Evaluation of alkali flooding combined with intermittent flow in carbonate reservoir

The majority of carbonate reservoir is oil-wet, which is an unfavorable condition for oil production. Generally, the total oil recovery after both primary and secondary recovery in an oil-wet reservoir is low. The amount of producible oil by enhanced oil recovery techniques is still large. Alkali substances are proven to be able to reverse rock wettability from oil-wet to water-wet, which is a favorable condition for oil production. However, the wettability reversal mechanism would require a noneconomical aging period to reach the maximum reversal condition. An intermittent flow with the optimum pausing period is then combined with alkali flooding (combination technique) to increase the wettability reversal mechanism and as a consequence, oil recovery is improved. The aims of this study are to evaluate the efficiency of the combination technique and to study the parameters that affect this method. In order to implement alkali flooding, reservoir rock and fluid properties were gathered, e.g. interfacial tension of fluids, rock wettability, etc. The flooding efficiency curves are obtained from core flooding and used as a major criterion for evaluation the performance of technique. The combination technique improves oil recovery when the alkali concentration is lower than 1% wt. (where the wettability reversal mechanism is dominant). The soap plug (that appears when high alkali concentration is used) is absent in this combination as seen from no drop of production rate. Moreover, the use of low alkali concentration limits alkali loss. This combination probably improves oil recovery also in the fractured carbonate reservoirs in which oil is uneconomically produced. The results from the current study indicate that the combination technique is an option that can improve the production of carbonate reservoirs. And a less quantity of alkali is consumed in the process.

Modulation of hypoxia-inducible factors as a therapeutic target for multiple myeloma

Hypoxia-inducible factor-1 alpha (HIF-1α) plays a critical role in survival and is associated with poor prognosis in solid tumors. The role of HIF-1α in multiple myeloma is not completely known. In the present study, we explored the effect of EZN2968, an locked nucleic acid antisense oligonucleotide against HIF-1α, as a molecular target in MM. A panel of MM cell lines and primary samples from MM patients were cultured in vitro in the presence of EZN2968 . Under normoxia culture condition, HIF-1α mRNA and protein expression was detectable in all MM cell lines and in CD138+ cells from newly diagnosed MM patients samples. Significant up-regulation of HIF-1α protein expression was observed after incubation with IL6 or IGF-I, confirming that HIF-1α can be further induced by biological stimuli. EZN2968 efficiently induces a selective and stable down-modulation of HIF-1α and decreased the secretion of VEGF released by MM cell. Treatment with EZN2968 gave rise to a progressive accumulation of cells in the S and subG0 phase. The analysis of p21, a cyclin-dependent kinase inhibitors controlling cell cycle check point, shows upregulation of protein levels. These results suggest that HIF-1α inhibition is sufficient for cell cycle arrest in normoxia, and for inducing an apoptotic pathways.. In the presence of bone marrow microenvironment, HIF-1α inhibition blocks MAPK kinase pathway and secretion of pro-surviaval cytokines ( IL6,VEGF,IL8) In this study we provide evidence that HIF-1α, even in the absence of hypoxia signal, is expressed in MM plasma cells and further inducible by bone marrow milieu stimuli; moreover its inhibition is sufficient to induce a permanent cell cycle arrest. Our data support the hypothesis that HIF-1α inhibition may suppress tumor growth by preventing proliferation of plasma cells through p21 activation and blocking pro-survival stimuli from bone marrow microenvironment.

Effect of hypoxia and hyperglycemia on cell bioenergetics

Mitochondria have a central role in energy supply in cells, ROS production and apoptosis and have been implicated in several human disease and mitochondrial dysfunctions in hypoxia have been related with disorders like Type II Diabetes, Alzheimer Disease, inflammation, cancer and ischemia/reperfusion in heart. When oxygen availability becomes limiting in cells, mitochondrial functions are modulated to allow biologic adaptation. Cells exposed to a reduced oxygen concentration readily respond by adaptive mechanisms to maintain the physiological ATP/ADP ratio, essential for their functions and survival. In the beginning, the AMP-activated protein kinase (AMPK) pathway is activated, but the responsiveness to prolonged hypoxia requires the stimulation of hypoxia-inducible factors (HIFs). In this work we report a study of the mitochondrial bioenergetics of primary cells exposed to a prolonged hypoxic period . To shine light on this issue we examined the bioenergetics of fibroblast mitochondria cultured in hypoxic atmospheres (1% O2) for 72 hours. Here we report on the mitochondrial organization in cells and on their contribution to the cellular energy state. Our results indicate that prolonged hypoxia cause a significant reduction of mitochondrial mass and of the quantity of the oxidative phosphorylation complexes. Hypoxia is also responsible to damage mitochondrial complexes as shown after normalization versus citrate synthase activity. HIF-1α plays a pivotal role in wound healing, and its expression in the multistage process of normal wound healing has been well characterized, it is necessary for cell motility, expression of angiogenic growth factor and recruitment of endothelial progenitor cells. We studied hypoxia in the pathological status of diabetes and complications of diabetes and we evaluated the combined effect of hyperglycemia and hypoxia on human dermal fibroblasts (HDFs) and human dermal micro-vascular endothelial cells (HDMECs) that were grown in high glucose, low glucose concentrations and mannitol as control for the osmotic challenge.

