CYTOTOXIC EFFECTS OF ALBIZIA ZYGIA (DC) J. F. MACBR, A GHANAIAN MEDICINAL PLANT, AGAINST HUMAN T-LYMPHOBLAST-LIKE LEUKEMIA, PROSTATE AND BREAST CANCER CELL LINES

Objective: The objectives of this study were to investigate the cytotoxic effects of extracts and fractions of Albizia zygia roots (AZR) on human T-lymphoblast-like leukemia (Jurkat), prostate cancer (LNCap) and breast cancer (MCF-7) cells and the apoptotic effect in Jurkat cells.Methods: Aqueous and hydroethanolic extracts were prepared and tested for cytotoxic effects on the cell lines using the tetrazolium-based colorimetric assay. Apoptosis induction was determined by DNA fragmentation, cell morphological changes, flow cytometric and mitochondrial membrane potential assays.Results: Both aqueous and hydroethanolic extracts were more cytotoxic to Jurkat cells than the other cell lines, with selective index (SI) values of 104.4 and 86.6, respectively. The SI values of the extracts on LNCap cells were 9.0 and 35.4, respectively. Some of the fractions were non-cytotoxic. Nevertheless petroleum ether fraction was cytotoxic towards MCF-7 cells with SI value of 2.4. The hydroethanolic extract exhibited apoptosis via induction of DNA fragmentation in Jurkat cells. Cell morphological changes were consistent with the extract-mediated cytotoxicity and DNA fragmentation. Flow cytometric and mitochondrial membrane potential assays also showed significant apoptotic induction confirming apoptosis by the AZR extract.Conclusion: This study has shown that AZR possesses anticancer activity by demonstrating a high selective toxicity against Jurkat cells. Furthermore, the hydroethanolic extract induced apoptosis in the Jurkat cells. Albizia zygia roots may be a source of novel compounds for the development of new anti-cancer agents.Keywords: Albizia zygia, Cancer cells, Cytotoxicity, Apoptosi

Challenges and perceptions of implementing mass testing, treatment and tracking in malaria control: a qualitative study in Pakro sub-district of Ghana.

BACKGROUND: Malaria remains endemic in Ghana despite several interventions. Studies have demonstrated very high levels of asymptomatic malaria parasitaemia in both under-five and school-age children. Mass testing, treatment and tracking (MTTT) of malaria in communities is being proposed for implementation with the argument that it can reduce parasite load, amplify gains from the other control interventions and consequently lead to elimination. However, challenges associated with implementing MTTT such as feasibility, levels of coverage to be achieved for effectiveness, community perceptions and cost implications need to be clearly understood. This qualitative study was therefore conducted in an area with on-going MTTT to assess community and health workers' perceptions about feasibility of scale-up and effectiveness to guide scale-up decisions. METHODS: This qualitative study employed purposive sampling to select the study participants. Ten focus group discussions (FGDs) were conducted in seven communities; eight with community members (n = 80) and two with health workers (n = 14). In addition, two in-depth interviews (IDI) were conducted, one with a Physician Assistant and another with a Laboratory Technician at the health facility. All interviews were recorded, transcribed, translated and analyzed using QSR NVivo 12. RESULTS: Both health workers and community members expressed positive perceptions about the feasibility of implementation and effectiveness of MTTT as an intervention that could reduce the burden of malaria in the community. MTTT implementation was perceived to have increased sensitisation about malaria, reduced the incidence of malaria, reduced household expenditure on malaria and alleviated the need to travel long distances for healthcare. Key challenges to implementation were doubts about the expertise of trained Community-Based Health Volunteers (CBHVs) to diagnose and treat malaria appropriately, side effects of Artemisinin-based Combination Therapies (ACTs) and misconceptions that CBHVs could infect children with epilepsy. CONCLUSION: The study demonstrated that MTTT was perceived to be effective in reducing malaria incidence and related hospital visits in participating communities. MTTT was deemed useful in breaking financial and geographical barriers to accessing healthcare. The interventions were feasible and acceptable to community members, despite observed challenges to implementation such as concerns about CBHVs' knowledge and skills and reduced revenue from internally generated funds (IGF) of the health facility

Prevalence of asymptomatic malaria parasitaemia following mass testing and treatment in Pakro sub-district of Ghana.

