A Treatment Option or Source of Bacterial Pathogen Transmission? The Case of Herbal Mixture in Nigeria

Herbal mixture such as agbo, has been used in recent years in Nigeria to treat various sicknesses including malaria, typhoid, dysentery and cholera. However, the bacteriological quality and safety is of paramount importance spurring the argument whether it is treatment option or sources of pathogen transmission. Hence this study was conducted to investigate the bacteriological analysis of agbo herbal preparations. Samples of herbal mixture were purchased from five different markets (Uselu, New Benin, Oba, Santana and Ogida Markets) in Benin City, Edo State, Nigeria. Bacteriological analysis was carried out using pour plate isolation method. Identification of isolated bacteria was based on their cultural, morphological, biochemical and molecular techniques. Antibiotic sensitivity pattern was carried out using disk diffusion method. The plasmid profile of multiple drug resistance bacterial genes isolated was also analyzed. Bacteriological analyses showed that the total bacterial counts (TBC) of all the test herbal samples obtained from the various markets ranged from 0.04 x 104 to 1.13 x 104cfu/ml. Eight bacterial species were identified and they include; Bacillus cereus, Bacillus subtilis, Escherichia coli, Lactobacillus casei, Serratia marcescens, Micrococcus varians, Pseudomonas aeruginosa and Staphylococcus aureus. The least occurring bacterial isolates were Serratia marcescens and Pseudomonas aeruginosa (5.26%) while the highest occurring was Bacillus cereus (21.05%). Isolated bacteria were resistant to commonly used antibiotics. Plasmid profile revealed presence of plasmid genes in the bacterial isolates. Since applications of herbal medicines for curative purposes is on the increase, there is need to monitor and ensure its bacteriological quality before distributing to final consumers

Antibacterial activity of Vernonia amygdalina leaf extracts against multidrug resistant bacterial isolates

This study was undertaken to investigate the phytochemical and antibacterial activities of Vernonia amygdalina leaf extract against clinical isolates obtained from the University of Benin Teaching Hospital, using agar well diffusion method. Phytochemicals present in Vernonia amygdalin included flavonoids, cardiac glycosides, reducing sugar, terpenoids and saponins. Ethanolic extract acted against with inhibition zones ranging from 7.0±0.0mm at 25mg/ml to 14.5±2.5mm at 200mg/ml against E. coli; 6.5±0.5mm at 100mg/ml to 9.0±2.0mm at 200mg/ml against S. aureus; 11.0±1.0mm at 50mg/ml to 16.5±5.0mm at 200mg/ml; 7.5±1.5mm at 25mg/ml to 11.5±0.5mm at 200mg/ml. Inhibition zones in aqueous extract ranged from 8.0±2.0mm at 25mg/ml to 12.5±1.5 at 200mg/ml against P. aeruginosa; 9.0±1.0mm at 50mg/ml to 15.0±1.5mm at 200mg/ml against S aureus. The minimum inhibitory concentration of ethanolic extract ranged from 25mg/ml in S. aureus, P. aeruginosa, B. subtilis and K. pneumoniae to 50mg/ml in E. coli. Minimum bactericidal concentration of the ethanol extract was 50mg/ml in P. aeruginosa and K. pneumonia and 100mg/ml for E. coli, S. aureus and B. subtilis. MBC of 200mg/ml was observed for B. subtilis, S. aureus and P. aeruginosa in the aqueous fraction of the plant. The most antibiotic resistant bacterial strain was S. aureus (80%) while the least resistant was P. aeruginosa (10%). The most resistant bacterial strain was S. aureus (80%) while the least resistant was P. aeruginosa (10%). The most effective antibiotics were perfloxacin, ciprofloxacin, septrin and choramphenicol. Vernonia amygdalina extract was found to be more potent than conventional antibiotics.Keywords: Antimicrobial, Phytochemical, Antibiotics, Susceptibility, Resistanc

A randomised controlled trial to assess the clinical effectiveness and safety of the endometrial scratch procedure prior to first-time IVF, with or without ICSI

