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Oxygen Tension (oxygen + tension)
Kinds of Oxygen Tension Terms modified by Oxygen Tension Selected AbstractsOxygen Tension Regulates the Expression of ANK (Progressive Ankylosis) in an HIF-1-Dependent Manner in Growth Plate Chondrocytes,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2009Raihana Zaka Abstract The proximal promoter region of ANK, a gene that codes for a protein that regulates the transport of inorganic pyrophosphate, contains two hypoxia responsive elements (HREs); therefore, we studied the expression and function of ANK at different oxygen tensions. ATDC5 and N1511 clonal chondrocytic cells were cultured in either hypoxia (2% O2) or normoxia (21% O2). Transcript and protein levels of ANK were depressed in hypoxic conditions, as were levels of extracellular pyrophosphate (ePPi). To determine whether HIF-1 was involved in the oxemic response, Hif-1, knockdown cells were exposed to varying oxygen conditions and ANK expression was assessed. Knockdown of Hif-1, resulted in low levels of expression of ANK in hypoxia and normoxia. Chromatin immunoprecipitation (ChIP) assays explored the binding of Hif-1, to ANK HREs and showed that Hif-1, is able to bind to the HREs of ANK more avidly in normoxia than in hypoxia. Furthermore, functional studies of Hif-1, activity using luciferase reporter assays of wildtype and mutagenized HREs showed that only HRE-1 binds Hif-1, in normoxia. Expression of ANK in growth plate and articular cartilage was low in hypoxic regions of the tissues, and higher levels of ANK expression were observed in the synovium and meniscus in regions that have a normally higher oxygen tension. The data suggest that ANK expression and function in vitro and in vivo are repressed in hypoxic environments and that the effect is regulated by HIF-1. [source] Acid-Base Balance and Oxygen Tension During Dialysis in Uremic Patients With Chronic Obstructive Pulmonary DiseaseARTIFICIAL ORGANS, Issue 12 2008Simone Manca-Di-Villahermosa Abstract Recent reports on the effects of dialysis on acid-base balance and metabolic acidosis correction in end-stage renal disease (ESRD) patients with chronic obstructive pulmonary disease (COPD) are lacking. Here, we compared acid-base balance and blood gasses among 14 patients with established COPD (group A) and eight patients with normal respiratory function (group B). The two groups were homogeneous for age, time on dialysis, and male/female ratio. At the beginning of dialysis, acid-base balance and blood gasses were comparable between patients of groups A and B. A significant difference between groups was observed only in pCO2 at 20 min, together with a delay in pH increase. Effective correction of acidosis was reported at the end of dialysis and is not significantly affected by COPD. Nevertheless, weight loss must be carefully monitored in these patients in order to prevent hyperhydration and worsening of respiratory function. [source] Improvement of Metabolic Performance of Cultured Hepatocytes by High Oxygen Tension in the AtmosphereARTIFICIAL ORGANS, Issue 1 2001Kennichi Yanagi Abstract: Maintaining metabolic functions of cultured hepatocytes at higher levels is an essential requirement for the development of a bioartificial liver. We investigated the effect of oxygen tension (10,40%) of the medium on immobilization efficiency and metabolic functions of cultured hepatocytes obtained from a rat for up to 4 days. Immobilization efficiencies of cultures in 10% oxygen showed a significantly lower value from those for the other conditions. The ammonium metabolic rate and the albumin secretion rate were significantly improved with an increase of dissolved oxygen tension for up to 2 days. These values remained similar in the later stage of the culture. The urea secretion rate showed similar values in all conditions. In conclusion, higher oxygen tension improved immobilization efficiency and metabolic functions of cultured rat hepatocytes in the earlier stage of culture for up to 2 days. [source] Differential Activation of ERK 1/2 and JNK in Normal Human Fibroblast-like Cells in Response to UVC Radiation Under Different Oxygen Tensions ,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2000Naoki Matsuda ABSTRACT The mechanisms by which mitogen-activated protein kinases (MAPK) respond to the input of UV-induced signal transduction pathways and the resulting biological functions are not well understood. We investigated whether the level of oxygen tension of culture was responsible for the differential activation of MAPK and different cellular outcomes in UVC-irradiated cells. The intracellular oxidative level of normal human fibroblast-like cells in a normal atmosphere (normoxic, 20% O2) was increased within 30 min after UVC irradiation. When cells were cultured at lower oxygen tension in the presence of an antioxidant N -acetyl- l -cysteine (NAC) or under physiologically hypoxic (5% O2) conditions, the elevation of the oxidative level by UV-irradiation was significantly reduced. Among MAPK, extracellular-signal related kinase (ERK) 1/2 was activated by UV regardless of the oxidative level, while c-Jun N-terminal kinase (JNK) activation was inhibited in NAC-treated and in hypoxic cultures. In addition, in cultures at lower oxygen tension, there was less apoptosis and cell survival was enhanced. These results suggest that UV-induced oxidative stress was responsible for intracellular signaling through the JNK pathway. Furthermore, the balance between ERK1/2 and JNK activities after UV irradiation under different oxygen tensions possibly modified cellular outcome in response to UV. [source] Laparoscopic surgery impairs tissue oxygen tension more than open surgeryBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2007E. Fleischmann Background: Wound infection remains a common and serious complication after colonic surgery. Although many colonic operations are performed laparoscopically, it remains unclear whether this has any impact on the incidence of wound infection. Subcutaneous tissue oxygenation is an excellent predictor of surgical wound infection. The impact of open and laparoscopic colonic surgery on tissue oxygenation was compared. Methods: Fifty-two patients undergoing elective open and laparoscopic left-sided colonic resections were evaluated in a prospective observational study. Anaesthesia management was standardized and intraoperative arterial partial pressure of oxygen was kept at 150 mmHg in both groups. Oxygen tension was measured in the subcutaneous tissue of the right upper arm. Results: At the start of surgery subcutaneous tissue oxygen tension (PsqO2) was similar in both groups (mean(s.d.) 65·8(17·2) and 63·7(23·6) mmHg for open and laparoscopic operations respectively; P = 0·714). Tissue oxygen remained stable in the open group, but dropped significantly in the laparoscopic group during the course of surgery (PsqO2 after operation 53·4(12·9) and 45·5(11·6) mmHg, respectively; P = 0·012). Conclusion: Laparoscopic colonic surgery significantly decreases PsqO2, an effect that occurs early in the course of surgery. As tissue oxygen tension is a predictor of wound infection, these results may explain why the risk of wound infection after laparoscopic surgery remains higher than expected. