Ali E.H.A.,Ain Shams University |
Elgoly A.H.M.,National Organization for Drug Control and Research NODCAR
Pharmacology Biochemistry and Behavior | Year: 2013
The aim of this work is to evaluate the impact of butyl paraben (BP) in brain of the pups developed for mothers administered BP from early pregnancy till weaning and its effect on studying the behavior, brain neurotransmitters and brain derived neurotrophic factor BDNF via comparing the results with valproic acid (VA) autistic-rat model preparing by a single oral injection dose of VA (800 mg/kg b.wt) at the 12.5 days of gestation. Butyl paraben was orally and subcutaneously administered (200 mg/kg b.wt) to pregnant rats from gestation day 1 to lactation day 21. The offspring male rats were subjected at the last 3 days of lactation to Morris water maze and three chamber sociability test then decapitated and the brain was excised and dissected to the cortex, hippocampus, cerebellum, midbrain and pons for the determination of norepinephrine, dopamine and serotonin (NE, DA and 5-HT) and cortex amino acids and whole brain BDNF. The results showed similar social and learning and memory behavioral deficits in VA rat model and the butyl paraben offspring in comparison with the controls. Also, some similar alterations were observed in monoamine content, amino acids and BDNF factor in the autistic-like model and butyl paraben offspring in comparison with the controls. The alterations were recorded notably in hippocampus and pons NE, midbrain DA, hippocampus and midbrain 5-HT, and frontal cortex GABA and asparagine. These data suggest that prenatal exposure to butyl paraben induced neuro-developmental disorders similar to some of the neurodevelopmental disorders observed in the VA model of autism. © 2013 Elsevier Inc. All rights reserved.
El-Moselhy M.A.,Minia University |
Taye A.,Minia University |
Sharkawi S.S.,Minia University |
El-Sisi S.F.I.,National Organization for Drug Control and Research NODCAR |
Ahmed A.F.,Zagazig University
Food and Chemical Toxicology | Year: 2011
This study was conducted to investigate the effect of curcumin, obtained from Curcuma longa, in comparison with rosiglitazone on the progression of insulin resistance and type 2 diabetes mellitus (T2DM) and the mechanisms underlying this effect. Insulin resistance and T2DM was induced in male Sprague Dawley rats by high fat diet (HFD) feeding for 60 and for 75. days representing two regimens of the study, protection and treatment. Prophylactic oral administration of curcumin (80. mg/kg), rosiglitazone (1. mg/kg), their combination, or vehicle (in control groups) was started along with HFD feeding in different groups. Treatment is achieved by oral administration of the previously mentioned agents in the last 15. days of HFD feeding after induction of insulin resistance and T2DM in rats. Curcumin showed an anti-hyperglycemic effect and improved insulin sensitivity, and this action may be attributed at least in part to its anti-inflammatory properties as evident by attenuating TNF-α levels in HFD fed rats, and its anti-lipolytic effect as evident by attenuating plasma free fatty acids. The curcumin effects are comparable to those of rosiglitazone, which indicate that they may act similarly. Finally we can say that, curcumin could be a beneficial adjuvant therapy in patients with T2DM. © 2011 Elsevier Ltd.
Safar M.M.,Cairo University |
Abdallah D.M.,Cairo University |
Arafa N.M.,National Organization for Drug Control and Research NODCAR |
Abdel-Aziz M.T.,Cairo University
Brain Research | Year: 2010
N-methyl-d-aspartate (NMDA) receptor antagonists appear to enhance the anticonvulsant activity of antiepileptic drugs in several models of epilepsy. Therefore, the current study evaluates the modulatory effect of magnesium (Mg2+), a non-competitive NMDA receptor antagonist, on a subprotective dose of valproate (VPA) against pentylenetetrazol (PTZ)-induced convulsions. Male Wister rats received either saline or PTZ (60 mg/kg, i.p.). The other three groups were pretreated with Mg2+ (40 mg/kg, p.o., 4 weeks), single subprotective dose of VPA (100 mg/kg, i.p.), or Mg2+ with VPA, before PTZ injection. PTZ provoked clonic convulsions, reduced GABA content, deranged brain redox status, and elevated nitric oxide (NO). Neither the subprotective dose of VPA nor Mg2+ alone guarded against clonic seizures invoked by PTZ, an effect that was achieved only by their combination and supported by a significant delay in seizure latency. Moreover, VPA leveled off glycine and aspartate, exerted no effect on glutamate, and unexpectedly reduced GABA and taurine levels. Mg2+ alone or in combination showed the same pattern on the aforementioned amino acids, except for taurine. All regimens restored glutathione (GSH) and total antioxidant capacity (TAC); however, only VPA normalized NO level. This study demonstrates that Mg2+ could enhance the antiepileptic efficacy of a subprotective dose of VPA, possibly by improving redox balance and modulation of some brain amino acids. © 2010 Elsevier B.V. All rights reserved.
