Ahmed Hamdy | Minia University (original) (raw)

Papers by Ahmed Hamdy

Background: Acalabrutinib (ACP-196) is a highly selective, potent, covalent inhibitor of Bruton t... more Background: Acalabrutinib (ACP-196) is a highly selective, potent, covalent inhibitor of Bruton tyrosine kinase (BTK), in development for the treatment of hematologic malignancies. Acalabrutinib has rapid absorption and a short pharmacokinetic (PK) half-life; twice daily dosing resulted in near complete and continuous BTK inhibition in patients with chronic lymphocytic leukemia (CLL) (Byrd JC, et al. 2016). CYP3A-mediated oxidation is the primary route of elimination for the marketed BTK inhibitor, ibrutinib (de Zwart et al., 2016). Coadministration of ibrutinib with ketoconazole (a strong CYP3A inhibitor) increased dose-normalized maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) by 29- and 24-fold, respectively, whereas coadministration of rifampin (a strong CYP3A inducer) decreased Cmax and AUC of ibrutinib by more than 13- and 10-fold, respectively (IMBRUVICA® (ibrutinib) package insert 2017). Grapefruit juice, which is known to contain...

Dans certains modes de realisation, cette invention comprend des methodes therapeutiques pour l&#... more Dans certains modes de realisation, cette invention comprend des methodes therapeutiques pour l'utilisation d'un inhibiteur de BTK pour traiter des cancers tumoraux solides par modulation du micro-environnement tumoral, notamment les macrophages, les monocytes, les mastocytes, les cellules T auxiliaires, les cellules T cytotoxiques, les cellules T regulatrices, les cellules tueuses naturelles, les cellules suppresseurs derivees de myeloides, les cellules B regulatrices, les neutrophiles, les cellules dendritiques, et les fibroblastes.

Journal of Water Reuse and Desalination, 2020

In this work, δMnO2 was anchored into graphene nanosheets via a mediated simple and eco-friendly ... more In this work, δMnO2 was anchored into graphene nanosheets via a mediated simple and eco-friendly approach to be used as a potential low-cost cathodic catalyst in microbial desalination cells (MDC). MnO2/G based MDC revealed a faster start-up and stable performance during the operation compared with the catalyst-free control MDC. The average chemical oxygen demand (COD) removal efficiencies were 85.11 ± 5.13 and 86.20 ± 4.85% and average columbic efficiencies throughout the operation cycles were 1.52 ± 0.32% and 0.70 ± 0.35% for MnO2/G based reactor and control reactor, respectively. The average desalination efficiencies were 15.67 ± 3.32 and 13.21 ± 2.61% for MnO2/G based reactor and control reactor, respectively. The superior catalytic performance of MnO2/G based cathode improved current generation which is the key desalination stimulus. MnO2/G based reactor revealed a lower internal resistance of 430 Ω compared with 485 Ω for the catalyst-free control reactor and, similarly, the m...

Egyptian Academic Journal of Biological Sciences. A, Entomology, Oct 1, 2018

This study was carried out during two successive years from October 2014 to September 2016. Resul... more This study was carried out during two successive years from October 2014 to September 2016. Results showed that the temperature and moisture R.H.% were significantly affected the mean abundance of the phytophagous mite O. mangiferus and its predator A. swirskii associated with mango orchard trees. The highest mean abundance of O. mangiferus was recorded in the summer season (2.96 ± 0.6 indv./leaf) and (1.33 ± 0.05 indv./leaf) for A. swirskii, respectively in the first year (from October 2014 to September 2015). On the other hand, the lowest mean abundance was recorded in the autumn (0.6 ± 0.11) for O. mangiferus, (0.23 ± 0.09 indv./leaf) for A. swirskii. The mean abundance of O. mangiferus populations increased to (3.43 ± 0.7 indv./leaf) in the second year of study in contrast to the populations of its predator. The results stated that the temperature had a significant effect on the population abundance of the phytophagous mite, O. mangiferus and its predator while the relative humidity had a negative effect on both populations.

