Atheroprotective effect of adjuvants in apolipoprotein E knockout mice

Strategies aimed at treating atherosclerosis by immunization protocols are emerging. Such protocols commonly use adjuvants as non-specific stimulators of immune responses. However, adjuvants are known to modify various disease processes. The aim of this study was to determine whether adjuvants alter the development of atherosclerosis. We performed immunization protocols in apolipoprotein E knockout mice (E degrees ) following chronic administration schedules commonly employed in experimental atherosclerosis. Our results point out a dramatic effect of several adjuvants on the development of atherosclerosis; three of the four adjuvants tested reduced lesion size. The Alum adjuvant, which is the adjuvant currently used in most vaccination protocols in humans, displayed a strong atheroprotective effect. Mechanisms accounting for atheroprotective effect of Freund's adjuvants included their capacity to increase both Th2 responses and anti-MDA-LDL IgM titers, and/or to impose atheroprotective lipoprotein profiles. The present study indicates that adjuvants have potent atheromodulating capabilities, and thus, implies that the choice of adjuvant is crucial in long-term immunization protocols in experimental atherosclerosis.     

Comparison of family reporting of pregnancy status with a post-mortem beta-HCG test in deceased women: a study in Pointe-Noire, Congo

OBJECTIVE: To compare family reports of pregnancy status in deceased women with a biological assessment of pregnancy using a post-mortem beta-HCG test. METHOD: We investigated the deaths of females of reproductive age registered at the Pointe Noire morgue from June 30 to October 18, 2001. A physician interviewed relatives about the circumstances of death, in particular whether the woman had been pregnant at the time of death, and whether she had delivered or had an abortion (induced or spontaneous) within the past 6 weeks. The bodies were then examined and blood samples taken for beta-HCG testing. RESULTS: Among 368 deaths of women of reproductive age registered, 34 deaths were identified as pregnancy-related: 23 by both the family interview and the beta-HCG test, five by beta-HCG test only and six were beta-HCG negative but the family had reported a recent delivery. CONCLUSION: In this setting, the approach based on family reports underestimates mortality during pregnancy by 24% and mortality during pregnancy or within 6 weeks postpartum by 15%.     

The use of insulin pumps with meal bolus alarms in children with type 1 diabetes to improve glycemic control

OBJECTIVE: The aim of this study was to determine whether the use of meal bolus alarms would result in fewer missed meal boluses per week in youth with type 1 diabetes using continuous subcutaneous insulin infusion (CSII) therapy. RESEARCH DESIGN AND METHODS: This was a randomized trial of 48 youth using CSII, who were in suboptimal glycemic control with HbA(1c) (A1C) values > or =8.0%. Twenty-four subjects were randomized to use a Deltec Cozmo insulin pump with meal bolus alarms (experimental group), while the other 24 subjects continued use of their current insulin pumps (control group) without meal bolus alarms. RESULTS: After 3 months of study, the number of missed meal boluses per week was significantly lower in the experimental group (from 4.9 +/- 3.7 to 2.5 +/- 2.5; P = 0.0005) but not significantly lower in the control group (from 4.3 +/- 2.7 to 4.2 +/- 3.9; P = 0.7610). Also after 3 months, the mean A1C value of the experimental group declined significantly (from 9.32 +/- 1.12 to 8.86 +/- 1.10; P = 0.0430). No significant decline in A1C was present for the control group (from 8.93 +/- 1.04 to 8.67 +/- 1.17; P = 0.1940). After 6 months of study, the significant decline in A1C from baseline in the experimental group was no longer present. Pooling of all available data from the control and experimental groups showed that at baseline and 3 and 6 months, the number of missed meal boluses per week was significantly correlated with A1C values. CONCLUSIONS: While meal bolus alarms may have the potential to improve suboptimal glycemic control in youth using CSII, our results demonstrated that these alarms had only a transient, modest effect in doing so.     

Dense fibrillar collagen matrices: a model to study myofibroblast behaviour during wound healing

Fibroblastic cells play an important part in wound healing. Human dermal fibroblasts seeded onto three-dimensional fibrillar collagen matrices migrate into the collagen network and differentiate into myofibroblasts. In order to evaluate the use of collagen matrices as model systems for studying myofibroblast phenotype during wound healing, myofibroblast behaviour migrating into dense or loose matrices was compared. The effect of collagen concentration on cell morphology, remodelling, proliferation and apoptosis of human myofibroblasts was evaluated. Myofibroblasts within dense collagen matrices (40 mg/ml) were spindle shaped, similar to cells observed during tissue repair. In contrast, cells within loose matrices (5mg/ml) were more rounded. Matrix hydrolysis activities (MT1-MMP and MMP2) did not differ between the two collagen concentrations. The myofibroblast proliferation rate was measured after 24h bromodeoxyuridine incorporation (BrdU). Cells in dense collagen matrices proliferated at a higher rate than cells in loose matrices at each culture time point tested. For example, 40% of cells in dense matrices were replicating compared to 10% of cells in loose matrices after 28 days in culture. Apoptotic cells were only detected in dense matrices from day 21 onwards when cells had already migrated into the collagen network. Taken together, these results show that a high collagen concentration has a stimulatory effect on myofibroblast proliferation and apoptosis, two important events in wound healing. Thus, dense matrices can be used to create controlled conditions to study myofibroblast phenotype.