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1.
S Afr Fam Pract (2004) ; 63(1): e1-e3, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34212751

RESUMO

In the wake of the coronavirus disease 2019 (COVID-19) pandemic, the links between poor hygiene, unclean environments and human health cannot be overemphasised, particularly in South Africa with its high incidence of infectious diseases and overburdened health system. One very controllable factor that is often overlooked is the poor disposal of litter and waste management and its adverse effects on public health. By wearing masks, regular handwashing and sanitising, as well as making sure that neighbourhoods and public spaces are clean and safe, the spread of COVID-19 and other diseases can be prevented.


Assuntos
COVID-19 , Controle de Doenças Transmissíveis/organização & administração , Saúde Ambiental/organização & administração , Recuperação e Remediação Ambiental , Saúde Pública/métodos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Transmissão de Doença Infecciosa/prevenção & controle , Humanos , Higiene/normas , Condições Sociais , Determinantes Sociais da Saúde , África do Sul/epidemiologia
2.
Pharmaceuticals (Basel) ; 14(4)2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33919737

RESUMO

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has reinforced the need for the development of new anti-TB drugs. The first line drug isoniazid inhibits InhA. This is a prodrug requiring activation by the enzyme KatG. Mutations in KatG have largely contributed to clinical isoniazid resistance. We aimed to design new 'direct' InhA inhibitors that obviate the need for activation by KatG, circumventing pre-existing resistance. In silico molecular modelling was used as part of a rational structure-based drug-design approach involving inspection of protein crystal structures of InhA:inhibitor complexes, including the broad spectrum antibiotic triclosan (TCS). One crystal structure exhibited the unusual presence of two triclosan molecules within the Mycobacterium tuberculosis InhA binding site. This became the basis of a strategy for the synthesis of novel inhibitors. A series of new, flexible ligands were designed and synthesised, expanding on the triclosan structure. Low Minimum Inhibitory Concentrations (MICs) were obtained for benzylphenyl compounds (12, 43 and 44) and di-triclosan derivative (39), against Mycobacterium bovis BCG although these may also be inhibiting other enzymes. The ether linked di-triclosan derivative (38) displayed excellent in vitro isolated enzyme inhibition results comparable with triclosan, but at a higher MIC (125 µg mL-1). These compounds offer good opportunities as leads for further optimisation.

3.
BMC Med Educ ; 20(1): 346, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023590

RESUMO

BACKGROUND: The rapid progression of diseases and the complex, changing landscape of healthcare has increased the awareness that interprofessional collaboration is essential in ensuring safe and effective healthcare delivery. However, to develop a "collaborative practice-ready" workforce, organisations need to invest in the application of alternative approaches to the training of healthcare professionals. PURPOSE OF THE STUDY: To describe the perceptions of healthcare professionals attending an HIV interprofessional collaborative initiative at a non-governmental organization research site in South Africa and to provide suggestions regarding the improvement of this educational programme. METHODS: Focus group discussions (December 2018 to January 2019), were conducted on a purposeful sample (N = 21) consisting of healthcare professionals (clinicians, pharmacists, pharmacy assistants, and nurses), and clinical trial staff (recruiters, administrators, QC officers, psychologists, counsellors) based at a research site, who were invited to attend a continuing medical education initiative on the pathogenesis and treatment of HIV. Qualitative content analysis was carried out to identify meaning units, which were then condensed and labelled with a code. This was further grouped to form categories. RESULTS: Five categories emerged: learning something new, acquiring from each other, promoting company culture, needing company buy-in and teaching methods matter. Interprofessional collaborative learning improved technical capacity, work relationships and company culture. The diversity in learning needs of the different professionals requires a structuring of a curriculum to meet the needs of all. The success of this initiative requires company buy-in/investment and recognition from leaders and higher management with regards to time and resources. Suggestions for improvement included: formalizing the training, introducing more lectures and pitching each topic at different levels i.e. basic, intermediate or advanced, thus ensuring maximum benefit for all. CONCLUSION: Inter-professional learning was perceived as highly valuable. This initiative has the potential to develop further but requires resources and company buy-in. All staff working (clinical and non-clinical) at the NGO site were represented in the interviews, thus ensuring a richer understanding of all perspectives relevant to the study site. The small sample size confined to a single research site, however, prevents these findings from being generalized and limits the applicability of its findings.


