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Purpose Carbohydrate (CHO) restriction could be a potent metabolic regulator of endurance exercise-induced muscle adaptations. Here, we determined whether post-exercise CHO restriction following strenuous exercise combining continuous cycling exercise (CCE) and sprint interval exercise could affect the gene expression related to mitochondrial biogenesis and oxidative metabolism in human skeletal muscle. Methods In a randomized cross-over design, 8 recreationally active males performed two cycling exercise sessions separated by 4 weeks. Each session consisted of 60-min CCE and six 30-s all-out sprints, which was followed by ingestion of either a CHO or placebo beverage in the post-exercise recovery period. Muscle glycogen concentration and the mRNA levels of several genes related to mitochondrial biogenesis and oxidative metabolism were determined before, immediately after, and at 3 h after exercise. Results Compared to pre-exercise, strenuous cycling led to a severe muscle glycogen depletion (> 90%) and induced a large increase in PGC1A and PDK4 mRNA levels (~ 20-fold and ~ 10-fold, respectively) during the acute recovery period in both trials. The abundance of the other transcripts was not changed or was only moderately increased during this period. CHO restriction during the 3-h post-exercise period blunted muscle glycogen resynthesis but did not increase the mRNA levels of genes associated with muscle adaptation to endurance exercise, as compared with abundant post-exercise CHO consumption. Conclusion CHO restriction after a glycogen-depleting and metabolically-demanding cycling session is not effective for increasing the acute mRNA levels of genes involved in mitochondrial biogenesis and oxidative metabolism in human skeletal muscle.

Current methods (plateau/secondary criteria) to determine maximal oxygen consumption ( $$ {\dot{\text{V}}} $$ O2max) are inconsistently achieved leading some to suggest the use of a verification phase (VP) to confirm $$ {\dot{\text{V}}} $$ O2max. To provide further evidence for the inclusion of a VP to confirm $$ {\dot{\text{V}}} $$ O2max in different fitness levels. Forty-nine participants (22 females; 21.9 ± 2.6 years, 24.3 ± 2.8 kg m−2, 45.27 ± 7.68 mL kg−1 min−1) had their $$ {\dot{\text{V}}} $$ O2 and heart rate measured during three graded exercise tests (GXT) on separate days each followed by a VP of differing intensity (85%, 95%, 105% final workload). Participants were divided into groups using norms adapted from American College of Sports Medicine $$ {\dot{\text{V}}} $$ O2max guidelines (30.47–61.47 mL kg−1 min−1). $$ {\dot{\text{V}}} $$ O2max was confirmed if the $$ {\dot{\text{V}}} $$ O2peak on the VP or an additional GXT was within ± 2 × typical error of the $$ {\dot{\text{V}}} $$ O2peak attained on the first GXT. There was no effect of test number so the third GXT was not included in comparison with VP. The $$ {\dot{\text{V}}} $$ O2peak from the first GXT was not different than either value attained following the VP at 95 or 105% workload or a second GXT (p > 0.999). The 85% VP $$ {\dot{\text{V}}} $$ O2peak was lower than the first GXT $$ {\dot{\text{V}}} $$ O2peak (p = 0.002). The VP confirmed the GXT $$ {\dot{\text{V}}} $$ O2peak on 73% of VP (no differences among fitness levels). Submaximal VP (85 and 95%) was less effective as 65% and 51% of participants achieved a higher $$ {\dot{\text{V}}} $$ O2peak on one of the GXT. The use of a VP at 105% or a second GXT was able to confirm the $$ {\dot{\text{V}}} $$ O2max value attained across a range of fitness levels.

The purpose of this study was to evaluate subjects with high-risk alcohol cardiotoxicity and patients with alcoholic cardiomyopathy (ACM) via dynamic 11C-Acetate positron emission tomography (PET) imaging as a myocardial oxidative metabolic probe. We recruited 37 subjects with chronic alcohol consumption [18 with moderate consumption (MC), 19 with heavy consumption (HC)], 5 ACM patients, and 12 healthy controls to receive dynamic 11C-Acetate PET scans. PET imaging data were analyzed to calculate kinetic parameters (e.g., Kmono, K1 and k2) based on the mono-exponential and one-tissue compartmental models. Myocardial oxygen consumption (MVO2) and myocardial external efficiency (MEE) were then derived from these kinetic parameters. MVO2 was significantly lowered in the HC group and in ACM patients (0.121± 0.018 and 0.111 ± 0.017 mL·g−1·min−1, respectively) compared with those in healthy controls and MC subjects (0.144 ± 0.023 and 0.146 ± 0.027 mL·g−1·min−1, respectively; P < .01). MEE was significantly reduced in ACM patients (13.0% ± 4.3%) compared with those of healthy controls (22.4% ± 4.6%, P < .01), MC subjects (20.1% ± 4.5%, P < .05), and HC subjects (22.3% ± 4.5%, P < .001). Functional assessment via dynamic 11C-Acetate PET imaging may represent a clinically feasible probe for identifying cohorts with high-risk cardiotoxicity due to addictive alcohol consumption and ACM.

