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Synthesis, anti-inflammatory activity and COX-1/COX-2 inhibition of novel substituted cyclic imides. Part 1: Molecular docking study.
No full textA group of cyclic imides (1-13) was designed for evaluation as selective COX-2 inhibitors and investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw edema model. Compounds 5b, 6b, 11b, 11c, 12b and 12c were proved to be potent COX-2 inhibitors with IC50 range of 0.1-1.0 μM. In vitro COX-1/COX-2 inhibition structure-activity studies identified compound 5b as a highly potent (IC50=0.1 μM), and an extremely selective [COX-2 (SI)=400] comparable to celecoxib [COX-2 (SI)>333.3], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50=104 mg/kg) relative to diclofenac (ED50=114 mg/kg). A Virtual screening was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors. Molecular modeling (docking) study showed that the CH3O substituents of 5b inserted deep inside the 2°-pocket of the COX-2 active site, where the O-atoms of such group underwent a H-bonding interaction with His90 (2.43, 2.83 Å), Arg513 (2.89 Å) and Tyr355 (3.34 Å). Docking study of the synthesized compound 5b into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor
Stereoselective HPLC analysis of tertatolol in rat plasma using macrocyclic antibiotic chiral stationary phase.
No full textEnantiomeric resolution of teratolol was achieved on a vancomycin macrocyclic antibiotic chiral stationary phase known as Chirobiotic V with UV detection set at 220 nm. The polar ionic mobile phase (PIM) consisted of methanol-glacial acetic acid-triethylamine (100:0.01:0.015, v/v/v) has been used at a flow rate of 0.8 ml min(-1) . The calibration curves in plasma were linear over the range of 5-500 ng ml(-1) for each enantiomer with detection limit of 2 ng ml(-1) . The proposed method was validated in compliance with the international conference on harmonization (ICH) guidelines. The developed method applied for the trace analyses of tertatolol enantiomers in plasma and for the pharmacokinetic study of tertatolol enantiomers in rat plasma. The assay proved to be suitable for therapeutic drug monitoring and chiral quality control for tertatolol formulations by HPLC
Technology evaluation: Kollicoat IR.
No full textIntroduction: Developments in industrial pharmacy are often linked to the discovery of pharmaceutical excipients. Although recently introduced as a material for immediate release coatings, Kollicoat IR already has other applications. Areas covered: In this review, the different properties and pharmaceutical applications of Kollicoat IR as an excipient are discussed. In the first part, the chemical structure and the physicochemical characteristics are examined. The second part is a presentation of the available Kollicoat IR products followed by a brief overview of the preclinical studies completed for its use as an instant release coating material. Expert opinion: Although the polymer was intended as an immediate release coating material for tablets, grafting PEG with polyvinyl alcohol to form this polymer provides physicochemical properties that lead to ever-broadening applications. Understanding its properties can lead to the development of a new use for Kollicoat IR. The addition of Kollicoat IR to an ethylcellulose or polyvinyl acetate tablet coat was successful at modifying the drug release rate. Designing a successful controlled release coat simply requires acknowledgment of the drug release mechanism from the mixture of polymers that includes Kollicoat IR. Moreover, the interaction between Kollicoat IR and poorly soluble drugs produces fast-dissolving solid dispersions prepared using hot stage extrusion, spray drying, or freeze drying
The use of spray-drying to enhance celecoxib solubility
No full textThe present research investigates the enhancement of the dissolution rate of celecoxib by using spray-drying to prepare a solid dispersion with various polymers, namely Kollicoat IR(®) (Kollicoat), polyvinyl alcohol (PVA) 22000, or polyethylene glycol 6000 (PEG). The investigated drug-to-polymer mass ratios were 1:1, 1:2, and 1:4 by weight. Hydroalcoholic or methylene chloride solvent systems were used. The obtained yields ranged from 65% to 78%, whereas the entrapment efficiencies were between 68% and 82%. The results revealed an increase in the dissolution rate of the prepared particles up to 200% within 20 min. The prepared particles were investigated using differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The increased dissolution rate was attributed to hydrogen bond formation between celecoxib and each polymer together with the reduced size of the formed particles offering a greater overall surface area. It was concluded that spray-drying may be considered a successful one-step technique to improve the dissolution rate of celecoxib when using Kollicoat, PVA, or PEG as the carrier polymer.