Assuntos
Práticas Interdisciplinares , Currículo , Humanos , Relações Interprofissionais , Farmacêuticos , Pesquisa Qualitativa , África do Sul
4.
JAC Antimicrob Resist ; 1(3): dlz060, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34222934

RESUMO

Objectives: To map published data of antimicrobial stewardship (AMS) interventions that are currently being carried out in hospitals and clinics in the public and private health sectors of South Africa in line with the antimicrobial resistance (AMR) strategy of South Africa. Methods: A systematic scoping review was conducted to identify AMS initiatives in the public and private health sectors of South Africa for the period 1 January 2000 to 31 March 2019. An electronic search of databases was made including PubMed, Scopus, a key medical journal (South African Medical Journal), University of KwaZulu-Natal (UKZN) WorldCat iCatalogue and AMR networks: Federation of Infectious Diseases Societies in South Africa (FIDSSA). Reference lists of published articles were also reviewed for inclusion. Keywords included 'antimicrobial antibiotic stewardship South Africa'. Findings: Of a total of 411 articles, using a stepwise screening process, 18 articles were selected for inclusion in the review. The interventions/initiatives were divided into four broad categories: (i) AMS intervention: prescription audits and usage; (ii) AMS intervention: education and its impact; (iii) other AMS interventions; and (iv) the role of different healthcare professionals in AMS. Conclusions: The data identifies a need for and the value of AMS in both the public and private health sectors of South Africa. Initiatives are carried out across both sectors but more attention needs to be focused on AMS implementation in line with the National AMR Strategy of South Africa. Collaboration between the different sectors will aid in overcoming the AMR challenge.

5.
Bioorg Med Chem Lett ; 27(3): 370-386, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28017531

RESUMO

Modern chemotherapy has significantly improved patient outcomes against drug-sensitive tuberculosis. However, the rapid emergence of drug-resistant tuberculosis, together with the bacterium's ability to persist and remain latent present a major public health challenge. To overcome this problem, research into novel anti-tuberculosis targets and drug candidates is thus of paramount importance. This review article provides an overview of tuberculosis highlighting the recent advances and tools that are employed in the field of anti-tuberculosis drug discovery. The predominant focus is on anti-tuberculosis agents that are currently in the pipeline, i.e. clinical trials.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose/dietoterapia , Antituberculosos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , DNA Bacteriano/química , DNA Bacteriano/metabolismo , Descoberta de Drogas , Farmacorresistência Bacteriana/efeitos dos fármacos , Genômica , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose/tratamento farmacológico
6.
J Biomol Struct Dyn ; 34(1): 135-51, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25671669

RESUMO

The PR20 HIV-1 protease, a variant with 20 mutations, exhibits high levels of multi-drug resistance; however, to date, there has been no report detailing the impact of these 20 mutations on the conformational and drug binding landscape at a molecular level. In this report, we demonstrate the first account of a comprehensive study designed to elaborate on the impact of these mutations on the dynamic features as well as drug binding and resistance profile, using extensive molecular dynamics analyses. Comparative MD simulations for the wild-type and PR20 HIV proteases, starting from bound and unbound conformations in each case, were performed. Results showed that the apo conformation of the PR20 variant of the HIV protease displayed a tendency to remain in the open conformation for a longer period of time when compared to the wild type. This led to a phenomena in which the inhibitor seated at the active site of PR20 tends to diffuse away from the binding site leading to a significant change in inhibitor-protein association. Calculating the per-residue fluctuation (RMSF) and radius of gyration, further validated these findings. MM/GBSA showed that the occurrence of 20 mutations led to a drop in the calculated binding free energies (ΔGbind) by ~25.17 kcal/mol and ~5 kcal/mol for p2-NC, a natural peptide substrate, and darunavir, respectively, when compared to wild type. Furthermore, the residue interaction network showed a diminished inter-residue hydrogen bond network and changes in inter-residue connections as a result of these mutations. The increased conformational flexibility in PR20 as a result of loss of intra- and inter-molecular hydrogen bond interactions and other prominent binding forces led to a loss of protease grip on ligand. It is interesting to note that the difference in conformational flexibility between PR20 and WT conformations was much higher in the case of substrate-bound conformation as compared to DRV. Thus, developing analogues of DRV by retaining its key pharmacophore features will be the way forward in the search for novel protease inhibitors against multi-drug resistant strains.


Assuntos
Inibidores da Protease de HIV/química , Protease de HIV/química , HIV-1/química , Sulfonamidas/química , Sítios de Ligação , Resistência a Múltiplos Medicamentos/genética , Protease de HIV/genética , Protease de HIV/metabolismo , HIV-1/enzimologia , Humanos , Ligação de Hidrogênio , Simulação de Dinâmica Molecular , Mutação , Conformação Proteica/efeitos dos fármacos , Termodinâmica
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