39 results on '"Elewa M"'
Search Results
2. Admission delays’ magnitude of traumatized patients in the emergency department of a hospital in Egypt: a cross-sectional study
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Saleh, H. M., Elsabagh, A. E., Elewa, M. G., Fawzy, A. A., Hassan, O. M., Comer, A. C., Abdelmonem, I. M., Hirshon, J. M., and El-Shinawi, M.
- Published
- 2018
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3. POS-800 DROXIDOPA FOR MANAGEMENT OF CHRONIC HYPOTENSION IN HAEMODIALYSIS
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Jayanti, A., primary, ELEWA, M., additional, Pimblett, P., additional, Morris, D., additional, and Chande, H., additional
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- 2021
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4. Evaluation of Digital Brixmeter Performance for Brix Measurement in Raw Sugar Solution.
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Elewa, M., El-Saady, G., Ibrahim, K., Tawfek, M., and Elhossieny, H.
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SUGAR industry , *SUGAR , *SOLID solutions , *SUCROSE , *FOOD industry - Abstract
The Brix value is an important factor in the sugar industry's extraction processes. Brix refers to the amount of sucrose in the raw sugar solution. The concentration of dissolved solids in a solution is measured by the degree Brix (symbol °Bx). One gram of sucrose in 100 grams of solution equals one-degree Brix. a New Suggested method for measuring brix was designed to be low-cost and accurate Brix measuring in raw sugar solutions. it was depended on Electronic sensors can directly measure the mass, and temperature of the solution to express the brix and give the result on the screen. Digital suggested brixmeter was made based on this method. It can be used manually on the production line and in various food industries. The aim of this paper was to evaluate the digital brixmeter performance for measuring brix in raw sugar solutions. Brix measurements were tested for a group of samples at different sizes to find the optimal measurement sizes can verify accurate brix degree value. The factors affecting the accuracy of the measurement were also studied. The results were compared with the brix read from accurate optical refractometer to check and a prove the accuracy of the proposed digital brixmeter. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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5. Issues on adjointness in multiple-valued logics
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Morsi, Nehad N. and Roshdy, Elewa M.
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- 2006
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6. Predictors of Hemorrhagic Transformation in Patients Receiving r-tPA
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Alosh, T K, primary, Aref, H, primary, Elewa, M K, primary, and Mohamed, A A, primary
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- 2020
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7. DEVELOPING A MACHINE FOR FERTILIZING VEGETABLE CROPS WITH COMPOST
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Werby, R., primary, Zaalouk, A., additional, El-Soaaly, I., additional, Mosallm, M., additional, and Elewa, M., additional
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- 2019
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8. Cone Beam Computed Tomography role in surgical treatment planning of Obstructive Sleep Apnea patients
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Aboelmaaty, Wael, primary, Isaac, Marco, additional, Elsobky, A., additional, and Elewa, M., additional
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- 2018
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9. Admission delays’ magnitude of traumatized patients in the emergency department of a hospital in Egypt: a cross-sectional study
- Author
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Saleh, H. M., primary, Elsabagh, A. E., additional, Elewa, M. G., additional, Fawzy, A. A., additional, Hassan, O. M., additional, Comer, A. C., additional, Abdelmonem, I. M., additional, Hirshon, J. M., additional, and El-Shinawi, M., additional
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- 2017
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10. Issues on adjointness in multiple-valued logics
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Nehad N. Morsi and Elewa M. Roshdy
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Discrete mathematics ,Information Systems and Management ,Inference ,Computer Science::Artificial Intelligence ,Computer Science Applications ,Theoretical Computer Science ,Conjunction (grammar) ,Algebra ,Artificial Intelligence ,Control and Systems Engineering ,Close relationship ,Rule of inference ,Modus ponens ,Commutative property ,Software ,Locard's exchange principle ,Associative property ,Mathematics - Abstract
We contribute to the theory of implications and conjunctions related by adjointness, in multiple-valued logics. We suggest their use in Zadeh's compositional rule of inference, to interpret generalized modus ponens inference schemata. We provide new complete characterizations of implications that distinguish left arguments, implications that satisfy the exchange principle, divisible conjunctions, commutative conjunctions, associative conjunctions and triangular norms. We also introduce and characterize pseudo-strict and pseudo-continuous implications and conjunctions, and we explore the close relationship between these two notions.
- Published
- 2006
11. Ultrafiltration by a super-hydrophilic regenerated cellulose membrane
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Naim, M. M., primary, El-Shafei, A. A., primary, Moneer, A. A., primary, and Elewa, M. M., primary
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- 2015
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12. Application of silver-, iron-, and chitosan- nanoparticles in wastewater treatment.
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Naim, M. M., El-Shafei, A. A., Elewa, M. M., and Moneer, A. A.
