PO2 Values Research Articles

Measuring the efficiency of pulmonary gas exchange using expired gas instead of arterial blood: comparing the "ideal" Po2 of Riley with end-tidal Po2.

When using a new noninvasive method for measuring the efficiency of pulmonary gas exchange, a key measurement is the oxygen deficit, defined as the difference between the end-tidal alveolar Po2 and the calculated arterial Po2. The end-tidal Po2 is measured using a rapid gas analyzer, and the arterial Po2 is derived from pulse oximetry after allowing for the effect of the Pco2 on the oxygen affinity of hemoglobin. In the present report we show that the values of end-tidal Po2 and Pco2 are highly reproducible, providing a solid foundation for the measurement of the oxygen deficit. We compare the oxygen deficit with the classical ideal alveolar-arterial Po2 difference (A-aDO2) as originally proposed by Riley, and now extensively used in clinical practice. This assumes Riley's criteria for ideal alveolar gas, namely no ventilation-perfusion inequality, the same Pco2 as arterial blood, and the same respiratory exchange ratio as the whole lung. It transpires that, in normal subjects, the end-tidal Po2 is essentially the same as the ideal value. This conclusion is consistent with the very small oxygen deficit that we have reported in young normal subjects, the significantly higher values seen in older normal subjects, and the much larger values in patients with lung disease. We conclude that this noninvasive measurement of the efficiency of pulmonary exchange is identical in many respects to that based on the ideal alveolar Po2, but that it is easier to obtain.

Nitric oxide mediates metabolic functions in the bivalve Arctica islandica under hypoxia.

The free radical nitric oxide (NO) is a powerful metabolic regulator in vertebrates and invertebrates. At cellular concentrations in the nanomolar range, and simultaneously reduced internal oxygen partial pressures (pO2), NO completely inhibits cytochrome-c-oxidase (CytOx) activity and hence mitochondrial- and whole-tissue respiration. The infaunal clam Arctica islandica regulates pO2 of hemolymph and mantle cavity water to mean values of <5 kPa, even in a completely oxygen-saturated environment of 21 kPa. These low internal pO2 values support a longer NO lifespan and NO accumulation in the body fluids and can thus trigger a depression of metabolic rate in the clams. Measurable amounts of NO formation were detected in hemocyte cells (~110 pmol NO 100−1 hemocytes h-1 at 6 kPa), which was not prevented in the presence of the NO synthase inhibitor L-NAME, and in the gill filaments of A. islandica. Adding a NO donor to intact gills and tissue homogenate significantly inhibited gill respiration and CytOx activity below 10 kPa. Meanwhile, the addition of the NO-oxidation product nitrite did not affect metabolic rates. The high nitrite levels found in the hemolymph of experimental mussels under anoxia do not indicate cellular NO production, but could be an indication of nitrate reduction by facultative anaerobic bacteria associated with tissue and/or hemolymph biofilms. Our results suggest that NO plays an important role in the initiation of metabolic depression during self-induced burrowing and shell closure of A. islandica. Furthermore, NO appears to reduce mitochondrial oxygen radical formation during surfacing and cellular reoxygenation after prolonged periods of hypoxia and anoxia.

Large Mass-Independent Oxygen Isotope Fractionations in Mid-Proterozoic Sediments: Evidence for a Low-Oxygen Atmosphere?

Earth's ocean-atmosphere system has undergone a dramatic but protracted increase in oxygen (O2) abundance. This environmental transition ultimately paved the way for the rise of multicellular life and provides a blueprint for how a biosphere can transform a planetary surface. However, estimates of atmospheric oxygen levels for large intervals of Earth's history still vary by orders of magnitude-foremost for Earth's middle history. Historically, estimates of mid-Proterozoic (1.9-0.8 Ga) atmospheric oxygen levels are inferred based on the kinetics of reactions occurring in soils or in the oceans, rather than being directly tracked by atmospheric signatures. Rare oxygen isotope systematics-based on quantifying the rare oxygen isotope 17O in addition to the conventionally determined 16O and 18O-provide a means to track atmospheric isotopic signatures and thus potentially provide more direct estimates of atmospheric oxygen levels through time. Oxygen isotope signatures that deviate strongly from the expected mass-dependent relationship between 16O, 17O, and 18O develop during ozone formation, and these "mass-independent" signals can be transferred to the rock record during oxidation reactions in surface environments that involve atmospheric O2. The magnitude of these signals is dependent upon pO2, pCO2, and the overall extent of biospheric productivity. Here, we use a stochastic approach to invert the mid-Proterozoic Δ17O record for a new estimate of atmospheric pO2, leveraging explicit coupling of pO2 and biospheric productivity in a biogeochemical Earth system model to refine the range of atmospheric pO2 values that is consistent with a given observed Δ17O. Using this approach, we find new evidence that atmospheric oxygen levels were less than ∼1% of the present atmospheric level (PAL) for at least some intervals of the Proterozoic Eon.

