The magnitude and the extinction duration of the cocaine-induced conditioned locomotion-activated response are related to the number of cocaine injections paired with the testing context in C57BL/6J mice

Behavioural activation repeatedly induced by a stimulant in rodents can persist in the absence of the drug if the animals are tested in the context where the drug was previously given, a phenomenon often explained in terms of Pavlovian conditioning. The aim of this study was to verify whether the amplitude of the putative CR (the drug-like activity) increases with the number of the US-CS associations (the number of drug-context pairings), one of the most representative rules of Pavlovian conditioning. The effect of the number of trials on the speed of extinction was also considered. C57BL/6J mice received 3, 6 or 12 once-daily injections of either saline or 12 mg/kg (-)-cocaine hydrochloride (s.c.) in the same test context, a photocell activity-box in which they were tested for 60 min after every injection. Other groups received the same treatments outside of the test context (being placed in a novel cage tub after each injection). Twenty-four hours after the last treatment session, all mice were challenged with saline in the test context (test for conditioned activity), extinction sessions taking place on the three subsequent days. Sensitisation to the locomotor-activating effect of cocaine developed only amongst the animals injected 6 or 12 times, the magnitude of the last sensitised response being comparable for these two injections regimen. On saline challenge, only the animals that had received 6 or 12 cocaine injections showed significant conditioned activity (CR), with the greatest response occurring following 12 injections. The 6-trial group reached the level of non-significance after fewer extinction sessions than the 12-trial group; however, the rates of extinction did not differ (comparable regression coefficients and quasi-parallel curves). These results suggest that the amplitude of the CR (cocaine-like stimulation after saline), and perhaps less convincingly the duration of extinction, are functions of the number of the US-CS (cocaine-context) pairings, supporting the Pavlovian nature of post-sensitisation placebo drug-like effects.     

Directional interference during bimanual coordination: is interlimb coupling mediated by afferent or efferent processes

The role of afferent information in bimanual directional interference was studied by means of a modulation of the response-produced information in one of both limbs. In Experiment 1, visual information was either present, withdrawn, or shown with a directional transformation on a LCD screen. In Experiment 2, the technique of muscle tendon vibration was used to bias the kinesthetic afferent information associated with movement. The findings revealed strong evidence for directional interference between both limbs. Nevertheless, no evidence could be advanced that the observed interference from the right onto the left limb movement was modulated by manipulation of the afferent sources of information. It is concluded that directional interference primarily emerges at the efferent level of movement planning and organization.     

A direct prefrontotectal tract against distractibility in the human brain

Distractibility, which can be defined as an attention deficit in which orientation toward irrelevant targets can be hardly inhibited, is commonly related to a dysfunction of the dorsolateral prefrontal cortex. Here, we show that increased distractibility, observed in a patient with an exceptionally small lesion located in the upper brainstem, may result from the interruption of a direct tract that connects the prefrontal cortex to the superior colliculus, a structure involved in both eye movement control and attentional shifts.     

Enhancing the sensitivity of a sustained attention task to frontal damage: convergent clinical and functional imaging evidence

Despite frequent reports of poor concentration following traumatic brain injury, studies have generally failed to find disproportionate time-on-task decrements using vigilance measures in this patient group. Using a rather different definition, neuropsychological and functional imaging research has however linked sustained attention performance to right prefrontal function--a region likely to be compromised by such injuries. These studies have emphasised more transitory lapses of attention during dull and ostensibly unchallenging activities. Here, an existing attention measure was modified to reduce its apparent difficulty or 'challenge'. Compared with the standard task, its capacity to discriminate traumatically head-injured participants from a control group was significantly enhanced. Unlike existing functional imaging studies, that have compared a sustained attention task with a no-task control, in study 2 we used positron emission tomography to contrast the two levels of the same task. Significantly increased blood flow in the dorsolateral region of the right prefrontal cortex was associated with the low challenge condition. While the results are discussed in terms of a frontal system involved in the voluntary maintenance of performance under conditions of low stimulation, alternative accounts in terms of strategy application are considered.     

