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

Potentiometric sensors selective for Cu(II) determination in real water samples and biological fluids based on graphene and multi-walled carbon nanotubes modified graphite electrodes

162-173Three newly synthesized Cu(II) ion selective electrodes based on 1,8-dihydoxyanthraquinone (DHAQ), as an ionophore, have been developed. Carbon paste electrode has been modified with DAHQ (sensor I), graphene and DHAQ (sensor II) and multi-walled carbon nanotubes (MWCNTs) and DHAQ (sensor III), in order to improve the conductivity and transduction of chemical signal to electrical signal. Under optimized conditions, the electrodes I, II and III revealed Nernstian slopes of 29.78 ± 0.17, 30.25 ± 0.12, and 30.55 ± 0.19 mV decade-1, respectively, at 25±1 °C covering a wide concentration range from 1×10–6 to 1×10−1 mol L–1 for sensors I and II and from 1×10–5 to 1×10−1 mol L–1 for sensor III with detection limit values of 8×10−7, 5×10−7, and 3.3×10−6 mol L-1, respectively. The response of the proposed electrodes is very fast and independent of pH in the range of 2.4–6.5 and the response mechanism is studied using IR, SEM and EDX analyses. Selectivity coefficients have been determined by applying separate solution method and matched potential method, where the obtained values indicated the good discrimination of Cu(II) from other cations by the proposed sensors. The developed sensors have been used successfully for quantitative determination of Cu(II) ions in different matrix of spiked real water samples and biological fluids (urine and serum). These sensors have also been used successfully as indicator electrodes in the potentiometric titration of Cu(II) with EDTA

Contemplation Impact of Pulp Seeds Cucurbita Pepo L. and its Paste on Oxidative Stress in Rats

Cucurbita Pepo L. seeds and seeds paste which are rich sources of phytochemicals and act as a rich source of antioxidants. The most important phytochemicals present in the cucurbits are cucurbitacin’s, saponins, carotenoids, phytosterols, and polyphenols. These bioactive phyto-constituents are responsible for the pharmacological effects including antioxidant effect. Aim of this study was to investigate the effect of Cucurbita Pepo L. seeds and seeds paste on rats suffering from oxidative stress. Thirty-six male albino rats were used in the experiment (Sprague-Dawley strain). The animals randomly divided 6 rats each group according to the following the first Group: Rats were fed basal diet and set as negative control. The other rats (n = 30) were fed on basal diet containing monosodium glutamate (120 mg/kg) for induce stress condition. After that, rats further divided into 5 groups (n = 6) each for six weeks as follows: -2nd Group: Rats were fed on basal diet containing monosodium glutamate and set as positive control. 3rd Group: Rats were fed on diet containing monosodium glutamate with addition of Cucurbita Pepo L. seeds 5%. 4th Group: Rats were fed on diet containing monosodium glutamate with addition of Cucurbita Pepo L. seeds 10%. 5th Group: Rats were fed on diet containing monosodium glutamate with addition of Cucurbita Pepo L. seeds paste 5%. 6th Group: Rats were fed on diet containing monosodium glutamate with addition of Cucurbita Pepo L. seeds paste 10%. The experimental period was six weeks; Blood samples were collected. At the end of the experiment, the results showed that using seeds 5% & 10% and seeds paste 5% & 10% in feeding the stressed rats increased (BWG%, FI, FER, Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx)) with highest results in group fed on 10% seeds paste and decreased (Urea, Creatinine, ALT, AST, IL-6 and INF-gamma) with lowest results in group fed on 10% Cucurbita Pepo L. seeds paste

Potentiometric Determination of Ketotifen Fumarate in Pharmaceutical Preparations and Urine Using Carbon Paste and PVC Membrane Selective Electrodes

