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The skin is the largest organ of the body. It serves many functions one of which is protection from the outside world, including chemical and microbiological insults. Skin ailments represent one of the most common complaints of patients in medical settings and account for significant loss of productivity in the workplace. Cutaneous toxicity from chemical exposures is responsible for many of these complaints. Skin reactions to chemicals often appear similar, but have many biological causes, including chemical irritation and sensitization (allergies). A primary goal of the cutaneous toxicologist is to predict the potential irritant and/or sensitization potential of chemicals. This chapter summarizes the varied effects that chemicals may have on the skin, including acute and chronic conditions. The chapter also describes the multiple methods to predict potential cutaneous chemical hazards that may be produced in the workplace or via consumer exposure to topical drugs and cosmetics. Important human, animal and in vitro methods to predict a chemical hazard are described.
The skin is the largest organ of the body. It serves many functions one of which is protection from the outside world, including chemical and microbiological insults. Skin ailments represent one of the most common complaints of patients in medical settings and account for significant loss of productivity in the workplace. Cutaneous toxicity from chemical exposures is responsible for many of these complaints. Skin reactions to chemicals often appear similar, but have many biological causes, including chemical irritation and sensitization (allergies). A primary goal of the cutaneous toxicologist is to predict the potential irritant and/or sensitization potential of chemicals. This chapter summarizes the varied effects that chemicals may have on the skin, including acute and chronic conditions. The chapter also describes the multiple methods to predict potential cutaneous chemical hazards that may be produced in the workplace or via consumer exposure to topical drugs and cosmetics. Important human, animal and in vitro methods to predict a chemical hazard are described.
Rationale The cognitive control dilemma describes the necessity to balance two antagonistic modes of attention: stability and flexibility. Stability refers to goal-directed thought, feeling, or action and flexibility refers to the complementary ability to adapt to an ever-changing environment. Their balance is thought to be maintained by neurotransmitters such as dopamine, most likely in a U-shaped rather than linear manner. However, in humans, studies on the stability-flexibility balance using a dopaminergic agent and/or measurement of brain dopamine are scarce. Objective The study aimed to investigate the causal involvement of dopamine in the stability-flexibility balance and the nature of this relationship in humans. Methods Distractibility was assessed as the difference in reaction time (RT) between distractor and non-distractor trials in a visual search task. In a randomized, placebo-controlled, double-blind, crossover study, 65 healthy participants performed the task under placebo and a dopamine precursor (L-DOPA). Using 18F-DOPA-PET, dopamine availability in the striatum was examined at baseline to investigate its relationship to the RT distractor effect and to the L-DOPA-induced change of the RT distractor effect. Results There was a pronounced RT distractor effect in the placebo session that increased under L-DOPA. Neither the RT distractor effect in the placebo session nor the magnitude of its L-DOPA-induced increase were related to baseline striatal dopamine. Conclusions L-DOPA administration shifted the stability-flexibility balance towards attentional capture by distractors, suggesting causal involvement of dopamine. This finding is consistent with current theories of prefrontal cortex dopamine function. Current data can neither confirm nor falsify the inverted U-shaped function hypothesis with regard to cognitive control.
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