Fulwah Yahya Alqahtani

Determination and characterization of metronidazole–kaolin interaction

The needs for safe, therapeutically effective antidiarrheal combination continuously lead to effective treatment. When administered simultaneously, metronidazole–kaolin interactions have been reported by FDA but not studied. This paper is the first to study metronidazole–kaolin interactions. Adsorption isotherms of a metronidazole–kaolin antidiarrheal combination from aqueous solutions at an in vivo simulated pH conditions were obtained at 37 ± 0.5 °C. Langmuir constants for the adsorption are 10.8225, 41.3223 mg g−1 and 11.60, 2.56 l g−1 aimed at the monolayer capacity, and the equilibrium constant at pH 1.2 and 6.8, respectively. pH effect on adsorption of known concentration of metronidazole by kaolin was also studied over the range 1.2–8. A gradual increase in the adsorbed amount was noted with increasing the pH. Elution studies by different eluents showed that drug recovery from adsorbent surface was pH-dependent via competitive mechanism. The elution followed the sequence: 0.1 M HCl > 0.1 M NaCl > H2O. Adsorption–desorption studies revealed physical adsorption. The equilibrium concentration of metronidazole decreased as the adsorbent concentration was increased in the systems. The dissolution profiles (USP) of commercially available tablets (Riazole® 500 mg) were obtained alone and in the presence of either (ORS®) rehydration salts and 9 or 18 g of kaolin powder. The percentage drug released versus time: 95.01% in 25 min, 101.02% in 30 min, 67.63% in 60 min, 60.59% in 60 min, respectively. The percentage drug released versus time was increased with ORS® due to common ion effect [Cl−], while, it was decreased with kaolin due to adsorption. The mechanism of reaction of Riazole® (500 mg) tablets in the different dissolution media, confirms with Korsmeyer–Peppas model. The interaction between metronidazole and kaolin was characterized by melting point determinations, differential scanning calorimetry analysis and infrared spectroscopy. The results obtained were suggestive of physical interaction between metronidazole and kaolin.

Measurement and evaluation of the effects of pH gradients on the antimicrobial and antivirulence activities of chitosan nanoparticles in Pseudomonas aeruginosa

Objective The purpose of this study was to study the antimicrobial activity of chitosan nanoparticles (CSNPs) on Pseudomonas aeruginosa with special emphasis on their sensitivity to pH and the effect of pH on their activity. Methodology Antimicrobial activity of CSNPs against Pseudomonas aeruginosa at different pH was tested using broth dilution method. Further assessment of antivirulence activity and sensitization of CSNPs on Pseudomonas aeruginosa were examined. Results Significant antimicrobial effects of CSNPs against Pseudomonas aeruginosa were detected at slightly acidic pH 5, whereas the activity was abolished at a pH of greater than 7. The antivirulence activity of CSNPs was then investigated and treatment with CSNPs (1000 ppm) resulted in a significant reduction or even complete inhibition of pyocyanin production by P. aeruginosa compared with untreated P. aeruginosa indicating the antivirulence activity of CSNPs. CSNPs also sensitized P. aeruginosa to the lytic effects of sodium dodecyl sulfate (SDS); such sensitization was not blocked by washing chitosan-treated cells prior to SDS exposure revealing that CSNPs disturb the outer membrane leading to irreversible sensitivity to detergent even at low concentration (100 ppm). Conclusions These findings highlight CSNPs as potentially useful as indirect antimicrobial agents for a variety of applications.

