Near-field optical investigation of three-dimensional photonic crystals.

We show that the coupling of light from an external pointlike light source into a three-dimensional photonic crystal depends on the relative launching position with respect to the crystal lattice as well as on the frequency of light. The results are obtained with a near-field technique which is used to acquire optical information beyond the diffraction limit and to access optical details within the unit cell of the crystal. The experiments are performed at frequencies near the second-order L-gap. As a result, the changes in the shape of the near-field pattern are explained by the photonic properties of the crystal.

Eating soya improves human memory.

RATIONALE: Soya foods are rich in isoflavone phytoestrogens with weak agonist activity at oestrogen receptors. Oestrogen treatment has been found to improve memory in men awaiting gender reassignment and in post-menopausal women. OBJECTIVE: To examine the effects of supervised high versus low soya diets on attention, memory and frontal lobe function in young healthy adults of both sexes. METHODS: Student volunteers were randomly allocated to receive, under supervision, a high soya (100 mg total isoflavones/day) or a low soya (0.5 mg total isoflavones/day) diet for 10 weeks. They received a battery of cognitive tests at baseline and then after 10 weeks of diet. RESULTS: Those receiving the high soya diet showed significant improvements in short-term (immediate recall of prose and 4-s delayed matching to sample of patterns) and long-term memory (picture recall after 20 min) and in mental flexibility (rule shifting and reversal). These improvements were found in males and females. In a letter fluency test and in a test of planning (Stockings of Cambridge), the high soya diet improved performance only in females. There was no effect of diet on tests of attention or in a category generation task. Those on the high soya diet rated themselves as more restrained and, after the tests of memory and attention, they became less tense than did those on the control diet. CONCLUSIONS: Significant cognitive improvements can arise from a relatively brief dietary intervention, and the improvements from a high soya diet are not restricted to women or to verbal tasks.

Local phase measurements of light in a one-dimensional photonic crystal.

For the first time the local optical phase evolution in and around a small, one-dimensional photonic crystal has been visualized with a heterodyne interferometric photon scanning tunnelling microscope. The measurements show an exponential decay of the optical intensity inside the crystal, which consists of a periodic array of subwavelength air rods fabricated in a conventional ridge waveguide. In addition it is found that the introduction of the air rods has a counterintuitive effect on the phase development inside the structure. The heterodyne detection scheme allows the detection of low-intensity scattered waves. In the vicinity of the scattering air rods phase singularities are found with a topological charge of plus or minus one.

Are lorazepam-induced deficits in attention similar to those resulting from aging?

The purpose of this experiment was to compare, in three tasks of attention, the impairment caused by lorazepam (1 and 2.5 mg) administered to young volunteers with the impairment that results from aging. Performance on digit cancellation (DC), digit-symbol substitution (DSS), and Paced Auditory Serial Addition Task (PASAT) was significantly impaired by lorazepam (2.5 mg) and was significantly worse in the middle-aged group (mean +/- SEM, aged 58.9+/-0.8 years) compared with the younger, IQ-matched group (20.7+/-0.2 years). However, there were interesting differences in the extent of impairments among the three tests. In the DC test, lorazepam (2.5 mg) produced a significantly greater impairment than was seen in either the middle-aged men or middle-aged women. However, in the DSS test, the middle-aged women were significantly more impaired than either the middle-aged men or the young volunteers tested after lorazepam (2.5 mg). In the PASAT, both the lorazepam (2.5 mg) group and the middle-aged women were more impaired than the middle-aged men. These results raise the important possibility of gender differences in age-related decline of attentional processes.

Nicotine has calming effects on stress-induced mood changes in females, but enhances aggressive mood in males.

In a double-blind, placebo-controlled study, we examined the effects of nicotine (2 mg administered by inhalator) on the cognitive performance of male and female non-smoking students and on mood changes following a moderately stressful task. The groups were matched for age and IQ, and did not differ in pre-test measures of anxiety, depression, extroversion and neuroticism or in their weekly alcohol or daily caffeine intake. Nicotine did not change performance in tests of attention and memory. Exposure to moderate stress significantly increased ratings of anxiety, discontent and aggression and nicotine blocked these mood changes in females, but enhanced them in males. This suggests that young women may start regular smoking as a form of stress self-medication, which implies that preventative and smoking cessation programmes would be more successful in women if they addressed issues of stress and anxiety, which may be core factors underlying initiation and maintenance of regular smoking.