DOI: 10.3109/03639045.2011.58742
Improvement effect of tomato seeds and vitamin C on potassium bromate induced renal injury in rats
No full textFifty-four adult male of white albino rats (Sprague Dawley Strain) were injected with a single intraperitoneal dose of potassium bromate at level 125 mg /kg body weight to induce renal injury. Rats classified into non treated positive control group and five treated groups that were tomato seeds powder, tomato seeds extract, vitamin C, tomato seeds powder with vitamin C and tomato seeds extract with vitamin C groups. The study was conducted for ten weeks. The results revealed that, the treatment of renal injured rats with tomato seeds powder or extract with or without vitamin C showed improvement of nutritional results as a significant increase in final
weight, weight gain and food intake compared to positive control group. The value of Food efficiency ratio (FER) was significantly increased in tomato seeds powder, tomato seeds extract, tomato seeds powder with vitamin C and tomato seeds extract with vitamin C groups compared to positive control group. Values of blood hemoglobin (HB), packed cell volume (PCV) and red blood cells; serum high density lipoprotein cholesterol (HDLc), glutathione transferase (GST), catalase & superoxide dismutase (SOD) , and kidney glutathione peroxidase (GPX) & glutathione transferase (GST) were significantly increased in all treated groups compared to positive control group. The values of serum cholesterol, cholesterol/HDLc ratio, triglyceride, low density lipoprotein cholesterol (LDLc), creatinine, uric acid, urea & nitric oxide (NO) and kidney malondialdehyde (MDA) were significantly decreased
compared to positive control group. White blood cells was significantly increased in tomato seeds powder with vitamin C and tomato seeds extract with vitamin C groups while the value of serum very low density lipoprotein cholesterol (VLDLc) was significantly decreased in tomato seeds powder, tomato seeds extract, tomato seeds
powder with vitamin C and tomato seeds extract with vitamin C groups compared to positive control group
Laser-assisted topical drug delivery by using a low-fluence fractional laser: Imiquimod and macromolecules.
No full textThe aim of this study was to evaluate the ability of a low-fluence fractional erbium:yttrim-aluminum-garnet (Er:YAG) laser, with a wavelength of 2940nm, for enhancing and controlling the skin permeation of imiquimod and macromolecules such as polypeptides and fluorescein isothiocyanate (FITC)-labeled dextran (FD). The in vitro permeation has been determined using a Franz diffusion cell, with porcine skin and nude mouse skin as the barriers. Hyperproliferative and ultraviolet (UV)-irradiated skins were also used as barrier models to mimic the clinical therapeutic conditions. Confocal laser scanning microscopy (CLSM) was used to examine the in vivo nude mouse skin uptake of peptide, FITC, and FD. Both in vitro and in vivo results indicated an improvement in permeant skin delivery by the laser. The laser fluence and number of passes were found to play important roles in controlling drug transport. Increases of 46- and 127-fold in imiquimod flux were detected using the respective fluences of 2 and 3J/cm(2) with 4 pulses. An imiquimod concentration of 0.4% from aqueous vehicle with laser treatment was sufficient to approximate the flux from the commercial cream with an imiquimod dose of 5% without laser treatment, indicating a reduction of the drug dose by 125-fold. The enhancement of peptide permeation was size and sequence dependent, with the smaller molecular weight (MW) and more-hydrophilic entities showing greater enhancing effect. Skin permeation of FD with an MW of at least 150kDa could be achieved with fractional laser irradiation. CLSM images revealed intense green fluorescence from the permeants after exposure of the skin to the laser. The follicular pathway was significant in laser-assisted permeation. Copyright © 2010. Published by Elsevier B.V.
