Pharmacokinetics of and CYP1A induction by pyridine and acetone in the rat: interactions and effects of route of exposure

1. Male Sprague-Dawley rats were exposed to either pyridine, acetone or a combination of both compounds by either intraperitoneal administration (100 mg/kg pyridine or 400 mg/kg acetone) or whole-body inhalation (200 ppm pyridine or 1000 ppm acetone). Plasma and tissue levels of both compounds were determined by gas chromatography/mass spectrometry. 2. Both chemicals were well distributed in the tissues examined following either route of exposure, with concentrations in the order kidney > liver > plasma > lung. 3. Plasma half-life of pyridine was 7 h following a single 100 mg/kg dose of the compound, and 8 h following the last dose of a 3-day, 8 h/day exposure to a 200 ppm inhalation dose of the compound. 4. Plasma half-life of acetone was 4 h and was independent of the route of exposure. 5. The pharmacokinetics of pyridine was not affected by co-exposure to acetone. Similarly, the pharmacokinetics of acetone was not affected by co-exposure to pyridine. 6. Ethoxyresorufin O-deethylase activity in lung and liver and methoxyresorufin O-demethylase activities in liver were induced by pyridine but not by acetone at the doses examined. Pyridine-induced ethoxyresorufin O-deethylase activity was higher following inhalation exposure than following i.p. administration of pyridine but did not parallel tissue levels of the compound.     

Chondrocyte implantation in the repair of chondral lesions of the knee: economics and quality of life

Exposure to low levels of chemicals indoors is often to a mixture of volatile organic compounds (VOCs). It is of interest to determine if the symptomatic and sensory responses can be attributed to a single chemical or to a mixture of chemicals. To determine if sensory or symptomatic responses differ with exposure to single or mixed VOCs, 100 female subjects participated in a 6-hr exposure study. Subjects were exposed to one of six equimolar concentrations equivalent to 24 mg/m3 toluene, control, m-xylene, n-butyl acetate, m-xylene plus n-butyl acetate, a mixture of 21 chemicals including n-butyl acetate and m-xylene, and to the same mixture of chemicals without n-butyl acetate and m-xylene (19 chemicals). The results indicated that there was no difference in reporting of symptoms or sensory responses between the exposures. When the control group was added, some variables, primarily odor intensity and nasal irritation, attained significance.     

Bioelectrical impedance analysis predicts outcome in patients with suspected bacteremia

We expanded a previously described rule-based computerized method to recognize the sensory irritating effect of airborne chemicals. Using 2-chlorobenzylchloride (CBC) as a sensory irritant, characteristic modifications of the normal breathing pattern of exposed mice were evaluated by measuring the duration of braking (TB) after inspiration and the resulting decrease in breathing frequency. From the measurement of TB, each breath was then classified as normal (N) or sensory irritation (S). Using increasing exposure concentrations, the classification S increased from < or = 2% (equivalent to sham-exposure) to 100% within a narrow exposure concentration range. The potency of CBC was then evaluated by calculating the concentration necessary to produce 50% of the breaths classified as S, i.e., S50. This approach is easier to use than obtaining RD50 (decrease in respiratory frequency by 50%) when high exposure concentrations are difficult to achieve. Detection limits were also established for this bioassay and experiments were conducted to obtain a level of response just around these limits, in order to delineate the practicality of using this bioassay at low exposure concentrations. Using this approach, sensory irritation was the only effect induced by CBC at low exposure concentrations. However, bronchoconstriction and pulmonary irritation were superimposed on this effect at higher exposure concentrations.     

