Lysophosphatidic acid (LPA) and adrenaline are weak platelet activators considered important for thrombus formation, and were previously shown to synergistically increase platelet aggregation. Here we investigate synergistic activation by LPA and adrenaline when measuring platelet adhesion. Platelet-rich plasma from healthy blood donors together with adrenaline and/or LPA were added to protein-coated microplates. Platelets were allowed to adhere and the amount of adhesion detected enzymatically. The LPA and adrenaline combination induced a synergistic increase of platelet adhesion to a normally non-adhesive albumin surface. The degree of synergy varied markedly between individuals; these variations could not be explained by age, gender, blood type or different amounts of platelets, oxidized low-density lipoprotein, insulin or glucose in plasma. There was a trend indicating increased synergistic effect for platelets sensitive to adrenaline stimulation. The synergistic effect was blocked by the alpha2-adrenoceptor antagonist yohimbine and inhibited by the ADP scavenger system creatine phosphate/creatine phosphokinase and antibodies against alphaIIbbeta3. Furthermore, platelets adhering to albumin after adrenaline and LPA treatment expressed P-selectin. In conclusion, LPA and adrenaline act synergistically to increase alphaIIbbeta3-mediated platelet adhesion to albumin, dependent on alpha2-adrenoceptor signalling and platelet secretion. We also confirm that synergistic platelet activation achieved with LPA and adrenaline is highly donor dependent. 相似文献
Three patients with Alzheimer's disease, a 68-year-old woman with mild dementia and 2 men (aged 64 and 72 years) with moderate dementia were treated orally with the cholinesterase inhibitor tacrine (tetrahydroaminoacridine), 80 mg daily, for several months. The patients were investigated using positron emission tomography (PET) prior to, and after 3 weeks and 3 months of treatment. The PET studies involved a multi-tracer system consisting of [18F]-fluoro-deoxy-glucose (18F-FDG) (tracer for glucose metabolism); 11C-butanol (cerebral blood flow) and (S)(−)- and (R)(+)-[N-11C-methyl]-nicotine (nicotinic receptors; cholinergic neural activity). Tacrine treatment increased the uptake of 11C-nicotine to the brain. Significant reduced difference in uptake between the two enantiomers (S)(−)- and (R)(+)11C-nicotine was observed in the frontal and temporal cortices after tacrine treatment in all three patients. The kinetic analysis indicated increased binding of (S)(−)11C-nicotine in brain compatible with a restoration of nicotinic cholinergic receptors. The most pronounced effect was observed after 3 weeks and 3 months treatment in the patient with mild dementia. An increase in cerebral glucose utilization was found in the 68-year-old patient with mild dementia but also slightly in the 64-year-old man with moderate dementia when treated with tacrine for 3 months. Tacrine administration did not affect cerebral blood flow. The PET data obtained after 3 weeks of tacrine treatment was paralleled by improvement in neuropsychological performance. This study shows in vivo by PET neurochemical effects induced in brain by treatment with tacrine to Alzheimer patients. Intervention with tacrine in the early course of the disease might be necessary for clinical improvement. 相似文献
In the present study, we comparatively evaluated the anticoagulant efficacy of the new direct thrombin inhibitor melagatran
in cord vs. adult plasma. In contrast to heparin, melagatran does not require antithrombin as a cofactor. Thus, anticoagulant
treatment with melagatran is of special interest in neonatal patients, whose plasma is relatively deficient in antithrombin.