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Cerebral oxygenation is reduced during hyperthermic exercise in humansACTA PHYSIOLOGICA, Issue 1 2010P. Rasmussen Abstract Aim:, Cerebral mitochondrial oxygen tension (PmitoO2) is elevated during moderate exercise, while it is reduced when exercise becomes strenuous, reflecting an elevated cerebral metabolic rate for oxygen (CMRO2) combined with hyperventilation-induced attenuation of cerebral blood flow (CBF). Heat stress challenges exercise capacity as expressed by increased rating of perceived exertion (RPE). Methods:, This study evaluated the effect of heat stress during exercise on PmitoO2 calculated based on a Kety-Schmidt-determined CBF and the arterial-to-jugular venous oxygen differences in eight males [27 ± 6 years (mean ± SD) and maximal oxygen uptake (VO2max) 63 ± 6 mL kg,1 min,1]. Results:, The CBF, CMRO2 and PmitoO2 remained stable during 1 h of moderate cycling (170 ± 11 W, ,50% of VO2max, RPE 9,12) in normothermia (core temperature of 37.8 ± 0.4 °C). In contrast, when hyperthermia was provoked by dressing the subjects in watertight clothing during exercise (core temperature 39.5 ± 0.2 °C), PmitoO2 declined by 4.8 ± 3.8 mmHg (P < 0.05 compared to normothermia) because CMRO2 increased by 8 ± 7% at the same time as CBF was reduced by 15 ± 13% (P < 0.05). During exercise with heat stress, RPE increased to 19 (19,20; P < 0.05); the RPE correlated inversely with PmitoO2 (r2 = 0.42, P < 0.05). Conclusion:, These data indicate that strenuous exercise in the heat lowers cerebral PmitoO2, and that exercise capacity in this condition may be dependent on maintained cerebral oxygenation. [source] Cerebral oxygenation decreases during exercise in humans with beta-adrenergic blockadeACTA PHYSIOLOGICA, Issue 3 2009T. Seifert Abstract Aim:, Beta-blockers reduce exercise capacity by attenuated increase in cardiac output, but it remains unknown whether performance also relates to attenuated cerebral oxygenation. Methods:, Acting as their own controls, eight healthy subjects performed a continuous incremental cycle test to exhaustion with or without administration of the non-selective beta-blocker propranolol. Changes in cerebral blood flow velocity were measured with transcranial Doppler ultrasound and those in cerebral oxygenation were evaluated using near-infrared spectroscopy and the calculated cerebral mitochondrial oxygen tension derived from arterial to internal jugular venous concentration differences. Results:, Arterial lactate and cardiac output increased to 15.3 ± 4.2 mm and 20.8 ± 1.5 L min,1 respectively (mean ± SD). Frontal lobe oxygenation remained unaffected but the calculated cerebral mitochondrial oxygen tension decreased by 29 ± 7 mmHg (P < 0.05). Propranolol reduced resting heart rate (58 ± 6 vs. 69 ± 8 beats min,1) and at exercise exhaustion, cardiac output (16.6 ± 3.6 L min,1) and arterial lactate (9.4 ± 3.7 mm) were attenuated with a reduction in exercise capacity from 239 ± 42 to 209 ± 31 W (all P < 0.05). Propranolol also attenuated the increase in cerebral blood flow velocity and frontal lobe oxygenation (P < 0.05) whereas the cerebral mitochondrial oxygen tension decreased to a similar degree as during control exercise (delta 28 ± 10 mmHg; P < 0.05). Conclusion:, Propranolol attenuated the increase in cardiac output of consequence for cerebral perfusion and oxygenation. We suggest that a decrease in cerebral oxygenation limits exercise capacity. [source] Oxygen-dependent ion transport in erythrocytesACTA PHYSIOLOGICA, Issue 3 2009A. Bogdanova Abstract The present contribution reviews current knowledge of apparently oxygen-dependent ion transport in erythrocytes and presents modern hypotheses on their regulatory mechanisms and physiological roles. In addition to molecular oxygen as such, reactive oxygen species, nitric oxide, carbon monoxide, regional variations of cellular ATP and hydrogen sulphide may play a role in the regulation of transport, provided that they are affected by oxygen tension. It appears that the transporter molecules themselves do not have direct oxygen sensors. Thus, the oxygen level must be sensed elsewhere, and the effect transduced to the transporter. The possible pathways involved in the regulation of transport, including haemoglobin as a sensor, and phosphorylation/dephosphorylation reactions both in the transporter and its upstream effectors, are discussed. [source] The influence of exercise on foot perfusion in diabetesDIABETIC MEDICINE, Issue 10 2007D. T. Williams Abstract Aims, Diabetic foot disease is associated with both macro- and microvascular disease. Exercise has both positive and negative effects on the perfusion of lower limbs with peripheral arterial occlusive disease (PAOD). We aimed to measure changes in foot perfusion following a brief period of lower-limb exercise in individuals with and without Type 2 diabetes and non-critical PAOD. Methods, Subjects were allocated to groups according to the presence or absence of diabetes, PAOD on colour duplex imaging and clinically detectable peripheral neuropaÍthy. Transcutaneous oxygen tension (TcPO2), transcutaneous carbon dioxide tension (TcPCO2), ankle-brachial pressure indices, toe pressures and toe-brachial pressure indices (TBI) were measured. Results, One hundred and sixteen limbs were studied in 61 subjects. Post-exercise, toe pressure and TBI increased in the non-diabetic group with arterial disease, but not in the groups with diabetes. Foot TcPO2 values increased in groups with diabetes and TcPCO2 decreased