Kratz F.,Tumor Biology Center |
Elsadek B.,Assiut University
Journal of Controlled Release | Year: 2012
Among serum proteins albumin and transferrin have attracted the most interest as drug carriers in the past two decades. Prior to that, their potential use was overshadowed by the advent of monoclonal antibodies that was initiated by Milstein and Koehler in 1975. Meanwhile intensive pursuit of exploiting transferrin, but above all albumin as an exogenous or endogenous carrier protein for treating various diseases, primarily cancer, rheumatoid arthritis, diabetes and hepatitis has resulted in several marketed products and numerous clinical trials. While the use of transferrin has clinically been primarily restricted to immunotoxins, albumin-based drug delivery systems ranging from albumin drug nanoparticles, albumin fusion protein, prodrugs and peptide derivatives that bind covalently to albumin as well as physically binding antibody fragments and therapeutically active peptides are in advanced clinical trials or approved products. For treating diabetes, Levemir® and Victoza® that are myristic acid derivatives of human insulin or glucagon-like peptide 1 (GLP-1) act as long-acting peptides by binding to the fatty acid binding sites on circulating albumin to control glucose levels. Levemir® from Novo Nordisk has already developed into a blockbuster since its market approval in 2004. Abraxane®, an albumin paclitaxel nanoparticle as a water-soluble galenic formulation avoiding the use of cremophor/ethanol, transports paclitaxel through passive targeting as an albumin paclitaxel complex to the tumor site and is superior to conventional Taxol® against metastatic breast cancer. INNO-206, an albumin-binding doxorubicin prodrug that also accumulates in solid tumors due to the enhanced permeability and retention (EPR) effect but releases the parent drug through acid cleavage, either intra- or extracellularly, is entering phase II studies against sarcoma. An expanding field is the use of albumin-binding antibody moieties which do not contain the fragment crystallizable (Fc) portion of, conventional immunoglobulin G (IgG) but are comprised of monovalent or bivalent light and/or heavy chains and incorporate an additional albumin-binding peptide or antibody domain. The most advanced antibody of this kind is ATN-103 (Ozoralizumab), a trivalent albumin-binding nanobody that neutralizes the pro-inflammatory tumor necrosis factor alpha (TNF-α) as a causative agent for exacerbating rheumatoid arthritis. ATN-103 is currently in multi-center phase II trials against this debilitating disease. In summary, because albumin as the most abundant circulating protein cannot only be used to improve the pharmacokinetic profile of therapeutically relevant peptides and the targeting moiety of antibodies but also for peptide-based targeting as well as low-molecular weight drugs to inflamed or malignant tissue, it is anticipated that R&D efforts of academia and the pharmaceutical industry in this field of drug delivery will prosper. © 2011 Elsevier B.V. All rights reserved.
Elsadek B.,Assiut University |
Kratz F.,Tumor Biology Center
Journal of Controlled Release | Year: 2012
Over the past decades, albumin has emerged as a versatile carrier for therapeutic and diagnostic agents, primarily for diagnosing and treating diabetes, cancer, rheumatoid arthritis and infectious diseases. Market approved products include fatty acid derivatives of human insulin or the glucagon-like-1 peptide (Levemir ® and Victoza ®) for treating diabetes, the taxol albumin nanoparticle Abraxane ® for treating metastatic breast cancer which is also under clinical investigation in further tumor indications, and 99mTc-aggregated albumin (Nanocoll ® and Albures ®) for diagnosing cancer and rheumatoid arthritis as well as for lymphoscintigraphy. In addition, an increasing number of albumin-based or albumin-binding drugs are in clinical trials such as antibody fusion proteins (MM-111) for treating HER2/neu positive breast cancer (phase I), a camelid albumin-binding nanobody anti-HSA-anti-TNF- α (ATN-103) in phase II studies for treating rheumatoid arthritis, an antidiabetic Exendin-4 analog bound to recombinant human albumin (phase I/II), a fluorescein-labeled albumin conjugate (AFL)-human serum albumin for visualizing the malignant borders of brain tumors for improved surgical resection, and finally an albumin-binding prodrug of doxorubicin (INNO-206) entering phase II studies against sarcoma and gastric cancer. In the preclinical setting, novel approaches include attaching peptides with high-affinity for albumin to antibody fragments, the exploitation of albumin-binding gadolinium contrast agents for magnetic resonance imaging, and physical or covalent attachment of antiviral, antibacterial, and anticancer drugs to albumin that are permanently or transiently attached to human serum albumin (HSA) or act as albumin-binding prodrugs. This review gives an overview of the expanding field of preclinical and clinical drug applications and developments that use albumin as a protein carrier to improve the pharmacokinetic profile of the drug or to target the drug to the pathogenic site addressing diseases with unmet medical needs. © 2011 Elsevier B.V.
