Dose-Response: An International Journal: Volume 8, Issue 4
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2010-31-12
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Dose-Response, Vol 8, no 4, Cover
(2010-12-01)
Dose-Response, Vol 8, no 4, Table of Contents
(2010-12-01)
TNF-α AND MICROGLIAL HORMETIC INVOLVEMENT IN NEUROLOGICAL HEALTH & MIGRAINE
(2010-12-01) Kraig, Richard P; Mitchell, Heidi M; Christie-Pope, Barbara; Kunkler, Phillip E; White, David M; Tang, Ya-Ping; Langan, George
Environmental enrichment, i.e., increased intellectual, social, and physical activity makes brain more resilient to subsequent neurological disease. The mechanisms for this effect remain incompletely defined, but evidence shows tumor necrosis factor-alpha (TNF- α) is involved. TNF-α, at acutely high levels, possesses the intrinsic capacity to enhance injury associated with neurological disease. Conversely, the effect of TNF-α at low-levels is nutritive over time, consistent with physiological conditioning hormesis. Evidence shows that neural activity triggers low-level pro-inflammatory signaling involving TNF-α. This low-level TNF-α signaling alters gene expression, resulting in an enhanced resilience to disease. Brain-immune signaling may become maladaptive when increased activity is chronic without sufficient periods of reduced activity necessary for nutritive adaptation. Such tonically increased activity may explain, for example, the transformation of episodic to chronic migraine with related increased susceptibility to spreading depression, the most likely underlying cause of this malady. Thus, TNF-α, whose function is to alter gene expression, and its principal cellular source, microglia, seem powerfully positioned to orchestrate hormetic immune signaling that establishes the phenotype of neurological health and disease from brain activity.
PHYTOTOXIC ANTIBIOTIC SULFADIMETHOXINE ELICITS A COMPLEX HORMETIC RESPONSE IN THE WEED LYTHRUM SALICARIA L.
(2010-12-01) Migliore, Luciana; Rotini, Alice; Cerioli, Nadia L; Cozzolino, Salvatore; Fiori, Maurizio
In order to evaluate the hormetic response of the weed Lythrum salicaria to drug expo- sure we investigated the effects of the antibiotic Sulfadimethoxine by growing Lythrum plants for 28 days on culture media containing different drug concentrations (between 0.005 and 50 mg.L-1). The antibiotic was absorbed by plants and can be found in plant tissue. The plant response was organ-dependent: roots, cotyledons and cotyledon petioles, were always affected by a toxic effect, whilst internodes and leaves length, showed a variable dose-depending response, with an increased growth at the lower drug concentrations and toxic effects at the higher ones. This variable response was probably dependant on different levels of local contamination resulting from a balance between accumulation rate and drug dilution in the increasing plant biomass. As a consequence, drug toxicity or hormetic response varied according to concentration and were different in each of the examined plant organ/tissue. Thus, even if hormesis can be considered a general plant response, each plant organ/tissue responds differently, depending on the local drug concentration and exposure time.
STOCHASTIC THRESHOLD MICRODOSE MODEL FOR CELL KILLING BY INSOLUBLE METALLIC NANOMATERIAL PARTICLES
(2010-12-01) Scott, Bobby R
This paper introduces a novel microdosimetric model for metallic nanomaterial-parti- cles (MENAP)-induced cytotoxicity. The focus is on the engineered insoluble MENAP which represent a significant breakthrough in the design and development of new products for consumers, industry, and medicine. Increased production is rapidly occurring and may cause currently unrecognized health effects (e.g., nervous system dysfunction, heart disease, cancer); thus, dose-response models for MENAP-induced biological effects are needed to facilitate health risk assessment. The stochastic threshold microdose (STM) model presented introduces novel stochastic microdose metrics for use in constructing dose- response relationships for the frequency of specific cellular (e.g., cell killing, mutations, neoplastic transformation) or subcellular (e.g., mitochondria dysfunction) effects. A key metric is the exposure-time-dependent, specific burden (MENAP count) for a given critical target (e.g., mitochondria, nucleus). Exceeding a stochastic threshold specific burden triggers cell death. For critical targets in the cytoplasm, the autophagic mode of death is triggered. For the nuclear target, the apoptotic mode of death is triggered. Overall cell survival is evaluated for the indicated competing modes of death when both apply. The STM model can be applied to cytotoxicity data using Bayesian methods implemented via Markov chain Monte Carlo.