This study compares between unmodified carbon paste (CPE; the paste has no ion pair) and polyvinyl chloride (PVC) membrane selective electrodes that were used in potentiometric determination of ketotifen fumarate (KTF), where sodium tetraphenylborate (NaTPB) was used as titrant. The performance characteristics of these sensors were evaluated according to IUPAC recommendations which reveal a fast, stable, and linear response for KTF over the concentration range of 10−7 to 10−2 mol L−1. The electrodes show Nernstian slope value of 52.51 ± 0.20 and 51.51 ± 0.25 mV decade−1 for CPE and PVC membrane electrodes at 30°C, respectively. The potential is nearly stable over the pH range 3.0–6.0 and 2.0–7.0 for CPE and PVC membrane electrodes, respectively. Selectivity coefficient values towards different inorganic cations, sugars, and amino acids reflect high selectivity of the prepared electrodes. The electrodes responses at different temperatures were also studied, and long operational lifetime of 12 and 5 weeks for CPE and PVC membrane electrodes, respectively, were found. These are used for determination of ketotifen fumarate using potentiometric titration, calibration, and standard addition methods in pure samples, its pharmaceutical preparations (Zaditen tablets), and biological fluid (urine). The direct potentiometric determination of KTF using the proposed sensors gave recoveries % of 98.97 ± 0.53 and 98.62 ± 0.74 with RSD 1.42 and 0.63% for CPE and PVC membrane selective electrodes, respectively. Validation of the method shows suitability of the proposed sensors for use in quality control assessment of KTF. The obtained results were in a good agreement with those obtained using the reported spectrophotometric method

Lymphocyte apoptosis in the pathogenesis of type 1 diabetes mellitus

Background: Beta cell apoptosis has been associated with insulin dependent diabetes mellitus (IDDM) onset in newly diagnosed diabetic patients. There is an emerging evidence that T cell-induced apoptosis is a dominant effector mechanism in diabetes mellitus type 1 (DM1). Pancreatic β-cells derived from newly diagnosed type 1 diabetics were found to have increased cell surface expression of Fas (CD95) compared to β-cells from healthy subjects. Objective: The study investigates the spontaneous lymphocyte apoptosis via CD95 molecule expression to demonstrate activation induced cell death in children with high risk of DM1 and in type 1 diabetics under insulin therapy. Methods: This study comprised 90 children and adolescents, divided into 3 groups. G(1) comprised 40 type-1 diabetics, their ages ranging from 8.0 to 17.0 years and disease duration between 2.0 and 12.0 years. G(2) (prediabetics) included 30 euglycaemic subjects who were first degree relatives of type 1 diabetics, with normal fasting blood glucose and positive first phase insulin release (FPIR) and/or positive islet cell (ICA) or glutamic acid decarboxylase (GAD) antibodies. G(3) comprised 20 healthy, age and sex matched subjects with no clinical or laboratory signs or family history of type-1DM. Patients were subjected to clinical evaluation with special emphasis on signs suggestive of microvascular complications. The study measurements included random blood sugar (RBS), glycosylated hemoglobin (HbA1c), urinary microalbumin assay and flow cytometric assessment of apoptosis by measuring CD95 percentage expression on CD3 lymphocytes. Results: The percentage of CD95 positive T-lymphocytes was significantly higher in prediabetics than in type-1 diabetics and controls (57.687±6.68, 45.01±6.648,16.75±4.98% respectively; p < 0.001). CD3 positive lymphocytes were significantly lower in prediabetics than type-1 diabetics and controls (52.93±11.64, 66.23±7.04, 63.910±3.4% respectively; p < 0.001). The percentage of CD95 on T-lymphocytes could not be correlated with age, insulin dose and RBS, but HbA1c was positively correlated with both CD3 lymphocytes and CD95% expression. Complicated type-1 diabetics showed higher CD95% expression compared to noncomplicated patients. Conclusion: Peripheral blood lymphocytes with CD95 antigen expression are increased in prediabetics. As CD95 is an important receptor for activation-induced cell death, CD95 mediated apoptosis could play a potential role in the pathogenesis of DM1.Keywords: lymphocyte apoptosis; CD95 system; type 1 DM; prediabetesEgypt J Pediatr Allergy Immunol 2008; 6(2): 57-6

Calli Essential Oils Synergize with Lawsone against Multidrug Resistant Pathogens.