Is benzodiazepine-induced amnesia due to deactivation of the left prefrontal cortex?

UNLABELLED: The amnesic properties of benzodiazepines result from an impairment in explicit (conscious) acquisition of new material. RATIONALE: Explicit encoding of new material has consistently resulted in an increase in regional cerebral blood flow (rCBF) in the left prefrontal cortex, as measured by positron emission tomography (PET). OBJECTIVE: PET was used to determine whether an amnesic dose of midazolam (0.075 mg/kg) attenuated activation in this area during explicit memory encoding. METHODS: A second condition (condition A) used a task to control for the automatic processing that occurs during explicit learning (condition E). RESULTS: The subjects who received midazolam (n=7) recognised significantly fewer words than those who received placebo (n=8), but were not impaired with regard to automatic processing. rCBF was significantly increased in the left prefrontal cortex during explicit encoding of word lists in all subjects and in the temporal lobe and parieto-occipital regions during automatic processing. rCBF was significantly decreased in the prefrontal, superior temporal and parieto-occipital regions following midazolam. The midazolam-induced deactivation in the prefrontal cortex did not affect rCBF activations induced by the explicit memory condition (E-A). CONCLUSIONS: These results suggest that a specific interaction with prefrontal cortex activation does not underlie the amnesic effect of midazolam. However, it remains possible that a threshold level of prefrontal rCBF is necessary for encoding and that, after midazolam, this was not reached.

Beneficial effects of glycine (bioglycin) on memory and attention in young and middle-aged adults.

The N-methyl D-aspartate receptor complex is involved in the mechanism of long-term potentiation, which is thought to be the biological basis of learning and memory. This complex can be manipulated in a number of ways, one of which is through the strychnine-insensitive glycine receptor coagonist site. The effects of Bioglycin(Konapharma, Pratteln, Switzerland), a biologically active form of the amino acid glycine, were therefore studied in healthy students (mean age, 20.7 years) and middle-aged men (mean age, 58.9 years) with tests that measured attention, memory and mood, using a double-blind, randomized, crossover design. Compared with the young group, the middle-aged group had significantly poorer verbal episodic memory, focused, divided, and sustained attention; they also differed in their subjective responses at the end of testing. Bioglycin significantly improved retrieval from episodic memory in both the young and the middle-aged groups, but it did not affect focused or divided attention. However, the middle-aged men significantly benefited from Bioglycin in the sustained-attention task. The effects of Bioglycin differed from those of other cognitive enhancers in that it was without stimulant properties or significant effects on mood, and it primarily improved memory rather than attention. It is likely to be of benefit in young or older people in situations where high retrieval of information is needed or when performance is impaired by jet lag, shift work, or disrupted sleep. It may also benefit the impaired retrieval shown in patients with schizophrenia, Parkinson's disease, and Huntington's disease.

Conditions under which lorazepam can facilitate retrieval.

Memory is composed of three stages: acquisition, consolidation, and retrieval. By impairing acquisition processes, benzodiazepines cause anterograde amnesia while leaving intact information learned before the drug was taken. In some circumstances, retrieval of this information is even improved by benzodiazepines. It has been hypothesized that this phenomenon is not a true facilitation of retrieval processes, but is the result of reduced interference from items presented after drug administration and is thus a secondary consequence of drug-induced amnesia. Experiment 1 investigated the effect of 0.5, 1, and 2.5 mg of lorazepam on explicit episodic memory in healthy young volunteers. The 1-mg dose was found to significantly improve recall of items presented before drug administration without causing amnesia for items presented after drug administration, thus excluding an interference explanation. Experiment 2 investigated the conditions necessary to obtain facilitated retrieval with 1 mg of lorazepam. The results showed that facilitation was found only when two lists of semantically related material were presented, but that both of the lists could be presented before drug administration, thus excluding an effect of lorazepam on consolidation. Facilitation could be demonstrated in both direct (free recall) and indirect (backwards reading) retrieval tasks and when all of the material was presented after lorazepam administration. This improved retrieval could therefore be of clinical relevance, but any benefits would be reduced at higher doses that at the same time impair acquisition of new information. However, because 1 mg of lorazepam is an effective anxiolytic dose, these results suggest that it is possible to combine effective anxiety reduction with some benefits to memory.

Does the sedation resulting from sleep deprivation and lorazepam cause similar cognitive deficits?

