7 research outputs found
Structural and molecular features of intestinal strictures in rats with Crohn's-like disease
AIM: To develop a new rat model we wanted to gain a
better understanding of stricture formation in Crohn鈥檚
disease (CD).
METHODS: Chronic colitis was induced locally by the
administration of 2,4,6-trinitrobenzenesulfonic acid
(TNBS). The relapsing inflammation characteristic
to CD was mimicked by repeated TNBS treatments.
Animals were randomly divided into control, once,
twice and three times TNBS-treated groups. Control
animals received an enema of saline. Tissue samples
were taken from the strictured colonic segments and
also adjacent proximally and distally to its 60, 90 or
120 d after the last TNBS or saline administrations.
The frequency and macroscopic extent of the strictures
were measured on digital photographs. The structural features of strictured gut wall were studied by light- and electron microscopy. Inflammation related alterations in TGF-beta 2 and 3, matrix metalloproteinases 9 (MMP9)
and TIMP1 mRNA and protein expression were determined
by quantitative real-time PCR and western blot
analysis. The quantitative distribution of caspase 9 was
determined by post-embedding immunohistochemistry.
RESULTS: Intestinal strictures first appeared 60 d
after TNBS treatments and the frequency of them
increased up to day 120. From day 90 an intact lamina
epithelialis, reversible thickening of lamina muscularis
mucosae and irreversible thickening of the muscularis
externa were demonstrated in the strictured colonic
segments. Nevertheless the morphological signs of
apoptosis were frequently seen and excess extracellular
matrix deposition was recorded between smooth muscle
cells (SMCs). Enhanced caspase 9 expression on day 90
in the SMCs and on day 120 also in myenteric neurons
indicated the induction of apoptosis. The mRNA
expression profile of TGF-betas after repeated TNBS
doses was characteristic to CD, TGF-beta 2, but not
TGF-beta 3 was up-regulated. Overexpression of MMP9
and down-regulation of TIMP1 were demonstrated. The
progressive increase in the amount of MMP9 protein in
the strictures was also obvious between days 90 and
120 but TIMP1 protein was practically undetectable at
this time.
CONCLUSION: These findings indicate that aligned
structural and molecular changes in the gut wall rather
than neuronal cell death play the primary role in
stricture formation
Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease
Background Patients with obstructive left main coronary artery disease are usually treated with coronary-artery bypass grafting (CABG). Randomized trials have suggested that drug-eluting stents may be an acceptable alternative to CABG in selected patients with left main coronary disease. Methods We randomly assigned 1905 eligible patients with left main coronary artery disease of low or intermediate anatomical complexity to undergo either percutaneous coronary intervention (PCI) with fluoropolymer-based cobalt-chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). Anatomic complexity was assessed at the sites and defined by a Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score of 32 or lower (the SYNTAX score reflects a comprehensive angiographic assessment of the coronary vasculature, with 0 as the lowest score and higher scores [no upper limit] indicating more complex coronary anatomy). The primary end point was the rate of a composite of death from any cause, stroke, or myocardial infarction at 3 years, and the trial was powered for noninferiority testing of the primary end point (noninferiority margin, 4.2 percentage points). Major secondary end points included the rate of a composite of death from any cause, stroke, or myocardial infarction at 30 days and the rate of a composite of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years. Event rates were based on Kaplan-Meier estimates in time-to-first-event analyses. Results At 3 years, a primary end-point event had occurred in 15.4% of the patients in the PCI group and in 14.7% of the patients in the CABG group (difference, 0.7 percentage points; upper 97.5% confidence limit, 4.0 percentage points; P=0.02 for noninferiority; hazard ratio, 1.00; 95% confidence interval, 0.79 to 1.26; P=0.98 for superiority). The secondary end-point event of death, stroke, or myocardial infarction at 30 days occurred in 4.9% of the patients in the PCI group and in 7.9% in the CABG group (P<0.001 for noninferiority, P=0.008 for superiority). The secondary end-point event of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years occurred in 23.1% of the patients in the PCI group and in 19.1% in the CABG group (P=0.01 for noninferiority, P=0.10 for superiority). Conclusions In patients with left main coronary artery disease and low or intermediate SYNTAX scores by site assessment, PCI with everolimus-eluting stents was noninferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction at 3 years. (Funded by Abbott Vascular; EXCEL ClinicalTrials.gov number, NCT01205776 .)