BACKGROUND: Global efforts to scale-up malaria control interventions are gaining steam. These include the use of Long-Lasting Insecticide Nets, Indoor Residual Spraying, Intermittent Preventive Treatment and Test, Treat and Track. Despite these, the drive for malaria elimination is far from being realistic in endemic communities in Africa. This is partly due to the fact that asymptomatic parasite carriage, not specifically targeted by most interventions, remains the bedrock that fuels transmission. This has led to mass testing, treatment and tracking (MTTT) as an alternative strategy to target asymptomatic individuals. We report the impact of MTTT on the prevalence of asymptomatic malaria parasitaemia over a one-year period in Ghana, hypothesizing that implementing MTTT could reduce the rate of asymptomatic parasitaemia. METHODS: A population of about 5000 individuals in seven communities in the Pakro sub-district of Ghana participated in this study. A register was developed for each community following a census. MTTT engaged trained community-based health volunteers who conducted house-to-house testing using RDTs every 4 months and treated positive cases with Artemisinin-based Combination Therapy. Between interventions, community-based management of malaria was implemented for symptomatic cases. RESULTS: MTTT Coverage was 98.8% in July 2017 and 79.3% in July 2018. Of those tested, asymptomatic infection with malaria parasites reduced from 36.3% (1795/4941) in July 2017 to 32.9% (1303/3966) in July 2018 (p = 0.001). Prevalence of asymptomatic parasitaemia among children under 15 years declined from 52.6% (1043/1984) in July 2017 to 47.5% (820/1728) in July 2018 (p = 0.002). Implementing MTTT significantly reduced asymptomatic parasitaemia by 24% from July 2017 to July 2018 after adjusting for age, ITN use and axillary temperature (OR = 0.76, CI = 0.67, 0.85 p ≤ 0.001). CONCLUSION: This study has demonstrated that implementing MTTT is feasible and could reduce the prevalence of asymptomatic malaria parasitaemia in children under 15 years of age. Furthermore, the use of community-based health volunteers could ensure high coverage at lower cost of implementation

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Flavonoid-Rich Extract of Dissotis rotundifolia Whole Plant Protects against Ethanol-Induced Gastric Mucosal Damage

Dissotis rotundifolia is a plant in the family Melastomataceae. The methanolic extract of the whole plant is reported to be rich in C-glycosylflavones such as vitexin and orientin. Though there are several reports on the ethnomedicinal use of this plant extract in stomach ulcers, experimental-based data is unavailable. The drive for carrying out this research was to obtain data on the possible ameliorative effect of the whole plant extract of Dissotis rotundifolia (DRE) in gastric ulcerations induced by ethanol in Sprague Dawley (SD) rats. SD rats were pretreated with 100, 300, and 500 mg/kg of DRE for 14 days after which an ulcerogen-ethanol was administered. Gross examinations of the stomach lining and histological analysis of gastric lesions were carried out coupled with an assessment of the antioxidant activity of gastric mucosa using MDA, GSH, CAT, and SOD as indicators. The data suggested a significant attenuation in gastric mucosal damage in DRE-pretreated ethanol-induced gastric ulcer reflected in the antioxidant status. There was also a reduction or absence of hemorrhage, edema, and leucocytes infiltration in DRE-treated groups compared to the negative control group. DRE conserved glutathione (GSH) levels, reduced malondialdehyde (MDA) levels, and enhanced catalase (CAT) and superoxide dismutase (SOD) enzyme levels. The present study shows that DRE possess protective effects against ethanol-induced ulcer damage in the stomach of rats, which could be attributed to its antioxidant activity

In vivo assessment of the toxic potential of Dissotis rotundifolia whole plant extract in Sprague–Dawley rats

Objective: To assess the toxic potential of Dissotis rotundifolia (D. rotundifolia) whole plant extract in Spraque–Dawley rats within a 2-week period of administration. Methods: Methanolic extract of D. rotundifolia was administered orally once daily at dose levels of 0, 100, 300 and 1000 mg/kg body weight for 14 days. Toxicity was assessed using mortality, clinical signs, body and organ weights, hematological indices, serum chemistry parameters and histopathological analyses. Results: There were no treatment-related mortalities or differences in clinical signs, hematology and serum biochemistry. This was confirmed by micrographs obtained from histopathological analysis. Conclusions: The results obtained from the sub-acute toxicological assessment of D. rotundifolia extract suggest that the extract is non-toxic at doses up to 1000 mg/kg/day administered for a period of 14 days

The Ethnopharmacological and Nutraceutical Relevance of Launaea taraxacifolia (Willd.) Amin ex C. Jeffrey

Launaea taraxacifolia (Willd.) Amin ex C. Jeffrey is a herb found mostly in tropical Africa. The plant, commonly found in West Africa, is used in the management of many diseases including cardiovascular, respiratory, haematological, endocrine, and metabolic diseases in Ghana, Nigeria, Benin, Serra Leone, and Senegal. This piece provides comprehensive and updated information on the traditional uses, phytochemical constituents, and pharmacological and toxicological information available on Launaea taraxacifolia to support its medicinal uses and also unearth knowledge gaps for future studies. An electronic literature search using search engines, namely, Google Scholar, ScienceDirect, and PubMed, was carried out to obtain information on the plant. Both common and scientific names of the plant were used as keywords for the search process. This paper captured information on Launaea taraxacifolia from 1985 to 2018. The search revealed that the leaves of the plant possess nutritional/pharmacological effects on diseases such as diabetes mellitus, hypertension, cancer, malaria, bacterial infections, and arthritis. The leaf has been shown to be a rich source of phytoconstituents such as flavonoids, phenolic acids, tannins, alkaloids, glycosides, coumarins, triterpenoids, ascorbic acid, lycopene, and β-carotene. Also, isolated phytoconstituents as well as the safety profile of the plant have been documented. This review on Launaea taraxacifolia has provided a one-stop documentation of information in support of the several purported ethnopharmacological uses of the plant. It also reveals information gaps such as the need to research into its pharmacokinetics, interactions with drugs of importance, and its development into a plant-based drug in order to expand its clinical use