Abdo M.A.B.,Assiut University
Engineering Structures | Year: 2012
Among different approaches developed for structural damage detection, changes in the measured static response have shown promise for locating structural damage. In this paper, an analytical study of the relationship between damage characteristics (location and severity) and changes in displacement curvatures is presented. Then a parametric study is carried out on using changes in displacement curvatures in structural damage detection. The influence of many parameters are investigated and applied numerically to two examples; an overhanging beam (statically determinate structure) and a two-span continuous beam (statically indeterminate structure) with different damage characteristics. The numerical results clarify that the displacement curvature, has the characteristic of localization at the damaged region. Also, the obtained results show that the displacement curvature, derived from static response only, can accurately locate single and multiple damages with different damage characteristics for specific load case. The merits as well as the disadvantages of using displacement curvature in structural damage detection are also discussed. © 2011 Elsevier Ltd.
Abdel-Aleem H.,Assiut University
The Cochrane database of systematic reviews | Year: 2013
Preterm birth is a major health problem and contributes to more than 50% of the overall perinatal mortality. Preterm birth has multiple risk factors including cervical incompetence and multiple pregnancy. Different management strategies have been tried to prevent preterm birth, including cervical cerclage. Cervical cerclage is an invasive technique that needs anaesthesia and may be associated with complications. Moreover, there is still controversy regarding the efficacy and the group of patients that could benefit from this operation. Cervical pessary has been tried as a simple, non-invasive alternative that might replace the above invasive cervical stitch operation to prevent preterm birth. To evaluate the efficacy of cervical pessary for the prevention of preterm birth in women with risk factors for cervical incompetence. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 September 2012), Current Controlled Trials and the Australian New Zealand Clinical Trials Registry (1 September 2012). We selected all published and unpublished randomised clinical trials comparing the use of cervical pessary with cervical cerclage or expectant management for prevention of preterm birth. We did not include quasi-randomised trials. Cluster-randomised or cross-over trials were not eligible for inclusion. Two review authors independently assessed trials for inclusion. The review included one randomised controlled trial. The study included 385 pregnant women with a short cervix of 25 mm or less who were between 18 to 22 weeks of pregnancy. The use of cervical pessary (192 women) was associated with a statistically significantly decrease in the incidence of spontaneous preterm birth less than 37 weeks' gestation compared with expectant management (22% versus 59 %; respectively, risk ratio (RR) 0.36, 95% confidence interval (CI) 0.27 to 0.49). Spontaneous preterm birth before 34 weeks was statistically significantly reduced in the pessary group (6% and 27% respectively, RR 0.24; 95% CI 0.13 to 0.43). Mean gestational age at delivery was 37.7 + 2 weeks in the pessary group and 34.9 + 4 weeks in the expectant group. Women in the pessary group used less tocolytics (RR 0.63; 95% CI 0.50 to 0.81) and corticosteroids (RR 0.66; 95% CI 0.54 to 0.81) than the expectant group. Vaginal discharge was more common in the pessary group (RR 2.18; 95% CI 1.87 to 2.54). Among the pessary group, 27 women needed pessary repositioning without removal and there was one case of pessary removal. Ninety-five per cent of women in the pessary group would recommend this intervention to other people. Neonatal paediatric care admission was reduced in the pessary group in comparison to the expectant group (RR 0.17; 95% CI 0.07 to 0.42). The review included only one well-designed randomised clinical trial that showed beneficial effect of cervical pessary in reducing preterm birth in women with a short cervix. There is a need for more trials in different settings (developed and developing countries), and with different risk factors including multiple pregnancy.
Kamel R.M.,Assiut University
Renewable and Sustainable Energy Reviews | Year: 2014
This paper presents survey about Fault Ride Through (FRT) techniques and controllers which employed with all wind generation system types. After presenting a comprehensive FRT survey, paper proposes three Fault Ride Through (FRT) controllers for keeping stability of Fixed Speed Wind Generation (FSWG) system serving in isolated Micro-Grid (MG). The first controller has been implemented by inserting Superconductor Fault Current Limiter (SFCL) in series with wind generator terminals during fault instant. The second proposed FRT controller is modifying the conventional Pitch Angle Controllers (PAC) to can spill and reduce high percentage of extracted mechanical wind power during and subsequent fault occurrence which in turns help stability improvement and restoration. Third FRT technique is performed by adapting the wind turbine gearbox ratio which forces the wind generation system to run far from the maximum power point. The best performance is obtained with the SFCL controller. Superior results are obtained when the three proposed FRT controllers are employed simultaneously. The three developed FRT controllers are simple, reliable and economical attractive. Effects of fault type on SFCL FRT controller performance are analyzed and investigated in details. The proposed SFCL FRT controller has been tested under single phase, double phase, phase to phase, and three phases to ground faults. Results display that the three phases to ground fault is the most severe type on SFCL FRT performance from stability point of view. On the other hand, double phase to ground fault is the most severe one from fluctuations and oscillations points of view. Parameters of the SFCL must be adjusted based on the three phases to ground fault. If the SFCL FRT controller is designed to can deal with three phases fault, it sure can deal with the other fault types successfully. © 2014 Elsevier Ltd.
