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Developmental changes in regulation of mitochondrial respiration by ADP and creatine in rat heart in vivo.

In saponin-skinned muscle fibers from adult rat heart and m. soleus the apparent affinity of the mitochondrial oxidative phosphorylation system for ADP (Km = 200-400 microM) is much lower than in isolated mitochondria (Km = 10-20 microM). This suggests a limited permeability of the outer mitochondrial membrane (OMM) to adenine nucleotides in slow-twitch muscle cells. We have studied the postnatal changes in the affinity of mitochondrial respiration for ADP, in relation to morphological alterations and expression of mitochondrial creatine kinase (mi-CK) in rat heart in vivo. Analysis of respiration of skinned fibers revealed a gradual decrease in the apparent affinity of mitochondria to ADP throughout 6 weeks post partum that indicates the development of mechanism which increasingly limits the access of ADP to mitochondria. The expression of mi-CK started between the 1st and 2nd weeks and reached the adult levels after 6 weeks. This process was associated with increases in creatine-activated respiration and affinity of oxidative phosphorylation to ADP thus reflecting the progressive coupling of mi-CK to adenine nucleotide translocase. Laser confocal microscopy revealed significant changes in rearrangement of mitochondria in cardiac cells: while the mitochondria of variable shape and size appeared to be random-clustered in the cardiomyocytes of 1 day old rat, they formed a fine network between the myofibrils by the age of 3 weeks. These results allow to conclude that in early period of development, i.e. within 2-3 weeks, the diffusion of ADP to mitochondria becomes progressively restricted, that appears to be related to significant structural rearrangements such as formation of the mitochondrial network. Later (after 3 weeks) the control shifts to mi-CK, which by coupling to adenine nucleotide translocase, allows to maximally activate the processes of oxidative phosphorylation despite limited access of ADP through the OMM.

Adenosine Diphosphate↗

Effect of the intravenous anesthetic 2,6-diisopropylphenol on respiration and energy production by rat brain synaptosomes.

The sensitivity of the mitochondrial energy production system to propofol (DPP) has been investigated in rat brain synaptosomes. DPP at 0.8 mM concentration produced a partial inhibition of coupled respiration, an apparent decrease of the oxygen uptake stimulation induced by CCCP and a full inhibition of the mitochondrial ATP production by synaptosomes. Higher concentrations of DPP (1 mM) fully abolish uncoupler-dependent stimulation and at 1.3 mM DPP also coupled respiration is completely blocked. Similar results were obtained when dinitrophenol replaced CCCP and phenol or propylbenzene replaced DPP. The presence of the alkyl residues seems critical for the DPP effect. In the presence of 30 mM glutamate both respiration and ATP production are enhanced but DPP effects are similar to those obtained in the absence of glutamate.

Adenosine Triphosphate↗

Temperature dependence of rat liver mitochondrial respiration with uncoupling of oxidative phosphorylation by fatty acids. Influence of inorganic phosphate.

The respiration rate of liver mitochondria in the course of succinate oxidation depends on temperature in the presence of palmitate more strongly than in its absence (in state 4). In the Arrhenius plot, the temperature dependence of the palmitate-induced stimulation of respiration has a bend at 22 degrees C which is characterized by transition of the activation energy from 120 to 60 kJ/mol. However, a similar dependence of respiration in state 4 is linear over the whole temperature range and corresponds to the activation energy of 17 kJ/mol. Phosphate partially inhibits the uncoupling effect of palmitate. This effect of phosphate is increased on decrease in temperature. In the presence of phosphate the temperature dependence in the Arrhenius plot also has a bend at 22 degrees C, and the activation energy increases from 128 to 208 kJ/mol in the range from 13 to 22 degrees C and from 56 to 67 kJ/mol in the range from 22 to 37 degrees C. Mersalyl (10 nmol/mg protein), an inhibitor of the phosphate carrier, similarly to phosphate, suppresses the uncoupling effect of laurate, and the effects of mersalyl and phosphate are not additive. The recoupling effects of phosphate and mersalyl seem to show involvement of the phosphate carrier in the uncoupling effect of fatty acids in liver mitochondria. Possible mechanisms of involvement of the phosphate carrier in the uncoupling effect of fatty acids are discussed.