The fast development of multi-drug resistant (MDR) organisms increasingly threatens global health and well-being. Plant natural products have been known for centuries as alternative medicines that can possess pharmacological characteristics, including antimicrobial activities. The antimicrobial activities of essential oil (Calli oil) extracted from the Calligonum comosum plant by hydro-steam distillation was tested either alone or when combined with lawsone, a henna plant naphthoquinone, against MDR microbes. Lawsone showed significant antimicrobial activities against MDR pathogens in the range of 200-300 µg/mL. Furthermore, Calli oil showed significant antimicrobial activities against MDR bacteria in the range of 180-200 µg/mL, Candida at 220-240 µg/mL and spore-forming Rhizopus fungus at 250 µg/mL. Calli oil's inhibition effect on Rhizopus, the major cause of the lethal infection mucormycosis, stands for 72 h, followed by an extended irreversible white sporulation effect. The combination of Calli oil with lawsone enhanced the antimicrobial activities of each individual alone by at least three-fold, while incorporation of both natural products in a liposome reduced their toxicity by four- to eight-fold, while maintaining the augmented efficacy of the combination treatment. We map the antimicrobial activity of Calli oil to its major component, a benzaldehyde derivative. The findings from this study demonstrate that formulations containing essential oils have the potential in the future to overcome antimicrobial resistance

Oxidative Stress in Hemodialysis Pediatric Patients

BACKGROUND: Oxidative stress may play a role in complications of hemodialysis patients as atherosclerosis, thrombosis, and inflammation. AIM: The aim of the study was to evaluate the oxidative stress in hemodialysis pediatric patients through measurement of oxidative stress enzymes as paraoxanase activity (PON), arylesterase activity (ASA), superoxide dismutase (SOD) and also non-enzymatic antioxidant vitamins as vitamins A, C and E levels. METHODS: The study included 50 hemodialysis pediatric patients with mean age 11.4 ± 5.4 years and 30 normal children of matched sex and age as a control group. Assessment of oxidative stresses was done using ELIZA technique. RESULTS: SOD, ASA, and vitamin C were significantly lower among hemodialysis patients in comparison to control group (p = 0.004, 0.004, > 0.001 respectively). CONCLUSION: The study concluded that oxidative stress was common finding in hemodialysis pediatric patients which may play a role in complications encountered among these patients

Design, Synthesis, and Biological Evaluation of Novel 3-Cyanopyridone/Pyrazoline Hybrids as Potential Apoptotic Antiproliferative Agents Targeting EGFR/BRAFV600E^{V600E} Inhibitory Pathways

A series of novel 3-cyanopyridone/pyrazoline hybrids (21–30) exhibiting dual inhibition against EGFR and BRAFV600E has been developed. The synthesized target compounds were tested in vitro against four cancer cell lines. Compounds 28 and 30 demonstrated remarkable antiproliferative activity, boasting GI50 values of 27 nM and 25 nM, respectively. These hybrids exhibited dual inhibitory effects on both EGFR and BRAFV600E pathways. Compounds 28 and 30, akin to Erlotinib, displayed promising anticancer potential. Compound 30 emerged as the most potent inhibitor against cancer cell proliferation and BRAFV600E. Notably, both compounds 28 and 30 induced apoptosis by elevating levels of caspase-3 and -8 and Bax, while downregulating the antiapoptotic Bcl2 protein. Molecular docking studies confirmed the potential of compounds 28 and 30 to act as dual EGFR/BRAFV600E inhibitors. Furthermore, in silico ADMET prediction indicated that most synthesized 3-cyanopyridone/pyrazoline hybrids exhibit low toxicity and minimal adverse effects

QUERCETIN NANOPARTICLES REPRESSED LIVER AND BRAIN TOXICITIES INDUCED BY TARTRAZINE IN RATS

Tartrazine (TZ) is an azobenzene artificial yellow dye for foods, drugs, and cosmetics. Quercetin is member of the flavonoid family. The current study investigated the protective effect of quercetin nanoparticles (QNPs) against TZ. Male albino rats were divided into group1:  control, group 2: TZ (50 mg/kg), group 3: QNPs (5 mg/kg), and group 4: QNPs+TZ. The results of the present study revealed that, the oral administration of TZ dye caused a significantly increased liver biomarkers. Also, a marked effect on lipid profile and blood parameters were shown. In addition TZ induced an elevation in the examined oxidative stress biomarkers and decrease in glutathione peroxidases and acetylcholine esterase. TZ diminished exploration and rearing in open field test as well as elevation in GABA content and apoptosis as well as changes in tissues by histopathological examination. In fact, the results showed good influence of QNPs in improving injuries associated with TZ administration. Keywords:  Tartrazine Dye, Quercetin Nanoparticles, Liver-Brain injuries