El-Shal M.A.,National Organization for Drug Control and Research NODCAR |
Attia A.K.,National Organization for Drug Control and Research NODCAR
Analytical and Bioanalytical Electrochemistry | Year: 2013
The oxidative behaviour of zolmitriptan was studied at a glassy carbon electrode in Britton-Robinson (BR) buffer solutions using cyclic, differential pulse and square wave voltammetric techniques. The oxidation process was shown to be irreversible over the pH range (2.0-6.0) and was diffusion controlled with some adsorption character. The analytical method was developed for the determination of zolmitriptan in BR buffer solution at pH 2.0 as supporting electrolyte. The anodic peak current varied linearly with zolmitriptan concentration in the following ranges: 4.0×10-8 to 3.2×10-7 M and 4.0×10-10 to 3.2×10-9 M of zolmitriptan with limits of detection of 2.0×10-8 M and 2.0×10-10 M by differential pulse and square wave methods, respectively. Validation parameters, such as sensitivity, accuracy, precision and recovery were evaluated. The proposed method was applied to the determination of zolmitriptan in the tablet dosage form. The results were compared with those obtained by the reported methods showing higher sensitivity of our proposed method. © 2013 by CEE.
Elqudaby H.M.,National Organization for Drug Control and Research NODCAR |
Mohamed G.G.,Cairo University |
El-Din G.M.G.,National Organization for Drug Control and Research NODCAR
Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy | Year: 2014
Charge transfer complexes of loperamide hydrochloride (LOP.HCl) and trimebutine (TB) drugs as electron donor with 2,3-dichloro-5,6-dicyano-p- benzoquinone (DDQ), tetracyanoethylene (TCNE) and 7,7,8,8- tetracyanoquinodimethane (TCNQ) as π-acceptors in acetonitrile were investigated spectrophotometrically to determine the cited drugs in pure and dosage forms. The reaction gives highly coloured complex species which are measured spectrophotometrically at 460, 415 and 842 nm in case of LOP.HCl and at 455, 414 and 842 nm in case of TB using DDQ, TCNE and TCNQ reagents, respectively. The optimum experimental conditions have been studied carefully and optimized. Beer's law was obeyed over the concentration ranges of 47.70-381.6, 21.50-150.5 and 10.00-100.0 μg mL-1 for LOP.HCl and 37.85-264.9, 38.75-310.0 and 7.75-155.0 μg mL-1 for TB using DDQ, TCNE and TCNQ reagents, respectively. Sandell sensitivity, standard deviation, relative standard deviation, limit of detection and quantification were calculated. The obtained data refer to high accuracy and precision of the proposed method. These results are also confirmed by inter and intra-day precision with percent recovery of 99.18-101.1% and 99.32-101.4% in case of LOP.HCl and 98.00-102.0% and 97.50-101.4% in case of TB using DDQ, TCNE and TCNQ reagents for intra- and inter-day, respectively. These data were compared with those obtained using official methods for the determination of the cited drugs. The stability constants of the CT complexes were determined. The final products of the reaction were isolated and characterized using FT-IR, 1H NMR, elemental analysis and thermogravimetric analysis (TG). The stoichiometry and apparent formation constant of the complexes formed were determined by applying the conventional spectrophotometric molar ratio method. © 2014 Elsevier B.V. All rights reserved.
