Search results for: drug kinetics
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2603

Search results for: drug kinetics

833 Prevalence of Polypharmacy in Elderly Cardiac Patients at King Fahad Cardiac Center (KFCC) in King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia

Authors: Mohamed N. Al-Arifi, Hessa Othman Al-Husein, Mostafa Q. Al Shamiri, Ragab Said, Syed Wajid, Salmeen D. Babelghaith

Abstract:

Polypharmacy was defined as a taking more than 4 medications per single patients (minor polypharmacy), patients who are taking more than 10 medications we considered as a major polypharmacy. This study was aimed to evaluate the prevalence of polypharmacy in elderly Saudi cardiac patient. A retrospective observational study was carried out at the department of CCU and cardiology unit of the King Fahad cardiac centre (KFCC) in King Khalid university hospital from May 2012 to October 2012. All Parameters was analyzed by using Statistical Packages for Social Science (SPSS) to conclude the result; tests of association were performed using the chi-square statistic. The mean age of patients was 70.1 ± 7.75 years, more than half 83 (51.6%) were males. The highest frequency of chronic diseases found were hypertension (91.0%) followed by, dyslipidemia (74.9%), and diabetes mellitus. Results showed that 82% had polypharmacy (>4 drugs) during the study period, and 47.9% had major polypharmacy. The incidence of inappropriate drug use was found to be higher with men than female (p = 0.984). In conclusion, this study revealed that high prevalence of polypharmacy and potentially inappropriate medications in elderly Saudi cardiac inpatients.

Keywords: cardiac inpatients, medications, polypharmacy, prevalence

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832 Adsorptive Media Selection for Bilirubin Removal: An Adsorption Equilibrium Study

Authors: Vincenzo Piemonte

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The liver is a complex, large-scale biochemical reactor which plays a unique role in the human physiology. When liver ceases to perform its physiological activity, a functional replacement is required. Actually, liver transplantation is the only clinically effective method of treating severe liver disease. Anyway, the aforementioned therapeutic approach is hampered by the disparity between organ availability and the number of patients on the waiting list. In order to overcome this critical issue, research activities focused on liver support device systems (LSDs) designed to bridging patients to transplantation or to keep them alive until the recovery of native liver function. In recirculating albumin dialysis devices, such as MARS (Molecular Adsorbed Recirculating System), adsorption is one of the fundamental steps in albumin-dialysate regeneration. Among the albumin-bound toxins that must be removed from blood during liver-failure therapy, bilirubin and tryptophan can be considered as representative of two different toxin classes. The first one, not water soluble at physiological blood pH and strongly bounded to albumin, the second one, loosely albumin bound and partially water soluble at pH 7.4. Fixed bed units are normally used for this task, and the design of such units requires information both on toxin adsorption equilibrium and kinetics. The most common adsorptive media used in LSDs are activated carbon, non-ionic polymeric resins and anionic resins. In this paper, bilirubin adsorption isotherms on different adsorptive media, such as polymeric resin, albumin-coated resin, anionic resin, activated carbon and alginate beads with entrapped albumin are presented. By comparing all the results, it can be stated that the adsorption capacity for bilirubin of the five different media increases in the following order: Alginate beads < Polymeric resin < Albumin-coated resin < Activated carbon < Anionic resin. The main focus of this paper is to provide useful guidelines for the optimization of liver support devices which implement adsorption columns to remove albumin-bound toxins from albumin dialysate solutions.

Keywords: adsorptive media, adsorption equilibrium, artificial liver devices, bilirubin, mathematical modelling

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831 Combination of Lamotrigine and Duloxetine: A Potential Approach for the Treatment of Acute Bipolar Depression

Authors: Kedar S. Prabhavalkar, Nimmy Baby Poovanpallil

Abstract:

Lamotrigine is approved for maintenance treatment of bipolar I disorder. However, its role in the treatment of acute bipolar depression is not well clear. Its efficacy in the treatment of major depressive disorders including refractory unipolar depression suggested the use of lamotrigine as an augmentation drug for acute bipolar depression. The present study aims to evaluate and perform a comparative analysis of the therapeutic effects of lamotrigine, an epileptic mood stabilizer, when used alone and in combination with duloxetine in treating acute bipolar depression at different doses of lamotrigine. Male swiss albino mice were used. For evaluation of efficacy of combination, immobility period was analyzed 30 min after the treatment from forced swim and tail suspension tests. Further amount of sucrose consumed in sucrose preference test was estimated. The combination of duloxetine and lamotrigine showed potentiation of antidepressant activity in acute models. Decrease in immobility time and increase in the amount of sucrose consumption in stressed mice were higher in combined group compared to lamotrigine monotherapy group. Brain monoamine levels were also attenuated more with combination compared to monotherapy. Results of the present study suggest potential role of lamotrigine and duloxetine combination in the treatment of acute bipolar depression.

Keywords: lamotrigine, duloxetine, acute bipolar depression, augmentation

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830 Study of the Formation Mechanism of Dipalmitoylphosphatidylcholine Liposomes and Calcium Ion Complexes

Authors: T. Mdzinarashvili, M. Khvedelidze, E. Shekiladze, S. Chinchaladze, M. Mdzinarashvili

Abstract:

The study of the possible interaction between calcium ions and lipids is of great importance for the studies of complexes of calcium drug-carrying nanoparticles. We prepared calcium-containing complex liposomes from Dipalmitoylphosphatidylcholine (DPPC) lipids and studied their thermodynamic properties. In calorimetric studies, we determined that the phase transition temperature of these complexes is close to 420 C. It was shown that both hydrophobic and hydrophilic connections take part in the formation of calcium nanoparticles. We were interested in hydrophilic bonds represented by hydrogen bonds. We have shown that these hydrogen bonds are formed between the phospholipid heads, and the main contributor is the oxygen atoms in the phosphoric acid residues. In addition, based on the amount of heat absorbed during the breaking of hydrogen bonds formed between calcium-containing nanoparticle complexes, it can be concluded that the hydrogen atoms in the head of DPPC lipids form hydrogen bonds between P=O and P-O groups of phosphate. The energy of heat absorption measured by the calorimeter is of the order obtained by breaking the hydrogen bonds we have specified. Thus, we conclude that our approach to the model of liposome formation from lipids is correct. As for calcium atoms - due to the fact that it is present in the form of positive ions in the liposome, they will connect only with negatively charged phosphorus ions.

