pO2 Levels Research Articles

Oxygen generating nanoparticles for improved photodynamic therapy of hypoxic tumours

Photodynamic therapy (PDT) is a clinically approved anti-cancer treatment that involves the activation of an otherwise inactive sensitiser drug with light, which in the presence of molecular oxygen, generates cytotoxic reactive oxygen species (ROS). As oxygen is a key requirement for the generation of ROS in PDT and given the fact that hypoxia is a characteristic of most solid cancerous tumours, treating hypoxic tumours using PDT can be a challenge. In this manuscript, we have prepared a CaO2 nanoparticle (NP) formulation coated with a pH-sensitive polymer to enable the controlled generation of molecular oxygen as a function of pH. The polymer coat was designed to protect the particles from decomposition while in circulation but enable their activation at lower pH values in hypoxic regions of solid tumours. The oxygen generating capability of the polymer coated NPs was demonstrated in aqueous solution with minimal oxygen produced at pH7.4, whereas it increased significantly when the pH was reduced to 6.2. The polymer coated CaO2 NPs were also observed to significantly increase tumour pO2 levels (p<0.05) in mice bearing ectopic human xenograft MIA PaCa-2 pancreatic tumours with an average increase in tumour pO2 of 6.5mmHg in the period 10–30min following administration. A statistically significant improvement in PDT mediated efficacy (p<0.001) was also observed when the particles were administered to mice bearing the same tumours 20min prior to PDT treatment. These results suggest that the polymer coated CaO2 NP formulation offers significant potential as an in situ method for oxygen generation to enhance the efficacy of treatments that depend on the presence of oxygen to elicit a cytotoxic effect.

Perfluorocarbon emulsions radiosensitise brain tumors in carbogen breathing mice with orthotopic GL261 gliomas.

BackgroundTumour hypoxia limits the effectiveness of radiation therapy. Delivering normobaric or hyperbaric oxygen therapy elevates pO2 in both tumour and normal brain tissue. However, pO2 levels return to baseline within 15 minutes of stopping therapy.AimTo investigate the effect of perfluorocarbon (PFC) emulsions on hypoxia in subcutaneous and intracranial mouse gliomas and their radiosensitising effect in orthotopic gliomas in mice breathing carbogen (95%O2 and 5%CO2).ResultsPFC emulsions completely abrogated hypoxia in both subcutaneous and intracranial GL261 models and conferred a significant survival advantage orthotopically (Mantel Cox: p = 0.048) in carbogen breathing mice injected intravenously (IV) with PFC emulsions before radiation versus mice receiving radiation alone. Carbogen alone decreased hypoxia levels substantially and conferred a smaller but not statistically significant survival advantage over and above radiation alone.ConclusionIV injections of PFC emulsions followed by 1h carbogen breathing, radiosensitises GL261 intracranial tumors.

Hyperoxia does not directly affect vascular tone in isolated arteries from mice.

Hospitalized patients often receive oxygen supplementation, which can lead to a supraphysiological oxygen tension (hyperoxia). Hyperoxia can have hemodynamic effects, including an increase in systemic vascular resistance. This increase suggests hyperoxia-induced vasoconstriction, yet reported direct effects of hyperoxia on vessel tone have been inconsistent. Furthermore, hyperoxia-induced changes in vessel diameter have not been studied in mice, currently the most used mammal model of disease. In this study we set out to develop a pressure-myograph model using isolated vessels from mice for investigation of pathways involved in hyperoxic vasoconstriction. Isolated conduit and resistance arteries (femoral artery and gracilis arteriole, respectively) from C57BL/6 mice were exposed to normoxia (PO2 of 80 mmHg) and three levels of hyperoxia (PO2 of 215, 375 and 665 mmHg) in a no-flow pressure myograph setup. Under the different PO2 levels, dose-response agonist induced endothelium-dependent vasodilation (acetylcholine, arachidonic acid), endothelium-independent vasodilation (s-nitroprusside), as well as vasoconstriction (norepinephrine, prostaglandin F2α) were examined. The investigated arteries did not respond to oxygen by a change in vascular tone. In the dose-response studies, maximal responses and EC50 values to any of the aforementioned agonists were not affected by hyperoxia either. We conclude that arteries and arterioles from healthy mice are not intrinsically sensitive to hyperoxic conditions. The present ex-vivo model is therefore not suitable for further research into mechanisms of hyperoxic vasoconstriction.