In vitro study of the osteocytes response to hypoxia and their regulation of bone homeostasis

Bone remodelling is a fundamental mechanism for removing and replacing bone during adaptation of the skeleton to mechanical loads. Skeletal unloading leads to severe hypoxia (1%O2) in the bone microenvironment resulting in imbalanced bone remodelling that favours bone resorption. Hypoxia, in vivo, is a physiological condition for osteocytes, 5% O2 is more likely physiological for osteocytes than 20% O2, as osteocytes are embedded deep inside the mineralized bone matrix. Osteocytes are thought to be the mechanosensors of bone and have been shown to orchestrate bone formation and resorption. Oxygen-deprived osteocytes seem undergo apoptosis and actively stimulate osteoclasts. Hypoxia and oxidative stress increase 150-kDa oxygen-regulated protein (ORP 150) expression in different cell types. It is a novel endoplasmic-reticulum-associated chaperone induced by hypoxia/ischemia. It well known that ORP 150 plays an important role in the cellular adaptation to hypoxia, as anti-apoptotic factor, and seems to be involved in osteocytes differentiations. The aims of the present study are 1) to determine the cellular and molecular response of the osteocytes at two different conditions of oxygen deprivation, 1% and 5% of O2 compared to the atmospheric oxygen concentration at several time points. 2) To clarify the role of hypoxic osteocytes in bone homeostasis through the detection of releasing of soluble factors (RANKL, OPG, PGE2 and Sclerostin). 3) To detect the activation of osteoclast and osteoblast induced by condition media collected from hypoxic and normoxic osteocytes. The data obtained in this study shows that hypoxia compromises the viability of osteocytes and induces apoptosis. Unlike in other cells types, ORP 150 in MLO-Y4 does not seem to be regulated early during hypoxia. The release of soluble factors and the evaluation of osteoclast and osteoblast activation shows that osteocytes, grown under severe oxygen deprivation, play a role in the regulation of both bone resorption and bone formation.

Effects of stochastic hypoxia events on the benthic communities of transitional waters

Hypoxia is one of the most important and faster spreading threats to marine life and its occurrence has significantly increased in the last century. The effects of hypoxia on marine organisms and communities has mostly been studied in light of the intensity of the disturbance but not a lot of attention has been given to its interaction with other stressors and the timing of its appearance. In this thesis I started to explore these topics through laboratory and manipulative field experiments. I studied the interactive effects of thermal stress and hypoxia on a European native bivalve species (Cerastoderma edule; Linnaeus, 1758 ) and a non native one (Ruditapes philippinarum; Adams & Reeve, 1850) through a laboratory experiment performed in the Netherlands. The non native species displayed a greater tolerance to oxygen depletion than the native one. The first field experiment was performed in an Italian brackish coastal lagoon (Pialassa Baiona) and tested the effects of different timing regimes of hypoxia on the benthic community. It emerged that the main factor affecting the community is the duration of the hypoxia. The ability of the communities to recover after repeated hypoxic periods was explored in the second manipulative field experiment. We imposed three different timing regimes of hypoxia on sediment patches in Pialassa Baiona and we monitored the changes of both the benthic and the microbial communities after the disturbances. The preliminary analyses of the data from this last work suggest that the experimental manipulations caused limited detrimental effects on the communities. Overall this thesis work suggests that the duration of hypoxic events, their repetitive nature and the associated thermal stress are key factors in determining their effects on the communities and that management measures should point towards a reduction of the duration of the single hypoxic periods more than their frequency.