Small chemicals like drugs tend to bind to proteins via noncovalent bonds, e.g. hydrogen bonds, salt bridges or electrostatic interactions. Some chemicals interact with other molecules than the actual target ligand, representing so-called ‘off-target' activities of drugs. Such interactions are a main cause of adverse side effects to drugs and are normally classified as predictable type A reactions. Detailed analysis of drug-induced immune reactions revealed that off-target activities also affect immune receptors, such as highly polymorphic human leukocyte antigens (HLA) or T cell receptors (TCR). Such drug interactions with immune receptors may lead to T cell stimulation, resulting in clinical symptoms of delayed-type hypersensitivity. They are assigned the ‘pharmacological interaction with immune receptors' (p-i) concept. Analysis of p-i has revealed that drugs bind preferentially or exclusively to distinct HLA molecules (p-i HLA) or to distinct TCR (p-i TCR). P-i reactions differ from ‘conventional' off-target drug reactions as the outcome is not due to the effect on the drug-modified cells themselves, but is the consequence of reactive T cells. Hence, the complex and diverse clinical manifestations of delayed-type hypersensitivity are caused by the functional heterogeneity of T cells. In the abacavir model of p-i HLA, the drug binding to HLA may result in alteration of the presenting peptides. More importantly, the drug binding to HLA generates a drug-modified HLA, which stimulates T cells directly, like an allo-HLA. In the sulfamethoxazole model of p-i TCR, responsive T cells likely require costimulation for full T cell activation. These findings may explain the similarity of delayed-type hypersensitivity reactions to graft-versus-host disease, and how systemic viral infections increase the risk of delayed-type hypersensitivity reactions.
Supplementation with fermented milk, containing live special probiotic L. casei DN-114 001, confers an enhanced therapeutic benefit on H. pylori eradication in children with gastritis on triple therapy.
Car dependence is a potent example of an issue that ecological public health should address. The public health community should advocate strongly for effective policies that reduce car use and increase active travel.
a b s t r a c tSome links between transport and health are widely known, such as active travel, physical (in)activity, air pollution and injuries. Others are not as apparent and are much less studied, for example social interactions. This article reviews the evidence that transport impacts on social interactions, and that social interactions impact on health. It is an updated version of part of chapter 5 from Health on the Move 2.There is growing evidence that aspects of transport influence social exclusion, social capital, social cohesion and social networks. Numerous studies have identified associations between these aspects of social interaction and morbidity and mortality. Community severance -where transport infrastructure or the speed or volume of traffic act as a physical or psychological barrier -impacts on individuals' travel, social networks, and the accessibility of goods, services and facilities, and has scope to influence health through a number of routes. With the development of more comprehensive measures, such as of community severance, it is likely that there will be stronger evidence that transport influences health through these pathways.
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