STUDY QUESTION: What is the clinical-effectiveness and safety of the endometrial scratch (ES) procedure compared to no ES, prior to usual first time in vitro fertilisation (IVF) treatment? SUMMARY ANSWER: ES was safe but did not improve pregnancy outcomes when performed in the mid-luteal phase prior to the first IVF cycle, with or without intracytoplasmic sperm injection (ICSI). WHAT IS KNOWN ALREADY: ES is an 'add-on' treatment that is available to women undergoing a first cycle of IVF, with or without ICSI, despite a lack of evidence to support its use. STUDY DESIGN, SIZE, DURATION: This pragmatic, superiority, open-label, multi-centre, parallel-group randomised controlled trial involving 1048 women assessed the clinical effectiveness and safety of the ES procedure prior to first time IVF, with or without ICSI, between July 2016 and October 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants aged 18-37 years undergoing their first cycle of IVF, with or without ICSI, were recruited from 16 UK fertility clinics and randomised (1:1) by a web-based system with restricted access rights that concealed allocation. Stratified block randomisation was used to allocate participants to TAU or ES in the mid-luteal phase followed by usual IVF with or without ICSI treatment. The primary outcome was live birth after completing 24 weeks gestation within 10.5 months of egg collection. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 1048 women randomised to TAU (n = 525) and ES (n = 523) were available for intention to treat analysis. In the ES group, 453 (86.6%) received the ES procedure. IVF, with or without ICSI, was received in 494 (94.1%) and 497 (95.0%) of ES and TAU participants respectively. Live birth rate was 37.1% (195/525) in the TAU and 38.6% (202/523) in the ES: an unadjusted absolute difference of 1.5% (95% CI -4.4% to 7.4%, P = 0.621). There were no statistical differences in secondary outcomes. Adverse events were comparable across groups. LIMITATIONS, REASONS FOR CAUTION: A sham ES procedure was not undertaken in the control group, however, we do not believe this would have influenced the results as objective fertility outcomes were used. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest trial that is adequately powered to assess the impact of ES on women undergoing their first cycle of IVF. ES was safe, but did not significantly improve pregnancy outcomes when performed in the mid-luteal phase prior to the first IVF or ICSI cycle. We recommend that ES is not undertaken in this population. STUDY FUNDING/COMPETING INTEREST(S): Funded by the National Institute of Health Research. Stephen Walters is an National Institute for Health Research (NIHR) Senior Investigator (2018 to present) and was a member of the following during the project: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Clinical Trials and Evaluation Committee (2011-2017), NIHR HTA Commissioning Strategy Group (2012 to 2017); NIHR Programme Grants for Applied Research Committee (2020 to present); NIHR Pre doctoral Fellowship Committee (2019 to present). Dr. Martins da Silva reports grants from AstraZeneca, during the conduct of the study; and is Associate editor of Human Reproduction and Editorial Board member of Reproduction and Fertility. Dr. Bhide reports grants from Bart's Charity and grants and non-financial support from Pharmasure Pharmaceuticals outside the submitted work. TRIAL REGISTRATION NUMBER: ISRCTN number: ISRCTN23800982. TRIAL REGISTRATION DATE: 31 May 2016. DATE OF FIRST PATIENT’S ENROLMENT: 04 July 2016

The stereochemistry of amide side chains containing carboxyl groups influences water exchange rates in EuDOTA-tetraamide complexes

Many Eu(III) complexes formed with DOTA-tetraamide ligands (where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) have sufficiently slow water exchange kinetics to meet the slow-to-intermediate condition required to serve as chemical exchange saturation transfer (CEST) contrast agents for MRI. This class of MRI contrast agents offers an attractive platform for creating biological sensors because water exchange is exquisitely sensitive to subtle ligand stereochemistry and electronic effects. Introduction of carboxyl groups or carboxyl ethyl ester groups on the amide substituents has been shown to slow water exchange in these complexes, but less is known about the orientation or position of these side-chain groups relative to the inner-sphere Eu(III)-bound water molecule. In this study, a series of Eu(III) complexes having one or more carboxyl groups or carboxyl esters at the δ-position of the pendant amide side chains were prepared. Initial attempts to prepare optically pure EuDOTA-[(S)-Asp]4 resulted in a chemically pure ligand consisting of a mixture of stereochemical isomers. This was traced to racemization of (S)-aspartate diethyl ester during the synthetic procedure. Nevertheless, NMR studies of the Eu(III) complexes of this mixture revealed that each isomer had a different water exchange rate, differing by a factor of 2 or more. A second controlled synthesis and CEST study of EuDOTA-[(S)-Asp]4 and cis-EuDOTA-[(S)-Asp]2[(R)-Asp]2 confirmed that the water exchange rates in these diastereomeric complexes are controlled by the axial versus equatorial orientation of the carboxyl groups on the amide side chains. These observations provide new insights toward the development of even more slowly water exchanging systems which will be necessary for practical in vivo applications