Di-(2-ethylhexyl) phthalate: a short-term repeated inhalation toxicity study including fertility assessment.

In a study of the 28-day inhalation toxicity of di-(2-ethylhexyl) phthalate (DEHP) aerosols, 9-wk-old Wistar rats, 27 males (mean weight 226 g) and 17 females (mean weight 155 g) per group, were exposed in head-nose inhalation systems to DEHP aerosols of respirable particle size (mass median aerodynamic diameter < or = 1.2 microns) or air (controls). Exposure for 6 hr per day, 5 days per wk for 4 wk to target concentrations of 0, 0.01, 0.05 and 1.0 mg/litre gave estimated doses of 230, 11 and 2.3 mg/kg/day for the males, and 360, 18 and 3.6 mg/kg/day for females, on the assumption of 100% deposition and absorption. Clinical investigation and blood chemistry parameters did not reveal any treatment-related effects. At the end of exposure a statistically significant (16%) increase in relative lung weights, accompanied by increased foam-cell proliferation and thickening of the alveolar septi, was found in the males of the highest dose group. Absolute liver weights were significantly (8.75%) increased in females and relative liver weights were increased in both sexes in the highest dose group, but there were no corresponding histological effects. All these effects were reversed during the 8-wk post-exposure period. No testicular toxicity was observed histologically and no impact on mating performance and male fertility was detected after two matings of treated males with untreated females, 2 and 6 wk after the end of exposure. Electron microscopic examination of liver samples from two male and two female rats per group at the end of exposure and after the 8-wk post-exposure period did not reveal clear substructural changes that could be attributed to exposure or to peroxisome proliferation. The no-observed-effect level for all exposure-related findings was 0.05 mg/litre under the conditions used.     

Decontamination methods for cytotoxic drugs. 1. Use of a bioluminescent technique to monitor the inactivation of methotrexate with chlorine–based agents

A new microbial bioluminescence assay has been used to monitor the loss of mutagenicity on inactivation of methotrexate by active chlorine–based agents. The drug was degraded to products that were non–active in this mutagen detection system, in agreement with previously described work. Presept granules appear to be a suitable alternative to sodium hypochlorite for inactivating solutions and surface spills of methotrexate. The bioluminescence assay appears to have potential for monitoring clean–up and decontamination procedures in areas where cytotoxic agents are used.     

Multifocal oscillatory potentials in CSNB1 and CSNB2 type congenital stationary night blindness

We evaluated the function of the inner retina in patients with congenital stationary night blindness of the complete (CSNB1) and the incomplete type (CSNB2) by recording multifocal oscillatory potentials (mf-OPs). The VERIS system was used to record mf-OPs from 61 areas of the central retina from 5 CSNB1 patients (4 with NYX gene mutation), 6 CSNB2 patients (2 with CACNA1F mutation) and 11 control subjects. For each subject group, the first- and second-order kernel responses for one eye were analysed and the amplitudes and implicit times of their major components compared to 5 concentric rings centred on the fovea. In CSNB1 patients, the mf-OP peak amplitudes of the first-order kernel responses showed a significant reduction of the first peak without significant reduction of the second, whereas in CSNB2 both peak amplitudes were barely discernable from noise for all eccentricities. In the second-order kernel, the third peak was reduced in CSNB1 patients, and again not discernable from noise in CSNB2 patients. The difference in amplitude between the control and CSNB1 groups was significant for the late components of the first- and the second-order kernel. Implicit times were not significantly altered. The difference in mf-OP amplitude between CSNB1 and CSNB2 patients reflects the different molecular mechanisms underlying the two types of disease, which differentially affect the postreceptoral pathways of cone signal processing. The well-preserved peak 2 amplitudes of first-order mf-OPs and peak 3 amplitudes of second-order mf-OPs in CSNB1 patients point to a major impact of OFF-pathway components on these responses which are not present in CSNB2 patients. In conclusion, our results show that CSNB1 and CSNB2 are two different types of disease, not only on a genetic but also on a pathophysiological level.     

Experience with local lymph node assay performance standards using standard radioactivity and nonradioactive cell count measurements

The local lymph node assay (LLNA) is the preferred test for identification of skin-sensitizing substances by measuring radioactive thymidine incorporation into the lymph node. To facilitate acceptance of nonradioactive variants, validation authorities have published harmonized minimum performance standards (PS) that the alternative endpoint assay must meet. In the present work, these standards were applied to a variant of the LLNA based on lymph node cell counts (LNCC) run in parallel as a control with the standard LLNA with radioactivity measurements, with threshold concentrations (EC3) being determined for the sensitizers. Of the 22 PS chemicals tested in this study, 21 yielded the same results from standard radioactivity and cell count measurements; only 2-mercaptobenzothiazole was positive by LLNA but negative by LNCC. Of the 16 PS positives, 15 were positive by LLNA and 14 by LNCC; methylmethacrylate was not identified as sensitizer by either of the measurements. Two of the six PS negatives tested negative in our study by both LLNA and LNCC. Of the four PS negatives which were positive in our study, chlorobenzene and methyl salicylate were tested at higher concentrations than the published PS, whereas the corresponding concentrations resulted in consistent negative results. Methylmethacrylate and nickel chloride tested positive within the concentration range used for the published PS. The results indicate cell counts and radioactive measurements are in good accordance within the same LLNA using the 22 PS test substances. Comparisons with the published PS results may, however, require balanced analysis rather than a simple checklist approach.     