¿Los gases venosos periféricos pueden reemplazar a los gases arteriales en la evaluación de pacientes críticos?

Arterial blood gas analysis is a routine study for ill patients, and provides a lot of information when it comes to making decisions. For a long time arterial blood gases have been used as reference for these decisions, which are often difficult. Arterial blood gases are often painful and technically demanding, often resulting in damage to the arterial wall, especially when repeated measurements are required. Pulse oximetry is a non-invasive alternative to arterial blood gases, but does not allow assessment of partial pressure of carbon dioxide (pCO2). Taking into account routine sampling in hospitals, and that it is often easier to take a sample of venous blood in which measurements can be made of the pH, pCO2, pO2, and bicarbonate and lactate levels, a review is presented of different studies that compare arterial and venous gases in multiple scenarios and determine the importance of these, as well as if peripheral venous gases could at some point replace the arterial gases, and showing that these are only comparable in the estimates of pH. For the time being, and until larger studies show otherwise, venous gases cannot replace arterial gases in acid-base and oxygenation analysis in critically ill patients.

Observational Study of Neural Respiratory Drive During Sleep at High Altitude.

Ventilation at altitude changes due to altered levels of pO2, pCO2 and the effect on blood pH. Nocturnal ventilation is particularly exposed to these changes. We hypothesized that an increasing neural respiratory drive (NRD) is associated with the severity of sleep-disordered breathing at altitude. Mountaineers were studied at sea level (London, United Kingdom), and at altitude at the Aconcagua (Andes, Argentina). NRD was measured as electromyogram of the diaphragm (EMGdi) overnight by a transesophageal multi-electrode catheter; results were reported for sea level, 3,380 m, 4,370 m, and 5,570 m. Four healthy subjects (3 men, age 31(3)years, body mass index 23.6(0.9)kg/m2, neck circumference 37.0(2.7)cm, forced expiratory volume in 1 second 111.8(5.1)%predicted, and forced vital capacity 115.5(6.3)%predicted) were studied. No subject had significant sleep abnormalities at sea level. Time to ascent to 3,380 m was 1 day, to 4,370 m was 5 days, and the total nights at altitude were 21 days. The oxygen desaturation index (4% oxygen desaturation index [ODI] 0.8(0.4), 22.0 (7.2), 61.4 (26.9), 144.9/hour, respectively) and the EMGdi (5.2 (1.9), 12.8 (5.1), 14.1 (3.4), 18.5%, respectively) increased with the development of periodic breathing at altitude, whereas the average SpO2 declined (97.5 (1.3), 84.8 (0.5), 81.0 (4.1), 68.5%, respectively). The average EMGdi correlated well with the 4%ODI (r = 0.968, p = 0.032). NRD sleep increases at altitude in relation to the severity of periodic breathing.

PHOSPHORUS FORMS AND ADSORPTION IN A TYPIC QUARTZIPSAMMENT CULTIVATED WITH SUGARCANE HARVESTED WITHOUT BURNING

ABSTRACT The objective of this study was to evaluate the adsorption of phosphorus (P) and changes in the concentrations of organic and inorganic forms of P in a Neossolo Quartzarênico (Typic Quartzipsamment) after 9 years of successive cultivation with sugar cane without burning to harvest. Therefore, two areas, one in which cane sugar was planted and a native forest reference area, located in the municipality of Paraipaba-CE, were selected. In each area, samples were collected at depths of 0−0.025, 0.025−0.05, 0.05−0.10, 0.10−0.20, and 0.20−0.30 m, and the levels of organic (Po) and inorganic (Pi) phosphorus obtained by sequential extraction, the remaining phosphorus, and the maximum adsorption capacity of phosphorus by the soil were determined. In general, the permanence of straw on the soil surface under sugarcane cultivation promoted the maintenance of Po levels in the surface layers of the profile. The Po accumulated predominantly in the Po fraction extracted with sodium bicarbonate in both areas. Regarding the Pi content, changes were more evident during cultivation due to the effect of successive phosphate fertilizer applications. The fraction extracted with 0.1 mol L -1 sodium hydroxide was the most representative, with the highest levels of P uptake. P adsorption was influenced by the initial content of the nutrient in the soil and no relationship between P adsorption and organic matter content was observed. The highest level of adsorption was observed in the bottom layer of the forest area (133.3 mg kg -1) and the lowest level of adsorption was observed on the surface layer of the area under sugarcane cultivation (59.5 kg mg-1).