in all groups with arterial disease. Increased chest TcPO2 and decreased TcPCO2 were demonstrated in the groups with diabetes. Conclusions, Elevations in foot TcPO2 and reductions in TcPCO2 indicate improved cutaneous perfusion response to local heating post-exercise. Elevated toe pressures in the non-diabetes group suggest that improved perfusion may be associated with enhanced lower limb macrovascular haemodynamics. However, improvements in TcPO2 and TcPCO2 at foot and chest sites in diabetes imply a global change in cutaneous perfusion. The results suggest that brief exercise results in an improvement in cutaneous perfusion in non-critical PAOD, particularly in individuals with diabetes. [source] Quantification of myoglobin deoxygenation and intracellular partial pressure of O2 during muscle contraction during haemoglobin-free medium perfusionEXPERIMENTAL PHYSIOLOGY, Issue 5 2010Hisashi Takakura Although the O2 gradient regulates O2 flux from the capillary into the myocyte to meet the energy demands of contracting muscle, intracellular O2 dynamics during muscle contraction remain unclear. Our hindlimb perfusion model allows the determination of intracellular myoglobin (Mb) saturation () and intracellular oxygen tension of myoglobin () in contracting muscle using near infrared spectroscopy (NIRS). The hindlimb of male Wistar rats was perfused from the abdominal aorta with a well-oxygenated haemoglobin-free Krebs,Henseleit buffer. The deoxygenated Mb (,[deoxy-Mb]) signal was monitored by NIRS. Based on the value of ,[deoxy-Mb],,,and,,were calculated, and the time course was evaluated by an exponential function model. Both,,and,,started to decrease immediately after the onset of contraction. The steady-state values of,,and,,progressively decreased with relative work intensity or muscle oxygen consumption. At the maximal twitch rate,,,and,,were 49% and 2.4 mmHg, respectively. Moreover, the rate of release of O2 from Mb at the onset of contraction increased with muscle oxygen consumption. These results suggest that at the onset of muscle contraction, Mb supplies O2 during the steep decline in,, which expands the O2 gradient to increase the O2 flux to meet the increased energy demands. [source] Oxygen sensing in hypoxic pulmonary vasoconstriction: using new tools to answer an age-old questionEXPERIMENTAL PHYSIOLOGY, Issue 1 2008Gregory B. Waypa Hypoxic pulmonary vasoconstriction (HPV) becomes activated in response to alveolar hypoxia and, although the characteristics of HPV have been well described, the underlying mechanism of O2 sensing which initiates the HPV response has not been fully established. Mitochondria have long been considered as a putative site of oxygen sensing because they consume O2 and therefore represent the intracellular site with the lowest oxygen tension. However, two opposing theories have emerged regarding mitochondria-dependent O2 sensing during hypoxia. One model suggests that there is a decrease in mitochondrial reactive oxygen species (ROS) levels during the transition from normoxia to hypoxia, resulting in the shift in cytosolic redox to a more reduced state. An alternative model proposes that hypoxia paradoxically increases mitochondrial ROS signalling in pulmonary arterial smooth muscle. Experimental resolution of the question of whether the mitochondrial ROS levels increase or decrease during hypoxia has been problematic owing to the technical limitations of the tools used to assess oxidant stress as well as the pharmacological agents used to inhibit the mitochondrial electron transport chain. However, recent developments in genetic techniques and redox-sensitive probes may allow us eventually to reach a consensus concerning the O2 sensing mechanism underlying HPV. [source] Hypoxia induces expression of a GPI-anchorless splice variant of the prion proteinFEBS JOURNAL, Issue 11 2008Yutaka Kikuchi The human prion protein (PrP) is a glycoprotein with a glycosylphosphatidylinositol (GPI) anchor at its C-terminus. Here we report alternative splicing within exon 2 of the PrP gene (PRNP) in the human glioblastoma cell line T98G. The open reading frame of the alternatively spliced mRNA lacked the GPI anchor signal sequence and encoded a 230 amino acid polypeptide. Its product, GPI-anchorless PrP (GPI, PrPSV), was unglycosylated and soluble in non-ionic detergent, and was found in the cytosolic fraction. We also detected low levels of alternatively spliced mRNA in human brain and non-neuronal tissues. When long-term passaged T98G cells were placed in a low-oxygen environment, alternatively spliced mRNA expression increased and expression of normally spliced PrP mRNA decreased. These findings imply that oxygen tension regulates GPI, PrPSV expression in T98G cells. [source] The influence of reproductive state on cardiac parameters and hypoxia tolerance in the Grass Shrimp, Palaemonetes pugioFUNCTIONAL ECOLOGY, Issue 6 2005J. A. GUADAGNOLI Summary 1In many crustaceans, female reproduction represents a time of increased metabolic demand. Palaemonetes pugio are typically hypoxia tolerant; but the energetic demands of reproduction may compromise their ability to tolerate hypoxic conditions. Given the correlation between cardiac output and metabolic demand, we used cardiac output (CO) to measure differences in metabolic demand in the life-history stages of P. pugeo. 2We hypothesized that (1) the cost of egg production would result in an increased CO for gravid females compared with non-gravid females; (2) those females that were both ovigerous and gravid would have an additional metabolic demand due to brooding behaviour (pleopod fanning) and hence an even greater CO; and (3) hypoxia tolerance would decrease with increasing reproductive demand. To test these hypotheses, we compared cardiac output across three reproductive states and at decreasing water oxygen tensions. 3Ovigerous females had significantly greater pleopod fanning frequency than non-ovigerous females at all oxygen tensions. Additionally, ovigerous/gravid females had significantly higher cardiac output at all oxygen tensions than gravid only or non-gravid females. 4Changes in cardiac output indicate that females became more sensitive to environmental oxygen tension with increasing reproductive demand. Non-gravid females were able to maintain cardiac output down to 15 mm Hg O2, whereas gravid and ovigerous/gravid females maintained cardiac output down to 50 mm Hg and 75 mm Hg O2, respectively. 