El-Demerdash E.,Ain Shams University
Toxicology and Applied Pharmacology | Year: 2011
Methyl palmitate (MP) has been shown earlier to inhibit Kupffer cells and rat peritoneal macrophages. To evaluate the potential of MP to inhibit the activation of other macrophages, RAW cells (macrophages of alveolar origin) were treated with varying concentrations of MP (0.25, 0.5, 1 mM). Assessment of cytotoxicity using MTT assay revealed that 0.25 and 0.5. mM are not toxic to RAW cells. MP was able to inhibit the phagocytic function of RAW cells. Treatment of cells with MP 24 hours prior to LPS stimulation significantly decreased nitric oxide release and altered the pattern of cytokines release; there was a significant decrease in TNF-α and a significant increase in IL-10 compared to the controls. However, there is a non-significant change in IL-6 level. Furthermore, phosphorylation of inhibitory kappa B (IκBα) protein was significantly decreased in RAW cells treated with 0.5. mM MP after LPS stimulation. Based upon the in-vitro results, it was examined whether MP treatment will be effective in preventing bleomycin-induced lung inflammation and fibrosis in-vivo. Bleomycin given by itself caused destruction of the lung architecture characterized by pulmonary fibrosis with collapse of air alveoli and emphysematous. Bleomycin induced a significant increase in hydroxyproline level and activated NF-κB, p65 expression in the lung. MP co-treatment significantly ameliorated bleomycin effects. These results suggest that MP has a potential of inhibiting macrophages in general. The present study demonstrated for the first time that MP has anti-inflammatory and antifibrotic effect that could be through NF-kB inhibition. Thus MP like molecule could be a promising anti-inflammatory and antifibrotic drug. © 2011 Elsevier Inc.
El-Naga R.N.,Ain Shams University
Toxicology and Applied Pharmacology | Year: 2014
Cisplatin is an effective anti-cancer drug; however, its clinical use is usually associated with nephrotoxicity as a dose-limiting side effect. Several molecular mechanisms have been found to be involved in this nephrotoxicity such as oxidative stress, inflammation and apoptosis. The aim of this study was to explore the potential nephroprotective effect of cardamonin, a flavone found in Alpinia plant, in a rat model of cisplatin-induced nephrotoxicity. The possible mechanisms underlying this nephroprotective effect were investigated. Cardamonin was given at two different doses; 10 and 30. mg/kg orally for two weeks, starting one week before giving a single nephrotoxic dose of cisplatin (7. mg/kg). Acute nephrtoxicity was evident by significantly increased blood urea nitrogen and serum creatinine levels. Also, cisplatin increased lipid peroxidation and depleted reduced glutathione level and superoxide dismutase. Additionally, cisplatin showed a marked pro-inflammatory response as evidenced by significant increase in tissue levels of IL-1β, TNF-α, NF-kB, iNOS, ICAM-1 and MCP-1. Pre-treatment with cardamonin significantly attenuated the nephrotoxic effects, oxidative stress and inflammation induced by cisplatin, in a dose-dependent manner. Also, cardamonin decreased caspase-3 expression and Bax/Bcl-2 ratio as compared to cisplatin group. Besides, cradamonin reversed cisplatin-induced decrease in EGF. Furthermore, up-regulation of NOX-1 was found to be involved in cisplatin-induced nephrotoxicity and its expression was significantly reduced by cardamonin. Histopathological examination further confirmed the nephroprotective effect of cardamonin. Moreover, pre-treatment with subtoxic concentration of cardamonin has significantly enhanced cisplatin cytotoxic activity in four different human cancer cell lines; hela, hepG2, PC3 and HCT116 cancer cell lines. In conclusion, these findings suggest that cardamonin improves therapeutic index of cisplatin and that NOX-1 is partially involved in the pathogenesis of cispaltin-induced nephrotoxicity. © 2013 Elsevier Inc.
El-Raggal T.M.,Ain Shams University
British Journal of Ophthalmology | Year: 2011
Purpose: To evaluate the safety and efficacy of combined intracorneal ring segments (KERARINGS) insertion and corneal collagen cross-linking (CXL) performed in one session or two sessions and to present the refractive outcomes. Setting: Magrabi Eye Hospital, Cairo, Egypt. Methods: This prospective comparative study included 16 eyes of 10 patients with progressive mild to moderate keratoconus that were randomly divided into two groups. Group 1 included nine eyes that underwent KERARINGS insertion followed by CXL 6 montsh later; group 2 included seven eyes that underwent the two procedures at the same day. In both groups channel creation was performed using the femtosecond laser (Intralase FS 60). Results: There was statistically significant improvement in both groups' uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA), with significant reduction in refractive error and keratometric values (p<0.05). There was no statistically significant difference between both groups regarding the changes in UDVA, CDVA and refractive error (p>0.05). However, group 2 revealed more statistically significant reduction of keratometric values on topographical examination (p=0.046). The stromal haze that developed in both groups was more marked and persistent in group 2 than in group 1. Conclusion: Combined KERARINGS insertion and CXL can be performed safely in one or two sessions. However, the same-session procedure appears to be more effective regarding the improvement in the corneal shape.
