Effects of short-term selenium exposure on respiratory activity and proximate body composition of early-life stages of Catla catla, Labeo rohita and Cirrhinus mrigala.

Metal exposure impairs respiration, increases metabolic demand, and reduces energy storage/fitness in aquatic species. Respiratory impairment and energy storage was examined in acute selenium-exposed Indian major carps, Catla catla, Labeo rohita and Cirrhinus mrigala fry and were correlated with exposure concentrations. Toxicity effects were determined in a renewal bioassay using 96 h lethal selenium concentrations. Species sensitivity distribution (SSD) was also used to derive predicted no-effect concentrations, toxicity exposure ratios, for selenium exposures to early-life fish stages. Mortality was proportional with increasing concentrations. Oxygen consumption and lipid content compared to moisture and ash and of all protein content in tissues of C. catla and C. mrigala indicates that lowered oxygen consumption is directly predictive of lowered lipid content and selenium-induced hypoxia impacts the energy/nutritional status of the early-life stage of carp. This cross-taxa comparison will have major implications for advancing impact assessment and allow better targeting of species for conservation measures.

Transdermal Delivery of a Hydrogen Sulphide Donor, ADT-OH Using Aqueous Gel Formulations for the Treatment of Impaired Vascular Function: an Ex Vivo Study.

PURPOSE: Hydrogen sulphide (H2S) is an important signalling molecule involved in the regulation of several physiological and pathophysiological processes. The objective of this study was to investigate the feasibility of transdermal delivery of ADT-OH, a H2S donor, by investigating the transdermal flux of aqueous gels loaded with penetration enhancers or liposomes. Furthermore, we explored the ability of permeated ADT-OH to promote angiogenesis and mitochondrial bioenergetics in HUVEC cells. METHODS: Aqueous hypromellose gels (5% w/v) were prepared with up to 10% v/v propylene glycol (PG) or deformable liposomes with 0.025% w/w ADT-OH. ADT-OH permeation from formulations across excised murine skin into PBS was quantified over 24 h using HPLC-UV detection. Media was collected and applied to HUVEC cells to evidence ADT-OH functionality following permeation. Tube formation assays were performed as indicative of angiogenesis and mitochondrial oxygen consumption was evaluated using a Seahorse XF24. RESULTS: Increasing the loading of PG caused an increase in ADT-OH permeation rate across skin and a decrease in dermal drug retention whereas liposomal gels produced a slow-release profile. Treatment of HUVEC's using conditioned media collected from the ADT-OH loaded permeation studies enhanced tube formation and the basal oxygen consumption rates after 30 min of treatment. CONCLUSIONS: These findings demonstrate that transdermal delivery of ADT-OH may provide a promising approach in the treatment of impaired vascular function. Gels prepared with 10% v/v PG have the potential for use in conditions requiring rapid H2S release whereas liposomal loaded gels for treatment requiring sustained H2S release.

Effects of Caffeine Intake on Cardiopulmonary Variables and QT Interval after a Moderate-Intensity Aerobic Exercise in Healthy Adults: A Randomized Controlled Trial.

Caffeine is considered a widely consumed natural and legal psychoactive stimulant with several effects on the body. The present study attempted to investigate the effects of caffeine consumed before and after a physical exercise on cardiovascular and cardiorespiratory functions in healthy adults. 36 healthy adult males were recruited and randomly allocated to one of the three (3) groups: group I (exercise without caffeine consumption), group II (caffeine beverage intake before exercise), and group III (caffeine beverage intake immediately after exercise). The heart rate (HR), QTc interval, blood pressure (BP), respiratory rate (RR), oxygen consumption (VO2), and carbon dioxide emission (VCO2) were measured at 0, 5, 10, and 15 min after the exercise. We observed a significant difference in all measured outcomes during the different recovery times in all the groups (p < 0.05). HR, RR, SBP, VO2, and VCO2 gradually decreased with time, DBP contrarily increased with time, and the QTc showed an irregular pattern. We can affirm that ingestion of caffeine before and after moderate aerobic exercise slows down the parasympathetic stimulation, heart rate recovery, and the recovery of HR and QTc with no major effects on BP, RR, VO2, and VCO2 in healthy adult men.

Effects of Short-Term Phosphate Loading on Aerobic Capacity under Acute Hypoxia in Cyclists: A Randomized, Placebo-Controlled, Crossover Study.

