Cyp2c44 Gene Disruption Exacerbated Pulmonary Hypertension and Heart Failure in Female but Not Male Mice

Epoxyeicosatrienoicacids (EETs), synthesized from arachidonic acid by epoxygenases of the CYP2C and CYP2J gene subfamilies, contribute to hypoxic pulmonary vasoconstriction (HPV) in mice. Despite their roles in HPV, it is controversial whether EETs mediate or ameliorate pulmonary hypertension (PH). A recent study showed that deficiency of Cyp2j did not protect male and female mice from hypoxia-induced PH. Since CYP2C44 is a functionally important epoxygenase, we hypothesized that knockout of the Cyp2c44 gene would protect both sexes of mice from hypoxia-induced PH. We tested this hypothesis in wild-type (WT) and Cyp2c44 knockout (Cyp2c44 (-/-)) mice exposed to normoxia (room air) and hypoxia (10% O2) for 5 weeks. Exposure of WT and Cyp2c44 (-/-) mice to hypoxia resulted in pulmonary vascular remodeling, increased pulmonary artery resistance, and decreased cardiac function in both sexes. However, in female Cyp2c44 (-/-) mice, compared with WT mice, (1) pulmonary artery resistance and right ventricular hypertrophy were greater, (2) cardiac index was lower, (3) left ventricular and arterial stiffness were higher, and (4) plasma aldosterone levels were higher, but (5) there was no difference in levels of EET in lungs and heart. Paradoxically and unexpectedly, we found that Cyp2c44 disruption exacerbated hypoxia-induced PH in female but not male mice. We attribute exacerbated PH in female Cyp2c44 (-/-) mice to elevated aldosterone and as-yet-unknown systemic factors. Therefore, we suggest a role for the human CYP2C genes in protecting women from severe PH and that this could be one of the underlying causes for a better 5-year survival rate in women than in men

Enhancing effects of chronic lithium on memory in the rat

Background: In spite of recent enrichment of neurochemical and behavioural data establishing a neuroprotective role lot lithium, its primary effects on cognitive functioning remain ambiguous. This study examines chronic lithium effects on spatial working memory and long-term retention. Methods: In three discrete experiments, rats subjected to 30 daily intraperitoneal injections (2 mmol/kg) of lithium (lithium groups: serum lithium = 0.5 +/- 0.4 mEq/l, 12 h post-injection) or saline (controls) were trained in 0-s delay T-maze alternation and then tested in 30-, 45- and 60-s delay alternation (Experiments 1, 2, 3, respectively). Animals from Experiment 1 were further tested in one-trial step-through passive avoidance under mild shock parameters (0.5 mA, 1 s). Retention was assessed 6 h later. Daily lithium or saline injections continued throughout behavioural testing. Results: Lithium animals were indistinguishable from controls during 0-delay alternation baseline (Experiments 1-3. accuracy > 88%) but showed significantly higher accuracy than controls at 30- and 45-s delays (93% versus 85% and 92% versus 82%, Experiments 1 and 2, respectively). At 60-s delay (Experiment 3) this beneficial effect of lithium was no longer apparent (lithium and control accuracy = 78%). In Experiment 4, the shock used did not Support 6-h passive avoidance retention in controls, whereas lithium animals showed significant step-through latency increases. Conclusions: Chronic lithium enhanced spatial working memory and promoted long-term retention of a weak aversive contingency. The results suggest that lithium may have potential as a cognitive enhancer. (c) 2006 Elsevier B.V. All rights reserved

The screening role of an introductory course in cognitive therapy training

Objective: This study examines the role of an introductory course in cognitive therapy and the relative importance of trainees’ characteristics in the selection process for an advanced course in cognitive therapy. Method: The authors assessed the files of all trainees who completed one academic year introductory course in cognitive therapy over the last seven consecutive years (N = 203). The authors examined variables such as previous training, overall involvement during the course, performance, and ability to relate to others, as well as the trainer’s evaluations of their performance. Results: Interaction skills in group situations and performance in written assignments were better predictors for admission into the advanced course. Conclusions: Trainees’ abilities to learn and to successfully relate to others in group situations are critical for entering an advanced cognitive therapy training course. These findings question the policy of full-scale training in cognitive therapy based merely on the candidates’ professional background, stressing instead the merits of an introductory course as an appropriate screening procedure