Synthesis and Evaluation of Antimicrobial Activity of Some 2-Morpholinomethylamino-4-(7-Unsubstituted/Substituted Coumarin-3-yl)-6-Chlorosubstitutedphenyl Pyrimidines

Purpose: To prepare some 2-morpholinomethylamino-4-(7 unsubstituted/substitutedcoumarin-3-yl)-6- chlorosubstitutedphenyl pyrimidines as antimicrobial agents.Methods: Some 2-morpholinomethylamino-4-(7 unsubstituted/substitutedcoumarin-3-yl)-6-chlorosubstitutedphenyl pyrimidines were prepared by reacting 2-amino-4-(7-substituted/unsubstituted coumarin-3 yl)-6-(chlorosubstitutedphenyl) pyrimidines with morpholine and formaldehyde. The chemical structures of the synthesized compounds were elucidated by their Fourier Transform infra-red (FTIR), 1H-nuclear magnetic resonance (1H-NMR) and mass spectra, as well as by elemental analysis. These compounds were investigated for their antimicrobial activity against ten bacteria and five fungi by serial plate dilution method using the standard drugs, ofloxacin and ketoconazole, respectively, and their minimum inhibitory concentrations (MICs) were determined.Results: A total of eighteen new compounds (1a-18a) were synthesized. Compound 3a (MIC = 75 μg/mL; p < 0.0001) and 15a (MIC = 125 μg/mL; p < 0.001) produced stronger antifungal activity than the standard drug, ketoconazole (MIC = 25 μg/mL; p < 0.0001) against P. citrinum. Compound 4adisplayed higher but moderate activity against Gram-positive bacterium, S. aureus (MIC = 100 μg/mL; p < 0.05) than the standard drug, ofloxacin (MIC = 25 μg/mL; p < 0.0001). Compound 4a also displayed higher but moderate activity against the Gram-negative bacterium, E. coli (MIC = 75 μg/mL; p < 0.0001) than the standard drug, ofloxacin (MIC = 12.5 μg/mL; p < 0.0001). The structure activity relationship analysis revealed that the chloro- substitution at position 2 of the phenyl ring along with a chlorobromosubstituted coumarin moiety of the synthesized compounds is critical for activity against Gram-positive bacteria, Gram negative bacteria and fungi.Conclusion: The synthesized compounds are relatively active antifungal agents but are weak antibacterial agents. However, they require further evaluation of their antifungal activity against other fungal strains to ascertain their broad spectrum activity.Keywords: Pyrimidine, Coumarin, Morpholine, Antibacterial, Antifungal, Structure-activity relationshi

Preparation and In-Vitro Evaluation of Controlled-Release Matrices of Losartan Potassium Using Ethocel Grade 10 and Carbopol 934P NF as Rate-Controlling Polymers

Controlled-release formulations are essential for those drugs that require fine tuning of their activity to increase the ratio between therapeutic vs. adverse effects. Losartan potassium is among those drugs whose adverse effects may somehow impair its purported benefits. Previous investigations have been carried out to ascertain the suitability of several polymers for being associated with losartan. This study is focused on the effects of Ethocel grade 10 and Carbopol 934P NF on losartan release. Flow and physical properties were assessed according to the protocols standardized by the pharmacopeia (USP-NF 29), and the drug release in phosphate buffer (pH = 6.8) was measured for 24 h. Data evidenced good to excellent flow and physical properties according to the drug/polymer ratio and the addition of co-excipients. The release rate in 24 h was found to be 63–69% to 79–82% without or with the addition of co-excipients, respectively, following zero-order kinetics. The results also suggest a significant difference with the release profile of a traditional release losartan formulation. The results suggest the suitability of Ethocel grade 10 and Carbopol 934P NF as components of a controlled-release losartan formulation

Nanotechnology integration for sars-cov-2 diagnosis and treatment: An approach to preventing pandemic

The SARS-CoV-2 outbreak is the COVID-19 disease, which has caused massive health devastation, prompting the World Health Organization to declare a worldwide health emergency. The corona virus infected millions of people worldwide, and many died as a result of a lack of particular medications. The current emergency necessitates extensive therapy in order to stop the spread of the coronavirus. There are various vaccinations available, but no validated COVID-19 treatments. Since its outbreak, many therapeutics have been tested, including the use of repurposed medications, nucleoside inhibitors, protease inhibitors, broad spectrum antivirals, convalescence plasma therapies, immune-modulators, and monoclonal antibodies. However, these approaches have not yielded any outcomes and are mostly used to alleviate symptoms associated with potentially fatal adverse drug reactions. Nanoparticles, on the other hand, may prove to be an effective treatment for COVID-19. They can be designed to boost the efficacy of currently available antiviral medications or to trigger a rapid immune response against COVID-19. In the last decade, there has been significant progress in nanotechnology. This review focuses on the virus’s basic structure, pathogenesis, and current treatment options for COVID-19. This study addresses nanotechnology and its applications in diagnosis, prevention, treatment, and targeted vaccine delivery, laying the groundwork for a successful pandemic fight

Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries:results of an internet-based global point prevalence survey

Summary: Background: The Global Point Prevalence Survey (Global-PPS) established an international network of hospitals to measure antimicrobial prescribing and resistance worldwide. We aimed to assess antimicrobial prescribing and resistance in hospital inpatients. Methods: We used a standardised surveillance method to collect detailed data about antimicrobial prescribing and resistance from hospitals worldwide, which were grouped by UN region. The internet-based survey included all inpatients (adults, children, and neonates) receiving an antimicrobial who were on the ward at 0800 h on one specific day between January and September, 2015. Hospitals were classified as primary, secondary, tertiary (including infectious diseases hospitals), and paediatric hospitals. Five main ward types were defined: medical wards, surgical wards, intensive-care units, haematology oncology wards, and medical transplantation (bone marrow or solid transplants) wards. Data recorded included patient characteristics, antimicrobials received, diagnosis, therapeutic indication according to predefined lists, and markers of prescribing quality (eg, whether a stop or review date were recorded, and whether local prescribing guidelines existed and were adhered to). We report findings for adult inpatients. Findings: The Global-PPS for 2015 included adult data from 303 hospitals in 53 countries, including eight lower-middle-income and 17 upper-middle-income countries. 86 776 inpatients were admitted to 3315 adult wards, of whom 29 891 (34·4%) received at least one antimicrobial. 41 213 antimicrobial prescriptions were issued, of which 36 792 (89·3%) were antibacterial agents for systemic use. The top three antibiotics prescribed worldwide were penicillins with β-lactamase inhibitors, third-generation cephalosporins, and fluoroquinolones. Carbapenems were most frequently prescribed in Latin America and west and central Asia. Of patients who received at least one antimicrobial, 5926 (19·8%) received a targeted antibacterial treatment for systemic use, and 1769 (5·9%) received a treatment targeting at least one multidrug-resistant organism. The frequency of health-care-associated infections was highest in Latin America (1518 [11·9%]) and east and south Asia (5363 [10·1%]). Overall, the reason for treatment was recorded in 31 694 (76·9%) of antimicrobial prescriptions, and a stop or review date in 15 778 (38·3%). Local antibiotic guidelines were missing for 7050 (19·2%) of the 36 792 antibiotic prescriptions, and guideline compliance was 77·4%. Interpretation: The Global-PPS showed that worldwide surveillance can be accomplished with voluntary participation. It provided quantifiable measures to assess and compare the quantity and quality of antibiotic prescribing and resistance in hospital patients worldwide. These data will help to improve the quality of antibiotic prescribing through education and practice changes, particularly in low-income and middle-income countries that have no tools to monitor antibiotic prescribing in hospitals. Funding: bioMérieux

Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): an analysis of paediatric survey data from 56 countries

BACKGROUND: Improving the quality of hospital antibiotic use is a major goal of WHO's global action plan to combat antimicrobial resistance. The WHO Essential Medicines List Access, Watch, and Reserve (AWaRe) classification could facilitate simple stewardship interventions that are widely applicable globally. We aimed to present data on patterns of paediatric AWaRe antibiotic use that could be used for local and national stewardship interventions. METHODS: 1-day point prevalence survey antibiotic prescription data were combined from two independent global networks: the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children and the Global Point Prevalence Survey on Antimicrobial Consumption and Resistance networks. We included hospital inpatients aged younger than 19 years receiving at least one antibiotic on the day of the survey. The WHO AWaRe classification was used to describe overall antibiotic use as assessed by the variation between use of Access, Watch, and Reserve antibiotics, for neonates and children and for the commonest clinical indications. FINDINGS: Of the 23 572 patients included from 56 countries, 18 305 were children (77·7%) and 5267 were neonates (22·3%). Access antibiotic use in children ranged from 7·8% (China) to 61·2% (Slovenia) of all antibiotic prescriptions. The use of Watch antibiotics in children was highest in Iran (77·3%) and lowest in Finland (23·0%). In neonates, Access antibiotic use was highest in Singapore (100·0%) and lowest in China (24·2%). Reserve antibiotic use was low in all countries. Major differences in clinical syndrome-specific patterns of AWaRe antibiotic use in lower respiratory tract infection and neonatal sepsis were observed between WHO regions and countries. INTERPRETATION: There is substantial global variation in the proportion of AWaRe antibiotics used in hospitalised neonates and children. The AWaRe classification could potentially be used as a simple traffic light metric of appropriate antibiotic use. Future efforts should focus on developing and evaluating paediatric antibiotic stewardship programmes on the basis of the AWaRe index. FUNDING: GARPEC was funded by the PENTA Foundation. GARPEC-China data collection was funded by the Sanming Project of Medicine in Shenzhen (SZSM2015120330). bioMérieux provided unrestricted funding support for the Global-PPS