The aim of this study was to evaluate the effects of sodium phosphate (SP) supplementation on aerobic capacity in hypoxia. Twenty-four trained male cyclists received SP (50 mg·kg-1 of FFM/day) or placebo for six days in a randomized, crossover study, with a three-week washout period between supplementation phases. Before and after each supplementation phase, the subjects performed an incremental exercise test to exhaustion in hypoxia (FiO2 = 16%). Additionally, the levels of 2,3-diphosphoglycerate (2,3-DPG), hypoxia-inducible factor 1 alpha (HIF-1α), inorganic phosphate (Pi), calcium (Ca), parathyroid hormone (PTH) and acid-base balance were determined. The results showed that phosphate loading significantly increased the Pi level by 9.0%, whereas 2,3-DPG levels, hemoglobin oxygen affinity, buffering capacity and myocardial efficiency remained unchanged. The aerobic capacity in hypoxia was not improved following SP. Additionally, our data revealed high inter-individual variability in response to SP. Therefore, the participants were grouped as Responders and Non-Responders. In the Responders, a significant increase in aerobic performance in the range of 3-5% was observed. In conclusion, SP supplementation is not an ergogenic aid for aerobic capacity in hypoxia. However, in certain individuals, some benefits can be expected, but mainly in athletes with less training-induced central and/or peripheral adaptation.

Blood product resuscitation mitigates the effects of aeromedical evacuation after polytrauma.

BACKGROUND: The combined injury of traumatic brain injury and hemorrhagic shock has been shown to worsen coagulopathy and systemic inflammation, thereby increasing posttraumatic morbidity and mortality. Aeromedical evacuation to definitive care may exacerbate postinjury morbidity because of the inherent hypobaric hypoxic environment. We hypothesized that blood product resuscitation may mitigate the adverse physiologic effects of postinjury flight. METHODS: An established porcine model of controlled cortical injury was used to induce traumatic brain injury. Intracerebral monitors were placed to record intracranial pressure, brain tissue oxygenation, and cerebral perfusion. Each of the 42 pigs was hemorrhaged to a goal mean arterial pressure of 40 ± 5 mm Hg for 1 hour. Pigs were grouped according to resuscitation strategy used-Lactated Ringer's (LR) or shed whole blood (WB)-then placed in an altitude chamber for 2 hours at ground, 8,000 ft, or 22,000 ft, and then observed for 4 hours. Hourly blood samples were analyzed for proinflammatory cytokines and lactate. Internal jugular vein blood flow was monitored continuously for microbubble formation with altitude changes. RESULTS: Cerebral perfusion, tissue oxygenation, and intracranial pressure were unchanged among the six study groups. Venous microbubbles were not observed even with differing altitude or resuscitation strategy. Serum lactate levels from hour 2 of flight to the end of observation were significantly elevated in 22,000 + LR compared with 8,000 + LR and 22,000 + WB. Serum IL-6 levels were significantly elevated in 22,000 + LR compared with 22,000 + WB, 8,000 + LR and ground+LR at hour 1 of observation. Serum tumor necrosis factor-α was significantly elevated at hour 2 of flight in 8,000 + LR versus ground+LR, and in 22,000 + LR vs. 22,000 + WB at hour 1 of observation. Serum IL-1ß was significantly elevated hour 1 of flight between 8,000 + LR and ground+LR. CONCLUSION: Crystalloid resuscitation during aeromedical transport may cause a prolonged lactic acidosis and proinflammatory response that can predispose multiple-injury patients to secondary cellular injury. This physiologic insult may be prevented by using blood product resuscitation strategies.

Biochemical and respiratory parameters in a gastropod Radix balthica exposed to diclofenac.

Diclofenac, an anti-inflammatory drug, is often detected in natural waters in the ng/L to µg/L range, posing a threat to aquatic organisms. The study focused on the effects of diclofenac in a gastropod mollusk Radix balthica. A 72-h exposure to environmentally relevant concentrations of diclofenac caused deviations from the baseline activities of the studied enzymes in the digestive gland of snails. Acetylcholinesterase activity was induced by the end of exposure, with the most pronounced increase at 3 µg/L. Results on glutathione-S-transferase activity were nonuniform, and no significant variations were observed in thiobarbituric acid reactive substances concentrations, indicating that diclofenac did not cause oxidative stress in the digestive gland of R. balthica at 0.04-4 µg/L range. Diclofenac lowered the oxygen consumption rate in snails in a concentration-dependent manner. At concentrations ≥0.9 µg/L, animals attempted to switch aquatic respiration to breathing air to regulate their metabolic needs. The study showed that diclofenac at environmentally relevant concentrations affected the fitness of R. balthica.