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WASTEWATER treatment ,SOLUTION (Chemistry) ,ESCHERICHIA coli ,IRON ,HEAVY metals ,GLUTARALDEHYDE - Abstract
Silver nanoparticles (Ag-NPs) play an important role in the electronic industry, whereas, Zerovalent iron (ZVI) has been widely investigated for environmental remediation due to its fairly strong reducing power and its ability to adsorb an array of important contaminants such as heavy metals and metalloids, while, chitosan nanoparticles (CS-NPs) have proven efficacy in removal of heavy metals, dyes and phenols from wastewater. In the present work, chemical methods have been conducted to prepare nanoparticles made from silver, iron, and chitosan. Ag-NPs were prepared from AgNO3 as starting material then the particles obtained were coated on filter paper; also, a cellulose acetate (CA) membrane was prepared after mixing the casting solution with Ag-NPs, then both subjected to Escherichia (E.) coli bacteria for testing their ability to destroy the bacteria. The E. coli was prepared according to a standard procedure and the colonies counted before and after treatment with treated filter paper and membrane. It is noteworthy that the present work contains a simple new method to prepare Ag-NPs. Results proved that Ag-NPs destroy the E. coli bacteria completely at room temperature in both filter paper and CA membrane. Also, Nano iron (nZVI) was prepared by reduction of ferric chloride by sodium borohydride, then filtered and used to remove Cu(II) ions from aqueous solution. CS-NPs were prepared by two methods, first by preparation of low molecular weight chitosan (LWCS) followed by its degradation to CS-NPs using different concentrations of H
2 O2 solution. The second method was done by preparing CS-NPs using AgNO3 . The CS-NPs membrane was able to biosorb 70.68 and 42.1% of NaCl from a 9.38 and 15.2 g/L salt solution respectively, whereas biosorption of CuSO4 was 59.8% from 12.5 g/L solution, due to the presence of numerous functional groups besides the amino and hydroxyl groups. [ABSTRACT FROM AUTHOR]- Published
- 2017
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13. MICROSTRUCTURAL MODELING OF INTRINSIC STRESSES IN MULTI-JUNCTION BASED PHOTOVOLTAIC
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Hatem, T., primary, Elewa, M., additional, and Salah, A., additional
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- 2014
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14. VIRTUAL INSTRUMENTATION BASED SYSTEMS FOR REAL-TIME PATH PLANNING OF MOBILE ROBOTS USING BIO-INSPIRED NEURAL NETWORKS
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HAMMAD, ABDALLAH, primary, YANG, SIMON X., additional, ELEWA, M. TAREK, additional, MANSOUR, HALA, additional, and ALI, SALAH, additional
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- 2011
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15. AERODYNAMIC PERFORMANCE OF A HIGH-TURNING TURBIN CASCADE WITH VARYING TIP CLEARANCE
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Shaalan, M, primary, AbdulGawad, A, additional, and Elewa, M, additional
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- 2011
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16. Structural analysis of OmpR a transcription regulator in the mutualistic bacterium, Xenorhabdus nematophila
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Borden, W., primary, Wolff, B., additional, Vogt, C., additional, Jordan, P., additional, Ayesh, M., additional, Brook, A., additional, Day, J., additional, Elewa, M., additional, Flesner, G., additional, Kuriga, L., additional, Lopez, H., additional, Maier, B., additional, Radke, J., additional, Yacoob, Z., additional, Klestinski, K., additional, Vogt, D., additional, and Forst, Steve, additional
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- 2009
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17. Factors associated with fatigue in a family medicine clinic in the United Arab Emirates.
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McIlvenny, S, DeGlume, A, Elewa, M, Fernandez, O, and Dormer, P
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OBESITY complications ,ANXIETY ,DEMOGRAPHY ,MENTAL depression ,EXERCISE ,FAMILY medicine ,FATIGUE (Physiology) ,OUTPATIENT services in hospitals ,SOCIAL change ,EDUCATIONAL attainment ,LIFESTYLES ,DISEASE prevalence ,SEVERITY of illness index ,CASE-control method - Abstract
Background: Fatigue is a common symptom in Family Medicine and it has many associated factors. The Arabian Gulf provides a unique setting for studying these factors, in particular the UAE where rapid development has been a prominent feature.Objectives: The aim of the study was to sample a group of GP attenders and examine the factors which were associated with fatigue in the UAE.Methods: A fatigue scale, psychological questionnaire, detailed history, physical examination and laboratory testing were administered to a sample of attenders at a Family Medicine clinic.Results: Fatigue was more prevalent than in western studies (males 34.0%, females 38. 2%). It was strongly associated with anxiety, especially in younger adults, and it has been recognized that rapid social change is felt most acutely in young adults and adolescents. Depression in females was also a factor. Lack of exercise, obesity and illiteracy played a minor role in the severity of fatigue.Conclusions: Fatigue appears to be a cultural 'idiom of distress', a way of expressing anxiety or depression in a rapidly changing society. [ABSTRACT FROM AUTHOR]- Published
- 2000
18. Toxicity of certain dyes as insecticides and their joint action withsome pyrethroids
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Ahmed, Y. M., Elewa, M. A., and Mostafa, A. M. A.
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PYRETHROIDS ,TOXICITY testing ,INSECTICIDES - Published
- 1985
19. Development of a selective COX-2 inhibitor: from synthesis to enhanced efficacy via nano-formulation.
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Elewa M, Shehda M, Hanna PA, Said MM, Ramadan S, Barakat A, and Abdel Aziz YM
- Abstract
Non-steroidal anti-inflammatory drugs NSAIDs are widely used for managing various conditions including pain, inflammation, arthritis and many musculoskeletal disorders. NSAIDs exert their biological effects by inhibiting the cyclooxygenase (COX) enzyme, which has two main isoforms COX-1 and COX-2. The COX-2 isoform is believed to be directly related to inflammation. Based on structure-activity relationship (SAR) studies of known selective COX-2 inhibitors, our aim is to design and synthesize a novel series of 2-benzamido- N -(4-substituted phenyl)thiophene-3-carboxamide derivatives. These derivatives are intended to be selective COX-2 inhibitors through structural modification of diclofenac and celecoxib. The compound 2-benzamido-5-ethyl- N -(4-fluorophenyl)thiophene-3-carboxamide VIIa demonstrated selective COX-2 inhibition with an IC
50 value of 0.29 μM and a selectivity index 67.24. This is compared to celecoxib, which has an IC50 value of 0.42 μM and a selectivity index 33.8. Molecular docking studies for compound VIIa displayed high binding affinity toward COX-2. Additionally, the suppression of protein denaturation with respect to albumin was performed as an indicative measure of the potential anti-inflammatory efficacy of the novel compounds. Compound VIIa showed potent anti-inflammatory activity with 93% inhibition and an IC50 value 0.54 μM. In comparison, celecoxib achieved 94% inhibition with an IC50 value 0.89 μM. Although molecule VIIa demonstrated significant in vitro anti-inflammatory activity, adhered to Lipinski's "five rules" (RO5) and exhibited promising drug-like properties, it showed indications of poor in vivo activity. This limitation is likely due to poor aqueous solubility, which impacts its bioavailability. This issue could be addressed by incorporating the drug in niosomal nanocarrier. Niosomes were prepared using the thin-film hydration technique. These niosomes exhibited a particle size of less than 200 nm, high entrapment efficiency, and an appropriate drug loading percentage. Transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) studies revealed that the niosomes were spherical and demonstrated compatibility of all of its components. The drug release study indicated that the pure drug had limited practicality for in vivo use. However, incorporating the drug into niosomes significantly improved its release profile, making it more suitable for practical use., Competing Interests: The authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)- Published
- 2024
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20. Impact of fecal microbiota transplantation in severe alcoholic hepatitis: A systematic review and meta-analysis.