Changes in Soil Phosphorus Fractions Resulting from Crop Residue Removal and Phosphorus Fertilizer

ABSTRACTIt is crucial to know how management factors influence soil test phosphorus (P) since non-point P sources for surface waters are becoming recognized as a problem throughout the USA. Phosphorus fertilizer and crop residue can impact the cycling of P in soils. An eight-year crop residue removal and P fertilization (0, 7.3, 14.7 and 29.4 kg P/ha) as triple superphosphate (TSP) experiment were conducted to determine the effect of P applications on soil P fractions. Significant differences in Bray-l extractable P were observed after only one year of P applications. Extractable P at the highest P rate was significantly higher than all the other rates. For each 5.6 kg P/ha added or removed, Bray-l P changed by 1 mg/kg. Fertilizer P applications did not significantly change the organic P (Po) levels, microbial P (Pm) or soil pH, whereas residue treatments had effects on them except for soil pH. Residue-retained plots had significantly higher Pm in the last two years of study, and Po in the 8th year, compared with residue-removed plots.

Iron regulatory protein 2 in ovarian endometrial cysts

Ovarian endometrial cysts cause some kinds of ovarian cancer, and iron is considered as one factor of carcinogenesis. In contrast, hypoxia is associated with progression, angiogenesis, metastasis, and resistance to therapy in cancer. We investigated hypoxia-induced perturbation of iron homeostasis in terms of labile iron, iron deposition, and iron regulatory protein (IRP) in ovarian endometrial cysts. Iron deposition, expression of IRPs, and a protein marker of hypoxia in human ovarian endometrial cysts were analyzed histologically. The concentration of free iron and the pO2 level of the cyst fluid of human ovarian cysts (n = 9) were measured. The expression of IRP2 under hypoxia was investigated in vitro by using Ishikawa cells as a model of endometrial cells. Iron deposition and the expression of IRP2 and Carbonic anhydrase 9 (CA9) were strong in endometrial stromal cells in the human ovarian endometrial cysts. The average concentration of free iron in the cyst fluid was 8.1 ± 2.9 mg/L, and the pO2 was 22.4 ± 5.2 mmHg. A cell-based study using Ishikawa cells revealed that IRP2 expression was decreased by an overload of Fe(II) under normoxia but remained unchanged under hypoxia even in the presence of excess Fe(II). An increase in the expression of IRP2 caused upregulation of intracellular iron as a result of the response to iron deficiency, whereas the protein was degraded under iron-rich conditions. We found that iron-rich regions existed in ovarian endometrial cysts concomitantly with the high level of IRP2 expression, which should generally be decomposed upon an overload of iron. We revealed that an insufficient level of oxygen in the cysts is the main factor for the unusual stabilization of IRP2 against iron-mediated degradation, which provides aberrant uptake of iron in ovarian endometrial stromal cells and can potentially lead to carcinogenesis.