A new Drosophila ultraviolet light-damaged DNA recognition endonuclease that selectively nicks a (6-4) photoproduct site

Airborne substances can stimulate both the olfactory and the trigeminal nerve in the nose, giving rise to odor and pungent (irritant) sensations, respectively. Nose, eye, and throat irritation constitute common adverse effects in indoor environments. We measured odor and nasal pungency thresholds for homologous aliphatic aldehydes (butanal through octanal) and carboxylic acids (formic, acetic, butanoic, hexanoic, and octanoic). Nasal pungency was measured in subjects lacking olfaction (i.e., anosmics) to avoid odor biases. Similar to other homologous series, odor and pungency thresholds declined (i.e., sensory potency increased) with increasing carbon chain length. A previously derived quantitative structure-activity relationship (QSAR) based on solvation energies predicted all nasal pungency thresholds, except for acetic acid, implying that a key step in the mechanism for threshold pungency involves transfer of the inhaled substance from the vapor phase to the receptive biological phase. In contrast, acetic acid - with a pungency threshold lower than predicted - is likely to produce threshold pungency through direct chemical reaction with the mucosa. Both in the series studied here and in those studied previously, we reach a member at longer chain-lengths beyond which pungency fades. The evidence suggests a biological cut-off, presumably based upon molecular size, across the various series.     

Sick building syndrome and HVAC system: MVOC from air filters

Growth and emissions of volatile metabolites of microorganisms on air filters are suspected to contribute to health complaints in ventilated rooms. To prove the microbiological production of volatile organic compounds (MVOC), concentrations of aldehydes and ketones were determined in two large HVAC systems. The in situ derivated aldehydes and ketones (as 2,4-dinitrophenyl-hydrazones) were analysed by HPLC and UV detection. The detection limit of each compound was 1 ppb (margin of error < 10%). Field measurements were carried out before and after the prefilters and the main filters, respectively, to investigate whether aldehydes and ketones increase in concentration after filters of HVAC systems. First results show that the compounds formaldehyde, acetaldehyde and acetone could be detected before and after the filters. The concentrations of these VOC after the filters were significantly increased--as a mean over twenty measurements--, especially as far as filters made of glass fibre are concerned. However the found concentrations were low and mostly comparable to outdoor findings. In simultaneous laboratory experiments pieces of used filter material of one HVAC system and unused filter pieces (for blank values) were examined in small incubation chambers to investigate the possible production of MVOC. For the incubation a temperature of 20 degrees C and a relative humidity of 95% was chosen. In these experiments an almost identical spectrum of compounds (formaldehyde and acetone) was found as in the field measurements. The concentrations of these compounds were higher in the chambers with the used filter pieces. The concentration of acetone ranged up to almost 12 mg/m3.--As our field experiments correspond with our laboratory experiments, we assume that the microbial production of volatile organic compounds in HVAC systems under operating conditions is possible.     

Examining the relationship between degree of handedness and degree of cerebral lateralization for processing facial emotion.

This paper examines the relationship between degree of handedness and degree of cerebral lateralization on a task of processing positive facial emotion in right-handed individuals. Three hundred and thirteen right-handed participants (157 women) were given two behavioral tests of lateralization: a handedness questionnaire and a chimeric faces test. Two further handedness measures were taken: familial lefthandedness and writing posture. Regression analysis showed that both degree of handedness and sex were predictive of degree of lateralization. Individuals who were strongly right-handed were also more strongly lateralized to the right hemisphere for the task. Men were more strongly lateralized than women. Data were reanalyzed for men and women separately. The relationship between handedness and lateralization remained for men only. Neither familial left-handedness nor writing posture were associated with cerebral lateralization for men or women. The results suggest a positive relationship between degree of handedness and degree of cerebral lateralization, and further that there is a sex difference in this relationship. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chemical exposure of deck crew on product tankers loading the cargo with the hatches open