Active mitochondrial respiration in cancer: a target for the drug.

The relative contribution of mitochondrial respiration and subsequent energy production in malignant cells has remained controversial to date. Enhanced aerobic glycolysis and impaired mitochondrial respiration have gained more attention in the metabolic study of cancer. In contrast to the popular concept, mitochondria of cancer cells oxidize a diverse array of metabolic fuels to generate a majority of the cellular energy by respiration. Several mitochondrial respiratory chain (MRC) subunits' expressions are critical for the growth, metastasis, and cancer cell invasion. Also, the assembly factors, which regulate the integration of individual MRC complexes into native super-complexes, are upregulated in cancer. Moreover, a series of anti-cancer drugs function by inhibiting respiration and ATP production. In this review, we have specified the roles of mitochondrial fuels, MRC subunits, and super-complex assembly factors that promote active respiration across different cancer types and discussed the potential roles of MRC inhibitor drugs in controlling cancer.

Changes in plasma concentration of kynurenine following intake of branched-chain amino acids are not caused by alterations in muscle kynurenine metabolism.

Administration of branched-chain amino acids (BCAA) has been suggested to enhance mitochondrial biogenesis, including levels of PGC-1α, which may, in turn, alter kynurenine metabolism. Ten healthy subjects performed 60 min of dynamic one-leg exercise at ∼70% of Wmax on two occasions. They were in random order supplied either a mixture of BCAA or flavored water (placebo) during the experiment. Blood samples were collected during exercise and recovery, and muscle biopsies were taken from both legs before, after, and 90 and 180 min following exercise. Ingestion of BCAA doubled their concentration in both plasma and muscle while causing a 30%-40% reduction (P < 0.05 vs. placebo) in levels of aromatic amino acids in both resting and exercising muscle during 3-h recovery period. The muscle concentration of kynurenine decreased by 25% (P < 0.05) during recovery, similar in both resting and exercising leg and with both supplements, although plasma concentration of kynurenine during recovery was 10% lower (P < 0.05) when BCAA were ingested. Ingestion of BCAA reduced the plasma concentration of kynurenic acid by 60% (P < 0.01) during exercise and recovery, whereas the level remained unchanged with placebo. Exercise induced a three- to fourfold increase (P < 0.05) in muscle content of PGC-1α1 mRNA after 90 min of recovery under both conditions, whereas levels of KAT4 mRNA and protein were unaffected by exercise or supplement. In conclusion, the reduction of plasma levels of kynurenine and kynurenic acid caused by BCAA were not associated with any changes in the level of muscle kynurenine, suggesting that kynurenine metabolism was altered in tissues other than muscle.

Prolonged cortisol elevation alters whole body and tissue metabolism in rainbow trout (Oncorhynchus mykiss).

Chronic elevation of circulating cortisol is known to have deleterious effects on fish, but information about the consequences of prolonged cortisol elevation on the metabolism of fish is scarce. To test the effects of chronic cortisol elevation on the aerobic performance of rainbow trout, we examined how two severities of chronically elevated plasma cortisol levels affected the oxygen uptake during rest and after exhaustive exercise using a high (HC) and a medium cortisol (MC) treatment. High cortisol doses significantly affected standard (SMR) and maximum metabolic rates (MMR) compared to control fish. In comparison, the medium cortisol treatment elevated maximum metabolic rates (MMR) but did not significantly influence SMR compared to a sham group (S) and control group (C). The medium cortisol treatment resulted in a significantly increased metabolic scope due to an elevation of MMR, an effect that was abolished in the HC group due to co-occuring elevations in SMR. The elevated SMR of the HC-treated fish could be explained by increased in vitro oxygen uptake rates (MO2) of specific tissues, indicating that the raised basal metabolism was caused, in part, by an increase in oxygen demand of specific tissues. Haematological results indicated an increased reliance on anaerobic metabolic pathways in cortisol-treated fish under resting conditions.

Role of photobleaching process of indocyanine green for killing neuroblastoma cells.