Keywords: DPPC, liposomes, calcium, complex nanoparticles

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829 SOCS3 Reverses Multidrug Resistance by Inhibiting MDR1 in Mammary Cell Carcinoma

Authors: S. Pradhan, D. Pradhan, G. Tripathy, T. Dasmohapatra

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Suppressors of cytokine signalling (SOCS3), a newly indentified anti-apoptotic molecule is a downstream effecter of the receptor tyrosine kinase-Ras signalling pathway. Current study has uncovered that SOCS3 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS3 on MDR, we analyzed the expression of P-gp and SOCS3 by immune-histochemistry and found there was positive correlation between them. At that point we effectively interfered with RNA translation by the contamination of siRNA of SOCS3 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flowcytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS3 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: SOCS3gene, breast cancer, multidrug resistance, MDR1 gene, RNA interference

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828 Permeable Reactive Pavement for Controlling the Transport of Benzene, Toluene, Ethyl-Benzene, and Xylene (BTEX) Contaminants

Authors: Shengyi Huang, Chenju Liang

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Volatile organic compounds such as benzene, toluene, ethyl-benzene, and xylene (BTEX) are common contaminants in environment, which could come from asphalt concrete or exhaust emissions of vehicles. The BTEX may invade to the subsurface environment via wet and dry atmospheric depositions. If there aren’t available ways for controlling contaminants’ fate and transport, they would extensively harm natural environment. In the 1st phase of this study, various adsorbents were screened for a suitable one to be an additive in the porous asphalt mixture. In the 2nd phase, addition of the selected adsorbent was incorporated with the design of porous asphalt concrete (PAC) to produce the permeable reactive pavement (PRP), which was subsequently tested for the potential of adsorbing aqueous BTEX as compared to the PAC, in the 3rd phase. The PRP was prepared according to the following steps: firstly, the suitable adsorbent was chosen based on the analytical results of specific surface area analysis, thermal-gravimetric analysis, adsorption kinetics and isotherms, and thermal dynamics analysis; secondly, the materials of coarse aggregate, fine aggregate, filler, asphalt, and fiber were tested in order to meet regulated specifications (e.g., water adsorption, soundness, viscosity etc.) for preparing the PRP; thirdly, the amount of adsorbent additive was determined in the PRP; fourthly, the prepared PAC and PRP were examined for their physical properties (e.g., abrasion loss, drain-down loss, Marshall stability, Marshall flow, dynamic stability etc.). As a result of comparison between PRP and PAC, the PRP showed better physical performance than the traditional PAC. At last, the Marshall Specimen column tests were conducted to explore the adsorption capacities of PAC and PRPs. The BTEX adsorption capacities of PRPs are higher than those obtained from traditional PAC. In summary, PRPs showed superior physical performance and adsorption capacities, which exhibit the potential of PRP to be applied as a replacement of PAC for better controlling the transport of non-point source pollutants.

Keywords: porous asphalt concrete, volatile organic compounds, permeable reactive pavement, non-point source pollution

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827 Point-Mutation in a Rationally Engineered Esterase Inverts its Enantioselectivity

Authors: Yasser Gaber, Mohamed Ismail, Serena Bisagni, Mohamad Takwa, Rajni Hatti-Kaul

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Enzymes are safe and selective catalysts. They skillfully catalyze chemical reactions; however, the native form is not usually suitable for industrial applications. Enzymes are therefore engineered by several techniques to meet the required catalytic task. Clopidogrel is recorded among the five best selling pharmaceutical in 2010 under the brand name Plavix. The commonly used route for production of the drug on an industrial scale is the synthesis of the racemic mixture followed by diastereomeric resolution to obtain the pure S isomer. The process consumes a lot of solvents and chemicals. We have evaluated a biocatalytic cleaner approach for asymmetric hydrolysis of racemic clopidogrel. Initial screening of a selected number of hydrolases showed only one enzyme EST to exhibit activity and selectivity towards the desired stereoisomer. As the crude EST is a mixture of several isoenzymes, a homology model of EST-1 was used in molecular dynamic simulations to study the interaction of the enzyme with R and S isomers of clopidogrel. Analysis of the geometric hindrances of the tetrahedral intermediates revealed a potential site for mutagenesis in order to improve the activity and the selectivity. Single point mutation showed dramatic increase in activity and inversion of the enantioselectivity (400 fold change in E value).

Keywords: biocatalysis, biotechnology, enzyme, protein engineering, molecular modeling

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826 Cocrystals of Etodolac: A Crystal Engineering Approach with an Endeavor to Enhance Its Biopharmaceutical Assets

Authors: Sakshi Tomar, Renu Chadha

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Cocrystallization comprises a selective route to the intensive design of pharmaceutical products with desired physiochemical and pharmacokinetic properties. The present study is focused on the preparation, characterization, and evaluation of etodolac (ET) co-crystals with coformers nicotinamide (ETNI) and Glutaric acid (ETGA), using cocrystallization approach. Preliminarily examination of the prepared co-crystal was done by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD). DSC thermographs of ETNI and ETGA cocrystals showed single sharp melting endotherms at 144°C and 135°C, respectively, which were different from the melting of drugs and coformers. FT-IR study points towards carbonyl-acid interaction sandwiched between the involving molecules. The emergence of new peaks in the PXRD pattern confirms the formation of new crystalline solid forms. Both the cocrystals exhibited better apparent solubility, and 3.8-5.0 folds increase in IDR were established, as compared to pure etodolac. Evaluations of these solid forms were done using anti-osteoarthritic activities. All the results indicate that etodolac cocrystals possess better anti-osteoarthritic efficacy than free drug. Thus loom of cocrystallization has been found to be a viable approach to resolve the solubility and bioavailability issues that circumvent the use of potential antiosteoarthritic molecules.