IL-11 and IL-17 expression in nasal polyps: relationship to collagen deposition and suppression by intranasal fluticasone propionate

OBJECTIVES/HYPOTHESIS: Chronic hyperplastic sinusitis (CHS) with nasal polyps (NP) is characterized by extensive mucosal thickening, goblet cell hyperplasia, and subepithelial fibrosis. These features are described to be part of remodeling in the lower airways. The cytokines interleukin (IL)-11 and IL-17 are believed to play a role in lower airway remodeling, but there has been very little work so far examining these cytokines and their relationship to fibrosis in CHS/NP. The aims of this study were to examine the deposition of collagens types I, III, and V in CHS/NP, evaluate the relationship of collagen deposition to expression of IL-11 and IL-17, and to examine the effect of treatment with intranasal fluticasone on these features. STUDY DESIGN: Sixteen subjects were included in this double-blind, placebo-controlled study. NP biopsies were obtained at the baseline and after 4 weeks of treatment with intranasal fluticasone propionate (FP, Flonase) or placebo. Normal control middle turbinate biopsies from eight nonallergic subjects without sinusitis were used as a control for cytokine and collagen expression. METHODS: Tissues were assessed for deposition of collagen types I, III, and V using immunocytochemistry. The expression of the cytokines IL-11 and IL-17 was examined by immunostaining or in situ hybridization. The pre- to posttreatment results were analyzed using paired t test, and the magnitude of changes were estimated using one-way analysis of variance (ANOVA) statistical test followed by least significance difference post hoc comparisons of means. RESULTS: Compared with normal control nasal turbinate tissues, collagen types I, III, and V were increased in all NP tissues, with a predominance of types III and V. Collagen deposition was most abundant in the submucosal connective tissue and in the basement membrane zone. FP treatment had no significant effect on deposition of any collagen type. Expression of IL-11 and IL-17 was also greatly increased in NP compared with control nasal turbinate tissues. IL-11 expression was observed in both inflammatory cells and the epithelium, whereas IL-17 expression was primarily associated with inflammatory cells. In the pretreatment NP, a correlation was found between the presence of IL-11 and collagen type I (r = 0.59, P =.02) and also between IL-17 and both CD4+ and CD8+ T lymphocytes (r = 0.52, P =.05; r = 0.60, P =.02, respectively). Treatment with FP significantly reduced IL-11 expression in subepithelial inflammatory cells and in the epithelial compartment. In contrast, although IL-17 expression was reduced by FP, this effect did not reach statistical significance. CONCLUSION: NP manifest an increased expression of collagen types III, V, and I and an increase in profibotic cytokines IL-11 and IL-17. A correlation exists between deposition of collagen type I and expression of IL-11, suggesting a possible role for IL-11 in NP remodeling. Collagen deposition was not reversed by FP treatment, whereas IL-11 expression was suppressed. These results are consistent with a partial insensitivity of NP to FP treatment but also suggest that longer-term treatment or perhaps earlier intervention with FP might reduce proinflammatory cytokine signals and ultimately have a beneficial effect in preventing airway remodeling in NP.     

Proportional assist ventilation decreases thoracoabdominal asynchrony and chest wall distortion in preterm infants

