Oxygen-dependent Processes Research Articles

Особливості кисень-залежних процесів у щурів з гострим поширеним перитонітом на тлі мерказоліл-індукованого гіпотиреозу

Мета роботи: дослідження впливу зниженої продукції тиреоїдних гормонів на стан кисень-залежних процесів.Матеріали і методи. У роботі використовували білих щурів лінії Вістар. Гіпотиреоз моделювали уведенням мерказолілу в дозі 25 мг/кг протягом 21-ї доби. Гострий поширений перитоніт моделювали уведенням 0,5 мл 10 % профільтрованої калової суспензії в черевну порожнину досліджуваних тварин. Визначали співвідношення фагоцитуючих клітин у місці ураження, продукування активних форм кисню системою фагоцитуючих мононуклеарів, спонтанний та індукований тест із нітросинім тетразолієм (НСТ-тест).Результати досліджень та їх обговорення. Проведеними дослідженнями встановлено, що наявність гіпотиреозу в експериментальних тварин, яким моделювали гострий поширений каловий перитоніт, супроводжувалась порушенням співвідношення кількості фагоцитуючих клітин у місці ушкодження, менш вираженим, ніж в еутиреоїдних щурів, зростанням активних форм кисню, а також показників спонтанного та індукованого НСТ-тесту і, як наслідок, зменшенням інтенсивності продукування ними активних форм кисню. За умов гіпотиреозу знижується кисень-залежна біоцидність нейтрофілів та зменшуються функціональні резерви фагоцитуючих клітин.

Жовчнокислотний спектр жовчі самців щурів при дії L-цистеїну

У гострих дослідах на щурах-самцях показано, що введення L-цистеїну (20 мг/кг, внутрішньопортально) зменшує вміст глікокон’югатів та вільних жовчних кислот і збільшує концентрацію таурокон’югатів у жовчі. Припускається, що екзогенне надходження амінокислоти створило умови для більш ефективного синтезу таурину із залученням його до реакцій кон’югації, однак зумовило Н2S-опосередкований пригнічувальний ефект на кисеньзалежні процеси при синтезі та транслокації окремих фракцій жовчних кислот через мембрани гепатоцитів.

On the effects of ENSO on ocean biogeochemistry in the Northern Humboldt Current System (NHCS): A modeling study

Abstract The response of the ocean biogeochemistry to intense El Nino Southern Oscillation (ENSO) events in the Northern Humboldt Current System (NHCS) is assessed with an eddy-resolving coupled physical-biogeochemical model. El Nino (EN) 1997–1998 and La Nina (LN) 1999–2000 are well reproduced, inducing large spatial and temporal variability of biogeochemical properties at three coastal upwelling centers along the Peruvian coast (Chimbote 9.4°S, Callao 12.1°S, and Pisco 14°S). During EN, the upper limit of the Oxygen Minimum Zone (OMZ) experiences an offshore displacement of, approximately, 60 km and a deepening of, approximately, 150 m when compared to neutral-ENSO conditions, thus ventilating the upper 100 m of the water column. In contrast, during LN, the OMZ tongue outcrops over the continental shelf deoxygenating the water column at all locations. During LN, at the southernmost location, enhanced Eddy Kinetic Energy (EKE) induces a leaking of the coastal nutrient inventory by horizontally advecting nitrogen from the nearshore region into the oligotrophic ocean. This leads to a reduction of biological production in the coastal zone. During EN, nitrification is an order of magnitude larger than denitrification in supplying the nitrite coastal pool. During LN peak, nitrification is reduced by 80%, while denitrification becomes equally important, evidencing a coupling between these two oxygen-dependent processes. The nitrogen removal due to suboxic activity is mostly controlled by the Anaerobic Ammonium Oxidation (Anammox) in the southern domain during neutral-ENSO conditions. Our results show that during EN, denitrification contributes with 60% of the total nitrogen removal. In contrast, Anammox contributes with 70% during LN. The outgassing of nitrous oxide (N2O), an intermediate product of denitrification, is reduced and enhanced during EN and LN, respectively, and it is strongly modulated by the spatiotemporal variability of oxygen in the environment.

