Low plasma levels of FGF-2 and PDGF-BB are associated with cardiovascular events in type II diabetes mellitus (diabetes heart study)

Objective: We tested associations of the growth factors VEGF, FGF-2, HGF and PDGF-BB with coronary artery calcium scores and cardiovascular events (CVD) in type 2 diabetes mellitus (T2DM). Methods: A cross-sectional study selected 40 frequency matched (by age, gender and race) subjects with T2DM from the first (0–111) and the third (> 1400) coronary artery calcium (CAC) score tertiles in the Diabetes Heart Study (DHS), in which 36 were with and 41 were without history of CVD events. Plasma levels of VEGF, FGF-2, HGF and PDGF-BB were measured in all subjects. Results: None of the growth factors was significantly different between the first and third CAC score tertiles. Mean plasma FGF-2 and PDGF-BB levels were significantly higher in the group without prior CVD events compared with the group with prior CVD events [mean(95%CI): 219.20 (194.42–247.15) vs. 152.93 (135.64–172.43) pg/ml, p = 0.03] and [mean(95%CI): 106.70 (89.12–127.74) vs. 61.56 (50.91–74.44) pg/ml, p = 0.03], respectively. Subgroup analysis in the first CAC tertile showed a significantly higher PDGF-BB levels in those without compared with those with CVD events [mean (95%CI): 208.36 (190.57–228.15) vs. 102.93 (80.64–125.21) pg/ml, p = 0.004]. Conclusion: Plasma growth factor levels were not significantly different between the extremes of CAC scores in T2DM. However, low plasma levels of PDGF-BB and FGF-2 are associated with prior cardiovascular events in T2DM. Studies are needed to confirm our results and also to establish temporality of this association.     

Direct angioplasty versus initial thrombolytic therapy for acute myocardial infarction: long-term follow-up and changes in practice pattern.

We retrospectively studied the outcomes of patients with acute myocardial infarction who were treated with either direct angioplasty or thrombolytics followed by angioplasty. Two patient cohorts were analyzed: a previously reported (in regard to short-term follow-up) group of 371 patients who now have long-term follow-up (mean, 3.4 years) of survival and event-free survival and a second group of 202 patients who have been treated since publication of our initial data. Both 1-year and 2-year survival were significantly better (p = 0.01 and 0.02, respectively) in the group that was treated with thrombolytics first. Event-free survival (i.e., no myocardial infarction, coronary artery bypass graft surgery, repeat angioplasty) was better overall (p < 0.01) for the group that was treated with thrombolytics first. The more recently treated group of patients also showed benefit in regard to both survival (p = 0.002) and event-free survival (p < 0.01) over a short-term follow-up period (mean, 39 weeks) for patients who were treated initially with thrombolytics as compared with those who were treated with direct angioplasty. Although the initial cohort was very similar to the treatment groups except for age (mean age for the direct angioplasty group was 62 +/- 12 years vs 57 +/- 11 years for thrombolytics first group, (p = 0.0002), several differences existed in the more recent treatment groups. The patients who were more recently treated with direct angioplasty were older, had lower mean ejection fraction, had more extensive coronary artery disease, and were more likely to have had prior coronary artery bypass grafting.(ABSTRACT TRUNCATED AT 250 WORDS)     

Microphysical space of a liver sinusoid device enables simplified long-term maintenance of chimeric mouse-expanded human hepatocytes

While many advanced liver models support hepatic phenotypes necessary for drug and disease studies, these models are characterized by intricate features such as co-culture with one of more supporting cell types or advanced media perfusion systems. These systems have helped elucidate some of the critical biophysical features missing from standard well-plate based hepatocyte culture, but their advanced designs add to their complexity. Additionally, regardless of the culture system, primary hepatocyte culture systems suffer from reproducibility issues due to phenotypic variation and expensive, limited supplies of donor lots. Here we describe a microfluidic bilayer device that sustains primary human hepatocyte phenotypes, including albumin production, factor IX production, cytochrome P450 3A4 drug metabolism and bile canaliculi formation for at least 14 days in a simple monoculture format with static media. Using a variety of channel architectures, we describe how primary cell phenotype is promoted by spatial confinement within the microfluidic channel, without the need for perfusion or co-culture. By sourcing human hepatocytes expanded in the Fah, Rag2, and Il2rg-knockout (FRG?-KO) humanized mouse model, utilizing a few hundred hepatocytes within each channel, and maintaining hepatocyte function for weeks in vitro within a relatively simple model, we demonstrate a basic primary human hepatocyte culture system that addresses many of the major hurdles in human hepatocyte culture research.     

Ureaplasma in lung. 2. Association with bronchopulmonary dysplasia in premature newborns

Infants with Ureaplasma urealyticum in the lower respiratory tract are at risk for chronic lung disease (CLD) or bronchopulmonary dysplasia (BPD) but causality has been difficult to prove. The goal of this study was to identify ureaplasma in human neonatal lung tissue using the in situ hybridization (ISH) procedure described in Part 1 (Exp. Mol. Pathol., in press) of this report. By correlating their presence with the histopathologic findings, it may be possible to provide further evidence of the pathogenicity of ureaplasmas and their association with BPD. Lung autopsy tissue from seven infants with positive cultures and seven infants with negative cultures for ureaplasma were included in the study. All culture-positive infants were positive for ureaplasma on ISH and all had histopathologic evidence of BPD. Two of the seven infants with negative cultures were positive for ureaplasma with ISH. Of interest, these two infants were also found to have BPD at autopsy. The other five infants with negative cultures were also negative for ureaplasma on ISH and had no evidence of BPD. This study correlates the presence of U. urealyticum by ISH with the finding of BPD on histopathologic evaluation and provides evidence that it has a role in the development of CLD.