On a drug-resistant malaria model with susceptible individuals without access to basic amenities

In this paper, a deterministic malaria transmission model in the presence of a drug-resistant strain is investigated. The model is studied using stability theory of differential equations, optimal control, and computer simulation. The threshold condition for disease-free equilibrium is found to be locally asymptotically stable and can only be achieved in the absence of a drug-resistant strain in the population. The existence of multiple endemic equilibria is also established. Both the Sensitivity Index (SI) of the model parameters and the Incremental Cost-Effectiveness Ratio (ICER) for all possible combinations of the disease-control measures are determined. Our results revealed among others that the most cost-effective strategy for drug-resistant malaria control is the combination of the provision of basic amenities (such as access to clean water, electricity, good roads, health care, and education) and treatment of infective individuals. Therefore, more efforts from policy-makers on the provisions of basic amenities and treatment of infectives would go a long way to combat the malaria epidemic.     

Tiliroside,a dietary glycosidic flavonoid,inhibits TRAF-6/NF-κB/p38-mediated neuroinflammation in activated BV2 microglia

Background

Tiliroside is a dietary glycosidic flavonoid which has shown in vivo anti-inflammatory activity. This study is aimed at evaluating the effect of tiliroside on neuroinflammation in BV2 microglia, and to identify its molecular targets of anti-neuroinflammatory action.

Methods

BV2 cells were stimulated with LPS + IFNγ in the presence or absence of tiliroside. TNFα, IL-6, nitrite and PGE₂ production was determined with ELISA, Griess assay and enzyme immunoassay, respectively. iNOS, COX-2, phospho-p65, phospho-IκBα, phospho-IKKα, phospho-p38, phospho-MK2, phosopho-MKK3/6 and TRAF-6 were determined by western blot analysis. NF-κB activity was also investigated using a reporter gene assay in HEK293 cells. LPS-induced microglia ROS production was tested using the DCFDA method, while HO-1 and Nrf2 activation was determined with western blot.

Results

Tiliroside significantly suppressed TNFα, IL-6, nitrite and PGE₂ production, as well as iNOS and COX-2 protein expression from LPS + IFNγ-activated BV2 microglia. Further mechanistic studies showed that tiliroside inhibited neuroinflammation by targeting important steps in the NF-κB and p38 signalling in LPS + IFNγ-activated BV2 cells. This compound also inhibited LPS-induced TRAF-6 protein expression in BV2 cells. Antioxidant activity of tiliroside in BV2 cells was demonstrated through attenuation of LPS + IFNγ-induced ROS production and activation of HO-1/Nrf2 antioxidant system.

Conclusions

Tiliroside inhibits neuroinflammation in BV2 microglia through a mechanism involving TRAF-6-mediated activation of NF-κB and p38 MAPK signalling pathways. These activities are possibly due, in part, to the antioxidant property of this compound.

General Significance

Tiliroside is a potential novel natural compound for inhibiting neuroinflammation in neurodegenerative disorders.     

Perceptions of doctors to adverse drug reaction reporting in a teaching hospital in Lagos, Nigeria

Background  

Spontaneous adverse drug reaction (ADR) reporting is the cornerstone of pharmacovigilance. ADR reporting with Yellow Cards has tremendously improved pharmacovigilance of drugs in many developed countries and its use is advocated by the World Health Organization (WHO). This study was aimed at investigating the knowledge and attitude of doctors in a teaching hospital in Lagos, Nigeria on spontaneous ADR reporting and to suggest possible ways of improving this method of reporting.