5These differences in CO suggest that metabolic demands of females change with reproductive state and, while gravid and ovigerous/gravid females appear more sensitive to low oxygen tensions, they are able to physiologically tolerate low environmental oxygen conditions. [source] The Hill equation: a review of its capabilities in pharmacological modellingFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2008Sylvain Goutelle Abstract The Hill equation was first introduced by A.V. Hill to describe the equilibrium relationship between oxygen tension and the saturation of haemoglobin. In pharmacology, the Hill equation has been extensively used to analyse quantitative drug,receptor relationships. Many pharmacokinetic,pharmacodynamic models have used the Hill equation to describe nonlinear drug dose,response relationships. Although the Hill equation is widely used, its many properties are not all well known. This article aims at reviewing the various properties of the Hill equation. The descriptive aspects of the Hill equation, in particular mathematical and graphical properties, are examined, and related to Hill's original work. The mechanistic aspect of the Hill equation, involving a strong connection with the Guldberg and Waage law of mass action, is also described. Finally, a probabilistic view of the Hill equation is examined. Here, we provide some new calculation results, such as Fisher information and Shannon entropy, and we introduce multivariate probabilistic Hill equations. The main features and potential applications of this probabilistic approach are also discussed. Thus, within the same formalism, the Hill equation has many different properties which can be of great interest for those interested in mathematical modelling in pharmacology and biosciences. [source] A study of the effect of a resistive heat moisture exchanger (trachinaze) on pulmonary function and blood gas tensions in patients who have undergone a laryngectomy: A randomized control trial of 50 patients studied over a 6-month periodHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2003Andrew Simpson Jones MD Abstract Background. Previous work from this department has shown that resistive tracheostomy filters increase the partial pressure of oxygen in capillary blood and also provide a significant amount of heat/moisture exchange. Until now it has not been shown whether there is any long-term beneficial effect and in particular whether raised tissue oxygenation is maintained using a practical filter device. Methods. We carried out a 6-month randomized control trial including 50 laryngectomees. Twenty-five patients were treated with the Liverpool Heat Moisture Exchange device incorporating an airway resistor (Trachinaze). Another 25 patients were treated with a placebo device. Relevant subjective and objective data were collected before and at the end of the study. The objective measurements were capillary oxygen tension (which parallels blood arterial tension), carbon dioxide tension, FEV1, FVC, and PIF. Patients were reviewed at intervals throughout the study. Data were analyzed using the Mann,Whitney U test and the paired t test to test the difference between the active device and placebo at 6 months. Results. Subjective lower airway parameters, including cough, number of chest infections, mucus production, and shortness of breath at rest, were significantly improved in the active group compared with the placebo group. The objective parameters FEV1, FVC, and PIF were not significantly different. Capillary oxygen tension, however, was highly significantly raised in the active group at 6 months. Conclusions. Trachinaze is highly superior to placebo at improving subjective pulmonary parameters, including shortness of breath. It is also superior in its ability to maintain an increased peripheral tissue oxygen tension over a 6-month period. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000,000, 2003 [source] Stimulation of NMDA and AMPA glutamate receptors elicits distinct concentration dynamics of nitric oxide in rat hippocampal slicesHIPPOCAMPUS, Issue 7 2009J.G. Frade Abstract Nitric oxide (,NO) is an intercellular messenger implicated in memory formation and neurodegeneration in the hippocampus. Owing to its physical and chemical properties, the concentration dynamics of ,NO is a critical issue in determining its bioactivity as a signaling molecule. Its production is closely related to glutamate N -methyl- D -aspartate (NMDA) receptors, following a rise in intracellular calcium levels. However, that dependent on ,-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors remains elusive and controversial, despite reports describing a role for these receptors in other brain regions, largely because of lack of quantitative and dynamic measurements of ,NO. Using a ,NO-selective microsensor inserted in the diffusional spread of ,NO in the CA1 region of rat hippocampal slices, we measured its real-time endogenous production, following activation of ionotropic glutamate receptors and under tissue physiological oxygen tension. Both NMDA and AMPA stimulation resulted in a concentration-dependent ,NO production but encompassing distinct kinetics for lag phases and slower rates of ,NO production were observed for AMPA stimulation. Robustness of the results was achieved instrumentally and pharmacologically, by means of nitric oxide synthase (NOS) inhibitors and antagonists of NMDA (D -(,)-2-amino-5-phosphonopentanoic acid, AP5) and AMPA (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide, NBQX) receptors. When using glutamate as a stimulus, ,NO production was of lower magnitude in the presence of AP5 plus NBQX than with AP5 alone, suggesting that even when NMDA receptors are inhibited Ca2+ rises to levels to induce a peak of ,NO from the background. Whereas extracellular Ca2+ was required for the ,NO signals, Philanthotoxin-4,3,3 (PhTX-4,3,3) a toxin used to target Ca2+ -permeable AMPA receptors, attenuated ,NO production. These observations are interpreted on basis of a distinct coupling between the glutamate receptors and neuronal NOS. A role for Ca2+ -permeable AMPA receptors in the Ca2+ activation of neuronal NOS is suggested. © 2008 Wiley-Liss, Inc. [source] The neuronal and endothelium-dependent relaxing responses of human corpus cavernosum under physiological oxygen tension last longer than previously expectedINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2004KAZUNORI KIMURA Abstract Background: Intracavernosal oxygen tension varies greatly in the process of erection. Blood extracted from the human penis demonstrates an increase from approximately 30 mmHg Po2 in the flaccid state to 100 mmHg in the erect state of the penis. In the present study, using these levels as a guide, we investigate how the NO-dependent relaxation of human corpus cavernosum changed under physiological oxygen tensions ranging from approximately 30 to 100 mmHg. Methods: Human penile tissue specimens were obtained at penile surgery with informed consent from the patients. The preparations were mounted in Krebs solution in an organ bath and the isometric tension was recorded. Krebs solutions of various oxygen tensions were prepared by bubbling 5% CO2 in N2 and O2. The NO-dependent relaxation caused by electrical field stimulation (EFS) and acetylcholine (ACh) was studied, and the amplitude and duration of relaxation evaluated. Results: The amplitude of relaxation induced by EFS was significantly decreased under physiological oxygen tension conditions (P < 0.01). The duration of the relaxant response induced by EFS and ACh was significantly prolonged in physiological oxygen tension conditions than in high oxygen tension (P < 0.01). However, there was no correlation between the duration of relaxation induced by EFS and each physiological oxygen tension level. The duration of relaxation induced by ACh was most prolonged at 60,69 mmHg oxygen tension. Conclusion: Physiologically, the effect of NO may last longer than was previously thought. In addition, it would seem that there is an optimal physiological oxygen tension for maximum ACh-induced relaxation. [source] Diffusion and Monod kinetics to determine in vivo human corneal oxygen-consumption rate during soft contact-lens wearJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2009Mahendra Chhabra Abstract The rate of oxygen consumption is an important parameter to assess the physiology of the human cornea. Metabolism of oxygen in the cornea is influenced by contact-lens-induced hypoxia, diseases such as diabetes, surgery, and drug treatment. Therefore, estimation of in vivo corneal oxygen-consumption rate is essential for gauging adequate oxygen supply to the cornea. Phosphorescence quenching of a dye coated on the posterior of a soft contact lens provides a powerful technique to measure tear-film oxygen tension (Harvitt and Bonanno, Invest Ophthalmol Vis Sci 1996;37:1026,1036; Bonanno et al., Invest Ophthalmol Vis Sci 2002;43:371,376). Unfortunately, previous work in establishing oxygen-consumption kinetics from transient postlens tear-film oxygen tensions relies on the simplistic assumption of a constant corneal-consumption rate. A more realistic model of corneal metabolism is needed to obtain reliable oxygen-consumption kinetics. Here, physiologically relevant nonlinear Monod kinetics is adopted for describing the local oxygen-consumption rate, thus avoiding aphysical negative oxygen tensions in the cornea. We incorporate Monod kinetics in an unsteady-state reactive-diffusion model for the cornea contact-lens system to determine tear-film oxygen tension as a function of time when changing from closed-eye to open-eye condition. The model was fit to available experimental data of in vivo human postlens tear-film oxygen tension to determine the corneal oxygen-consumption rate. Reliance on corneal oxygen diffusivity and solubility data obtained from rabbits is no longer requisite. Excellent agreement is obtained between the proposed model and experiment. We calculate the spatial-averaged in vivo human maximum corneal oxygen-consumption rate as Q = 1.05 × 10,4 mL/(cm3 s). The calculated Monod constant is Km = 2.2 mmHg. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009 [source] Oxygen Tension Regulates the Expression of ANK (Progressive Ankylosis) in an HIF-1-Dependent Manner in Growth Plate Chondrocytes,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2009Raihana Zaka Abstract The proximal promoter region of ANK, a gene that codes for a protein that regulates the transport of inorganic pyrophosphate, contains two hypoxia responsive elements (HREs); therefore, we studied the expression and function of ANK at different oxygen tensions. ATDC5 and N1511 clonal chondrocytic cells were cultured in either hypoxia (2% O2) or normoxia (21% O2). Transcript and protein levels of ANK were depressed in hypoxic conditions, as were levels of extracellular pyrophosphate (ePPi). To determine whether HIF-1 was involved in the oxemic response, Hif-1, knockdown cells were exposed to varying oxygen conditions and ANK expression was assessed. Knockdown of Hif-1, resulted in low levels of expression of ANK in hypoxia and normoxia. Chromatin immunoprecipitation (ChIP) assays explored the binding of Hif-1, to ANK HREs and showed that Hif-1, is able to bind to the HREs of ANK more avidly in normoxia than in hypoxia. Furthermore, functional studies of Hif-1, activity using luciferase reporter assays of wildtype and mutagenized HREs showed that only HRE-1 binds Hif-1, in normoxia. Expression of ANK in growth plate and articular cartilage was low in hypoxic regions of the tissues, and higher levels of ANK expression were observed in the synovium and meniscus in regions that have a normally higher oxygen tension. The data suggest that ANK expression and function in vitro and in vivo are repressed in hypoxic environments and that the effect is regulated by HIF-1. [source] Hypoxia suppresses runx2 independent of modeled microgravityJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2004Christopher Ontiveros Bone loss is a consequence of skeletal unloading as seen in bed rest and space flight. Unloading decreases oxygenation and osteoblast differentiation/function in bone. Previously we demonstrated that simulation of unloading in vitro, by culturing differentiating mouse osteoblasts in a horizontal rotating wall vessel (RWV), results in suppressed expression of runx2, a master transcriptional regulator of osteoblast differentiation. However, the RWV is able to reproduce in a controlled fashion at least two aspects of disuse that are directly linked, model microgravity and hypoxia. Hypoxia in the RWV is indicated by reduced medium oxygen tension and increased expression of GAPDH and VEGF. To uncouple the role of model microgravity from hypoxia in suppressed