Keywords: bioavailability, etodolac, nicotinamide, osteoarthritis

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825 Molecular Characterization and Phylogenetic Analysis of Influenza a(H3N2) Virus Circulating during the 2010-2011 in Riyadh, Saudi Arabia

Authors: Ghazanfar Ali, Fahad N Almajhdi

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This study provides data on the viral diagnosis and molecular epidemiology of influenza A(H3N2) virus isolated in Riyadh, Saudi Arabia. Nasopharyngeal aspirates from 80 clinically infected patients in the peak of the 2010-2011 winter seasons were processed for viral diagnosis by RT-PCR. Sequencing of entire HA and NA genes of representative isolates and molecular epidemiological analysis were performed. A total of 06 patients were positive for influenza A, B and respiratory syncytial viruses by RT-PCR assays; out of these only one sample was positive for influenza A(H3N2) by RT-PCR. Phylogenetic analysis of the HA and NA gene sequences showed identities higher than 99-98.8 % in both genes. They were also similar to reference isolates in HA sequences (99 % identity) and in NA sequences (99 % identity). Amino acid sequences predicted for the HA gene were highly identical to reference strains. The NA amino acid substitutions identified did not include the oseltamivir-resistant H275Y substitution. Conclusion: Viral isolation and RT-PCR together were useful for diagnosis of the influenza A (H3N2) virus. Variations in HA and NA sequences are similar to those identified in worldwide reference isolates and no drug resistance was found.

Keywords: influenza A (H3N2), genetic characterization, viral isolation, RT-PCR, Saudi Arabia

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824 Antidiabetic Effect of Aqueous Extract of Cedrus deodara Roxb. Heartwood in Alloxan-Induced Diabetic Rats

Authors: Sourabh Jain, Vikas Jain, Dharmendar Kumar

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The present study investigated the antidiabetic potential of Cedrus deodara heart wood aqueous extract. Aqueous extract of Cedrus deodara was found to reduce blood sugar level in alloxan induced diabetic rats. Reduction in blood sugar could be seen from 5th day after continuous administration of the extract and on 21st day sugar levels were found to be reduced by 40.20%. Oxidative stress produced by alloxan was found to be significantly lowered by the administration of Cedrus deodara aqueous extract (500 mg/kg). This was evident from a significant decrease in lipid per oxidation level in liver induced by alloxan. The level of Glutathione, Catalase, Superoxide dismutase and Glutathione-S-Transferase in liver, kidney and pancreas tissue were found to be increased significantly after drug administration. The results obtained in the present study suggest that the Cedrus deodara aqueous extract effectively and significantly reduced the oxidative stress induced by alloxan and produced a reduction in blood sugar level.

Keywords: Cedrus deodara, heartwood, antioxidant, anti-diabetic, anti-inflammatory

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823 Contribution of Crime Scene and Autopsy Investigation to the Solving of the Case in the Case of Death as a Result of Self-Harm

Authors: Murat Mert, Yusuf Ozer, Fatih Kolay

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Behaviour of giving harm to the body in literature has been named as “self-injury”, “self-mutilation” ve “self-harm”. “Self-injury”, or “self-mutilation” is generally used for the same meaning and mentioned as an action which is committed to the body itself directly. As is seen that alcohol and drug users have injured their bodies because of deprivation, whereas behaviour of self-injury in some societies is accepted as religious and cultural, it has nevertheless been diagnosed in people who have a borderline personality disorder, histrionic personality disorder, psychotic personality disorder and mood disorder. There has not been any direct self-murder tendency in people having self-harmed. However, death cases can be seen together with loss of consciousness depending on loss of blood by exceeding the limit in the course of injury action. 34- year old – male person who was alcohol addicted, having had a psycological treatment beforehand, had mutilated his small intestine together with fatty tissue by cutting his body with a razor-blade at the thought of insects strolling around the body (delirium tremens) due to deprivation attack and had died in the result of various cuts. In this study, crime scene investigation and death mechanism of the person having had self-harmed in a result of abstinence syndrome will be explained. Relevant criteria which differentiate this case from homicide will be examined.

Keywords: self-injury, autopsy, abstinence syndrome, CSI

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822 Preventive and Attenuative Effect of Vitamin E on Selenite-induced Cataract in Rat

Authors: Seyedeh Zeinab Peighambarzadeh, Mehdi Tavana

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Cataract is the most common cause of blindness worldwide and its incidence will increase as the World’s population ages. Even in modern ophthalmology, there is no effective medical treatment for cataract except surgery. Development of a drug which could prevent or delay the onset of cataract will lessen this burden and reduce the number of blind patients waiting for cataract surgery. This study was undertaken to evaluate the protective effect of vitamin E on Selenite-induced Cataract in Sprague-dawely rats. Cataracts were induced in rats by administration of sodium selenite. On postpartum day ten, in group I, saline was injected subcutaneously. Group II rat pups received subcutaneous injection of vitamin E (60mg/kg B.W.) at day 8 postpartum and every other day thereafter. Group III and IV rat pups received a subcutaneous injection of sodium selenite (13mg/kg B.W.) at day 10 postpartum. Group IV also received subcutaneous injection of vitamin E (60mg/kg B.W.) at day 8 postpartum and every other day thereafter. The development of cataract in rats was assessed clinically by slit-lamp biomicroscope from day 14 up to postpartum day 28. After sacrifice, extricated pup lenses were analyzed for total and soluble protein concentrations and eletrophoretic pattern (SDS-PAGE). There was no opacification of lens in Group I and II. There was mature cataract in 95% of Group III. In group IV, 55% of rats developed sub capsular or cortical cataract. Cataractous and biochemical changes of the crystalline lens proteins due to selenite can be retard or prevented by vitamin E.

