Potentiometric determination of oxybutynin hydrochloride in pharmaceutical formulations at modified carbon paste electrodes

324-332New potentiometric sensitive and selective modified carbon paste (MCPE) electrodes based on ion pair formation between phosphotungestic acid (PTA), sodium tetraphenyl borate (NaTPB), phosphomolybdic acid (PMA) or ammonium reineckate (RN) and oxybutynin hydrochloride (Ox.HCl) has been developed. The proposed electrodes have Nernstian slope values of 58.50±0.71, 58.71±1.20, 54.80±1.30 and 59.20±0.70 mV decade−1 for electrodes modified with 20, 10, 5 and 10 mg of Ox-TPB (electrode I), Ox-RN (electrode II), Ox-PMA (electrode III) and Ox-PTA (electrode IV) ion pairs, respectively. It is found that the dynamic drug concentration range at 25 °C is 1.0×10−5–1.0×10−2 mol L−1. The response of MCPEs is pH independent in the range 2.0–6.0 with a fast response time of 10 s for electrode I and 12 s for electrodes II-IV. These electrodes have good Nernstian response in the temperature range 10–60 °C with slope (isothermal coefficient) equal 0.791×10−3, 0.769×10−3, 0.629×10−3 and 1.277×10−3 V/°C for electrodes I, II , III and IV respectively. These small values indicate the high thermal stability of the electrodes. The MCPEs have shown a relatively long life time of 36 days. A pure and pharmaceutical formulation of Ox.HCl has quantified using calibration and standard addition methods and the obtained results agreed with that of the official HPLC method. Validation parameters have been optimized according to ICH recommendations. Limits of detection and quantification are calculated under the optimized conditions. For the analytical applications, pharmaceutical dose form has performed. Various interferents have been used to investigate the interference in the analytical application and found that the proposed method would be well adopted for real sample analysis

Potentiometric determination of oxybutynin hydrochloride in pharmaceutical formulations at modified carbon paste electrodes

324-332New potentiometric sensitive and selective modified carbon paste (MCPE) electrodes based on ion pair formation between phosphotungestic acid (PTA), sodium tetraphenyl borate (NaTPB), phosphomolybdic acid (PMA) or ammonium reineckate (RN) and oxybutynin hydrochloride (Ox.HCl) has been developed. The proposed electrodes have Nernstian slope values of 58.50±0.71, 58.71±1.20, 54.80±1.30 and 59.20±0.70 mV decade−1 for electrodes modified with 20, 10, 5 and 10 mg of Ox-TPB (electrode I), Ox-RN (electrode II), Ox-PMA (electrode III) and Ox-PTA (electrode IV) ion pairs, respectively. It is found that the dynamic drug concentration range at 25 °C is 1.0×10−5–1.0×10−2 mol L−1. The response of MCPEs is pH independent in the range 2.0–6.0 with a fast response time of 10 s for electrode I and 12 s for electrodes II-IV. These electrodes have good Nernstian response in the temperature range 10–60 °C with slope (isothermal coefficient) equal 0.791×10−3, 0.769×10−3, 0.629×10−3 and 1.277×10−3 V/°C for electrodes I, II , III and IV respectively. These small values indicate the high thermal stability of the electrodes. The MCPEs have shown a relatively long life time of 36 days. A pure and pharmaceutical formulation of Ox.HCl has quantified using calibration and standard addition methods and the obtained results agreed with that of the official HPLC method. Validation parameters have been optimized according to ICH recommendations. Limits of detection and quantification are calculated under the optimized conditions. For the analytical applications, pharmaceutical dose form has performed. Various interferents have been used to investigate the interference in the analytical application and found that the proposed method would be well adopted for real sample analysis

Evaluation of Bond Strength Between Carbon Fiber Reinforced Polymer (CFRP) Composites with Modified Epoxy Resins and Concrete