Contrasting with several theories of ageing, bats are mammals with remarkable longevity despite their high metabolic rate, living on average three times more than other mammals of equal size. The question of how bats live a long time has attracted considerable attention, and they have thus been related to immortal fantasy characters like Dracula in the novel by Bram Stoker. Several ecological and physiological features, such as reduction in mortality risks, delayed sexual maturation and hibernation, have been linked to bats' long lifespan. However, there is still very little information about the molecular mechanisms associated with the longevity of bats. In this regard, the present work tries to summarize current knowledge about how bats can live for so long, taking into consideration nutritional factors, oxidative metabolism, protein homeostasis, stress resistance, DNA repair, mitochondrial physiology and cancer resistance.

Near-infrared spectroscopy (NIRS) has become an increasingly valuable tool to monitor tissue oxygenation (Toxy) in vivo. Observations of changes in the absorption of light with Toxy have been recognized as early as 1876, leading to a milestone NIRS paper by Jobsis in 1977. Changes in the absorption and scatting of light in the 700–850-nm range has been successfully used to evaluate Toxy. The most practical devices use continuous-wave light providing relative values of Toxy. Phase-modulated or pulsed light can monitor both absorption and scattering providing more accurate signals. NIRS provides excellent time resolution (~ 10 Hz), and multiple source–detector pairs can be used to provide low-resolution imaging. NIRS has been applied to a wide range of populations. Continued development of NIRS devices in terms of lower cost, better detection of both absorption and scattering, and smaller size will lead to a promising future for NIRS studies.

This study focused on the steady-state phase of exercise to evaluate the relative contribution of metabolic instability (measured with NIRS and haematochemical markers) and muscle activation (measured with EMG) to the oxygen consumption ($${\dot{V}O_2}$$ V ˙ O 2 ) slow component ($${\dot{V}O_2}{_s}{_c}$$ V ˙ O 2 s c ) in different intensity domains. We hypothesized that (i) after the transient phase, $${\dot{V}O_2}$$ V ˙ O 2 , metabolic instability and muscle activation tend to increase differently over time depending on the relative exercise intensity and (ii) the increase in $${\dot{V}O_2}{_s}{_c}$$ V ˙ O 2 s c is explained by a combination of metabolic instability and muscle activation. Eight active men performed a constant work rate trial of 9 min in the moderate, heavy and severe intensity domains. $${\dot{V}O_2}$$ V ˙ O 2 , root mean square by EMG (RMS), deoxyhaemoglobin by NIRS ([HHb]) and haematic markers of metabolic stability (i.e. [La−], pH, HCO3−) were measured. The physiological responses in different intensity domains were compared by two-way RM-ANOVA. The relationships between the increases of [HHb] and RMS with $${\dot{V}O_2}$$ V ˙ O 2 after the third min were compared by simple and multiple linear regressions. We found domain-dependent dynamics over time of $${\dot{V}O_2}$$ V ˙ O 2 , [HHb], RMS and the haematic markers of metabolic instability. After the transient phase, the rises in [HHb] and RMS showed medium–high correlations with the rise in $${\dot{V}O_2}$$ V ˙ O 2 ([HHb] r = 0.68, p r = 0.59, p = 0.002). Moreover, the multiple linear regression showed that both metabolic instability and muscle activation concurred to the $${\dot{V}O_2}{_s}{_c}$$ V ˙ O 2 s c (r = 0.75, [HHb] p = 0.005, RMS p = 0.042) with metabolic instability possibly having about threefold the relative weight compared to recruitment. Seventy-five percent of the dynamics of the $${\dot{V}O_2}{_s}{_c}$$ V ˙ O 2 s c was explained by [HHb] and RMS.

Impaired oxidative metabolism is one of multi-variate factors leading to exercise intolerance in heart failure patients. The purpose of the study was to demonstrate the use of dynamic 31P magnetic resonance spectroscopy (MRS) and 31P magnetic resonance imaging (MRI) techniques to measure PCr resynthesis rate post-exercise as a biomarker for oxidative metabolism in skeletal muscle in HF patients and controls. In this prospective imaging study, we recruited six HF patients and five healthy controls. The imaging protocol included 31P-MRS, spectrally selective 3D turbo spin echo for 31P-MRI, and Dixon multi-echo GRE for fat–water imaging on a 3 T clinical MRI scanner. All the subjects were scanned pre-exercise, during plantar flexion exercise, and post-exercise recovery, with two rounds of exercise for 31P -MRS and 31P-MRI, respectively. Unpaired t-tests were used to compare 31P-MRS and 31P-MRI results between the HF and control cohorts. The results show that PCr resynthesis rate was significantly slower in the HF cohort compared to the controls using 31P-MRS (P = 0.0003) and 31P-MRI (P = 0.0014). 31P-MRI showed significant differences between the cohorts in muscle groups (soleus (P = 0.0018), gastrocnemius lateral (P = 0.0007) and gastrocnemius medial (P = 0.0054)). The results from this study suggest that 31P-MRS/31P-MRI may be used to quantify lower leg muscle oxidative metabolism in HF patients, with 31P-MRI giving an additional advantage of allowing further localization of oxidative metabolism deficits. Upon further validation, these techniques may serve as a potentially useful clinical imaging biomarker for staging and monitoring therapies in HF-patients.

