Influence of Moringa oleifera leaves on atherogenic lipids and glycaemia evolution in HIV-infected and uninfected malnourished patients

Objectives: The study evaluated mineral composition of “Togolese ecotype” of Moringa oleifera leaves and its effect on anthropometric parameters, atherogenic lipids and glycaemia during nutritional recovery in HIV negative and HIV positive malnourished patients after daily use of the leaves powder. Methodology and results: Patients aged from 12 months to 8 years, consumed every day for 15 weeks the leaves powder. Results showed that powder is rich in proteins, micronutrients and induced BMI increase in both patients (p C 0.001). Biochemical parameters determination showed decrease in total cholesterol, triglycerides, LDL-cholesterol (p C 0.01), atherogenicity index (AI) correlated with HDL-cholesterol increase (p C 0.001) in HIV negative. Increase in triglycerides, LDL-cholesterol, AI (p C 0.001) correlated with HDLcholesterol decrease (p C 0.001) is observed in HIV positive. Total cholesterol decreased more in HIV positive asymptomatic and increased in patients treated with ARV drugs (p C 0.0001). Glycaemia level is decreased in both patients of the study. Conclusion and application of findings: This study confirms higher concentrations of proteins, micronutrients, hypolipidemic potential and hypocholesterolemic activity of M. oleifera leaves. This explained nutritional recovery and reduction of atherogenic lipids. Positive effect of the powder on cholesterol metabolism is due to beta-sitosterol, bioactive phytoconstituent of the leaves which fixed LDL particles and thought to be through the lowering significantly of their plasma concentrations. Reduction of glycaemia in both patients confirms also hypoglycemic properties of leaves with high concentration of polyphenols and antioxydants. The lowering of atherogenic risk and glycaemia after regular consumption of M. oleifera leaves powder is more significant in HIV negative than HIV positive patients. Results of this study bring information which will make it possible to pediatrics and nutritionists to adapt better use of M. oleifera leaves to combat malnutrition and the follow-up of HIV positive persons and in particular those on antiretroviral treatment. Key words: Moringa oleifera, malnutrition, atherogenic lipids, glycaemia, HIV/AIDS

Radiation Protection Knowledge and Awareness of Naturally Occurring Radioactive Materials among Underground Goldmine Workers in Ghana

The level of knowledge and awareness of naturally occurring radioactive materials and indoor radon among underground goldmine workers were measured using a well-structured closed ended five-point likert scale questionnaire using a one sample T test for the analysis. There was a significant relationship between the awareness and knowledge of NORM and radon gas among the underground workers apart from the awareness and knowledge of the increased risk of cancer due to exposure of radon for workers who smoke. The level of awareness and knowledge is positively correlated with the level of education of respondents and negatively correlated to the years of service and age of respondents, but the ANOVA table indicates a statistical significance between the demographic data and the awareness and knowledge of radon gas and NORM in their working environment with an adjusted R2 of 46.1%. Keywords: NORM, Indoor radon, correlation, awareness, knowledge. DOI: 10.7176/IKM/13-3-04 Publication date:April 30th 202

TIME SERIES ANALYSIS OF RADON CONCENTRATION AT DIFFERENT DEPTHS IN AN UNDERGROUND GOLDMINE

Indoor radon concentrations were collected monthly over a period of one year in 10 different levels in an underground goldmine and the data was analysed using a four moving average time series to determine the relationship between depths of the underground mine and the indoor radon concentration. The detectors were installed in batches within four quarters. The measurements were carried out using LR115 solid state nuclear track detectors. Statistical models are applied in the prediction and analysis of the radon concentration at various depths. The time series model predicted a positive relationship between the depth of the underground mine and the indoor radon concentration. Thus, elevated radon concentrations are expected at deeper levels of the underground mine, but the relationship was insignificant at the 5% level of significance with a negative adjusted R2 (R2 = – 0.021) due to an appropriate engineering and adequate ventilation rate in the underground mine. Keywords: LR115, Radon Concentration, Time Series, Underground goldmine, DOI: 10.7176/APTA/87-03 Publication date: April 30th 202