Person or thing oriented: A comparative study of individual differences of first‐year engineering students and practitioners

AbstractBackgroundEngineering practice is meant to advance the human condition, yet curricula do not appear to fully promote the human‐centered philosophy of engineering in implementation. The educational system may inadvertently signal to students that engineering is a career choice better suited for those preferring to work with things rather than people. This framing of the profession prompts questions regarding student interests when compared to those of practicing engineers and how such interests become concrete through education and introduction into the profession.Purpose/HypothesisWe compare engineering students' and practitioners' interest in working with people or things in their environment. We examine gender differences for each sample.Design/MethodsMultiple analysis of variance was used to examine the samples of practicing engineers (n = 339) and first‐year engineering students (n= 383). A multiple‐group confirmatory factor analysis provides evidence of measurement invariance and justifies the use of the person–thing orientation (PO–TO) scale structure for both samples.ResultsDetailed PO values reveal that students' PO scores (n = 383, M = 3.313) are more than one and a half points lower than practicing engineer counterparts examined (n = 339, M = 4.836). However, no significant difference between practicing engineers and students was found for TO. Further, statistically significant differences in PO and TO were found between male and female participants within both samples, students and practicing engineers.ConclusionsDifferences detected in PO and TO across the samples suggest possible environmental factors influencing student perspectives of the engineering profession. This condition may inadvertently discourage more diverse students from pursuing engineering.

The comparison of tracheostomy and translaryngeal intubation regarding free radical formation and pulmonary effects.

Our aim in this study was to compare the blood gas changes, the malondialdehyde (MDA) and endogenous antioxidant glutathione (GSH) levels in blood and lung tissues after ischemia/reperfusion, the histopathological damage in lung tissue in rats provided respiratory support with mechanical ventilation after translaryngeal intubation and tracheostomy. Group 1 rats were provided mechanical ventilator support after translaryngeal intubation, Group 2 mechanical ventilator support after tracheostomy, and Group 3 was the control group where rats were only anesthetized. Three groups were compared for blood gas changes, MDA, GSH, and histopathological changes. Blood gas evaluation showed a more marked increase in pO2 values and decline in pCO2 values in Group 2 than Group 1 (p<0.05), and higher serum MDA levels in Group 1 than Group 2 (p<0.05). Tissue GSH levels in Groups 1 and 2 were higher than the control group, but this difference was not statistically significant (p>0.05). In terms of histopathological scoring, the damage score in Group 1 was higher than in Group 2 (p<0.05). This is the first study to show tracheostomy to be more advantageous than translaryngeal intubation in terms of blood gases, ischemia/reperfusion damage, and structural changes in the lung tissue.

Hypobaric hypoxia preconditioning protects against hypothalamic neuron apoptosis in heat-exposed rats by reversing hypothalamic overexpression of matrix metalloproteinase-9 and ischemia.

Background: Hypoxia-inducible factor-1α (HIF-1α), heat shock protein-72 (HSP-72), hemeoxygenase-1 (HO-1), and matrix metalloproteinase-9 (MMP-9) have been identified as potential therapeutic targets in the brain for cerebral ischemia. To elucidate their underlying mechanisms, we first aimed to ascertain whether these proteins participate in the pathogenesis of heat-induced ischemic damage to the hypothalamus of rats. Second, we investigated whether hypobaric hypoxia preconditioning (HHP) attenuates heat-induced hypothalamic ischemic/hypoxic injury by modulating these proteins in situ.Methods: Anesthetized rats treated with or without HHP were subjected to heat stress. Hypothalamic ischemic/hypoxic damage was evaluated by measuring hypothalamic levels of cerebral blood flow (CBF), partial oxygen pressure (PO2), and hypothalamic temperature via an implanted probe. Hypothalamic apoptotic neurons were counted by measuring the number of NeuN/caspase-3/DAPI triple-stained cells. Hypothalamic protein expression of HIF-1α, HSP-72, HO-1, and MMP-9 was determined biochemically.Results: Before the start of the thermal experiments, rats were subjected to 5 hours of HHP (0.66 ATA or 18.3% O2) daily for 5 consecutive days per week for 2 weeks, which led to significant loss of body weight, reduced brown adipose tissue (BAT) wet weight and decreased body temperature. The animals were then subjected to thermal studies. Twenty minutes after heat stress, heat-exposed rats not treated with HHP displayed significantly higher core and hypothalamic temperatures, hypothalamic MMP-9 levels, and numbers of hypothalamic apoptotic neurons but significantly lower mean blood pressure, hypothalamic blood flow, and PO2 values than control rats not exposed to heat. In heat-exposed rats, HHP significantly increased the hypothalamic levels of HIF-1α, HSP-72, and HO-1 but significantly alleviated body and hypothalamic hyperthermia, hypotension, hypothalamic ischemia, hypoxia, neuronal apoptosis and degeneration.Conclusions: HHP may protect against hypothalamic ischemic/hypoxic injury and overexpression of MMP-9 by upregulating the hypothalamic expression of HIF-1α, HSP-72, and HO-1 in rats subjected to heatstroke.