It is notoriously difficult to assess the contribution of the sedative effects of benzodiazepines to the cognitive impairments that they produce. The purpose of the present experiment was to determine whether a similar pattern of cognitive impairment would be seen in conditions when subjects felt equally sleepy as the result of sleep deprivation. The effects of a sedative dose of lorazepam (2.5 mg) in healthy volunteers was therefore compared with the effects of acute sleep deprivation (a night on-call) in a group of junior doctors and the effects of chronically disturbed sleep due to snoring. Lorazepam, acute sleep deprivation, and chronic sleep disturbance all significantly increased subjective sedation. In addition, lorazepam significantly impaired performance in two tests of psychomotor speed and caused significant anterograde amnesia. Semantic and short-term memory were not impaired by lorazepam, nor was there any impairment in executive function. The only deficit found following acute sleep deprivation was in a test of semantic memory, generating examples from a difficult category. The only significant deficit in the group suffering from chronically disturbed sleep, compared with age-matched controls, was in executive function, and there was a nearly significant impairment in sustained attention. These results suggest that, despite the common factor of increased subjective sedation, the profile of cognitive impairment in the two sleep deprivation groups are neither similar to each other nor to that seen following an acute dose of lorazepam.

The influence of alcoholism and cirrhosis on benzodiazepine receptor function.

In a previous study we reported that the affinity of the platelet benzodiazepine receptor was greater in alcoholic cirrhotic patients compared with normal controls and that there were detectable ligands for the neuronal benzodiazepine receptor in plasma from both alcoholic and nonalcoholic cirrhotic patients. The aim of the present study was to assess the separate contributions of alcoholism and cirrhosis to the presence of ligands in plasma for the neuronal and peripheral benzodiazepine receptors and to changes in peripheral benzodiazepine receptor binding in platelets. These parameters were measured in 10 alcoholic cirrhotics, 9 nonalcoholic cirrhotics, 7 alcoholics with a normal liver function, and 15 nonalcoholic subjects and normal liver function. Both groups of alcoholics had been abstinent for several months and the nonalcoholic groups had abstained for 24 h before the study. The concentration of ligands for the peripheral benzodiazepine receptor were significantly higher in both cirrhotic groups compared with the other two groups, suggesting that cirrhosis was responsible for this accumulation. Furthermore, the cirrhotic patients with detectable concentrations of these ligands had significantly poorer episodic memory than those without ligands. However, the presence of ligands for the peripheral benzodiazepine receptor did not correlate with the change in receptor affinity, which was increased in the alcoholic cirrhotic group compared with all other groups. Neither cirrhosis nor alcoholism altered the peripheral benzodiazepine receptor number. The cirrhotic patients with detectable ligands for the neuronal benzodiazepine receptor showed psychomotor slowing and executive dysfunction. The results suggest that the ligands for the peripheral benzodiazepine receptor may contribute to some of the cognitive deficits seen in hepatic encephalopathy, but are not responsible for the receptor affinity change seen in the alcoholic cirrhotics. This affinity change is not solely due to the effects of alcohol and could possibly serve as a marker for those at risk for developing alcoholic cirrhosis.

Changes in tonic immobility and the GABA-benzodiazepine system in response to handling in the chick.

Changes in the GABA-benzodiazepine system were investigated following regular handling of male chicks. Compared with handling-naive chicks, those exposed to 10 days of gentle handling required a larger number of inductions and had a lower duration of tonic immobility. Corresponding biochemical changes occurred, with handling-habituated chicks having a significantly lower basal [14C]GABA release from archistriatal slices and a reduction in the Bmax of [3H]muscimol binding in the forebrain. Benzodiazepine binding in the archistriatum was investigated using in vitro quantitative receptor autoradiography. Binding was localised in the anterior, mediale, dorsalis, and ventralis intermedium nuclei of the archistriatum, and there was significantly more binding in the anterior and ventralis intermedium/mediale archistriatum nuclei than in the dorsalis intermedium archistriatum nuclei. Benzodiazepine binding was not altered after handling in any of the investigated nuclei of the archistriatum. The results suggest that whereas several days of gentle handling in chicks leads to a decrease in forebrain GABAA receptors and a decrease in GABA release from the archistriatum, there are no accompanying changes in benzodiazepine receptors. Regular handling exerts a specific effect on chicks: it reduces their fear or human beings but not that of novel places or objects. It is possible that the pattern of biochemical changes observed in the present study may be specifically associated with this particular behavioural modification rather than with a change in general fearfulness.