Keywords: preventive effect, selenite-induced cataract, vitamin E, rat

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821 Comparative Growth Kinetic Studies of Two Strains Saccharomyces cerevisiae Isolated from Dates and a Commercial Strain

Authors: Nizar Chaira

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Dates, main products of the oases, due to their therapeutic interests, are considered highly nutritious fruit. Several studies on the valuation biotechnology and technology of dates are made, and several products are already prepared. Isolation of the yeast Saccharomyces cerevisiae, naturally presents in a scrap of date, optimization of growth in the medium based on date syrup and production biomass can potentially expand the range of secondary products of dates. To this end, this paper tries to study the suitability for processing dates technology and biotechnology to use the date pulp as a carbon source for biological transformation. Two strains of Saccharomyces cerevisiae isolated from date syrup (S1, S2) and a commercial strain have used for this study. After optimization of culture conditions, production in a fermenter on two different media (date syrup and beet molasses) was performed. This is followed by studying the kinetics of growth, protein production and consumption of sugars in crops strain 1, 2 and the commercial strain and on both media. The results obtained showed that a concentration of 2% sugar, 2.5 g/l yeast extract, pH 4.5 and a temperature between 25 and 35°C are the optimal conditions for cultivation in a bioreactor. The exponential phase of the specific growth rate of a strain on both media showed that it is about 0.3625 h-1 for the production of a medium based on date syrup and 0.3521 h-1 on beet molasses with a generation time equal to 1.912 h and on the medium based on date syrup, yeast consumes preferentially the reducing sugars. For the production of protein, we showed that this latter presents an exponential phase when the medium starts to run out of reducing sugars. For strain 2, the specific growth rate is about 0.261h-1 for the production on a medium based on date syrup and 0207 h-1 on beet molasses and the base medium syrup date of the yeast consumes preferentially reducing sugars. For the invertase and other metabolits, these increases rapidly after exhaustion of reducing sugars. The comparison of productivity between the three strains on the medium based on date syrup showed that the maximum value is obtained with the second strain: p = 1072 g/l/h as it is about of 0923 g/l/h for strain 1 and 0644 g/l/h for the commercial strain. Thus, isolates of date syrup are more competitive than the commercial strain and can give the same performance in a shorter time with energy gain.

Keywords: date palm, fermentation, molasses, Saccharomyces, syrup

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820 Analysis of in Vitro Biocompatibility Studies of Silicate-Based Bioceramic Cements: A Scoping Review

Authors: Olphiara Rodolpheza Alexandre, Carla David, Rafael Guerra Lund, Nadia Ferreira

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Due to the increasing demand for biomaterials in the dental field, especially in endodontics, calcium silicate-based cements (CSCs) have gained prominence because of their biocompatibility and tissue regeneration capabilities. Originating from Mineral Trioxide Aggregate (MTA), the first bioceramic in endodontics derived from Portland cement, these materials are becoming increasingly prevalent in the market. For any drug released to the market, pharmacovigilance must ensure the absence of adverse health effects on consumers through rigorous toxicological testing. Although these materials have undergone in vitro and in vivo testing, such tests have typically been conducted over a limited period. Some effects may only become apparent after several years, and these studies are generally carried out on a non-specific population. However, the variety of calcium silicate-based products, including cement and sealers, raises questions about their toxicity, particularly considering potential long-term effects not addressed in existing studies. While the scientific literature includes comparative studies on the toxicity of these materials, the consistency of their conclusions is often controversial. Therefore, this project aims to map the scientific evidence from in vitro biocompatibility studies, including those investigating the toxicity of calcium silicate-based bioceramics.

Keywords: toxicity, toxicity test, bioceramics, calcium silicate, genotoxicity

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819 Review of Correlation between Tacrolimus Pharmacotherapy and Infection after Organ Transplantation

Authors: Zahra Tolou-Ghamari

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Introduction: After allogeneic organ transplantation, in order to lower the rate of rejectiontacrolimus is given. In fact, infection is reported as the most complication of tacrolimus that might be associated with higher susceptibility by its’ long term use. Aim: This study aims to review the association between the occurrence of infections after organ transplantation following the administration of tacrolims. Materials and Methods: Scientific literature on the pharmacotherapy of tacrolimus after organ transplantation and infections were searched using PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/), Web of Science, and Scopus. Results: In order to prevent acute and chronic rejection, the potent immunosuppressive drug tacrolimus administered as a calcineurin inhibitor after organ transplantation. Its’ most frequent infectious complication is reported as urinary tract infection. Virulent strain of recombinant Literiamonocytogenes, in addition to an increase in bacterial burden in the liver and spleen tissues, was reported in the animal experimental study. The consequence of aggressive events and recipients total area under the cureve exposure to immunosuppressive could be as considered as surrogate markers for individual infection’s risk evaluation. Conclusion: Transplant surgery and duration of hospital stay could determinate the risk of infection during the first month of organ transplantation. Despite administration of antiviral drugs, opportunistic infection such as cytomegalovirus could increase the risk of infection during month 1 to year after transplantation.

