Predictive modelling of a novel anti-adhesion therapy to combat bacterial colonisation of burn wounds

As the development of new classes of antibiotics slows, bacterial resistance to existing antibiotics is becoming an increasing problem. A potential solution is to develop treatment strategies with an alternative mode of action. We consider one such strategy: anti-adhesion therapy. Whereas antibiotics act directly upon bacteria, either killing them or inhibiting their growth, anti-adhesion therapy impedes the binding of bacteria to host cells. This prevents bacteria from deploying their arsenal of virulence mechanisms, while simultaneously rendering them more susceptible to natural and artificial clearance. In this paper, we consider a particular form of anti-adhesion therapy, involving biomimetic multivalent adhesion molecule 7 coupled polystyrene microbeads, which competitively inhibit the binding of bacteria to host cells. We develop a mathematical model, formulated as a system of ordinary differential equations, to describe inhibitor treatment of a Pseudomonas aeruginosa burn wound infection in the rat. Benchmarking our model against in vivo data from an ongoing experimental programme, we use the model to explain bacteria population dynamics and to predict the efficacy of a range of treatment strategies, with the aim of improving treatment outcome. The model consists of two physical compartments: the host cells and the exudate. It is found that, when effective in reducing the bacterial burden, inhibitor treatment operates both by preventing bacteria from binding to the host cells and by reducing the flux of daughter cells from the host cells into the exudate. Our model predicts that inhibitor treatment cannot eliminate the bacterial burden when used in isolation; however, when combined with regular or continuous debridement of the exudate, elimination is theoretically possible. Lastly, we present ways to improve therapeutic efficacy, as predicted by our mathematical model

The Effect of Bacteria on Epidermal Wound Healing

Epidermal wound healing is a complex process that repairs injured tissue. The complexity of this process increases when bacteria are present in a wound; the bacteria interaction determines whether infection sets in. Because of underlying physiological problems infected wounds do not follow the normal healing pattern. In this paper we present a mathematical model of the healing of both infected and uninfected wounds. At the core of our model is an account of the initiation of angiogenesis by macrophage-derived growth factors. We express the model as a system of reaction-diffusion equations, and we present results of computations for a version of the model with one spatial dimension

Trace element behaviour in soils developed along the slopes of Mt. Cameroon, West Africa

A geochemical study of trace elements in soil profiles developed on basaltic parent materials of unknown ages along the slopes of Mt. Cameroon was carried out. The study objectives included vertical description of element dispersion, element mobility and relating element distribution to weathering intensity. Twenty five soil samples from 6 sites (between 30 to 1017 m a.s.l.) were collected and analysed for trace element concentrations by ICP-MS technique. The weathering status of these soils, (derived from chemical weathering indices) indicate that the most weathered profiles are located at higher elevations with lower mean annual precipitation. Higher losses in Cu, Co and Zr in the moderately weathered profiles in the zones of high leaching are linked to the comparatively higher dissolution of Fe-bearing minerals such as magnetite to which resulted in higher Fed/FeT ratios. Organic matter may account for low mobility of Cu and Pb, while for Zn, the Mn-Al system may control Zn retardation at low elevations. Ni and Sr were highly mobilised at all elevations while Pb, Rb and Sr showed evidence of atmospheric deposition. Comparatively higher inputs of dust-derived minerals in the lower elevation could also affect the distribution of TE. Suggestions are therefore made for the existence of an inflection point within this elevational bracket marked by incongruent dissolution of primary silicate minerals (particularly Feminerals)

Polymorphism of the endothelin-1 gene (rs5370) is a potential contributor to sickle cell disease pathophysiology

Sickle cell disease has been shown to demonstrate extensive variability in disease severity among and between individuals, the variability highlighted by differing genetic haplotypes. Despite the abundance of reports of functional significance due to polymorphisms of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) genes, the role of these polymorphisms in mediating sickle cell disease pathophysiology among African Americans is presently unclear. To deconvolute their potential significance among African Americans with sickle cell disease, we examined the genetic diversity and haplotype frequency of eNOS and ET-1 polymorphisms in disease (n = 331) and control (n = 379) groups, with a polymerase–chain reaction restriction fragment length polymorphism assay. We report that genotypic and allelic frequencies of eNOS variants are not significantly different between groups. eNOS homozygote mutants, which had been shown to have clinical significance elsewhere, showed no statistical significance in our study. On the other hand, and contrary to previous report among Africans with sickle cell disease, the endothelin-1 homozygous mutant variant showed significant difference in genotypic (p = 2.84E-12) and allelic frequencies (p = 2.20E-16) between groups. The most common haplotype is the combination of T786C homozygote wild-type variant with homozygote mutant variants of G5665T (ET-1) and Glu298Asp (eNOS). These results show that endothelin-1 (rs5370) polymorphism, rather than endothelial nitric oxide synthase polymorphism might play a significant role in disease severity or individual clinical outcomes among African Americans with sickle cell disease. This would have profound implications for designing and/or advancing personalized care for sickle cell patients and relieving disease complications