Shebl M.,Ain Shams University
Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy | Year: 2014
The 1:1 condensation of o-acetoacetylphenol and 1,2-diaminopropane under condition of high dilution gives the mono-condensed Schiff base, (E)-3-(1-aminopropan-2-ylimino)-1-(2-hydroxyphenyl)butan-1-one. The mono-condensed Schiff base has been used for further condensation with isatin to obtain the new asymmetrical dicompartmental Schiff base ligand, (E)-3-(2-((E)-4-(2-hydroxyphenyl)-4-oxobutan-2-ylideneamino) propylimino)indolin-2-one (H3L) with a N2O3 donor set. Reactions of the ligand with metal salts give a series of new binuclear complexes. The ligand and its metal complexes were characterized by elemental analyses, IR, 1H and 13C NMR, electronic, ESR and mass spectra, conductivity and magnetic susceptibility measurements as well as thermal analyses. The analytical and spectroscopic tools showed that the complexes can be formulated as: [(HL)(VO)2(SO4)(H 2O)]·4H2O, [(HL)Fe2Cl4(H 2O)3]·EtOH, [(HL)Fe2(ox)Cl 2(H2O)3]·2H2O, [(L)M 2(OAc)(H2O)m]·nH2O; M = Co, Ni or Cu, m = 4, 0 and n = 2, 3, [(HL)Cu2Cl]Cl·6H2O and [(L)(UO2)2(OAc)(H2O)3] ·6H2O. The metal complexes exhibited octahedral geometrical arrangements except copper complexes that exhibited tetrahedral geometries and uranyl complex in which the metal ion is octa-coordinated. The Schiff base and its metal complexes were evaluated for antimicrobial activity against Gram positive bacteria (Staphylococcus aureus), Gram negative bacteria (Escherichia coli) and fungi (Candida albicans and Aspergillus flavus). The ligand and some of its complexes were found to be biologically active. The DNA-binding properties of the copper complexes (6 and 7) have been investigated by electronic absorption, fluorescence and viscosity measurements. The results obtained indicate that these complexes bind to DNA via an intercalation binding mode with an intrinsic binding constant, Kb of 1.34 × 10 4 and 2.5 × 104 M-1, respectively. © 2013 Elsevier B.V. All rights reserved.
Abdel-Rahman O.,Ain Shams University
Critical Reviews in Oncology/Hematology | Year: 2016
Till now, the prognosis of advanced gastric cancer looked dreadful; thus the search for newer better approaches for this lethal disease has been a strategic target for cancer researchers. In recent years, important immunobiological aspects of the tumor have been revealed with the subsequent proposal of immune check point inhibitors to target these pathways. Clinically, unselected use of immune checkpoint inhibitors in gastric cancer has been deemed with failure; in contrast to the clear success of more recent studies reporting on the use of pembrolizumab in molecularly selected patients. This may illustrate that any future use of immune checkpoint inhibitors in gastric cancer has to be molecularly supported. This review provides a delicate dissection of the clinical and immunobiological considerations underlying the use of these agents in addition to a thorough review of the published clinical data of immune checkpoint inhibitors in gastric cancer. © 2015 Elsevier Ireland Ltd.
Aboul-Fotouh S.,Ain Shams University
Pharmacology Biochemistry and Behavior | Year: 2013
Multiple evidences suggest that depression is accompanied by an induction of oxidative/nitrosative stress (O&NS) pathways and by a reduced antioxidant status. Coenzyme Q10 (CoQ10) is an essential cofactor in the mitochondrial electron transport pathway and has a powerful antioxidant capacity. Methods This study investigated the effect of chronic treatment with CoQ10 (25, 50, 100 and 150 mg/kg/day, i.p. for 3 weeks) on depressive-like behavior and hippocampal, O&NS, and DNA damage, induced by chronic restraint stress (CRS), an experimental model of depression, in rats. Results CoQ10 showed a significant antidepressant effect, as evidenced by amelioration of CRS-induced behavioral aberrations in forced swimming and open field tests, elevated corticosterone level and body weight loss. Moreover, CoQ10 dose-dependently restored the hippocampal catalase, glutathione peroxidase and reduced glutathione and decreased the hippocampal malondialdehyde, nitric oxide and 8-hydroxy-2′- deoxyguanosine levels, which indicated a potential protective effect of CoQ10 against hippocampal O&NS lipid peroxidation and DNA damage. Conclusion CoQ10 possesses antidepressant activity and can protect against CRS-induced hippocampal DNA damage which could be mediated in part by maintaining mitochondrial function and its well documented antioxidant properties. Therefore, CoQ10 may have a potential therapeutic value for the management of depressive disorders. However, further research, is still required to characterize the mechanism of the antidepressant effect of CoQ10 and extend these results before the safe application in humans. © 2013 Elsevier Inc.