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Taha AM, Abouelmagd K, Nada SA, Mahmoud AM, Nguyen D, Sharma S, and Elewa M
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Background and Aim: Severe alcoholic hepatitis (SAH) is a serious condition with few treatments. By modifying the gut-liver axis, fecal microbiota transplantation (FMT) was proposed as a treatment for SAH. The purpose of this meta-analysis was to evaluate the efficacy of FMT versus the standard of care (SOC) in improving SAH patient survival rates., Methods: A thorough search of electronic databases was conducted till September 2023. The survival rates of SAH patients undergoing FMT versus SOC were compared. Using Review Manager 5.4, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated., Results: The meta-analysis consisted of six studies with a total of 371 patients with SAH. Patients who received FMT had significantly higher survival rates at 1 and 3 months compared to those who received SOC, with pooled OR of 2.91 (95% CI: 1.56-5.42, P = 0.0008) and 3.07 (95% CI: 1.81-5.20, P < 0.0001), respectively. However, the survival advantage disappeared after 6 months (OR: 2.96, 95% CI: 0.99-8.85, P = 0.05) and 1 year of follow-up (OR: 1.81, 95% CI: 0.44-7.46, P = 0.41)., Conclusion: This meta-analysis highlights the potential of FMT to significantly improve short-term survival rates in SAH patients. However, the survival benefit did not last 6-12 months. These findings call for additional research into the effectiveness of FMT over the long term, along with strategies for extending the survival benefit., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
- Published
- 2024
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21. Droxidopa for Management of Chronic Hypotension in Hemodialysis.
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Jayanti A and Elewa M
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- 2024
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22. Synthesis, Docking, and DFT Studies on Novel Schiff Base Sulfonamide Analogues as Selective COX-1 Inhibitors with Anti-Platelet Aggregation Activity.
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Aziz YMA, Nafie MS, Hanna PA, Ramadan S, Barakat A, and Elewa M
- Abstract
Selective COX-1 inhibitors are preferential therapeutic targets for platelet aggregation and clotting responses. In this study, we examined the selective COX-1-inhibitory activities of four newly synthesized compounds, 10 - 13 , along with their abilities to inhibit platelet aggregation against ADP and collagen. The target compounds 10 - 13 were synthesized using the conventional method, sonication, and microwave-assisted methods. Microanalytical and spectral data were utilized to elucidate the structures of the new compounds 10 - 13 . Additionally, a spectral NMR experiment [NOESY] was conducted to emphasize the configuration around the double bond of the imine group C=N. The obtained results revealed no observed correlation between any of the neighboring protons, suggesting that the configuration at the C=N double bond is E . Biological results revealed that all the screened compounds 10 - 13 might serve as selective COX-1 inhibitors. They showed IC
50 values ranging from 0.71 μM to 4.82 μM against COX-1 and IC50 values ranging from 9.26 μM to 15.24 μM against COX-2. Their COX-1 selectivity indices ranged between 2.87 and 18.69. These compounds show promise as promising anti-platelet aggregation agents. They effectively prevented platelet aggregation induced by ADP with IC50 values ranging from 0.11 μM to 0.37 μM, surpassing the standard aspirin with an IC50 value of 0.49 μM. Additionally, they inhibited the platelet aggregation induced by collagen with IC50 values ranging from 0.12 μM to 1.03 μM, demonstrating superior efficacy compared to aspirin, which has an IC50 value of 0.51 μM. In silico molecular modeling was performed for all the target compounds within the active sites of COX-1 and COX-2 to rationalize their selective inhibitory activities towards COX-1. It was found that the binding interactions of the designed compounds within the COX-1 active site had remained unaffected by the presence of celecoxib. Molecular modeling and DFT calculations using the B3LYP/6-31+G (d,p) level were performed to study the stability of E -forms with respect to Z -forms for the investigated compounds. A strong correlation was observed between the experimental observations and the quantum chemical descriptors.- Published
- 2024
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23. Thyroid eye disease in Eastern Province of Saudi Arabia: clinical profile and correlation with vitamin D deficiency.