Acid-base balance parameters of follicular fluid and venous blood in cattle

The study aimed to compare differences of physiological acid-base balance (ABB) parameters in follicular fluid (FF) and venous blood (VB) and to evaluate ABB parameters in FF collected from different ovarian follicles in dairy cows and heifers. The ABB parameters (pH, pCO2, pO2, HCO3– and base excess (BE)) in the FF of the preovulatory follicle, of the dominant follicle on the 9th day of the cycle and of the superovulatory estrous follicles were compared to VB. Similarly, the dynamics of the ABB profile in FF and VB were monitored in repeated sampling in a group of heifers stimulated by follicle-stimulating hormone (FSH). Higher values of pH and pO2 and lower values of pCO2, HCO3– and BE were found in FF compared to VB in all experiments. Laterality of ovaries, time of sampling, ovarian activity or stimulation of the follicular development by FSH did not significantly influence ABB parameters. We found higher pH (7.392 ± 0.027 vs. 7.364 ± 0.032) and pO2 (13.83 ± 2.20 kPa vs. 4.50 ± 0.67 kPa), lower pCO2 (5.70 ± 0.39 kPa vs. 6.54 ± 0.61 kPa), HCO3– (25.51 ± 1.52 mmol/l vs. 26.86 ± 2.12 mmol/l) and BE (1.14 ± 1.57 mmol/l vs. 1.95 ± 2.2 mmol/l) in FF compared to VB in all non-stimulated cows. Similar relationships between FF and VB were found in all FSH stimulated cows. The study provides as yet unknown knowledge on the physiology of follicular fluid in cattle.

Comparison of Nasal bi-level Positive Airway Pressure Versus High-flow Nasal Cannula as a Means of Noninvasive Respiratory Support in Pediatric Cardiac Surgery.

Background:Noninvasive respiratory support is often used in preventing postextubation respiratory failure in neonates and infants after cardiac surgery.Aim:We compared the efficacy of nasal Bilevel Positive Airway Pressure (N/BiPAP) with that of High- flow Nasal Cannula(HFNC) in prevention of post extubation respiratory failure and maintenance of gas exchange in neonates and infants undergoing cardiac surgery. The incidence of complications related to the use of these modes were also compared.Settings and Design:This is a retrospective review of medical records of patients in pediatric cardiac intensive unit of a high-volume center.Methods:A total of 100 patients who received noninvasive respiratory support postextubation were divided into N/BiPAP group and HFNC group. The two groups were compared for postextubation respiratory failure, gas exchange in arterial blood gas at 24 h of extubation, and incidence of complications, namely pneumothorax, abdominal distension, and device–interface-related pressure ulcers.Results:Fifty patients each received N/BiPAP and HFNC after extubation. Patients who received N/BiPAP were younger (2.68 ± 2.97 months vs. 6.94 ± 4.04 months, P = 0.001) and had longer duration of postoperative ventilation (106.98 ± 79.02 h vs. 62.72 ± 46.14 h, P = 0.001). The reintubation rates were similar (20% [n = 10] in N/BiPAP group vs. 8% [n = 4] in HFNC group, P = 0.074). The mean arterial PO2 values at 24 h of extubation was 119.17 ± 56.07 mmHg for N/BiPAP group versus 123.32 ± 64.33 mmHg for HFNC group (P = 0.732). Arterial PCO2 values at 24 h were similar (43.97 ± 43.64 mmHg in N/BiPAP vs. 37.67 ± 4.78 mmHg in HFNC, P = 0.318). N/BiPAP group had higher incidence of abdominal distension (16% [n = 8] vs. nil in HFNC group, P = 0.003) and interface-related pressure ulcers (86% [n = 43] vs. 14% [n = 7] P = 0.006).Conclusion:N/BiPAP and HFNC have comparable efficacy in preventing reintubation and maintaining gas exchange. HFNC has fewer complications compared to N/BiPAP.

The influence of delayed sample processing time on PO2 values in critically ill patients with sepsis-induced leucocytosis

Background: The extent of error, from collection to processing, when measuring PO2, PCO2 and pH in arterial blood samples drawn from critically ill patients with sepsis and leucocytosis, is unknown. Methods: Twenty-nine patients with sepsis and a leucocyte count &gt; 12 000/mm3, who had routine arterial blood analysis were included in the study. Blood was drawn into two 1 ml heparinised glass syringes. One syringe was cooled on ice and tested at 60 minutes. The other syringe was used for analysis at 0, 10, 30 and 60 minutes. Differences in measurements, from the Time-0 results, were described. For PO2, linear mixed models estimated the impact of time to processing, controlling for the potentially confounding and moderating effects of Time-0 leucocyte count and fractional inspired oxygen concentration respectively. Results: PO2 exhibited the most pronounced changes over time at ambient temperature: The mean (SD) relative differences at 10, 30 and 60 minutes were -4.72 (8.82), -13.66 (10.25), and -25.12 (15.55)% respectively; and mean (SD) absolute differences -0.88 (1.49), -2.37 (1.89) and -4.32 (3.06) kPa. For pH, at 60 minutes, the mean (SD) relative and absolute differences were -0.27 (0.45)% and -0.02 (0.03) respectively; for PCO2, 6.16 (7.80)% and 0.25 (0.35) kPa. The median differences for the on-ice 60-minute sample for pH and PCO2 were 0.019 and -0.12 (both P &lt; 0.001), and for PO2 0.100 (P: 0.216). The model estimated that average PO2 decreased by 5% per 10 minute delay in processing (95% CI for effect: 0.94 to 0.96; P &lt; 0.001) at the average leucocyte count, with more rapid declines at higher counts, though with substantial inter-patient variation. Conclusion: Delayed blood gas analysis in samples stored at ambient temperature results in a statistically and clinically significant progressive decrease in arterial PO2, which may alter clinical decision-making in septic patients.