Exposure of the deck crew to volatile hydrocarbon compounds and polycyclic aromatic hydrocarbon PAH compounds was observed and monitored on two Norwegian product tankers. The tankers were loading their cargo with the hatches open during the monitoring period. One of the tankers loaded gas oil. This type of cargo is not volatile, and very low concentrations of the monitored chemical PAH compounds were found on this tanker. The second tanker loaded gasoline. On this tanker high concentrations of hydrocarbon compounds were found; benzene was as high as 55 ppm, toluene was as high as 34 ppm, hydrocarbon compounds in the C5-C7 range were as high as 570 ppm, n-hexane was as high as 25 ppm. The levels of PAH-compounds were low. None of the seamen working on the deck did use respiratory protective equipment during the work. The exposure of the deck crew to volatile hydrocarbon compounds ought to be reduced on product tankers. Better routines concerning the use of respiratory protective equipment is an immediate action which ought to take place. Loading volatile cargo like gasoline with the hatches open should be avoided.     

Lateralized agonistic responses and hindlimb use in toads

The recent discovery of forepaw preferences (handedness) in toad species has provided some insight into the evolution of brain lateralization. We tested the prediction that, as in higher vertebrates, visual lateralization and other motor preferences (footedness) also exists in toad species. During feeding periods, South American cane toads, Bufo marinus, showed a population bias to strike with the tongue at other toads occupying their left visual field. This is the first demonstration of lateralized visual behaviour in an amphibian species. Tongue striking at an individual's eyes or head may sometimes delay its approach to prey already seen by the attacker, or may dislodge prey from its mouth. In addition, we report hindlimb preferences (footedness) for contact righting in three species of toad (B. marinus, the European green toad, B. viridis, and the European common toad, B. bufo). After being fully overturned on to their back on a horizontal surface, toads initiated and completed righting using the hindlimbs and with only perfunctory use of the forepaws. Together, the findings of visual lateralization and footedness demonstrate that in toads, as in higher vertebrates, behavioural lateralization is not restricted to handedness. The hypothesis that lateralized brain functions in birds and mammals might have arisen from a common lateralized ancestor is therefore supported. Copyright 1998 The Association for the Study of Animal Behaviour.     

Building-related illness and employee lost time following application of hot asphalt roof: a call for prevention

Industrial hygiene sampling within an office building during and following a roof renovation revealed low-level exposure to high-boiling organic compounds, associated with complaints of eye and upper respiratory tract irritation among building occupants. Health complaints continued substantially beyond the time frame of the renovation completion, despite a lack of objective industrial hygiene findings for volatile organic compounds (VOCs) and microbiological contamination, and a lack of consistent medical findings among employees evaluated by an occupational physician. An analysis of employee attendance records suggests lost attendance and reduced productivity costs. Preventive strategies include proper planning and scheduling of building renovations to prevent employee exposure to asphalt roof emissions.     

Origin of nondisjunction in trisomy 8 and trisomy 8 mosaicism

OBJECTIVES: This study explores reactions to low-level chemical challenge, aiming at the development of test procedures for assessing individual sensitivity to smells and chemicals. METHODS: Subjects with symptoms and neuropsychological test results compatible with toxic encephalopathy type 2A (TE-2A) and 2B (TE-2B) and unexposed referents (N=12 in each group) were challenged in an exposure chamber. Toluene exposure was started at 11 mg/m3, and it followed a geometric progression scale with a ratio of 2, until reaching 180 mg/m3. In a counterbalanced design, the subjects were similarly exposed to n-butyl acetate starting at a concentration of 14 mg/m3 and increasing to 228 mg/m3. At each exposure level, smell intensity was measured on a 7-step category scale. Mucous membrane irritation and annoyance reactions were rated on visual analogue scales. RESULTS: Both TE groups showed high sensitivity to the low-level solvent challenge, which provoked immediate annoyance and fatigue reactions. In particular the TE-2B group related smell intensity to various annoyance dimensions during exposure to n-butyl acetate, a pattern not observed during toluene exposure. The reference group clearly separated smell intensity and annoyance reactions in both exposure conditions. CONCLUSIONS: The reaction of the TE cases suggests that chemical sensitivity can be distinguished from normal annoyance reactions by the inability to differentiate between smell intensity and an experience of irritation from mucous membranes in air concentrations well below the trigeminal irritation threshold level. Fatigue coreactivity in challenges to single substances below the neurotoxic level may also be important.     