2,4-Dinitrophenol↗

Respiration in the open ocean.

A key question when trying to understand the global carbon cycle is whether the oceans are net sources or sinks of carbon. This will depend on the production of organic matter relative to the decomposition due to biological respiration. Estimates of respiration are available for the top layers, the mesopelagic layer, and the abyssal waters and sediments of various ocean regions. Although the total open ocean respiration is uncertain, it is probably substantially greater than most current estimates of particulate organic matter production. Nevertheless, whether the biota act as a net source or sink of carbon remains an open question.

Animals↗

Winter forest soil respiration controlled by climate and microbial community composition.

Most terrestrial carbon sequestration at mid-latitudes in the Northern Hemisphere occurs in seasonal, montane forest ecosystems. Winter respiratory carbon dioxide losses from these ecosystems are high, and over half of the carbon assimilated by photosynthesis in the summer can be lost the following winter. The amount of winter carbon dioxide loss is potentially susceptible to changes in the depth of the snowpack; a shallower snowpack has less insulation potential, causing colder soil temperatures and potentially lower soil respiration rates. Recent climate analyses have shown widespread declines in the winter snowpack of mountain ecosystems in the western USA and Europe that are coupled to positive temperature anomalies. Here we study the effect of changes in snow cover on soil carbon cycling within the context of natural climate variation. We use a six-year record of net ecosystem carbon dioxide exchange in a subalpine forest to show that years with a reduced winter snowpack are accompanied by significantly lower rates of soil respiration. Furthermore, we show that the cause of the high sensitivity of soil respiration rate to changes in snow depth is a unique soil microbial community that exhibits exponential growth and high rates of substrate utilization at the cold temperatures that exist beneath the snow. Our observations suggest that a warmer climate may change soil carbon sequestration rates in forest ecosystems owing to changes in the depth of the insulating snow cover.

Bacteria↗

The two Drosophila cytochrome C proteins can function in both respiration and caspase activation.

Cytochrome C has two apparently separable cellular functions: respiration and caspase activation during apoptosis. While a role of the mitochondria and cytochrome C in the assembly of the apoptosome and caspase activation has been established for mammalian cells, the existence of a comparable function for cytochrome C in invertebrates remains controversial. Drosophila possesses two cytochrome c genes, cyt-c-d and cyt-c-p. We show that only cyt-c-d is required for caspase activation in an apoptosis-like process during spermatid differentiation, whereas cyt-c-p is required for respiration in the soma. However, both cytochrome C proteins can function interchangeably in respiration and caspase activation, and the difference in their genetic requirements can be attributed to differential expression in the soma and testes. Furthermore, orthologues of the apoptosome components, Ark (Apaf-1) and Dronc (caspase-9), are also required for the proper removal of bulk cytoplasm during spermatogenesis. Finally, several mutants that block caspase activation during spermatogenesis were isolated in a genetic screen, including mutants with defects in spermatid mitochondrial organization. These observations establish a role for the mitochondria in caspase activation during spermatogenesis.

Amino Acid Sequence↗

Inhibition of mitochondrial respiration by nitric oxide rapidly stimulates cytoprotective GLUT3-mediated glucose uptake through 5'-AMP-activated protein kinase.

Recently, we have reported that the inhibition of mitochondrial respiration by nitric oxide (NO) leads to an up-regulation of glycolysis and affords cytoprotection against energy failure through the stimulation of AMPK (5'-AMP-activated protein kinase) [Almeida, Moncada and Bolanos (2004) Nat. Cell Biol. 6, 45-51]. To determine whether glucose transport contributes specifically to this effect, we have now investigated the possible role of NO in modulating glucose uptake through GLUT3, a facilitative high-affinity glucose carrier that has been suggested to afford cytoprotection against hypoglycaemic episodes. To do so, GLUT3-lacking HEK-293T cells (human embryonic kidney 293T cells) were transformed to express a plasmid construction encoding green fluorescent protein-tagged GLUT3 cDNA. This carrier was preferentially localized to the plasma membrane, was seen to be functionally active and afforded cytoprotection against low glucose-induced apoptotic death. Inhibition of mitochondrial respiration by NO triggered a rapid, cGMP-independent enhancement of GLUT3-mediated glucose uptake through a mechanism that did not involve transporter translocation. Furthermore, the functional disruption of AMPK by the RNA interference strategy rendered cells unable to respond to NO by activating GLUT3-mediated glucose uptake. These results suggest that the inhibition of mitochondrial respiration by NO activates AMPK to stimulate glucose uptake, thereby representing a novel survival pathway during pathophysiological conditions involving transient reductions in the supply of cellular glucose.