The influence of delayed sample processing time on PO2 values in critically ill patients with sepsis-induced leucocytosis

Background: The extent of error, from collection to processing, when measuring PO2, PCO2 and pH in arterial blood samples drawn from critically ill patients with sepsis and leucocytosis, is unknown. Methods: Twenty-nine patients with sepsis and a leucocyte count &gt; 12 000/mm3, who had routine arterial blood analysis were included in the study. Blood was drawn into two 1 ml heparinised glass syringes. One syringe was cooled on ice and tested at 60 minutes. The other syringe was used for analysis at 0, 10, 30 and 60 minutes. Differences in measurements, from the Time-0 results, were described. For PO2, linear mixed models estimated the impact of time to processing, controlling for the potentially confounding and moderating effects of Time-0 leucocyte count and fractional inspired oxygen concentration respectively. Results: PO2 exhibited the most pronounced changes over time at ambient temperature: The mean (SD) relative differences at 10, 30 and 60 minutes were -4.72 (8.82), -13.66 (10.25), and -25.12 (15.55)% respectively; and mean (SD) absolute differences -0.88 (1.49), -2.37 (1.89) and -4.32 (3.06) kPa. For pH, at 60 minutes, the mean (SD) relative and absolute differences were -0.27 (0.45)% and -0.02 (0.03) respectively; for PCO2, 6.16 (7.80)% and 0.25 (0.35) kPa. The median differences for the on-ice 60-minute sample for pH and PCO2 were 0.019 and -0.12 (both P &lt; 0.001), and for PO2 0.100 (P: 0.216). The model estimated that average PO2 decreased by 5% per 10 minute delay in processing (95% CI for effect: 0.94 to 0.96; P &lt; 0.001) at the average leucocyte count, with more rapid declines at higher counts, though with substantial inter-patient variation. Conclusion: Delayed blood gas analysis in samples stored at ambient temperature results in a statistically and clinically significant progressive decrease in arterial PO2, which may alter clinical decision-making in septic patients.

Pharmacological Increase of Hb-O2 Affinity with a Voxelotor Analog Does Not Decrease Brain Tissue pO2 or Limit O2 Extraction in Brain Tissues of Sickle Cell Mice

