Activation of proinflammatory mediators in heart transplants from brain-dead donors: evidence from a model of chronic rat cardiac allograft rejection.
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Animals↗
Biomedical subjects
M Taal
Publications and source records attributed to M Taal.
Activation of the heart by donor brain death accelerates acute rejection after transplantation.
BACKGROUND: Donor brain death upregulates expression of inflammatory mediators in the heart. It is hypothesized that these nonspecific changes trigger and amplify acute rejection in unmodified recipients compared with hearts from normal living donors. We examined the inflammatory and immunological consequences of gradual-onset donor brain death on cardiac allografts after transplantation. METHODS AND RESULTS: Functioning hearts were engrafted from normotensive donors after 6 hours of ventilatory support. Hearts from brain-dead rats (Fisher, F344) were rejected significantly earlier (mean+/-SD, 9. 3+/-0.6 days) by their (Lewis) recipients than hearts from living donor controls (11.6+/-0.7 days, P=0.03). The inflammatory response of such organs was accelerated, with rapid expression of cytokines, chemokines, and adhesion molecules and brisk infiltration of associated leukocyte populations. Upregulation of major histocompatibility class II antigens increased organ immunogenicity. Acute rejection evolved in hearts from brain-dead donors more intensely and at a significantly faster rate than in controls. CONCLUSIONS: Donor brain death is deleterious to transplanted hearts. The resultant upregulation of inflammatory factors provokes host immune mechanisms and accelerates the acute rejection process in unmodified hosts.
Animals↗
IHG-2, a mesangial cell gene induced by high glucose, is human gremlin. Regulation by extracellular glucose concentration, cyclic mechanical strain, and transforming growth factor-beta1.
We used cloning in silico coupled with polymerase chain reaction to demonstrate that IHG-2 is part of the 3'-untranslated region of gremlin, a member of the DAN family of secreted proteins that antagonize the bioactivities of members of the transforming growth factor (TGF)-beta superfamily. Mesangial cell gremlin mRNA levels were induced by high glucose, cyclic mechanical strain, and TGF-beta1 in vitro, and gremlin mRNA levels were elevated in the renal cortex of rats with streptozotocin-induced diabetic nephropathy in vivo. gremlin expression was observed in parallel with induction of bone morphogenetic protein-2 (BMP-2), a target for gremlin in models of cell differentiation. Together these data indicate that (a) IHG-2 is gremlin, (b) gremlin is expressed in diabetic nephropathy in vivo, (c) both glycemic and mechanical strain stimulate mesangial cell gremlin expression in vitro, (d) high glucose induces gremlin, in part, through TGFbeta-mediated pathways, and (e) Gremlin is a potential endogenous antagonist of BMPs within a diabetic glomerular milieu.
3' Untranslated Regions↗
A randomised, double-blind comparison of the efficacy and safety of citalopram compared to mianserin in elderly, depressed patients with or without mild to moderate dementia.
Depression is the most common psychiatric disorder among the elderly and in old age may interact with emotional and cognitive functioning. Depression in old age has been shown to be associated with degenerative changes in the brain. It is, therefore, important that in this patient population antidepressants with a favourable tolerability profile, such as the selective serotonin reuptake inhibitors (SSRIs), are examined for both antidepressant efficacy and effect on cognitive function and emotional impairment. This randomised, double-blind study compared the efficacy and tolerability of citalopram and mianserin in 336 elderly, depressed patients with or without dementia. Patients received either citalopram 20-40 mg/day or mianserin 30-60 mg/day for 12 weeks. The treatments were equivalent with respect to change in Montgomery-Asberg Depression Rating Scale (MADRS) total score; patients in both treatment groups responded well. Patients with dementia showed a smaller decrease in total MADRS score than patients without dementia. Both treatments were well tolerated with a relatively low incidence of adverse events. Fatigue and somnolence were more frequent with mianserin, while insomnia was more frequent with citalopram. Overall, this study showed that the two treatments were equivalent in efficacy, and that citalopram is an effective, well-tolerated and non-sedative treatment for elderly depressed patients with or without dementia.
Aged↗
Stimulating adolescents' decision-making.
The aim of the present study was to investigate the relationship between adolescents' decision-making and their sense of control over the future. In order to raise their knowledge of decision-making, 98 lower-middle class junior high school pupils, 11- to 14-years-olds, participated in a training programme "Pros and Cons". The programme presented themes such as responsibility, plans, choice and alternatives. The experimental group was compared with 122 junior high school pupils who did not participate in the programme, within a quasi-experimental design. Results of the study indicated that increased knowledge of decision-making raises pupils' sense of control over their achievements and their perception of school as an instrument for their future career.
Achievement↗
Positive and negative effects of a child sexual abuse prevention program.
This study evaluated a sexual abuse prevention program for sixth, seventh, and eighth graders ranging from 8 to 12 years of age. Six questionnaires concerning feelings of control, choice of protection strategy, perceived feasibility of refusing to cooperate with the intruder, appreciation of touch, school relationships, and social anxiety were used. Subjects were 161 children who participated in the program and a control group of 131 children. Results indicated short term overall effects of the program for the choice of safety strategies. Immediately after participation in the program the youngest and the oldest children felt less in control of an abusive interaction, the youngest pupils thought that refusal was less feasible but they appreciated physical touch more than before. These effects, however, were only of a short duration. In the long run children thought refusing more feasible and younger children showed less social anxiousness. As an unwanted side effect of the program the oldest children developed feelings of discomfort about being touched. Relationships with classmates and the teacher were not influenced by the intervention. It is suggested that the behavioral and attitudinal effects of the program could be ameliorated by extending the number or duration of the lessons.
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