Heterogeneous Fenton's-like catalysis for degradation of colchicine coupled with extraction of its biologically active metabolite

Work performed in Professor Huddersman's laboratory at De Montfort University by visiting Researcher (academic lecturer) from Faculty of Pharmacy, Assiut University, Egypt The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Nowadays, drug pollution; a form of water pollution caused by some pharmaceuticals and their metabolites resulting from consumers, industry and hospitals was reported. Colchicine (CLN) is considered one of the pharmaceutical wastewater contaminants which are not eliminated completely in municipal sewage treatment plants and are discharged into receiving water. Due to the higher toxicity of CLN, a novel heterogeneous Fenton's-like catalysis was established for complete degradation of CLN. So, a highly sensitive and specific liquid chromatographic method with quadrupole mass spectrometry (LC/Q-MS) was developed and validated for estimation of CLN in its pure form and in the presence of its degradation product. Herein, GraceSmart RP C18 column was utilized for separation of the cited drug (Retention time tR= 5.578 min) using methanol: water (55: 45, v/v) at 1.0 mL/min. Detection was performed by Agilent 6120 Quadrupole MS detector in a positive ionization mode. Thereafter and for the first time, degradation of CLN by heterogeneous Fenton's-like catalysis using modified polyacrylonitrile (PAN) as a catalyst with H2O2 in aqueous acidic medium was performed. This process was firstly optimized by HPLC/UV detection at 248 nm using the aforementioned chromatographic conditions. As a result, CLN degraded completely within 30 min. The only observed degradation product was the biologically active, potent and less toxic antitumor metabolite of CLN (3- demethyl CLN) which was collected, extracted, and analyzed by Fourier Transfer- Infrared Spectroscopy (FTIR) and 13Carbon- Nuclear Magnetic Resonance (13C-NMR). Finally, this method is eco-friendly and complies with the requirements of the green chemistry. It is suitable for complete removal of CLN and/or its metabolite contaminants from wastewater samples and estimation of the target drug without any interference from its degradation products. However, further study is required to expand the method applicability to the pharmaceutical wastewater treatment as well the production of 3- demethyl CLN on a large scale

Effect of poly(ethylene glycol) on insulin stability and cutaneous cell proliferation in vitro following cytoplasmic delivery of insulin-loaded nanoparticulate carriers – A potential topical wound management approach

We describe the development of a nanoparticulate system, with variation of poly(ethylene glycol) (PEG) content, capable of releasing therapeutic levels of bioactive insulin for extended periods of time. Recombinant human insulin was encapsulated in poly(d,l-lactide-co-glycolide) nanoparticles, manufactured with variation in poly(ethylene glycol) content, and shown to be stable for 6days using SDS-PAGE, western blot and MALDI MS. To determine if insulin released from this sustained release matrix could stimulate migration of cell types normally active in dermal repair, a model wound was simulated by scratching confluent cultures of human keratinocytes (HaCaT) and fibroblasts (Hs27). Although free insulin was shown to have proliferative effect, closure of in vitro scratch fissures was significantly faster following administration of nano-encapsulated insulin. This effect was more pronounced in HaCaT cells when compared to Hs27 cells. Variation in PEG content had the greatest effect on NP size, with a lesser influence on scratch closure times. Our work supports a particulate uptake mechanism that provides for intracellular insulin delivery, leading to enhanced cell proliferation. When placed into an appropriate topical delivery vehicle, such as a hydrogel, the extended and sustained topical administration of active insulin delivered from a nanoparticulate vehicle shows promise in promoting tissue healing

MINIMIZING THE TRANSPLANT DECAY DEVELOPMENT VIA CA APPLICATION AND MODIFIED ATMOSPHERE INCREASED STRAWBERRY YIELD

This study was carried out at the Strawberry Improvement Center Experimental Farm, Nobaria, Beheira Governorate and the Horticulture Research Station, Bar-rage, Kalubia Governorate during 2001/2002 and 2002/2003 seasons. The study aimed to investigate the effect of calcium nutrition (0, 13and 26 kg/fed. Ca) and modified atmosphere storage (10,20, 30 and 40% CO2) on the post harvest decay of cold stored strawberry transplants and their subsequent fruit production. The results indicated that increasing the rate of calcium application during the transplant growth period and carbon dioxide concentration around transplants during the cold storage resulted in significant decrements in transplant decay, infection percentage, disease severity of roots and crowns. There was a positive relationship between cal-cium nutrition and early yield. Moreover, the highest calcium rate gave the highest total yield while no significant difference was noticed between control and 13 kg/fed treatments. This study concluded that adding Ca++ at 26 Kg /fed as fertiga-tion of calcium nitrate (13% Ca) to the growing strawberry transplants followed by modified atmosphere storage (40% CO2) during the prolonged cold storage allowed maintenance of transplant quality and increased their yield while minimizing decay development