Sickle Cell Disease (SCD) is characterized by hemolytic anemia, vaso-occlusion, and progressive end-organ damage. The underlying mechanism of SCD is the polymerization of sickle hemoglobin (HbS) that occurs when sickle erythrocytes (SS RBCs) are partially deoxygenated in microcirculation, leading to SCD pathophysiologic features. One of the most devastating complications of SCD occurs in the central nervous system (CNS), where overt stroke or repeated silent cerebral infarcts lead to significant physical and neurocognitive consequences. In SCD, the brain's response to insufficient oxygen (O2) delivery is balanced by increased blood flow to preserve O2 supply. However, the systemic endothelial dysfunction in SCD limits the capacity for vascular regulatory and compensatory changes to preserve appropriate tissue oxygenation, especially in tissues with high O2 demand like the brain. Low hemoglobin (Hb) levels and increased cerebral blood flow (CBF) are associated with increased stroke risk, suggesting that anemia-induced tissue hypoxia is an important factor contributing to subsequent morbidity in SCD patients. Voxelotor (GBT440) is a small molecule, HbS polymerization inhibitor being developed by Global Blood Therapeutics (GBT) for the treatment of SCD. By addressing the underlying mechanism of SCD, voxelotor has the potential to be disease-modifying and alleviate the clinical manifestations of SCD. Mechanistically, voxelotor increases Hb-O2 affinity and delays the transition from oxyHb to deoxyHb under hypoxic conditions. This study assessed the impact of a pharmacologically mediated increase in Hb-O2 affinity on brain tissue oxygenation under both normoxic and hypoxic conditions in Townes transgenic sickle mice (SCD mice). Two compounds that increase the Hb-O2 affinity with similar potency, voxelotor and an analog to voxelotor, GBT1118, were considered for the study. The target for Hb occupancy with test compounds was ≥30% based on the therapeutic target occupancies observed with voxelotor in clinical studies. The effects of increased Hb-O2 affinity on brain tissue oxygenation were assessed directly with O2-specific microelectrodes in a cranial window and indirectly with hypoxyprobe staining (pimonidazole) of brain tissue. Unique to this SCD model, the targeted Hb occupancy (≥30%) could not be consistently achieved by voxelotor. In contrast, repeat oral dosing of GBT1118 at 200 mg/kg/day for 2 weeks in SCD mice achieved steady state concentrations of 802 ± 81 µM (mean ± SD; n=5), corresponding to a Hb occupancy of 44 ± 5%. Consequently, GBT1118 decreased the p50 (partial pressure of O2 at which Hb is 50% saturated) values of SCD mouse blood from 39 ± 0.8 mmHg (Vehicle-dosed) to 21 ± 1.6 mmHg (GBT1118-dosed). While we could not achieve the desired Hb occupancy (≥30%) with voxelotor in this model, the Hb occupancy and change in p50 achieved with GBT1118 afforded us the opportunity to ask whether significantly increasing Hb-O2 affinity affects brain O2 tension. Measurements of cortical O2 tension (pO2) showed no difference in pO2 values under normoxia (21% O2) (Figure A), and slightly higher pO2 values under hypoxia (10% O2) (Figure B) for GBT1118-dosed SCD mice compared with vehicle-dosed SCD mice. Collectively across all brain tissues, the GBT1118-induced increase in Hb-O2 affinity reduced tissue hypoxia in SCD mice under hypoxia as measured by pimonidazole staining (Figure C). Together, these results indicate that a pharmacological increase of Hb-O2 affinity does not decrease cortical tissue pO2 in SCD mice and may reduce brain hypoxia under hypoxic conditions. Figure Disclosures Dufu: Global Blood Therapeutics: Employment, Equity Ownership. Lucas:Global Blood Therapeutics: Research Funding. Muller:Global Blood Therapeutics: Research Funding. Williams:Global Blood Therapeutics: Research Funding. Zhang:Global Blood Therapeutics: Employment, Equity Ownership. Rademacher:Global Blood Therapeutics: Employment, Equity Ownership. Alt:Global Blood Therapeutics: Employment, Equity Ownership. Oksenberg:Global Blood Therapeutics: Employment, Equity Ownership. Cabrales:Global Blood Therapeutics: Research Funding.

PP-14, a Novel Structurally-Enhanced Antisickling Allosteric Hemoglobin Effector, Increases Oxygen Affinity and Disrupts Hemoglobin S Polymer Formation

We have previously designed and investigated novel allosteric effectors of hemoglobin (AEHs), as potential targeted treatment of sickle cell disease (SCD). In general, AEHs transiently covalently bind to hemoglobin (Hb), increase its affinity for O2, increasing the fraction of oxygenated sickle Hb (HbS), thus reducing HbS polymerization and countering red blood cell (RBC) sickling. In the current study, we designed a novel class of AEH molecules, incorporating a secondary mechanism of action (MOA), which is independent of Hb O2-affinity by interacting with the F-helix of deoxygenated HbS to directly destabilize its polymerization. Here, we report current results from our in-vitro and in-vivo studies with a representative AEH compound (PP-14). First, we assessed the anti-sickling properties in-vitro by incubating 0.5, 1, and 2 mM of PP-14 with whole blood suspensions from a subject with homozygous SCD (SS, hematocrit: 20%) under hypoxic conditions, with subsequent RBC sickling assessment by microscopy. Next, we subjected the samples to anoxia (100% N2 gas) to demonstrate the O2-affinity-independent antisickling mechanism. Subsequently, we tested residual samples for the degree of Hb modification (i.e., HbS-AEH adduct formation) and O2-affinity (p50) shifts. In a second experiment to further assess the secondary MOA, we subjected SS blood samples treated with various concentrations of PP-14 to hypoxia in the Hemox analyzer, which permitted us to obtain aliquot samples at defined pO2 values to establish pO2-dependent sickling. Additionally, we conducted in silico and in-vitro ADME studies to evaluate possible metabolic inhibition of a panel of CYP enzymes. Finally, we conducted a preliminary in-vivo PK/PD study in wild-type mice administered single doses of PP-14 via the oral (P.O.: 100-200 mg/kg) and intraperitoneal (I.P.: 75 mg/kg) routes. Serial blood samples were collected for up to 52 h after P.O., and up to 30 h after I.P. administration, and samples were assayed to quantify PP-14 concentrations. Residual blood samples were assayed for in-vivo Hb-AEH adduct formation, and the corresponding change in O2-affinity (Δp50, %). Our in-vitro studies demonstrated concentration-dependent inhibition of cell sickling of 25.5±11%, 44.4±3.8% and 90.8±1%, at 0.5, 1 and 2 mM of PP-14, respectively. HbS was modified correspondingly (38.9±9%, 55.7±4.9 %, and 92.4±9.8%), and was correlated linearly with the left-shift in OEC (Δp50 values of 11.3±5.1%, 29.0±13.2%, and 67.5±8.2%). Importantly, the antisickling effect was sustained under anoxic conditions (100% N2), strongly supporting the notion of a secondary, O2-affinity-independent MOA. Furthermore, we observed a dose-dependent delay in sickling, with initiation of sickling recorded at a pO2 level of 40 mmHg in absence of PP-14; and at 30 and 20 mmHg at 0.5, and 1 mM PP-14 concentrations, respectively. Complete inhibition of sickling was observed at 2 mM PP-14 through the lowest recorded pO2 level of 1.5 mmHg, a unique, effect not previously observed in any analogous AEH. In-vitro partitioning studies demonstrated that &amp;gt;90% of PP-14 partitioned into the RBC compartment when whole blood was incubated with 100-300 µM concentrations. Metabolic studies using pooled human liver microsomes (HLM) and isozyme-specific probe substrates suggested that up to 100 µM PP-14 did not inhibit CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 or CYP2B6. Wild-type mice after I.P. administration of PP-14 (75 mg/kg, n=5) showed peak concentrations in blood at 7 hrs (416.3±81.2 µM), with corresponding PD effects (Δp50 of 41.6±13.5%; modified Hb levels of 43.6±8.0%). Orally-treated mice had peak drug concentrations after 10-24 hrs, (~150 µM at 200 mg/kg, n= 2), with corresponding PD effects (Δp50 of 36.5±7.0%; modified Hb levels of 28.8±4.9%), which declined by 52 hrs. Overall, our data confirm that PP-14 is novel antisickling AEH with a secondary, O2-independent MOA in addition to the primary O2-dependent effect, as demonstrated by the inhibition of sickling under anoxic conditions. Additionally, PP-14 showed: excellent partitioning into the RBC compartment; acceptable in-silico ADME properties and in-vivo oral bioavailability; PD effects; and low liability for metabolic drug-drug interactions. Further studies to investigate formal detailed pharmacokinetic properties, and biological activity after single- or repeat-doses in a SCD mouse model are ongoing. Disclosures Safo: Sanofi: Consultancy, Research Funding; Virginia Commonwealth University: Patents &amp; Royalties. Pagare:Virginia Commonwealth University: Patents &amp; Royalties. Ghatge:Virginia Commonwealth University: Patents &amp; Royalties. Rivella:Meira GTx, Ionis Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Disc medicine, Protagonist, LIPC, Meira GTx: Consultancy. Hines:Functional Fluidics: Equity Ownership. Liu:Functional Fluidics: Employment. Zhang:Virginia Commonwealth University: Patents &amp; Royalties. Venitz:Virginia Commonwealth University: Patents &amp; Royalties. Abdulmalik:The Children's Hospital of Philadelphia: Patents &amp; Royalties: Provisional Patent.