Egyptian Dental Journal, 2017

Statement of problem: A new CAD/CAM technology for the fabrication of metal copings for metal-cer... more Statement of problem: A new CAD/CAM technology for the fabrication of metal copings for metal-ceramic restorations has been introduced. However, no sufficient data on the internal fit of metal-ceramic restorations produced by this method is available yet. Purpose: This study was performed to compare the internal gap between abutment teeth and posterior fixed dental prosthesis (FDPs) fabricated utilizing yttria-stabilized tetragonal zirconia polycrystals and Gold Platinum metal ceramic alloy frameworks. Materials and Methods: A randomized controlled clinical trial was performed, twenty FPDs were fabricated with yttria-stabilized zirconia poly crystals (Y-TZP-IPS e.max zir CAD) and metal-ceramic (MC Au-Pt) as follow(n=10): thirty patients were randomly selected for internal fit measurements. The internal fit of the FPDs frameworks were measured using replica technique. Data was analyzed with (ANOVA) test, followed by Tukey's post hoc test. Results: The internal gap, according to the thickness of the replica, was measured under magnification at the following locations: cervical, axial, and occlusal (cusp-tips and central). The internal gaps of FPDs with zirconia frameworks were significantly larger in cervical

Egyptian Dental Journal, 2017

Purpose: This in vitro study measured the adhesive properties of 10-MDP and MPE containing resin ... more Purpose: This in vitro study measured the adhesive properties of 10-MDP and MPE containing resin cements, using two types of zirconia surface treatments; selective infiltration etching(SIE) and airborne particle abrasion (APA) to translucent zirconia (3M, ESPE). Statement of Problem: Due to translucent zirconia modified composition (alumina content reduced to tenth of its weight) bonding strength to different resin cements after different surface treatments should be investigated adequately. Materials and Methods:Sixty sintered Lava plus high translucency disks(3M,ESPE)were randomly divided into three study groups according to their surface treatment: (a) polished surface (control group); (b) air borne particle abraded (grit blasted) with 50 µm aluminum trioxide (APA); and (c) selective infiltration etching (SIE). Zirconia disks (15x2mm) were then bonded to 60 composite resin disks (8x4mm) using two different resin composite cements (Clearfil SA and Rely X). Resin-zirconia adhesion strength was evaluated using the microshear bond strength test (MSBS) after 24 hour of storage in deionized water at 37˚C. One way ANOVA and Scheffé s posthoc tests were used to analyze the data (p<0.001). Then fractured samples were studied under SEM and classified according to failure pattern. Results: Different types of resin cement and surface treatment significantly influenced the MSBS (P<0.001). The highest mean MSBS values were recorded with MDP containing resin cement (Clearfil SA) in both SIE (26.18 ±1.12 MPa) and APA (21.67±1.34) groups. Bond strength values were reduced significantly in control group when using the two types of cements. Regarding failure pattern, MDP groups showed cohesive and MPE and control groups showed adhesive type. Conclusion: SIE and APA in combination with 10-MDP containing resin cement established a strong durable bond to zirconia substrates than MPE groups. SIE and APA showed significant higher bond strength values than control groups.

Blood, 2015

Background: Signaling through the B-cell receptor (BCR) results in cell survival and proliferatio... more Background: Signaling through the B-cell receptor (BCR) results in cell survival and proliferation, and this pathway is critical for the progression of many B-cell malignancies, such a chronic lymphocytic leukemia (CLL). BTK, a TEC family kinase, is essential to the BCR signaling cascade. The recent approval of the first-in-class BTK inhibitor for the treatment certain B-cell malignancies, ibrutinib, has validated BTK as a clinical target. ACP-196 is a novel, second generation inhibitor of BTK with an IC50of 3 nM against purified BTK and EC50 of 8 nM in a human whole-blood CD69 B-cell activation assay. In vivo, oral administration of ACP-196 inhibits BCR-induced CD69 expression in murine splenic lymphocytes with an ED50 of 1.3 mg/kg compared with 2.9 mg/kg for ibrutinib. ACP-196 also has improved target specificity over ibrutinib with 323-,94-, 19- and 9-fold selectivity over the other TEC kinase familymembers (ITK, TXK, BMX, and TEC, respectively) and no activity against EGFR (Cove...

Blood Advances, 2019

Key PointsAcalabrutinib had good tolerability in patients with relapsed or refractory CLL who wer... more Key PointsAcalabrutinib had good tolerability in patients with relapsed or refractory CLL who were intolerant to ibrutinib. Acalabrutinib demonstrated a high response rate (81%) in patients with relapsed or refractory CLL who were intolerant to ibrutinib.

