Selected Phytoestrogens Distinguish Roles of ERα Transactivation and Ligand Binding for Anti-Inflammatory Activity.

Estrogen receptor α (ERα) is a ligand-activated transcriptional activator that is also involved vascular inflammation and atherosclerosis. Whether different ligands may affect this activity has not been explored. We screened a panel of phytoestrogens for their role in ERα binding and transcriptional transcription, and correlated the findings to anti-inflammatory activities in vascular endothelial cells stably expressing either a wild-type or mutant form of ERα deficient in its membrane association. Taxifolin and silymarin were "high binders" for ERα ligand binding; quercetin and curcumin were "high activators" for ERα transactivation. Using these phytoestrogens as functional probes, we found, in endothelial cells expressing wild-type ERα, the ERα high activator, but not the ERα high binder, promoted ERα nuclear translocation, estrogen response element (ERE) reporter activity, and the downstream gene expression. In endothelial cells expressing membrane association-deficient mutant ERα, the ERα nuclear translocation was significantly enhanced by taxifolin and silymarin, which still failed to activate ERα. Inflammation response was examined using the systemic or vascular inflammation inducers lipopolysaccharide or oxidized low-density lipoprotein. In both cases, only the ERα high activator inhibited nuclear translocation of nuclear factor κB, JNK, and p38, and the production of inflammatory cytokines IL-1ß and TNFα. We confirm a threshold nuclear accumulation of ERα is necessary for its transactivation. The anti-inflammatory activity of phytoestrogens is highly dependent on ERα transactivation, less so on the ligand binding, and independent of its membrane association. A pre-examination of phytoestrogens for their mode of ERα interaction could facilitate their development as better targeted receptor modifiers.

Designing and implementing interventions to change clinicians' practice in the management of uncomplicated malaria: lessons from Cameroon.

BACKGROUND: Effective case management of uncomplicated malaria is a fundamental pillar of malaria control. Little is known about the various steps in designing interventions to accompany the roll out of rapid diagnostic tests (RDTs) and artemisinin-based combination therapy (ACT). This study documents the process of designing and implementing interventions to change clinicians' practice in the management of uncomplicated malaria. METHODS: A literature review combined with formative quantitative and qualitative research were carried out to determine patterns of malaria diagnosis and treatment and to understand how malaria and its treatment are enacted by clinicians. These findings were used, alongside a comprehensive review of previous interventions, to identify possible strategies for changing the behaviour of clinicians when diagnosing and treating uncomplicated malaria. These strategies were discussed with ministry of health representatives and other stakeholders. Two intervention packages - a basic and an enhanced training were outlined, together with logic model to show how each was hypothesized to increase testing for malaria, improve adherence to test results and increase appropriate use of ACT. The basic training targeted clinicians' knowledge of malaria diagnosis, rapid diagnostic testing and malaria treatment. The enhanced training included additional modules on adapting to change, professionalism and communicating effectively. Modules were delivered using small-group work, card games, drama and role play. Interventions were piloted, adapted and trainers were trained before final implementation. RESULTS: Ninety-six clinicians from 37 health facilities in Bamenda and Yaounde sites attended either 1-day basic or 3-day enhanced training. The trained clinicians then trained 632 of their peers at their health facilities. Evaluation of the training revealed that 68% of participants receiving the basic and 92% of those receiving the enhanced training strongly agreed that it is not appropriate to prescribe anti-malarials to a patient if they have a negative RDT result. CONCLUSION: Formative research was an important first step, and it was valuable to engage stakeholders early in the process. A logic model and literature reviews were useful to identify key elements and mechanisms for behaviour change intervention. An iterative process with feedback loops allowed appropriate development and implementation of the intervention. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01350752.

Impact of natural resources and research on cancer treatment and prevention: A perspective from Cameroon.

Cancer is a significant public health concern and treatment poses a problem and is frequently unsuccessful. As such, continuous efforts in the search for new agents and therapies to improve survival are required. A considerable number of plant extracts and isolated compounds possess significant anti-proliferative or pro-apoptotic effects. The majority of biologically active compounds belong to terpenoids, phenolics and alkaloids. Terpenoid plants such as Hypericum lanceolatum and a few alkaloid plants have been found to be potent anti-parasitic agents but have exhibited poor antimicrobial effects. The screening of medicinal plants for anticancer drugs has provided modern medicine with effective cytotoxic pharmaceuticals. Numerous medicinal plants have traditionally been used for the treatment of various ailments. However, a number of these medicinal plants have not been standardized and their mechanisms of actions are generally unknown. Active drug discovery research using local medicinal plants is ongoing. Some of these plant-derived compounds, including 3,39-dimethoxy-49-O-ß-d-xylopyronosylellagic acid, have been tested for their potential use as anticancer agents. This review discussed the scope and possibility of natural products as anticancer remedy.

Malaria prevalence and treatment of febrile patients at health facilities and medicine retailers in Cameroon.

OBJECTIVE: To investigate the quality of malaria case management in Cameroon 5 years after the adoption of artemisinin-based combination therapy (ACT). Treatment patterns were examined in different types of facility, and the factors associated with being prescribed or receiving an ACT were investigated. METHODS: A cross-sectional cluster survey was conducted among individuals of all ages who left public and private health facilities and medicine retailers in Cameroon and who reported seeking treatment for a fever. Prevalence of malaria was determined by rapid diagnostic tests (RDTs) in consenting patients attending the facilities and medicine retailers. RESULTS: Among the patients, 73% were prescribed or received an antimalarial, and 51% were prescribed or received an ACT. Treatment provided to patients significantly differed by type of facility: 65% of patients at public facilities, 55% of patients at private facilities and 45% of patients at medicine retailers were prescribed or received an ACT (P = 0.023). The odds of a febrile patient being prescribed or receiving an ACT were significantly higher for patients who asked for an ACT (OR = 24.1, P < 0.001), were examined by the health worker (OR = 1.88, P = 0.021), had not previously sought an antimalarial for the illness (OR = 2.29, P = 0.001) and sought treatment at a public (OR = 3.55) or private facility (OR = 1.99, P = 0.003). Malaria was confirmed in 29% of patients and 70% of patients with a negative result were prescribed or received an antimalarial. CONCLUSIONS: Malaria case management could be improved. Symptomatic diagnosis is inefficient because two-thirds of febrile patients do not have malaria. Government plans to extend malaria testing should promote rational use of ACT; though, the introduction of rapid diagnostic testing needs to be accompanied by updated clinical guidelines that provide clear guidance for the treatment of patients with negative test results.