Hypertension accelerates cerebral tissue PO2 disruption in Alzheimer’s disease

This study measured stimulus-evoked brain tissue oxygenation changes in a mouse model of Alzheimer disease (AD) and further explored the influence of exercise and angiotensin II-induced hypertension on these changes. in vivo two-photon phosphorescence lifetime microscopy was used to investigate local changes in brain tissue oxygenation following whisker stimulation. During rest periods, PO2 values close to the arteriolar wall were lower in the AD groups and the PO2 spatial decay as a function of distance to arteriole was increased by hypertension. During stimulation, tissue PO2 response had a similar spatial dependence across groups. Tissue PO2 response in post-stimulation period was larger in AD groups (e.g., AD6 and ADH6) than in the controls (WT6 and WTH6). After a 3-month voluntary exercise period, some of these changes were reversed in AD mice. This provides novel insight into tissue oxygen delivery and the impact of blood pressure control and exercise on brain tissue oxygenation in AD.

Effect of Pulmonary Rehabilitation on the Value of the Inspiratory Capacity-to-Total Lung Capacity (IC/TLC) Ratio to Determine Response to Pulmonary Rehabilitation in Patients with Chronic Obstructive Pulmonary Disease.

In patients with chronic obstructive pulmonary disease (COPD), the inspiratory capacity-to-total lung capacity (IC/TLC) ratio has been found to be correlated with mortality and a reduced exercise capacity. Pulmonary rehabilitation (PR) is known to improve the exercise capacity and respiratory functions of patients with COPD. Our study aims to examine the impact of PR on the IC/TLC ratio in patients with COPD. We included a total of 122 patients with COPD who received PR therapy twice a week over a period of 8 weeks in an outpatient clinic. Patients' mean age was 62.5 (±8.2), and 15 patients (12.3%) were female. Post-PR FEV1, TLCO, and pO2 values, and the 6mWD, dyspnea, and quality-of-life (QoL) scores indicated a statistically significant improvement (p<0.05 for all). Patients were grouped as follows: patients with IC/TLC >0.25 as Group 1 and IC/TLC ≤0.25 as Group 2. Both groups exhibited a significantly increased post-PR 6 mWT distance (375-420, 336-400 meters) with no difference between the groups. We observed a significantly increased FEV1% in both groups after the PR (p=0.007, 0.004). Again, QoL questionnaires and Modified Medical Research Council scores significantly improved for both groups (p<0.001). Although no post-PR IC/TLC improvement was detected in patients with good prognosis, we identified an IC/TLC improvement in the poor prognosis group (Group 2) (p=0.002). COPD patients with IC/TLC ≤0.25 benefit from the PR just as those COPD patients with IC/TLC >0.25.