Indocyanine green (ICG) is an FDA-approved near infrared (NIR) imaging agent for diagnosis and imaging guided surgery. It also exhibits phototoxicity under high-dose NIR irradiation, expanding its application as a photo-therapeutic agent. Since ICG's efficiency as a type II photosensitizer has been controversial due to its low triplet state yield, other mechanisms have been explored. While claims of toxic decomposition products, accompanied by irreversible ICG photobleaching, were proposed as the main mechanism, evidences from systemic studies are lacking. In this work, we aimed to unravel the factors affecting ICG photobleaching and the associated photo-killing effect on neuroblastoma, one of the most common pediatric tumors but often escapes therapy. Specifically, we examined how albumin-induced ICG stabilization affects the ICG photobleaching process, and the effect of photobleached ICG on cell proliferation and viability of neuroblastoma cells. It was found that ICG photobleaching was significant only under aerobic conditions and was more efficient in solutions with higher concentration ICG monomers, which were stabilized from aggregates by the presence of BSA while increasing photobleaching and associated oxygen consumption. Photobleached ICG inhibited cell proliferation, indicating another effect of tumor treatment by ICG. Taken together, while enhanced photobleaching by BSA-bound ICG monomers may reduce the photodynamic effect targeting cellular components, the photoproducts directly contribute to tumor growth inhibition and assist in a secondary mechanism to stop tumor growth.

Fluoride sensitivity in freshwater snail, Bellamya bengalensis (Lamarck, 1882): An integrative biomarker response assessment of behavioral indices, oxygen consumption, haemocyte and tissue protein levels under environmentally relevant exposure concentrations.

There is limited information on fluoride toxicity and risk overview on ecotoxicological risks to aquatic invertebrate populations particularly molluscan taxa. This necessitated the assessment of toxicity responses in the freshwater snail, Bellamya bengalensis exposed to environmentally relevant concentrations of sodium fluoride. Under lethal exposures (150, 200, 250, 300, 400 and 450 mg/l), the median lethal concentrations (LC50) were determined to be 422.36, 347.10, 333.33 and 273.24 mg/l for B. bengalensis at 24, 48, 72 and 96 h respectively. The rate of mortality of the snails was increased significantly with elevated concentrations of the toxicant. The magnitude of toxicity i.e., toxicity factor at different time scale was also higher with increased exposure duration. Altered behavioural changes i.e., crawling movement, tentacle movement, clumping tendency, touch reflex and mucous secretion in exposed snail with elevated concentrations and exposure duration. Similarly, oxygen consumption rate of the treated snail also lowered significantly during 72 and 96 h of exposure. Under 30-day chronic exposures (Control-0.00 mg/L; T1-27.324 mg/L; T2-54.648 mg/L), protein concentrations in gonad and hepatopancreas of exposure groups was significantly lowered. Chronic exposures also revealed lowered haemocytes counts in exposure groups. The potential for loss of coordination, respiratory distress and physiological disruption in organisms exposed to environmentally relevant concentrations of fluoride was demonstrated by this study. The estimation and magnitude of toxicity responses are necessary for a more accurate estimation of ecological risks to molluscan taxa and invertebrate populations under acute and chronic fluoride exposures in the wild.

Mitochondrial fusion and fission are required for proper mitochondrial function and cell proliferation in fission yeast.

Mitochondria form a branched tubular network in many types of cells, depending on a balance between mitochondrial fusion and fission. How mitochondrial fusion and fission are involved in regulating mitochondrial function and cell proliferation is not well understood. Here, we dissected the roles of mitochondrial fusion and fission in mitochondrial function and cell proliferation in fission yeast. We examined mitochondrial membrane potential by staining cells with DiOC6 and assessed mitochondrial respiration by directly measuring oxygen consumption of cells with a dissolved oxygen respirometer. We found that defects in mitochondrial fission or fusion reduce mitochondrial membrane potential and compromise mitochondrial respiration while the absence of both mitochondrial fusion and fission restores wild type-like respiration, normal membrane potential, and tubular networks of mitochondria. Moreover, we found that the absence of either mitochondrial fission or fusion prolongs the cell cycle and that the absence of both mitochondrial fusion and fission significantly delays cell cycle progression after nitrogen replenishment. The prolonged/delayed cell cycle is likely due to the deregulation of Cdc2 activation. Hence, our work not only establishes an intimate link between mitochondrial morphology and function but also underscores the importance of mitochondrial dynamics in regulating the cell cycle.

