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Hildegard Christ

Publications and source records attributed to Hildegard Christ.

4 recordsLinked to original sources

Plasmin modulates vascular endothelial growth factor-A-mediated angiogenesis during wound repair.

Plasmin-catalyzed cleavage of the vascular endothelial growth factor (VEGF)-A isoform VEGF165 results in loss of its carboxyl-terminal heparin-binding domain and significant loss in its bioactivity. Little is known about the in vivo significance of this process. To investigate the biological relevance of the protease sensitivity of VEGF165 in wound healing we assessed the activity of a VEGF165 mutant resistant to plasmin proteolysis (VEGF165(A111P)) in a genetic mouse model of impaired wound healing (db/db mouse). In the present study we demonstrate that in this mouse model plasmin activity is increased at the wound site. The stability of the mutant VEGF165 was substantially increased in wound tissue lysates in comparison to wild-type VEGF165, thus indicating a prolonged activity of the plasmin-resistant VEGF165 mutant. The db/db delayed healing phenotype could be reversed by topical application of wild-type VEGF165 or VEGF165(A111P). However, resistance of VEGF165 to plasmin cleavage resulted in the increased stability of vascular structures during the late phase of healing due to increased recruitment of perivascular cells and delayed and reduced endothelial cell apoptosis. Our data provide the first indication that plasmin-catalyzed cleavage regulates VEGF165-mediated angiogenesis in vivo. Inactivation of the plasmin cleavage site Arg110/Ala111 may preserve the biological function of VEGF165 in therapeutic angiogenesis under conditions in which proteases are highly active, such as wound repair and inflammation.

Animals↗

Data from the StEP TWO programme showing the effect on blood pressure and different parameters for obesity in overweight and obese primary school children.

UNLABELLED: Obesity in childhood, which is associated with cardiovascular risk factors such as hypertension, is on the increase. Countermeasures are necessary. In this paper, we present the baseline and final data from the StEP TWO programme, a prospective study to prevent overweight and obesity in primary schools. METHODS: We recorded and calculated, from 1689 children, anthropometric data, including analyses of bioelectric impedance, waist and hip circumferences, body mass index and its standard deviation, and the ratio of waist to hip. Blood pressure was measured after 5 minutes at rest. From the three schools involved in a programme of intervention, 121 children were invited to take part, and 40 (33.1 per cent) completed the programme. The effect was compared with 155 overweight and obese children identified at the 4 control schools. RESULTS: 830 (49.5 per cent) boys and 848 girls (50.5 per cent) took part. Their mean age was 8.2 plus or minus 1.3 years, their height was 1.31 plus or minus 0.09 metres, they weighed 30.0 plus or minus 8.2 kilograms, and their mean index of body mass was 17.1 plus or minus 2.9 kilograms per metre squared. Of the children, 7.3 per cent were obese, 10.4 per cent were overweight, 75.7 per cent had normal weights, and 6.6 per cent were underweight. Resting hypertension was observed in 2.3 per cent of the children. Increased blood pressure was associated with a higher body weight, body mass index, standard deviation score for body mass index, and waist and hip circumferences (each p < 0.001), but not with the ratio of waist to hip. Hypertension at rest was also found in 11.0 per cent of obese children, 4.4 per cent of those who were overweight, 1.2 per cent of those with normal weight, and 1.0 per cent of underweight children (p < 0.001). After the intervention, the increase of the body mass index tended to be lower in those in whom we had intervened (p = 0.069), and in these the decrease of the standard deviation score for body mass index was significantly higher (p = 0.028). Systolic blood pressure was reduced by about 10 millimetres of mercury in those in whom we had intervened (p = 0.002), while there were no changes in the control group. Diastolic blood pressure was lowered by 3 millimetres of mercury, but this was not significant. CONCLUSION: Obese children had the highest values for systolic and diastolic blood pressure. Increased levels of blood pressure are associated with other parameters of obesity, such as the circumference of the waist and hip. Early preventive measurements in childhood are necessary, and appropriate intervention appears to be effective.

Blood Pressure↗

The influence of tutor qualification on the process and outcome of learning in a problem-based course of basic medical pharmacology.

Limited access to expert tutors is a problem that can be addressed by using tutors from different stages of medical or non-medical (under-, post-) graduate education. To address whether such differences in qualification affect the results of process evaluation by participants or their learning outcome (exam results), we analysed the data of a 4-year prospective study performed with 787 3rd-year medical students (111 groups of 5-10 participants) taking an obligatory problem-based learning (PbL)-course of basic pharmacology. We compared peer tutors (undergraduate medical students, >/=4th year), non-expert (junior) staff tutors (physicians, pharmacists, veterinarians, biologists, or chemists during postgraduate education), and expert (senior) staff tutors (completed postgraduate education). Evaluation scores related to PbL gave the highest values for senior staff-led groups. The tutor's performance score of peer-led groups did not differ from those of staff-led groups, but the score obtained from groups tutored by junior staff was lower than that obtained with senior staff tutors. Students' weekly preparation time tended to be lower in peer-led groups, while learning time spent specifically on exam preparation seemed to be increased compared to PbL-groups of staff tutors. As a putative confounding variable, tutors' experience in coaching PbL-groups was also investigated. Groups led by experienced tutors, defined as tutors with at least one term of previous PbL tutoring, were found to have significantly higher evaluation scores. Interestingly, neither tutors' subject-matter expertise (peer students, junior staff, or senior staff) nor their teaching-method expertise showed any influence on PbL-groups' mean test scores in a written exam. This indicates that the effect of tutor expertise on the learning process is not associated with a difference in learning outcome when just factual knowledge is assessed by traditional methods.

Analysis of Variance↗