Sex differences in benzodiazepine binding in the frontal cortex and amygdala of the rat 24 hours after restraint stress.

Marked sex differences have been reported in behavioural responses of rats 24 h after exposure to a brief period of restraint (RT) stress. In the present study, differences in benzodiazepine (BZ) binding between male and female rat litter-mates randomly allocated to control or RT groups were investigated 24 h after RT. Scatchard analysis, using [3H] flunitrazepam, was carried out on the the frontal cortex and amygdala. In the frontal cortex, females had a significantly lower affinity and a greater number of BZ receptors than males; males, but not females, showed increased affinity after RT. In the amygdala, there was a tendency towards a greater number of BZ receptors in females, with no effect of RT on receptor number or affinity. These results provide evidence of sex differences in BZ binding both under basal conditions and 24 h after RT, which could contribute to the behavioural sex differences already reported.

Cognitive impairments of alcoholic cirrhotic patients: correlation with endogenous benzodiazepine receptor ligands and increased affinity of platelet receptors.

OBJECTIVES: To determine whether differences in cognitive function between alcoholic and non-alcoholic cirrhotic patients relate to differences in endogenous ligands for the benzodiazepine receptor and/or benzodiazepine binding. METHODS: Seventeen grade-I hepatic encephalopathic patients (nine alcoholic, eight non-alcoholic) were compared with 10 matched controls on plasma concentrations of endogenous ligands for the neuronal benzodiazepine receptor, benzodiazepine binding in platelets, and performance on tests of cognitive function. RESULTS: Both groups of patients were impaired on verbal recall and on reaction time tasks compared with controls; alcoholic patients were also impaired on Reitan's trails test and digit cancellation. Four of the 17 patients had detectable concentrations of endogenous benzodiazepine ligands and they were more impaired than other patients on trails and cancellation tests. The groups did not differ in the density of benzodiazepine platelet receptors, but receptor affinity was higher in alcoholic patients than in controls; furthermore, receptor affinity correlated with the time to complete the cancellation task and with reaction time. CONCLUSION: Alcoholic cirrhotic patients may have enhanced concentrations of ligands for neuronal and peripheral benzodiazepine receptors and these may contribute to cognitive impairments in these patients.

Behavioural and neurochemical responses of male and female chicks to cat odour.

In the first experiment male chicks were exposed to neutral and cat odours at days 4, 7, or 10 after hatching. Of the chicks tested at day 4, few made contact with either odour cloth, but those tested at day 7 made fewer contacts with the cat odour cloth, compared with the neutral odour, spent less time in contact with it, and spent more time in the zone furthest from the cloth. These clear differences were not seen in the group tested at day 10. In a second experiment, the behaviour of day 7 male chicks was compared in the presence of neutral, disinfectant, chick blood or cat odours, and the most extreme differences were between neutral and cat odours. In a third experiment, both male and female chicks were exposed to cat odour at day 7 and both showed similar avoidance. After exposure to cat odour both sexes showed significantly reduced GABA enhancement of benzodiazepine binding; which is a change associated with increased fear. However, after exposure to cat odour, they also showed significant decreases in 5-HT availability evidenced by lower basal and K(+)-evoked [3H]-5-HT release and, in the male chicks only, by an increased [3H]-5-HT uptake from archistriatal slices. These changes in 5-HT function are in the direction associated with reduced fear and would, therefore, seem to be adaptive and compensatory in function. Neither male nor female chicks showed any differences in [14C]-GABA release or uptake as a result of exposure to cat odour. Although the pattern of response to cat odour was the same in both male and female chicks at day 7, there were significant sex differences in 5-HT and GABA tone and benzodiazepine binding; these sex differences were also found in day 10 chicks. The importance of these for sex differences in trait anxiety is discussed.

Short-term rebound anxiolytic effects and long-term changes in platelet benzodiazepine binding after pentylenetetrazole-kindling in two strains of rat.

