Closely spaced recurrent hippocampal seizures elicit two types of heightened epileptogenesis: a rapidly developing, transient kindling and a slowly developing, enduring kindling

Kindling is widely accepted as a model of chronic epilepsy as well as a model of plasticity in the nervous system. Conventional kindling studies have used infrequent stimuli (separated by many hours) to establish a fully kindled state in which enhanced responses (kindled motor seizures and protracted afterdischarges) are consistently triggered by stimuli that initially did not elicit such responses. The enhanced responses occur even after a prolonged stimulus-free interval. Whereas the establishment of a kindled state with traditional stimulus protocols takes several weeks, our previous work showed that kindling could take place much more quickly when the interstimulus interval was set at 30 min (rapid kindling). In this report we tested whether rapid kindling protocols share with traditional kindling protocols the ability to establish a fully kindled state. Using different stimulus protocols involving recurrent hippocampal seizures, we characterized two types of kindling. 'Rapid kindling' developed over hours, but was transient, with a decay rate of a few days so that a fully kindled state did not persist. In contrast, 'slow kindling' developed over several weeks and was enduring, apparently permanent, being associated with a fully kindled state. These findings suggest that, while having certain similarities, the two types of kindling arise from dissimilar mechanisms. The existence of these two types of kindling has implications for epileptogenesis in humans. Moreover, the protocols developed in this work provide a useful means to control for the effects of seizures that are not related to mechanisms underlying a fully kindled state.     

Effect of vitamin E on the anticoagulant response to warfarin

To clarify whether vitamin E enhances the pharmacologic effect of warfarin, we completed a double-blind clinical trial in which 21 subjects taking chronic warfarin therapy were randomized to receive either vitamin E or placebo. None of the subjects who received vitamin E had a significant change in the international normalized ratio, and thus it appears that vitamin E can safely be given to patients who require chronic warfarin therapy.     

Naloxone''s effects on operant responding depend upon level of deprivation

Treadmill exercise activates the hypothalamic-pituitary-adrenal axis and evokes metabolic responses proportional to exercise intensity and duration. To determine whether glucocorticoid administration would alter humoral and metabolic regulation during exercise, we administered 4 mg dexamethasone (DEX) or placebo to 11 normal, moderately trained men (19-42 yr old) in a double blinded random fashion 4 h before high intensity intermittent treadmill running. Plasma levels of ACTH, cortisol, arginine vasopressin (AVP), lactate, and glucose were measured before, during, and after exercise. A wide range of ACTH responses were seen in the DEX-treated group and arbitrarily defined as two subsets of individuals according to their responses to dexamethasone: DEX nonsuppressors and DEX suppressors. Exercise-induced increases in heart rate and circulating concentrations of cortisol, AVP, lactate, and glucose were all significantly greater (P < 0.05) in nonsuppressors (n = 4) compared to suppressors (n = 7) after both placebo and DEX administration. Interestingly, heart rate, AVP, and lactate responses were unaltered by DEX alone in both groups. In summary, this study demonstrates that normal individuals exhibit differential neuroendocrine and metabolic responses to exercise and pituitary/adrenal suppression after pretreatment with DEX. These findings reflect marked individual differences in the stress response to exercise that may derive from or lead to differential glucocorticoid negative feedback sensitivity in humans.     

alpha-Melanocyte stimulating hormone inhibits tumour necrosis factor-alpha stimulated intercellular adhesion molecule-1 expression in normal cutaneous human melanocytes and in melanoma cell lines

alpha-Melanocyte stimulating hormone (alpha-MSH) was found significantly to reduce tumour necrosis factor-alpha (TNF-alpha) stimulated upregulation of intercellular adhesion molecule-1 (ICAM-1) in normal adult cutaneous melanocytes. The maximum inhibitory response to alpha-MSH was obtained at around 10(-10) mol/L alpha-MSH when cells were coincubated with alpha-MSH and TNF-alpha for 24 h. alpha-MSH had little or no effect on basal ICAM-1 expression in melanocytes and the effects of alpha-MSH could be mimicked with 3-isobutyl-1-methylxanthine (IBMX). Preliminary data in three human melanoma cell lines also showed alpha-MSH and forskolin to be effective in significantly reducing TNF-alpha stimulated ICAM-1 expression over 24 h. The extent of the inhibition varied from cell line to cell line and was greatest in those cells with the highest number of alpha-MSH receptors. These data suggest that alpha-MSH has the ability to oppose the action of the pro-inflammatory cytokine TNF-alpha on melanocytes and melanoma cells.     

Immunohistochemical localisation of alpha1B-adrenergic receptors in the rat iris

This article reports results from a meta-analysis on adult age differences in the negative priming effect (21 studies on identity negative priming and 8 on location negative priming). Both younger and older adults were found to be susceptible to the negative priming effect in identity and location tasks. Effect sizes were homogeneous for both tasks, indicating that the data are adequately described without reference to moderator variables. State trace analysis on identity tasks, in which mean latencies in negative priming conditions were regressed onto mean latencies in baseline conditions, showed (a) that in both age groups the negative priming effect is proportional rather than additive and (b) that the negative priming effect is smaller in older adults as compared with younger adults.