Antioxidants & Redox Signaling, 2016

Aim: Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventu... more Aim: Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventuates in kidney fibrosis. Oxidative stress plays a critical role in hyperglycemia-induced glomerular injury. We explored the hypothesis that mammalian target of rapamycin complex 2 (mTORC2) mediates podocyte injury in diabetes. Results: High glucose (HG)-induced podocyte injury reflected by alterations in the slit diaphragm protein podocin and podocyte depletion/apoptosis. This was paralleled by activation of the Rictor/mTORC2/Akt pathway. HG also increased the levels of Nox4 and NADPH oxidase activity. Inhibition of mTORC2 using small interfering RNA (siRNA)-targeting Rictor in vitro decreased HG-induced Nox1 and Nox4, NADPH oxidase activity, restored podocin levels, and reduced podocyte depletion/apoptosis. Inhibition of mTORC2 had no effect on mammalian target of rapamycin complex 1 (mTORC1) activation, described by our group to be increased in diabetes, suggesting that the mTORC2 activation by HG could mediate podocyte injury independently of mTORC1. In isolated glomeruli of OVE26 mice, there was a similar activation of the Rictor/mTORC2/Akt signaling pathway with increase in Nox4 and NADPH oxidase activity. Inhibition of mTORC2 using antisense oligonucleotides targeting Rictor restored podocin levels, reduced podocyte depletion/apoptosis, and attenuated glomerular injury and albuminuria. Innovation: Our data provide evidence for a novel function of mTORC2 in NADPH oxidasederived reactive oxygen species generation and podocyte apoptosis that contributes to urinary albumin excretion in type 1 diabetes. Conclusion: mTORC2 and/or NADPH oxidase inhibition may represent a therapeutic modality for diabetic kidney disease. Antioxid. Redox Signal. 25, 703-719.

Revista Brasileira de Reumatologia, 2016

Background: Rheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic... more Background: Rheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition. Objectives: The aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677 T and A1298 C), transforming growth factor-␤1 (TGF-␤1 T869 C) and lymphotoxin-␣ (LT-␣ A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor-alpha (TNF-␣), B-Cell Activating Factor (BAFF), and osteopontin. Methods: A total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677 T and A1298 C, TGF-␤1 T869 C and LT-␣ A252G polymorphisms using a methodology based on PCR-RFLP. Also serum levels of TNF-␣, osteopontin and BAFF were measured by ELISA kits. Results: The CT genotype and T allele of MTHFR C677 T and GG genotype and G allele of LT-␣ A252G are associated with the risk of RA and with higher levels of the pro-inflammatory cytokine, TNF-␣ in patients with rheumatoid arthritis. Conclusion: Our findings suggest that there is association between MTHFR C677 T and LT-␣ A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population.

The Egyptian Journal of Internal Medicine, 2015

Vascular complications are the main cause of morbidity and mortality in type 2 diabetic patients.... more Vascular complications are the main cause of morbidity and mortality in type 2 diabetic patients. Genetic susceptibility is associated with the evolution of diabetic complications. One such gene is the lamin A and C gene located on chromosome 1q21, a susceptibility locus for type 2 diabetes mellitus, and encodes nuclear lamins A and C. The LMNA 1908 C/T polymorphism has been reported to be associated with dyslipidemia, metabolic syndrome, and obesity, suggesting that this polymorphism increases the risk of atherosclerosis and vascular disease. The present study aims to elucidate the association between the LMNA 1908 C/T single nucleotide polymorphism and the prevalence of vascular complications in a sample of type 2 diabetic Egyptian patients. Materials and methods Genomic DNA from 47 type 2 diabetic patients with vascular complications and 20 control participants was analyzed for the LMNA 1908 C/T polymorphism using PCR-RFLP. Results Carriers of the LMNA 1908 T-allele showed a signifi cantly higher prevalence in patients with diabetic nephropathy than carriers of the C-allele (P < 0.05). Multiple regression analysis showed that the LMNA 1908 T-allele tended to be independent risk factor for diabetic nephropathy (P = 0.012, odds ratio = 5.460). Conclusion The fi ndings of this study suggest that the LMNA 1908 C/T single nucleotide polymorphism is associated with the development of diabetic nephropathy in Egyptian type 2 diabetic patients.