The effect of hypoxia on hearing function

Background/aimThis study was conducted to determine the critical partial oxygen pressure (pO2) value that would impair hearing function by evaluating the effects of hypoxia on hearing function in subjects diagnosed with chronic obstructive pulmonary disease (CPOD).Materials and methodsThe study included 25 male and 5 female patients referred to our clinic who were diagnosed with COPD, according to spirometry and PaO2 values, and who did not show pathology upon autoscopic examination. The control group consisted of 14 female and 16 male patients who had no lung disease and were in the same age range as the COPD group.ResultsA statistically significant difference was found between the two groups for distortion-product otoacoustic emission (DPOAE) (P < 0.001). The COPD group was divided into two groups according to pO2 levels (pO2 ≤ 70 and pO2 > 70) in order to find a critical pO2 level which might cause significant change at a certain audiological extent.ConclusionHypoxia causes long-term decline in hearing thresholds, deterioration of DPOAE results, and prolongation of I–V interpeak latency in auditory brainstem response. However, the critical oxygen level that disrupts hearing function could not be determined.

Prognostic value of blood gas parameters and end-tidal carbon dioxide values in out-of-hospital cardiopulmonary arrest patients

Background/aimThis study aimed to evaluate the usefulness of blood gas and end-tidal carbon dioxide (EtCO2) measurements for predicting return of spontaneous circulation (ROSC) and for evaluating post-ROSC neurological survival.Materials and methodsThis was a prospective case control study utilizing Atatürk University’s database of adult nontraumatic patients (over 18 years old) with out-of-hospital cardiac arrest (OHCA) over the course of a year. The neurological status of the patients was evaluated after 1 h at ROSC and at hospital discharge, as defined by the cerebral performance category score. The blood gas parameters pH, PO2, PCO2, lactate, and BE were compared with EtCO2 from capnography and arteriol/alveolar carbon dioxide difference (AaDCO2) by using both blood gas and capnography upon admission to the emergency department and at ROSC.ResultsA total of 155 patients were included in the study to form the control group with ROSC. The PO2, PCO2, and AaDCO2 values showed a prognostic marker for the supply of ROSC (P < 0.05). The EtCO2, lactate, and BE values measured by the blood gas were found to be insignificant in the prediction of ROSC (P > 0.05). Conversely, AaDCO2 was found to be significant in ROSC estimation (P < 0.05), but not in neurological evaluation (P > 0.05).ConclusionBlood gas parameters and EtCO2 are sufficient in predicting ROSC. The value of AaDCO2 calculated using EtCO2 and PO2 may be used in predicting the prognosis of OHCA patients, but this value does not provide any conclusions concerning neurological survival.

Understanding the electrocatalytic activity of transition metal nanoparticles for solid oxide cell fuel electrodes

In this work, we utilized the concept of decoupling the electrocatalytic activity from the current conducting phase of solid oxide cell fuel electrodes to investigate the electrochemical performance of three different transition metals, namely Ni, Co, and Fe. It was found that the nickel and cobalt infiltrated cells had comparable performances in both 4% H2O/H2 and 50% H2O/H2. Furthermore, iron nanoparticles were found to be the better electrocatalyst at low pO2 values, however at higher pO2 values the iron infiltration became the inferior catalyst. Investigating the temperature dependence of the polarization resistance in terms of activation energy and pre-exponential factor showed interesting differences between the metal catalysts and a dependence on the gas atmosphere. The results were analyzed by developing a model based on the harmonic oscillator, the model allows for correlating changes in activation energy and pre-exponential factor with kinetic parameters of the electrode reaction. The model indicates that at higher pO2 values, iron nanoparticles experience a surface blockade, i.e. strong bonding of the reactants to the catalytic sites. For the nickel electrocatalyst, an increase in steam content according to the model leads to an increase in the turnover frequency, which is in good agreement with earlier reports in literature.

Structural Stabilization of Mullite Films Exposed to Oxygen Potential Gradients at High Temperatures

The oxygen shielding properties of polycrystalline Al4+2xSi2−2xO10−x (mullite) films applied as environmental barrier coatings (EBCs) on SiC fiber-reinforced SiC matrix composites (SiC/SiC) are determined by the grain boundary (GB) diffusion of oxide ions in the films, from the higher oxygen partial pressure (PO₂) surface to the lower PO₂ surface, with simultaneous GB diffusion of Al ions in the opposite direction. Herein, strategies to improve the oxygen shielding and phase stability of these films when applied to SiC/SiC substrates through bond coats are proposed, based on oxygen permeation data for mullite at high temperatures. The validity of these strategies is verified using experimental trials at 1673 K with bilayer specimens consisting of mullite films and bond coat substrates, serving as model EBCs. The data show that employing a bond coat made of β’-SiAlON rather than Si provides a source of Al for the overlying mullite film that greatly improves the phase stability of the film in the vicinity of the junction interface. Because the minimum equilibrium PO₂ values required to form SiO2 due to oxidation of the β’-SiAlON on a thermodynamic basis are significantly larger than those for oxidation of Si, the inward GB diffusion of oxide ions is effectively retarded, resulting in excellent oxygen shielding characteristics.