Time-Course Analysis of Gene Expression During the Saccharomyces cerevisiae Hypoxic Response.

Many cells experience hypoxia, or low oxygen, and respond by dramatically altering gene expression. In the yeast Saccharomyces cerevisiae, genes that respond are required for many oxygen-dependent cellular processes, such as respiration, biosynthesis, and redox regulation. To more fully characterize the global response to hypoxia, we exposed yeast to hypoxic conditions, extracted RNA at different times, and performed RNA sequencing (RNA-seq) analysis. Time-course statistical analysis revealed hundreds of genes that changed expression by up to 550-fold. The genes responded with varying kinetics suggesting that multiple regulatory pathways are involved. We identified most known oxygen-regulated genes and also uncovered new regulated genes. Reverse transcription-quantitative PCR (RT-qPCR) analysis confirmed that the lysine methyltransferase EFM6 and the recombinase DMC1, both conserved in humans, are indeed oxygen-responsive. Looking more broadly, oxygen-regulated genes participate in expected processes like respiration and lipid metabolism, but also in unexpected processes like amino acid and vitamin metabolism. Using principle component analysis, we discovered that the hypoxic response largely occurs during the first 2 hr and then a new steady-state expression state is achieved. Moreover, we show that the oxygen-dependent genes are not part of the previously described environmental stress response (ESR) consisting of genes that respond to diverse types of stress. While hypoxia appears to cause a transient stress, the hypoxic response is mostly characterized by a transition to a new state of gene expression. In summary, our results reveal that hypoxia causes widespread and complex changes in gene expression to prepare the cell to function with little or no oxygen.

Parameterization of biogeochemical sediment–water fluxes using in situ measurements and a diagenetic model

Abstract. Diagenetic processes are important drivers of water column biogeochemistry in coastal areas. For example, sediment oxygen consumption can be a significant contributor to oxygen depletion in hypoxic systems, and sediment–water nutrient fluxes support primary productivity in the overlying water column. Moreover, nonlinearities develop between bottom water conditions and sediment–water fluxes due to loss of oxygen-dependent processes in the sediment as oxygen becomes depleted in bottom waters. Yet, sediment–water fluxes of chemical species are often parameterized crudely in coupled physical–biogeochemical models, using simple linear parameterizations that are only poorly constrained by observations. Diagenetic models that represent sediment biogeochemistry are available, but rarely are coupled to water column biogeochemical models because they are computationally expensive. Here, we apply a method that efficiently parameterizes sediment–water fluxes of oxygen, nitrate and ammonium by combining in situ measurements, a diagenetic model and a parameter optimization method. As a proof of concept, we apply this method to the Louisiana Shelf where high primary production, stimulated by excessive nutrient loads from the Mississippi–Atchafalaya River system, promotes the development of hypoxic bottom waters in summer. The parameterized sediment–water fluxes represent nonlinear feedbacks between water column and sediment processes at low bottom water oxygen concentrations, which may persist for long periods (weeks to months) in hypoxic systems such as the Louisiana Shelf. This method can be applied to other systems and is particularly relevant for shallow coastal and estuarine waters where the interaction between sediment and water column is strong and hypoxia is prone to occur due to land-based nutrient loads.

Особливості оксигензалежних процесів у щурів зі стрептозотоциніндукованим діабетом

Особливості оксигензалежних процесів у щурів зі стрептозотоциніндукованим діабетом

Mathematical modeling of dormant cell formation in growing biofilm.