Open Journal of Gastroenterology, 2015

Background: Spontaneous bacterial peritonitis (SBP) is a life-threatening infection occurring in ... more Background: Spontaneous bacterial peritonitis (SBP) is a life-threatening infection occurring in 8%-30% of ascitic cirrhotic patients; different laboratory diagnostics play a pivotal role for rapid and effective management of SBP patients. Polymorphonuclear leucocytic (PMNLs) count in Ascitic fluid (AF) is the mainstay for the diagnosis, whereas the diagnostic role of alternative biomarkers is rather controversial. In many studies, serum lipopolysaccharide binding protein (LBP) was elevated and Complement 3 (C3) level was significantly consumed in AF of SBP patients. Objectives: To evaluate the diagnostic value of serum LBP and AF C3 in HCV-cirrhotics with SBP in relation to other well-established serum and AF markers. Patients and Methods: One hundred and twenty patients with HCV-cirrhosis and ascites were enrolled and consented: 50 patients with non-SBP ascites in group A and 70 ascitic patients diagnosed with SBP according to clinical suspicion and PMLs count in AF ≥ 250 cells/mm 3 in group B in addition to 15 healthy individuals considered as a control group. Serum LBP, CBC, kidney and liver function tests, CRP, fasting and 2 h PP blood glucose and HCV antibodies were measured. AF samples were sent for C3 level, culture, PMNLs count, LDH, CRP, total proteins and albumin. Results: In patients with SBP, the level of serum LBP was not significantly high (p > 0.05) with best cut off value at 0.4500 and poor AUC (<0.6) with low sensitivity and specificity (53.3% & 57.7%, respectively). AF C3 was significantly reduced in AF (p < 0.001) with best cut off value at 144.2 and almost excellent AUC (0.889) with good sensitivity and specificity (82% & 84%, respectively). AF culture showed significant difference between both patients groups (p < 0.05) but with low sensitivity (33.3%). Serum and AF CRP and AF PMNLs count were of high significance in SBP diagnosis (p < 0.001). Conclusion: Serum LBP level showed low significance while AF C3 was significantly reduced in patients with SBP. AF culture showed significant difference between both groups but with low sensitivity while serum, AF levels of CRP and AF * Corresponding author. PMNLs count were highly significant, and the latter is still considered the gold standard for SBP diagnosis.

Cancer Research, 2014

Recent recognition of B-cell receptor (BCR) signaling as a critical factor in the progression of ... more Recent recognition of B-cell receptor (BCR) signaling as a critical factor in the progression of B-cell malignancies, including non-Hodgkin lymphoma (NHL), has resulted in the development of numerous targeted therapeutics that inhibit this signaling pathway. Ibrutinib, a small molecule inhibitor of Bruton tyrosine kinase (Btk) a key signaling molecule in the BCR pathway, has demonstrated significant clinical activity in a broad range of B-cell cancers. ACP-196 is a second generation Btk inhibitor with increased target selectivity and enhanced in vivo potency compared with ibrutinib and, thus, may represent an improvement over its predecessor. With the following studies, we sought to evaluate ACP-196 in canine models of B-cell NHL with the ultimate goal of providing the preclinical data necessary to move ACP-196 into human clinical trials. Using two immunophenotypically confirmed canine B-cell lymphoma cell lines, CLBL-1 and 17-71, we demonstrate potent in vitro inhibition of activat...

Annals of hematology, 2015

The objective in this study was to characterize the pattern of the treatment-related lymphocytosi... more The objective in this study was to characterize the pattern of the treatment-related lymphocytosis curve in chronic lymphocytic leukemia (CLL) patients treated with ibrutinib, and assess the relationship between the baseline factors and absolute lymphocyte counts (ALC). The PCYC-1102-CA study was a five-arm phase Ib/II open-label, nonrandomized, multicenter study in CLL/SLL. The arms and accruals were 420 and 840 mg/day treatment-naive elderly CLL/SLL (N = 27 and N = 4, respectively), 420 and 840 mg/day relapsed/refractory CLL/SLL (N = 27 and N = 34, respectively), and 420 mg/day high-risk CLL/SLL (N = 24). The results were generated through statistical modeling using data from a clinical trial (PCYC-1102) in five cohorts of treatment-naïve or relapsed/refractory CLL patients treated at 420 and 840 mg daily of ibrutinib. In cases in which the initial increase in ALC doubles by day 28, it takes patients longer to reach their maximum ALC when compared with those with a lower rate of i...

Iranian journal of kidney diseases, 2010

Brown tumors with non-neoplastic process are noticed in patients with end-stage renal disease suf... more Brown tumors with non-neoplastic process are noticed in patients with end-stage renal disease suffering from a severe form of secondary hyperparathyroidism. Herein, we report a patient with chronic kidney allograft failure returned back to hemodialysis who experienced manifestations of cauda equina compression secondary to a lumbar brown tumor. Also, we had another patient on hemodialysis with a demineralized lesion affecting the cervical vertebrae. Although brown tumor is a rare complication, these two cases highlighted the importance of neurological symptoms in uremic patients. Spinal decompression surgery, in order to alleviate pressure on neurological structures, together with subtotal parathyroidectomy, were highly indicated.

Proceedings of SPE Asia Pacific Oil and Gas Conference and Exhibition, 2002

... References: 1-Heikal S., Kamal M., Nosseir M., 1998: “Improved Field Recovery by Controlling ... more ... References: 1-Heikal S., Kamal M., Nosseir M., 1998: “Improved Field Recovery by Controlling Gas Prduction in Hetrogeneous Gas Injection Reservoir,” SPE 39646. 2-El Hamalawy F., Swidan N., El Fatah, G., Barden I., : “ A ...

