Betulinic Acid–Doxorubicin-Drug combination induced apoptotic death via ROS stimulation in a relapsed AML MOLM-13 cell model

In this study, cell death regulation and induction in AML cell line from a relapsed MLL-rearranged cell model (MOLM-13) was investigated with doxorubin (Dox) and betulinic acid (BetA), singly and in combination. CyQUANT Direct® and Annexin V/propidium iodide double staining were used to measure the cytotoxic and cell death induction effects of the compounds, respectively. Reactive oxygen species (ROS) generation was measured using 2′,7′-dichlorofluorescin diacetate staining. Expressions of proteins and genes were examined by Western blot and reverse transcription polymerase chain reaction analysis, respectively. BetA (20 μM) and Dox (1 μM) indicated a synergistic growth inhibitory effect on MOLM-13 cells. The combined drug caused more cells to reside in irreversible late apoptotic stage compared to the single treatments (p < 0.05). Elevation in ROS may be the synergistic mechanism involved in MOLM-13 cell death since ROS can directly disrupt mitochondrial activity. In contrast, in leukaemic U-937 cells, the combination treatments attenuated Dox-induced cell death. Dox and the drug combination selectively reduced (p < 0.05) a recently reported anti-apoptotic Bcl-2 protein isoform p15-20-Bcl-2 in MOLM-13 by our group, without affecting the usually reported p26-Bcl-2-α. Further studies using known inhibitors of apoptosis are required to confirm the potential of Dox-BetA combination to modulate these pathways

Evidence for the outcomes and impact of clinical pharmacy: context of UK hospital pharmacy practice

Objectives: The role of clinical pharmacists in hospitals has evolved and continues to expand. In the UK, outside of a few national policy drivers, there are no agreed priorities, measures or defined outcomes for hospital clinical pharmacy (CP). This paper aims to (1) highlight the need to identify and prioritise specific CP roles, responsibilities and practices that will bring the greatest benefit to patients and health systems and (2) describe systematic weaknesses in current research methodologies for evaluating CP services and propose a different approach. Method: Published reviews of CP services are discussed using the Economic, Clinical and Humanistic Outcomes framework. Recurring themes regarding study methodologies, measurements and outcomes are used to highlight current weaknesses in studies evaluating CP. Results: Published studies aiming to demonstrate the economic, clinical or humanistic outcomes of CP often suffer from poor research design and inconsistencies in interventions, measurements and outcomes. This has caused difficulties in drawing meaningful conclusions regarding CP’s definitive contribution to patient outcomes. Conclusion: There is a need for more research work in National Health Service (NHS) hospitals, employing a different paradigm to address some of the weaknesses of existing research on CP practice. We propose a mixed-methods approach, including qualitative research designs, and with emphasis on cost-consequence analyses for economic evaluations. This approach will provide more meaningful data to inform policy and demonstrate the contribution of hospital CP activities to patient care and the NHS

Substance use during pregnancy: time for policy to catch up with research

The phenomenon of substance abuse during pregnancy has fostered much controversy, specifically regarding treatment vs. punishment. Should the pregnant mother who engages in substance abuse be viewed as a criminal or as someone suffering from an illness requiring appropriate treatment? As it happens, there is a noticeably wide range of responses to this matter in the various states of the United States, ranging from a strictly criminal perspective to one that does emphasize the importance of the mother's treatment. This diversity of dramatically different responses illustrates the failure to establish a uniform policy for the management of this phenomenon. Just as there is lack of consensus among those who favor punishment, the same lack of consensus characterizes those states espousing treatment. Several general policy recommendations are offered here addressing the critical issues. It is hoped that by focusing on these fundamental issues and ultimately detailing statistics, policymakers throughout the United States will consider the course of action that views both pregnant mother and fetus/child as humanely as possible