DOI: 10.1016/j.jconrel.2011.03.01
Group Profiling in E-Service Portals
No full textNowadays Service activities are social and involve different types of individuals that should be considered. Thus, group profiling can be used to connect similar customers together and recommend providers based on group evaluation. Accordingly, this paper proposes a new approach that recommends providers, based on group profiling and ranking, to be used in e-service portals. This approach focuses on group profiling and cluster users based on Ant Colony Clustering (ACC) method. In addition, the approach has been tested and three measures have been recorded including speed, aggregation precision, and result accuracy. The result of such test has shown that this approach is promising and has a high quality result
Arabic Educational Programs for Children with Learning Difficulties
No full textIn this paper, we describe the design of interactive educational programs for Arabic-speaking children with Learning Difficulties (LDs). The programs were developed in the context of a software engineering course and focused on two reading and writing skills that are known to be challenging for school-aged children with LDs. Using this computer-based learning program enables a profile of achievement and progress to be automatically generated, and has the potential to be an affordable and targeted method of remedial learning for children receiving support for their LDs in resource rooms of schools.King Saud Universit
Alpha-lipoic acid rebalances redox and immune-testicular milieu in septic rats
No full textIn the present study, lipopolysaccharide(LPS), as an immune modulator in male adult rats and alpha-lipoic acid (ALA), as a powerful biological antioxidant and anti-inflammatory, are examined to help understanding the role of the immune and redox perturbation in testicular dysfunction with a possible protection. A total of 60 male Swiss albino rats were divided into 5 groups (10/group) respectively as follows Saline, ALA-vehicle, ALA (200 mg/kg), LPS (5 mg/kg) started with 20 rats and LPS + ALA. Obtained data from previously reported study, in our laboratory, and from the present one revealed that LPS induced marked reductions in sperm's count, motility and resulted in deterioration of the testicular histological features. In addition, LPS decreased testicular reduced glutathione (GSH) level and lactate dehydrogenase isoenzyme-x (LDH-x) activity. However, it increased testicular levels of malondialdehyde (MDA), nitric oxide (NO) and 8-hydroxydeoxyguanosine (8-HDG) in testicular DNA, along with increased serum IL-2 level. In contrast, rats pretreated with ALA showed almost complete normalization of all the tested parameters. In conclusion, LPS induced perturbation of the immune-testicular barrier as a result of redox imbalance with a subsequent testicular dysfunction. Pretreatment with ALA ameliorated all these effects by its immune-modulator and antioxidant mechanisms suggesting a protective role against male infertility in septic or severely infected patients. Published by Elsevier Ireland Ltd
Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through modulation of oxidative stress genes expression.
No full textDiabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion and/or action. One of the most important complications of this metabolic disease is diabetic nephropathy. Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Recent studies have established that metformin, an oral hypoglycemic drug, possesses antioxidant effects. However, whether metformin can protect against diabetic nephropathy has not been reported before. The overall objectives of the present study are to elucidate the potential nephroprotective effect of metformin in a rat diabetic nephropathy model and explore the exact underlying mechanism(s) involved. The effect of metformin on the biochemical changes associated with hyperglycemia induced by streptozotocin was investigated in rat kidney tissues. In addition, energy nucleotides (AMP and ATP), and Acetyl-CoA in the kidney homogenates and mitochondria, and the mRNA expression of oxidative stress and pro-inflammatory mediators were assessed. Our results showed that treatment of normoglycemic rats with metformin caused significant increase in ATP, Acetyl-CoA, and CoA-SH contents in kidney homogenates and mitochondria along with profound decrease in AMP level. On the other hand, treatment of diabetic nephropathy rats with metformin normalized all biochemical changes and the energy status in kidney tissues. At the transcriptional levels, metformin treatment caused significant restoration in diabetic nephropathy-induced oxidative stress mRNA levels, particularly GSTα, NQO1, and CAT genes, whereas inhibited TNF-α and IL-6 pro-inflammatory genes. Our data lend further credence for the contribution of metformin in the nephroprotective effect in addition to its well known hypoglycemic action