Myocardial efficiency measured by 11C-acetate positron emission tomography (PET) has successfully been used in clinical research to quantify mechanoenergetic coupling. The objective of this study was to establish the repeatability of myocardial external efficiency (MEE) and work metabolic index (WMI) by non-invasive concepts. Ten healthy volunteers (63 ± 4 years) were examined twice, one week apart, using 11C-acetate PET, cardiovascular magnetic resonance (CMR), and echocardiography. Myocardial oxygen consumption from PET was combined with stroke work data from CMR, echocardiography, or PET to obtain MEE and WMI for each modality. Repeatability was estimated as the coefficient of variation (CV) between test and retest. MEECMR, MEEEcho, and MEEPET values were 21.9 ± 2.7%, 16.4 ± 3.7%, and 23.8 ± 4.9%, respectively, P

Non-invasive approaches to investigate myocardial efficiency can help track the progression of heart failure (HF). This study evaluates the repeatability and reproducibility of 11C-acetate positron emission tomography (PET) imaging of oxidative metabolism. Dynamic 11C-acetate PET scans were performed at baseline and followup (47 ± 22 days apart) in 20 patients with stable HF with reduced ejection fraction. Two observers blinded to patients’ clinical data used FlowQuant® to evaluate test–retest repeatability, as well as intra- and inter-observer reproducibility of 11C-acetate tracer uptake and clearance rates, for the measurement of myocardial oxygen consumption (MVO2), myocardial external efficiency (MEE), work metabolic index (WMI), and myocardial blood flow. Reproducibility and repeatability were evaluated using intra-class-correlation (ICC) and Bland–Altman coefficient-of-repeatability (CR). Test–retest correlations and repeatability were better for MEE and WMI compared to MVO2. All intra- and inter-observer correlations were excellent (ICC = 0.95-0.99) and the reproducibility values (CR = 3%-6%) were significantly lower than the test–retest repeatability values (22%-54%, P

The goal of our study was to assess the influence of chronic exposure to hypoxia on mitochondrial oxidative metabolism in human umbilical vein endothelial cells (EA.hy926 line) cultured for 6 days at 1% O2 tension. The hypoxia-induced effects were elucidated at the cellular and isolated mitochondria levels. Hypoxia elevated fermentation but did not change mitochondrial biogenesis or the aerobic respiratory capacity of endothelial cells. In endothelial cells, hypoxia caused a general decrease in mitochondrial respiration during carbohydrate, fatty acid, and amino acid oxidation but increased exclusively ketogenic amino acid oxidation. Hypoxia induced an elevation of intracellular and mitochondrial reactive oxygen species (ROS) formation, although cell viability was unchanged and antioxidant systems (superoxide dismutases SOD1 and SOD2, and uncoupling proteins (UCPs)) were not increased. In mitochondria from hypoxic cells, the opposite change was observed at the respiratory chain level, i.e., considerably elevated expression and activity of complex II, and decreased expression and activity of complex I were observed. The elevated activity of complex II resulted in an increase in succinate-sustained mitochondrial ROS formation, mainly through increased reverse electron transport. A hypoxia-induced decrease in UCP2 expression and activity was also observed. It can be concluded that the exposure to chronic hypoxia induces a shift from aerobic toward anaerobic catabolic metabolism. The hypoxia-induced increase in intracellular and mitochondrial ROS formation was not excessive and may be involved in endothelial signaling of hypoxic responses. Our results indicate an important role of succinate, complex II, and reverse electron transport in hypoxia-induced adjustments in endothelial cells.

While the formation and concentration of urine are better understood, how kidney epithelial cells generate the energy to drive these functions has remained unclear. A study now reveals that shear stress originating from urinary flow is sensed by the primary cilia of cortical epithelial cells and stimulates lipolysis and oxidative metabolism.

Selective autophagy of organelles is critical for cellular differentiation, homeostasis, and organismal health. Autophagy of the ER (ER-phagy) is implicated in human neuropathy but is poorly understood beyond a few autophagosomal receptors and remodelers. By using an ER-phagy reporter and genome-wide CRISPRi screening, we identified 200 high-confidence human ER-phagy factors. Two pathways were unexpectedly required for ER-phagy. First, reduced mitochondrial metabolism represses ER-phagy, which is opposite of general autophagy and is independent of AMPK. Second, ER-localized UFMylation is required for ER-phagy to repress the unfolded protein response via IRE1a. The UFL1 ligase is brought to the ER surface by DDRGK1 to UFMylate RPN1 and RPL26 and preferentially targets ER sheets for degradation, analogous to PINK1-Parkin regulation during mitophagy. Our data provide insight into the cellular logic of ER-phagy, reveal parallels between organelle autophagies, and provide an entry point to the relatively unexplored process of degrading the ER network.

