Mohamed M. Elmazar

Honey-based hydrogel: In vitro and comparative In vivo evaluation for burn wound healing

Honey was used to treat wounds since ancient times till nowadays. The present study aimed at preparing a honey-based hydrogel and assay its antimicrobial properties and wound healing activity; in-vitro and in-vivo. Topical honey hydrogel formulations were prepared using three honey concentrations with gelling agents; chitosan and carbopol 934. The prepared formulae were evaluated for pH, spreadability, swelling index, in-vitro release and antimicrobial activity. The pH and spreadability were in the range of 4.3–6.8 and 5.7–8.6u2009cm, respectively. Chitosan-based hydrogel showed higher in-vitro honey release with diffusional exponent ‘nu2009≤u20090.5 indicates Fickian diffusion mechanism. Hydrogel formulae were assessed for in-vitro antimicrobial activity using Disc Diffusion antibiotic sensitivity test against common burn infections bacteria; Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia and Streptococcus pyogenes. The 75% honey-chitosan hydrogel showed highest antimicrobial activity. This formula was tested for in-vivo burn healing using burn-induced wounds in mice. The formula was evaluated for burn healing and antibacterial activities compared to commercial product. 75% honey-chitosan hydrogel was found to possess highest healing rate of burns. The present study concludes that 75% honey-chitosan hydrogel possesses greater wound healing activity compared to commercial preparation and could be safely used as an effective natural topical wound healing treatment.

Anti-tumor efficacy of an integrated methyl dihydrojasmonate transdermal microemulsion system targeting breast cancer cells: In vitro and in vivo studies

Targeting solid tumors transdermally is an emerging approach that is currently under intense investigation. In this context, microemulsions are reported as one of the most favored carriers for successful transdermal drug delivery. Thereby, these nano-carriers were utilized in this study for the delivery of a phytochemical, namely methyl dihydrojasmonate (MDHJ), which has previously demonstrated an anticancer effect. Accordingly, pseudoternary phase diagrams were constructed using several combinations of oils, surfactants and co-surfactants and following the water titration method. Two systems were selected and an experimental design (Simplex Lattice Mixture Design) was utilized to select formulations for further investigation through an ex vivo permeation study through mouse skin. Transdermal fluxes were determined reaching a value of 0.07μlcm-2h-1. Cytotoxicity studies were carried out where the selected superlative formulation was further investigated on MCF-7 cell lines and scored an IC50 of 42.2μl/ml (equivalent to 8.3μl/ml drug). Further, in vivo investigations were performed using Ehlirch solid carcinoma and histopathological examination of the tumor cells evaluating the tumor volume differences, tumor inhibition percentages and the necrotic effect of the formulation compared to control, placebo and pure drug. The obtained results showed significant anticancer effects of the selected formulation when applied on the tumor bearing mice skin.

Pharmacokinetic Evaluation of Empagliflozin in Healthy Egyptian Volunteers Using LC-MS/MS and Comparison with Other Ethnic Populations

The present study considered the pharmacokinetic evaluation of empagliflozin after administration to Egyptian volunteers, and the results were compared with other ethnic populations. The FDA recognizes that standard methods of defining racial subgroups are necessary to compare results across pharmacokinetic studies and to assess potential subgroup differences. The design of the study was as an open labeled, randomized, one treatment, one period, single dose pharmacokinetic study. The main pharmacokinetic parameters estimated were Cmax, Tmax, t1/2, elimination rate constant, AUC0-t and AUC0-inf. The insignificant difference in pharmacokinetic parameters between Egyptians and white German subjects suggests that no dose adjustment should be considered with administration of 25u2009mg empagliflozin to Egyptian population. A new LC-MS/MS method was developed and validated, allowing sensitive estimation of empagliflozin (25–600u2009ng mL−1) in human plasma using dapagliflozin as an internal standard (IS). The method was applied successfully on the underlying pharmacokinetic study with enhanced sample preparation that involved liquid-liquid extraction. Multiple Reaction Monitoring (MRM) of the transition pairs of m/z 449.01 to 371.21 for empagliflozin and m/z 407.00 to 328.81 for dapagliflozin (IS) was employed utilizing negative mode Electro Spray Ionization (ESI). The validated LC-MS/MS method is suitable for further toxicodynamic and bioequivalence studies.

The FXR Agonist, Obeticholic Acid, Suppresses HCC Proliferation & Metastasis: Role of IL-6/STAT3 Signalling Pathway

The nuclear receptor, farnesoid X receptor (FXR), has been recently considered as a tumor suppressor in HCC. IL-6/Janus kinase 2 (Jak-2)/signal transducer and activator of transcription 3 (STAT3) pathway has been implicated as a key player in many cancer types. This study aimed at investigating the potential effect of the FXR agonist, obeticholic acid (OCA), on HCC and the involvement of IL-6/STAT3 pathway. The potential regulation of STAT3 by its main feedback inhibitor target gene, the suppressor of cytokine signaling 3 (SOCS3), triggered by OCA was also explored. Cytotoxicity studies were performed on HepG2, Huh7, and SNU-449 cell lines using OCA alone and combined with the FXR antagonist guggulsterone (Gugg). OCA cytotoxic effect was significantly hampered in presence of Gugg. OCA also caused cell cycle arrest and inhibited invasion and migration of HCC cells. Decrease in STAT3 phosphorylation and SOCS3 upregulation were also observed. Moreover, Jak-2, IL-1β, and IL-6 levels were decreased. These results were correlated with an upregulation of FXR and small heterodimer partner (SHP) levels. Effects of OCA on IL-6/STAT3 main key players were reversed in presence of Gugg. Overall, these findings suggest a potential effect of OCA in HCC via interfering with IL-6/STAT3 signalling pathway in vitro.