Transport of juvenile dusky grouper Epinephelus marginatus under different packing densities: Metabolic and haematological responses

The aim of this study was to investigate a suitable packing density for the transport of juvenile dusky grouper, Epinephelus marginatus, based on the evaluation of stress responses in blood. After acclimation, fish were placed in plastic bags and transported for 8 hr on paved road at densities of 28, 45 and 64 g/L. Water quality was monitored before and after transport. Blood was collected before, upon arrival (0 hr), after 2 and 24 hr of transport. Plasma cortisol, blood glucose, partial pressures of O2 (pO2) and CO2 (pCO2), blood pH and HCO3− were evaluated. Blood smears were prepared for the verification of leucocyte profile and neutrophils:lymphocyte ratio (N:L). Blood pCO2, pH and HCO3− increased significantly after transport for all treatments compared with pre-transport. Glucose levels increased at the higher density whereas no effects were observed on plasma cortisol and pO2 levels. Upon arrival, all treatments showed lymphopenia and neutrophilia which increased N:L ratio. Although lymphopenia was observed in higher densities until 2 hr after transport, haematological parameters were fully restored within 24 hr post transport. Furthermore, no mortalities were observed throughout the experimental period. Based on the transient physiological changes observed in this study, juvenile dusky grouper can be safely transported in plastic bags for 8 hr at a density of up to 64 g/L.

The relative influence of hematocrit and red blood cell velocity on oxygen transport from capillaries to tissue.

Oxygen transport to parenchymal cells occurs mainly at the microvascular level and depends on convective RBC flux, which is proportional in an individual capillary to the product of capillary hematocrit and RBC velocity. This study investigates the relative influence of these two factors on tissue PO2 . A simple analytical model is used to quantify the respective influences of hematocrit, RBC velocity, and RBC flow on tissue oxygenation around capillaries. Predicted tissue PO2 levels are compared with a detailed computational model. Hematocrit is shown to have a larger influence on tissue PO2 than RBC velocity. The effect of RBC velocity increases with distance from the arterioles. Good agreement between analytical and numerical results is obtained, and the discrepancies are explained. Significant dependence of MTCs on RBC velocity at low hematocrit is demonstrated. For a given RBC flux in a capillary, the PO2 in the surrounding tissue increases with increasing hematocrit, as a consequence of decreasing IVR to diffusive oxygen transport from RBCs to tissue. These results contribute to understanding the effects of blood flow changes on oxygen transport, such as those that occur in functional hyperemia in the brain.

Assessment of intratumor hypoxia by integrated 18F-FDG PET / perfusion CT in a liver tumor model.

ObjectivesHypoxia in solid tumors occurs when metabolic demands in tumor cells surpass the delivery of oxygenated blood. We hypothesize that the 18F-fluorodeoxyglucose (18F-FDG) metabolism and tumor blood flow mismatch would correlate with tumor hypoxia.MethodsLiver perfusion computed tomography (CT) and 18F-FDG positron emission tomography (PET) imaging were performed in twelve rabbit livers implanted with VX2 carcinoma. Under CT guidance, a fiber optic probe was inserted into the tumor to measure the partial pressure of oxygen (pO2). Tumor blood flow (BF) and standardized uptake value (SUV) were measured to calculate flow-metabolism ratio (FMR). Tumor hypoxia was further identified using pimonidazole immunohistochemical staining. Pearson correlation analysis was performed to determine the correlation between the imaging parameters and pO2 and pimonidazole staining.ResultsWeak correlations were found between blood volume (BV) and pO2 level (r = 0.425, P = 0.004), SUV and pO2 (r = -0.394, P = 0.007), FMR and pimonidazole staining score (r = -0.388, P = 0.031). However, there was stronger correlation between tumor FMR and pO2 level (r = 0.557, P < 0.001).ConclusionsFMR correlated with tumor oxygenation and pimonidazole staining suggesting it may be a potential hypoxic imaging marker in liver tumor.

Polymorphism 4G/5G of the plasminogen activator inhibitor 1 gene as a risk factor for the development of allergic rhinitis symptoms in patients with asthma.