Summary Objective Obesity is a major health problem associated with high morbidity and mortality. NSAID activated gene, (NAG-1) is a TGF-β superfamily member reported to alter adipose tissue levels in mice. We investigated whether hNAG-1 acts as a regulator of adiposity and energy metabolism. Design/Subjects hNAG-1 mice, ubiquitously expressing hNAG-1, were placed on a control or high fat diet (HFD) for 12 weeks. hNAG-1 expressing B16/F10 melanoma cells were used in a xenograft model to deliver hNAG-1 to obese C57BL/6 mice. Results As compared to wild-type littermates, transgenic hNAG-1 mice have less white fat and brown fat despite equivalent food intake, improved glucose tolerance, lower insulin levels and are resistant to dietary- and genetic-induced obesity. hNAG-1 mice are more metabolically active with higher energy expenditure. Obese C57BL/6 mice treated with hNAG-1 expressing xenografts show decreases in adipose tissue and serum insulin levels. hNAG-1 mice and obese mice treated with hNAG-1 expressing xenografts show increased thermogenic gene expression (UCP1, PGC1α, ECH1, Cox8b, Dio2, Cyc1, PGC1β, PPARα, Elvol3) in brown adipose tissue (BAT) and increased expression of lipolytic genes (Adrb3, ATGL, HSL) in both white adipose tissue (WAT) and BAT, consistent with higher energy metabolism Conclusion hNAG-1 modulates metabolic activity by increasing the expression of key thermogenic and lipolytic genes in BAT and WAT. hNAG-1 appears to be a novel therapeutic target in preventing and treating obesity and insulin resistance.

The purpose of this study was to investigate the relationship between sympathetic innervation, contractile function, and the oxidative metabolism of the non-infarcted myocardium in patients with prior myocardial infarction.In 19 patients (14 men, 5 women, 65 ± 9 years) after prior myocardial infarction, sympathetic innervation was assessed by (11)C-hydroxyephedrine (HED) positron emission tomography (PET). Oxidative metabolism was quantified using (11)C-acetate PET. Left ventricular systolic function was measured by echocardiography with speckle tracking technique.The (11)C-HED retention was positively correlated with left ventricular ejection fraction (LVEF) (r = 0.566, P0.05), and negatively with peak longitudinal strain in systole in the non-infarcted myocardium (r = -0.561, P0.05). Kmono, as an index of oxidative metabolism, was significantly correlated with rate pressure product (r = 0.649, P0.01), but not with (11)C-HED retention (r = 0.188, P = 0.442). Furthermore, there was no significant correlation between Kmono and LVEF (r = 0.106, P = 0.666) or peak longitudinal strain in systole (r = -0.256, P = 0.291) in the non-infarcted myocardium. When the patients were divided into two groups based on the median value of left ventricular end-systolic volume index (LVESVI) (41 mL), there were no significant differences in age, sex, and rate pressure product between the groups. However, the large LVESVI group (41 mL) was associated with reduced (11)C-HED retention and peak longitudinal strain in systole, whereas Kmono was similar between the groups.This study indicates that remodeled LV after myocardial infarction is associated with impaired sympathetic innervation and function even in the non-infarcted myocardial tissue. Furthermore, oxidative metabolism in the non-infarcted myocardium seems to be operated by normal regulatory mechanisms rather than pre-synaptic sympathetic neuronal function.

Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO(2)) in patients with chronic heart failure using (11)C-acetate positron emission tomography (PET).We prospectively enrolled 21 patients with severe heart failure. (11)C-acetate PET was performed before and after activation of the CCM device. In 12 patients an additional stress study with dobutamine was performed.Under resting conditions, the values of myocardial blood flow (MBF), MVO(2) and work metabolic index (WMI, reflecting myocardial efficiency) with the CCM device activated did not differ significantly from the values with the device deactivated. MBF was 0.81 ± 0.18 ml min(-1) g(-1) with the device off and 0.80 ± 0.15 ml min(-1) g(-1) with the device on (p = 0.818), MVO(2) was 6.81 ± 1.69 ml/min/100 g with the device off and 7.15 ± 1.62 ml/min/100 g with the device on (p = 0.241) and WMI was 4.94 ± 1.14 mmHg ml/m(2) with the device off and 5.21 ± 1.36 mmHg ml/m(2) with the device on (p = 0.344). Under dobutamine stress, the values of MBF, MVO(2) and WMI with the CCM device activated did not differ from the values with the device deactivated, but were significantly increased compared with the values obtained under resting conditions.These results indicate that CCM does not induce increased MVO(2), even under stress conditions.

Pollen beetle (Meligethes aeneus F.) (PB) causes very serious problems in oilseed rape (Brassica napus var. oleifera L.) cultivations in Poland and other European countries. Pyrethroid insecticides are the most frequently used type for controlling PB in Poland. This chemical group has been used in Poland since the beginning of the 1980’s and its strong selection pressure on PB resulted in some level of resistance of this pest to many active substances. The aim of this investigation was to analyze, with the use of synergists, the main mechanisms responsible for resistance of PB to pyrethroids. The results indicate the main resistance factor in Polish PB populations to be monooxygenase enzymes.

