22 resultados para CONNECTIVITY DISTRIBUTION
Resumo:
The aim of the current study is to examine the influence of the channel external environment on power, and the effect of power on the distribution network structure within the People’s Republic of China. Throughout the study a dual research process was applied. The theory was constructed by elaborating the main theoretical premises of the study, the channel power theories, the political economy framework and the distribution network structure, but these marketing channel concepts were expanded with other perspectives from other disciplines. The main method applied was a survey conducted among 164 Chinese retailers, complemented by interviews, photographs, observations and census data from the field. This multi-method approach enabled not only to validate and triangulate the quantitative results, but to uncover serendipitous findings as well. The theoretical contribution of the current study to the theory of marketing channels power is the different view it takes on power. First, earlier power studies have taken the producer perspective, whereas the current study also includes a distributor perspective to the discussion. Second, many power studies have dealt with strongly dependent relationships, whereas the current study examines loosely dependent relationships. Power is dependent on unequal distribution of resources rather than based on high dependency. The benefit of this view is in realising that power resources and power strategies are separate concepts. The empirical material of the current study confirmed that at least some resources were significantly related to power strategies. The study showed that the dimension resources composed of technology, know-how and knowledge, managerial freedom and reputation was significantly related to non-coercive power. Third, the notion of different outcomes of power is a contribution of this study to the channels power theory even though not confirmed by the empirical results. Fourth, it was proposed that channel external environment other than the resources would also contribute to the channel power. These propositions were partially supported thus providing only partial contribution to the channel power theory. Finally, power was equally distributed among the different types of actors. The findings from the qualitative data suggest that different types of retailers can be classified according to the meaning the actors put into their business. Some are more business oriented, for others retailing is the only way to earn a living. The findings also suggest that in some actors both retailing and wholesaling functions emerge, and this has implications for the marketing channels structure.
Resumo:
The blood-brain barrier (BBB) is a unique barrier that strictly regulates the entry of endogenous substrates and xenobiotics into the brain. This is due to its tight junctions and the array of transporters and metabolic enzymes that are expressed. The determination of brain concentrations in vivo is difficult, laborious and expensive which means that there is interest in developing predictive tools of brain distribution. Predicting brain concentrations is important even in early drug development to ensure efficacy of central nervous system (CNS) targeted drugs and safety of non-CNS drugs. The literature review covers the most common current in vitro, in vivo and in silico methods of studying transport into the brain, concentrating on transporter effects. The consequences of efflux mediated by p-glycoprotein, the most widely characterized transporter expressed at the BBB, is also discussed. The aim of the experimental study was to build a pharmacokinetic (PK) model to describe p-glycoprotein substrate drug concentrations in the brain using commonly measured in vivo parameters of brain distribution. The possibility of replacing in vivo parameter values with their in vitro counterparts was also studied. All data for the study was taken from the literature. A simple 2-compartment PK model was built using the Stella™ software. Brain concentrations of morphine, loperamide and quinidine were simulated and compared with published studies. Correlation of in vitro measured efflux ratio (ER) from different studies was evaluated in addition to studying correlation between in vitro and in vivo measured ER. A Stella™ model was also constructed to simulate an in vitro transcellular monolayer experiment, to study the sensitivity of measured ER to changes in passive permeability and Michaelis-Menten kinetic parameter values. Interspecies differences in rats and mice were investigated with regards to brain permeability and drug binding in brain tissue. Although the PK brain model was able to capture the concentration-time profiles for all 3 compounds in both brain and plasma and performed fairly well for morphine, for quinidine it underestimated and for loperamide it overestimated brain concentrations. Because the ratio of concentrations in brain and blood is dependent on the ER, it is suggested that the variable values cited for this parameter and its inaccuracy could be one explanation for the failure of predictions. Validation of the model with more compounds is needed to draw further conclusions. In vitro ER showed variable correlation between studies, indicating variability due to experimental factors such as test concentration, but overall differences were small. Good correlation between in vitro and in vivo ER at low concentrations supports the possibility of using of in vitro ER in the PK model. The in vitro simulation illustrated that in the simulation setting, efflux is significant only with low passive permeability, which highlights the fact that the cell model used to measure ER must have low enough paracellular permeability to correctly mimic the in vivo situation.