AMP-Activated Protein Kinases↗

The effects on respiration in the cat of the sudden excitation of cerebral vascular nociceptors by carbon dioxide.

1. Injection of CO2-saturated saline in a distal direction into either a vertebral artery or an internal maxillary artery in pentobarbitone-anaesthetized cats produced abrupt changes in respiration. Vertebral-artery injections produced a transient inhibition of respiration, followed by a stimulation of it. Internal-maxillary-artery injections produced only the inhibition. 2. Injections during inspiration usually shortened that inspiration, reduced its volume and prolonged the following expiration. In the first 30% of an expiration they prolonged that expiration, but given in the next 50% they shortened it. In the last 20% of expiration internal-maxillary-artery injections again slightly prolonged the expiration. 3. Phenyl diguanide injected into either a vertebral or an internal maxillary artery also produced abrupt effects on respiration. 4. The effects of CO2-saturated saline were abolished by intravenous acetazolamide, suggesting that nociceptors may be affected by a change in local pH. 5. The effects may arise from the excitation of vascular nociceptors, and our observations may suggest a way of studying in animals the receptors responsible for headache.

Acetazolamide↗

Investigations into the mechanism of action of a novel nitric oxide generator on cellular respiration.

Nitric oxide may regulate cellular respiration by competition with oxygen at mitochondrial cytochrome oxidase. Using an astrocyte-derived cell line, we have compared the mechanism of action of the nitric oxide-generating compound Roussin's black salt with that of sodium nitroprusside on cellular oxygen consumption. Intense light exposure induced the release of large quantities of nitric oxide from both of the donor compounds. However, in room light only Roussin's black salt generated low levels of the radical. Simultaneous measurement of oxygen consumption and of nitric oxide production demonstrated that sodium nitroprusside only had inhibitory actions when exposed to intense light (nitric oxide release), whereas Roussin's black salt had inhibitory actions in room light. Extracellular haemoglobin did not prevent the inhibition of respiration rate induced by Roussin's black salt even though stimulation of nitric oxide release on light exposure was markedly reduced. Preincubation of cells with Roussin's black salt and subsequent measurement of levels of light-liberated nitric oxide demonstrated that the compound was rapidly internalised. The uptake of sodium nitroprusside was minimal. These data suggest that, in contrast to sodium nitroprusside, the cellular internalisation of Roussin's black salt allows site-directed nitric oxide release and very effective inhibition of cellular respiration.

Animals↗

Effect of oxygen on sleep quality, cognitive function and sympathetic activity in patients with chronic heart failure and Cheyne-Stokes respiration.

BACKGROUND: Cheyne-Stokes respiration disrupts sleep, leading to daytime somnolence and cognitive impairment. It is also an independent marker of increased mortality in heart failure. This study evaluated the effectiveness of oxygen therapy for Cheyne-Stokes respiration in heart failure. METHODS: Eleven patients with stable heart failure and Cheyne-Stokes breathing were studies. Oxygen and air were administered for 4 weeks in a double-blind, cross-over study. Sleep and disordered breathing was assessed by polysomnography. Symptoms were assessed using the Epworth Sleepiness Scale, visual analogue and quality of lift scores. Cognitive function was assessed by neuropsychometric testing. Overnight urinary catecholamine excretion was used as a measure of sympathetic nerve activity. RESULTS: Ninety-seven percent of apnoeas were central in origin. Oxygen therapy reduced the central apnoea rate (18.4 +/- 4.1 vs 3.8 +/- 2.1 per hour; p = 0.05) and periodic breathing time (33.6 +/- 7.4 vs 10.7 +/- 3.9% of actual sleep time; p = 0.003). Oxygen did not improve sleep quality, patient symptoms or cognitive failure. Oxygen reduced urinary noradrenaline excretion (8.3 +/- 1.5 vs 4.1 +/- 0.6 nmol.mmol-1 urinary creatinine; p = 0.03). CONCLUSION: Oxygen stabilized sleep disordered breathing and reduced sympathetic activity in patients with heart failure and Cheyne-Stokes respiration. We were unable to demonstrate an effect on either patient symptoms or cognitive function.

