The effects of acute stress on human prefrontal working memory systems.

We examined the relationship between acute stress and prefrontal-cortex (PFC) based working memory (WM) systems using behavioral (Experiment 1) and functional magnetic resonance imaging (fMRI; Experiment 2) paradigms. Subjects performed a delayed-response item-recognition task, with alternating blocks of high and low WM demand trials. During scanning, participants performed this task under three stress conditions: cold stress (induced by cold-water hand-immersion), a room temperature water control (induced by tepid-water hand-immersion), and no-water control (no hand-immersion). Performance was affected by WM demand, but not stress. Cold stress elicited greater salivary cortisol readings in behavioral subjects, and greater PFC signal change in fMRI subjects, than control conditions. These results suggest that, under stress, increases in PFC activity may be necessary to mediate cognitive processes that maintain behavioral organization.

Emotional disclosure and closeness toward offenders.

Two studies tested whether emotional disclosure increases feelings of closeness toward offenders. In Study 1, participants recalled either someone who had offended them or a neutral acquaintance. "Disclosure" participants then expressed their thoughts and feelings regarding their targets, and "suppression" participants described their targets nonemotionally. As predicted, disclosure increased closeness toward offenders but not toward acquaintances. Study 2 extended these results by including a good friend to test whether disclosure selectively increases closeness toward offenders, and not simply toward any person who evokes strong feelings. This prediction was confirmed. Furthermore, the disclosure effect remained reliable even after controlling for mood. Studies 1 and 2 also showed that closeness toward offenders, but not toward friends or acquaintances, was positively related to the proportion of emotion-related words disclosed. Collectively, these findings suggest that confronting the emotions associated with an offense may be an important first step toward forgiveness.

Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity.

A series of compounds possessing both H(1) histamine receptor antagonist and 5-lipoxygenase (5-LO) inhibitory activities was synthesized. The H(1)-binding scaffolds of cetirizine, efletirizine, and loratadine were linked to a lipophilic N-hydroxyurea, the 5-LO inhibiting moiety of zileuton. Both activities were observed in vivo, as was increased CYP3A4 inhibition compared to their respective single-function drugs. Selected analogs in the series were shown to be orally active in guinea pig models.

5-lipoxygenase inhibitors with histamine H(1) receptor antagonist activity.

A series of novel compounds with both 5-lipoxygenase (5-LO) inhibitory and histamine H(1) receptor antagonist activity were designed for the treatment of asthma. These dual-function compounds were made by connecting 5-LO and H(1) pharmacophores,N-hydroxyureas and benzhydryl piperazines, respectively. A range of in vitro activities was observed, with the furan analog 10 demonstrating both activities in an animal model. The activities observed were compared to single-function drugs.

Lesion induced new neuron incorporation in the adult hypothalamus of the avian brain.

Cell loss in most adult vertebrate brain regions is thought to be irreversible. Here, we explore the effects of electrolytic lesions on the induction of cell proliferation and newborn neurons in the ventromedial nuclei (VMN) of the hypothalamus in young and adult ring doves. The hypothalamus does not normally recruit new neurons. Bromodeoxyuridine (BrdU) and tritiated thymidine ([3H]Thy) were used to identify cells born before and after bilateral electrolytic lesions. Hu and NeuN were used to identify neurons. TUNEL test for apoptosis and 3A7 antibodies were used to identify morphological changes of pre-existing cells. Lesions produced significantly more newborn cells in the subventricular zone (SVZ). The rate of cell proliferation peaked at 7-14 days postlesion. A fraction of these newborn cells were neuronal precursor and began to migrate away along the radial glial fibers 2 weeks after lesion. During this period, the outer area of the lesion site was marked with massive apoptosis and re-expression of radial glial-like fibers. In birds that survived 5 months, we found newly differentiated neurons in the outer area of the lesion site. We conclude that electrolytic lesion can invoke neuronal recruitment in the adult hypothalamus. We further suggest that lesion-induced apoptosis and re-expression of developmental mechanisms might be involved in the recruitment process.