Keywords: transplant, infection, tacrolimus, kidney

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818 Towards Computational Fluid Dynamics Based Methodology to Accelerate Bioprocess Scale Up and Scale Down

Authors: Vishal Kumar Singh

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Bioprocess development is a time-constrained activity aimed at harnessing the full potential of culture performance in an ambience that is not natural to cells. Even with the use of chemically defined media and feeds, a significant amount of time is devoted in identifying the apt operating parameters. In addition, the scale-up of these processes is often accompanied by loss of antibody titer and product quality, which further delays the commercialization of the drug product. In such a scenario, the investigation of this disparity of culture performance is done by further experimentation at a smaller scale that is representative of at-scale production bioreactors. These scale-down model developments are also time-intensive. In this study, a computation fluid dynamics-based multi-objective scaling approach has been illustrated to speed up the process transfer. For the implementation of this approach, a transient multiphase water-air system has been studied in Ansys CFX to visualize the air bubble distribution and volumetric mass transfer coefficient (kLa) profiles, followed by the design of experiment based parametric optimization approach to define the operational space. The proposed approach is completely in silico and requires minimum experimentation, thereby rendering a high throughput to the overall process development.

Keywords: bioprocess development, scale up, scale down, computation fluid dynamics, multi-objective, Ansys CFX, design of experiment

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817 The Protective Effects of Naringenin on Iodoacetamide-Induced Ulcerative Colitis in Rats

Authors: Yomna T. Abdou, Hala F. Zaki, Sanaa A. Kenawy

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Naringenin is a flavanone, a type of flavonoid, found in fruits such as grapefruit, oranges, and tomatoes, was found to possess antioxidant, anti-inflammatory and antitumor effects. The present study was conducted to investigate the protective effect of naringenin on iodoacetamide-induced ulcerative colitis (UC) in rats. Male Wistar rats were pretreated with sulfasalazine (300 mg/kg, p.o.) as standard anti-inflammatory drug or naringenin (50 mg/kg, p.o.) for 7 consecutive days then UC was induced by intracolon administration of 0.1 ml (2%) iodoacetamide dissolved in 1% methylcelluose. One week later, animals were scarificed and the colonic tissues were dissected. Colon inflammation was evident by elevation in colon tumor necrosis factor alpha (TNFα) and interleukin-8 (IL-8) as well as inducible nitric oxide synthase (iNOS) enzyme, prostaglandin- E2 (PG-E2) and myeloperoxidase (MPO) activities. Additionally, oxidative stress was manifested by increased colon lipoperoxidation (MDA), glutathione (GSH) depletion, elevated nitric oxide (NO) content and glutathione peroxidase (GPx) activity. Pretreatment with naringenin largely mitigated these alterations. The present study reinforces the hypothetical use of naringenin as an anti-inflammatory complement to conventional UC treatment and could be considered in the dietary prevention of intestinal inflammation and related disorders.

Keywords: iodoacetamide, naringenin, sulfasalazine, ulcerative colitis

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816 Health Sector Budgetary Allocations and Their Implications on Health Service Delivery and Universal Health Coverage in Uganda

Authors: Richard Ssempala, Francis Kintu, Christine K. Tashobya

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Funding for health remains a key constraint facing many developing countries, Uganda inclusive. Uganda’s health sector budget to the national budgetary allocation has stagnated between 8.2% to 10% over the years. Using data collected from different government documents, we sought to establish the implications of the budget allocation over the period (FY2010/11-2018/19) on health services delivery in Uganda to inform policymakers specifically Members of Parliament who are critical in making sectorial allocation on the steps they can adapt to change the terrain of health financing in Uganda. Findings revealed that the contribution of public funding to the health sector is low (15.7%) with private sources (42.6%) and donors contributing much more, with the bulk of private funds, are out of pocket. The study further revealed that low budget allocation had been manifested in inadequate and poorly motivated health workers, essential drug stock-outs that ultimately contribute to poor access to services, catastrophic health expenditures, and high morbidity rates. We recommend for a substantial and sustained increase in the government health budget, optimizing the available resources by addressing wastages, prioritizing health promotion, prevention and finally, institutionalizing the National Health Insurance Scheme.

Keywords: budget allocations, universal health coverage, health service delivery, Uganda

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815 Functional Characterization of Transcriptional Regulator WhiB Proteins of Mycobacterium Tuberculosis

Authors: Sonam Kumari

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Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, possesses a remarkable feature of entering into and emerging from a persistent state. The mechanism by which Mtb switches from the dormant state to the replicative form is still poorly characterized. Proteome studies have given us an insight into the role of certain proteins in giving stupendous virulence to Mtb, but numerous dotsremain unconnected and unaccounted. The WhiB family of proteins is one such protein that is associated with developmental processes in actinomycetes.Mtb has seven such proteins (WhiB1 to WhiB7).WhiB proteins are transcriptional regulators; their conserved C-terminal HTH motif is involved in DNA binding. They regulate various essential genes of Mtbby binding to their promoter DNA. Biophysical Analysis of the effect of DNA binding on WhiB proteins has not yet been appropriately characterized. Interaction with DNA induces conformational changes in the WhiB proteins, confirmed by steady-state fluorescence and circular dichroism spectroscopy. ITC has deduced thermodynamic parameters and the binding affinity of the interaction. Since these transcription factors are highly unstable in vitro, their stability and solubility were enhanced by the co-expression of molecular chaperones. The present study findings help determine the conditions under which the WhiB proteins interact with their interacting partner and the factors that influence their binding affinity. This is crucial in understanding their role in regulating gene expression in Mtbandin targeting WhiB proteins as a drug target to cure TB.