Nm23-H1 activator phenylbutenoid dimer exerts cytotoxic effects on metastatic breast cancer cells by inducing mitochondrial dysfunction only under glucose starvation.

Mitochondrial oxidative phosphorylation (OXPHOS) has become an attractive target in anti-cancer studies in recent years. In this study, we found that a small molecule phenylbutenoid dimer NMac1 (Nm23-H1 activator 1), (±)-trans-3-(3,4-dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl]cyclohex-1-ene, a previously identified anti-metastatic agent, has novel anti-proliferative effect only under glucose starvation in metastatic breast cancer cells. NMac1 causes significant activation of AMPK by decreasing ATP synthesis, lowers mitochondrial membrane potential (MMP, ΔΨm), and inhibits oxygen consumption rate (OCR) under glucose starvation. These effects of NMac1 are provoked by a consequence of OXPHOS complex I inhibition. Through the structure-activity relationship (SAR) study of NMac1 derivatives, NMac24 was identified as the most effective compound in anti-proliferation. NMac1 and NMac24 effectively suppress cancer cell proliferation in 3D-spheroid in vivo-like models only under glucose starvation. These results suggest that NMac1 and NMac24 have the potential as anti-cancer agents having cytotoxic effects selectively in glucose restricted cells.

Effect of Waters Enriched in O2 by Injection or Electrolysis on Performance and the Cardiopulmonary and Acid-Base Response to High Intensity Exercise.

Several brands of water enriched with O2 (O2-waters) are commercially available and are advertised as wellness and fitness waters with claims of physiological and psychological benefits, including improvement in exercise performance. However, these claims are based, at best, on anecdotal evidence or on a limited number of unreliable studies. The purpose of this double-blind randomized study was to compare the effect of two O2-waters (~110 mg O2·L-1) and a placebo (10 mg O2·L-1, i.e., close to the value at sea level, 9-12 mg O2·L-1) on the cardiopulmonary responses and on performance during high-intensity exercise. One of the two O2-waters and the placebo were prepared by injection of O2. The other O2-water was enriched by an electrolytic process. Twenty male subjects were randomly allocated to drink one of the three waters in a crossover study (2 L·day-1 × 2 days and 15 mL·kg-1 90 min before exercise). During each exercise trial, the subjects exercised at 95.9 ± 4.7% of maximal workload to volitional fatigue. Exercise time to exhaustion and the cardiopulmonary responses, arterial lactate concentration and pH were measured. Oxidative damage to proteins, lipids and DNA in blood was assessed at rest before exercise. Time to exhaustion (one-way ANOVA) and the responses to exercise (two-way ANOVA [Time; Waters] with repeated measurements) were not significantly different among the three waters. There was only a trend (p = 0.060) for a reduction in the time constant of the rapid component of VO2 kinetics with the water enriched in O2 by electrolysis. No difference in oxidative damage in blood was observed between the three waters. These results suggest that O2-water does not speed up cardiopulmonary response to exercise, does not increase performance and does not trigger oxidative stress measured at rest.

Non-Randomized Trial of Dornase Alfa for Acute Respiratory Distress Syndrome Secondary to Covid-19.

Background: The most severe cases of Coronavirus-Disease-2019 (COVID-19) develop into Acute Respiratory Distress Syndrome (ARDS). It has been proposed that oxygenation may be inhibited by extracellular deoxyribonucleic acid (DNA) in the form of neutrophil extracellular traps (NETs). Dornase alfa (Pulmozyme, Genentech) is recombinant human deoxyribonuclease I that acts as a mucolytic by cleaving and degrading extracellular DNA. We performed a pilot study to evaluate the effects of dornase alfa in patients with ARDS secondary to COVID-19. Methods: We performed a pilot, non-randomized, case-controlled clinical trial of inhaled dornase for patients who developed ARDS secondary to COVID-19 pneumonia. Results: Improvement in arterial oxygen saturation to inhaled fraction of oxygen ratio (PaO2/FiO2) was noted in the treatment group compared to control at day 2 (95% CI, 2.96 to 95.66, P-value = 0.038), as well as in static lung compliance at days 3 through 5 (95% CI, 4.8 to 19.1 mL/cmH2O, 2.7 to 16.5 mL/cmH2O, and 5.3 to 19.2 mL/cmH2O, respectively). These effects were not sustained at 14 days. A reduction in bronchoalveolar lavage fluid (BALF) myeloperoxidase-DNA (DNA : MPO) complexes (95% CI, -14.7 to -1.32, P-value = 0.01) was observed after therapy with dornase alfa. Conclusion: Treatment with dornase alfa was associated with improved oxygenation and decreased DNA : MPO complexes in BALF. The positive effects, however, were limited to the time of drug delivery. These data suggest that degradation of extracellular DNA associated with NETs or other structures by inhaled dornase alfa can be beneficial. We propose a more extensive clinical trial is warranted. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT04402970.