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Alali M, Alkulaib NS, Alkhars A, Albadri K, Al Hassan S, Elewa M, Aldairi W, Alsaqer SK, Al-Abdulqader RA, and Alhammad F
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- Humans, Female, Adult, Male, Saudi Arabia epidemiology, Retrospective Studies, Prospective Studies, Vitamin D, Graves Ophthalmopathy epidemiology, Graves Ophthalmopathy therapy, Vitamin D Deficiency epidemiology
- Abstract
Purpose: To obtain clinical data about disease activity and severity of thyroid eye disease (TED) in a tertiary eye hospital in the Eastern Province of Saudi Arabia and to correlate this data with vitamin D levels., Methods: A clinical observational study was conducted in a specialized eye hospital in Saudi Arabia. It included prospective enrollment of Saudi patients with confirmed TED to evaluate activity and severity according to Clinical Activity Score (CAS) and European Group on Graves' Orbitopathy (EUGOGO), respectively, and also for blood investigation, including thyroid profile and vitamin D levels. In addition, some retrospective data collection included previous medical and surgical treatment and complications., Results: A total of 74 TED patients were included, with a median age of 42 years and a female predominance of 64.9%. Smokers were 18.9%. A family history of thyroid disease was noted in 12.16% of patients. There were 10.8% of patients with active TED. A moderate to severe severity level was observed in 71% of the cases, mild in 15%, and sight-threatening in 6%. Smoking and older age were associated with the active form of TED. There was a 48.4% prevalence of vitamin D deficiency among TED patients and it was not associated with TED severity or activity., Conclusions: This is the first study demonstrating the clinical profile of TED among Saudi patients. Smoking and older age were associated with TED. Vitamin D deficiency among TED patients was not worse than that of the general Saudi population.
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- 2024
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24. Population Pharmacokinetics of Topiramate in Patients with Epilepsy Using Nonparametric Modeling.
- Author
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Elewa M, Alghanem SS, Al-Hashel J, Thussu A, Al-Lanqawi Y, and Matar K
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- Humans, Child, Preschool, Topiramate therapeutic use, Retrospective Studies, Fructose therapeutic use, Fructose pharmacokinetics, Carbamazepine therapeutic use, Seizures drug therapy, Benzodiazepines therapeutic use, Anticonvulsants therapeutic use, Anticonvulsants pharmacokinetics, Epilepsy drug therapy
- Abstract
Background: Topiramate (TPM) is used for the treatment of various epileptic seizures and the prevention of migraine. This study aimed to develop a population pharmacokinetic model and identify covariates that influence TPM behavior in patients with epilepsy in Kuwait., Methods: Data were collected retrospectively from 108 patients (2 years old and above) with epilepsy who were treated with oral TPM and 174 TPM blood samples from 3 hospitals in Kuwait from 2009 to 2016. Data were randomly divided into 2 groups for model development and validation. The population pharmacokinetic model was built using the nonparametric modeling algorithm (Pmetrics). The model was evaluated internally through the visual predictive check method and externally using a new data set., Results: A 1-compartment model with first-order elimination fitted the data well. Covariates showing a significant effect on the elimination rate constant were renal function and coadministration of carbamazepine (CBZ). The mean estimated clearance was 2.11 L/h; this was 50% higher for patients coadministered with CBZ. Age and sex were essential covariates for the volume of distribution (V). The visual predictive check of the final model could predict the measured concentrations. External validation further confirmed the favorable predictive performance of the model with low bias and imprecision for predicting the concentration in a particular population., Conclusions: TPM elimination was increased with CBZ coadministration and was affected by renal function. Meanwhile, age and sex were the main predictors for V. The predictive performance of the final model proved to be valid internally and externally., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2023
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25. Left-sided valvular heart disease in dialysis recipients: a single-centre observational study.
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Elewa M, Mitra S, and Jayanti A
- Abstract
Background: With the increasing prevalence of chronic kidney disease, the number of people receiving renal replacement is expected to increase by 50% by 2030. Cardiovascular mortality remains significantly higher in this population. The presence of valvular heart disease (VHD) in patients with end-stage renal disease is associated with poor survival. In a dialysis cohort, we assessed the prevalence and characteristics of patients with significant VHD, the association with clinical parameters and the impact on survival., Methods: Echocardiographic parameters for dialysis recipients from a single centre in the UK were collected. Significant left-sided heart disease (LSHD) was defined as moderate or severe left valvular lesions or left ventricular systolic dysfunction (LVSD) (ejection fraction <45%) or both. Baseline demographic and clinical characteristics were ascertained., Results: In 521 dialysis recipients {median age 61 years [interquartile range (IQR) 50-72], 59% male}, 88% were on haemodialysis and the median dialysis vintage was 2.8 years (IQR 1.6-4.6). A total of 238 (46%) had evidence of LSHD: 102 had VHD, 63 had LVSD and 73 had both. Overall, 34% had evidence of left-sided VHD. In multivariable regression analysis, age and use of cinacalcet were associated with higher odds of VHD {odds ratio [OR] 1.03 [95% confidence interval (CI) 1.02-1.05] and OR 1.85 [95% CI 1.06-3.23], respectively}, while the use of phosphate binders was associated with increased odds of aortic stenosis [AS; OR 2.64 (95% CI 1.26-5.79)]. The 1-year survival was lower in VHD [78% versus 86% (95% CI 0.72-0.84 and 0.83-0.90), respectively] and in LSHD [78% versus 88% (95% CI 0.73-0.83 and 0.85-0.92), respectively]. In AS, the 1-year survival was 64% (95% CI 0.49-0.82). Using propensity score matching to adjust for age, diabetes and low serum albumin, AS was significantly associated with lower survival ( P = .01). LSHD was significantly associated with worse survival ( P = .008) compared with survival in LVSD ( P = .054)., Conclusion: A high proportion of dialysis patients have clinically significant LSHD. This was associated with higher mortality. In valvular heart disease, the development of AS is independently associated with higher mortality in dialysis patients., Competing Interests: S.M. is member of the CKJ editorial board, Vice Chair EUDIAL, European Renal Association and Chair, Dialysis Society, UK., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)
- Published
- 2023
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26. Synthesis, molecular modeling, selective aldose reductase inhibition and hypoglycemic activity of novel meglitinides.