Background: Acalabrutinib (ACP-196) is a highly selective, potent, covalent inhibitor of Bruton t... more Background: Acalabrutinib (ACP-196) is a highly selective, potent, covalent inhibitor of Bruton tyrosine kinase (BTK), in development for the treatment of hematologic malignancies. Acalabrutinib has rapid absorption and a short pharmacokinetic (PK) half-life; twice daily dosing resulted in near complete and continuous BTK inhibition in patients with chronic lymphocytic leukemia (CLL) (Byrd JC, et al. 2016). CYP3A-mediated oxidation is the primary route of elimination for the marketed BTK inhibitor, ibrutinib (de Zwart et al., 2016). Coadministration of ibrutinib with ketoconazole (a strong CYP3A inhibitor) increased dose-normalized maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) by 29- and 24-fold, respectively, whereas coadministration of rifampin (a strong CYP3A inducer) decreased Cmax and AUC of ibrutinib by more than 13- and 10-fold, respectively (IMBRUVICA® (ibrutinib) package insert 2017). Grapefruit juice, which is known to contain...

Dans certains modes de realisation, cette invention comprend des methodes therapeutiques pour l&#... more Dans certains modes de realisation, cette invention comprend des methodes therapeutiques pour l'utilisation d'un inhibiteur de BTK pour traiter des cancers tumoraux solides par modulation du micro-environnement tumoral, notamment les macrophages, les monocytes, les mastocytes, les cellules T auxiliaires, les cellules T cytotoxiques, les cellules T regulatrices, les cellules tueuses naturelles, les cellules suppresseurs derivees de myeloides, les cellules B regulatrices, les neutrophiles, les cellules dendritiques, et les fibroblastes.

Journal of Water Reuse and Desalination, 2020

In this work, δMnO2 was anchored into graphene nanosheets via a mediated simple and eco-friendly ... more In this work, δMnO2 was anchored into graphene nanosheets via a mediated simple and eco-friendly approach to be used as a potential low-cost cathodic catalyst in microbial desalination cells (MDC). MnO2/G based MDC revealed a faster start-up and stable performance during the operation compared with the catalyst-free control MDC. The average chemical oxygen demand (COD) removal efficiencies were 85.11 ± 5.13 and 86.20 ± 4.85% and average columbic efficiencies throughout the operation cycles were 1.52 ± 0.32% and 0.70 ± 0.35% for MnO2/G based reactor and control reactor, respectively. The average desalination efficiencies were 15.67 ± 3.32 and 13.21 ± 2.61% for MnO2/G based reactor and control reactor, respectively. The superior catalytic performance of MnO2/G based cathode improved current generation which is the key desalination stimulus. MnO2/G based reactor revealed a lower internal resistance of 430 Ω compared with 485 Ω for the catalyst-free control reactor and, similarly, the m...

Egyptian Academic Journal of Biological Sciences. A, Entomology, Oct 1, 2018

This study was carried out during two successive years from October 2014 to September 2016. Resul... more This study was carried out during two successive years from October 2014 to September 2016. Results showed that the temperature and moisture R.H.% were significantly affected the mean abundance of the phytophagous mite O. mangiferus and its predator A. swirskii associated with mango orchard trees. The highest mean abundance of O. mangiferus was recorded in the summer season (2.96 ± 0.6 indv./leaf) and (1.33 ± 0.05 indv./leaf) for A. swirskii, respectively in the first year (from October 2014 to September 2015). On the other hand, the lowest mean abundance was recorded in the autumn (0.6 ± 0.11) for O. mangiferus, (0.23 ± 0.09 indv./leaf) for A. swirskii. The mean abundance of O. mangiferus populations increased to (3.43 ± 0.7 indv./leaf) in the second year of study in contrast to the populations of its predator. The results stated that the temperature had a significant effect on the population abundance of the phytophagous mite, O. mangiferus and its predator while the relative humidity had a negative effect on both populations.