Separating brain processing of pain from that of stimulus intensity

Regions of the brain network activated by painful stimuli are also activated by nonpainful and even nonsomatosensory stimuli. We therefore analyzed where the qualitative change from nonpainful to painful perception at the pain thresholds is coded. Noxious stimuli of gaseous carbon dioxide (n = 50) were applied to the nasal mucosa of 24 healthy volunteers at various concentrations from 10% below to 10% above the individual pain threshold. Functional magnetic resonance images showed that these trigeminal stimuli activated brain regions regarded as the "pain matrix." However, most of these activations, including the posterior insula, the primary and secondary somatosensory cortex, the amygdala, and the middle cingulate cortex, were associated with quantitative changes in stimulus intensity and did not exclusively reflect the qualitative change from nonpainful to pain. After subtracting brain activations associated with quantitative changes in the stimuli, the qualitative change, reflecting pain-exclusive activations, could be localized mainly in the posterior insular cortex. This shows that cerebral processing of noxious stimuli focuses predominately on the quantitative properties of stimulus intensity in both their sensory and affective dimensions, whereas the integration of this information into the perception of pain is restricted to a small part of the pain matrix.     

A rapid solution to align the severely malpositioned premaxilla in bilateral cleft lip and palate patients.

OBJECTIVE: To describe a laboratory modification of the maxillary cast to make an improved nasoalveolar molding plate used in presurgical orthopedics for infants with bilateral cleft lip and palate. CONCLUSIONS: Modifying the nasoalveolar molding plate may reduce the presurgical treatment time for the bilateral cleft lip and palate patient.     

Pain Affects Visual Orientation: an Eye-Tracking Study

Because of its unique evolutionary relevance, it is understood that pain automatically attracts attention. So far, such attentional bias has mainly been shown for pain-related stimuli whereas little is known about shifts in attentional focus after actual painful stimulation. This study investigated attentional shifts by assessing eye movements into the direction of painful stimulation. Healthy participants were presented either a blank screen or a picture showing a natural scene while painful electrical stimuli were applied to the left or right hand. In general, painful stimulation reduced exploratory behavior as reflected by less and slower saccades as well as fewer and longer fixations. Painful stimulation on the right hand induced a rightward bias (ie, increased initial saccades, total number and duration of fixations to the right hemifield of the screen). Pain applied to the left hand as well as no pain induced a leftward bias that was largest for the direction of first saccades. These findings are in line with previous observations of attentional biases toward pain-related information and highlight eye tracking as a valuable tool to assess involuntary attentional consequences of pain. Future studies are needed to investigate how the observed changes in eye movements relate to pain-induced changes in perception and cognition.

Emotional effects on time-to-contact judgments: arousal,threat, and fear of spiders modulate the effect of pictorial content

Recently, responses to looming visual stimuli have been shown to depend on the emotional content of the stimulus. A threatening stimulus is judged to arrive sooner compared to a neutral stimulus, possibly buying the organism time to prepare defensive actions. Here, we explored the underlying mechanism. We found that time-to-contact judgments of threatening pictures did not differ from those of highly arousing pleasant pictures (Experiment 1), suggesting that arousal, not fear, modulates the perception of looming. Specific fear modulated the effects of arousal (Experiment 2): Spider-fearful participants’ judgments showed a threat advantage effect, while non-fearful participants’ judgments were less affected by emotional content. In Experiment 3, arrival times were less overestimated when pictures induced arousal. However, this effect interacted with the valence of the stimulus: For unpleasant stimuli, arousal induced shorter time-to-contact judgments, whereas for pleasant stimuli, an inverted U-shaped relation was found. We propose a general content effect to explain the overestimation with neutral pictures: Pictorial content may draw visual attention to inner contours instead of to the outer edges of the picture. This could delay time-to-contact judgments according to the known size-arrival effect. Our results add to the growing literature examining affective influences on visual perception.     

Psychophysiological and vocal measures in the detection of guilty knowledge.

The Guilty Knowledge Test (GKT) and its variant, the Guilty Actions Test (GAT), are both psychophysiological questioning techniques aiming to detect guilty knowledge of suspects or witnesses in criminal and forensic cases. Using a GAT, this study examined the validity of various physiological and vocal measures for the identification of guilty and innocent participants in a mock crime paradigm. Electrodermal, respiratory, and cardiovascular measures successfully differentiated between the two groups. A logistic regression model based on these variables achieved hit rates of above 90%. In contrast to these results, the vocal measures provided by the computerized voice stress analysis system TrusterPro were shown to be invalid for the detection of guilty knowledge.