Central Part of the Auditory Analyser in Children with Type 1 Diabetes

Aim. The present article assesses the state of the central part of the auditory analyser in children with type 1 diabetes.Materials and methods. The study included 71 children with type 1 diabetes mellitus who were treated at the Endocrinology Department of the Children’s Territorial Clinical Hospital from September 2017 to February 2018. The children’s age ranged from 7 to 15 years (8±2.6). Group A comprised 34 children who were fi rst diagnosed with type 1 diabetes, with the duration of clinical manifestations not exceeding 3 months; whereas group B included 37 children who had been suffering from type 1 diabetes for 1–5 years. The control group was represented by 30 children of the same age group without a somatic pathology (group K). The functional state of the central part of the auditory analyser was assessed when studying brainstem evoked potentials of short, middle and long latency.Results. In the course of studying short-latency brainstem evoked potentials at a broadband-click stimulus frequency of 10 Hz and an intensity of 70 dB, the latent periods of peaks and peak-topeak intervals were analysed in groups A, B and K. Statistically signifi cant differences were observed for I and V latent periods of peaks, as well as for the I–V inter-peak interval. At a click stimulus intensity of 70 dB, peaks and peak-to-peak intervals of middle-latency brainstem evoked potentials revealed differences in the values of NO, PO, Na, Pa and NO–PO between the groups of patients with type 1 diabetes and the control group. Greater statistical differences, as compared to the control group, were observed in the latent periods of long-latency brainstem evoked potentials for interval P1 in group A and intervals P2 and N2 in group B (unfavourable course) during 100 dB stimulation at a repetition frequency of 1 Hz in a time window of 50 ms. The presence of differences between groups A and B in the parameters of peak P2 (p ≤ 0.07), as well as peak intervals P2–N2, N1–N2, N1–P1, N2–P2 and N1–P2, may indicate signifi cant differences in the centres of the auditory analyser (p ≤ 0.1). At the same time, the maximum activity of the studied parameters was found in the group of patients with newly diagnosed type 1 diabetes.Conclusions. The study of different types of brainstem evoked potentials, characterising the central parts of the auditory analyser, in children with type 1 diabetes allowed the authors to register functional disorders both in the brainstem segment and in the cortical structures. This fact indirectly indicates initial manifestations of diabetic neuropathy in the studied category of patients and can be used in the future for diagnosing CNS disorders.

Comparison of Anesthesia Techniques Used in Cesarean Deliveries on the Neonate - Anesthesia Techniques and Neonate?

Background: Though there are many studies on the effects of anesthesia methods used for cesarean section on the newborn, research on this topic still continues. In our prospective observational study, we investigated the effects of different anesthesia techniques used in routine cesarean deliveries on early neonatal outcomes in our hospital. Methods: This prospective, observational, randomized study included a total of 222 ASA II risk group pregnant women undergoing elective cesarean section at term (38-41 weeks’ gestation) without fetal distress. The women were randomized into three groups. In the general anesthesia with propofol group (Group P, n = 74), anesthesia was induced with 2 mg∙kg-1 propofol and 0.6-0.9 mg∙kg-1 rocuronium. In the general anesthesia with thiopental sodium group (Group T, n = 74), anesthesia was induced with 5 mg∙kg-1 thiopental sodium and 0.6-0.9 mg∙kg-1 rocuronium. Women in the spinal anesthesia group (Group SA, n = 74) were administered 0.5% (10 mg) hypertonic bupivacaine and 10 mcg fentanyl. Results: There were no significant differences between Group SA, Group P, and Group T in terms of delivery time; neonatal 1- and 5-min Apgar scores; neonatal jaundice rates; neonatal systolic, diastolic, or mean blood pressure or peak heart rate; neonatal intensive care requirement; pH, PCO2, PO2 values in cord blood gas; or neonatal glucose and lactate values. The rate of ephedrine use was significantly higher in Group SA than in Group P and Group T. Maternal satisfaction score was higher in Group SA at postoperative 4 hours and in Group P at 24 hours. The number of newborns taken into intensive care unit in Group T was significantly higher in the 1st hour, 4th hour, 5th hour and total. Respectively p value (0.006, 0,048, 0,048, and 0,005). Pain on injection was present in 55% of patients (n = 81), mild in 36% (n = 54), and severe in 18% (n = 27). Myoclonies occurred in 4% of patients (n = 7) and local rash in 6% of patients (n = 10). Differences between formulations did not reach statistical significance. Conclusion: None of the three anesthesia methods showed superiority after elective cesarean delivery. However, spinal anesthesia and general anesthesia with propofol are more appropriate for pregnant women in terms of effects on the neonate.