Plasminogen activator inhibitor-1 (PAI-1) is a glycoprotein which has a role in tissue remodelling after inflammatory processes. The objective is to investigate the frequency of PAI-1 gene polymorphism (4G/5G) in patients with a lung ventilation dysfunction in asthma and allergic rhinitis. Genomic DNA was isolated and genotypes of polymorphism of PAI-1 4G/5G and ABO were determined using the methods of RT-PCR and PCR-SSP. Study group includes 145 adult patients diagnosed with chronic asthma, with all clinically relevant parameters and the laboratory markers of pO2, IgE and eosinophils in sputum and nasal swab. In the processing of data, appropriate statistical tests (Kolmogorov-Smirnov test, median, interquartile ranges, χ 2 and Mann-Whitney U tests) were used. Patients with symptoms of allergic rhinitis were significantly younger and had an almost four time higher levels of IgE (P = 0.001), higher pO2 (P = 0.002) and PEF (P = 0.036), compared to those who do not have these symptoms. Genotype PAI 4G/4G is significantly more common in patients with allergic rhinitis (28.1% vs. 16.1%; P = 0.017) compared to the genotype 5G/5G. Carriers of the genotype 4G/5G also have a borderline statistical significance. There were no statistically significant difference in the incidence of allergic rhinitis in the carriers of any ABO genotypes. The frequency of PAI genotype 4G/4G is significantly more common in patients with allergic rhinitis. The results suggest that the carriers of at least one 4G allele are at a higher risk for developing symptoms of allergic rhinitis in asthma.

Impaired Cerebral Oxygenation, But Preserved Cerebrovascular Reactivity, In An Animal Model of Hepatic Encephalopathy

Introduction: We have recently obtained evidence of energy deficiency, in the form of impaired lactate release, in the brains of cirrhotic animals with hepatic encephalopathy (HE). Previous reports of cerebral hypoperfusion in patients with HE indicated that cerebral oxygen supply could also be compromised [[1]Philips B.J. Armstrong I.R. Pollock A. Lee A. Cerebral blood flow and metabolism in patients with chronic liver disease undergoing orthotopic liver transplantation.Hepatology. 1998; 27: 369-376Crossref PubMed Scopus (43) Google Scholar]. Decreased lactate and reduced oxygen supply may lead to the CNS energy deficiency and have important neurological consequences, particularly in patients with advanced cirrhosis. Objectives: In this study we assessed cerebral tissue oxygen tension and CO2 cerebrovascular reactivity in an animal model of HE. Methods: HE was induced by bile duct ligation (BDL) and after 4 weeks rats were anesthetized with α-chloralose (100 mg kg−1), instrumented for arterial blood pressure recording and artificially ventilated. Blood gas tensions and pH were monitored and maintained within the physiological ranges in both BDL (n = 10) and sham operated (n = 6) rats. Cerebral tissue PO2 was monitored by fluorescence method (Oxylite™, Oxford Optronics). After a small craniotomy, optical sensors were placed in the somatosensory cortex and sealed. PO2 at baseline and in response to systemic hypercapnia (10% CO2; 5 min) was recorded. Results: At the similar levels of blood PO2 (120 ± 4 vs. 113 ± 4 mmHg) and PCO2 (34 ± 1 vs. 35 ± 2 mmHg), BDL rats had a significantly lower brain PO2 (15.3 ± 2 mmHg; n = 10) compared to the shams (26 ± 2 mmHg; n = 6; P = 0.001). Systemic hypercapnia resulted in similar increases in cerebral PO2 in BDL and sham animals (ΔPO2 21 ± 2 vs. 24 ± 2 mmHg; P = 0.6). However, the peak increases in parenchymal PO2 was significantly smaller in BDL rats when compared to sham-operated animals; 36 ± 4 ± 2 vs. 50 ± 3 mmHg (P = 0.03). Additionally, under anesthesia, the mean systemic arterial blood pressure was found to be significantly lower in BDL animals (60 ± 3 vs. 84 ± 8 mmHg; P = 0.04). Conclusion: In the BDL model of HE, cerebral tissue oxygen tension is compromised but cerebrovascular reactivity to CO2 appears to be preserved. The cause of the low basal PO2 remains unknown however; low systemic arterial blood pressure could be a contributing factor considering the maximum increase in PO2 induced by hypercapnia was lower in BDL animals indicating decreased brain perfusion. The authors have none to declare.