Rehabilitation and strengthening of concrete structures are becoming more significant in civil engineering applications. The use of externally bonded Fiber Reinforced Polymers (FRP) is one of the methods to strengthen and rehabilitate reinforced concrete members, providing noticeable improvement to their capacity in resisting load. Carbon Fiber Reinforced Polymer (CFRP) is used along with epoxy resins to evaluate the bond strength of two commercially available epoxies (EPON 828 and EPON 862) between CFRP and concrete. In addition, three new combinations that resulted from mixing the two epoxies were examined. The mechanical properties of epoxy resins are significantly weaker than this of the CFRP making the epoxy characteristics the determining factor in the quality of the bond strength. Three-point flexural test was conducted to examine the bond strength between the CFRP composites and concrete. Further, differential scanning calorimetry was conducted to examine the glass transition temperature of the resultant epoxies. The results showed that the optimum composition was a mixture of 70% of epoxy 828 and 30% of epoxy 862. Therefore, achieving better bond strength and high glass transition temperature, resulting in CFRP composite with higher fire resistance

EGFR tyrosine kinase targeted compounds

In this study, we illustrate computer aided drug design of new benzothiazole and pyrimido[2,1-b]benzothiazole derivatives as epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors. Compounds 1-5 were screened at NCI, USA, for antitumor activity against non-small cell lung cancer (NCI-H522), colon cancer (HCT-116, HCT-15 and HT29) and breast cancer (MDA-MB-468 and MDA-MB-231/ATCC) cell lines in which EGFR is overexpressed in varying levels. Results indicated that these compounds are more potent antitumor agents compared to erlotinib against HT29 and MDA-MB-231/ATCC cell lines. Compound 3 showed GI50 value of 22.3 nM against NCI-H522 cell line, while erlotinib exhibited GI50 value of 1 μM against the same cell line. In addition, these compounds were studied for their EGFR tyrosine kinase inhibitory activity. Virtual screening utilizing molecular modeling and QSAR techniques enabled the understanding of the pharmacophoric requirements for antitumor activity. Docking the designed compounds into the ATP binding site of EGFR-TK domain was done to predict the analogous binding mode of these compounds to the EGFR-TK inhibitors

Suppressive efficiency of Kojic acid from Aspergillus tamarii MM11 against HepG-2 cell line derived from human liver cancer

Purpose: To evaluate the antioxidant and cytotoxic properties of Kojic acid (KOJIC ACID) from Aspergillus tamarii MM11 against HepG-2 cell line derived from human liver cancer.Methods: The crude extract of A. tamarii MM11 was dissolved in a mixture of CH2Cl2/MeOH (85:15) and separation was done using silica gel chromatography using gradient size exclusion chromatograph. The non-polar oily fractions were subjected to gas chromatography-mass  spectrometric (GC-MS) analysis. Kojic acid structure was identified by x-beam crystallography and spectroscopic methods. Total antioxidant properties of KOJIC ACID were evaluated by using 1,1-diphenyl-2- picrylhydrazyl (DPPH) against ascorbic acid as a reference. The cytotoxic activity of KOJIC ACID from A. tamarii MM11 was investigated on the human cell line of liver cancer (HepG-2) using a sulforhodamine B (SRB) assay based on a cell density determination by the measurement of cellular protein content.Result: Highly bioactive Kojic acid was isolated as the main product. A. tamarii MM11 Kojic acid showed good antioxidant activity with half-maximal inhibitory concentration of IC50 at concentrations of 10.34 compared to 6.79 μg/mL for ascorbic acid. Kojic acid also showed good cytotoxic activity against HepG-2 cell line of human liver cancer with IC50 at 6.20 compared to 3.25 μg/mL of reference drug doxorubicin.Conclusion: Kojic acid produced naturally from A. tamarii MM11 shows good antioxidant and cytotoxic activity against HepG-2 cell line derived from  human liver cancer. These findings suggest that Kojic acid can be therapeutically used as an antitumor drug after further in vivo studies. Keywords: Aspergillus tamarii, Secondary metabolites, Kojic acid, Anticancer, Liver cance

Prognostic Role of Elevated Myeloperoxidase in Patients with Acute Coronary Syndrome: A Systemic Review and Meta-Analysis