Keywords: tuberculosis, WhiB proteins, mycobacterium tuberculosis, nucleic acid binding

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814 Photocatalytic Degradation of Naproxen in Water under Solar Irradiation over NiFe₂O₄ Nanoparticle System

Authors: H. Boucheloukh, S. Rouissa, N. Aoun, M. Beloucifa, T. Sehili, F. Parrino, V. Loddo

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To optimize water purification and wastewater treatment by heterogeneous photocatalysis, we used NiFe₂O₄ as a catalyst and solar irradiation as a source of energy. In this concept, an organic substance present in many industrial effluents was chosen: naproxen ((S)-6-methoxy-α-methyl-2-naphthaleneacetic acid or 2-(6-methoxynaphthalenyl) propanoic), a non-steroidal anti-inflammatory drug. The main objective of this study is to degrade naproxen by an iron and nickel catalyst, the degradation of this organic pollutant by nickel ferrite has been studied in a heterogeneous aqueous medium, with the study of the various factors influencing photocatalysis such as the concentration of matter and the acidity of the medium. The photocatalytic activity was followed by HPLC-UV andUV-Vis spectroscopy. A first-order kinetic model appropriately fitted the experimental data. The degradation of naproxen was also studied in the presence of H₂O₂ as well as in an aqueous solution. The new hetero-system NiFe₂O₄/oxalic acid is also discussed. The fastest naproxen degradation was obtained with NiFe₂O₄/H₂O₂. In a first-place, we detailed the characteristics of the material NiFe₂O₄, which was synthesized by the sol-gel methods, using various analytical techniques: visible UV spectrophotometry, X-ray diffraction, FTIR, cyclic voltammetry, luminescent discharge optical emission spectroscopy.

Keywords: naproxen, nickelate, photocatalysis, oxalic acid

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813 Preparation and Characterizations of Hydroxyapatite-Sodium Alginate Nanocomposites for Biomedical Applications

Authors: Friday Godwin Okibe, Christian Chinweuba Onoyima, Edith Bolanle Agbaji, Victor Olatunji Ajibola

Abstract:

Polymer-inorganic nanocomposites are presently impacting diverse areas, specifically in biomedical sciences. In this research, hydroxyapatite-sodium alginate has been prepared, and characterized, with emphasis on the influence of sodium alginate on its characteristics. In situ wet chemical precipitation method was used in the preparation. The prepared nanocomposite was characterized with Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), with image analysis, and X-Ray Diffraction (XRD). The FTIR study shows peaks characteristics of hydroxyapatite and confirmed formation of the nanocomposite via chemical interaction between sodium alginate and hydroxyapatite. Image analysis shows the nanocomposites to be of irregular morphologies which did not show significant change with increasing sodium alginate addition, while particle size decreased with increase in sodium alginate addition (359.46 nm to 109.98 nm). From the XRD data, both the crystallite size and degree of crystallinity also decreased with increasing sodium alginate composition (32.36 nm to 9.47 nm and 72.87% to 1.82% respectively), while the specific surface area and microstrain increased with increasing sodium alginate composition (0.0041 to 0.0139 and 58.99 m²/g to 201.58 m²/g respectively). The results show that the formulation with 50%wt of sodium alginate (HASA-50%wt), possess exceptional characteristics for biomedical applications such as drug delivery.

Keywords: nanocomposite, sodium alginate, hydroxyapatite, biomedical, FTIR, XRD, SEM

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812 Quality of Life of Patients on Oral Antiplatelet Therapy in Outpatient Cardiac Department Dr. Hasan Sadikin Central General Hospital Bandung

Authors: Andhiani Sharfina Arnellya, Mochammad Indra Permana, Dika Pramita Destiani, Ellin Febrina

Abstract:

Health Research Data, Ministry of Health of Indonesia in 2007, showed coronary heart disease (CHD) or coronary artery disease (CAD) was the third leading cause of death in Indonesia after hypertension and stroke with 7.2% incidence rate. Antiplatelet is one of the important therapy in management of patients with CHD. In addition to therapeutic effect on patients, quality of life is one aspect of another assessment to see the success of antiplatelet therapy. The purpose of this study was to determine the quality of life of patients on oral antiplatelet therapy in outpatient cardiac department Dr. Hasan Sadikin central general hospital, Bandung, Indonesia. This research is a cross sectional by collecting data through quality of life questionnaire of patients which performed prospectively as primary data and secondary data from medical record of patients. The results of this study showed that 54.3% of patients had a good quality of life, 45% had a moderate quality of life, and 0.7% had a poor quality of life. There are no significant differences in quality of life-based on age, gender, diagnosis, and duration of drug use.

Keywords: antiplatelet, quality of life, coronary artery disease, coronary heart disease

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811 Whole Coding Genome Inter-Clade Comparison to Predict Global Cancer-Protecting Variants

Authors: Lamis Naddaf, Yuval Tabach

Abstract:

In this research, we identified the missense genetic variants that have the potential to enhance resistance against cancer. Such field has not been widely explored, as researchers tend to investigate mutations that cause diseases, in response to the suffering of patients, rather than those mutations that protect from them. In conjunction with the genomic revolution, and the advances in genetic engineering and synthetic biology, identifying the protective variants will increase the power of genotype-phenotype predictions and can have significant implications on improved risk estimation, diagnostics, prognosis and even for personalized therapy and drug discovery. To approach our goal, we systematically investigated the sites of the coding genomes and picked up the alleles that showed a correlation with the species’ cancer resistance. We predicted 250 protecting variants (PVs) with a 0.01 false discovery rate and more than 20 thousand PVs with a 0.25 false discovery rate. Cancer resistance in Mammals and reptiles was significantly predicted by the number of PVs a species has. Moreover, Genes enriched with the protecting variants are enriched in pathways relevant to tumor suppression like pathways of Hedgehog signaling and silencing, which its improper activation is associated with the most common form of cancer malignancy. We also showed that the PVs are more abundant in healthy people compared to cancer patients within different human races.