An evaluation of E. coli in urinary tract infection in emergency department at KAMC in Riyadh, Saudi Arabia: retrospective study

BackgroundUrinary tract infection (UTIS) is a common infectious disease in which level of antimicrobial resistance are alarming worldwide. Therefore, this study aims to describe the prevalence and the resistance pattern of the main bacteria responsible for UTIS Escherichia coli (E. coli).MethodsRetrospective chart review for patients admitted to emergency department and diagnosed with UTIS at KAMC, in Riyadh, Saudi Arabia between January to March 2008 was performed. Antimicrobial susceptibility to ampicillin, augmentin (amoxicillin/clavulanate), cefazolin, co-trimoxazole (sulfamethoxazole/trimethoprim), ciprofloxacin, and nitrofurantoin, and cefpodoxime was determined for 101 E. coli urinary isolates.ResultsEscherichia coli was the most prevalent pathogen contributing to UTIS representing 93.55, 60.24, and 45.83% of all pathogen isolated from urine culture of pediatric, adult, and elderly, respectively. High rates of resistance to ampicillin (82.76, 58, and 63.64%) and co-trimoxazole (51.72, 42, and 59.09%), among E. coli isolated from pediatric, adult and elderly respectively. Nitrofurantoin was the most active agent, followed by ciprofloxacin, augmentin and cefazolin. 22.77% of E. coli isolates exhibited multiple drug resistance (MDR). Among 66 and 49 isolates resistant to ampicillin and co-trimoxazole, respectively, 34.84 and 42.85% were MDR. In contrast, all isolates resistant to augmentin and nitrofurantoin were MRD, while 72.7 and 82.4% of isolates resistant to ciprofloxacin and cefazolin were MDR.ConclusionsHigh resistance was observed to ampicillin and co-trimoxazole which commonly used as empirical treatments for UTIS, limiting their clinical use. This necessitates continuous surveillance for resistance pattern of uropathogens against antibiotics.

Photo-catalytic Killing of HeLa Cancer Cells Using Facile Synthesized Pure and Ag Loaded WO 3 Nanoparticles

Chemotherapy, the most commonly used therapeutic method for cancer, has the inherent constraint of low bioavailability. A number of physical cancer therapeutic treatments like radiation, ultrasound, photo-acoustic/photo thermal, microwave therapies are based on locating the afflicted sites with the help of imaging, but the serious drawbacks of these treatment options are that they damage the neighboring normal tissues and/or induce undesired cancer metastasis. In addition, these methods of treatment are very expensive and not in the reach of a common man especially in the developing countries. Therefore, innovative, less invasive and cost effective treatment methods with the help of less toxic drugs have been sought for treating cancer. In this work, photo-catalytic method of killing cancer cells, using the nanostructured silver loaded tungsten oxide (Ag/WO3) as photo-catalysts, in conjunction with broadband UV radiation is presented. Ag/WO3with two different mass ratios of Ag and WO3 (1% Ag/WO3 and 3% Ag/WO3) were synthesized, characterized and these nanostructured materials served as photo-catalysts in the process of killing cancer cells by photo-catalytic method. The advantage of loading Ag in WO3 is quite evident from the observed increase in the photo-catalytic killing of the HeLa cells. This photo-catalytic enhancement was effectively caused by the development of Schottky junction between Ag in WO3, which led to a substantial inhibition of photo-generated charge recombination and also by the stimulation of surface plasmon resonance in silver nanoparticles, which led to the enhanced visible light absorption by the material.

Chemical composition and antimicrobial, antioxidant, and anti-inflammatory activities of Lepidium sativum seed oil

Lepidium sativum (garden cress) seed oil was examined for its antimicrobial, antioxidant, and anti-inflammatory activities. The oil was obtained by hydrodistillation, where gas chromatography coupled with mass spectrometry that utilized to study its chemical composition. Microdilution method was used to test the antimicrobial effect of oil against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, Klebsiella pneumoniae, and Candida albicans. The antioxidant activity was assessed by radical scavenging activity assay using 2,2-diphenyl-1-picrylhydrazyl radical. The major constituents found in the oil were 7,10-hexadecadienoic acid, 11-octadecenoic acid, 7,10,13-hexadecatrienoic acid, and behenic acid. The minimum inhibitory concentration (MIC) against all pathogens was 47.5 mg/ml, except for Salmonella enterica, which showed MIC of 90 mg/ml. The oil demonstrated antioxidant activity in a dose dependent pattern, with a half maximal inhibitory concentration (IC50) value of 40 mg/ml, and exerted anti-inflammatory activity, wherein 21% protection was shown at a concentration of 300 μg/ml. Thus, L. sativum seed oil shows antimicrobial, antioxidant, and anti-inflammatory properties.

