Time-dependent involvement of the dorsal hippocampus in trace fear conditioning in mice

Hippocampal and amygdaloid neuroplasticity are important substrates for Pavlovian fear conditioning. The hippocampus has been implicated in trace fear conditioning. However, a systematic investigation of the significance of the trace interval has not yet been performed. Therefore, this study analyzed the time-dependent involvement of N-methyl-D-aspartate (NMDA) receptors in the dorsal hippocampus in one-trial auditory trace fear conditioning in C57BL/6J mice. The NMDA receptor antagonist APV was injected bilaterally into the dorsal hippocampus 15 min before training. Mice were exposed to tone (conditioned stimulus [CS]) and footshock (unconditioned stimulus [US]) in the conditioning context without delay (0 s) or with CS-US (trace) intervals of 1-45 s. Conditioned auditory fear was determined 24 h after training by the assessment of freezing and computerized evaluation of inactivity in a new context; 2 h later, context-dependent memory was tested in the conditioning context. NMDA receptor blockade by APV markedly impaired conditioned auditory fear at trace intervals of 15 s and 30 s, but not at shorter trace intervals. A 45-s trace interval prevented the formation of conditioned tone-dependent fear. Context-dependent memory was always impaired by APV treatment independent of the trace interval. The results indicate that the dorsal hippocampus and its NMDA receptors play an important role in auditory trace fear conditioning at trace intervals of 15-30-s length. In contrast, NMDA receptors in the dorsal hippocampus are unequivocally involved in contextual fear conditioning independent of the trace interval. The results point at a time-dependent role of the dorsal hippocampus in encoding of noncontingent explicit stimuli. Preprocessing of long CS-US contingencies in the hippocampus appears to be important for the final information processing and execution of fear memories through amygdala circuits.     

Is harm avoidance an essential feature of patients with panic disorder?

OBJECTIVE: Previous studies on the Tridimensional Personality Questionnaire (TPQ) in patients with panic disorder (PD) have failed to support Cloninger's hypothesis that PD is not specifically related to any of the 3 personality dimensions. In most studies, patients with PD had clearly higher harm avoidance (HA) scores. This finding, however, could be biased by comorbid personality disorders in the samples. In the present study, we examined the TPQ scores in 43 patients without comorbid personality disorders. METHOD: The differences between PD patients without personality disorders and control subjects were examined by hierarchical analyses of variance. RESULTS: We found that PD patients without personality disorders had higher HA scores than control subjects, whereas significant differences were not demonstrated for the novelty seeking and reward dependence dimensions. CONCLUSION: Our results indicate that repeated demonstrations of elevated HA scores in patients with PD are not crucially influenced by comorbid personality disorders.     

Psychological characteristics of patients with chronic obstructive pulmonary disease: a review

OBJECTIVE: The aim of this study was to review research on psychological characteristics in chronic obstructive pulmonary disease (COPD) patients and to summarize the findings of associations between psychological variables and various aspects of life, illness, and health in COPD patients. METHODS: The following databases were searched: Medline, PsycINFO, and the Cochrane Library. RESULTS: A total of 81 studies, published between 1968 and 2004, was identified. The reviewed studies indicated that patients suffering from COPD have a high prevalence of psychological disorders and may function at a reduced level of efficiency due to neuropsychological impairments. Psychological characteristics also seemed to be associated with functional disability and reduced quality of life. CONCLUSION: Psychological characteristics are important variables that interact with physical symptoms, and they should be taken into account when treating COPD patients. More studies with rigorous methodological designs are needed to describe the role of psychological variables in COPD accurately and reliably.     

Behavioural characterisation of transgenic mice overexpressing galanin under the PDGF-B promoter

The behavioural phenotype of transgenic mice (3-5-months old) overexpressing galanin (GalOE mice) under the platelet-derived growth factor B (PDGF-B) promoter was evaluated in a battery of tests, including locomotor cages, light-dark exploration test, elevated plus-maze and the Porsolt forced swim test. Learning and memory were assessed in the Morris water maze task. GalOE mice showed a slight increase in spontaneous locomotor activity assessed in the locomotor cages, but the amphetamine-induced increase in locomotor activity was somewhat lower in GalOE mice. Anxiety-like behaviour in light-dark exploration and elevated plus-maze tests did not differ between genotypes. In the Porsolt forced swim test, GalOE mice displayed an increased time of immobility, indicative of increased learned helplessness possibly reflecting increased stress-susceptibility and/or depression-like behaviour. GalOE mice showed normal learning and memory retention in the Morris water maze tasks. These data support the hypothesis that galanin may have a role in functions related to mood states, including affective disorders.     