We evaluated the anticoagulant action of increasing amounts of melagatran (0.1–2.0 μmol/l) in both cord and adult plasma by
means of calibrated automated thrombography (CAT) with respect to the lag time until the onset of thrombin formation, time
to thrombin peak maximum (TTP), endogenous thrombin potential (ETP), and thrombin peak height. Melagatran exhibited approximately
the same ability to prolong lag times or TTPs in both cord and adult plasma. Similar concentrations (IC50) of melagatran were required to double the lag times (0.44±0.04 μmol/l vs. 0.52±0.05 μmol/l) or to double the TTPs (0.91±0.08 μmol/l
vs. 1.06±0.09 μmol/l) in cord vs. adult plasma. Melagatran exhibited a higher ability to suppress ETPs or thrombin peak heights
in cord vs. adult plasma. Markedly lower concentrations (IC50) of melagatran were required to suppress ETPs (0.27±0.03 μmol/l vs. 0.70±0.06 μmol/l) or thrombin peak heights by 50% (0.29±0.03 μmol/l
vs. 0.53±0.04 μmol/l) in cord vs. adult plasma. We conclude that our results suggest a higher ability of melagatran to suppress
thrombin formation in cord vs. adult plasma. Thus, lower amounts of melagatran might be required in neonates undergoing antithrombotic
therapy. 相似文献
AbstractBackground: There exist few recovery and occupation-based interventions for mental health service users. Balancing Everyday Life (BEL) is a new occupation-based lifestyle intervention that was created to fill this need.Aim: To gain group leaders’ and participants’ perspectives of the BEL intervention content and format, including factors that helped, hindered, and could be improved.Methods: A constructivist grounded theory method guided data collection and analysis. Interviews took place with 12 BEL group leaders and 19 BEL participants from out-patient psychiatry settings and community-based day centers in Sweden.Results: BEL’s structure and content were appreciated, yet flexibility was desired to adapt to participant needs. BEL could act as a bridge, helping participants connect with others, and to a more engaged and balanced everyday life. Facilitating factors included a person-focused (versus illness-focused) approach, physical and emotional environments, and connection. Barriers included room resources. More sessions were desired for the intervention.Conclusion: Group leaders and participants experienced BEL as a useful tool to instigate meaningful change and connection in the participants’ lives. The combination of a positive person-focused approach and group support was appreciated. These results could inform future research, evaluation, and development of occupation-focused lifestyle interventions for mental health service users. 相似文献
Background: The Individual Enabling and Support (IES) model is an adapted, supported employment program developed to meet motivational, cognitive and time-use needs of people with affective disorders. Vocational programs for this target group have been developed but more knowledge is needed about the important characteristics and perceived usefulness of the programs. The aim of this study was to illustrate the IES model and process from multiple perspectives.
Methods: Five participants were included in this multiple-case study. The material comprised interviews with participants, intervention documents, memos and interviews with employment specialists. Within and cross-case analyzes and an analytical generalization were performed.
Results: The cases illustrated different IES processes, and the theme; Enabling engagement in return to work (RTW) was formulated. Continuous support from the employment specialist and a focus on personal resources and motivation were essential to overcome low self-confidence regarding RTW. Motivational, cognitive and time-use strategies gave an opportunity to learn new behavior and coping strategies for job seeking, getting employed and working.
Conclusion: Providing a combination of these strategies integrated with supported employment could promote self-efficacy and engagement in the RTW process among people on sick leave due to an affective disorder. 相似文献
BackgroundPsychotic-like experiences (PLE) are present in nonclinical populations, yet their association with brain structural variation, especially markers of early neurodevelopment, is poorly understood. We tested the hypothesis that cortical surface gyrification, a putative marker of early brain development, is associated with PLE in healthy subjects. MethodsWe analyzed gyrification from 3 Tesla MRI scans (using CAT12 software) and PLE (positive, negative, and depressive symptom dimensions derived from the Community Assessment of Psychic Experiences, CAPE) in 103 healthy participants (49 females, mean age 29.13 ± 9.37 years). A subsample of 63 individuals completed tasks from the Wechsler Adult Intelligence Scale and Controlled Oral Word Association Test. Estimated IQ and a composite neuropsychological score were used to explore mediation pathways via cognition. ResultsPositive PLE distress was negatively associated with gyrification of the left precuneus. PLE depression dimension showed a negative association with gyrification in the right supramarginal and temporal region. There was no significant mediating effect of cognition on these associations. ConclusionOur results support a neurobiological psychosis spectrum, for the first time linking an early developmental imaging marker (rather than volume) to dimensional subclinical psychotic symptoms. While schizophrenia risk, neurodevelopment, and cognitive function might share genetic risk factors, additional mediation analyses did not confirm a mediating effect of cognition on the gyrification-psychopathology correlation. 相似文献
This paper describes a substantial part of the international mentoring network of students and young investigators in electrocardiology that developed around Dr. Galen Wagner (1939–2016), including many experiences of his mentees and co-mentors.The paper is meant to stimulate thinking about international mentoring as a means to achieve important learning experiences and personal development of young investigators, to intensify international scientific cooperation, and to stimulate scientific production. 相似文献