Odor-associated health complaints: competing explanatory models.
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Physical symptoms may be reported in workplace and community settings in which odorous airborne chemicals are present. Despite the relative frequency of such reports, clinicians, public health authorities and sensory scientists often experience difficulty interpreting odor-associated symptoms. The approach to interpretation advocated in this review involves: (i) understanding the toxicology of the agent(s) involved (in particular their relative irritant and odorant potencies); (ii) assessing exposure parameters (i.e. concentration and duration). Depending upon exposure concentration, duration and relative irritant and odorant potencies, a variety of pathophysiological mechanisms may be invoked in explaining odor-associated health symptoms. Some of these imputed mechanisms fall under the traditional scope of toxicology and others involve attitudinal and/or behavioral responses to odors. (+info)
Irritation of gastrointestinal mucosa by new glycosyl derivative of diclofenac in comparison with diclofenac in rats.
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We have obtained new glycosyl derivative of diclofenac 3 and studied its ulcerogenic effect in the gastrointestinal system. Diclofenac as free acid 1 and its derivative 3 were administered to rats per os in a single dose 20 mg/kg and in 5 doses of 5 mg/kg. Single dose of derivative 3 caused less irritation than 1; after multiple administration no irritating effect of derivative 3 was seen. (+info)
Neuroplasticity induced by tooth pulp stimulation in trigeminal subnucleus oralis involves NMDA receptor mechanisms.
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We have recently demonstrated that application of the mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces significant increases in jaw muscle electromyographic (EMG) activity and neuroplastic changes in trigeminal (V) subnucleus caudalis. Since subnucleus oralis (Vo) as well as caudalis receives projections from molar pulp afferents and is also an integral brain stem relay of afferent input from orofacial structures, we tested whether MO application to the exposed pulp induces neuroplastic changes in oralis neurons and whether microinjection of MK-801, a noncompetitive NMDA antagonist, into the Vo influences the pulp/MO-induced neuroplastic changes in chloralose/urethan-anesthetized rats. Single neuronal activity was recorded in Vo, and neurons classified as low-threshold mechanoreceptive (LTM), wide dynamic range (WDR), nociceptive-specific (NS), deep (D), or skin/mucosa and deep (S + D). The spontaneous activity, mechanoreceptive field (RF) size, mechanical threshold, and response to suprathreshold mechanical stimuli applied to the neuronal RF were assessed prior to and throughout a 40- to 60-min period after MO application to the maxillary molar pulp. In animals pretreated with saline microinjection (0.3 microl) into the Vo, MO application to the pulp produced a significant increase in spontaneous activity, expansion of the pinch or deep RF, decrease in the mechanical threshold, and increase in response to suprathreshold mechanical stimuli of the nociceptive (WDR, NS, and S + D) neurons except for those nociceptive neurons having their RF only in the intraoral region. The pulpal application of MO did not produce any significant neuroplastic changes in LTM neurons. Furthermore, in animals pretreated with MK-801 microinjection (3 microg/0.3 microl) into the Vo, MO application to the pulp did not produce any significant changes in the RF and response properties of nociceptive neurons. In other animals pretreated with saline (0.3 microl) or MK-801 (3 microg/0.3 microl) microinjected into the Vo, mineral oil application to the pulp did not produce any significant changes in RF and response properties of nociceptive neurons. These findings indicate that the application of MO to the tooth pulp can induce significant neuroplastic changes in oralis nociceptive neurons and that central NMDA receptor mechanisms may be involved in these neuroplastic changes. (+info)
In vivo-matured Langerhans cells continue to take up and process native proteins unlike in vitro-matured counterparts.
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We have been able to identify the cell subset derived from Langerhans cells in the total dendritic cell population of the peripheral lymph node and hence to follow their trafficking under normal physiological conditions as well as upon skin irritation. As expected, the rapid mobilization of Langerhans cells triggered by inflammatory signals into the draining lymph node correlated with an up-regulation of costimulatory molecules and with an enhanced immunostimulatory capacity. Surprisingly, however, these cells, instead of shutting down, maintain the capacity to capture and process protein Ags during the couple of days they stay alive in stark contrast to in vitro-matured dendritic cells. (+info)
An animal model to assess aversion to intra-oral capsaicin: increased threshold in mice lacking substance p.
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Despite the widespread consumption of products containing chemicals that irritate the oral mucosa, little is known about the underlying neural mechanisms nor is there a corresponding animal model of oral irritation. We have developed a rodent model to assess aversion to capsaicin in drinking water, using a paired preference paradigm. This method was used to test the hypothesis that the neuromodulator substance P (SP) plays a role in the detection of intra-oral capsaicin. 'Knockout' (KO) mice completely lacking SP and neurokinin A due to a disruption of the preprotachykinin A gene and a matched population of wild-type (WT) mice had free access to two drinking bottles, one containing water and the other capsaicin at various concentrations. Both KO and WT mice showed a concentration-dependent aversion to capsaicin. KO mice consumed significantly more capsaicin than WT at a single near threshold (1.65 microM) concentration, indicating that SP plays a limited role in the detection and rejection of oral irritants. (+info)
Pathology of ocular irritation with acetone, cyclohexanol, parafluoroaniline, and formaldehyde in the rabbit low-volume eye test.