Understanding the dynamics of dormant cells in microbial biofilms, in which the bacteria are embedded in extracellular matrix, is important for developing successful antibiotic therapies against pathogenic bacteria. Although some of the molecular mechanisms leading to bacterial persistence have been speculated in planktonic bacterial cell, how dormant cells emerge in the biofilms of pathogenic bacteria such as Pseudomonas aeruginosa remains unclear. The present study proposes four hypotheses of dormant cell formation; stochastic process, nutrient-dependent, oxygen-dependent, and time-dependent processes. These hypotheses were implemented into a three-dimensional individual-based model of biofilm formation. Numerical simulations of the different mechanisms yielded qualitatively different spatiotemporal distributions of dormant cells in the growing biofilm. Based on these simulation results, we discuss what kinds of experimental studies are effective for discriminating dormant cell formation mechanisms in biofilms.

Oxygen as a critical determinant of bone fracture healing-a multiscale model.

A timely restoration of the ruptured blood vessel network in order to deliver oxygen and nutrients to the fracture zone is crucial for successful bone healing. Indeed, oxygen plays a key role in the aerobic metabolism of cells, in the activity of a myriad of enzymes as well as in the regulation of several (angiogenic) genes. In this paper, a previously developed model of bone fracture healing is further improved with a detailed description of the influence of oxygen on various cellular processes that occur during bone fracture healing. Oxygen ranges of the cell-specific oxygen-dependent processes were established based on the state-of-the art experimental knowledge through a rigorous literature study. The newly developed oxygen model is compared with previously published experimental and in silico results. An extensive sensitivity analysis was also performed on the newly introduced oxygen thresholds, indicating the robustness of the oxygen model. Finally, the oxygen model was applied to the challenging clinical case of a critical sized defect (3mm) where it predicted the formation of a fracture non-union. Further model analyses showed that the harsh hypoxic conditions in the central region of the callus resulted in cell death and disrupted bone healing thereby indicating the importance of a timely vascularization for the successful healing of a large bone defect. In conclusion, this work demonstrates that the oxygen model is a powerful tool to further unravel the complex spatiotemporal interplay of oxygen delivery, diffusion and consumption with the several healing steps, each occurring at distinct, optimal oxygen tensions during the bone repair process.

Clinical and biochemical rationale for ozone therapy in patients with chronic viral hepatitis B and C

Aim. To explore the clinical and pathogenic role of lipid peroxidation, protective antioxidant system in association with biochemical indicators of liver functional state, and the effect of intravenous ozone therapy on these processes in patients with chronic viral hepatitis B and C, with the presence of liver cell cytolysis. Methods. Lipid peroxidation, antioxidant protection and biochemical indicators of liver functional state and their relation to liver functional state were studied in 184 patients with chronic viral hepatitis B and C using comprehensive clinical and biochemical methods. Intravenous ozone therapy was used in 50 patients with chronic hepatitis B and C to correct membrane disaorders. Results. Ozone therapy has shown a positive effect on lipid peroxidation processes and activity of antioxidant system, stimulating oxygen-dependent processes, improving liver function and well-being of patients with chronic viral hepatitis B and C. The association between lipid peroxidation products blood level and the intensity of liver cell cytolysis was revealed, there was no such association with the viral load level. Conclusion. In patients with chronic viral hepatitis B and C with active liver cell cytolysis, ozone therapy leads to clinical remission and normalizes liver functional state, lipid peroxidation and antioxidant enzymes activity.

The process of phagocytosis in the antigenic load and their correction

Using experimental data an analysis of the changes of the oxygen-dependent and oxygen independent enzymatic processes in neutrophilic granulocytes of rats that had simulated chronic immune complex process with placental polybiolinum correction has been carried out. It was established, that under conditions of chronic immune complex process enzymatic processes in neutrophilic granulocytes get activated. Application of placental polybiolinum restored grasping ability of neutrophils and reduced the activity of the oxygen-dependent and oxygen independent enzymatic processes in neutrophilic granulocytes, which in turn leads to the normalization of the integration processes.