Egyptian Dental Journal, 2017

Statement of problem: A new CAD/CAM technology for the fabrication of metal copings for metal-cer... more Statement of problem: A new CAD/CAM technology for the fabrication of metal copings for metal-ceramic restorations has been introduced. However, no sufficient data on the internal fit of metal-ceramic restorations produced by this method is available yet. Purpose: This study was performed to compare the internal gap between abutment teeth and posterior fixed dental prosthesis (FDPs) fabricated utilizing yttria-stabilized tetragonal zirconia polycrystals and Gold Platinum metal ceramic alloy frameworks. Materials and Methods: A randomized controlled clinical trial was performed, twenty FPDs were fabricated with yttria-stabilized zirconia poly crystals (Y-TZP-IPS e.max zir CAD) and metal-ceramic (MC Au-Pt) as follow(n=10): thirty patients were randomly selected for internal fit measurements. The internal fit of the FPDs frameworks were measured using replica technique. Data was analyzed with (ANOVA) test, followed by Tukey's post hoc test. Results: The internal gap, according to the thickness of the replica, was measured under magnification at the following locations: cervical, axial, and occlusal (cusp-tips and central). The internal gaps of FPDs with zirconia frameworks were significantly larger in cervical

Egyptian Dental Journal, 2017

Purpose: This in vitro study measured the adhesive properties of 10-MDP and MPE containing resin ... more Purpose: This in vitro study measured the adhesive properties of 10-MDP and MPE containing resin cements, using two types of zirconia surface treatments; selective infiltration etching(SIE) and airborne particle abrasion (APA) to translucent zirconia (3M, ESPE). Statement of Problem: Due to translucent zirconia modified composition (alumina content reduced to tenth of its weight) bonding strength to different resin cements after different surface treatments should be investigated adequately. Materials and Methods:Sixty sintered Lava plus high translucency disks(3M,ESPE)were randomly divided into three study groups according to their surface treatment: (a) polished surface (control group); (b) air borne particle abraded (grit blasted) with 50 µm aluminum trioxide (APA); and (c) selective infiltration etching (SIE). Zirconia disks (15x2mm) were then bonded to 60 composite resin disks (8x4mm) using two different resin composite cements (Clearfil SA and Rely X). Resin-zirconia adhesion strength was evaluated using the microshear bond strength test (MSBS) after 24 hour of storage in deionized water at 37˚C. One way ANOVA and Scheffé s posthoc tests were used to analyze the data (p<0.001). Then fractured samples were studied under SEM and classified according to failure pattern. Results: Different types of resin cement and surface treatment significantly influenced the MSBS (P<0.001). The highest mean MSBS values were recorded with MDP containing resin cement (Clearfil SA) in both SIE (26.18 ±1.12 MPa) and APA (21.67±1.34) groups. Bond strength values were reduced significantly in control group when using the two types of cements. Regarding failure pattern, MDP groups showed cohesive and MPE and control groups showed adhesive type. Conclusion: SIE and APA in combination with 10-MDP containing resin cement established a strong durable bond to zirconia substrates than MPE groups. SIE and APA showed significant higher bond strength values than control groups.

Blood, 2015

Background: Signaling through the B-cell receptor (BCR) results in cell survival and proliferatio... more Background: Signaling through the B-cell receptor (BCR) results in cell survival and proliferation, and this pathway is critical for the progression of many B-cell malignancies, such a chronic lymphocytic leukemia (CLL). BTK, a TEC family kinase, is essential to the BCR signaling cascade. The recent approval of the first-in-class BTK inhibitor for the treatment certain B-cell malignancies, ibrutinib, has validated BTK as a clinical target. ACP-196 is a novel, second generation inhibitor of BTK with an IC50of 3 nM against purified BTK and EC50 of 8 nM in a human whole-blood CD69 B-cell activation assay. In vivo, oral administration of ACP-196 inhibits BCR-induced CD69 expression in murine splenic lymphocytes with an ED50 of 1.3 mg/kg compared with 2.9 mg/kg for ibrutinib. ACP-196 also has improved target specificity over ibrutinib with 323-,94-, 19- and 9-fold selectivity over the other TEC kinase familymembers (ITK, TXK, BMX, and TEC, respectively) and no activity against EGFR (Cove...

Blood Advances, 2019

Key PointsAcalabrutinib had good tolerability in patients with relapsed or refractory CLL who wer... more Key PointsAcalabrutinib had good tolerability in patients with relapsed or refractory CLL who were intolerant to ibrutinib. Acalabrutinib demonstrated a high response rate (81%) in patients with relapsed or refractory CLL who were intolerant to ibrutinib.

