Preparation, structural characterization, antimicrobial and anticancer activities, DFT and molecular docking studies of a nano ferrocenyl Schiff base and its metal complexes

1319-1337An organometallic Schiff base (2-(1-((4-aminopyridin-3-yl)imino)ethyl)cyclopenta-2,4-dien-1-yl) (cyclopenta-2,4-dien-1-yl)iron (L) and eight transition metal complexes have been prepared by reacting 3,4-diaminopyridine with 2-acetylferrocene in 1:1 molar ratio for ligand formation and by reacting Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) chlorides with ligand in 1:1 molar ratio for complexes formation. All prepared compounds have been characterized by using elemental analysis (C, H, N, M), molar conductance, IR, UV-Vis, 1H-NMR, SEM and mass spectral analysis. Also, their TG and DTG behaviors have been studied. All complexes have an octahedral structure. The ligand coordinated to the metal ions through the nitrogen atoms of azomethine and amino groups. In addition, computational studies of the synthesized Schiff base ligand have been carried out by the DFT/B3LYP method. The antimicrobial activities of the ligand and its metal complexes have been studied by using different bacterial species [Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium] and fungal species included [Aspergillus fumigatus and Candida albicans]. Moreover, the prepared compounds have been evaluated for anticancer activities against breast cancer (MCF-7) and normal melanocytes (HFB-4) cell lines. Docking studies have been used to determine the probable binding mode between the ligand and its Cd(II) complex with the active site of 3HB5, 2HQ6 and 1GS4 receptors

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

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

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

Two Spectrophotometric Assays for Dopamine Derivatives in Pharmaceutical Products and in Biological Samples of Schizophrenic Patients Using Copper Tetramine Complex and Triiodide Reagent

Two simple, rapid, and sensitive spectrophotometric methods are proposed for the determination of levodopa (LD). The first method is based on coupling of 4-aminoantipyrine (4-AAP) with one of the dopamine derivatives (LD, CD) to give a new ligand that reacts with copper tetramine complex to give intensely colored chelates. The colored products are quantified spectrophotometrically at 525 and 520 nm for LD and CD, respectively. The optimization of the experimental conditions is described. The method has been used for the determination of 19.7–69.0 and 18.1–54.3 μg mL(−1) of LD and CD, respectively. The accuracy of the method is achieved by the values of recovery (100 ± 0.2%) and the precision is supported by the low standard deviation (SD = 0.17–0.59) and relative standard deviation (CV = 0.4%–1.54%) values. The second method is based on the formation of ion-pair iodinated inner sphere or outer sphere colored complexes between the LD and triiodide ions at pH 5 and room temperature (23 ± 3(°)C). This method has been used for the determination of LD within the concentration range 39.44–78.88 μg mL(−1) with SD = 0.22–0.24 and recovery percent = 100 ± 0.3%. The sensitivity of the two methods is indicated by Sandell's sensitivity of 0.014–0.019 g cm(−2). The results of the two methods are compared with those of the official method. The interference of common drug additives, degradation products, and excipients was also studied. The proposed methods were applied successfully to the determination of the LD-CD synthetic mixture and Levocare drug. The determination of LD in urine of some schizophrenic patients was applied with good precision and accuracy. The reliability of the methods was established by parallel determinations against the official British pharmacopoeia method

Preparation, structural characterization, antimicrobial and anticancer activities, DFT and molecular docking studies of a novel nano ferrocenyl Schiff base and its metal complexes

Novel organometallic Schiff base (2-(1-((4-aminopyridin-3-yl)imino)ethyl)cyclopenta-2,4-dien-1-yl) (cyclopenta-2,4-dien-1-yl)iron (L) and eight transition metal complexes were prepared by reacting 3,4-diaminopyridine with 2-acetylferrocene in 1:1 molar ratio for ligand formation and by reacting Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) chlorides with ligand in 1:1 molar ratio for complexes formation. All prepared compounds were characterized by using elemental analysis (C, H, N, M), molar conductance, IR, UV-Vis, 1H-NMR, SEM and mass spectral analysis. Also, their TG and DTG behaviors were studied. All complexes have an octahedral structure. The ligand coordinated to the metal ions through the nitrogen atoms of azomethine and amino groups. In addition, computational studies of the synthesized Schiff base ligand have been carried out by the DFT/B3LYP method. The antimicrobial activities of the ligand and its metal complexes were studied by using different bacterial species [Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium] and fungal species included [Aspergillus fumigatus and Candida albicans]. Moreover, the prepared compounds have been evaluated for anticancer activities against breast cancer (MCF-7) and normal melanocytes (HFB-4) cell lines. Docking studies were used to determine the probable binding mode between the ligand and its Cd(II) complex with the active site of 3HB5, 2HQ6 and 1GS4 receptors

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020