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Salem MG, Abdel Aziz YM, Elewa M, Nafie MS, Elshihawy HA, and Said MM
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- Aldehyde Reductase metabolism, Benzamides chemical synthesis, Benzamides chemistry, Dose-Response Relationship, Drug, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Humans, Hypoglycemic Agents chemical synthesis, Hypoglycemic Agents chemistry, Models, Molecular, Molecular Structure, Structure-Activity Relationship, Aldehyde Reductase antagonists & inhibitors, Benzamides pharmacology, Enzyme Inhibitors pharmacology, Hypoglycemic Agents pharmacology
- Abstract
In the present study, a novel generation of selective aldose reductase ALR2 inhibitors with significant hypoglycemic activities was designed and modulated based on rhodanine scaffold joined to an acetamide linker in between two lipophilic moieties. The synthesis of the novel compounds was accomplished throughout simple chemical pathways. Molecular docking was performed on B-cell membrane protein SUR1, aldehyde reductase ALR1 and aldose reductase ALR2 active sites. Compounds 10B, 11B, 12B, 15C, 16C, 26F and 27F displayed the highest hypoglycemic activities with 80.7, 85.2, 87, 82.3, 83.5, 81.4 and 85.3% reduction in blood glucose levels, respectively. They were more potent than the standard hypoglycemic agent repaglinide with 65.4% reduction in blood glucose level. Compounds 12B and 15C with IC
50 0.29 and 0.35 µM were more potent than the standard ALR2 inhibitor epalrestat with IC50 0.40 µM. They were selective towards ALR2 over ALR1 134 and 116 folds, respectively. Molecular docking studies matched with the in-vitro and in-vivo results to elucidate the dual activities of both compounds 12B and 15C as potent antagonists for ALR2 over ALR1 and good agonists for the SUR1 protein., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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27. Discovery of Potent Dual EGFR/HER2 Inhibitors Based on Thiophene Scaffold Targeting H1299 Lung Cancer Cell Line.
- Author
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Elrayess R, Abdel Aziz YM, Elgawish MS, Elewa M, Yassen ASA, Elhady SS, Elshihawy HA, and Said MM
- Abstract
Dual targeting of epidermal growth factor receptor (EGFR) and human EGFR-related receptor 2 (HER2) is a proven approach for the treatment of lung cancer. With the aim of discovering effective dual EGFR/HER2 inhibitors targeting non-small cell lung cancer cell line H1299, three series of thieno[2,3-d][1,2,3]triazine and acetamide derivatives were designed, synthesized, and biologically evaluated. The synthesized compounds displayed IC
50 values ranging from 12 to 54 nM against H1299, which were superior to that of gefitinib ( 2 ) at 40 µM. Of the synthesized compounds, 2-(1 H -pyrazolo[3,4-b]pyridin-3-ylamino)- N -(3-cyano4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)acetamide ( 21a ) achieved the highest in vitro cytotoxic activity against H1299, with an IC50 value of 12.5 nM in situ, and 0.47 and 0.14 nM against EGFR and HER2, respectively, values comparable to the IC50 of the approved drug imatinib ( 1 ). Our synthesized compounds were promising, demonstrating high selectivity and affinity for EGFR/HER2, especially the hinge region forming a hydrophobic pocket, which was mediated by hydrogen bonding as well as hydrophobic and electrostatic interactions, as indicated by molecular modeling. Moreover, the designed compounds showed good affinity for T790M EGFR, one of the main mutants resulting in acquired drug resistance. Furthermore, both pharmacokinetic and physicochemical properties of the designed compounds were within the appropriate range for human usage as predicted by the in Silico ADME study. The designed compound ( 21a ) might serve as an encouraging lead compound for the discovery of promising anti-lung cancer agents targeting EGFR/HER2.- Published
- 2020
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28. Synthesis, 3D-QSAR, and Molecular Modeling Studies of Triazole Bearing Compounds as a Promising Scaffold for Cyclooxygenase-2 Inhibition.
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Elrayess R, Elgawish MS, Elewa M, Nafie MS, Elhady SS, and Yassen ASA
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Targeting of cyclooxygenase-2 (COX-2) has emerged as a powerful tool for therapeutic intervention because the overexpression of this enzyme is synonymous with inflammation, cancer, and neurodegenerative diseases. Herein, a new series of 1,2,4-triazole Schiff bases scaffold with aryl and heteroaryl systems 9a-12d were designed, synthesized, structurally elucidated, and biologically evaluated as a potent COX-2 blocker. The rationale beyond the current study is to increase the molecule bulkiness allowing a selective binding to the unique hydrophobic pocket of COX-2. Among the triazole-thiazole hybrids, the one with the para-methoxy moiety linked to a phenyl ring 12d showed the highest In vitro selectivity by COX-2 inhibition assay (IC
50 of 0.04 μM) and in situ anti-inflammatory activity when evaluated using the protein denaturation assay (IC50 of 0.88 μM) in comparison with commercially available selective COX-2 inhibitor, Celecoxib (IC50 of 0.05 μM). Towards the COX-2 selectivity, ligand-based three dimensional quantitative structures activity relationship (3D-QSAR) employing atomic-based and field-based approaches were performed and resulted in the necessity of triazole and thiazole/oxazole scaffolds for COX-2 blocking. Furthermore, the molecular modeling study indicated a high selectivity and promising affinity of our prepared compounds to COX-2, especially the hydrophobic pocket and the mouth of the active site holding hydrogen-bonding, hydrophobic, and electrostatic interactions. In Silico absorption, delivery, metabolism, and excretion (ADME) predictions showed that all the pharmacokinetic and physicochemical features are within the appropriate range for human use.- Published
- 2020
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29. Pharmacophore modeling, 3D-QSAR, synthesis, and anti-lung cancer evaluation of novel thieno[2,3-d][1,2,3]triazines targeting EGFR.