Khiralla G.M.,National Organization for Drug Control and Research NODCAR
Food Science and Technology Research | Year: 2015
The study aimed to isolate and characterize probiotic strains with potential cholesterol degrading activity. Fourteen lactic acid bacteria isolated from lamb meat were screened on mineral salt agar supplemented with 0.2% cholesterol (MSC agar). Cell-free supernatants (CFSs) of these isolates were used as a crude source of extracellular cholesterol degrading enzymes. CFSs of GMK01, GMK02 and GMK03 isolates displayed high ability to degrading cholesterol (86.4, 86.1 and 84.6%, respectively). These isolates were identified as Lactobacillus sakei GMK01, Lactobacillus rhamnosus GMK02 and Leuconostoc mesenteroides GMK03. Strains were resistant to low acidity (pH 2.5) and bile salts (0.3%), able to adhesion to Caco-2 cells and have low rate of antibiotic resistance. Living cells of these strains were able to degrade cholesterol in MSC broth even after treatment with simulated gastrointestinal juice. The maximum cholesterol degradation (about 90%) was obtained on the third day. 4-cholesten-3-one was detected as a degradation product of cholesterol by Leuconostoc mesenteroides GMK03. The studied strains degrade cholesterol by different mechanisms and may suggest a new possibility for the mechanism underlying cholesterol degradation by LAB. In conclusion, the isolated strains could be suggested as potential pharmaceutical probiotic strains for food industry and human nutrition. © 2015, Japanese Society for Food Science and Technology.
Nesseem D.I.,National Organization for Drug Control and Research NODCAR |
Eid S.F.,National Organization for Drug Control and Research NODCAR |
El-Houseny S.S.,National Organization for Drug Control and Research NODCAR
Life Sciences | Year: 2011
Aim: The purpose of this study was to develop transdermal films (TFs) with the addition of different polymer ratios that incorporated 0.5% tenoxicam in order to ensure maximum controlled and sustained drug release capacity. Tenoxicam is a non-steroidal anti-inflammatory drug (NSAID) widely used in the treatment of rheumatic diseases and characterized by its efficacy and reduced side effects in comparison to other NSAIDs. Main methods: Transdermal films of tenoxicam were designed with the Eudragit L30D-55copolymer with permeation enhancers like polyethylene glycol (PEG) and propylene glycol (PG) incorporated at different concentrations using the casting evaporation technique. Evaluations of these formulae were performed through mechanical characterizations and Fourier Transform Infrared Spectroscopy [FTIR]. In-vitro release studies were performed during 24 h using diffusion cells. The film formulations with optimum in vitro-release rate have been taken up for testing of the anti-inflammatory effects and the sustaining action of tenoxicam. The in-vivo studies performed included carrageenan-induced hind paw edema and skin biopsies in Wistar rats. Key findings: Formulation (F7) had the best effective combination [glycerol (0.25 g), PEG200 (0.5 g), PEG400 (1 g) and PG (10%) and 0.5% dispersed drug] among all of the tenoxicam TF formulations studied. Also, this formula had the highest release value than formula 1 (F1) that contains [glycerol (2.5 g), PEG200 (0.5 g), PEG400 (0.5 g) and 0.5% dissolved drug] or a commercially available gel after 24 h. FTIR revealed that there was an interaction between the polymer and the drug. The drug-polymer interaction occurring between tenoxicam and Eudragit L30D-55 seems to cause a drag effect, leading to a delay of the tenoxicam release from the Eudragit L film. Significance: When the films were applied half an hour before the subplantar injection of carrageenan in the hind paw of Wistar rats, it was observed that formula F7 provided maximum inhibition of paw edema in rats over 24 h in contrast to both formula F1 and the marketed piroxicam gel as a reference. This was also confirmed histopathologically from skin biopsies. Thus, we show that tenoxicam can be formulated into transdermal films to sustain its release characteristics, and the polymeric composition of PEG200/PEG400 at a ratio of 1:2 and 10% PG was found to be the best choice to manufacture tenoxicam TF. © 2011 Elsevier Inc. All rights reserved.