Adoption of financial innovation in the Ghanaian banking industry

This century has been full of innovations: new technologies, new products, new services and a plethora of new industries have emerged. Yet the call for innovation in business, especially in financial services, has never been more intense. Although research on this topic exists, there is no empirical evidence regarding the critical factors influencing customer adoption of electronic banking innovation in Ghana’s banking industry. The aim of this article is therefore to investigate the factors influencing the adoption of financial innovation in Ghana’s banking industry. Surveys were conducted involving 405 clients of the six major banks in the country. Using logistical regression, the results amongst other things show that innovation attributes such as lack of complexity, compatibility and perceived usefulness provided by financial innovation, increase the likelihood of e-banking adoption. In light of these findings, the study recommends that banks should focus on designing both useful and easy-to-use e-banking products that will attract potential and existing customers.Keywords: e-banking, financial innovation, Ghana, technology, West Afric

Assessment of Water Quality Parameters of Kpeshie Lagoon of Ghana

A study was carried out on the Kpeshi Lagoon to identify the chemical and physical characteristics of the water. A lot of industrial activities are carried out around the Lagoon and it is being gradually turned into a place of refuse damp. Standard methods were used for determining of chemical and physical characteristics of water samples. Trace metal ions were determined by atomic absorption spectrometry. The lagoon recorded mean pH and conductivity values of 6.32&plusmn; 2.20 and 87.31 ms/cm&plusmn;19.14 respectively. Nutrient and organic matter were found to be the most frequent cause of pollution of the lagoon with mean sulphate, nitrate and phosphate concentrations of 11852 mg/l&plusmn;2915.08, 2905.71 mg/l&plusmn;616.52 and 487.14 mg/l&plusmn;257.02 respectively. Iron (Fe) and aluminum (Al) recorded the highest concentration of 13.2 mg/l&plusmn;3.47 and 13.6 mg/l&plusmn; 4.29 respectively in water sample. Fish sample revealed calcium and potassium as having the highest concentration of 15709 mg/kg&plusmn;75.35 and 5999.94 mg/kg&plusmn;87.30 respectively with sodium and aluminum recording 3775.70 mg/kg&plusmn; 24.80 and 708.47mg/kg &plusmn; 4.95 respectively. The results as compared to the WHO guidelines indicate that the Lagoon is highly contaminated.Keywords: Kpeshi lagoon, nutrients, trace metals

Evaluation of the effectiveness of Eladi Keram for the treatment of acne vulgaris: a randomised controlled pilot study

Introduction: Acne is a multifactorial and common skin disease which can significantly affect the quality of life of sufferers. In this study, a topical herbal preparation traditionally used in Ayurvedic medicine was evaluated as a treatment for individuals with acne on their shoulders and backs. Methods: Study participants were randomly assigned either to treatment (Eladi Keram) or vehicle control (coconut oil) groups under double blind conditions and instructed on its daily home application. Standardised lesion counting and acne grading were conducted in accordance with US Food and Drug Administration guidelines and with reference to the Leeds Acne Grading Technique. Participants were assessed for severity of the condition at commencement and on day 28 of treatment. Results: The treatment group showed improvements of 42% (p < 0.005) on the Investigators Global Assessment scale, a 60% (p < 0.05) reduction in inflammatory lesions, a 59% (p < 0.05) reduction in non-inflammatory lesions, and a 59% (p < 0.005) reduction in combined lesion count. The control group showed no statistically significant changes for these criteria. Conclusion: This study is the first reported clinical evaluation of Eladi Keram as a treatment for acne and findings suggest that it could be effective in reducing inflammatory and non-inflammatory lesions, warranting further investigation by means of a larger scale clinical trial

Knowledge on Sexually Transmitted Infections among school-going adolescents in the Sunyani West District of Ghana