Keywords: comparative genomics, machine learning, cancer resistance, cancer-protecting alleles

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810 Hydrogen Production By Photoreforming Of n-Butanol And Structural Isomers Over Pt Doped Titanate Catalyst

Authors: Hristina Šalipur, Jasmina Dostanić, Davor Lončarević, Matej Huš

Abstract:

Photocatalytic water splitting/alcohol photoreforming has been used for the conversion of sunlight energy in the process of hydrogen production due to its sustainability, environmental safety, effectiveness and simplicity. Titanate nanotubes are frequently studied materials since they combine the properties of photo-active semiconductors with the properties of layered titanates, such as the ion-exchange ability. Platinum (Pt) doping into titanate structure has been considered an effective strategy in better separation efficiency of electron-hole pairs and lowering the overpotential for hydrogen production, which results in higher photocatalytic activity. In our work, Pt doped titanate catalysts were synthesized via simple alkaline hydrothermal treatment, incipient wetness impregnation method and temperature-programmed reduction. The structural, morphological and optical properties of the prepared catalysts were investigated using various characterization techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM), N2 physisorption, and diffuse reflectance spectroscopy (DRS). The activities of the prepared Pt-doped titanate photocatalysts were tested for hydrogen production via photocatalytic water splitting/alcohol photoreforming process under simulated solar light irradiation. Characterization of synthesized Pt doped titanate catalysts showed crystalline anatase phase, preserved nanotubular structure and high specific surface area. The result showed enhancement of activity in photocatalytic water splitting/alcohol photoreforming in the following order 2-butanol>1-butanol>tert-butanol, with obtained maximal hydrogen production rate of 7.5, 5.3 and 2 mmol g-1 h-1, respectively. Different possible factors influencing the hole scavenging ability, such as hole scavenger redox potential and diffusivity, adsorption and desorption rate of the hole scavenger on the surface and stability of the alcohol radical species generated via hole scavenging, were investigated. The theoretical evaluation using density functional theory (DFT) further elucidated the reaction kinetics and detailed mechanism of photocatalytic water splitting/alcohol photoreforming.

Keywords: hydrogen production, platinum, semiconductor, water splitting, density functional theory

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809 The Biology of Persister Cells and Antibiotic Resistance

Authors: Zikora K. G. Anyaegbunam, Annabel A. Nnawuihe, Ngozi J. Anyaegbunam, Emmanuel A. Eze

Abstract:

The discovery and production of new antibiotics is unavoidable in the fight against drug-resistant bacteria. However, this is only part of the problem; we have never really had medications that could completely eradicate an infection. All pathogens create a limited number of dormant persister cells that are resistant to antibiotic treatment. When the concentration of antibiotics decreases, surviving persisters repopulate the population, resulting in a recurrent chronic infection. Bacterial populations have an alternative survival strategy to withstand harsh conditions or antibiotic exposure, in addition to the well-known methods of antibiotic resistance and biofilm formation. Persister cells are a limited subset of transiently antibiotic-tolerant phenotypic variations capable of surviving high-dose antibiotic therapy. Persisters that flip back to a normal phenotype can restart growth when antibiotic pressure drops, assuring the bacterial population's survival. Persister cells have been found in every major pathogen, and they play a role in antibiotic tolerance in biofilms as well as the recalcitrance of chronic infections. Persister cells has been implicated to play a role in the establishment of antibiotic resistance, according to growing research. Thusthe need to basically elucidate the biology of persisters and how they are linked to antibiotic resistance, and as well it's link to diseases.

Keywords: persister cells, phenotypic variations, repopulation, mobile genetic transfers, antibiotic resistance

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808 Determination of Verapamil Hydrochloride in Tablets and Injection Solutions With the Verapamil-Selective Electrode and Possibilities of Application in Pharmaceutical Analysis

Authors: Faisal A. Salih

Abstract:

Verapamil hydrochloride (Ver) is a drug used in medicine for arrythmia, angina and hypertension as a calcium channel blocker. For the quantitative determination of Ver in dosage forms, the HPLC method is most often used. A convenient alternative to the chromatographic method is potentiometry using a Verselective electrode, which does not require expensive equipment, can be used without separation from the matrix components, which significantly reduces the analysis time, and does not use toxic organic solvents, being a "green", "environmentally friendly" technique. It has been established in this study that the rational choice of the membrane plasticizer and the preconditioning and measurement algorithms, which prevent nonexchangeable extraction of Ver into the membrane phase, makes it possible to achieve excellent analytical characteristics of Ver-selective electrodes based on commercially available components. In particular, an electrode with the following membrane composition: PVC (32.8 wt %), ortho-nitrophenyloctyl ether (66.6 wt %), and tetrakis-4-chlorophenylborate (0.6 wt % or 0.01 M) have the lower detection limit 4 × 10−8 M and potential reproducibility 0.15–0.22 mV. Both direct potentiometry (DP) and potentiometric titration (PT) methods can be used for the determination of Ver in tablets and injection solutions. Masses of Ver per average tablet weight determined by the methods of DP and PT for the same set of 10 tablets were (80.4±0.2 and80.7±0.2) mg, respectively. The masses of Ver in solutions for injection, determined by DP for two ampoules from one set, were (5.00±0.015 and 5.004±0.006) mg. In all cases, good reproducibility and excellent correspondence with the declared quantities were observed.

Keywords: verapamil, potentiometry, ion-selective electrode, pharmaceutical analysis

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807 Examination of Contaminations in Fabricated Cadmium Selenide Quantum Dots Using Laser Induced Plasma Spectroscopy

Authors: Walid Tawfik, W. Askam Farooq, Sultan F. Alqhtani

Abstract:

Quantum dots (QDots) are nanometer-sized crystals, less than 10 nm, comprise a semiconductor or metallic materials and contain from 100 - 100,000 atoms in each crystal. QDots play an important role in many applications; light emitting devices (LEDs), solar cells, drug delivery, and optical computers. In the current research, a fundamental wavelength of Nd:YAG laser was applied to analyse the impurities in homemade cadmium selenide (CdSe) QDots through laser-induced plasma (LIPS) technique. The CdSe QDots were fabricated by using hot-solution decomposition method where a mixture of Cd precursor and trioctylphosphine oxide (TOPO) is prepared at concentrations of TOPO under controlled temperatures 200-350ºC. By applying laser energy of 15 mJ, at frequency 10 Hz, and delay time 500 ns, LIPS spectra of CdSe QDots samples were observed. The qualitative LIPS analysis for CdSe QDs revealed that the sample contains Cd, Te, Se, H, P, Ar, O, Ni, C, Al and He impurities. These observed results gave precise details of the impurities present in the QDs sample. These impurities are important for future work at which controlling the impurity contents in the QDs samples may improve the physical, optical and electrical properties of the QDs used for solar cell application.