Mineral chemistry and phase equilibrium constraints on the origin of accretions formed during copper flash smelting

This paper delves into the constraints on the nature, origin and thermal evolution of the accretions formed in the uptake shaft of the flash smelting furnace operated by Atlantic Copper in Huelva, Spain, outlining recommended practices for preventing accretion buildup. The accretions were investigated using quantitative electron probe microanalysis, X-ray diffraction and digital imaging techniques, and the experimental data on mineral composition, crystal chemistry and textural relationships were interpreted in terms of thermodynamic phase equilibrium in the SiO2-Fe-O-S system. The results suggest that two distinct types of accretions were formed by the fractional crystallization of two coexisting immiscible melts, under changing conditions of oxygen partial pressure (pO2). The type I accretion of magnetite + delafossite ± cuprite ± tridymite ± metallic copper crystallized from a fractionating copper-rich melt at pO2 above about 10−5 atm, while the type II accretion of magnetite + fayalite + metallic copper + chalcocite derived from a melt with lower copper concentration when pO2 levels dropped below that critical level. Phase compositions and textures were consistent with a cooling history of both compositionally contrasting liquids from about 1,250 °C, the liquidus temperature of magnetite, to eutectic or near-eutectic temperatures of around 1,100 °C. The maintenance of appropriate temperatures — above the liquidus temperature of magnetite — and oxygen partial pressure levels may be critical for the prevention of accretion buildup.

In vivo electron paramagnetic resonance oximetry and applications in the brain.

Molecular oxygen (O2) is essential to brain function and mechanisms necessary to regulate variations in delivery or utilization of O2 are crucial to support normal brain homeostasis, physiology and energy metabolism. Any imbalance in cerebral tissue partial pressure of O2 (pO2) levels may lead to pathophysiological complications including increased reactive O2 species generation leading to oxidative stress when tissue O2 level is too high or too low. Accordingly, the need for oximetry methods, which assess cerebral pO2 in vivo and in real time, is imperative to understand the role of O2 in various metabolic and disease states, including the effects of treatment and therapy options. In this review, we provide a brief overview of the common in vivo oximetry methodologies for measuring cerebral pO2. We discuss the advantages and limitations of oximetry methodologies to measure cerebral pO2 in vivo followed by a more in-depth review of electron paramagnetic resonance oximetry spectroscopy and imaging using several examples of current electron paramagnetic resonance oximetry applications in the brain.

Influence of power output on pedalling biomechanical parameters in cyclists of different competitive levels

Introduction Cycling performance depends on several physiological and biomechanical parameters (Faria et al. 2005). The influence of biomechanical factors such as pedalling technique is still an issue of debate (Leirdal and Ettema 2011). Several studies demonstrated that pedal force effectiveness (FE, %, ratio of the force perpendicular to the crank and the total force applied to the pedal) has also been used as a gold standard measure of pedalling technique in cycling. However, FE depends on several constraints such as power output (PO, W), pedalling cadence, body position, fatigue, and cycling experience (Bini et al. 2013). Studies showed that large increase in PO (i.e. from 60% to 98% of the maximal aerobic power [MAP]) led to higher FE. Additionally, a recent study showed that professional cyclists have better pedalling technique than elite or club cyclists (Garcia-Lopez et al. 2016). The purpose of this study was to assess the influence of PO on pedalling technique in cyclists of different competitive levels using FE as a performance clue.  Methods 37 male road cyclists of different competitive levels (elite [19] and professional [18]) performed all testing sessions on a Bikefitting ergometer (Shimano, Pedal Analyzer, Dynamics Lab, Sittard, Netherland) that has been used to assess FE in seated position. Firstly, the personal bike position of each cyclist was reported on the ergometer. Then, the cyclists were required to perform exercises at four level of PO (55, 70, 85 and 100% of MAP). In order to keep an individual combination between muscular force and pedalling cadence, the cyclists were asked to keep their preferred pedalling cadence during each level of PO. The main parameter measured was FE whereas the balance between propulsive and resistive forces (%) was also measured as a secondary parameter. A two-way ANOVA was used to analyse the influence of both the PO and the competitive level on FE.  Results The figure 1 shows an increase in FE with PO (+26.4% from 55 to 100% of MAP, p < 0.001). Even if the competitive level did not influence FE, the increase of FE according to PO was higher (+36.1%) in professional cyclists than elite cyclists (+19.1%). Additionally, the coefficient of variation (CV, %) decreased with PO (CV55% = 16.2 %, CV70% = 15.0 %, CV85% =  12.8 % and CV100% = 11.0%). For all PO and competitive levels, FE was correlated with both PO (r = 0.47, p < 0.001) and the balance between propulsive and resistive forces (r = 0.82, p  < 0.001). Finally, the resistive forces were significantly (p < 0.001) decreased from 15.8 to 5% between 55 and 100% of MAP during the upstroke.  Conclusions The main findings of this study show that FE was influenced by the level of PO and was independent of the competitive level. Yet, professional cyclists increased faster FE with the level of PO suggesting that their pedalling technique was further improved in high levels of PO as compared with elite cyclists. Previous studies showed that an increase in PO induced an increase in FE (Zameziati et al. 2006). In this study, for a given PO, the increase in FE was due to a lower resistive force. Concerning the effect of competitive level, previous studies have shown no difference in FE between cyclists of different competitive levels (Sanderson et al. 2000) whereas another study (Garcia-Lopez et al. 2016) demonstrated that professional cyclists had better pedalling technique than elite cyclists. Finally, it appears that with the increase of PO, the professional cyclists improve their pedalling efficiency both by increasing FE and decreasing the resistive force during the upstroke of the pedalling cycle.