The relationship between myocardial oxidative metabolism and pressure overload in aortic valve stenosis (AS) is not fully elucidated. We identified the determinants of myocardial oxidative metabolism by measuring its changes after aortic valve replacement (AVR) in patients with AS.Myocardial 11C-acetate clearance rate constant (Kmono), an index of oxidative metabolism, was measured non-invasively by using positron emission tomography in 16 patients with moderate to severe AS and 7 healthy controls. The severity of AS was assessed by echocardiography. Of 16 patients, 5 were reexamined at 1 month after AVR.Kmono was significantly higher in patients with AS than healthy controls by 42% (0.068±0.014 vs 0.048±0.007/min, p0.01). Kmono was significantly correlated with age (r=0.58, p0.01), left ventricular (LV) mass index (r=0.61, p0.01) and estimated systolic LV pressure (r=0.81, p0.001) measured by echocardiography. By multivariate analysis, estimated LV systolic pressure was an independent predictor of Kmono (β=0.93, p0.01). After AVR, Kmono (from 0.075±0.012 to 0.061±0.014/min, p=0.043) and LV mass index (from 183±49 to 124±41 g/ml2, p=0.043) were significantly decreased despite no significant changes in rate-pressure product.Myocardial oxygen metabolism was increased in patients with AS, which was decreased after AVR. The increased myocardial oxidative metabolism in AS was largely attributable to the pressure overload of the LV.

Nitric oxide has been strongly implicated in the development of tissue infarction in response to focal cerebral ischemia. Nitric oxide and its derivatives can inhibit components of the electron transport chain, providing a likely target for these substances in ischemic and post-ischemic brain. Lactate content is increased during post-ischemic reperfusion in tissue destined to become infarcted, consistent with impairment of mitochondrial respiration. To investigate the possible involvement of nitric oxide in generating these changes, we have tested the effect of 7-nitroindazole, a nitric oxide synthase (NOS) inhibitor, on the content of lactate and other metabolites during early reperfusion following temporary focal ischemia. This treatment inhibited total NOS by approximately 50%. However, the treatment did not significantly affect the marked increases in lactate in post-ischemic brain nor did it alter the recovery of other energy-related metabolites. These findings indicate that inhibition of oxidative metabolism is probably not the primary site of the deleterious effects of nitric oxide and derivatives during early post-ischemic reperfusion.

Nonischemic dilated cardiomyopathy (NIDCM) is associated with left ventricular remodeling, hypertrophy, and mitochondrial metabolic abnormalities in vitro. We evaluated the hypothesis that energy supply, as judged by the rate of myocardial oxidative metabolism, is inadequate to meet oxygen demand in patients with NIDCM compared with normal subjects.We used positron emission tomography to determine the myocardial carbon 11 acetate decay rate (kmono) as an index of energy supply, and we compared kmono with the rate-pressure product (RPP) as an index of metabolic demand in 7 patients with NIDCM and 7 normal subjects. The mean kmono value (SEM) was 0.060 +/- 0.006 min(-1) in NIDCM patients versus 0.054 +/- 0.002 in normal subjects (P = not significant). The RPP was 9949 +/- 931 beats/min.mm Hg in NIDCM patients and 6521 +/- 476 in normal subjects (P = .007). The relationship of kmono to this index of demand (kmono/RPP) was 6.2 x 10(-6) in NIDCM patients but was 8.5 x 10(-6) in normal subjects (P = .003). Thus RPP, as an index of myocardial oxygen demand, was poorly matched by the rate of oxidative metabolism in those patients with NIDCM. The kmono was closely related to RPP in normal subjects (r = 0.83, P = .02) but not in NIDCM patients. Furthermore, there was no significant relationship between kmono and wall stress as another index of oxygen demand.These results are consistent with a mitochondrial metabolic abnormality in heart failure. This metabolic mismatch detected by positron emission tomography may contribute to the pathophysiology of congestive heart failure and left ventricular remodeling.

This study aimed to quantify oxidative metabolism in masseter muscle using near-infrared spectroscopy, in particular for denture wearers. Fourteen normal dentate subjects without malocclusion (ND group, 25-50 years) participated in the quantification of oxidative metabolism. Eleven partially edentulous patients without occlusal stops (PD group, 64-80 years) and ten edentulous patients (CD group, 57-84 years) also participated after prosthodontic treatment. Oxidative metabolism was recorded during gum chewing, maximum clenching and regulated clenching at 5 kgf. The oxygenated hemoglobin at 5 kgf clenching level was normalized to the oxygenated hemoglobin at the lowest blood flow and expressed as oxygen consumption rate (OCR). The relationship of the OCR to the maximum clenching force was analyzed using Pearson's correlation coefficient, and differences between the PD and CD groups were tested by unpaired Student's t-test. The OCR showed a significant negative correlation with maximum clenching force in the ND group. The OCR of the PD group was significantly greater than that of the CD group, although the difference in maximum clenching force was not significant between both groups. These results suggest that the aerobic ability of masseter muscle in complete denture wearers is relatively greater than in partial denture wearers with same age level.

The fibroblast growth factor 21 (FGF21)-β-Klotho pathway orchestrates a switch to oxidative metabolism during fasting and starvation and has been implicated as a signal connecting nutrition, growth, reproduction and longevity. Two new studies in mice show that Fgf21 interacts directly with the brain circadian clock to coordinate activity and reproduction as part of the adaptation to fasting.

