http://www.back-in-business-physiotherapy.com/images/files/DescendingControl.pdf

Descending control of pain.

For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from...

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Hormones and endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose responses

Local effector functions of capsaicin-sensitive sensory nerve endings : involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides

A positive temperature coefficient is the term which has been used to indicate that an increase in solubility occurs as the temperature is raised, whereas a negative coefficient indicates a decrease in solubility with rise in temperature.

Effect of Temperature

Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation.

We have described recently an acetylcholinesterase (AChE) knockout mouse. While comparing the tissue distribution of AChE and butyrylcholinesterase (BChE), we found that extraction buffers containing Triton X-100 strongly inhibited mouse BChE activity. In contrast, buffers with Tween 20 caused no inhibition of BChE. Conventional techniques grossly underestimated BChE activity by up to 15-fold. In Tween 20 buffer, the intestine, serum, lung, liver, and heart had higher BChE than AChE activity. Only brain had higher AChE than BChE activity in AChE +/+ mice. These findings contradict the dogma, based mainly on observations in Triton X-100 extracts, that BChE is a minor cholinesterase in animal tissues. AChE +/- mice had 50% of normal AChE activity and AChE -/- mice had none, but all mice had similar levels of BChE activity. BChE was inhibited by Triton X-100 in all species tested, except rat and chicken. Inhibition was reversible and competitive with substrate binding. The active site of rat BChE was unique, having an arginine in place of leucine at position 286 (human BChE numbering) in the acyl-binding pocket of the active site, thus explaining the lack of inhibition of rat BChE by Triton X-100. The generally high levels of BChE activity in tissues, including the motor endplate, and the observation that mice live without AChE, suggest that BChE has an essential function in nullizygous mice and probably in wild-type mice as well.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1471-4159.2000.751320.x

Abundant tissue butyrylcholinesterase and its possible function in the acetylcholinesterase knockout mouse.

Highly Potent, Selective, and Low Cost Bis-tetrahydroaminacrine Inhibitors of Acetylcholinesterase STEPS TOWARD NOVEL DRUGS FOR TREATING ALZHEIMER'S DISEASE

Stephen Brimijoin

Papers

Abundant tissue butyrylcholinesterase and its possible function in the acetylcholinesterase knockout mouse.

Highly Potent, Selective, and Low Cost Bis-tetrahydroaminacrine Inhibitors of Acetylcholinesterase STEPS TOWARD NOVEL DRUGS FOR TREATING ALZHEIMER'S DISEASE

Axonal transport of substance P in the vagus and sciatic nerves of the guinea pig

Acetylcholinesterase promotes beta-amyloid plaques in cerebral cortex.

Molecular forms of acetylcholinesterase in brain, nerve and muscle: nature, localization and dynamics