Thoracoabdominal asynchrony (TAA) and chest wall distortion (CWD) are commonly seen in preterm infants secondary to a highly compliant rib cage and poor compensation of distorting forces by inspiratory rib cage muscles. Continuous positive airway pressure (CPAP) reduces TAA and CWD by stenting the chest wall. We hypothesized that application of positive airway pressure only during inspiration and in proportion to an infant's inspiratory effort should have a similar but more pronounced effect than CPAP alone. A ventilator providing airway pressure changes in proportion to flow and volume generated by an infant (proportional assist ventilation) was used to unload the respiratory pump during inspiration. Ten preterm infants were studied [birth weight, 745 (635-1175) g; gestational age, 26.5 (24-31) wk; postnatal age 3 (1-7) d; medium (range)]. TAA and CWD were determined by respiratory inductive plethysmography. TAA was expressed as the phase angle between the rib cage and abdominal motion and CWD as the total compartmental displacement ratio. In addition, we measured tidal volume with a pneumotachograph and esophageal and airway pressure deflections with pressure transducers. Measurements were obtained during alternating periods of CPAP and two different degrees of support (Gain 1 = 1.09 +/- 0.68, Gain 2 = 1.84 +/- 0.84 cm H(2)O/mL) that were provided by a proportional assist ventilator. Phase angle and the total compartmental displacement ratio decreased with increasing gain compared with CPAP alone. Peak airway pressure increased from 0.6 to 3.8 to 7.6 cm H(2)O above positive end-expiratory pressure (PEEP) with CPAP, Gain 1, and Gain 2, respectively, as tidal volume increased from 2.8 to 4.1 to 4.7 mL/kg. Esophageal pressure changes decreased only little with increasing gain. Chest wall excursion increased and abdominal movement decreased, indicating a redistribution of tidal volume between chest and abdomen. We conclude that proportional assist ventilation reduces TAA and CWD by generating a small increase in airway pressure that occurs in synchrony and in proportion to each inspiratory effort.     

Responses of Chub (Leuciscus cephalus) Populations to Chemical Stress,Assessed by Genetic Markers,DNA Damage and Cytochrome P4501A Induction

Indicators of effects at the population level (genetic variation using allozymes) and early indicators of pollution (EROD activity and DNA strand break formation) were analysed in chub (Leuciscus cephalus) living in weakly and heavily contaminated stations of the Rhône River watershed. The genetic erosion was mainly detected in a fish population living in a contaminated small river system, through modifications in allelic and genotypic frequencies for PGM-2 locus and could be linked to a genetic bottleneck and to the reduced gene flow from upstream unable to maintain or restore the genetic diversity. In a contaminated large river system, the genetic diversity for PGM-2 and other loci was maintained and was probably the consequence of a high gene flow from upstream, linked to a sustained drift of larvae and juveniles in the system. A convergent increase of the frequency of the 90 allele at PGM-2 was observed in two contaminated stations compared with the reference station, this trend being confirmed on a more extensive geographic scale over the Rhône River basin. A high level of EROD activity was detected in both contaminated sites but only the fish in the large river system showed a significant DNA damage level compared to the reference population. The low DNA damage level and high hepato-somatic ratio characterized the impacted population of the small river system and could be associated to a chronic high-level exposure of fish to pollutants which selected individuals exhibiting a high level of DNA damage repair. In the two contaminated systems, some genotypes at the PGM-2 and EST-2 loci showed a low level of DNA damage and/or a high EROD activity and may be considered as being tolerant to pollutants. A higher tolerance of the most heterozygous fish was also detected in the contaminated large system and confirmed that a high level of heterozygosity may be necessary for survival in such a system.     

Keratographie (Hornhauttätowierung) bei Hornhautleukom

BACKGROUND: Since antiquity attempts have been made to minimize disfigurement and stigmatization of patients with leukoma. Keratography is a relatively new method for imprinting color pigments into the corneal stroma with an entomological needle. MATERIALS AND METHODS: Keratography was performed in 20 patients at the University Eye Hospital, Munich, between November 1997 and September 1999. Patients had either a leukoma that did not tolerate prothesis or had another cloudy corneal disease. The operation was carried out in our outpatient clinic under local anesthesia. RESULTS: There was a single operation in three patients, two operations in nine, three operations in six, and four operations in two. Postoperatively 33% of patients complained of pain. No postoperative bacterial keratitis or perforation occurred. CONCLUSION: All patients were highly satisfied. The long-term stability of color pigments must still be evaluated.