Inhibition of human glutathione transferases by multidrug resistance chemomodulators in vitro

Reversal of the drug-resistance phenotype in cancer cells usually involves the use of a chemomodulator that inhibits the function of a resistance-related protein. The aim of this study was to investigate the effects of MDR chemomodulators on human recombinant glutathione S-transferase (GSTs) activity. IC₅₀ values for 15 MDR chemomodulators were determined using 1-chloro-dinitrobenzene (CDNB), cumene hydroproxide (CuOOH) and anticancer drugs as substrates. GSTs A1, P1 and M1 were inhibited by O⁶-benzylguanine (IC₅₀s around 30 μM), GST P1-1 by sulphinpyrazone (IC₅₀ = 66 μM), GST A1-1 by sulphasalazine, and camptothecin (34 and 74 μM respectively), and GST M1-1 by sulphasalazine, camptothecin and indomethacin (0.3, 29 and 30 μM respectively) using CDNB as a substrate. When ethacrynic acid (for GST P1-1), CuOOH (for A1-1) and 1,3-bis (2-chloroethyl)-1-nitrosourea (for GST M1-1) were used as substrates, these compounds did not significantly inhibit the GST isoforms. However, progesterone was a potent inhibitor of GST P1-1 (IC₅₀ = 1.4 μM) with ethacrynic acid as substrate. These results suggest that the target of chemomodulators in vivo could be a specific resistance-related protein.     

Effects of exotic guava (Psidium guajava L.) invasion on soil properties in Limpopo,South Africa

Many studies in South Africa have examined the impacts of alien plants on ecosystems, but none have assessed the impact of guava (Psidium guajava L.) invasion on soil properties. In this study, soils underneath guava-invaded sites were assessed to determine if they had different soil physico-chemical properties (pH, P, C, N, Na, K, Ca, Mg, moisture, penetration resistance, infiltration and water repellency) as compared to soils underneath uninvaded sites. Comparisons were made from three different sites over three autumn months. Results show that soil pH was significantly (p < 0.005) higher underneath uninvaded than guava-invaded sites. Soil P was three times higher underneath guava-invaded as compared to invaded sites. The soils collected underneath guava-invaded sites had a significantly (p < 0.001) higher moisture content and were less compact but more repellent than soils from the uninvaded sites. Infiltration rate was significantly (p < 0.001) higher in the uninvaded than the guava-invaded sites. The study concludes that guava invasion alters some soil properties, thus creating favourable conditions for its growth and making it potentially more invasive. From a management standpoint, guava removal is encouraged; however, given guava's socio-economic importance more research on cost and benefits is required.     

Assessing,with limited resources,the ecological outcomes of wetland restoration: a South African case

Resources for evaluating the ecological outcomes of ecosystem restoration projects are often limited, especially within government‐funded programs. In order to rapidly assess the ecological outcomes of wetland restoration, an improved approach has been developed, which was applied in the assessment of the ecological outcomes at nine restoration sites of South Africa's Working for Wetlands program. The sites encompass a diversity of restoration problems and land use contexts. The approach begins by distinguishing hydrogeomorphic (HGM) units, for which ecological condition is assessed and reported for hydrology, geomorphology, and vegetation pre‐ and post‐restoration. These three components are closely linked but, as demonstrated at some of the sites, may respond differentially to restoration interventions. For most HGM units, overall ecological condition was improved by between 10 and 30%, with the greatest contribution of restoration generally being to the hydrology component. Having determined the integrity and costs of the interventions, cost‐effectiveness is then reported in South African Rands per hectare equivalent restored, which was found to vary by more than an order of magnitude across the HGM units assessed. Cost‐effectiveness must be interpreted in the light of the long‐term integrity of the interventions, the site's landscape context, and the contribution of restoration to ecosystem services provision. Some sites may be considerably less cost‐effective than others, but the cost may nonetheless be justified if the sites make key contributions to ecosystem services provision. The study was conducted in the context of a formative evaluation and the findings are envisaged to improve wetland restoration practice.     