Divergent serum metabolomic, skeletal muscle signaling, transcriptomic, and performance adaptations to fasted versus whey protein-fed sprint interval training.

Sprint interval training (SIT) is a time-efficient alternative to endurance exercise, conferring beneficial skeletal muscle metabolic adaptations. Current literature has investigated the nutritional regulation of acute and chronic exercise-induced metabolic adaptations in muscle following endurance exercise, principally comparing the impact of training in fasted and carbohydrate-fed (CHO) conditions. Alternative strategies such as exercising in low CHO, protein-fed conditions remain poorly characterized, specifically pertaining to adaptations associated with SIT. Thus, this study aimed to compare the metabolic and performance adaptations to acute and short-term SIT in the fasted state with preexercise hydrolyzed (WPH) or concentrated (WPC) whey protein supplementation. In healthy males, preexercise protein ingestion did not alter exercise-induced increases in PGC-1α, PDK4, SIRT1, and PPAR-δ mRNA expression following acute SIT. However, supplementation of WPH beneficially altered acute exercise-induced CD36 mRNA expression. Preexercise protein ingestion attenuated acute exercise-induced increases in muscle pan-acetylation and PARP1 protein content compared with fasted SIT. Acute serum metabolomic differences confirmed greater preexercise amino acid delivery in protein-fed compared with fasted conditions. Following 3 wk of SIT, training-induced increases in mitochondrial enzymatic activity and exercise performance were similar across nutritional groups. Interestingly, resting muscle acetylation status was downregulated in WPH conditions following training. Such findings suggest preexercise WPC and WPH ingestion positively influences metabolic adaptations to SIT compared with fasted training, resulting in either similar or enhanced performance adaptations. Future studies investigating nutritional modulation of metabolic adaptations to exercise are warranted to build upon these novel findings.NEW & NOTEWORTHY These are the first data to show the influence of preexercise protein on serum and skeletal muscle metabolic adaptations to acute and short-term sprint interval training (SIT). Preexercise whey protein concentrate (WPC) or hydrolysate (WPH) feeding acutely affected the serum metabolome, which differentially influenced acute and chronic changes in mitochondrial gene expression, intracellular signaling (acetylation and PARylation) resulting in either similar or enhanced performance outcomes when compared with fasted training.

Oxidative metabolism in the cardiorespiratory system after an acute exposure to nickel-doped nanoparticles in mice.

There is an increasing concern over the harmful effects that metallic nanoparticles (NP) may produce on human health. Due to their redox properties, nickel (Ni) and Ni-containing NP are particularly relevant. Hence, the aim of this study was to establish the toxicological mechanisms in the cardiorespiratory oxidative metabolism initiated by an acute exposure to Ni-doped-NP. Mice were intranasally instilled with silica NP containing Ni (II) (Ni-NP) (1 mg Ni (II)/kg body weight) or empty NP as control, and 1 h after exposure lung, plasma, and heart samples were obtained to assess the redox metabolism. Results showed that, NP were mainly retained in the lungs triggering a significantly increased tissue O2 consumption rate, leading to Ni-NP-increased reactive oxygen species production by NOX activity, and mitochondrial H2O2 production rate. In addition, an oxidant redox status due to an altered antioxidant system showed by lung GSH/GSSG ratio decreased, and SOD activity increased, resulting in an increased phospholipid oxidation. Activation of circulating polymorphonuclear leukocytes, along with GSH/GSSG ratio decreased, and phospholipid oxidation were found in the Ni-NP-group plasma samples. Consequently, in distant organs such as heart, Ni-NP inhalation alters the tissue redox status. Our results showed that the O2 metabolism analysis is a critical area of study following Ni-NP inhalation. Therefore, this work provides novel data linking the redox metabolisms alterations elicited by exposure to Ni (II) adsorbed to NP and cardiorespiratory toxicity.