Comparison of pressure vs. volume controlled ventilation on oxygenation parameters of obese patients undergoing laparoscopic cholecystectomy.

Background & Objective:There is no special guideline for the best ventilation mode during laparoscopic anesthesia in obese patients and there are too many studies with different controversial points. The aim of this study was to compare the effect of pressure controlled ventilation (PCV) vs. volume controlled ventilation (VCV) on respiratory and oxygenation parameters in patients undergoing laparoscopic cholecystectomy.Methods:Seventy patients with 30 <BMI<40 and ASA physical status I-II were studied in this randomized prospective trial. Anesthesia was started with VCV and after creation of pneumoperitoneum; the patients were randomized into PCV or VCV groups. Ventilation parameters were adjusted to a CO2 target of 35-40 mmHg. Hemodynamic and oxygenation parameters and respiratory parameters like plateau, mean airway and peak pressure were recorded for all patients during the study.Results:Patients in VCV group needed higher tidal volume and respiratory rate to maintain target CO2 in 35 and 55 minutes after the study. Plateau pressure and mean airway pressure in two groups didn’t have significant difference between two groups but peak airway pressure in 35 and 55 minutes after pneumoperitoneum was significantly higher in VCV group than PCV group. There were no significant differences between two groups regarding PO2, PCO2 and pH, except 35 and 55 minutes after pneumoperitoneum. In mentioned times, patients in PCV group had significantly higher PO2 levels compared to VCV group.Conclusion:Despite some beneficial effects regarding plateau, mean airway pressure and oxygenation parameters with PCV, there was no significant clinical difference between PCV and VCV in obese patients undergoing laparoscopic cholecystectomy.

Umbilical cord blood leptin concentration - What does it imply?

Objective: The significance of the placental or umbilical cord leptin levels remains unresolved in spite of their well-documented function. In the current study we investigated, whether, leptin concentration that mirrors the fetal health is influenced by type of birth, placental weight, cord length, sex, weight, pO2 and pH parameters. Methods: Umbilical cord blood samples were collected post placental delivery (n=40) from both normal and caesarian deliveries with all demographical information. Leptin concentration was determined form cord blood plasma, while fresh cord blood was used for blood gas analysis. Results: The average leptin concentrations of male and female fetal umbilical cord were 16.6 ± 1.6 and 18.2 ± 0.6 ng/ml respectively. The maximum threshold of the umbilical vein leptin concentrations were 15.3 ± 0.6 and 18.3 ± 1.2 ng/ml in male and females respectively. There was a direct relationship observed with the birthweight and leptin concentration. The mean pH 7.117 ± 0.02 and pO2 19.74 ± 2.01 mmHg did not significantly correlate with leptin levels. Discussion: Leptin concertation were significantly high in normal delivery than caesarian section. Placental weight or umbilical cord length did not affect the leptin concentration. We did not observe any significant alteration in pH or pO2 levels influencing leptin. However, the most remarkable correlation was leptin with birth weight, which explains the best utilization of the maternal fuel resources in the development of the fetus. We did observe a level in female babies. Conclusion: Overall, the placental leptin concentration mirrors the health status of the fetus and weight metabolism.