Kostandy B.B.,Assiut University
Neurological Sciences | Year: 2012
Although being a physiologically important excitatory neurotransmitter, glutamate plays a pivotal role in various neurological disorders including ischemic neurological diseases. Its level is increased during cerebral ischemia with excessive neurological stimulation causing the glutamate-induced neuronal toxicity, excitotoxicity, and this is considered the triggering spark in the ischemic neuronal damage. The glutamatergic stimulation will lead to rise in the intracellular sodium and calcium, and the elevated intracellular calcium will lead to mitochondrial dysfunction, activation of proteases, accumulation of reactive oxygen species and release of nitric oxide. Interruption of the cascades of glutamate-induced cell death during ischemia may provide a way to prevent, or at least reduce, the ischemic damage. Various therapeutic options are suggested interrupting the glutamatergic pathways, e.g., inhibiting the glutamate synthesis or release, increasing its clearance, blocking of its receptors or preventing the rise in intracellular calcium. Development of these strategies may provide future treatment options in the management of ischemic stroke. © Springer-Verlag 2011.
Elsabahy M.,Texas A&M University |
Elsabahy M.,Assiut University |
Wooley K.L.,Texas A&M University
Chemical Society Reviews | Year: 2012
Polymeric nanoparticles-based therapeutics show great promise in the treatment of a wide range of diseases, due to the flexibility in which their structures can be modified, with intricate definition over their compositions, structures and properties. Advances in polymerization chemistries and the application of reactive, efficient and orthogonal chemical modification reactions have enabled the engineering of multifunctional polymeric nanoparticles with precise control over the architectures of the individual polymer components, to direct their assembly and subsequent transformations into nanoparticles of selective overall shapes, sizes, internal morphologies, external surface charges and functionalizations. In addition, incorporation of certain functionalities can modulate the responsiveness of these nanostructures to specific stimuli through the use of remote activation. Furthermore, they can be equipped with smart components to allow their delivery beyond certain biological barriers, such as skin, mucus, blood, extracellular matrix, cellular and subcellular organelles. This tutorial review highlights the importance of well-defined chemistries, with detailed ties to specific biological hurdles and opportunities, in the design of nanostructures for various biomedical delivery applications. © 2012 The Royal Society of Chemistry.
Abo-Khalil A.G.,Assiut University
Renewable Energy | Year: 2012
This paper presents a new synchronization algorithm for grid connection of a doubly fed induction generator (DFIG) in a variable speed wind generation system. Stator flux-oriented vector control for back-to-back PWM converters in the DFIG rotor circuit is used for synchronization process. By controlling the rotor . d-axis current, the magnitude of the stator EMF is adjusted to be equal to the grid voltage. PLL circuit is used to compensate for the phase shift between the stator EMF and the grid voltage. By controlling the turbine pitch angle, the generator speed is determined to adjust the stator frequency to be equal to the grid. The experimental results show a smooth synchronization and fast dynamic responses. Compared to the existing DFIG synchronization algorithms, the proposed method gives fast starting and can take only 2 cycles to be performed and has satisfactory performance and better robustness than existing methods. © 2012 Elsevier Ltd.
Hamad M.A.A.,Assiut University
International Communications in Heat and Mass Transfer | Year: 2011
In this paper, we examine the convective flow and heat transfer of an incompressible viscous nanofluid past a semi-infinite vertical stretching sheet in the presence of a magnetic field. The governing partial differential equations with the auxiliary conditions are reduced to ordinary differential equations with the appropriate corresponding conditions via scaling transformations. The analytical solutions of the resulting ODEs are obtained, and from which the analytical solutions of the original problem are presented. The influence of pertinent parameters such as the magnetic parameter, the solid volume fraction of nanoparticles and the type of nanofluid on the flow, heat transfer, Nusselt number and skin friction coefficient is discussed. Comparison with published results is presented. © 2010 Elsevier Ltd.
Kamel R.M.,Assiut University
Applied Energy | Year: 2014
This paper proposes and designs two novels Fault Ride Through (FRT) controllers for maintaining Fixed Speed Wind Generation system (FSWGs) stability during fault events. The first technique has been implemented by increasing the wind turbine blade pitch angle with maximum possible rate to reduce the mechanical extracted wind power and consequently suppress wind generation system acceleration. The second FRT technique has been verified by adapting gear ratio of wind generation system to run far from optimum maximum power point and help FRT process. Effectiveness of the two proposed FRT techniques has been proven by accurate simulation of the most severe disturbance conditions. Also, Results indicated that second technique gives faster response than the first one. Without employing any FRT technique, FSWGs cannot keep its stability and the standalone Micro-Grid (MG) transfers to the blackout mode. Implementation the two FRT techniques requires no additional hardware. Only, control algorithms need little modification to deal with fault event and help FRT process. This fact makes the two proposed FRT techniques are simple, practical and highly economical attractive. © 2013 Elsevier Ltd.