From heroin epidemics to methamphetamine epidemics: Modelling substance abuse in a South African province

The global rise in the use of methamphetamine has been documented to have reached epidemic proportions. Researchers have focussed on the social implications of the epidemic. A typical drug use cycle consists of concealed drugs use after initiation, addiction, treatment-recovery-relapse cycle, whose dynamics are not well understood. The model by White and Comiskey [41], on heroin epidemics, treatment and ODE modelling, is modified to model the dynamics of methamphetamine use in a South African province. The analysis of the model is presented in terms of the methamphetamine epidemic threshold R₀. It is shown that the model has multiple equilibria and using the center manifold theory, the model exhibits the phenomenon of backward bifurcation where a stable drug free equilibrium co-exists with a stable drug persistent equilibrium for a certain defined range of R₀. The stabilities of the model equilibria are ascertained and persistence conditions established. Furthermore, numerical simulations are performed; these include fitting the model to the available data on the number of patients with methamphetamine problems. The implications of the results to drug policy, treatment and prevention are discussed.     

Modelling HIV/AIDS in the presence of an HIV testing and screening campaign

Preventing and managing the HIV/AIDS epidemic in South Africa will dominate the next decade and beyond. Reduction of new HIV infections by implementing a comprehensive national HIV prevention programme at a sufficient scale to have real impact remains a priority. In this paper, a deterministic HIV/AIDS model that incorporates condom use, screening through HIV counseling and testing (HCT), regular testing and treatment as control strategies is proposed with the objective of quantifying the effectiveness of HCT in preventing new infections and predicting the long-term dynamics of the epidemic. It is found that a backward bifurcation occurs if the rate of screening is below a certain threshold, suggesting that the classical requirement for the basic reproduction number to be below unity though necessary, is not sufficient for disease control in this case. The global stabilities of the equilibria under certain conditions are determined in terms of the model reproduction number R₀. Numerical simulations are performed and the model is fitted to data on HIV prevalence in South Africa. The effects of changes in some key epidemiological parameters are investigated. Projections are made to predict the long-term dynamics of the disease. The epidemiological implications of such projections on public health planning and management are discussed.     

Recovery of microbial diversity and activity during bioremediation following chemical oxidation of diesel contaminated soils

To improve the coupling of in situ chemical oxidation and in situ bioremediation, a systematic analysis was performed of the effect of chemical oxidation with Fenton's reagent, modified Fenton's reagent, permanganate, or persulfate, on microbial diversity and activity during 8 weeks of incubation in two diesel-contaminated soils (peat and fill). Chemical oxidant and soil type affected the microbial community diversity and biodegradation activity; however, this was only observed following treatment with Fenton's reagent and modified Fenton's reagent, and in the biotic control without oxidation. Differences in the highest overall removal efficiencies of 69 % for peat (biotic control) and 59 % for fill (Fenton's reagent) were partially explained by changes in contaminant soil properties upon oxidation. Molecular analysis of 16S rRNA and alkane monooxygenase (alkB) gene abundances indicated that oxidation with Fenton's reagent and modified Fenton's reagent negatively affected microbial abundance. However, regeneration occurred, and final relative alkB abundances were 1–2 orders of magnitude higher in chemically treated microcosms than in the biotic control. 16S rRNA gene fragment fingerprinting with DGGE and prominent band sequencing illuminated microbial community composition and diversity differences between treatments and identified a variety of phylotypes within Alpha-, Beta-, and Gammaproteobacteria. Understanding microbial community dynamics during coupled chemical oxidation and bioremediation is integral to improved biphasic field application.     

Assessing the effects of native and alien plant ash on mosquito abundance

Plant invasions have been linked to displacement of native vegetation and altering of fire regimes and might influence vector mosquito populations by altering habitats or nutrient inputs. Whereas wildfire effects on terrestrial ecosystems are relatively well‐studied, ash depositions into aquatic ecosystems and effects on semi‐aquatic taxa such as mosquitoes have remained overlooked. Here, we investigated mosquito colonization in water treated with ash from native plants [quinine tree (Rauvolfia caffra), Transvaal milk plum (Englerophytum magalismontanum), apple leaf (Philenoptera violacea)] and invasive alien plants [i.e., lantana (Lantana camara), guava (Psidium guajava), red river gum (Eucalyptus camaldulensis)] in containers at two ash concentrations (i.e., 1, 2 g/L). Overall, there was no statistically clear difference in colonization between ash from native and alien species. We recorded colonization by two mosquito genera (Culex spp. and Anopheles spp.), with Culex generally much more abundant than Anopheles. Few differences were identified among the plants, with statistically clear effects of ash type and concentration on larval and pupal stages. High Culex egg and larval abundances were shown in lantana and apple leaf treatments compared to controls, and milkplum versus controls for pupae of both genera. Further research is required to elucidate the influence of nutrient inputs from different ash species on vector mosquito population dynamics.     