- Author
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Elrayess R, Abdel Aziz YM, Elgawish MS, Elewa M, Elshihawy HA, and Said MM
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Cell Proliferation drug effects, Density Functional Theory, Dose-Response Relationship, Drug, ErbB Receptors antagonists & inhibitors, ErbB Receptors metabolism, Humans, Lung Neoplasms metabolism, Lung Neoplasms pathology, Models, Molecular, Molecular Structure, Triazines chemical synthesis, Triazines chemistry, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, Lung Neoplasms drug therapy, Quantitative Structure-Activity Relationship, Triazines pharmacology
- Abstract
Two series of thieno[2,3-d][1,2,3]triazine derivatives were designed, synthesized, and biologically evaluated as potential epidermal growth factor receptor (EGFR) inhibitors targeting the non-small-cell lung cancer cell line H1299. Most of the synthesized compounds displayed IC
50 values ranging from 25 to 58 nM against H1299, which are superior to that of gefitinib (40 µM). 3-(5,6,7,8-Tetrahydro-7H-cyclohexa[4:5]thieno[2,3-d]-1,2,3-triazin-4-ylamino)benzene-1,3-diamine (6b) achieved the highest cytotoxic activity against H1299 with an IC50 value of 25 nM; it had the ability to decrease the EGFR concentration in H1299 cells from 7.22 to 2.67 pg/ml. In vitro, the IC50 value of compound 6b was 0.33 nM against EGFR, which is superior to that of gefitinib at 1.9 nM and erlotinib at 4 nM. The three-dimensional quantitative structure-activity relationships and molecular modeling studies revealed comparable binding modes of compound 6b, gefitinib, and erlotinib in the EGFR active site. The in silico ADME (absorption, distribution, metabolism, and excretion) prediction parameters of this compound revealed promising pharmacokinetic and physicochemical properties. Moreover, DFT (density functional theory) calculations showed the high reactivity of compound 6b toward the EGFR compared with other compounds. The designed compound 6b might serve as an encouraging lead compound for the discovery of promising anti-lung cancer agents targeting EGFR., (© 2020 Deutsche Pharmazeutische Gesellschaft.)- Published
- 2020
- Full Text
- View/download PDF
30. Synthesis and molecular modeling of novel non-sulfonylureas as hypoglycemic agents and selective ALR2 inhibitors.
- Author
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Salem MG, Aziz YMA, Elewa M, Elshihawy HA, and Said MM
- Subjects
- Aldehyde Reductase metabolism, Animals, Diabetes Complications metabolism, Diabetes Mellitus, Experimental metabolism, Dose-Response Relationship, Drug, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Hypoglycemic Agents chemical synthesis, Hypoglycemic Agents chemistry, Mice, Mice, Inbred BALB C, Models, Molecular, Molecular Structure, Structure-Activity Relationship, Sulfonylurea Compounds chemical synthesis, Sulfonylurea Compounds chemistry, Aldehyde Reductase antagonists & inhibitors, Diabetes Complications drug therapy, Diabetes Mellitus, Experimental drug therapy, Enzyme Inhibitors pharmacology, Hypoglycemic Agents pharmacology, Sulfonylurea Compounds pharmacology
- Abstract
Novel non-sulfonylureas derivatives bearing an acetamide linker between a spirohydantoin scaffold and a phenyl ring were prepared and their hypoglycemic activity was estimated in vivo. Their abilities to discriminate in vitro between aldehyde reductase (ALR1) and aldose reductase (ALR2) were determined. The molecular docking and the in silico prediction studies were performed to rationalize the obtained biological results and to predict the physicochemical properties and drug-likeness scores of the new compounds. N-(2,4-Dichlorophenyl)-2-(2',4'-dioxospiro[fluorene-9,5'-imidazolidine]-3'-yl)acetamide (3e) displayed an 84% reduction in blood glucose level superior to that of repaglinide 66% and showed an IC
50 value of 0.37 μM against ALR2 that is superior to that of sorbinil 3.14 µM. Compound (3e) was selective 96 fold towards ALR2 which is closely related to serious diabetic complications. Based on the identification of this hit candidate, a new generation of safe and effective antidiabetic agents could be designed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
31. Molecular modelling and synthesis of spiroimidazolidine-2,4-diones with dual activities as hypoglycemic agents and selective inhibitors of aldose reductase.
- Author
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Salem MG, Abdel Aziz YM, Elewa M, Elshihawy HA, and Said MM
- Subjects
- Aldehyde Reductase chemistry, Animals, Catalytic Domain, Mice, Inbred BALB C, Molecular Docking Simulation, Aldehyde Reductase antagonists & inhibitors, Enzyme Inhibitors chemistry, Hydantoins chemistry, Hypoglycemic Agents chemistry, Sulfonamides chemistry
- Abstract
Novel derivatives of spiroimidazolidinedione were synthesized and evaluated as hypoglycemic agents through binding to sulfonylurea receptor 1 (SUR1) in pancreatic beta-cells. Their selectivity index was calculated against both aldehyde reductase (ALR1) and aldose reductase (ALR2). Aldehyde reductase is a key enzyme in the polyol pathway that is involved in the etiology of the secondary diabetic complications. All structures were confirmed by microanalysis and by IR,
1 H NMR,13 C NMR and EI-MS spectroscopy. The investigated compounds were subjected to molecular docking and an in silico prediction study to determine their free energy of binding (ΔG) values and predict their physicochemical properties and drug-likeness scores. Compound 1'-(5-chlorothiophene-2-ylsulfonyl)spiro[cyclohexane-1,5'-imidazolidine]-2',4'-dione showed IC50 0.47 µM and 79% reduction in blood glucose level with a selectivity index 127 for ALR2., (Copyright © 2018 Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