The physiological and behavioural characteristics associated with adolescence increase the risk of contracting HIV and other sexually transmitted infections which may have devastating effects on their sexual and reproductive health. The aim of this study was to assess the knowledge of sexually transmitted infections of school going adolescents in the Sunyani West District of Ghana. A cross-sectional study design was used in gathering appropriate survey data from 316 senior high school students. Descriptive and univariate analyses were conducted using STATA version 14.0 software. The age group 16 - 18 years were the majority of respondents. More male than female adolescents knew about all four areas of knowledge as regards sexually transmitted infections. The study showed a statistically significant association (P = 0.001) between level of knowledge of sexually transmitted infections among adolescents and their class/form. Adolescents had good knowledge about sexually transmitted infections despite some misconceptions that could affect their sexual behaviour. Educational levels of students have to be considered in the design of sex education curriculum

Herb-drug interaction: Effect of aqueous extract of Bridelia ferruginea leaves on the pharmacokinetics of metformin

The concurrent use of herbal medicines and orthodox drugs, especially in the treatment and management of chronic ailments, may result in clinically significant herb-drug interactions. Bridelia ferruginea Benth (Euphorbiaceae) is a common medicinal plant with known anti-diabetic properties and has been reported to be taken alongside the orthodox medicine, metformin. The aim of this study was to investigate the effect of aqueous extract of B. ferruginea leaves on the pharmacokinetics of metformin in female Sprague-Dawley rats. Reconstituted freeze dried extract of B. ferruginea leaves (30 mg/kg), and metformin (7 mg/kg) were administered concurrently as a single dose to female Sprague-Dawley rats. Whole blood samples (1 ml) were aseptically withdrawn by tail bleeding at 1, 2, 4, 8, and 24 h after administration of the single dose for pharmacokinetics analyses. Concurrent administration of metformin and B. ferruginea significantly affected (P &lt; 0.05) all the pharmacokinetics parameters of metformin except for the time to attain the maximum concentration (Tmax), which increased but insignificantly. Whereas the area under the curve, maximum whole blood concentration (Cmax) and half-life (T½) of metformin decreased significantly in the presence of B. ferruginea, the elimination rate constant (Kel), clearance (Cl), absorption rate constant (Ka), and volume of distribution (Vd) of metformin increased significantly in the presence of B. ferruginea. Therefore, in clinical practice, patients should be advised on the implication of concurrent administration of metformin and B. ferrruginea

Doxorubicin selectively induces apoptosis through the inhibition of a novel isoform of Bcl‑2 in acute myeloid leukaemia MOLM‑13 cells with reduced Beclin 1 expression

The overexpression of anti-apoptotic Bcl-2 in acute myeloid leukaemia (AML) may contribute to difficulties in eradicating these cells during chemotherapy. In the present study, doxorubicin (Dox) was evaluated for its potential to induce selective apoptotic cell death in AML MOLM-13 cells and to modulate autophagy through Bcl-2 and Beclin 1 protein expression. Annexin V/propidium iodide and 5(6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) flow cytometric analyses were conducted to determine the effects of Dox on cell death and cell proliferation, respectively, following 48 h of co-incubation with AML MOLM-13 or U-937 monocytic cells. The protein expression levels of Bcl-2 and Beclin 1 in untreated and treated cells were quantified by western blot analysis. Dox reduced the viability of MOLM-13 cells partly by inhibiting cell division and inducing cell apoptosis. Dox demonstrated a level of selectivity in its cytotoxicity against MOLM-13 compared to U-937 cells (P<0.05). Dox induced a significant decrease in Beclin 1 protein levels in MOLM-13 cells without significantly affecting the protein levels in U-937 monocytes. A novel Bcl-2 15-20 kDa (p15-20-Bcl-2) isoform was found to be selectively expressed in AML MOLM-13 cells (but absent in the leukaemic cell lines tested, OCI-AML2, CML K562 and U-937). Dox induced a highly significant inhibition of p15-20-Bcl-2 at concentrations of 0.5, 0.75 and 1 µM (P<0.01). However, the usual 26 kDa Bcl-2 (p26-Bcl-2-α) isoform protein expression was not affected by the drug in either the MOLM-13 or U-937 cells. It was thus postulated that Dox exhibited some selectivity by targeting the p15-20-Bcl-2 isoform in MOLM-13 cells and activating Beclin 1 to induce cell death