Зміни процесів вільнорадикального окиснення ліпідів і білків, антиоксидантного захисту у щурів із гіпофункцією щитоподібної залози на тлі дефіциту йоду та міді

Thyroid status, copper balance, correlation of processes of peroxide oxidation of lipids (POL), proteins (POP), antioxidant defence (AOD) were examined in experiments on rats with hypofunction of thyroid gland under iodine monodeficit (HTGI) and combined iodine and copper deficit (HTGI+Cu). It was determined that a combined deficit of microelements is accompanied by a distribution of copper content between different tissues (increase in red blood cell mass and cerebrum, decrease in myocardium), essential changes of indexes of hypotalamo-hypophysis-thyroid axis, oxygen-dependent metabolism, antiradical defense, exacerbating the effects of negative influence of each of them on organism. It was established that HTGI+Cu causes a suppression of oxygen-dependent processes. In thyroid gland, it is shown a decrease of content of dyenic conjugates (DC) by 69,70% , of TBA-reacting products (TBA-RP) by 47,72% in diencephalon, the volume of modified proteins (VMP) - by 37,10-98,98% in the tissues of diencephalons. The results obtained let us to suggest a pivotal role ofmicroelement dysbalance and metabolic mechanisms in pathogenesis of cardiological pathology under thyroid dysfunction. The development of HTGI +Cu exhausts the resources of AOD: decreases the activity of catalase (on 47,05%), superoxide dismutase (on 33,13%), ceruloplasmine (on 33,93%) and saturation of transferrin with iron (on 56,76%) against the background of selective rise in the activity of glu-tationreductase (in 2,8 time) in comparison with the control data. The long-term disturbances ofantyoxidative defence can be the reason of manifestation of oxygendependent processes and the development of pathological changes in separate physiological systems of organism.

Oxygen saturation trends in the first hour of life in healthy full-term neonates born at moderate altitude

Transition from a parallel circulation in utero to an in-series circulation immediately after birth is partly an oxygen-dependent process. Relative hypoxemia with increasing altitude above sea level exerts a certain degree of stress on oxygen-dependent metabolic processes throughout the body. The present study aimed to determine the reference values for oxygen saturation and the pre-ductal and post-ductal oxygen saturation trends during the first 60 min of life in healthy full-term neonates born at moderate altitude (1500-2500 m) using pulse oximetry. This descriptive study was carried out over a period of three months started from July 2011 in the Neonatology Department of King Abdulaziz Specialist Hospital, Taif, Saudi Arabia. In this observational study, arterial oxygen saturation in the right hand and right foot of each infant was recorded by pulse oximetry immediately after birth and continuously within the first 60 min of life. The respiratory rate, heart rate, and blood pressure were measured at birth and at 1 h after birth. Cord blood gas and haemoglobin levels were also measured. The study was conducted in a hospital situated at an altitude of 1640 m above sea level. Immediately after birth, the mean pre-ductal SpO2 in the right hand was 68% (51-80%); in the right foot, the mean post-ductal SpO2 was 60% (40-77%). This difference was statistically significant (p < 0.01); however, it became statistically insignificant at 20 min (4-45 min) and disappeared at 25 min, when the SpO2 in both limbs equalised at 88% (83-96%). SpO2 levels > 94% were reached after 13 min (4-35) min pre-ductally and after 22 min (10-45 min) post-ductally. The mean respiratory rate, heart rate, and mean blood pressure at birth were 56/min, 140/min, and 34 mmHg, respectively; at 60 min, they were 40/min, 123/min, and 47 mmHg, respectively. This study defined normal range of SpO2 values in healthy full-term neonates born at moderate altitude in the first 60 minutes of life. These are expected to serve as base line data for normal neonates born at similar altitudes. With regard to pre-ductal and post-ductal oxygen saturation levels, cut-off values lower than those used at sea level should be adopted for neonates born at moderate altitudes.