Analyses of HIV-1 integrase sequences prior to South African national HIV-treatment program and available of integrase inhibitors in Cape Town, South Africa

HIV-Integrase (IN) has proven to be a viable target for highly specific HIV-1 therapy. We aimed to characterize the HIV-1 IN gene in a South African context and identify resistance-associated mutations (RAMs) against available first and second generation Integrase strand-transfer inhibitors (InSTIs). We performed genetic analyses on 91 treatment-naïve HIV-1 infected patients, as well as 314 treatmentnaive South African HIV-1 IN-sequences, downloaded from Los Alamos HIV Sequence Database. Genotypic analyses revealed the absence of major RAMs in the cohort collected before the broad availability of combination antiretroviral therapy (cART) and INSTI in South Africa, however, occurred at a rate of 2.85% (9/314) in database derived sequences. RAMs were present at IN-positions 66, 92, 143, 147 and 148, all of which may confer resistance to Raltegravir (RAL) and Elvitegravir (EVG), but are unlikely to affect second-generation Dolutegravir (DTG), except mutations in the Q148 pathway. Furthermore, protein modeling showed, naturally occurring polymorphisms impact the stability of the intasome-complex and therefore may contribute to an overall potency against InSTIs. Our data suggest the prevalence of InSTI RAMs, against InSTIs, is low in South Africa, but natural polymorphisms and subtype-specific differences may influence the effect of individual treatment regimens

CPP-ZFN: A potential DNA-targeting anti-malarial drug

<p>Abstract</p> <p>Background</p> <p>Multidrug-resistant <it>Plasmodium </it>is of major concern today. Effective vaccines or successful applications of RNAi-based strategies for the treatment of malaria are currently unavailable. An unexplored area in the field of malaria research is the development of DNA-targeting drugs that can specifically interact with parasitic DNA and introduce deleterious changes, leading to loss of vital genome function and parasite death.</p> <p>Presentation of the hypothesis</p> <p>Advances in the development of zinc finger nuclease (ZFN) with engineered DNA recognition domains allow us to design and develop nuclease of high target sequence specificity with a mega recognition site that typically occurs only once in the genome. Moreover, cell-penetrating peptides (CPP) can cross the cell plasma membrane and deliver conjugated protein, nucleic acid, or any other cargo to the cytoplasm, nucleus, or mitochondria. This article proposes that a drug from the combination of the CPP and ZFN systems can effectively enter the intracellular parasite, introduce deleterious changes in its genome, and eliminate the parasite from the infected cells.</p> <p>Testing the hypothesis</p> <p>Availability of a DNA-binding motif for more than 45 triplets and its modular nature, with freedom to change number of fingers in a ZFN, makes development of customized ZFN against diverse target DNA sequence of any gene feasible. Since the <it>Plasmodium </it>genome is highly AT rich, there is considerable sequence site diversity even for the structurally and functionally conserved enzymes between <it>Plasmodium </it>and humans. CPP can be used to deliver ZFN to the intracellular nucleus of the parasite. Signal-peptide-based heterologous protein translocation to <it>Plasmodium</it>-infected RBCs (iRBCs) and different <it>Plasmodium </it>organelles have been achieved. With successful fusion of CPP with mitochondrial- and nuclear-targeting peptides, fusion of CPP with 1 more <it>Plasmodium </it>cell membrane translocation peptide seems achievable.</p> <p>Implications of the hypothesis</p> <p>Targeting of the <it>Plasmodium </it>genome using ZFN has great potential for the development of anti-malarial drugs. It allows the development of a single drug against all malarial infections, including multidrug-resistant strains. Availability of multiple ZFN target sites in a single gene will provide alternative drug target sites to combat the development of resistance in the future.</p