Inhibition of human glutathione transferases by multidrug resistance chemomodulators in vitro

Reversal of the drug-resistance phenotype in cancer cells usually involves the use of a chemomodulator that inhibits the function of a resistance-related protein. The aim of this study was to investigate the effects of MDR chemomodulators on human recombinant glutathione S-transferase (GSTs) activity. IC50 values for 15 MDR chemomodulators were determined using 1-chloro-dinitrobenzene (CDNB), cumene hydroproxide (CuOOH) and anticancer drugs as substrates. GSTs A1, P1 and M1 were inhibited by O6-benzylguanine (IC50s around 30 microM), GST P1-1 by sulphinpyrazone (IC50 = 66 microM), GST Al-1 by sulphasalazine, and camptothecin (34 and 74 microM respectively), and GST M1-1 by sulphasalazine, camptothecin and indomethacin (0.3, 29 and 30 microM respectively) using CDNB as a substrate. When ethacrynic acid (for GST P1-1), CuOOH (for A1-1) and 1,3-bis (2-chloroethyl)-1-nitrosourea (for GST M1-1) were used as substrates, these compounds did not significantly inhibit the GST isoforms. However, progesterone was a potent inhibitor of GST P1-1 (IC50 = 1.4 microM) with ethacrynic acid as substrate. These results suggest that the target of chemomodulators in vivo could be a specific resistance-related protein.     

Modelling Hospitalization,Home-Based Care,and Individual Withdrawal for People Living with HIV/AIDS in High Prevalence Settings

In sub-Saharan Africa, the model of care for people who are living with HIV/AIDS has changed from hospital care to home-based care. In this paper, a mathematical model describing the dynamics of HIV transmission, hospitalization, and home-based care is constructed and analysed. The model reproduction number R _e is determined and discussed. The equilibria are determined and analysed in terms of R _e . It is shown that if R _e <1, the disease free equilibrium is both locally and globally asymptotically stable. The model has a unique endemic equilibrium and is locally asymptotically stable whenever R _e >1. Five cases arise in the discussion of R _e pertaining to intervention strategies. Numerical simulations are done to compare the impact of each strategy on the dynamics of HIV/AIDS. The model is fitted to the prevalence data estimates from UNAIDS on Zimbabwe. The implications of some key epidemiological parameters are investigated numerically. Projections are made to determine the possible long term trends of the prevalence of HIV in Zimbabwe.     

Activity concentrations of <Superscript>226</Superscript>Ra, <Superscript>228</Superscript>Th,and <Superscript>40</Superscript>K in different food crops from a high background radiation area in Bitsichi,Jos Plateau,Nigeria

One of the three goals of the United Nations for sustainable food security is to ensure that all people have access to sufficient, nutritionally adequate, and safe food. Decades of tin mining in the Bitsichi area of the Jos Plateau, Nigeria, have left a legacy of polluted water supplies, impoverished agricultural land, and soil containing abnormally high levels of naturally occurring radioactive elements. In order to ascertain the radiological food safety of the population, different crops that constitute the major food nutritive requirements were collected directly across farmlands in the area. The activity concentrations of ²²⁶Ra, ²²⁸Th, and ⁴⁰K were determined in the food and soil samples using γ-ray spectrometry. Additionally, in situ gamma dose rate measurements were performed on the farms using a pre-calibrated survey meter. The corresponding activity concentrations in the food crops ranged from below detection limit (BDL) to 684.5 Bq kg⁻¹ for ⁴⁰K, from BDL to 83.5 Bq kg⁻¹ for ²²⁶Ra, and from BDL to 89.8 Bq kg⁻¹ for ²²⁸Th. Activity concentrations of these radionuclides were found to be lower in cereals than in tubers and vegetables. As for the soil samples, activity concentrations of these radionuclides varied from BDL to 166.4 Bq kg⁻¹, from 10.9 to 470.6 Bq kg⁻¹, and from 122.7 to 2,189.5 Bq kg⁻¹ for ⁴⁰K, ²²⁶Ra, and ²²⁸Th, respectively. Average external gamma dose rates were found to vary across the farms from 0.50 ± 0.01 to 1.47 ± 0.04 μSv h⁻¹. Due to past mining activities, the soil radioactivity in the area has been modified and the concentration level of the investigated natural radionuclides in the food crops has also been enhanced. However, the values obtained suggest that the dose from intake of these radionuclides by the food crops is low and that harmful health effects are not expected.