Formulation and evaluation of docetaxel nanosuspensions: In-vitro evaluation and cytotoxicity

Objective The aim of the present study was to formulate the anticancer drug; docetaxel (DOX) as nanoparticles to enhance its biological activity. Methodology Solvent precipitation method was used to prepare DOX-loaded nanoparticles and was stabilized by different concentrations of hydroxypropyl methylcellulose (HPMC, E5) and sodium deoxycholate (SDC). Results The results showed that the particle size of the prepared DOX nanoparticles stabilized by SDC was small in comparison to those stabilized by the corresponding HPMC concentrations. The smallest particle size (83.97 nm) was obtained by using SDC as stabilizer at 5% level with zeta potential of −13.6 mV. It was concluded that increasing the stabilizer concentration resulted in increase in both initial and overall cumulative drug release. The release rate in case of nanoparticles stabilized by 5% SDC was 33% and 87% after 1 and 24 h respectively. The results showed that a significant reduction in the viability of FRO cells was observed at all tested time intervals in case of nanoparticles stabilized by 5% SDC at concentrations of 100 and 1000 μM/ml. In contrast, no signs of cytotoxicity was observed for nanoparticles stabilized by 5% HPMC at 10 and 100 μM/ml concentrations.

Preparation, characterization, and antibacterial activity of diclofenac-loaded chitosan nanoparticles

Emerging antibiotic resistance necessitates the development of new therapeutic approaches. Many studies have reported the antimicrobial activity of diclofenac sodium (DIC) and chitosan nanoparticles (CNPs). Hence, this study aimed to prepare non-antibiotic DIC-loaded CNPs (DIC.CNPs) and characterize their in vitro antibacterial activity. DIC.CNPs were prepared from low and high molecular weight (LMW and HMW, respectively) chitosan using an ionic gelation method. Prepared NPs were characterized, and their antibacterial activity against gram-positive Staphylococcus aureus and Bacillus subtilis was evaluated using the agar diffusion and broth dilution methods. The particle size, polydispersity index (PDI), and encapsulation efficiency of the formulated DIC.CNPs increased with increasing MW of chitosan. The prepared NPs showed a narrow size distribution with low PDI values (0.18 and 0.24) and encapsulation efficiency (29.3% and 31.1%) for LMW.DIC.CNPs and HMW.DIC.CNPs, respectively. The in vitro release profile of DIC from the DIC.CNPs was biphasic with a burst release followed by slow release and was influenced by the MW of chitosan. DIC.CNPs exhibited significantly higher antibacterial activity against S. aureus (minimum inhibitory concentration [MIC90] LMW.DIC.CNPs = 35 µg/mL and MIC90 HMW.DIC.CNPs = 18 µg/mL) and B. subtilis (MIC90 LMW.DIC.CNPs = 17.5 µg/mL and MIC90 HMW.DIC.CNPs = 9 µg/mL) than DIC alone did (MIC90 DIC = 250 and 50 µg/mL against S. aureus and B. subtilis, respectively). The antibacterial activity was influenced by pH and the MW of chitosan. Collectively, these results may suggest the potential usefulness of DIC.CNPs as non-antibiotic antibacterial agent necessitating further future studies to asses the stability of DIC.CNPs prepared.