Aged↗

The maturation and coordination of sucking, swallowing, and respiration in preterm infants.

OBJECTIVES: Our objectives were to establish normative maturational data for feeding behavior of preterm infants from 32 to 36 weeks of postconception and to evaluate how the relation between swallowing and respiration changes with maturation. STUDY DESIGN: Twenty-four infants (28 to 31 weeks of gestation at birth) without complications or defects were studied weekly between 32 and 36 weeks after conception. During bottle feeding with milk flowing only when infants were sucking, sucking efficiency, pressure, frequency, and duration were measured and the respiratory phase in which swallowing occurs was also analyzed. Statistical analysis was performed by repeated-measures analysis of variance with post hoc analysis. RESULTS: The sucking efficiency significantly increased between 34 and 36 weeks after conception and exceeded 7 mL/min at 35 weeks. There were significant increases in sucking pressure and frequency as well as in duration between 33 and 36 weeks. Although swallowing occurred mostly during pauses in respiration at 32 and 33 weeks, after 35 weeks swallowing usually occurred at the end of inspiration. CONCLUSIONS: Feeding behavior in premature infants matured significantly between 33 and 36 weeks after conception, and swallowing infrequently interrupted respiration during feeding after 35 weeks after conception.

Bottle Feeding↗

Progesterone stimulates respiration through a central nervous system steroid receptor-mediated mechanism in cat.

We have examined the effect on respiration of the steroid hormone progesterone, administered either intravenously or directly into the medulla oblongata in anesthetized and paralyzed male and female cats. The carotid sinus and vagus nerves were cut, and end-tidal PCO2 and temperature were kept constant with servo-controllers. Phrenic nerve activity was used to quantitate central respiratory activity. Repeated doses of progesterone (from 0.1 to 2.0 micrograms/kg, cumulative) caused a sustained (greater than 45 min) facilitation of phrenic nerve activity in female and male cats; however, the response was much more variable in females. Progesterone injected into the region of nucleus tractus solitarii, a respiratory-related area in the medulla oblongata, also caused a prolonged stimulation of respiration. Progesterone administration at high concentration by both routes also caused a substantial hypotension. Identical i.v. doses of other classes of steroid hormones (17 beta-estradiol, testosterone, and cortisol) did not elicit the same respiratory effect. Pretreatment with RU 486, a progesterone-receptor antagonist, blocked the facilitatory effect of progesterone. We conclude that progesterone acts centrally through a steroid receptor-mediated mechanism to facilitate respiration.

Animals↗

Oxygen and carbon isotopic compositions of gases respired by humans.

Oxygen-isotope fractionation associated with respiration in human individuals at rest is linearly related to the fraction of the O2 utilized in the respiration process. The slope of this relationship is affected by a history of smoking, by vigorous exercise, and by the N2/O2 ratio of the inhaled gas. For patients who suffer anemia-related diseases, the slope of this relationship is directly proportional to their level of hemoglobin. These results introduce a new approach for studying the mechanisms of O2 consumption in human respiration and how they are affected by related diseases.

Adult↗

Laboratory evaluation of pressure differential-based respirable dust detector tube.