Current challenges and concepts in the preparation of root canal systems: a review

Nickel-titanium rotary instruments are important adjuncts in endodontic therapy. This review attempts to identify factors that influence shaping outcomes with these files, such as preoperative root-canal anatomy and instrument tip design. Other, less significant factors include operator experience, rotational speed, and specific instrument sequence. Implications of various working length definitions and desired apical widths are correlated with clinical results.Despite the existence of one ever-present risk factor, dental anatomy, shaping outcomes with nickel-titanium rotary instruments are mostly predictable. Current evidence indicates that wider apical preparations are feasible. Nickel-titanium rotary instruments require a preclinical training period to minimize separation risks and should be used to case-related working lengths and apical widths. However, and despite superior in vitro results, randomized, clinical trials are required to evaluate outcomes when using nickel-titanium instruments.     

Prostasomes are secreted from poorly differentiated cells of prostate cancer metastases

BACKGROUND: Prostasomes are small (40-500 nm), granule-like bodies, found in normal epithelial cells of the prostate and secreted into the prostate duct system. Also poorly differentiated prostate cancer cells are producing prostasomes, since we could isolate and purify prostasomes from vertebral metastases with biochemical methods. To find out whether these prostasomes are secreted into extracellular sites of the metastases, we used electron microscopy. METHODS: Small biopsies from vertebral metastases of prostate cancer, taken directly from the operating field at surgery, were immediately fixated, embedded in plastic and processed for electron microscopy. RESULTS: We found that prostasomes could be identified extracellularly in the interstitial tissues as well as in the cytoplasm of the metastatic cells. CONCLUSION: We conclude that prostasomes produced by the cells of vertebral metastases of prostate cancer are distributed both intracellularly and extracellularly in the interstitial spaces of the tissue. Thus, prostasomes of metastases could perhaps be exploited as targets for immunodiagnosis and/or immunotherapy.     

The citrus-derived flavonoid naringenin exerts uterotrophic effects in female mice at human relevant doses

Gavage administration of the citrus flavonoid naringenin, 3',4,5,7-tetrahydroxyflavanon for 4 consecutive days, to immature female mice (postnatal day 17-20) at 4 or 100 mg/kg b.wt. significantly increased uterine weights 3 and 4 times, respectively. Analysis of uterine oestrogen receptor alpha revealed that naringenin significantly increased the cytosolic concentration of oestrogen receptor alpha, whereas in nuclei the oestrogen receptor alpha concentration was significantly decreased as compared to the solvent control. This was in contrast to the positive control 17 beta-oestradiolacetate which acted as a true oestrogen by increasing the concentration of both total and nuclear oestrogen receptor alpha. Both naringenin and 17 beta-oestradiolacetate, however, significantly, induced nuclear oestrogen receptor alpha in the liver, suggesting a tissue specific effect of naringenin on oestrogen receptor alpha distribution. In order to investigate the tissue levels at which the uterotrophic effect was observed, the distribution of an oral dose of tritiated naringenin (4 mg/kg) was investigated in 3-week-old female mice. The radioactivity content (ng naringenin equivalents/g tissue) was found to be highest in the gastrointestinal-tract, followed by the kidneys and liver. Uterus and ovaries were also found to contain relatively high and approximately equal amounts of naringenin. The concentration of naringenin in uterus and ovaries was found to be ten times higher as compared to the mammary tissue. The urinary excretion of more than 25% of the administered dose, within 8 hr after dosing indicated that naringenin is absorbed extensively in mice. The plasma concentration of 0.5 microM found in the present study is similar to the peak plasma concentration of naringenin (0.6 microM) observed in man following ingestion of 400-760 ml of orange juice (Erlund et al. 2001). This could be taken to suggests that ingestion of orange juice and other citrus fruits and juices may give rise to sufficiently high tissue levels of naringenin in man to exert a biological effect.     

Disruption of EphA/ephrin-a signaling in the nigrostriatal system reduces dopaminergic innervation and dissociates behavioral responses to amphetamine and cocaine

We have investigated functional roles of EphA/ephrin-A signaling in the development and function of the nigrostriatal system by overexpressing a soluble, broad-range EphA receptor antagonist in the central nervous system of transgenic mice. Adult transgenic mice showed a 30-40% reduction in the total volume of the substantia nigra (SN) without detectable differences in the number of dopaminergic neurons. Using fluorogold retrograde tracing from the striatum, we detected a 40-50% reduction in the number of dopaminergic neurons that could be traced from this structure in transgenic mice, suggesting that, a lower proportion of these cells were able to reach the striatum after disruption of EphA/ephrin-A signaling. In spite of this, total dopamine content in the striatum of transgenic mice was comparable to wild type. Analysis of locomotor activity and its regulation by pharmacological treatments that stimulate dopaminergic transmission revealed an unexpected dissociation of the behavioral responses to amphetamine and cocaine. In particular, transgenic mice were relatively insensitive to amphetamine while retaining normal responsiveness to cocaine, which, to the best of our knowledge, represents the first report of a dissociation of the behavioral responses to these two psychostimulants. Together, these results reveal an unexpected role for EphA/ephrin-A signaling in the normal connectivity and function of midbrain dopaminergic neurons.