The role of CDKN2B in cardiovascular risk in ethnic Saudi Arabs: A validation study

BACKGROUND Genome-wide association studies (GWASs) have yielded a wealth of information furnishing support for the variability in genetic predisposition to disease. However, the actual impact of such findings on any particular ethnic population needs to be validated through replication studies. In the present study, we verified recent findings of a GWAS demonstrating a strong association for the cyclin-dependent kinase 4 inhibitor B (CDKN2B) genomic region with coronary artery disease (CAD)/myocardial infarction (MI) in ethnic Saudi Arabs. METHODOLOGY We genotyped 8 CDKN2B SNPs for cardiovascular risk in 4650 Saudi Arabs, comprising 2429 CAD cases (1860 males; 569 female) and 2221 controls (1189 male; 1032 female) by Taqman assay. RESULTS Four SNPs, rs4977574_A [0.56(0.50-0.63); p < 0.0001], rs10757274_A [0.87(0.77-0.97); p = 0.014], rs10738607_A [0.89(0.80-1.00); p = 0.043] and rs1333045_T [0.54(0.48-0.61); p < 0.0001] residing on the CDKN2B gene were significantly associated with CAD following multivariate adjustments for MI, HTN and DM, while four others were weakly associated with the disease. Likewise, three SNPs, rs1412829_G [0.84(0.72-0.97); p = 0.019], rs564398_C [0.81(0.70-0.94); p = 0.006], rs4977756_G [0.87(0.76-0.99); p = 0.036] were significantly associated with MI after multivariate adjustments for CAD, HTN and DM, while the other five displayed borderline associations. CONCLUSIONS Our findings strongly support the notion of a critical role for the CDKN2B gene locus as a cardiovascular risk in ethnic Arabs. The study also demonstrates the importance of replication studies in ascertaining the role of a genomic sequence in disease.

Determination of Lead and Cadmium Contents and Microbial Contamination Assessment in Kohl used in Libyan Markets

This study aims to determine some heavy metals such as lead (Pb) and cadmium (Cd) content in traditional eye cosmetics known as kohl, which is available in Tripoli markets in Libya. An analytical test was performed for ten kohl samples using flame atomic absorption spectrophotometer (AA280-FS). The overall mean (n= 6) concentration for each heavy metal was analyzed. The results of nine kohl samples (2-10) showed that the concentrations of lead and cadmium in these samples were within the range of 12.92-76.14% and 0.3616.87% respectively. These high concentrations of Pb and Cd were over the safe limits set by the world health organization standards (WHO-2012/FAO-2013). Thus the continuous use of these types/brands of kohl can increase the absorption of lead and cadmium into the human body and elevate the health hazards. However; only one kohl sample (No.1) was found to have 0.004% and 0.02% of Pb and Cd respectively. All the kohl samples were evaluated for presence of microbial contamination by culture and staining techniques. No evidence for contamination of the samples by fungi; samples 7 and 8 were free from bacterial contamination; other samples were contaminated with bacillus species which might cause ocular infection and conjunctivitis.

Stability and In Vitro Dissolution Studies of Metronidazole Tablets and Infusions

The aim of this study was to compare metronidazole tablets (500 mg) and infusions (500 mg/100 mL) obtained from Saudi and Egyptian suppliers. Evaluation of the tablets included weight variation, hardness, friability, drug content, disintegration time, and dissolution profiles. Stability of the tablets in their original packages after 3-month storage at various temperatures (75% relative humidity) was evaluated, and degradation kinetics was determined. The infusion solutions underwent accelerated stability testing. The Q10 method was used to estimate the shelf life of metronidazole infusions at room temperatures (75% relative humidity) of various climates. Results revealed that all tablets complied with USP specifications, and degradation was slowest at room temperature (20 °C). The mechanism of drug release for all tablets at all temperatures conformed to the Korsmeyer–Peppas model. Metronidazole intravenous infusion solutions stored at 40 °C or 50 °C for 90 days exhibited good stability. The studied Saudi infusion brand is more stable than Egyptian one. The metronidazole tablets and infusion solutions complied with USP specifications and showed similar results in quality control testing. Standard quality control measures should be maintained to ensure safety and efficacy of drug products, especially in climates with extreme temperatures.