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Khiralla G.M.,National Organization for Drug Control and Research NODCAR
Food Science and Technology Research

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. Source

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

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. Source

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

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. Source

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

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. Source

Ibrahim T.M.,National Organization for Drug Control and Research NODCAR
Der Pharma Chemica

Three simple, precise, accurate, and economical UV spectrophotometric methods have been developed and validated for the routine estimation of diclazuril in active pharmaceutical ingredient (API) and drug product. Diclazuril was estimated at 286.2 nm in UV-spectroscopic method (Method A), 260 nm in first order derivative spectroscopy (Method B) and scanned at 300 - 273 nm in Area Under Curve method (Method C).Linearity range was found to be 2 -22 μg/ml (Correlation coefficient r2 = 0.9996 in method A, r2 = 0.09997 in method B and r2 = 0.9995 in method C) in all three methods. The molar absorptivity was found to be 1.6×104 Lmol-1 cm-1 in method A, 2.038x103 Lmol-1 cm-1 in method B, and 5.5x104 Lmol-1 cm-1 in method C. These methods were tested and validated for various parameters according to ICH guidelines. The proposed methods were successfully applied for the determination of Diclazuril in drug product (powder). The results demonstrated that the procedure is accurate, precise and reproducible (% relative standard deviation < 1%), while being simple, cheap and less time consuming and can be suitably applied for the estimation of Diclazuril in powder dosage forms. Source

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