Assessment of Olfactory Function and Androstenone Odor Thresholds in Humans With or Without Functional Occlusion of the Vomeronasal Duct.

To obtain information on the possible role of the vomeronasal duct (VND) in odor perception and human pheromone detection, the present study investigated different aspects of olfactory function, including thresholds for androstenone in adults with or without detectable VNDs. The study also examined correlations between detection thresholds of androstenone odor and general olfactory function. Subjects' olfaction was assessed with tests for odor identification, odor discrimination, and phenyl ethyl alcohol odor threshold. Measurements were performed on 1 side only, with and without covering the VND. Subjects with or without detectable VNDs did not differ in olfactory sensitivity or androstenone odor thresholds. A small but significant correlation was found between detection thresholds of androstenone and general olfactory function. Finally, covering of the VND did not affect olfactory function or androstenone sensitivity. Results suggest that the human VND does not play a major role in sensitivity toward odorants or the preception of androstenone. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of cerebral dominance: Evidence from time-sharing asymmetry in children.

Used a dual-task procedure as a measure of speech lateralization in 151 normal, right-handed, 3–12 yr old children. Ss engaged in unimanual finger tapping with and without concurrent speech. It was hypothesized that if speech is left lateralized, talking should disrupt right-hand tapping (an instance of intrahemispheric interference) more than left-hand tapping (an instance of interhemispheric interference). Results for 2 different verbal tasks show the predicted overall asymmetry but no developmental trend in degree of asymmetry. The data suggest that lateralization is as marked in young children as in older children. About 70% of the Ss showed the predicted effect; there was no significant change in incidence as a function of grade level. Analyses of verbal production indicated that the performance asymmetry could not be attributed to an asymmetrical trade-off between talking and tapping. No sex differences in performance asymmetry were found. The results contradict the traditional model of progressive lateralization but corroborate the developmental invariance frequently observed using perceptual measures of language lateralization. (46 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of long-term aerosol pentamidine for Pneumocystis carinii prophylaxis on pulmonary function

OBJECTIVE: To compare the reliability of clinical seizure lateralization in temporal lobe epilepsy patients with unitemporal and bitemporal independent interictal spikes and unilateral hippocampal atrophy or sclerosis (HA/HS) on MRI scan. PATIENTS AND METHODS: We studied 11 patients with unitemporal and 10 patients with bitemporal interictal spikes. We calculated a spike ratio by dividing the number of spikes ipsilateral to the side of HA/HS by those occurring contralaterally. RESULTS: Clinical seizure lateralization was correct, i.e., ipsilateral to the side of HA/HS, significantly more often in the unitemporal group. Spike ratios were significantly higher in seizures that were lateralized correctly as compared with both incorrectly and nonlateralized seizures. Within the individual patients, a significant positive correlation between spike ratios and the proportion of correctly lateralized seizures was found. We identified three categories of symptoms according to lateralization accuracy. Category 1 symptoms (version, postictal paresis, and early ictal vomiting/retching) lateralized to the side of HA/HS in 100% of patients in the uni- and bitemporal groups. Category 2 symptoms (dystonic posturing, mouth deviation, postictal dysnomia/dysphasia, and ictal speech) provided a 100% correct lateralization in the unitemporal but not in the bitemporal patients. Category 3 symptoms (nonversive early head turning and unilateral upper extremity automatisms) yielded erroneous lateralization in both patient groups. CONCLUSIONS: We conclude that reliable clinical seizure lateralization in mesial temporal lobe epilepsy can only be achieved in patients with unitemporal interictal spikes, whereas clinical lateralization in patients with bitemporal spikes must be viewed cautiously.     

Investigating models of affect: Relationships among EEG alpha asymmetry, depression, and anxiety.