Pyruvate and Glutamine Define the Effects of Cholecystokinin and Ethanol on Mitochondrial Oxidation, Necrosis, and Morphology of Rat Pancreatic Acini.

OBJECTIVES: The objective of this study was to test whether pyruvate and glutamine affect the ethanol and cholecystokinin (CCK) effects on the mitochondrial function, viability, and morphology of rat pancreatic acini. METHODS: Respiration was measured with Clark oxygen electrode. Mitochondrial membrane potential, reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H), cell morphology, and viability were studied with fluorescence microscopy. RESULTS: In vitro, CCK (0.1 nM) caused pyruvate-dependent stimulation of basal and uncoupled respiration, and the effects were abolished by ethanol (20 mM). The combination of ethanol with CCK (2 hours) caused necrosis of approximately 40% acinar cells in medium with glucose, but not with pyruvate and/or glutamine. Cholecystokinin (10 nM) or ethanol with 0.1 nM CCK caused plasma membrane blebbing not related to apoptosis only when both glutamine and pyruvate were present. Glutamine, but not pyruvate, decreased NAD(P)H level and prevented the effects of ethanol with CCK on mitochondrial membrane potential and NAD(P)H, but, in combination with CCK and ethanol, decreased the uncoupled respiration. In vivo, the combination of ethanol (4 g/kg) and CCK (20 pmol/kg) suppressed basal and uncoupled respiration and caused acinar cell blebbing, but not necrosis. CONCLUSIONS: The lack of sufficient substrate supply in vitro makes pancreatic acinar cells susceptible to necrosis caused by ethanol and CCK in clinically relevant concentrations.

Na+-Coupled Respiration and Reshaping of Extracellular Polysaccharide Layer Counteract Monensin-Induced Cation Permeability in Prevotella bryantii B14.

Monensin is an ionophore for monovalent cations, which is frequently used to prevent ketosis and to enhance performance in dairy cows. Studies have shown the rumen bacteria Prevotella bryantii B14 being less affected by monensin. The present study aimed to reveal more information about the respective molecular mechanisms in P.bryantii, as there is still a lack of knowledge about defense mechanisms against monensin. Cell growth experiments applying increasing concentrations of monensin and incubations up to 72 h were done. Harvested cells were used for label-free quantitative proteomics, enzyme activity measurements, quantification of intracellular sodium and extracellular glucose concentrations and fluorescence microscopy. Our findings confirmed an active cell growth and fermentation activity of P.bryantii B14 despite monensin concentrations up to 60 µM. An elevated abundance and activity of the Na+-translocating NADH:quinone oxidoreductase counteracted sodium influx caused by monensin. Cell membranes and extracellular polysaccharides were highly influenced by monensin indicated by a reduced number of outer membrane proteins, an increased number of certain glucoside hydrolases and an elevated concentration of extracellular glucose. Thus, a reconstruction of extracellular polysaccharides in P.bryantii in response to monensin is proposed, which is expected to have a negative impact on the substrate binding capacities of this rumen bacterium.

The Effects of Sodium Phosphate Supplementation on the Cardiorespiratory System and Gross Efficiency during Exercise under Hypoxia in Male Cyclists: A Randomized, Placebo-Controlled, Cross-Over Study.

The main aim of this study was to evaluate the effects of six days of tri-sodium phosphate (SP) supplementation on the cardiorespiratory system and gross efficiency (GE) during exercise under hypoxia in cyclists. Twenty trained male cyclists received SP (50 mg·kg-1 of fat-free mass/day) or placebo for six days in a randomized, cross-over study, with a three-week washout period between supplementation phases. Before and after each supplementation phase, the subjects performed an incremental exercise test to exhaustion under normobaric hypoxia (FiO2 = 16%, ~2500 m). It was observed that short-term SP supplementation led to a decrease in heart rate, an increase in stroke volume, and an improvement in oxygen pulse (VO2/HR) during low and moderate-intensity exercise under hypoxia. These changes were accompanied by an increase in the serum inorganic phosphate level by 8.7% (p < 0.05). No significant changes were observed in serum calcium levels. GE at a given workload did not change significantly after SP supplementation. These results indicated that SP promotes improvements in the efficiency of the cardiorespiratory system during exercise in a hypoxic environment. Thus, SP supplementation may be beneficial for endurance exercise in hypoxia.