Abdel-Rahman O.,Ain Shams University
Critical Reviews in Oncology/Hematology | Year: 2015
The prognosis of advanced gastric cancer has been dreadful with the majority of patients dying of their disease within 1 year of the diagnosis. In the advanced stage several therapeutic options can be discussed, including molecular targeted agents, but biological predicting factors are lacking. A number of molecular targets have been studied over the last decade bringing to several phase II studies; however very few agents moved into phase III clinical trials. The VEGFR-2 inhibitor monoclonal antibody ramucirumab has been recently approved in advanced progressing gastric cancer. This article reviews the basic science as well as clinical data of VEGF signaling in advanced gastric cancer with special emphasis on the different VEGF targeting agents tested previously in this disease. © 2014 Elsevier Ireland Ltd.
Abdel-Rahman O.,Ain Shams University
Critical Reviews in Oncology/Hematology | Year: 2015
Thyroid cancer is the most common endocrine malignancy, representing 1% of all human malignancies; its incidence has been escalating worldwide during the last decades. In recent years important molecular pathways contributing to tumor progression and worse survival rates have been identified in iodine-refractory differentiated thyroid carcinoma (DTC) with the consequent development of molecular therapeutics to target these specific oncogenic pathways. For example, a positive correlation has been found between expression of vascular endothelial growth factor (VEGF) and a more aggressive phenotype of DTC. This has led to the widespread adoption of VEGF-targeted therapeutics in the preclinical and clinical settings. In this review we will provide an overview of the different aspects of the use of VEGF-pathway-oriented treatments in iodine-refractory DTC with particular focus on future prospects. © 2014 Elsevier Ireland Ltd.
Salman A.G.,Ain Shams University
Journal of Cataract and Refractive Surgery | Year: 2013
Purpose: To evaluate the effectiveness and safety of transepithelial corneal collagen crosslinking (CXL) in children with keratoconus and the refractive changes induced by this treatment. Setting: Ophthalmology Department, Ain-Shams University Hospitals, Cairo, Egypt. Design: Prospective comparative case series. Methods: Patients younger than 18 years with bilateral keratoconus had transepithelial CXL with the use of transepithelial riboflavin. The other eye was used as a control and was treated conservatively. The uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and corneal tomography at 12 months were the main outcome measures. Results: The mean age of the 22 patients (22 eyes) was 15.7 years ± 2.1 (SD). After transepithelial CXL, the improvement in the mean UDVA was statistically significant (from 0.95 ± 0.34 logMAR to 0.68 ± 0.45 logMAR) (P<.05). No eye lost lines of preoperative UDVA; 1 eye lost 1 line of preoperative CDVA. There was no improvement in the control group in UDVA or CDVA (P>.05). The mean simulated keratometry (K) decreased by a mean of 2.03 diopters (D), with mean flattening of the apical K by 2.20 D; both results were statistically significant (P<.05). In the control group, the simulated K increased by a mean of 0.59 D (P>.05), with mean steepening of the apical K by 2.9 D (P<.05). No significant changes occurred in the endothelial cell count in either group. Conclusion: Preliminary results of transepithelial CXL in children with keratoconus were encouraging, with no evidence of progression of keratoconus over 12 months. Financial Disclosure: The author has no financial or proprietary interest in any material or method mentioned. © 2013 ASCRS and ESCRS.
Hasanien H.M.,Ain Shams University
IEEE Transactions on Industrial Electronics | Year: 2011
Particle swarm optimization (PSO) is a computational intelligence-based technique that is not largely affected by the size and nonlinearity of the problem and can converge to the optimal solution in many problems where most analytical methods fail to converge. The PSO algorithm is applied to the design optimization problem of a permanent-magnet type transverse flux linear motor (TFLM). The objective of the optimization is to reduce the motor weight while maximizing the thrust force as well as minimizing the detent force of the motor. The stator pole length, the air gap length, the winding window width, and the stator pole width define the search space for the optimization problem. Response surface methodology (RSM) is well adapted to obtain an analytical model of the motor weight, detent force, and thrust force. The RSM enables objective functions to be easily created and a great computational time to be saved. Finite element computations are used for numerical experiments on geometrical design variables in order to determine the coefficients of a second-order analytical model for the RSM. The finite element analysis based model is verified by experimental results. The effectiveness of the proposed PSO model is then compared with that of the conventional optimization models and genetic algorithms model. With this proposed PSO technique, the weight of the initially designed TFLM and its detent force can be reduced, as well as its thrust force can be increased. © 2010 IEEE.