Indole-3- carbinol enhances sorafenib cytotoxicity in hepatocellular carcinoma cells: A mechanistic study.

Sorafenib is the only chemotherapeutic agent currently approved for unresectable hepatocellular carcinoma (HCC). However, poor response rates have been widely reported. Indole-3-carbinol (I3C) is a potential chemopreventive phytochemical. The present study aimed to explore the potential chemomodulatory effects of I3C on sorafenib in HCC cells as well as the possible underlying mechanisms. I3C exhibited a greater cytotoxicity in HepG2 cells compared to Huh-7 cells (pu2009<u20090.0001). Moreover, the co-treatment of HepG2 cells with I3C and sorafenib was more effective (pu2009=u20090.002). Accordingly, subsequent mechanistic studies were carried on HepG2 cells. The results show that the ability of I3C to enhance sorafenib cytotoxicity in HCC cells could be partially attributed to increasing the apoptotic activity and decreasing the angiogenic potentials. The combination had a negative effect on epithelial-mesenchymal transition (EMT). Increased NOX-1 expression was also observed which may indicate the involvement of NOX-1 in I3C chemomodulatory effects. Additionally, the combination induced cell cycle arrest at the G0/G1 phase. In conclusion, these findings provide evidence that I3C enhances sorafenib anti-cancer activity in HCC cells.

Wharton’s jelly-derived mesenchymal stem cells combined with praziquantel as a potential therapy for Schistosoma mansoni -induced liver fibrosis

Liver fibrosis is one of the most serious consequences of S. mansoni infection. The aim of the present study was to investigate the potential anti-fibrotic effect of human Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) combined with praziquantel (PZQ) in S. mansoni-infected mice. S. mansoni-infected mice received early (8th week post infection) and late (16th week post infection) treatment with WJMSCs, alone and combined with oral PZQ. At the 10th month post infection, livers were collected for subsequent flow cytometric, histopathological, morphometric, immunohistochemical, gene expression, and gelatin zymographic studies. After transplantation, WJMSCs differentiated into functioning liver-like cells as evidenced by their ability to express human hepatocyte-specific markers. Regression of S. mansoni-induced liver fibrosis was also observed in transplanted groups, as evidenced by histopathological, morphometric, and gelatin zymographic results besides decreased expression of three essential contributors to liver fibrosis in this particular model; alpha smooth muscle actin, collagen-I, and interleukin-13. PZQ additionally enhanced the beneficial effects observed in WJMSCs-treated groups. Our results suggest that combining WJMSCs to PZQ caused better enhancement in S. mansoni-induced liver fibrosis, compared to using each alone.

Cost-Effectiveness of the Combined Use of Warfarin and Low-Dose Aspirin versus Warfarin Alone in Egyptian Patients with Aortic Valve Replacements: A Markov Model

BACKGROUNDnThe combination of antiplatelet and anticoagulant therapy significantly reduces the rate of thromboembolic events in patients with heart valves compared with anticoagulant therapy alone. Cost-effectiveness of this therapy in Egypt, however, has not yet been established.nnnOBJECTIVEnThe aim of the present study was to evaluate the cost-effectiveness of the combined use of warfarin and low-dose aspirin (100 mg) versus warfarin alone in patients with mechanical aortic heart valve prostheses who began therapy at the age of 50 to 60 years over a 5-year period from the perspective of the medical providers.nnnMETHODSnA cohort Markov process model with five health states (recovery, reoperation, bleeding, thromboembolism, and death) based on Egyptian clinical practice was derived from published sources. The clinical parameters were derived from meta-analyses of randomized controlled trials of patients with mechanical valve prostheses. The quality of life of the health states was derived using the available published data. Direct medical costs were obtained from four top-rated governmental cardiology hospitals in Egypt. All costs and effects were discounted at 3.5% annually. All costs were converted using the purchasing power parity rate and are reported in US

Thermoresponsive gels containing gold nanoparticles as smart antibacterial and wound healing agents

for the financial year of 2013.nnnRESULTSnThe total quality-adjusted life-years (QALYs) were estimated to be 1.1616 and 1.1199 for the warfarin plus aspirin group and the warfarin group, respectively, which resulted in a difference of 0.0416 QALYs. The total costs for the warfarin plus aspirin group and the warfarin group were US

Repositioning of Omarigliptin as a once-weekly intranasal Anti-parkinsonian Agent.

307.33 and US

The sole and combined effect of simvastatin and platelet rich fibrin as a filling material in induced bone defect in tibia of albino rats

315.25, respectively (the difference was US