210Po in Human Saliva of Smokeless Tobacco Users.

The occurrence and mobility of Po in oral smokeless tobacco products (STPs) were determined because its effects on human health must be taken into account. This research was subdivided into two parts: determination by alpha spectrometry of the Po activity concentration in 16 oral smokeless tobacco products of different brands purchased in local specialty stores in Europe and evaluation of its percent extraction into an artificial salivary gland during sucking or chewing operations. Polonium-210 was detected in all samples, and its concentrations ranged from 3.46 to 14.8 Bq kg (mean value of 7.45 ± 3.82 Bq kg). The highest concentration was found in chewing tobacco. The samples showed no significant difference in the content of Po level. The data obtained in this study show that the polonium, although poorly extracted (12.8 ± 8.96%) by artificial saliva, is not totally retained within the smokeless tobacco products, with a consequent potential health hazard associated with oral use of these products.

P2.04-027 Targeting Adenosine A2B Receptor for Modulation of Tumor Microenvironment, Primary Tumor Growth, and Lung Metastasis: Topic: Esophageal Cancer and Other Malignancies

Our work addresses two poorly understood areas of tumor metastases; the first is how tumor-conditioned immune cells initiate and drive premetastatic niche evolution and secondary tumor establishment and secondly, how the tumor microenvironment (TME) conditions shape the tumor immune response and function. We have developed a model that is fully capable of addressing these biological questions through in vivo EPR monitoring of the primary TME that allows simultaneous measurements of tumor pO2, pH, and inorganic phosphate (Pi) levels, which are parameters implicated in tumor metastasis and demonstrates how the TME contributes to metastasis. In combination, we employ an in vivo immune/tumor cell imaging platform in which mice are fitted with cutaneous window chambers containing syngeneic lung tissue transplant to create a lung metastatic site in which differentially-labeled tumor and immune subsets will be imaged via multiphoton microscopy. Our EPR methodology accurately monitors TME changes that occur with tumor growth as well as their modulation by pharmacological inhibition of the A2B adenosine receptor, giving reason to the use of specific A2B receptor inhibitors as anti-tumor and anti-metastatic therapeutics. A2B inhibition prevented the accumulation of Pi in the tumor interstitial space for every tumor model tested, which includes lung adenocarcinoma, breast adenocarcinoma, colon carcinoma, and melanoma. The exact role this plays in tumor initiation and progression is not completely elucidated but correlates with the reduction of tumor lung metastases and tumor growth. Secondly, our window chamber model enables spatiotemporal analysis of pre-metastatic niche enrichment, individual tumor cell recruitment, and subsequent secondary tumor growth with specific focus on metastatic lung disease. To our knowledge, no model exists capable of unifying these aspects of tumor biology and immunity. The project will lead to understanding a key process of metastasis and thus allow targeted immunotherapies to block metastasis and thus eliminate, or greatly reduce, the lethal aspect of cancer. Future work will also examine the potential anti-tumor therapeutic strategy of using specific A2B adenosine receptor antagonists for TME modulation. Of which, PBF-1129 is undergoing pre-clinical and IND-enabling studies and demonstrates high anti-tumor efficacy, suggesting the possibility for clinical trials with A2B antagonists for cancer therapy in the nearest future. Lastly, our methodology is targeting a glaring hole in the understanding of tumor metastasis, meaning the forthcoming information from our work holds great promise to identify novel therapeutic strategies aimed at greatly diminishing the chief cause of cancer morbidity.