The approach-withdrawal and valence-arousal models both predict that depressive and anxious profiles will be associated with relatively reduced left frontal and increased right frontal activity respectively, while the valence-arousal model also proposes a dissociation by lower and higher right parietotemporal activity, respectively. Recent work further suggests that subtypes of anxiety disorders may be characterized by distinctive patterns of activity depending on their type of arousal (anxious arousal/apprehension). The aim of this study was to investigate the relationships among nonclinical depression/anxiety and lateralized frontal/parietotemporal activity by categorizing participants (N = 428) on the basis of both negative mood and alpha EEG. Key findings include: (i) greater right frontal lateralization in anxious participants, symmetrical frontal activity in depressed/comorbid, and left frontal lateralization in healthy controls; (ii) right frontal lateralization in anxious arousal participants, left frontal and right parietotemporal lateralization in anxious apprehension; (iii) bilateral increase in frontal and increased right parietotemporal activity in depressed/comorbid participants. Findings support predictions for frontal but not posterior regions. Grouping on the basis of EEG may not be reciprocally predictive of negative mood groupings, suggesting involvement of additional factors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Seeing and imagining in the cerebral hemispheres: A computational approach.

Visual recognition, navigation, tracking, and imagery are posited to share certain high-level processing subsystems. A theory of some of these subsystems is formulated, developed in light of an analysis of problems that must be solved by the visual system and the constraints on the solutions to these problems. Inferences about perceptual subsystems are used to develop a theory of how mental images are generated. Support for this theory is adduced from studies of split-brain patients and a review of relevant neuropsychological findings. A computational mechanism is developed to account for how visual function becomes lateralized in the brain; this mechanism is used to predict how the hypothesized processing subsystems become lateralized. Some critical tests of the theory of lateralization of perceptual processing subsystems are reported, and the theory is extended to account for the lateralization of image-transformation subsystems and is used to account for the almost ubiquitous variability evident in the neuropsychological literature on lateralization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

One-sided limb preference is linked to alternating-limb locomotion in anuran amphibians.

Amphibians provide a unique opportunity for identifying possible links between lateralized behaviors, locomotion, and phylogeny and for addressing the origin of lateralized behaviors of higher vertebrates. Five anuran species with different locomotive habits were tested for forelimb and hind limb preferences during 2 stereotyped behavior sequences-wiping a foreign object off their snout and righting themselves from the overturned position. The experiments were analyzed in a broader context of previous findings on anuran lateralization involving 11 anuran species that were studied within the same experimental paradigms. This analysis shows that one-sided forelimb and hind limb motor lateralization in anurans is strongly associated with alternating-limb locomotion and other unilateral limb activity. Conclusions reached for anuran amphibians may be applicable to other vertebrates possessing paired appendages-the degree of lateralization in motor response depends on the mode of locomotion used by a species. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hemispheric asymmetry for emotional stimuli detected with fMRI

Current brain models of emotion processing hypothesize that positive (or approach-related) emotions are lateralized towards the left hemisphere, whereas negative (or withdrawal-related) emotions are lateralized towards the right hemisphere. Brain imaging studies, however, have so far failed to document such hemispheric lateralization. In a functional magnetic resonance imaging (fMRI) study, 14 female subjects viewed alternating blocks of emotionally valenced positive and negative pictures. When the experience of valence was equated for arousal, overall brain reactivity was lateralized towards the left hemisphere for positive pictures and towards the right hemisphere for negative pictures. This study provides direct support for the valence hypothesis, under conditions of equivalent arousal, by means of functional brain imaging.     

