Oleanolic acid: a novel cardioprotective agent that blunts hyperglycemia-induced contractile dysfunction.

Diabetes constitutes a major health challenge. Since cardiovascular complications are common in diabetic patients this will further increase the overall burden of disease. Furthermore, stress-induced hyperglycemia in non-diabetic patients with acute myocardial infarction is associated with higher in-hospital mortality. Previous studies implicate oxidative stress, excessive flux through the hexosamine biosynthetic pathway (HBP) and a dysfunctional ubiquitin-proteasome system (UPS) as potential mediators of this process. Since oleanolic acid (OA; a clove extract) possesses antioxidant properties, we hypothesized that it attenuates acute and chronic hyperglycemia-mediated pathophysiologic molecular events (oxidative stress, apoptosis, HBP, UPS) and thereby improves contractile function in response to ischemia-reperfusion. We employed several experimental systems: 1) H9c2 cardiac myoblasts were exposed to 33 mM glucose for 48 hr vs. controls (5 mM glucose); and subsequently treated with two OA doses (20 and 50 µM) for 6 and 24 hr, respectively; 2) Isolated rat hearts were perfused ex vivo with Krebs-Henseleit buffer containing 33 mM glucose vs. controls (11 mM glucose) for 60 min, followed by 20 min global ischemia and 60 min reperfusion ± OA treatment; 3) In vivo coronary ligations were performed on streptozotocin treated rats ± OA administration during reperfusion; and 4) Effects of long-term OA treatment (2 weeks) on heart function was assessed in streptozotocin-treated rats. Our data demonstrate that OA treatment blunted high glucose-induced oxidative stress and apoptosis in heart cells. OA therapy also resulted in cardioprotection, i.e. for ex vivo and in vivo rat hearts exposed to ischemia-reperfusion under hyperglycemic conditions. In parallel, we found decreased oxidative stress, apoptosis, HBP flux and proteasomal activity following ischemia-reperfusion. Long-term OA treatment also improved heart function in streptozotocin-diabetic rats. These findings are promising since it may eventually result in novel therapeutic interventions to treat acute hyperglycemia (in non-diabetic patients) and diabetic patients with associated cardiovascular complications.

Vividness of visual imagery and social desirable responding: correlations of the vividness of visual imagery questionnaire with the balanced inventory of desirable responding and the Marlowe-Crowne scale.

Correlational research investigating the relationship between scores on self-report imagery questionnaires and measures of social desirable responding has shown only a weak association. However, researchers have argued that this research may have underestimated the size of the relationship because it relied primarily on the Marlowe-Crowne scale (MC; Crowne & Marlowe, Journal of Consulting Psychology, 24, 349-354, 1960), which loads primarily on the least relevant form of social desirable responding for this particular context, the moralistic bias. Here we report the analysis of data correlating the Vividness of Visual Imagery Questionnaire (VVIQ; Marks, Journal of Mental Imagery, 19, 153-166, 1973) with the Balanced Inventory of Desirable Responding (BIDR; Paulhus, 2002) and the MC scale under anonymous testing conditions. The VVIQ correlated significantly with the Self-Deceptive Enhancement (SDE) and Agency Management (AM) BIDR subscales and with the MC. The largest correlation was with SDE. The ability of SDE to predict VVIQ scores was not significantly enhanced by adding either AM or MC. Correlations between the VVIQ and BIDR egoistic scales were larger when the BIDR was continuously rather than dichotomously scored. This analysis indicates that the relationship between self-reported imagery and social desirable responding is likely to be stronger than previously thought.

Effect of human chorionic gonadotrophin on in vitro contractions of stimulated detrusor muscle strips of female rats.

AIMS: We studied the effect of human chorionic gonadotrophin (hCG) on the in vitro detrusor muscle contractions in female rats. METHODS: Two adjacent detrusor muscle strips from the bladder dome of 18 female Wistar rats (230-250 gm) were mounted in an organ bath for the recording of isometric tension. Carbachol (10(-9)-10(-3) M), alpha,beta methylene adenosine 5'-triphosphate (ATP) (10(-9)-10(-3) M) and potassium chloride (KCl) (10(-4)-10(-3) M) were applied (n = 6 x 3 groups). Concentration-response curves, before and after the addition of hCG (100 iu/mL) or oxybutynin (10(-5) M) to either muscle strip, were compared. RESULTS: All curves were displaced to the right by hCG in a concentration-dependent manner with significant inhibition of contractions induced by carbachol (P < 0.001) and KCl (P = 0.016) but not those induced by alpha,beta-methylene ATP (P = 0.4). Estimated order of potency of inhibition was carbachol>KCl>alpha,beta-methylene ATP. The overall inhibitory effect of hCG was significantly less than oxybutynin (P < 0.001). CONCLUSIONS: hCG significantly inhibited in vitro detrusor contractions induced by depolarization (KCl) and cholinergic (carbachol) but not purinergic (alpha,beta-methylene ATP) stimulation in a dose-dependent manner in female rats.

Combined estrogen and ghrelin administration decreases expression of p27(kip1) and proportion of isomyosin type I in the striated urethral and anal sphincters and levator ani of old ovariectomized rats.

We compared estrogen and/or ghrelin effects on pelvic floor muscles in old versus young adult ovariectomized rats. Ovariectomized Fisher 344 rats (18 and 3 months old, n = 24 x 2) received 42 daily intraperitoneal 17-beta estradiol (10 microg kg(-1)), ghrelin (2 microg kg(-1)), both, or vehicle (n = 6 x 4/group). Cytoplasmic p27(kip1) expression and isomyosin I proportion in striated urethral and anal sphincters and levator ani were measured, respectively, by Western blot analysis and gel electrophoresis with immunohistochemistry of muscle ghrelin receptors and radioimmunoassay of circulating growth hormone. In young adult rats, estrogen significantly decreased cytoplasmic p27(kip1) and isomyosin I signal intensities. In old rats, ghrelin and estrogen/ghrelin significantly decreased both intensities with greater estrogen/ghrelin effect. Ghrelin receptors were not immunostained in any muscle. Estrogen and/or ghrelin significantly increased or decreased, respectively, circulating growth hormone in old and young adult rats. Estrogen/ghrelin administration reversed pelvic floor muscle ageing changes in old ovariectomized rats through growth hormone production.