runx2 expression, we cultured osteoblasts under modeled microgravity (oxygenated, horizontal RWV rotation), hypoxia (vertical RWV rotation), or both conditions (horizontal RWV rotation). The expression, DNA binding activity and promoter activity of runx2, was suppressed under hypoxic but not normoxic modeled microgravity RWV conditions. Consistent with a role for hypoxia in suppression of runx2, direct exposure to hypoxia alone is sufficient to suppress runx2 expression in osteoblasts grown in standard tissue culture plates. Taken together, our findings indicate that hypoxia associated with skeletal unloading could be major suppressor of runx2 expression leading to suppressed osteoblast differentiation and bone formation. © 2004 Wiley-Liss, Inc. [source] Control of human articular chondrocyte differentiation by reduced oxygen tensionJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2004Christopher L. Murphy Cell number is often a limiting factor in studies of chondrocyte physiology, particularly for human investigations. Chondrocytes can be readily proliferated in monolayer culture, however, differentiated phenotype is soon lost. We therefore endeavored to restore normal phenotype to human chondrocytes after serial passage in monolayer culture by manipulating cell morphology and oxygen tension towards the in vivo state. Third passage cells were encapsulated in alginate and exposed to either 20% or more physiologic 5% oxygen tensions. To assess cell phenotype, gene expression was measured using TaqMan real-time PCR. Encapsulated, primary chondrocytes cultured in 20% oxygen were used as a positive reference. Passaged human chondrocytes were fibroblastic in appearance and had lost normal phenotype as evidenced by a decrease in expression of collagen II, aggrecan, and sox9 genes of 66, 6, and 14 fold, respectively; with concomitant high expression of type I collagen (22 fold increase). A partial regaining of the differentiated phenotype was observed by encapsulation in 20% oxygen; however, even after 4 weeks, collagen II gene expression was not fully restored. Collagen II and aggrecan expression were increased, on average, 3 fold, in 5% oxygen tension compared to 20% cultures. Furthermore, matrix glycosaminoglycan (GAG) levels were significantly increased in reduced oxygen. In fact, after 4 weeks in 5% oxygen, encapsulated third passage cells had collagen II expression fully regained and aggrecan and sox9 levels actually exceeding primary cell levels in 20% oxygen. Our results show that the phenotype of serially passaged human articular chondrocytes is more fully restored by combining encapsulation with culture in more physiological levels of oxygen. Sox9, an essential transcription factor for chondrocyte differentiation is strongly implicated in this process since its expression was upregulated almost 27 fold. These findings have implications for the optimal conditions for the in vitro culture of chondrocytes. © 2004 Wiley-Liss, Inc. [source] Hyper osmolality does not modulate natriuretic peptide concentration in patients after coronary artery surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2009E. L. HONKONEN Background: The heart secretes natriuretic peptides (NPs) in response to myocardial stretch. Measuring NP concentrations is a helpful tool in guiding treatment. It has been suggested that sodium ion and hyperosmolality could affect NP excretion. If this is true, peri-operative NP measurements could be inconsistent when hypertonic solutions are used. With different osmolalities but equal volumes of hydroxyethyl starch (HES) , and hypertonic saline (HS) , infusions, this double-blinded study tested the hypothesis that osmolality modulates the excretion of NPs. Methods: Fifty coronary surgery patients were randomized to receive within 30 min 4 ml/kg either HS or HES post-operatively. Samples for analysis of atrial NP (ANP), brain NP (BNP), plasma and urine sodium and osmolality and urine oxygen tension were obtained before and 60 min after starting the infusions and on the first post-operative morning. The haemodynamic parameters were measured at the same time points. Results: Plasma osmolality and sodium increased only in the HS group. Changes in plasma BNP and ANP levels did not differ between the groups (P=0.212 and 0.356). There were no correlations between NP levels and osmolality or sodium at any time point. In the HS group, urine volume was higher (3295 vs. 2644 ml; P<0.05) and the need for furosemide treatment was less (0.4 vs. 3.8 mg; P<0.01) than in the HES group. Conclusions: The absence of effects of plasma sodium content or hyperosmolality on NP release validates the value of NPs as a biomarker in peri-operative patients. [source] Oxygen accelerates the accumulation of mutations during the senescence and immortalization of murine cells in cultureAGING CELL, Issue 6 2003Rita A. Busuttil Summary Oxidative damage is a causal factor in aging and cancer, but it is still not clear how DNA damage, the cellular responses to such damage and its conversion to mutations by misrepair or misreplication contribute to these processes. Using transgenic mice carrying a lacZ mutation reporter, we have previously shown that mutations increase with age in most organs and tissues in vivo. It has also been previously shown that mouse cells respond to oxidative stress, typical of standard culture conditions, by undergoing cellular senescence. To understand better the consequences of oxidative stress, we cultured mouse embryo fibroblasts (MEFs) from lacZ mice under physiological oxygen tension (3%) or the high oxygen tension (20%) associated with standard culture, and determined the frequency and spectrum of mutations. Upon primary culture, the mutation frequency was found to increase approximately three-fold relative to the embryo. The majority of mutations were genome rearrangements. Subsequent culture in 20% oxygen resulted in senescence, followed by spontaneous immortalization. Immortalization was accompanied by an additional three-fold increase in mutations, most of which were G:C to T:A transversions, a signature mutation of oxidative DNA damage. In 3% oxygen, by contrast, MEFs did not senesce and the mutation frequency and spectrum remained similar to primary cultures. These findings demonstrate for the first time the impact of oxidative stress on the genomic integrity of murine cells during senescence and