Preclinical studies on quinelorane, a potent and highly selective D2-dopaminergic agonist

Quinelorane (LY163502) has the endocrine, neurochemical and behavioral profile of a potent and highly selective D2-dopaminergic agonist. The administration of quinelorane produced dose-related decreases in serum prolactin concentration of reserpinized, male rats and increases in serum corticosterone concentration of male rats. The minimum effective doses (MED) for these effects were 10 and 30 micrograms/kg i.p., respectively. Quinelorane induced increases in 3-methoxy-4-hydroxyphenylglycol-sulfate levels in the brain stem (MED, 30 micrograms/kg i.p.) and decreases in hypothalamic epinephrine levels (MED, 100 micrograms/kg i.p.) in male rats as determined by high-pressure liquid chromatography with electrochemical detection methods. Quinelorane induced increases in extracellular ascorbic acid as determined by in vivo voltammetry in the nucleus accumbens and striatum of male rats. Quinelorane produced concentration-dependent suppression of K+-evoked release of acetylcholine from superfused caudate slices, with an IC50 of approximately 10(-8)M. Quinelorane administration produced dose-related increases in compulsive, contralateral turning in male rats with unilateral nigrostriatal lesions and increases in locomotor activity and stereotypic behavior in male rats. In dogs, quinelorane administration produced dose-related increases in emetic response with an ED50 of 7 micrograms/kg i.v. Quinelorane administration also produced dose-related decreases in the striatal concentrations of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic (MED, 1 microgram/kg i.p. for both metabolites) as determined by high-pressure liquid chromatography with electrochemical detection methods and decreases in extracellular concentrations of homovanillic acid in the nucleus accumbens and striatum as determined by in vivo voltammetry., Quinelorane produced concentration-dependent decreases in K+-evoked dopamine release from superfused striatal slices (IC50 = 3 X 10(-9) M).(ABSTRACT TRUNCATED AT 250 WORDS)     

警惕性-护理的要素

护理及其它卫生保健职业在其实践过程中基本的要求是照护,专业的警惕性是护理中照护的要素。本文运用历史学和理论学为基础结合专业的警惕性,探讨它的构成要素。介绍了护理诊断的两种形式(中心和监视诊断)。中心诊断是指护士对指定计划完成和实施措施的评估,北美护理诊断学会批准了这种类型的诊断。监视诊断是护士评估预期的患者的风险,为突发事件做准备。整体而言,职业和术语研究者要扩大护理诊断术语使其标准化,以利于护士对患者安全的警惕性进行有效的沟通和实践。     

Peer mentoring of adults with spinal cord injury: a transformational leadership perspective

Purpose: Drawing from the tenets of transformational leadership theory, the purpose of this study was to examine the nature of effective peer mentoring of adults with a spinal cord injury (SCI) from the perspective of mentees.

Methods: The study utilised a qualitative methodology (informed by a social constructionist approach), involving 15 adult mentees with a SCI (mean age?=?47.2; mean time since injury?=?14.5 years), in which data were obtained via semi-structured interviews.

Results: The results revealed that effective mentoring, as used by mentors with SCIs, closely aligns with the core components of transformational leadership. Specifically, all four dimensions of transformational leadership (idealised influence, inspirational motivation, individualised consideration and intellectual stimulation) as displayed by mentors with a SCI were evident in their interactions with mentees. Participants who perceived their mentors to use transformational leadership behaviours reported increases in motivation, self-confidence, hope and overall well-being, relatedness with their mentor, greater comfort/acceptance of their situation, a redefined sense of their limitations, as well as greater engagement in various life pursuits.

Conclusions: Displays of transformational leadership by peer mentors (i.e. transformational mentoring) were reported by mentees to be associated with a range of adaptive psychological and behavioural outcomes. The results have the potential to inform the development and dissemination of peer mentor-based interventions and initiatives.

• Implications for Rehabilitation

• Within the context of spinal cord injury (SCI) rehabilitation, positive peer mentorship is reflected in mentors’ use of transformational leadership behaviours (idealised influence, inspirational motivation, individualised consideration and intellectual stimulation).

• When SCI peer mentors use transformational leadership behaviours, mentees report a redefined sense of their limitations, and increased self-confidence, hope, motivation, acceptance, participation and overall well-being.

• The results of this study have the potential to inform future longitudinal and experimental research concerning the (causal) effects of peer mentoring on mentee outcomes. In particular, research should examine the effects of peer-mentorship training, informed by the tenets of transformational leadership theory, in relation to the mentee outcomes assessed in this qualitative study.

     

Hematopoietic Progenitor Cell Rolling in Bone Marrow Microvessels: Parallel Contributions by Endothelial Selectins and Vascular Cell Adhesion Molecule 1

We have used intravital microscopy to study physiologically perfused microvessels in murine bone marrow (BM). BM sinusoids and venules, but not adjacent bone vessels, supported rolling interactions of hematopoietic progenitor cells. Rolling did not involve L-selectin, but was partially reduced in wild-type mice treated with antibodies to P- or E-selectin and in mice that were deficient in these two selectins. Selectin-independent rolling was mediated by α4 integrins, which interacted with endothelial vascular cell adhesion molecule (VCAM)-1. Parallel contribution of the endothelial selectins and VCAM-1 is not known to direct blood cell trafficking to other noninflamed tissues. This combination of constitutively expressed adhesion molecules may thus constitute a BM-specific recruitment pathway for progenitor cells analogous to the vascular addressins that direct selective lymphocyte homing to lymphoid organs.     

Altered behavioral response to a D2 agonist, LY141865, in spontaneously hypertensive rats exhibiting biochemical and endocrine responses similar to those in normotensive rats

LY141865, a dopamine agonist selective for D2 dopamine receptors, caused hypomotility at low doses (0.01 and 0.1 mg/kg) and hypermotility at high doses (1 and 10 mg/kg) after i.p. injection into normotensive rats (WKY). In age-matched hypertensive rats (SHR), LY141865 caused hypomotility (not hypermotility) at all of these doses. The basal locomotor activity was higher in SHR than in WKY, but striatal concentrations of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and of serotonin and its metabolite, 5-hydroxyindoleacetic acid, were not different between the two groups of rats. The specific binding of a dopamine receptor radioligand, tritiated pergolide, in striatum and mesolimbic regions, did not differ in SHR compared with WKY. In contrast to the lack of locomotor stimulation in SHR, other dopaminergic responses to LY141865 occurred in SHR as well as WKY. For instance, LY141865 decreased striatal and mesolimbic concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid, increased striatal and mesolimbic concentrations of acetylcholine, decreased hypothalamic concentrations of epinephrine, increased serum corticosterone concentration and decreased serum prolactin concentration in SHR as in WKY. Because radioligand-labeled dopamine receptors and several LY141865 responses mediated by dopamine receptors did not differ appreciably in SHR compared with WKY, the lack of behavioral hypermotility in response to LY141865 in SHR may be due to abnormalities in some synaptic mechanisms beyond dopamine receptor activation that are involved in the expression of increased locomotion in response to the dopamine agonist.     

The "hybrid flip-over" technique for anterior leaflet prolapse repair

Repair of the anterior mitral leaflet or bi-leaflet prolapse is technically more demanding than repair of the posterior mitral leaflet. Although several techniques have been proposed for the repair of anterior mitral leaflet prolapse during bi-leaflet repair, practical challenges remain, including the determination of the appropriate length for artificial chords. Herein we describe a novel and reproducible technique for bi-leaflet mitral valve repair, including those with extensive anterior mitral leaflet prolapse.