Ismail N.S.,National Organization for Drug Control and Research NODCAR
Iranian Journal of Pharmaceutical Sciences | Year: 2016
The utility of carbon paste electrode for the determination of flavoxate HCl modified with flavoxate-tetraphenylborate (FLX-TPB) and flavoxate-phosphotungestic acid (FLX-PTA) ion-pairs in batch mode is demonstrated. The electrodes revealed a Nernstian response over a wide concentration ranges 1.39×10-5-1x10-2 mol L-1 and1×10-5-1x10-2 mol L-1 using FLX-TPB and FLX-PTA, respectively. The detection limits of these sensors are 1.39×10-5 mol L-1, and 1x10-6 mol L-1 using FLX-TPB and FLX-PTA, respectively. The best performance was obtained with carbon paste composition of 5% flavoxate-tetraphenylborate or flavoxate-phosphotungestate, 47.5% graphite and 47.5% o-nitro phenyloctyl ether (o-NPOE). The sensors exhibit a very fast response time (5-7 s) and good selectivity in presence of inorganic cations, sugars and aminoacids. The proposed sensors show great improvement in comparison with other previously reported sensors. The sensors were successfully applied to monitoring of flavoxate in pure solution and pharmaceutical formulation (Genurin tablet) with recovery ranges from 97.2-101.0% and 98.1-101.6% using FLX-TPB and FLX-PTA, respectively. © 2016, Iranian Association of Pharmaceutical Scientists. All rights reserved.
Shukr M.H.,National Organization for Drug Control and Research NODCAR |
Metwally G.F.,National Organization for Drug Control and Research NODCAR
Tropical Journal of Pharmaceutical Research | Year: 2013
Purpose: To formulate topical gels containing various essential oils and evaluate their antibacterial activity against methicillin-resistant Staphylococcus Aureus (MRSA) skin infections. Methods: The four essential oils namely, lemon grass, rosemary, thyme and basil were steam-distilled and then evaluated for their antibacterial activity against MRSA. Lemon grass and thyme oils were chosen for further studies, including analysis of their composition by gas chromatography-mass spectrometry (GC/MS). Gels were formulated using carbopol 940, hydroxypropylmethyl cellulose, sodium carboxymethy cellulose with lemon grass oil and evaluated for their physical appearance, pH, spreadability rheological properties, antibacterial activity against MRSA and skin irritation in human volunteers. The selected gels were prepared with thyme oil alone or in combination with lemon grass oil and compared with that containing lemon grass oil alone. Results: The minimum inhibitory concentration (MIC) of lemon grass and thyme oils were 30 and 4 μl/ml, respectively. Carbopol 940 gel (0.75 %) containing lemon grass oil showed good physical characteristics, including spreadability and rheological properties; it also showed the strongest antibacterial activity of the gels tested. No significant difference (p ≤ 0.05), were observed between the characteristics of the gels containing thyme oil alone and in combination with lemon grass oil. The antibacterial activity of the gel containing the two oils was approximately the sum of those containing the individual oils. No signs or symptoms of lesions, redness or itching were found when the gels were applied to the skin. Conclusion: The carbopol 940 gel containing lemon grass and thyme oils possess good antibacterial activity against MRSA when applied to human skin, and exhibit no skin irritation. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved.
Shukr M.,National Organization for Drug Control and Research NODCAR
Archives of Pharmacal Research | Year: 2014
Topical anesthesia is a safe and cost-effective method considered as the first-choice in many procedures. The objective of the present study was to develop ocular inserts as a new form of lidocaine HCl to give a sufficient level of anesthetic. Ocuserts were prepared using HPMC and PVA in different ratios with lidocaine HCl alone and lidocaine HCl β-cyclodextrins complex. Drug polymer interactions were studied by Fourier transform infrared spectroscopic studies. The prepared ocular inserts were characterized by means of ocusert thickness, weight variation, folding endurance, surface pH, moisture absorption, drug content and in-vitro drug release. Stability study was conducted on selected formulations, and in vivo evaluation of lidocaine HCl was also carried out. The results revealed that F7 formulations containing drug β-cyclodextrins with 4 % HPMC and 2 % PVA were found to have good physical characteristics and appropriate flexibility. In addition to the highest initial and cumulative percentage of drug released in vitro. The selected F7 ocuserts retained their characteristics during the stability study. The results of in vivo study showed that the addition of β-cyclodextrins in F7 significantly increase the drug content in the aqueous humor when compared with F3 ocuserts containing lidocaine HCl alone. © 2013 The Pharmaceutical Society of Korea.