32. EPR Oximetry Sensor-Developing a TAM Derivative for In Vivo Studies.
- Author
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Boś-Liedke A, Walawender M, Woźniak A, Flak D, Gapiński J, Jurga S, Kucińska M, Plewiński A, Murias M, Elewa M, Lampp L, Imming P, and Tadyszak K
- Subjects
- Alanine Transaminase metabolism, Animals, Cell Line, Tumor, Cell Survival drug effects, Electron Spin Resonance Spectroscopy, Fluorescent Dyes chemistry, Fluorescent Dyes toxicity, Free Radicals chemistry, HT29 Cells, Humans, Liver drug effects, Liver metabolism, Mice, Mice, Inbred BALB C, Solutions chemistry, Toxicity Tests, Acute, Transaminases metabolism, Trityl Compounds chemical synthesis, Trityl Compounds toxicity, Oximetry methods, Oxygen analysis, Trityl Compounds chemistry
- Abstract
Oxygenation is one of the most important physiological parameters of biological systems. Low oxygen concentration (hypoxia) is associated with various pathophysiological processes in different organs. Hypoxia is of special importance in tumor therapy, causing poor response to treatment. Triaryl methyl (TAM) derivative radicals are commonly used in electron paramagnetic resonance (EPR) as sensors for quantitative spatial tissue oxygen mapping. They are also known as magnetic resonance imaging (MRI) contrast agents and fluorescence imaging compounds. We report the properties of the TAM radical tris(2,3,5,6-tetrachloro-4-carboxy-phenyl)methyl, (PTMTC), a potential multimodal (EPR/fluorescence) marker. PTMTC was spectrally analyzed using EPR and characterized by estimation of its sensitivity to the oxygen in liquid environment suitable for intravenous injection (1 mM PBS, pH = 7.4). Further, fluorescent emission of the radical was measured using the same solvent and its quantum yield was estimated. An in vitro cytotoxicity examination was conducted in two cancer cell lines, HT-29 (colorectal adenocarcinoma) and FaDu (squamous cell carcinoma) and followed by uptake studies. The stability of the radical in different solutions (PBS pH = 7.4, cell media used for HT-29 and FaDu cells culturing and cytotoxicity procedure, full rat blood and blood plasma) was determined. Finally, a primary toxicity test of PTMTC was carried out in mice. Results of spectral studies confirmed the multimodal properties of PTMTC. PTMTC was demonstrated to be not absorbed by cancer cells and did not interfere with luciferin-luciferase based assays. Also in vitro and in vivo tests showed that it was non-toxic and can be freely administrated till doses of 250 mg/kg BW via both i.v. and i.p. injections. This work illustrated that PTMTC is a perfect candidate for multimodal (EPR/fluorescence) contrast agent in preclinical studies.
- Published
- 2018
- Full Text
- View/download PDF
33. Synthesis and EPR-spectroscopic characterization of the perchlorotriarylmethyl tricarboxylic acid radical (PTMTC) and its 13 C labelled analogue (13C-PTMTC).
- Author
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Elewa M, Maltar-Strmečki N, Said MM, El Shihawy HA, El-Sadek M, Frank J, Drescher S, Drescher M, Mäder K, Hinderberger D, and Imming P
- Abstract
A hydrophilic tris(tetrachlorotriaryl)methyl (tetrachloro-TAM) radical labelled 50% with
13 C at the central carbon atom was prepared. The mixture of isotopologue radicals was characterised by continuous wave and pulsed X-band electron paramagnetic spectroscopy (EPS). For the pharmaceutical and medical applications planned, the quantitative influence of oxygen, viscosity, temperature and pH on EPR line widths was studied in aqueous buffer, DMSO, water-methanol and water-glycerol mixtures. Under in vivo conditions, pH can be disregarded. There is a clear oxygen dependence of the width of the12 C isotopologue single EPR line in aqueous solutions while changes in rotational motion (viscosity) are observable only in the doublet lines of the central carbon of the13 C isotopologue. The tetrachloro-TAM proved to be very stable as a solid. Its thermal decay was determined quantitatively by thermal annealing. Towards ascorbic acid as a reducing agent and towards an oocyte cell extract it had a half-life of approx. 60 and 10 min. Thus for in vivo applications, 50%13 C tetrachloro-TAMs are suitable for selective and simultaneous oxygen and macroviscosity measurements in a formulation, e.g. nanocapsules.- Published
- 2017
- Full Text
- View/download PDF
34. Bulk liquid pertraction of NaCl from aqueous solution using carrier-mediated transport.
- Author
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Naim MM, El-Shafei AA, Moneer AA, Elewa MM, and Kandeel WG
- Abstract
In the present work, removal of NaCl using the bulk liquid membrane (BLM) technique has been investigated, using a simple apparatus for conducting the experiments. Variables investigated were volume ratio of donor phase (DP) to receptor phase (RP), presence of sequestering agent (SA) in RP, type of organic liquid membrane (LM), quantity of mobile carrier (MC) in the LM. Stirring speed and volume of LM were kept constant at 100 rpm and 130 ml, respectively. The mass transfer of NaCl was analysed based on kinetic laws of two consecutive irreversible first-order reactions, and kinetic parameters (k
1d , k2m , k2r , , tmax , , and ) for the transport of NaCl were investigated. The values obtained demonstrate that the process is diffusionally controlled. Results indicate that the membrane entrance and exit rate constants (k1 , k2 ) increase with decreasing DP:RP ratio and with decrease in quantity of MC, and quantity of SA, and the presence of dichloroethane (DCE) is preferred to chloroform (CF) as LM.- Published
- 2016
- Full Text
- View/download PDF
35. Synthesis, Characterization, and Nanoencapsulation of Tetrathiatriarylmethyl and Tetrachlorotriarylmethyl (Trityl) Radical Derivatives—A Study To Advance Their Applicability as in Vivo EPR Oxygen Sensors.
