Chronic corticosterone exposure during adolescence reduces impulsive action but increases impulsive choice and sensitivity to yohimbine in male Sprague-Dawley rats

Chronic stress during adolescence is associated with an increased risk for alcoholism and addictive disorders. Addiction is also associated with increased impulsivity, and stress during adolescence could alter cortical circuits responsible for response inhibition. Therefore, the present study determined the effect of chronic exposure to the stress hormone corticosterone (CORT) during adolescence on tests of impulsivity in adulthood and examined possible biochemical mechanisms. Male Sprague-Dawley rats were exposed to CORT by their drinking water during adolescence (post-natal day 30-50). The rats were then tested in adulthood to assess behavior on the 5-choice serial reaction time task (5CSRTT), stop-signal reaction time task (SSRTT), and the delay-discounting task, which differentially assess attention, impulsive action, and impulsive choice. Yohimbine-induced impulsivity on the 5CSRTT and biochemical analysis of the lateral orbital frontal cortex (lOFC) was also assessed owing to the ability of yohimbine to activate the hypothalamic-pituitary-adrenal axis and influence impulsivity. Adolescent CORT-treated rats were found to behave largely like controls on the 5CSRTT, but did show reduced premature responses when the intertrial interval was increased. Nevertheless, the CORT-treated rats tended to have more yohimbine-induced impulsive responses at low doses on this task, which was not found to be due to increased pCREB in the lOFC, but could be related to a higher expression/activity of the AMPA receptor subunit GluR1. Adolescent CORT-treated rats performed more accurately on the SSRTT, but showed greater impulsivity on the delay-discounting task, as indicated by steeper discounting functions. Therefore, adolescent CORT exposure reduced impulsive action but increased impulsive choice, indicating that chronic stress hormone exposure in adolescence can have long-term consequences on behavior.     

Design for obtaining the half-axial projection

A device for obtaining the half-axial projection complementing single plane cine equipment is described. The design enables a single technician to raise and lower the patient's upper half of the body between 0° and 20° of longitudinal deviation from the rotating cradle, set between 0° and 70° of horizontal deviation. Materials cost less than $100 and can be assembled by personnel in most hospitals.     

Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study

OBJECTIVES: The objective of the study was to evaluate the effect of an angiotensin receptor blocker on left ventricular (LV) structure and function when added to prescribed heart failure therapy. BACKGROUND: The clinical benefit derived from heart failure therapy is attributed to the regression of LV remodeling. METHODS: At 302 multinational sites, 5,010 patients in New York Heart Association (NYHA) classification II to IV heart failure taking angiotensin-converting enzyme inhibitor (ACEI) and/or beta-blocker (BB) were randomized into valsartan and placebo groups and followed for a mean of 22.4 months. Serial echocardiographic measurements of left ventricular internal diastolic diameter (LVIDd) and ejection fraction (EF) were recorded. Total study reproducibility calculated to 90% power at 5% significance defined detectable differences of 0.09 cm for LVIDd and 0.86% for EF. RESULTS: Baseline LVIDd and EF for valsartan and placebo groups were similar: 3.6 +/- 0.5 versus 3.7 +/- 0.5 (cm/m(2)) and 26.6 +/- 7.3 versus 26.9 +/- 7.0 (%). Mean group changes from baseline over time were compared. Significant decrease in LVIDd and increase in EF began by four months, reached plateau by one year, and persisted to two years in valsartan compared with placebo patients, irrespective of age, gender, race, etiology, NYHA classification, and co-treatment therapy. Changes at 18 months were -0.12 +/- 0.4 versus -0.05 +/- 0.4 (cm/m(2)), p < 0.00001 for LVIDd, and +4.5 +/- 8.9 versus +3.2 +/- 8.6 (%), p < 0.00001 for EF. The exception occurred in patients taking both ACEI and BB as co-treatment, in whom the decrease in LVIDd and increase in EF were no different between valsartan and placebo groups. CONCLUSIONS: The Val-HeFT echocardiographic substudy of 5,010 patients with moderate heart failure demonstrated that valsartan therapy taken with either ACEI or BB reversed LV remodeling.     