Plasmodium falciparum Parasites Are Killed by a Transition State Analogue of Purine Nucleoside Phosphorylase in a Primate Animal Model

Plasmodium falciparum causes most of the one million annual deaths from malaria. Drug resistance is widespread and novel agents against new targets are needed to support combination-therapy approaches promoted by the World Health Organization. Plasmodium species are purine auxotrophs. Blocking purine nucleoside phosphorylase (PNP) kills cultured parasites by purine starvation. DADMe-Immucillin-G (BCX4945) is a transition state analogue of human and Plasmodium PNPs, binding with picomolar affinity. Here, we test BCX4945 in Aotus primates, an animal model for Plasmodium falciparum infections. Oral administration of BCX4945 for seven days results in parasite clearance and recrudescence in otherwise lethal infections of P. falciparum in Aotus monkeys. The molecular action of BCX4945 is demonstrated in crystal structures of human and P. falciparum PNPs. Metabolite analysis demonstrates that PNP blockade inhibits purine salvage and polyamine synthesis in the parasites. The efficacy, oral availability, chemical stability, unique mechanism of action and low toxicity of BCX4945 demonstrate potential for combination therapies with this novel antimalarial agent

Novel therapeutic strategies targeting HIV integrase

Integration of the viral genome into host cell chromatin is a pivotal and unique step in the replication cycle of retroviruses, including HIV. Inhibiting HIV replication by specifically blocking the viral integrase enzyme that mediates this step is an obvious and attractive therapeutic strategy. After concerted efforts, the first viable integrase inhibitors were developed in the early 2000s, ultimately leading to the clinical licensure of the first integrase strand transfer inhibitor, raltegravir. Similarly structured compounds and derivative second generation integrase strand transfer inhibitors, such as elvitegravir and dolutegravir, are now in various stages of clinical development. Furthermore, other mechanisms aimed at the inhibition of viral integration are being explored in numerous preclinical studies, which include inhibition of 3' processing and chromatin targeting. The development of new clinically useful compounds will be aided by the characterization of the retroviral intasome crystal structure. This review considers the history of the clinical development of HIV integrase inhibitors, the development of antiviral drug resistance and the need for new antiviral compounds

A review of the frequencies of Plasmodium falciparum Kelch 13 artemisinin resistance mutations in Africa.

Artemisinin resistance (AR) emerged in South East Asia 13 years ago and the identification of the resistance conferring molecular marker, Plasmodium falciparum Kelch 13 (Pfk13), 7 years ago has provided an invaluable tool for monitoring AR in malaria endemic countries. Molecular Pfk13 surveillance revealed the resistance foci in the Greater Mekong Subregion, an independent emergence in Guyana, South America, and a low frequency of mutations in Africa. The recent identification of the R561H Pfk13 AR associated mutation in Tanzania, Uganda and in Rwanda, where it has been associated with delayed parasite clearance, should be a concern for the continent. In this review, we provide a summary of Pfk13 resistance associated propeller domain mutation frequencies across Africa from 2012 to 2020, to examine how many other countries have identified these mutations. Only four African countries reported a recent identification of the M476I, P553L, R561H, P574L, C580Y and A675V Pfk13 mutations at low frequencies and with no reports of clinical treatment failure, except for Rwanda. These mutations present a threat to malaria control across the continent, since the greatest burden of malaria remains in Africa. A rise in the frequency of these mutations and their spread would reverse the gains made in the reduction of malaria over the last 20 years, given the lack of new antimalarial treatments in the event artemisinin-based combination therapies fail. The review highlights the frequency of Pfk13 propeller domain mutations across Africa, providing an up-to-date perspective of Pfk13 mutations, and appeals for an urgent and concerted effort to monitoring antimalarial resistance markers in Africa and the efficacy of antimalarials by re-establishing sentinel surveillance systems

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa

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