Background. Myocardial inflammation following acute ischemic injury has been linked to poor cardiac remodeling and heart failure. Many studies have linked myeloperoxidase (MPO), a neutrophil and inflammatory marker, to cardiac inflammation in the setting of acute coronary syndrome (ACS). However, the prognostic role of MPO for adverse clinical outcomes in ACS patients has not been well established. Methods. MEDLINE and Cochrane databases were searched for studies from 1975 to March 2018 that investigated the prognostic value of serum MPO in ACS patients. Studies which have dichotomized patients into a high MPO group and a low MPO group reported clinical outcomes accordingly and followed up patients for at least 30 days to be eligible for enrollment. Data were analyzed using random-effects model. Sensitivity analyses were conducted for quality control. Results. Our meta-analysis included 13 studies with 9090 subjects and a median follow-up of 11.4 months. High MPO level significantly predicted mortality (odds ratio (OR) 2.03; 95% confidence interval (CI): 1.40-2.94; ), whereas it was not significantly predictive of major adverse cardiac events and recurrent myocardial infarction (MI) (OR 1.28; CI: 0.92-1.77, and OR 1.23; CI: 0.96-1.58, , respectively). Hypertension, diabetes mellitus, and age did not affect the prognostic value of MPO for clinical outcomes, whereas female gender and smoking status have a strong influence on the prognostic value of MPO in terms of mortality and recurrent MI (metaregression coefficient -8.616: 95% CI -14.59 to -2.633, and 4.88: 95% CI 0.756 to 9.0133, , respectively). Conclusions. Our meta-analysis suggests that high MPO levels are associated with the risk of mortality and that MPO can be incorporated in risk stratification models that guide therapy of high-risk ACS patients

Microwave-assisted synthesis and antitumor evaluation of a new series of thiazolylcoumarin derivatives

A new series of thiazolylcoumarin derivatives was synthesized. The designed strategy embraced a molecular hybridization approach which involves the combination of the thiazole and coumarin pharmacophores together. The new hybrid compounds were tested for in vitro antitumor efficacy over cervical (Hela) and kidney fibroblast (COS-7) cancer cells. Compounds 5f, 5h, 5m and 5r displayed promising efficacy toward Hela cell line. In addition, 5h and 5r were found to be the most active candidates toward COS-7 cell line. The four active analogs, 5f, 5h, 5m and 5r were screened for in vivo antitumor activity over EAC cells in mice, as well as in vitro cytotoxicity toward W138 normal cells. Results illustrated that 5r has the highest in vivo activity, and that the four analogs are less cytotoxic than 5-FU toward W138 normal cells. In this study, 3D pharmacophore analysis was performed to investigate the matching pharmacophoric features of the synthesized compounds with trichostatin A. In silico studies showed that the investigated compounds meet the optimal needs for good oral absorption with no expected toxicity hazards

Deciphering the therapeutic potential of trimetazidine in rheumatoid arthritis via targeting mi-RNA128a, TLR4 signaling pathway, and adenosine-induced FADD-microvesicular shedding: In vivo and in silico study