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The ocular irritation responses to 11 different surfactants and two concentrations of acetic acid and sodium hydroxide have been shown to depend on the extent of initial injury, despite marked differences in the processes leading to tissue damage. The purpose of these studies was to determine the extent to which this fundamental relationship applies to other nonsurfactants. Ten microl of acetone (ACT). cyclohexanol (CY), parafluoroaniline (PF), or 37% formaldehyde (FA) was directly applied to the cornea of the right eye of each rabbit. Eyes and eyelids were macroscopically scored for signs of irritation beginning 3 hours after dosing and periodically until recovery or 35 days. Tissues were obtained for light microscopic examination after 3 hours and on days 1, 3, and 35. Initial corneal injury was characterized quantitatively at 3 hours and I day using in vivo confocal microscopy (CM) and by postmortem quantitation of dead corneal epithelial cells and keratocytes using a Live Dead Assay (L/D, Molecular Probes) and scanning laser CM. Corneal changes over time were characterized quantitatively using in vivo CM performed at 3 hours and 1, 3, 7, 14, and 35 days. The changes with ACT were consistent with mild irritation. Corneal injury was limited to the epithelium and superficial stroma, with the mean normalized depth of injury (NDI) being less than 10% with the majority of regions showing no stromal injury. Changes with CY and PF were consistent with moderate to severe irritation, and FA caused severe irritation. Specifically, corneal injury by CY and PF tended to involve the epithelium and anterior stroma, with the mean NDI being 10.4% to 23.8%, while injury with FA involved the epithelium, deep stroma, and at times the endothelium. Interestingly, with FA significantly less injury was observed at 3 hours with a dramatic increase in injury observed at 1 day and thereafter. In conclusion, these results continue to support and extend our hypothesis that ocular irritation is principally defined by the extent of initial injury despite clear differences in the means by which irritants cause tissue damage. We believe this approach can be applied to developing alternative assays based on injury to ex vivo eyes or injury to an in vitro corneal equivalent system. (+info)
Pathology of ocular irritation with bleaching agents in the rabbit low-volume eye test.
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Despite differences in the processes leading to tissue damage, the ocular irritation response to various surfactants, two concentrations of an acid and an alkali, and an acetone, alcohol, aromatic amine, and aldehyde has been shown to depend on the extent of initial injury. The purpose of this study was to assess the extent to which this fundamental relationship exists for bleaching agents in the rabbit low-volume eye test. Ten microl of sodium perborate monohydrate (NaBO3), sodium hypochlorite (NaOCl), 10% hydrogen peroxide (H2O2), and 15% H2O2 was applied directly to the cornea of the right eye of each rabbit. Macroscopic assessments for irritation were made 3 hours after dosing and periodically until 35 days. Light microscopic examinations were conducted on tissues obtained at 3 hr and on 1, 3, and 35 days. In vivo confocal microscopy (CM) and measurements of dead corneal epithelial cells and keratocytes at 3 hours and 1 day were used to characterize quantitatively initial corneal injury, while in vivo CM performed at 3 hours and 1, 3, 7, 14, and 35 days was used to characterize quantitatively the corneal changes over time. The changes with NaBO3 and NaOCl were consistent with mild irritancy. For both, corneal injury was limited to the epithelium and superficial stroma. The changes with 10% H202 and 15% H2O2 were consistent with severe irritation. Both concentrations affected the epithelium and deep stroma, with 15% H2O2 also at times affecting the endothelium. However, unlike other irritants previously studied, with 10% H2O2 and 15% H2O2 there was an incongruity between the extent of epithelial and stromal injury, with stromal injury being more extensive than epithelial injury. A similar, although less dramatic, effect was observed with NaBO3. Additionally, there was still significant keratocyte loss at 35 days with 10% H2O2 and 15% H2O2 even though the eyes at times were considered to be macroscopically normal. These observations highlight the need to include both epithelial and stromal components in an ex vivo or in vitro alternative assay. In conclusion, these results continue to support and extend our hypothesis that ocular irritation is principally defined by the extent of initial injury despite clear differences in the means by which irritants cause tissue damage. Importantly, we have identified unique differences in the ocular injury and responses occurring with bleaching agents that are important to consider in the development and validation of alternative ocular irritation tests to characterize a broad range of materials differing in type and irritancy. (+info)
Nasal, eye, and skin irritation in dockyard painters.
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OBJECTIVES: To determine whether the risk of irritant symptoms in painters is related to their exposure to paint. METHODS: The prevalences of skin, eye and nasal symptoms were compared in 260 United Kingdom and 109 Chinese dockyard painters, 539 British community controls, and 255 Chinese dockyard controls, relative to their exposure to paints. RESULTS: Painters showed an excess of irritant symptoms compared with controls. Adjusted relative risks (RRs) (95% confidence interval (95% CI) were: for skin irritation 1.58 (1.19 to 2.08) in British painters and 2.68 (1.73 to 4.09) in Chinese painters; for eye irritation, 1.41 (0.98 to 2.05) and 3.01 (1.90 to 4.76); and for nasal irritation, 1.53 (1.10 to 2.14) and 6.73 (3.53 to 12.82), respectively. Exposure duration-response relations were found for these symptoms; the risks decreased with time after exposure ended. CONCLUSIONS: Irritant symptoms occur more often in dockyard painters than in controls, and this is likely to be a response to exposure to paint. (+info)