Although there were no differences in response to an acute injection of pentylenetetrazole (PTZ), there were strain differences in the development of kindled seizures to repeated injections (PTZ; 30 mg/kg 3 times weekly for 13 injections), with Wistar rats reaching stage 4 or 5 of clonic-tonic seizures, but hooded Lister rats reaching only stage 2 or 3 of convulsive waves axially through the body. The strains also reacted differently to a test dose of PTZ (20 mg/kg) one week after the end of kindling, with the Wistar strain showing stage 3 and the Lister strain stage 2 seizures. When the rats were tested 24 h after the end of the kindling injections there was an anxiolytic effect in the social interaction test, in both the low light, familiar and the low light, unfamiliar test conditions that reached significance in the Wistar strain. The Wistar kindled rats showed an anxiolytic effect in the elevated plus-maze test of anxiety when they were tested 24 h after the end of kindling. The anxiolytic effects found 24 h after kindling could not be due to the seizure 24 h earlier, since no changes were found in rats tested 24 h after a single seizure from PTZ (60 mg/kg). When the rats were tested 1 week after the end of kindling there were no changes, compared with vehicle-injected controls, in either test of anxiety. There was no change in benzodiazepine binding in platelets of the kindled Lister rats but there was a significant increase in the kindled Wistar rats 1 week after the end of kindling and also 24 h after a single PTZ seizure. The pattern of increased platelet benzodiazepine binding did not correspond with the time course of rebound anxiolytic effects. However, after kindling it seems that there are long-lasting changes in benzodiazepine binding that are similar to the short-term increases that are found following a single seizure.

Handling alters habituation and response to stimulus change in the holeboard.

The responses of rats that had been extensively handled for 18 days were compared in the holeboard with those of rats that had received handling for only 4 days before the test. The extensively handled group showed slower between-day habituation of exploratory head-dipping. They did not differ in the number of head-dips, but spent longer head-dipping, at holes with objects than at those without. The less-handled group did not differ in the time spent head-dipping, but made more head-dips at empty holes. Both groups reacted similarly to the removal of the objects on day 4. However, the extensively handled rats showed a greater response of increased head-dipping when a novel object was introduced on day 5. The groups did not differ in their locomotor activity, but the extensively handled group made more rears. The results are discussed with respect to the neurochemical changes that have been found after repeated handling.

Oxaprozin dose proportionality.

Twelve normal subjects each received single 300-, 600-, and 1200-mg oral doses of oxaprozin according to a three-period crossover design. Total drug plasma concentrations did not increase in proportion to the dose administered. Total clearance (CIo) and volume of distribution (Vd) increased with dose, though elimination t1 2 remained unchanged. The fraction of unbound oxaprozin in plasma (fup) varied linearly with total plasma concentration: it increased from 0.068 per cent at 10 micrograms/ml to 0.180 per cent at 170 micrograms/ml. A parameter fup was therefore introduced to express the average degree of unbound drug plasma for a given dose, and to allow the calculation of unbound volume of distribution (Vdu) and intrinsic clearance (CIi) as if binding were constant. Even though fup increased with dose, the overall binding in the body (fub approximately 0.52 per cent) was relatively stable. Neither Vdu nor CIi changed with dose; hence, unbound oxaprozin kinetics can be considered to be linear. Protein binding had no effect on unbound oxaprozin plasma levels within the given dose range, and there was a one-to-one proportionality between the dose administered and the unbound drug concentration in plasma.

Protein binding and clearance of oxaprozin, a highly bound anti-inflammatory agent.

Conventional dialysis cells were used in initial attempts to determine the binding characteristics of oxaprozin (4,5-diphenyl-2-oxazolepropionic acid, Wy-21,743). Equilibration required dialysis times up to 22 hours at 37 degrees C resulting in deterioration of plasma proteins, which in turn leads to highly variable binding values. In contrast, dialysis with Dianorm cells requires less than 4 hours to reach equilibrium. The configuration of the cell optimizes the contact between the solutes and the membrane and allows for a more efficient mixing and exchanging of the solute. The percentage of unbound drug was linearly related to total drug in human plasma samples to which oxaprozin in clinically relevant concentrations (55-405 micrograms/ml) had been added. Likewise, a linear relationship between total drug concentration and the percentage unbound was observed in specimens from a pharmacokinetic study in healthy volunteers. Clearance of total oxaprozin from plasma correlated with the percentage unbound drug. Thus the higher clearance observed under steady-state conditions (where concentrations are higher than following single dose administration) was caused by a larger unbound fraction available to the elimination sites.

Evaluation of a DNA polymerase-deficient mutant of E. coli for the rapid detection of carcinogens.

Differential growth inhibition of two E. coli cultures was evaluated as a rapid screening technique for chemical carcinogens. Of the carcinogens tested, only "direct acting" carcinogens produced positive results. Furthermore, this test is not a quantitative assay in that neither was a dose--response relationship seen nor did potent carcinogens necessarily show a greater response than weaker carcinogens.