative period, at 3 months after surgery and at 3 years after surgery. Paired Student's t tests and an ANOVA, followed by a Bonferroni post hoc test, were used to examine group differences. RESULTS: The cognitive and behavioral test performance of the patients did not deteriorate during either the short or the long term following intervention. Moreover, the patients' clinical and demographic characteristics did not predict behavioral or cognitive changes, and neither the surgical approach nor the topography, multiplicity, or size of the aneurysms affected the results. CONCLUSIONS: In either the short or the long term following clipping for patients with incidental unruptured intracranial aneurysms, behavioral and cognitive functions had no significant change from baseline. The intervention demonstrated high efficacy and was associated with a low morbidity rate.

Microsurgical clipping in forty patients with unruptured anterior cerebral circulation aneurysms: an investigation into cognitive outcome.

OBJECTIVE: It is a consensus that most unruptured intracranial aneurysms (UIA) can be treated with acceptably low morbidity. However, some studies recently reported postoperative cognitive impairment, suggesting that it could be attributable to surgical damage. Our goal is to evaluate cognitive function before and after microsurgical clipping in patients with UIA. METHOD: A consecutive series of 40 patients who underwent microsurgical clipping for UIA were studied. The cognitive assessment (Mini Mental State Examination, MMSE) was performed immediately before and at least one month after surgery. Paired Student's "t" test and analysis of variance (ANOVA) were used for statistical purposes. RESULTS: The mean MMSE score in the preoperative analysis was 28.12 (SD, 1.34). In the postoperative period the mean MMSE score was 28.40 (SD, 1.46). Paired Student's "t" test was applied to the scores and no significant difference was found (p = 0.315). ANOVA did not find independent associations between MMSE scores and age, hypertension, smoking, dyslipidemia, education, aneurysm location, number, laterality or size. CONCLUSION: The present study suggests that microsurgical clipping for UIA does not result in major cognitive dysfunction as determined by the MMSE.

Microsurgical clipping in forty patients with unruptured anterior cerebral circulation aneurysms: an investigation into cognitive outcome / Clipagem microcirúrgica em 40 pacientes com aneurisma de circulação cerebral anterior não-roto: uma investigação cognitiva

OBJECTIVE: It is a consensus that most unruptured intracranial aneurysms (UIA) can be treated with acceptably low morbidity. However, some studies recently reported postoperative cognitive impairment, suggesting that it could be attributable to surgical damage. Our goal is to evaluate cognitive function before and after microsurgical clipping in patients with UIA. METHOD: A consecutive series of 40 patients who underwent microsurgical clipping for UIA were studied. The cognitive assessment (Mini Mental State Examination, MMSE) was performed immediately before and at least one month after surgery. Paired Student's "t" test and analysis of variance (ANOVA) were used for statistical purposes. RESULTS: The mean MMSE score in the preoperative analysis was 28.12 (SD, 1.34). In the postoperative period the mean MMSE score was 28.40 (SD, 1.46). Paired Student's "t" test was applied to the scores and no significant difference was found (p=0.315). ANOVA did not find independent associations between MMSE scores and age, hypertension, smoking, dyslipidemia, education, aneurysm location, number, laterality or size. CONCLUSION: The present study suggests that microsurgical clipping for UIA does not result in major cognitive dysfunction as determined by the MMSE.

OBJETIVO: É consenso que a maioria dos aneurismas intracranianos não-rotos (AINR) podem ser tratados com aceitável taxa de morbidade. Entretanto, alguns estudos reportaram déficits cognitivos no pós-operatório, sugerindo que poderiam ser atribuídos ao dano cirúrgico. O objetivo desse estudo é avaliar a função cognitiva antes e após clipagem microcirúrgica em pacientes com AINR. MÉTODO: Uma série de 40 pacientes com AINR submetidos à clipagem microcirúrgica foi estudada. A avaliação cognitiva (Mini Exame do Estado Mental, MEEM) foi realizada antes e após a intervenção cirúrgica. A análise estatística foi realizada com teste "t" de Student e análise de variância (ANOVA). RESULTADOS: A média dos escores do MEEM na análise pré-operatória foi 28,12 (DP, 1,34). No período pós-operatório, a média dos escores foi 28,40 (DP, 1,46). Não houve diferença estatística (teste "t" de Student; p=0,315). A ANOVA não encontrou associações independentes entre os escores de MEEM e idade, hipertensão, tabagismo, dislipidemia, educação e características dos aneurismas (topografia, número, lado e tamanho). CONCLUSÃO: O presente estudo sugere que a clipagem microcirúrgica não está associada a danos cognitivos maiores em pacientes com AINR.

Metabolic effects of p-coumaric acid in the perfused rat liver.

The p-coumaric acid, a phenolic acid, occurs in several plant species and, consequently, in many foods and beverages of vegetable origin. Its antioxidant activity is well documented, but there is also a single report about an inhibitory action on the monocarboxylate carrier, which operates in the plasma and mitochondrial membranes. The latter observation suggests that p-coumaric acid could be able to inhibit gluconeogenesis and related parameters. The present investigation was planned to test this hypothesis in the isolated and hemoglobin-free perfused rat liver. Transformation of lactate and alanine into glucose (gluconeogenesis) in the liver was inhibited by p-coumaric acid (IC50 values of 92.5 and 75.6 microM, respectively). Transformation of fructose into glucose was inhibited to a considerably lower degree (maximally 28%). The oxygen uptake increase accompanying gluconeogenesis from lactate was also inhibited. Pyruvate carboxylation in isolated intact mitochondria was inhibited (IC50 = 160.1 microM); no such effect was observed in freeze-thawing disrupted mitochondria. Glucose 6-phosphatase and fructose 1,6-bisphosphatase were not inhibited. In isolated intact mitochondria, p-coumaric acid inhibited respiration dependent on pyruvate oxidation but was ineffective on respiration driven by succinate and beta-hydroxybutyrate. It can be concluded that inhibition of pyruvate transport into the mitochondria is the most prominent primary effect of p-coumaric acid and also the main cause for gluconeogenesis inhibition. The existence of additional actions of p-coumaric acid, such as enzyme inhibitions and interference with regulatory mechanisms, cannot be excluded.

The action of quercetin on the mitochondrial NADH to NAD(+) ratio in the isolated perfused rat liver.

It has been suggested that active forms of quercetin ( o-semiquinones) are able to oxidize NADH in mammalian cells. The purpose of this study was to investigate this proposition by measuring the beta-hydroxybutyrate to acetoacetate ratio as an indicator of the mitochondrial NADH/NAD (+) redox ratio in the isolated perfused rat liver. The NADH to NAD (+) ratio was reduced by quercetin; half-maximal reduction occurred at a concentration of 32.6 microM. Additionally, quercetin (25 to 300 microM) stimulated the Krebs cycle ( (14)CO (2) production) and inhibited oxygen uptake (50 to 300 microM). Low quercetin concentrations (25 microM) stimulated oxygen uptake. The results of the present work confirm the hypothesis that quercetin is able to participate in the oxidation of NADH in mammalian cells, shifting the cellular conditions to a more oxidized state (prooxidant activity). Stimulation of the Krebs cycle was probably caused by the increased NAD (+) availability whereas the decreased NADH availability and the inhibition of mitochondrial energy transduction could be the main causes for oxygen uptake inhibition.