immortalization. [source] Temperature-dependent changes in energy metabolism, intracellular pH and blood oxygen tension in the Atlantic codJOURNAL OF FISH BIOLOGY, Issue 6 2003F. J. Sartoris The effect of acute increase in temperature on oxygen partial pressure (Po2) was measured in the gill arches of Atlantic cod Gadus morhua between 10 and 19° C by use of oxygen microoptodes. Oxygen saturation of the gill blood under control conditions varied between 90 and 15% reflecting a variable percentage of arterial or venous blood in accordance with the position of each optode in the gill arch. The data obtained suggested that arterial Po2 remained more or less constant and arterial oxygen uptake did not become limiting during warming. A progressive drop in venous Po2, however, was observed at >10° C indicating that excessive oxygen uptake from the blood is not fully compensated for by circulatory performance, until finally, Po2 levels fully collapse. In a second set of experiments energy and acid,base status of white muscle of Atlantic cod in vivo was measured by magnetic resonance (31P-NMR) spectroscopy in unanaesthetized and unimmobilized fish in the temperature range between 13 and 21° C. A decrease in white muscle intracellular pH (pHi) with temperature occurred between 10 and 16° C (,pH per ° C = ,0·025 per ° C). In white muscle temperature changes had no influence on high-energy phosphates such as phosphocreatine (PCr) or ATP except during exposure to high critical temperatures (>16° C), indicating that white muscle energy status appears to be relatively insensitive to thermal stress if compared to the thermal sensitivity of the whole animal. The data were consistent with the hypothesis of an oxygen limitation of thermal tolerance in animals, which is set by limited capacity of oxygen supply mechanisms. In the case of Atlantic cod circulatory rather than ventilatory performance may be the first process to cause oxygen deficiency during heat stress. [source] Regional dynamics of the fMRI-BOLD signal response to hypoxia-hypercapnia in the rat brainJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2003Sridhar S. Kannurpatti PhD Abstract Purpose To examine the regional blood oxygenation level-dependent (BOLD) signal response to rapid changes in arterial oxygen tension. Materials and Methods Functional MR imaging (fMRI) was carried out in five male Sprague-Dawley rats anesthetized with Sodium Pentobarbital. Rats were subjected to different durations of apnea as a rapid, graded, and reversible hypoxic-hypercapnic stimulus. Dynamics of the BOLD signal response were studied on a pixel-by-pixel basis in the cerebral cortex, hippocampus, third ventricle, and thalamus in the rat brain. Results Apnea induced a BOLD signal drop in all the brain regions studied, the magnitude of which increased with longer durations of the stimulus. The signal recovered to preapnic baseline levels after resumption of normal ventilation. Regional variation in the BOLD signal dynamics was observed with the magnitude of the BOLD signal change in the hippocampus being the least, followed by a relatively larger change in the thalamus, cerebral cortex, and third ventricle. The time (t0) for the signal change after the onset of the stimulus was estimated for every pixel. Time delay maps generated show the highest onset time values in the hippocampus followed by the thalamus, cerebral cortex, and third ventricle. Conclusion The regional dynamics of the BOLD signal in the brain in response to apnea may vary depending on the rate of oxygen metabolism in addition to cerebral blood flow (CBF). J. Magn. Reson. Imaging 2003;17:641,647. © 2003 Wiley-Liss, Inc. [source] Isofurans, but not F2 -isoprostanes, are increased in the substantia nigra of patients with Parkinson's disease and with dementia with Lewy body diseaseJOURNAL OF NEUROCHEMISTRY, Issue 3 2003Joshua P. Fessel Abstract F2 -isoprostanes (F2 -IsoPs) are well-established sensitive and specific markers of oxidative stress in vivo. Isofurans (IsoFs) are also products of lipid peroxidation, but in contrast to F2 -IsoPs, their formation is favored when oxygen tension is increased in vitro or in vivo. Mitochondrial dysfunction in Parkinson's disease (PD) may not only lead to oxidative damage to brain tissue but also potentially result in increased intracellular oxygen tension, thereby influencing relative concentrations of F2 -IsoPs and IsoFs. In this study, we attempted to compare the levels of F2 -IsoPs and IsoFs esterified in phospholipids in the substantia nigra (SN) from patients with PD to those of age-matched controls as well as patients with other neurodegenerative diseases, including dementia with Lewy body disease (DLB), multiple system atrophy (MSA), and Alzheimer's disease (AD). The results demonstrated that IsoFs but not F2 -IsoPs in the SN of patients with PD and DLB were significantly higher than those of controls. Levels of IsoFs and F2 -IsoPs in the SN of patients with MSA and AD were indistinguishable from those of age-matched controls. This preferential increase in IsoFs in the SN of patients with PD or DLB not only indicates a unique mode of oxidant injury in these two diseases but also suggests different underlying mechanisms of dopaminergic neurodegeneration in PD and DLB from those of MSA. [source] The effect of oxygen tension on the in vitro assay of human osteoblastic connective tissue progenitor cellsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 10 2008Sandra M. Villarruel Abstract Connective tissue progenitors (CTPs) are defined as the heterogeneous set of stem and progenitor cells that reside in native tissues and are capable of proliferation and differentiation into one or more connective tissue phenotypes. CTPs play important roles in tissue formation, repair, and remodeling. Therefore, in vitro assays of CTP prevalence and biological potential have important scientific and clinical relevance. This study evaluated oxygen tension as an important variable in optimizing in vitro conditions for quantitative assays of human CTPs. Bone marrow aspirates were collected from 20 human subjects and cultured using established medium conditions at ambient oxygen tensions of 1, 5, 10, and 20%. Colony-forming efficiency (CFE), proliferation, and colony density were assessed. CFE and proliferation were greatest at 5% O2. Traditional conditions using atmospheric oxygen tension (20% O2) reduced CFE by as much as 32%. CFE and proliferation at 1% O2 were less than 5% O2 but comparable to that seen at 20% O2, suggesting that CTPs are relatively resilient under hypoxic conditions, a fact that may be relevant to their function in wound repair and their potential use in tissue engineering applications involving transplantation into settings of moderate to severe hypoxia. These data demonstrate that optimization of quantitative assays for CTPs will require control of oxygen tension. