In Silico Simulation of Corticosteroids Effect on an NFkB- Dependent Physicochemical Model of Systemic Inflammation

During the onset of an inflammatory response signaling pathways are activated for "translating" extracellular signals into intracellular responses converging to the activation of nuclear factor (NF)-kB, a central transcription factor in driving the inflammatory response. An inadequate control of its transcriptional activity is associated with the culmination of a hyper-inflammatory response making it a desired therapeutic target. Predicated upon the nature of the response, a systems level analysis might provide rational leads for the development of strategies that promote the resolution of the response.A physicochemical host response model is proposed to integrate biological information in the form of kinetic rules and signaling cascades with pharmacokinetic models of drug action for the modulation of the response. The unifying hypothesis is that the response is triggered by the activation of the NFkB signaling module and corticosteroids serve as a template for assessing anti-inflammatory strategies. The proposed in silico model is evaluated through its ability to predict and modulate uncontrolled responses. The pre-exposure of the system to hypercortisolemia, i.e. 6 hr before or simultaneously with the infectious challenge "reprograms" the dynamics of the host towards a balanced inflammatory response. However, if such an intervention occurs long before the inflammatory insult a symptomatic effect is observed instead of a protective relief while a steroid infusion after inducing inflammation requires much higher drug doses.We propose a reversed engineered inflammation model that seeks to describe how the system responds to a multitude of external signals. Timing of intervention and dosage regimes appears to be key determinants for the protective or symptomatic effect of exogenous corticosteroids. Such results lie in qualitative agreement with in vivo human studies exposed both to LPS and corticosteroids under various time intervals thus improving our understanding of how interacting modules generate a behavior

Experience of initiating collaboration of traditional healers in managing HIV and AIDS in Tanzania

RefereedCollaboration between traditional healers and biomedical practitioners is now being accepted by many African countries south of the Sahara because of the increasing problem of HIV/AIDS. The key problem, however, is how to initiate collaboration between two health systems which differ in theory of disease causation and management. This paper presents findings on experience learned by initiation of collaboration between traditional healers and the Institute of Traditional Medicine in Arusha and Dar-es-Salaam Municipalities, Tanzania where 132 and 60 traditional healers respectively were interviewed. Of these 110 traditional healers claimed to be treating HIV/AIDS. The objective of the study was to initiate sustainable collaboration with traditional healers in managing HIV/AIDS. Consultative meetings with leaders of traditional healers' associations and government officials were held, followed by surveys at respective traditional healers' "vilinge" (traditional clinics). The findings were analysed using both qualitative and quantitative methods. The findings showed that influential people and leaders of traditional healers' association appeared to be gatekeepers to access potential good healers in the two study areas. After consultative meetings these leaders showed to be willing to collaborate; and opened doors to other traditional healers, who too were willing to collaborate with the Institute of Traditional Medicine in managing HIV/AIDS patients. Seventy five percent of traditional healers who claimed to be treating HIV/AIDS knew some HIV/AIDS symptoms; and some traditional healers attempted to manage these symptoms. Even though, they were willing to collaborate with the Institute of Traditional Medicine there were nevertheless some reservations based on questions surrounding sharing from collaboration. The reality of past experiences of mistreatment of traditional healers in the colonial period informed these reservations. General findings suggest that initiating collaboration is not as easy as it appears to be from the literature, if it is to be meaningful; and thus we are calling for appropriate strategies to access potential healers targeted for any study designed with sustainability in mind.Tanzania HIV/AIDS Commissio