Pollution of the work environment by volatile anesthetics and nitrous oxide]

Anaesthetic personnel is exposed to different workload conditions. The individual impact is influenced by external factors and human stress stability. Different symptoms reported to be present in anaesthetic personnel are comparable to symptoms of the sick building syndrome, defined by the WHO in the 90's. They are caused by work-induced distress and the exposure to chemical hazards. In anaesthesia, health defects by anaesthetic vapours and gases have been deplored for many years. After the Russian anaesthesiologist Vaisman published a report in 1967, controlled studies concerning cancerogenicity and teratogenicity of volatile anaesthetics under workspace conditions were carried out. In 1989, time-weighted average exposure threshold limit values of 5 ppm were released in the Federal Republic of Germany for halothane. In 1993 thresholds for enflurane (20 ppm) and nitrous oxide (100 ppm) were released. TLV concentrations for the new anaesthetic agents desflurane and sevoflurane have not yet been defined by authorities. Factors influencing workplace concentrations of anaesthetic gases are the anaesthetic procedures, apparatus leakage, air conditioning, fresh gas flow and the function of the scavenging system. Although cancerogenicity, mutagenicity, teratogenicity and reduction of fertility are discussed as effects of chronic exposure to anaesthetic gases, several review articles doubted the results of studies, finding positive correlations of incidence of occupational disease and the exposure to the volatile and gaseous substances. Mainly coexisting factors like smoke-induced exposure to polybromated biphenyls, disturbance in circadian rhythm, stress and enclosure in narrow exposure systems, increasing teratogenicity and cancerogenicity in animal experiments, are considered to promote unreliability of the studies. All reviewers do not discuss the fact, that all of these co-factors are present in the reality of the anaesthetic workplace. Thus, the studies by Corbett, enthusiastically criticized by different reviewers, simulate the all-day reality of the anaesthetic workplace more precisely than controlled experiments conducted, for example, by Eger and co-workers. The results of animal experiments and retrospective studies therefore do not justify realization of large controlled prospective studies but require the overall revision of the anaesthesiological workplace and the reduction of occupational waste gas exposure to the lowest possible levels below all chronic exposure threshold values.     

Influence of gender and acetone pretreatment on benzene metabolism in mice exposed by nose-only inhalation

Benzene (BZ) requires oxidative metabolism catalyzed by cytochrome P-450 2E1 (CYP 2E1) to exert its hematotoxic and genotoxic effects. We previously reported that male mice have a two-fold higher maximum rate of BZ oxidation compared with female mice; this correlates with the greater sensitivity of males to the genotoxic effects of BZ as measured by micronuclei induction and sister chromatid exchanges. The aim of this study was to quantitate levels of BZ metabolites in urine and tissues, and to determine whether the higher maximum rate of BZ oxidation in male mice would be reflected in higher levels of hydroxylated BZ metabolites in tissues and water-soluble metabolites in urine. Male and female B6C3F, mice were exposed to 100 or 600 ppm 14C-BZ by nose-only inhalation for 6 h. An additional group of male mice was pretreated with 1% acetone in drinking water for 8 d prior to exposure to 600 ppm BZ; this group was used to evaluate the effect of induction of CYP 2E1 on urine and tissue levels of BZ and its hydroxylated metabolites. BZ, phenol (PHE), and hydroquinone (HQ) were quantified in blood, liver, and bone marrow during exposure and postexposure, and water-soluble metabolites were analyzed in urine in the 48 h after exposure. Male mice exhibited a higher flux of BZ metabolism through the HQ pathway compared with females after exposure to either 100 ppm BZ (32.0 2.03 vs. 19.8 2.7%) or 600 ppm BZ (14.7 1.42 vs. 7.94 + 0.76%). Acetone pretreatment to induce CYP 2E1 resulted in a significant increase in both the percent and mass of urinary HQ glucuronide and muconic acid in male mice exposed to 600 ppm BZ. This increase was paralleled by three- to fourfold higher steady-state concentrations of PHE and HQ in blood and bone marrow of acetone-pretreated mice compared with untreated mice. These results indicate that the higher maximum rate of BZ metabolism in male mice is paralleled by a greater proportion of the total flux of BZ through the pathway for HQ formation, suggesting that the metabolites formed along this pathway may be responsible for the genotoxicity observed following BZ exposure.