This article provides an overview of the role of oxygen in wound healing. The understanding of this role has undergone a major evolution from its long-recognized importance as an essential factor for oxidative metabolism, to its recognition as an important cell signal interacting with growth factors and other signals to regulate signal transduction pathways. Our laboratory has been engaged in the study of animal models of skin ischemia to explore in vivo the impact of hypoxia as well as the use of oxygen as a therapeutic agent either alone or in combination with other agents such as growth factors. We have demonstrated a synergistic effect of systemic hyperbaric oxygen and growth factors that has been substantiated by Hunt's group. Within the past 10 years research in the field of wound healing has given new insight into the mechanism of action of hypoxia and hyperoxia as modifiers of the normal time-course of wound healing. The article concludes with a discussion of why hypoxia and hyperoxia intercurrently play an important role in wound healing. Hypoxia-inducible factor 1 is crucial in that interplay.

To estimate the effect of artificial ventilation on regional cerebral blood flow, cardiovascular regulation, and cerebral oxidative metabolism in newborns.Comparison of three randomized treatment groups of newborn piglets: Group 1 (artificially ventilated sham-operated group; n =7); group 2 (artificially ventilated group with normoxia and moderate normocapnic hypoxia; n =7); group 3 (spontaneously breathing group with normoxia and moderate normocapnic hypoxia; n =6).Animals were anesthetized with 0.5% isoflurane in 70% nitrous oxide and 30% oxygen. Groups 1 and 2 were artificially ventilated. Animals in group 3 breathed spontaneously. Moderate normocapnic hypoxia was induced in groups 2 and 3 for 1 h by lowering the inspiratory oxygen fraction from 0.35 to 0.11. Mode of ventilation induced at most marginal effects on global cerebrovascular response, cardiovascular regulation, and cerebral oxidative metabolism. However, under normoxic conditions, regional cerebral blood flow of the medulla oblongata, pons, mesencephalon, thalamus, and cerebellum were markedly reduced in artificially ventilated piglets ( P0.05). Moderate normocapnic hypoxia led to a marked increase in regional cerebral blood flow, which was significantly lower in the medulla oblongata, pons, mesencephalon, thalamus, and cerebellum of artificially ventilated piglets ( P0.05).Artificial ventilation clearly induces reduced neuronal activity in the brain stem and cerebellum of newborn piglets. This is suggested by a considerably reduced blood flow in these regions under normoxia and moderate normocapnic hypoxia. However, there is no relevant detrimental effect on cardiovascular regulation and brain oxidative metabolism.

The oxidative hypothesis of cardiovascular disease (CVD) has undergone tremendous changes during the past few years. Innumerable new proatherogenic effects have been added to the existing list that could be attributed to oxidative stress. However, both animal and human trials with a variety of antioxidants have failed to establish unambiguously a protective role for antioxidants in the prevention of CVD. This could be because of poor choice and dosage of antioxidants, incompatible experimental models, oxidative metabolism of the antioxidant, unrealistic expectations, and other reasons. More importantly, recent studies suggest that oxidative stress also could induce antioxidant enzymes in both cell culture and in vivo systems. In lieu of the potential of known deterrents of CVD such as exercise, estrogens, and the consumption of polyunsaturated fatty acids to induce an oxidative stress, the possibility that natural enhancement of antioxidant defense in the artery could better serve to deter CVD cannot be ignored. Thus, if oxidative stress does play a role in CVD, it may be better, in the absence of suitable animal models that respond to antioxidants, to adhere to behavioral and dietary changes that have been shown to benefit CVD.

P450 enzymes comprise a superfamily of heme-containing proteins that catalyze oxidative metabolism of structurally diverse chemicals. Over the past few years, there has been significant progress in P450 research on many fronts and the information gained is currently being applied to both drug development and clinical practice. Recently, a major accomplishment occurred when the structure of a mammalian P450 was determined by crystallography. Results from these studies will have a major impact on understanding structure-activity relationships of P450 enzymes and promote prediction of drug interactions. In addition, new technologies have facilitated the identification of several new P450 alleles. This information will profoundly affect our understanding of the causes attributed to interindividual variations in drug responses and link these differences to efficacy or toxicity of many therapeutic agents. Finally, the recent accomplishments towards constructing P450 null animals have afforded determination of the role of these enzymes in toxicity. Moreover, advances have been made towards the construction of humanized transgenic animals and plants. Overall, the outcome of recent developments in the P450 arena will be safer and more efficient drug therapies.

Biophoton emission from germinating soybean under adverse circumstance has been observed by high sensitive imaging system based on ICCD detector. It is found that the intensity of biophoton emission from the injured position of the cotyledon is enhanced obviously compared with the intact position. In addition, a strong biophoton emission has been detected at the tip of the root when the root is supplied with water after drought. The emission induced by wounding may be associated with the defense response of plants. The emission during the process of convalescence after drought may be the results of the changes of oxidative metabolism in cells.

The effect of SO 3 2− , S2−, NO 3 − , and NH 4 + on activity of the peroxidase-hydrogen peroxide system in human peripheral blood neutrophils was studied by the cytochemical method. We showed that the effect of these xenobiotics on neutrophils is similar to that on plants.