Antioxidants & Redox Signaling, 2016

Aim: Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventu... more Aim: Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventuates in kidney fibrosis. Oxidative stress plays a critical role in hyperglycemia-induced glomerular injury. We explored the hypothesis that mammalian target of rapamycin complex 2 (mTORC2) mediates podocyte injury in diabetes. Results: High glucose (HG)-induced podocyte injury reflected by alterations in the slit diaphragm protein podocin and podocyte depletion/apoptosis. This was paralleled by activation of the Rictor/mTORC2/Akt pathway. HG also increased the levels of Nox4 and NADPH oxidase activity. Inhibition of mTORC2 using small interfering RNA (siRNA)-targeting Rictor in vitro decreased HG-induced Nox1 and Nox4, NADPH oxidase activity, restored podocin levels, and reduced podocyte depletion/apoptosis. Inhibition of mTORC2 had no effect on mammalian target of rapamycin complex 1 (mTORC1) activation, described by our group to be increased in diabetes, suggesting that the mTORC2 activation by HG could mediate podocyte injury independently of mTORC1. In isolated glomeruli of OVE26 mice, there was a similar activation of the Rictor/mTORC2/Akt signaling pathway with increase in Nox4 and NADPH oxidase activity. Inhibition of mTORC2 using antisense oligonucleotides targeting Rictor restored podocin levels, reduced podocyte depletion/apoptosis, and attenuated glomerular injury and albuminuria. Innovation: Our data provide evidence for a novel function of mTORC2 in NADPH oxidasederived reactive oxygen species generation and podocyte apoptosis that contributes to urinary albumin excretion in type 1 diabetes. Conclusion: mTORC2 and/or NADPH oxidase inhibition may represent a therapeutic modality for diabetic kidney disease. Antioxid. Redox Signal. 25, 703-719.

Revista Brasileira de Reumatologia, 2016

Background: Rheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic... more Background: Rheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition. Objectives: The aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677 T and A1298 C), transforming growth factor-␤1 (TGF-␤1 T869 C) and lymphotoxin-␣ (LT-␣ A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor-alpha (TNF-␣), B-Cell Activating Factor (BAFF), and osteopontin. Methods: A total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677 T and A1298 C, TGF-␤1 T869 C and LT-␣ A252G polymorphisms using a methodology based on PCR-RFLP. Also serum levels of TNF-␣, osteopontin and BAFF were measured by ELISA kits. Results: The CT genotype and T allele of MTHFR C677 T and GG genotype and G allele of LT-␣ A252G are associated with the risk of RA and with higher levels of the pro-inflammatory cytokine, TNF-␣ in patients with rheumatoid arthritis. Conclusion: Our findings suggest that there is association between MTHFR C677 T and LT-␣ A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population.

The Egyptian Journal of Internal Medicine, 2015

Vascular complications are the main cause of morbidity and mortality in type 2 diabetic patients.... more Vascular complications are the main cause of morbidity and mortality in type 2 diabetic patients. Genetic susceptibility is associated with the evolution of diabetic complications. One such gene is the lamin A and C gene located on chromosome 1q21, a susceptibility locus for type 2 diabetes mellitus, and encodes nuclear lamins A and C. The LMNA 1908 C/T polymorphism has been reported to be associated with dyslipidemia, metabolic syndrome, and obesity, suggesting that this polymorphism increases the risk of atherosclerosis and vascular disease. The present study aims to elucidate the association between the LMNA 1908 C/T single nucleotide polymorphism and the prevalence of vascular complications in a sample of type 2 diabetic Egyptian patients. Materials and methods Genomic DNA from 47 type 2 diabetic patients with vascular complications and 20 control participants was analyzed for the LMNA 1908 C/T polymorphism using PCR-RFLP. Results Carriers of the LMNA 1908 T-allele showed a signifi cantly higher prevalence in patients with diabetic nephropathy than carriers of the C-allele (P < 0.05). Multiple regression analysis showed that the LMNA 1908 T-allele tended to be independent risk factor for diabetic nephropathy (P = 0.012, odds ratio = 5.460). Conclusion The fi ndings of this study suggest that the LMNA 1908 C/T single nucleotide polymorphism is associated with the development of diabetic nephropathy in Egyptian type 2 diabetic patients.