Вплив L-аргініну на показники кисневого балансу печінки та її жовчосекреторну функцію

In acute experiments on anesthetized rats we showed that L-arginine causes an increase in oxygen-dependent synthetic processes in the liver, particularly associated with mitochondrial polyenzyme systems biosynthesis of bile acids with simultaneous activation in hepatocytes tissue respiration. The level of oxygen tension in the gland is not changed. Implementation of these effects partly involves nitric oxide. In addition, the L-arginine inhibits cholepoiesis without involving to the reaction NO. Dose-dependent influence L-arginine on the bile cholates content may indicate a different effect of this amino acids on metabolic transformation of bile acids such as hydroxylation and conjugation.

Detection of Metabolic Key Enzymes of Methane Turnover Processes in Cold Seep Microbial Biofilms

In anoxic environments, methane oxidation is conducted in a syntrophic process between methanotrophic archaea (ANME) and sulfate reducing bacteria (SRB). Microbial mats consisting of ANME, SRB and other microorganisms form methane seep-related carbonate buildups in the anoxic bottom waters of the Black Sea Crimean shelf. To shed light on the localization of the biochemical processes at the level of single cells in the Black Sea microbial mats, we applied antibody-based markers for key enzymes of the relevant metabolic pathways. The dissimilatory adenosine-5′-phosphosulfate (APS) reductase, methyl-coenzyme M reductase (MCR) and methanol dehydrogenase (MDH) were selected to localize sulfate respiration, reverse methanogenesis and aerobic methane oxidation, respectively. The key enzymes could be localized by double immunofluorescence and immunocytochemistry at light- and electron microscopic levels. In this study we show that sulfate reduction is conducted synchronized and in direct proximity to reverse methanogenesis of ANME archaea. Microcolonies in interspaces between ANME/SRB express methanol dehydrogenase, which is indicative for oxidation of C1 compounds by methylotrophic or methanotrophic bacteria. Thus, in addition to syntrophic AOM, oxygen-dependent processes are also conducted by a small proportion of the microbial population.

Disorders of Oxygen-Dependent Processes in Periodontal Tissues under Prolonged Immobilization Stress and the Ways of Their Pharmacological Correction

Disorders of Oxygen-Dependent Processes in Periodontal Tissues under Prolonged Immobilization Stress and the Ways of Their Pharmacological Correction

Hyperbare Oxygenation bei nekrotisierenden Weichteilinfektionen: Pro

Necrotizing soft tissue infections are a complex pathological spectrum of symptoms and result in a significantly increased risk of mortality depending on the degree of dissemination as well as the underlying bacterial infection. Hyperbaric oxygen therapy (HBOT) can significantly improve the effectiveness of a multidisciplinary treatment concept consisting of surgical debridement, critical care and antibiotic treatment. HBOT itself assists solid wound healing by bactericidal and bacteriostatic effects and by increasing the oxygen supply up to the cellular level resulting in an optimization of oxygen-dependent metabolic processes. The efficacy of treatment in a centre of cooperating specialized departments can therefore be increased by utilizing HBOT as adjunct treatment. Nevertheless, if a HBOT facility is available, excluding HBOT is equivalent to omission of an effective therapy option to the disadvantage of patients.

The effect of a sauna on blood oxygen transport and the prooxidant-antioxidant balance in untrained subjects

The effect of sauna on blood oxygen transport and the prooxidant-antioxidant state was studied in 18- to 22-year-old men. The course of heat treatment was performed once a week for five months, i.e., twenty procedures in total. A sauna procedure consisted of two exposures for 5 and 10 min at a temperature of 85–90°C and humidity of 10–15%. In young men, dry-air bath exposure resulted in respiratory alkalosis, increased pO2, and a decreased affinity of hemoglobin to oxygen in the venous blood, which increased the transportation of O2 to tissues. A single sauna procedure was associated with the development of oxidative stress, which was expressed as an enhancement of free radical processes and a decrease in antioxidant defense. Oxidative stress intensity decreased after the course of heat treatment. An elevation of nitric oxide formation could modify oxygen-dependent processes in the body.