The effect of zinc (Zn) on cellular oxidative metabolism is complex and could be explained by multiple complementary interactions. In this study, we evaluated the impact of Zn on the pro-oxidant/antioxidant balance of HaCaT keratinocytes. Cells were submitted to a diffusible metal chelator able to induce intracellular Zn deprivation, TPEN, in combination or not with Zn chloride (ZnCl2), in the culture medium. The intracellular amount of Zn, copper (Cu), and iron (Fe) was determined, as well as CuZnSOD and MnSOD activities and glutathione reserves. The consequence of the modulation of Zn concentration on lipid peroxidation was also evaluated. TPEN induced a significant dose-dependent decrease in intracellular Zn and Cu (from 394-181 and 43-21 microg/g protein, respectively, after 6 h of TPEN 50 microM). No significant change in intracellular Fe concentration was found following TPEN exposure. The SOD activities were unchanged after 6 h of TPEN 50 microM application, either CuZnSOD or MnSOD. Cells exposure to TPEN induced a deep time- and dose-dependent decrease in their glutathione content (from 65-8 microM/g protein after 6 h of TPEN 50 microM), and a concomitant increase in glutathione in the cell-culture supernatants. No significant change in lipid peroxidation products was detected.

Orthophosphate concentration of baker's yeast Saccharomyces cerevisiae was investigated during dynamic conditions. As an example for those dynamics in cell metabolism the transition from glucose limitation to glucose excess (Crabtree-effect) was choosen. As a result of the metabolic switch from complete to partial oxidative metabolism, the cytoplasmic phosphate concentration increased suddenly from 8.4 mM to a maximum of 17.5 mM and transiently decreased to a minimum of 7.0 mM.

The peripheral blood neutrophils and the neutrophils accumulated into a skin-window experimental exudate were compared for their ability to release superoxide anion (O 2 − ) and for their fatty acid composition, determined by capillary gaschromatography. The basal O 2 − release and the phorbol myristate acetate (PMA)-induced O 2 − release were not significantly different in the two neutrophil populations, while in response to formyl-methionyl-leucyl-phenylalanine (fMLP) the exudate cells showed an activity that was two fold higher than that of blood cells. The most significant changes of fatty acid composition of exudate versus blood cells were the following: i) increase of C16∶0 (palmitic acid) from 21.3±1.2% to 23.5±1.3% (+ 10.2%) of total fatty acids (p

Albino rats were subjected to local (the head) or total X-ray Irradiation in doses of 0.5, 1.0, 2.0, and 4.0 Gy, and the dynamics of concentrations of the products of lipid peroxidation (LP) in the brain and blood were compared. Activation of LP was shown to result predominantly from a direct local radiation effect. Transport of LP products from the irradiated brain with blood and, probably, some other mechanisms determine the development of general shifts in LP indices. Radiation impairment of the whole body by the same radiation dose considerably increases the reactive mobilization of antioxidative mechanisms, which results in a suppression of the second peak of concentration of the LP products, up to its total disappearance.

Background Polyunsaturated fatty acids are popular dietary supplements advertised to contribute to weight loss by increasing fat metabolism in liver, but the effects on overall muscle metabolism are less established. We evaluated the effects of conjugated linoleic acid (CLA) or combination omega 3 on metabolic characteristics in muscle cells. Methods Human rhabdomyosarcoma cells were treated with either DMSO control, or CLA or combination omega 3 for 24 or 48 hours. RNA was determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mitochondrial content was determined using flow cytometry and immunohistochemistry. Metabolism was quantified by measuring extracellular acidification and oxygen consumption rates. Results Omega 3 significantly induced metabolic genes as well as oxidative metabolism (oxygen consumption), glycolytic capacity (extracellular acidification), and metabolic rate compared with control. Both treatments significantly increased mitochondrial content. Conclusion Omega 3 fatty acids appear to enhance glycolytic, oxidative, and total metabolism. Moreover, both omega 3 and CLA treatment significantly increase mitochondrial content compared with control.

Effects of prednisolone, estradiol, and testosterone on the transport of Ca2+ and the respiration induced by it in the heart and liver mitochondria of rats were studied. Prednisolone and testosterone were found to reduce the Ca-accumulating capacity of the mitochondria, the rates of ion entry and exit, and the rate of Ca2+-induced respiration. Estradiol, while inhibiting Ca2+ transport across mitochondrial membrane, did not influence the respiration in the phase of Ca2+ absorption, but accelerated it in the phase of ion exit. These data suggest that due to their lipophilic properties, the steroids become incorporated in the mitochondrial membrane, thereby changing its viscosity and permeability and limiting the mobility of transmitter proteins.

Positron emission tomography-derived 11C-labeled acetate kinetics have been shown to reflect myocardial oxidative metabolism. The objective of the study was to use this metabolic imaging technique in combination with an evaluation of left ventricular work as an index of ventricular mechanical efficiency.The effects of ventricular ejection fraction and loading on this index were studied quantitatively in a canine experimental model. There was a curvilinear relationship between efficiency and the end-diastolic volume per unit mass (r = 0.84), which appeared to integrate the main determinants of left ventricular mechanical performance successfully and allowed the detection of a decreased ventricular efficiency in acute experimental heart failure.This approach appears to have the potential to assess the energetic working point of the ventricle in clinical heart disease and follow the effects of therapy. The data demonstrate the feasibility of an estimate of ventricular efficiency that relies on noninvasive data-acquisition techniques.