Open Journal of Gastroenterology, 2015

Background: Spontaneous bacterial peritonitis (SBP) is a life-threatening infection occurring in ... more Background: Spontaneous bacterial peritonitis (SBP) is a life-threatening infection occurring in 8%-30% of ascitic cirrhotic patients; different laboratory diagnostics play a pivotal role for rapid and effective management of SBP patients. Polymorphonuclear leucocytic (PMNLs) count in Ascitic fluid (AF) is the mainstay for the diagnosis, whereas the diagnostic role of alternative biomarkers is rather controversial. In many studies, serum lipopolysaccharide binding protein (LBP) was elevated and Complement 3 (C3) level was significantly consumed in AF of SBP patients. Objectives: To evaluate the diagnostic value of serum LBP and AF C3 in HCV-cirrhotics with SBP in relation to other well-established serum and AF markers. Patients and Methods: One hundred and twenty patients with HCV-cirrhosis and ascites were enrolled and consented: 50 patients with non-SBP ascites in group A and 70 ascitic patients diagnosed with SBP according to clinical suspicion and PMLs count in AF ≥ 250 cells/mm 3 in group B in addition to 15 healthy individuals considered as a control group. Serum LBP, CBC, kidney and liver function tests, CRP, fasting and 2 h PP blood glucose and HCV antibodies were measured. AF samples were sent for C3 level, culture, PMNLs count, LDH, CRP, total proteins and albumin. Results: In patients with SBP, the level of serum LBP was not significantly high (p > 0.05) with best cut off value at 0.4500 and poor AUC (<0.6) with low sensitivity and specificity (53.3% & 57.7%, respectively). AF C3 was significantly reduced in AF (p < 0.001) with best cut off value at 144.2 and almost excellent AUC (0.889) with good sensitivity and specificity (82% & 84%, respectively). AF culture showed significant difference between both patients groups (p < 0.05) but with low sensitivity (33.3%). Serum and AF CRP and AF PMNLs count were of high significance in SBP diagnosis (p < 0.001). Conclusion: Serum LBP level showed low significance while AF C3 was significantly reduced in patients with SBP. AF culture showed significant difference between both groups but with low sensitivity while serum, AF levels of CRP and AF * Corresponding author. PMNLs count were highly significant, and the latter is still considered the gold standard for SBP diagnosis.

Cancer Research, 2014

Recent recognition of B-cell receptor (BCR) signaling as a critical factor in the progression of ... more Recent recognition of B-cell receptor (BCR) signaling as a critical factor in the progression of B-cell malignancies, including non-Hodgkin lymphoma (NHL), has resulted in the development of numerous targeted therapeutics that inhibit this signaling pathway. Ibrutinib, a small molecule inhibitor of Bruton tyrosine kinase (Btk) a key signaling molecule in the BCR pathway, has demonstrated significant clinical activity in a broad range of B-cell cancers. ACP-196 is a second generation Btk inhibitor with increased target selectivity and enhanced in vivo potency compared with ibrutinib and, thus, may represent an improvement over its predecessor. With the following studies, we sought to evaluate ACP-196 in canine models of B-cell NHL with the ultimate goal of providing the preclinical data necessary to move ACP-196 into human clinical trials. Using two immunophenotypically confirmed canine B-cell lymphoma cell lines, CLBL-1 and 17-71, we demonstrate potent in vitro inhibition of activat...

Annals of hematology, 2015

The objective in this study was to characterize the pattern of the treatment-related lymphocytosi... more The objective in this study was to characterize the pattern of the treatment-related lymphocytosis curve in chronic lymphocytic leukemia (CLL) patients treated with ibrutinib, and assess the relationship between the baseline factors and absolute lymphocyte counts (ALC). The PCYC-1102-CA study was a five-arm phase Ib/II open-label, nonrandomized, multicenter study in CLL/SLL. The arms and accruals were 420 and 840 mg/day treatment-naive elderly CLL/SLL (N = 27 and N = 4, respectively), 420 and 840 mg/day relapsed/refractory CLL/SLL (N = 27 and N = 34, respectively), and 420 mg/day high-risk CLL/SLL (N = 24). The results were generated through statistical modeling using data from a clinical trial (PCYC-1102) in five cohorts of treatment-naïve or relapsed/refractory CLL patients treated at 420 and 840 mg daily of ibrutinib. In cases in which the initial increase in ALC doubles by day 28, it takes patients longer to reach their maximum ALC when compared with those with a lower rate of i...

Iranian journal of kidney diseases, 2010

Brown tumors with non-neoplastic process are noticed in patients with end-stage renal disease suf... more Brown tumors with non-neoplastic process are noticed in patients with end-stage renal disease suffering from a severe form of secondary hyperparathyroidism. Herein, we report a patient with chronic kidney allograft failure returned back to hemodialysis who experienced manifestations of cauda equina compression secondary to a lumbar brown tumor. Also, we had another patient on hemodialysis with a demineralized lesion affecting the cervical vertebrae. Although brown tumor is a rare complication, these two cases highlighted the importance of neurological symptoms in uremic patients. Spinal decompression surgery, in order to alleviate pressure on neurological structures, together with subtotal parathyroidectomy, were highly indicated.

Proceedings of SPE Asia Pacific Oil and Gas Conference and Exhibition, 2002

... References: 1-Heikal S., Kamal M., Nosseir M., 1998: “Improved Field Recovery by Controlling ... more ... References: 1-Heikal S., Kamal M., Nosseir M., 1998: “Improved Field Recovery by Controlling Gas Prduction in Hetrogeneous Gas Injection Reservoir,” SPE 39646. 2-El Hamalawy F., Swidan N., El Fatah, G., Barden I., : “ A ...