EFFECTS OF SOWING DATE AND PINCHING ON BROCCOLI SEED PRODUCTION

A field experiment was conducted at the exper-imental farm of the Faculty of Agriculture, Ain Shams University, Shoubra Elkheima, Kalubia governorate, during 2002/2003 and 2003/2004 seasons to study the effects of three sowing dates, i.e., the first of each of September, October and November, and four pinching treatments (pinching the apical head just after appearance, pinching the main head at the marketable stage, pinching the axillary head just after appearance (disbudding) and without pinching) on broccoli plants (Brassica olerasea var Italica), cultivar “Emperor”. Plants were grown in Kaliobia under loamy soil conditions. Plants of the second sowing date (first of October) produced the tallest plants and the highest number of leaves per plant. Plants grown on the first of October plantation, pinching the main head at the marketable stage or the com-bination between them recorded the highest values of number of siliques/ plant, number of seeds/ plant, and seed yield

The metabolomic analysis of five Mentha species: cytotoxicity, anti-Helicobacter assessment, and the development of polymeric micelles for enhancing the anti-Helicobacter activity

Mentha species are medicinally used worldwide and remain attractive for research due to the diversity of their phytoconstituents and large therapeutic indices for various ailments. This study used the metabolomics examination of five Mentha species (M. suaveolens, M. sylvestris, M. piperita, M. longifolia, and M. viridis) to justify their cytotoxicity and their anti-Helicobacter effects. The activities of species were correlated with their phytochemical profiles by orthogonal partial least square discriminant analysis (OPLS-DA). Tentatively characterized phytoconstituents using liquid chromatography high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS) included 49 compounds: 14 flavonoids, 10 caffeic acid esters, 7 phenolic acids, and other constituents. M. piperita showed the highest cytotoxicity to HepG2 (human hepatoma), MCF-7 (human breast adenocarcinoma), and CACO2 (human colon adenocarcinoma) cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. OPLS-DA and dereplication studies predicted that the cytotoxic activity was related to benzyl glucopyranoside-sulfate, a lignin glycoside. Furthermore, M. viridis was effective in suppressing the growth of Helicobacter pylori at a concentration of 50 mg mL−1. OPLS-DA predicted that this activity was related to a dihydroxytrimethoxyflavone. M. viridis extract was formulated with Pluronic® F127 to develop polymeric micelles as a nanocarrier that enhanced the anti-Helicobacter activity of the extract and provided minimum inhibitory concentrations and minimum bactericidal concentrations of 6.5 and 50 mg mL−1, respectively. This activity was also correlated to tentatively identified constituents, including rosmarinic acid, catechins, carvone, and piperitone oxide

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

IAEA activities on 67Cu, 186Re, 47Sc Theranostic radionuclides and Radiopharmaceuticals

Despite interesting properties, the use of 67Cu, 186Re and 47Sc theranostic radionuclides in preclinical studies and clinical trials is curtailed by their limited availability due to a lack of widely established production methods. An IAEA Coordinated Research Project (CRP) was initiated to identify important technical issues related to the production and quality control of these emerging radionuclides and related radiopharmaceuticals, based on the request from IAEA Member States. The international team worked on targetry, separation, quality control and radiopharmaceutical aspects of the radionuclides obtained from research reactors and cyclotrons leading to preparation of a standard recommendations for all Member States. The CRP was initiated in 2016 with fourteen participants from thirteen Member States from four continents. Extraordinary results on the production, quality control and preclinical evaluation of selected radionuclides were reported in this project that was finalized in 2020. The outcomes, outputs and results of this project achieved by participating Member States are described in this minireview