The role of intra- and extracellular calcium in beta-adrenergic regulation of rat's heart have been shown. It was found that oxidative metabolism of resistant and non-resistant animals to hypoxia is under control of 2 different intracellular calcium pools. The role of intracellular calcium is more important in non-resistant to hypoxia rats.

The first phase of the healing process is characterized by the development of an inflammatory reaction involving migration of inflammatory cells and release of inflammatory mediators. In a previous study, we have demonstrated that the water soluble tetrachlorodecaoxygen complex (TCDO), first synthetized to promote wound healing, inhibits polymorphonuclear (PMN) migration. The aim of the present study was to investigate the activity of TCDO on the progression of an acute non-specific inflammatory reaction, on the release of 6-keto-PGF1 alpha and PGE2 and on PMN oxidative metabolism in the rat. Injected in the pleural cavity, TCDO (15 mumoles/rat) significantly decreased the number of exudative cells while 1.5 mumoles/rat inhibited PMN oxidative metabolism ex vivo (assessed by chemiluminescent assay and measurement of O2- generation) after stimulation of the cells by opsonized zymosan. Similar observations were made in vitro after incubation of PMNs with various concentrations of TCDO (300 to 3 microM). The effect was dose-related and highly significant up to the concentration of 3 microM. In parallel, TCDO decreased the amounts of 6-keto-PGF1 alpha and PGE2 in exudates harvested 1 hour after the intrapleural injection of isologous serum. Effects were significantly different from control levels, from 1.5 to 0.03 mumoles/rat for 6-keto-PGF1 alpha and from 1.5 to 0.01 mumoles/rat for PGE2. This effect was observed when TCDO was injected at the same time or 1 hour before the isologous serum but not later. TCDO also inhibited LTB4 generation in vitro after PMN stimulation by calcium ionophore A23187, at concentrations up to 150 microM. The effects of TCDO in vivo and in vitro on rat PMN functions and inflammatory mediator release mimic certain activities of anti-inflammatory drugs. These properties may be beneficial in the very early stages of the wound healing process.

We present a 5-year-old boy with a severe form of X-linked chronic granulomatous disease and hypersensitivity to sulphamides preventing prophylaxis with trimethoprim-sulphomethoxazole. Bone marrow transplantation was performed after preconditioning with busulphan and cyclophosphamide. The immediate post-transplant period was without complications. Complete chimerism was demonstrated and post-transplant oxidative metabolism was normal. The patient is asymptomatic 30 months after the graft.Bone marrow transplantation in cases of chronic granulomatous disease is controversial, although it could be useful in selected very severe cases in which prophylactic therapy is problematic.

The effects of animal and biotechnological cytochrome C and its hemtetradecapeptide in a heme-isomolar dose on the cerebral bloodflow, oxygen and glucose consumption, and pH of the ischemized brain were studied in cat experiments. Cytochrome of both types and hemtetradecapeptide increased the consumption of oxygen and glucose by ischemized brain tissue and somewhat reduced the development of acidosis. The shifts of oxidative metabolism parameters of the ischemized brain correlated with inhibition of the development of postischemic hypoperfusion of the brain.

Adaptation of muscle to endurance exercise training involves the coordinated expression of genes involved in oxidative metabolism, resulting in increased endurance. A recent study shows that small-molecule activators of two pathways thought to transduce these effects can enhance the effects of training, or even substitute for it.

To assess the biventricular response of the clearance rate of carbon-11 acetate as an index of myocardial oxidative metabolism to increase in work-load, dynamic positron emission tomography was performed at rest and during dobutamine infusion in 14 normal subjects. The clearance rate constant (Kmono) of the left ventricular (LV) myocardium increased during dobutamine infusion (0.112 +/- 0.020 min-1 vs 0.065 +/- 0.015 min-1 at rest) (P0.001) in proportion to the increase in the pressure-rate product. Kmono in the right ventricular (RV) myocardium also increased (0.080 +/- 0.018 min-1 vs 0.034 +/- 0.013 min-1 at rest) (P0.001), with an excellent correlation with the LV Kmono (r = 0.920). The fact that the increase in RV Kmono during dobutamine infusion was greater (158% +/- 81%) than that in LV Kmono (79% +/- 39%) (P0.005) indicates a greater increase in oxidative metabolism in the RV in response to inotropic stimulation in normal subjects.

Sepsis is the leading cause of mortality in the ICU. Sepsis morbidity and mortality are increasing through the years. Infection control depends on adequate microbe recognition and satisfactory cell activation. Paradoxically it has been seen that in sepsis cell activation can be both good and harmful to the host.

Spontaneous and Bacillus anthracis induced luminol-dependent chemiluminescence of neutrophils was studied in six patients with the cutaneous form of anthrax. Spontaneous chemiluminescence in anthrax was decreased compared to the healthy controls (p0.05). B. anthracis, opsonized by complement-containing sera from patients, induced chemiluminescence in neutrophils from control donors but not from patients. B. anthracis, opsonized by complement-free sera from the patients, did not cause an increase in chemiluminescence response in either the patient or the control neutrophils. Also, B. anthracis, opsonized with normal sera and nonopsonized, did not induce chemiluminescence in either patient or control neutrophils. It was concluded that oxidative metabolism by neutrophils is impaired in anthrax, whereas the functional capacity of antibodies seems to be unaffected.