Rheumatoid arthritis (RA) is a debilitating autoimmune condition characterized by chronic synovitis, joint damage, and inflammation, leading to impaired joint functionality. Existing RA treatments, although effective to some extent, are not without side effects, prompting a search for more potent therapies. Recent research has revealed the critical role of FAS-associated death domain protein (FADD) microvesicular shedding in RA pathogenesis, expanding its scope beyond apoptosis to include inflammatory and immune pathways. This study aimed to investigate the intricate relationship between mi-RNA 128a, autoimmune and inflammatory pathways, and adenosine levels in modulating FADD expression and microvesicular shedding in a Freund’s complete adjuvant (FCA) induced RA rat model and further explore the antirheumatoid potency of trimetazidine (TMZ). The FCA treated model exhibited significantly elevated levels of serum fibrogenic, inflammatory, immunological and rheumatological diagnostic markers, confirming successful RA induction. Our results revealed that the FCA-induced RA model showed a significant reduction in the expression of FADD in paw tissue and increased microvesicular FADD shedding in synovial fluid, which was attributed to the significant increase in the expression of the epigenetic miRNA 128a gene in addition to the downregulation of adenosine levels. These findings were further supported by the significant activation of the TLR4/MYD88 pathway and its downstream inflammatory IkB/NFB markers. Interestingly, TMZ administration significantly improved, with a potency similar to methotrexate (MTX), the deterioration effect of FCA treatment, as evidenced by a significant attenuation of fibrogenic, inflammatory, immunological, and rheumatological markers. Our investigations indicated that TMZ uniquely acted by targeting epigenetic miRNA128a expression and elevating adenosine levels in paw tissue, leading to increased expression of FADD of paw tissue and mitigated FADD microvesicular shedding in synovial fluid. Furthermore, the group treated with TMZ showed significant downregulation of TLR4/MYD88 and their downstream TRAF6, IRAK and NF-kB. Together, our study unveils the significant potential of TMZ as an antirheumatoid candidate, offering anti-inflammatory effects through various mechanisms, including modulation of the FADD-epigenetic regulator mi-RNA 128a, adenosine levels, and the TLR4 signaling pathway in joint tissue, but also attenuation of FADD microvesicular shedding in synovial fluid. These findings further highlight the synergistic administration of TMZ and MTX as a potential approach to reduce adverse effects of MTX while improving therapeutic efficacy.Peer Reviewe

DIVERSITY OF BACILLUS GENOTYPES IN SOIL SAMPLES FROM EL-OMAYED BIOSPHERE RESERVE IN EGYPT

Sequencing of the 16S rDNA hypervariant region was applied to determine the presence and composition of Bacillus species in 40 soil samples randomly collected from different habitats in El-Omayed biosphere reserve, Egypt. Although purified cultures showed 18 different phenotypes that were morphologically distinct on a sporulation medium plate, only 4 different nucleotide sequences designated Seq A, B, C and D were revealed. Computational analysis of DNA sequence data suggested that 17 of these isolates are closely related members of the Bacillus cereus/thuringiensis group (Seq B, C and D) and one isolate is belonging to the Bacillus subtilis group (Seq A). Further phenotypic investigations confirmed the diversity of the 17 novel Bacillus cereus/thuringiensis isolates and indicated that the new Bacillus subtilis group isolate is a Bacillus amyloliquefaciens strain. A simple phenotypic discrimination key that can be applied for distinguishing between such closely related Bacillus cereus/thuringiensis members is presented

Serum Asymmetric Dimethylarginine, and Adiponectin as Predictors of Atherosclerotic Risk among Obese Egyptian Children

BACKGROUND: Obesity is associated with an increased risk of developing hyperinsulinemia, dyslipidemia, hypertension, premature atherosclerosis, and coronary artery disease in the future.AIM: This study is designed to assess the relationship between serum adiponectin, asymmetric dimethylarginine (ADMA), and lipid profile among Egyptian overweight and obese children.METHODS: This cross sectional case control study included 40 selected pre-pubertal overweight and obese children, 24 girls (60%) and 16 boys (40%) aged between 5 to 13 years (8.85 ± 2.7 years), from new cases attending the National nutrition institute clinic during 2013. Forty apparently healthy children of matched age and sex were recruited as a control group.RESULTS: Obese group showed highly significant higher levels of serum ADMA, triglycerides, and total cholesterol compared with healthy controls (P <0.000 in all). However, serum adiponectin levels were highly significant lower in obese children compared to healthy controls (P < 0.000). Serum ADMA showed significant positive correlations with height, serum total cholesterol and serum triglycerides levels and significant negative correlation with the body mass index and weight for age z score.  Serum adiponectin showed significant negative correlations with BMI, weight, and weight for age z score and significant positive correlation with serum triglycerides. By linear regression analysis; serum adiponectin, and serum triglycerides levels were significant predictors of high serum ADMA level (p =0.045 and 0.015 respectively). BMI, weight, height and serum triglycerides were significant predictors of low serum adiponectin levels (p = 0.005, 0.022, 0.026 and 0.015 respectively).CONCLUSIONS: Our results revealed that ADMA, Adiponectin and lipid profile can be considered as predictive biomarkers in prediction and prevention of atherosclerotic risk in the future among overweight and obese Egyptian children