- Author
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Frank J, Elewa M, Said MM, El Shihawy HA, El-Sadek M, Müller D, Meister A, Hause G, Drescher S, Metz H, Imming P, and Mäder K
- Subjects
- Electron Spin Resonance Spectroscopy methods, Hydrophobic and Hydrophilic Interactions, Molecular Structure, Oximetry, Trityl Compounds chemistry, Free Radicals chemistry, Oxygen chemistry, Trityl Compounds chemical synthesis
- Abstract
Tissue oxygenation plays an important role in the pathophysiology of various diseases and is often a marker of prognosis and therapeutic response. EPR (ESR) is a suitable noninvasive oximetry technique. However, to reliably deploy soluble EPR probes as oxygen sensors in complex biological systems, there is still a need to investigate and improve their specificity, sensitivity, and stability. We reproducibly synthesized various derivatives of tetrathiatriarylmethyl and tetrachlorotriarylmethyl (trityl) radicals. Hydrophilic radicals were investigated in aqueous solution mimicking physiological conditions by, e.g., variation of viscosity and ionic strength. Their specificity was satisfactory, but the oxygen sensitivity was low. To enhance the capability of trityl radicals as oxygen sensors, encapsulation into oily core nanocapsules was performed. Thus, different lipophilic triesters were prepared and characterized in oily solution employing oils typically used in drug formulations, i.e., middle-chain triglycerides and isopropyl myristate. Our screening identified the deuterated ethyl ester of D-TAM (radical 13) to be suitable. It had an extremely narrow single EPR line under anoxic conditions and excellent oxygen sensitivity. After encapsulation, it retained its oxygen responsiveness and was protected against reduction by ascorbic acid. These biocompatible and highly sensitive nanosensors offer great potential for future EPR oximetry applications in preclinical research.
- Published
- 2015
- Full Text
- View/download PDF
36. Desalination of simulated seawater by purge-air pervaporation using an innovative fabricated membrane.
- Author
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Naim M, Elewa M, El-Shafei A, and Moneer A
- Subjects
- Polymers, Salinity, Seawater, Solutions, Temperature, Water, Membranes, Artificial, Sodium Chloride isolation & purification, Water Purification instrumentation
- Abstract
An innovative polymeric membrane has been invented, which presents a breakthrough in the field of desalination membranes. It can desalinate simulated seawater of exceptionally high concentration to produce a high flux of potable water with over 99.7% salt rejection (%SR) in a once-through purge-air pervaporation (PV) process. A set-up was constructed for conducting the desalination experiments and the effect of initial salt solution concentration (Ci) and pervaporation temperature (Tpv) on the water flux (J), %SR, separation factor, and pervaporation separation index were determined. The membrane was prepared by the phase-inversion technique, of a specially formulated casting solution consisting of five ingredients, after which the membrane was subjected to a post-treatment by which certain properties were conferred. The results confirmed that the salinity of the pervaporate was independent of Ci (all %SR above 99.7). The best result was at Tpv=70 °C, where J varied from 5.97 to 3.45 l/m2 h for Ci=40-140 g NaCl/l, respectively. The membrane morphology was confirmed to be asymmetric. The contact angle was immeasurable, indicating the membrane to be super-hydrophilic. Activation energies computed using Arrhenius law were, under all conditions investigated, less than 20 kJ/mol K.
- Published
- 2015
- Full Text
- View/download PDF
37. Cyclin-dependent kinase-inhibitor 1 (CDKN1A) in the squamous epithelium of the oropharynx: possible implications of molecular biology and compartmentation.
- Author
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Wagner M, Klussmann JP, Fangmann R, Linder R, Elewa ME, Eidt S, Rose VM, Jungehulsing M, and Schulze HJ
- Subjects
- Apoptosis, Biomarkers, Tumor metabolism, Carcinoma, Squamous Cell metabolism, Cell Compartmentation, Cell Differentiation, Cyclin-Dependent Kinase Inhibitor p21, Genomic Imprinting, Humans, Keratinocytes physiology, Mutation, Oropharyngeal Neoplasms metabolism, Oropharynx metabolism, Polymorphism, Genetic, Prognosis, Tumor Suppressor Protein p53 physiology, Carcinoma, Squamous Cell diagnosis, Cyclins genetics, Cyclins metabolism, Cyclins physiology, Oropharyngeal Neoplasms diagnosis
- Abstract
The cdknlA gene encodes CDKN1A, a protein that regulates cell cycle progression, terminal differentiation, and apoptosis. Polymorphisms or loss of heterozygosity of this usually biallelically expressed gene have no major impact on carcinogenesis. The prevalence of somatic mutations in malignancies is low. Gene rearrangements involving cdknlA are scarce. CDKN1A is expressed in both premalignant and malignant lesions. While the prognostic value of nuclear CDKN1A expression is controversial, the prognostic value of its recently discovered cytoplasmic accumulation is simply unknown. CDKN1A translocates from the nucleus to the cytoplasm when cleaved by caspase-like activities during early apoptosis. The presence of cytoplasmic catabolites (e.g.: p14) might therefore indicate apoptosis. We found no correlation between nuclear and cytoplasmic anti-CDKN1A immunoreactivity in our samples of oropharyngeal squamous cell carcinoma. CDKN1A Cap20, CDKN1, CDKN1A, CDKNA1, Cip-1, Mda-6, P21, Pic1, Sdi-1, Waf-1.
- Published
- 2001
38. Mating of musca domestica vicina in the laboratory.
- Author
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Mosallam SS, Elewa ME, Mahmoud WA, and Gad AM
- Subjects
- Animals, Copulation, Female, Fertility, Male, Temperature, Houseflies physiology
- Published
- 1988
39. Oviposition of Musca domestica vicina.
- Author
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Mosallam SS, Elewa ME, Mahmoud WA, and Gad AM
- Subjects
- Animals, Egypt, Female, Seasons, Houseflies physiology, Oviposition
- Published
- 1988
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