Peculiarities of functional activity of circulating phagocytes in patients with different forms of drug-resistant pulmonary tuberculosis

Functional activity of circulating phagocytes (macrophages and neutrophils — Ns) was studied in 30 patients with infiltrative and 30 patients with fibro-cavernous pulmonary tuberculosis (IPT and FCPT, respectively), characterized by similar biological properties of mycobacterium tuberculosis (MTB), dissemination of the process, and manifestations of intoxication. Differences of the functional activity of both types of cells depending on the PT form were found: a more significant increase in the oxygen-depending activity in FCPT while bactericide potential estimated with the zymosan induced NST-test was more pronounced in IPT patients. These data correlate with the blood levels of neopterin and elastase, the markers of the mononuclear and neutrophil activity, respectively. Involvement of adenosine deaminase (ADA) and neopterin in realization of intracellular oxygen-dependent processes was demonstrated. Results of the multivariate analysis of the whole set of the studied phagocyte parameters, reflecting their different roles in this pathological process demonstrated a prevailing role of mononuclears in newly diagnosed IPT and neutrophils in the chronic progressive process.

Boron PLA for oxygen sensing & hypoxia imaging

Oxygen is essential for many forms of life and its depletion in the body and the environment can lead to deleterious effects. Low oxygen conditions, even anoxia, are associated with eutrophication of lakes and rivers, wherein an over abundance of nutrients often caused by pollution result in excessive plant growth and decay, threatening water quality, ecosystem balance, and aquatic life. In the body, low oxygen conditions or hypoxia may be generalized, as can occur at high altitude or during strenuous exercise, or localized in particular tissues, when there is a mismatch between oxygen supply and demand. Hypoxia is present in many important diseases as well. Low oxygen levels in tumors are often associated with biochemical changes, increased invasiveness, cancer progression, and resistance to radiation and chemotherapies. Vascular blockage in strokes, heart attacks, and peripheral artery disease, which is common in diabetes, are other situations where oxygen levels can drop precipitously and cause great damage to affected tissues. Clearly, innovative sensing technologies that provide new insight into these many oxygen dependent processes can impact global society in significant ways.

Hypoxia inducible factors regulate pluripotency and proliferation in human embryonic stem cells cultured at reduced oxygen tensions

Human embryonic stem (hES) cells are routinely cultured under atmospheric, 20% oxygen tensions but are derived from embryos which reside in a 3–5% oxygen (hypoxic) environment. Maintenance of oxygen homeostasis is critical to ensure sufficient levels for oxygen-dependent processes. This study investigates the importance of specific hypoxia inducible factors (HIFs) in regulating the hypoxic responses of hES cells. We report that culture at 20% oxygen decreased hES cell proliferation and resulted in a significantly reduced expression of SOX2, NANOG and POU5F1 (OCT4) mRNA as well as POU5F1 protein compared with hypoxic conditions. HIF1A protein was not expressed at 20% oxygen and displayed only a transient, nuclear localisation at 5% oxygen. HIF2A (EPAS1) and HIF3A displayed a cytoplasmic localisation during initial hypoxic culture but translocated to the nucleus following long-term culture at 5% oxygen and were significantly upregulated compared with cells cultured at 20% oxygen. Silencing of HIF2A resulted in a significant decrease in both hES cell proliferation and POU5F1, SOX2 and NANOG protein expression while the early differentiation marker, SSEA1, was concomitantly increased. HIF3A upregulated HIF2A and prevented HIF1A expression with the knockdown of HIF3A resulting in the reappearance of HIF1A protein. In summary, these data demonstrate that a low oxygen tension is preferential for the maintenance of a highly proliferative, pluripotent population of hES cells. While HIF3A was found to regulate the expression of both HIF1A and HIF2A, it is HIF2A which regulates hES cell pluripotency as well as proliferation under hypoxic conditions.