Population Estimation Mining Using Satellite Imagery

Abstract. Many countries around the world regularly collect census data. This census data provides statistical information regarding populations to in turn support decision making processes. However, traditional approaches to the collation of censes data are both expensive and time consuming. The analysis of high resolution satellite imagery provides a useful alternative to collecting census data which is significantly cheaper than traditional methods, although less accurate. This paper describes a technique for mining satellite imagery, to extract census information, founded on the use of classification techniques coupled with a graph based representation of the relevant imagery. The fundamental idea is to build a classifier that can label households according to “family size ” which can then be used to collect census data. To act as a focus for the work training data obtained from villages lying some 300km to the northwest of Addis Ababa in Ethiopia was used. The nature of each household in the segmented training data was captured using a tree-based representation. Each tree represented household had a “family size ” class label associated with it. This data was then used to build a classifier that can be used to predict household sizes according to the nature of the tree-based structure

Lateral epicondyle to the joint line distance is a precise landmark for determination of an accurate knee joint line: an observational retrospective study

Abstract Purpose To assess a quantitative and reproducible association between the position of the knee joint line and recognizable anatomical landmarks around it in order to help in restoring joint line in arthroplasty cases. Methods Magnetic resonance imaging (MRI) of 130 normal knees were investigated. Anatomical measurements of the knee joint distances on the obtained planes were performed manually by distance measurements using a ruler tool, followed by 6 anatomical bony landmarks determination about the knee to identify the joint line which included the joint line, medial epicondyle, lateral epicondyle, medial flare, lateral flare, and proximal tibiofibular joint. The entire process was examined twice by two independent fellowship trained musculoskeletal radiologists, with a 2‐week interval between the first and second sets of readings. Results The lateral epicondyle to the joint line of the knee (LEJL) could be a reliable landmark for accurate distance measurements for the knee joint line level, with an absolute distance of 24.4 ± 2.8 mm. The analysis showed that the femorotibial ratio between the LEJL and proximal tibiofibular joint (PTFJ) was 1.0 (LEJL/PTFJJL = 1.0 ± 0.1), confirming the location of the knee joint at the midpoint between the lateral epicondyle and PTFJ, revealing two identifiable landmarks. Conclusions LEJL is the most precise landmark for determination of an accurate knee joint line because the knee is located at the midline between the lateral epicondyle and PTFJ. These reproducible quantitative relationships can be widely employed in various imaging modalities to help restore the knee JL in arthroplasty surgeries

In Silico Analysis of Honeybee Venom Protein Interaction with Wild Type and Mutant (A82V + P375S) <em>Ebola</em> Virus Spike Protein

Venom from different organisms was used in ancient times to treat a wide range of diseases, and to combat a variety of enveloped and non-enveloped viruses. The aim of this in silico research was to investigate the impact of honeybee venom proteins and peptides against Ebola virus. In the current in silico study, different online and offline tools were used. RaptorX (protein 3D modeling) and PatchDock (protein–protein docking) were used as online tools, while Chimera and LigPlot + v2.1 were used for visualizing protein–protein interactions. We screened nine venom proteins and peptides against the normal Ebola virus spike protein and found that melittin, MCD and phospholipase A2 showed a strong interaction. We then screened these peptides and proteins against mutated strains of Ebola virus and found that the enzyme phospholipase A2 showed a strong interaction. According to the findings, phospholipase A2 found in honeybee venom may be an effective source of antiviral therapy against the deadly Ebola virus. Although the antiviral potency of phospholipase A2 has been recorded previously, this is the first in silico analysis of honeybee phospholipase A2 against the Ebola viral spike protein and its more lethal mutant strain