Keywords: cadmium selenide, TOPO, LIPS spectroscopy, quantum dots

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806 Experimental and Finite Element Analysis of Large Deformation Characteristics of Magnetic Responsive Hydrogel Nanocomposites Membranes

Authors: Mallikarjunachari Gangapuram

Abstract:

Stimuli-responsive hydrogel nanocomposite membranes are gaining significant attention these days due to their potential applications in various engineering fields. For example, sensors, soft actuators, drug delivery, remote controlled therapy, water treatment, shape morphing, and magnetic refrigeration are few advanced applications of hydrogel nanocomposite membranes. In this work, hydrogel nanocomposite membranes are synthesized by embedding nanometer-sized (diameter - 300 nm) Fe₃O₄ magnetic particles into the polyvinyl alcohol (PVA) polymer. To understand the large deformation characteristics of these membranes, a well-known experimental method ball indentation technique is used. Different designing parameters such as membrane thickness, the concentration of magnetic particles and ball diameter on the viscoelastic properties are studied. All the experiments are carried out without and with a static magnetic field. Finite element simulations are carried out to validate the experimental results. It is observed, the creep response decreases and Young’s modulus increases as the thickness and concentration of magnetic particles increases. Image analysis revealed the hydrogel membranes are undergone global deformation for ball diameter 18 mm and local deformation when the diameter decreases from 18 mm to 0.5 mm.

Keywords: ball indentation, hydrogel membranes, nanocomposites, Young's modulus

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805 Additional Usage of Remdesivir with the Standard of Care in Patients with Moderate And Severe COVID-19: A Tertiary Hospital’s Experience

Authors: Pugazhenthan Thangaraju

Abstract:

Background: Since the pandemic began, more than millions of people have become infected with COVID-19. Globally, researchers are working for safe and effective treatments for this disease. Remdesivir is a drug that has been approved for the treatment of COVID-19. Many aspects are still being considered that may influence the future use of remdesivir. Aim: To assess the safety and efficacy of Remdesivir in hospitalized adult patients diagnosed with moderate and severe COVID-19. Methods: It was a record-based retrospective cohort study conducted between April 1st, 2020 and June 30th, 2021 at the tertiary care teaching hospital All India Institutes of Medical Sciences (AIIMS), Raipur Results: There were a total of 10,559 medical records of COVID-19 patients of which 1034 records were included in this study. Overall, irrespective of the survival status, there was statistical significant difference observed between the WHO score at the time of admission and discharge. Clinical improvement among the survivors was found to be statistically significant. Conclusion: Remdesivir's potential efficacy against coronaviruses has so far been limited to in vitro studies and animal models. However, information about COVID-19 is rapidly expanding. Several clinical trials for the treatment of COVID-19 with remdesivir are now underway. However, the findings of this study support remdesivir as a promising agent in the fight against SARS-CoV-2.

Keywords: Remdesivir, COVID-19, SARS-CoV-2, antiviral, RNA-dependent RNA polymerase, viral pneumonia

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804 Mathematical Study of CO₂ Dispersion in Carbonated Water Injection Enhanced Oil Recovery Using Non-Equilibrium 2D Simulator

Authors: Ahmed Abdulrahman, Jalal Foroozesh

Abstract:

CO₂ based enhanced oil recovery (EOR) techniques have gained massive attention from major oil firms since they resolve the industry's two main concerns of CO₂ contribution to the greenhouse effect and the declined oil production. Carbonated water injection (CWI) is a promising EOR technique that promotes safe and economic CO₂ storage; moreover, it mitigates the pitfalls of CO₂ injection, which include low sweep efficiency, early CO₂ breakthrough, and the risk of CO₂ leakage in fractured formations. One of the main challenges that hinder the wide adoption of this EOR technique is the complexity of accurate modeling of the kinetics of CO₂ mass transfer. The mechanisms of CO₂ mass transfer during CWI include the slow and gradual cross-phase CO₂ diffusion from carbonated water (CW) to the oil phase and the CO₂ dispersion (within phase diffusion and mechanical mixing), which affects the oil physical properties and the spatial spreading of CO₂ inside the reservoir. A 2D non-equilibrium compositional simulator has been developed using a fully implicit finite difference approximation. The material balance term (k) was added to the governing equation to account for the slow cross-phase diffusion of CO₂ from CW to the oil within the gird cell. Also, longitudinal and transverse dispersion coefficients have been added to account for CO₂ spatial distribution inside the oil phase. The CO₂-oil diffusion coefficient was calculated using the Sigmund correlation, while a scale-dependent dispersivity was used to calculate CO₂ mechanical mixing. It was found that the CO₂-oil diffusion mechanism has a minor impact on oil recovery, but it tends to increase the amount of CO₂ stored inside the formation and slightly alters the residual oil properties. On the other hand, the mechanical mixing mechanism has a huge impact on CO₂ spatial spreading (accurate prediction of CO₂ production) and the noticeable change in oil physical properties tends to increase the recovery factor. A sensitivity analysis has been done to investigate the effect of formation heterogeneity (porosity, permeability) and injection rate, it was found that the formation heterogeneity tends to increase CO₂ dispersion coefficients, and a low injection rate should be implemented during CWI.

Keywords: CO₂ mass transfer, carbonated water injection, CO₂ dispersion, CO₂ diffusion, cross phase CO₂ diffusion, within phase CO2 diffusion, CO₂ mechanical mixing, non-equilibrium simulation

Procedia PDF Downloads 174