Assessment of exposure to occupational dusts is a first step in reducing exposures to harmful dust concentrations. A new type of respirable dust sampler was developed and compared side-by-side to personal gravimetric samplers in the laboratory. The new sampler correlates filter back pressure with mass accumulation to provide mid-shift- and end-of-shift determinations of cumulative exposure. The sampler uses a small low flow rate pump to draw dust through a small detector tube that contains a porous urethane foam respirable classification section and glass fiber filter that collects respirable dust. Six different coal dusts were aerosolized in a laboratory dust chamber and a total of 119 triplicate observations were obtained. For individual coal types, the correlation coefficients were between 0.87 and 0.97. The precision of the two methods was similar, with the percent relative standard deviation of the personal samplers of 12 percent and the new detector method of 14 percent. For all coal types tested th data were best described by a power function where delta P = 1.43 mass (0.85), with a correlation coefficient of 0.73. The method becomes more accurate at higher dust loadings such that all laboratory data with mass loadings greater than an equivalent concentration of 2 mg/m3 fall within +/- 25 percent of the power function. Assessment of the method under field conditions is in progress.

Dust↗

Management of respiration in MND/ALS patients: an evidence based review.

This systematic review comprises an objective appraisal of the evidence in regard to the management of respiration in patients with motor neuron disease (MND/ALS). Studies were identified through computerised searches of 32 databases. Internet searches of websites of drug companies and MND/ALS research web sites, 'snow balling' and hand searches were also employed to locate any unpublished study or other 'grey literature' on respiration and MND/ALS. Since management of MND/ALS involves a number of health professionals and care workers, searches were made across multiple disciplines. No time frame was imposed on the search in order to increase the probability of identifying all relevant studies, although there was a final limit of March 2005. Recommendations for patient and carer-based guidelines for the clinical management of respiration for MND/ALS patients are suggested on the basis of qualitative analyses of the available evidence. However, these recommendations are based on current evidence of best practice, which largely comprises observational research and clinical opinion. There is a clear need for further evidence, in particular randomised and non-randomised controlled trials on the effects of non-invasive ventilation and additional larger scale cohort studies on the issues of initial assessment of respiratory symptoms, and management and timing of interventions.

Amyotrophic Lateral Sclerosis↗

The physiological consequences of wearing industrial respirators: a review.

The American Industrial Hygiene Association (AIHA) and American Conference of Govermental Industrial Hygienists (ACGIH) Respiratory Protective Devices Manual, published in 1963, has as its primary source of physiological background the work of Silverman and co-workers performed during World War II. The adoption of permanent OSHA standards governing work tasks requiring workers to use respirators has created a need for further evaluation of the physiological effects of wearing a respirator. This review was undertaken to meet the need of an in-depth evaluation of the currently available psychophysiological data. It was concluded that it was of the utmost importance to develop a physiological and psychological medical screening examination to determine the capability of the worker to use a respirator.

Body Temperature Regulation↗

Respirable dust control in grinding gray iron castings.

High speed grinding of gray iron castings long has been associated with excessive exposure to crystalline silica. Not all workers engaged in these operations are protected by conventional ventilation techniques. Dust in the air that has been entrained by the spinning grinding wheel and not captured in the grinder hood has been postulated to be a major exposure source. A pilot grinding operation was constructed, and the size distribution and concentration of airborne particles were measured with the aerodynamic particle sizer (APS). Various control measures proved effective in reducing the respirable dust concentration: increased exhaust ventilation, and installation of baffles and/or the use of an air jet to deflect the entrained air stream. The concentration of respirable dust is the breathing zone was reduced approximately 20-fold through the combined use of increased ventilation, interior baffles, and an air jet. The air jet and baffle utilized at the base ventilation rate reduced the respirable dust concentration by a factor of three to four, whereas the baffle alone halved the concentration.

Air Pollutants, Occupational↗

Quantitative respirator fit testing: dynamic pressure versus aerosol measurement.

A noninvasive, fast, inexpensive new fit testing method has been invented which relates the slope of the pressure decay inside a respirator during breath-holding to the fit of the respirator on the wearer's face. The dynamic pressure test has been compared with the conventional aerosol test at different leakage levels. The results of this comparison show that the sensitivity of the dynamic pressure test is similar to that of the aerosol test. The pressure test, however, is independent of leak site and probe location and can be performed on respirators before and after their use.

Aerosols↗