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1390,1397, 2008 [source] Arterial oxygen tension increase 2,3 h after hyperbaric oxygen therapy: a prospective observational studyACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2007B. Ratzenhofer-Komenda Background:, Inhalation of hyperbaric oxygen (HBO) has been reported to decrease arterial oxygen tension (PaO2) in the early period after exposure. The current investigation aimed at evaluating whether and to what extent arterial blood gases were affected in mechanically ventilated intensive care patients within 6 h after HBO treatment. Methods:, Arterial blood gases were measured in 11 ventilated subjects [nine males, two females, synchronized intermittent mandatory ventilation (SIMV) mode] undergoing HBO therapy for necrotizing soft tissue infection (seven patients), burn injury (two patients), crush injury (one patient) and major abdominal surgery (one patient). Blood gases were obtained with the patients in the supine position under continuous analgesia and sedation before the hyperbaric session (baseline), during isopression, after decompression, after each transport, and 1, 2, 3 and 6 h after exposure. Heart rates and blood pressures were recorded. Intensive care unit (ICU) ventilator settings remained unchanged. Transport and chamber ventilator settings were adjusted to baseline with maintenance of tidal volumes and positive end-expiratory pressure (PEEP) levels. The hyperbaric protocol consisted of 222.9 kPa (2.2 absolute atmospheres) and a 50-min isopression phase. The paired Wilcoxon's test was used. Results:, Major findings (median values, 25%/75% quantiles) as per cent change of baseline: PaO2 values decreased by 19.7% (7.0/31.7, P < 0.01) after 1 h and were elevated over baseline by 9.3% (1.5/13.7, P < 0.05) after 3 h. SaO2, alveolar-arterial oxygen tension difference and PaO2/FiO2 ratio behaved concomitantly. Acid-base status and carbon dioxide tension were unaffected. Conclusion:, Arterial oxygen tension declines transiently after HBO and subsequently improves over baseline in intensive care patients on volume-controlled mechanical ventilation. The effectiveness of other ventilation modes or a standardized recruitment manoeuvre has yet to be evaluated. [source] Red blood cells attenuate sinusoidal endothelial cell injury by scavenging xanthine oxidase-dependent hydrogen peroxide in hyperoxic perfused rat liverLIVER INTERNATIONAL, Issue 3 2000Satoru Motoyama Abstract:Aims/Background: Rat liver perfused with an oxygenated buffered solution alone results in degenerative changes even when the perfusion flow is accelerated to give a sufficient oxygen supply. On the other hand, perfusion media supplemented with red blood cells (RBCs) preserve the viability of the liver. The present study was conducted to clarify how RBCs protect the isolated perfused liver. Methods: The liver was perfused with and without RBCs in a perfusate equilibrated with supra-physiological oxygen tension at regulated inflow pressures, and controlled hepatic oxygen consumption. We examined alanine aminotransferase and purine nucleoside phosphorylase activity in the perfusate as specific markers of liver cells injury. Hydrogen peroxide (H2O2) production and morphological changes were determined using cerium electron microscopy. Apoptosis was detected by measuring CPP 32 protease activity and using TdT-mediated dUTP-digoxigenin nick end-labeling. Results: When the liver was perfused with RBC-free buffer, H2O2 production and consequent injury progressing to apoptosis were initiated in the sinusoidal endothelial cells (SECs). After SECs were injured, H2O2 appeared in the hepatocytes. H2O2 production and associated degenerative changes were attenuated both morphologically and enzymatically by the addition of RBCs, a specific xanthine oxidase (XOD) inhibitor and the H2O2 radical scavenger, catalase. Conclusions: In the liver perfused with RBC-free buffer, H2O2 production and consequent injury were initiated in SECs. RBCs attenuate liver injury by scavenging XOD-dependent H2O2. [source] Pulmonary gas exchange abnormalities in liver transplant candidatesLIVER TRANSPLANTATION, Issue 9 2002Rosmawati Mohamed Abnormal diffusing capacity is the commonest pulmonary dysfunction in liver transplant candidates, but severe hypoxemia secondary to hepatopulmonary syndrome and significant pulmonary hypertension are pulmonary vascular manifestations of cirrhosis that may affect the perioperative course. We prospectively assessed the extent of pulmonary dysfunction in patients referred for liver transplantation. A total of 57 consecutive patients with chronic liver disease were evaluated. All patients had a chest radiograph, standing arterial blood gas on room air, pulmonary function testing, and Doppler echocardiogram. Those patients with arterial hypoxaemia (PaO2 < 10 kPa) also underwent 99mTc-macroaggregated albumin lung scan, and nine patients had agitated normal saline injection during echocardiography to define further the existence of pulmonary vascular dilatation. Reduced diffusing capacity for carbon monoxide less than 75% of the predicted value was found in 29 of 57 (51%) patients. Although elevated alveolar-arterial oxygen tension difference was detected in 35% (20/57) of the patients, only four (7%) patients had hypoxemia. We were unable to find evidence of intrapulmonary vascular dilatation either on the lung scan or saline-enhanced echocardiography in any of these patients. Reduction in diffusing capacity for carbon monoxide was noted in 75% (18/24) of patients who were transplanted for primary biliary cirrhosis and was accompanied by widened alveolar-arterial oxygen tension in 10 out of 18 (56%) of patients. This study shows that in liver transplant candidates, diffusion impairment and widened alveolar-arterial oxygen tension difference were frequently detected, especially in patients with primary biliary cirrhosis. [source] | |||||||||||||||||||||||||||||||||||||