A novel bioadhesive intranasal delivery system for inactivated influenza vaccines

The aim of the current studies was to evaluate a bioadhesive delivery system for intranasal administration of a flu vaccine, in combination with a mucosal adjuvant (LTK63). A commercially available influenza vaccine, containing hemagglutinin (HA) from influenza/A Johannesberg H1N1 1996, and LTK63 or LTR72 adjuvants, which are genetically detoxified derivatives of heat labile enterotoxin from Escherichia coli, were administered IN in a bioadhesive delivery system, which comprised esterified hyaluronic acid (HYAFF) microspheres, to mice, rabbits and micro-pigs at days 0 and 28. For comparison, additional groups of animals were immunized intranasally with the HA vaccine alone, with soluble HA+LTK63, or IM with HA. In all three species, the groups of animals receiving IN immunization with the bioadhesive microsphere formulations, including LT mutants, showed significantly enhanced serum IgG responses (P<0.05) and higher hemagglutination inhibition (HI) titers in comparison to the other groups. In addition, the bioadhesive formulation also showed a significantly enhanced nasal wash IgA response (P<0.05). Most encouragingly, in pigs, the bioadhesive microsphere vaccine delivery system induced serum immune responses following IN immunization, which were significantly more potent than those induced by traditional IM immunization at the same vaccine dose (P<0.05).     

Reproducibility of left ventricular internal dimensions with M mode echocardiography: Effects of heart size,body position and transducer angulation

Analysis was made of the variables of heart size, body position and transducer angle affecting the reproducibility of left ventricular internal dimensions as measured with M mode echocardiography. Echocardiograms were recorded in 24 subjects as the thorax was incrementally rotated and tilted. Transducer angle was noted from a three plane level attached to the probe. Constants were the technician, transducer placement and the interpreter. Heart rates varied insignificantly; respirations were held. Groups A and B were defined by their initial left ventricular internal dimensions at end-diastole (LVID_d): 49 ± 5.9 and 73 ± 8.6 mm (group mean ± standard deviation). With body position constant the measurement error between duplicate recordings of LVID_d was ± 1.2 mm (coefficient of variation = 1.8 percent) in Group A and ±4.5 mm (coefficient of variation = 4.6 percent) in Group B (p <0.001). Transducer angle varied 12 ° between duplicate recordings in both groups. As the position of the thorax changed, the transducer followed, maintaining approximately the same incline with the chest wall. In both groups errors for combined LVID_d recorded with rotation and tilt, respectively, were unchanged from the duplication error. Thus, when the spatial orientation between the transducer and heart is held constant, it is the size of the heart that determines the reproducibility of the measurement of left ventricular internal dimensions.     

Severity of left ventricular remodeling defines outcomes and response to therapy in heart failure: Valsartan heart failure trial (Val-HeFT) echocardiographic data

OBJECTIVES: The objective of this study was to test the hypothesis that the severity of left ventricular remodeling predicts the response to treatment and outcomes in chronic heart failure. BACKGROUND: Reversal of remodeling should produce the most favorable outcome in patients with the most severe remodeling. METHODS: In 5010 heart failure patients on background therapy and randomized to valsartan and placebo, serial recordings of left ventricular internal diastolic diameter (LVIDd) and ejection fraction (EF) were read at sites that had to meet qualifying standards before participating. Baseline LVIDd and EF were pooled across treatments and retrospectively grouped by quartiles Q1 to Q4, representing best to worst. Kaplan-Meier survival curves were obtained by the log-rank test. Q1 was compared with Q4 for mortality and combined mortality and morbidity (M + M) from Cox regression risk ratios (RRs). Valsartan versus placebo changes from baseline in LVIDd and EF were analyzed by quartiles from analysis of covariance. Valsartan and placebo were compared by RRs for M + M. RESULTS: Survival rates were greater in the better quartiles for LVIDd and EF (p < 0.00001). The RR for Q1 versus Q4 in events approached 0.5 for both LVIDd and EF (p < 0.0001). An LVIDd decrease and EF increase were quartile-dependent and greater with valsartan than placebo at virtually all time points. The RR for M + M outcomes favored valsartan in the worse quartiles. CONCLUSIONS: Stratification by baseline severity of remodeling showed that patients with worse LVIDd and EF are at highest risk for an event, yet appear to gain the most anti-remodeling effect and clinical benefit with valsartan treatment.     

术中经食管超声心动图评估主动脉粥样硬化斑块的意义

目的：研究心脏直视手术中经食道超声心动图（ＴＥＥ）检测升部、弓部主动脉粥样硬化斑块的意义。方法：８０例心脏直视手术患者在术中行ＴＥＥ检查，平均年龄６３．６±８．４岁，其中６９（８６．３％）例冠状动脉重建术（ＣＡＢＧ）。当检出有意义斑块时，选择性地行七项相关的修改手术方案。结果：共检出升部、弓部主动脉有意义斑块分别有２例和１９例。根据ＴＥＥ的发现修改手术方案３０次。本研究无一例围术期脑血管意外并发症，仅３例一过性脑缺血发作。结论：在设备条件许可时，６５岁以上心脏直视手术患者尤其是ＣＡＢＧ，术中应行ＴＥＥ检查和监测。当检出有意义斑块时，应及时修改手术方案，可降低围术期脑血管意外并发症。