A method of preparing woven Dacron aortic grafts to prevent interstitial hemorrhage

Severe and even fatal hemorrhage may be caused by bleeding through the interstices of a fabric graft. Improved fabrication of grafts with appropriate porosity for the conditions encountered has provided better hemostasis. Yet in some situations, bleeding through the fabric still presents a problem. A method of preclotting with autologous platelet rich plasma (PRP) and autoclaving is described. Gross and microscopic studies along with clinical applications confirm the effectiveness of the technique.     

Coronary perfusion and muscle lengthening increase cardiac contraction: different stretch-triggered mechanisms

An increase in coronary perfusion, transversal stretch of the myocardium, increases developed force (F(dev)) (Gregg effect) through activation of stretch-activated ion channels (SACs). Lengthening of the muscle, longitudinal stretch of the myocardium, causes an immediate increase in F(dev) followed by a slow F(dev) increase (Anrep effect). In isometrically contracting perfused papillary muscles of Wistar rats, we investigated whether both effects were based on similar stretch-induced mechanisms by measuring F(dev) and intracellular Ca(2+) concentration ([Ca(2+)](i)) after a muscle length increase from 85% to 95% L(max) (length at which maximal isometric force develops) at low and high coronary perfusion before and after inhibition of SACs with gadolinium (10 micromol/l Gd(3+)). The increase of F(dev) and peak [Ca(2+)](i) by the Gregg effect was of similar magnitude as the Anrep effect (from 3.5 +/- 0.8 to 3.9 +/- 1.2 mN/mm(2) and from 3.0 +/- 0.7% to 3.8 +/- 0.9% normalized [Ca(2+)](i), means +/- SE). SAC blockade completely blunted the increase of F(dev) and peak [Ca(2+)](i) by the Gregg effect; however, it did not affect the Anrep effect. The slow force response, but not the calcium response, was augmented by an increase in coronary perfusion. Therefore, increased coronary perfusion, transversal stretch of the myocardium, and muscle lengthening, longitudinal stretch of the myocardium, increase myocardial contraction in the rat through different stretch-triggered mechanisms.     

Smoking in Relation to Coronary Atherosclerotic Plaque Burden,Volume and Composition on Intravascular Ultrasound

Background

This study aimed to evaluate the relationship between cigarette smoking and coronary atherosclerotic burden, volume and composition as determined in-vivo by grayscale and virtual histology (VH) intravascular ultrasound (IVUS).

Methods and Results

Between 2008 and 2011, (VH-)IVUS of a non-culprit coronary artery was performed in 581 patients undergoing coronary angiography. To account for differences in baseline characteristics, current smokers were matched to never smokers by age, gender and indication for catheterization, resulting in 280 patients available for further analysis. Coronary atherosclerotic plaque volume, burden, composition (fibrous, fibro-fatty, dense calcium and necrotic core) and high-risk lesions (VH-IVUS derived thin-cap fibroatheroma (TCFA), plaque burden ≥70%, minimal luminal area ≤4.0 mm²) were assessed. Cigarette smoking showed a tendency towards higher coronary plaque burden (mean±SD, 38.6±12.5% in current versus 36.4±11.0% in never smokers, p = 0.080; and odds ratio (OR) of current smoking for plaque burden above versus below the median 1.69 (1.04–2.75), p = 0.033). This effect was driven by an association in patients presenting with an acute coronary syndrome (ACS) (current smokers, plaque burden 38.3±12.8% versus never smokers, plaque burden 35.0±11.2%, p = 0.049; OR 1.88 (1.02–3.44), p = 0.042). Fibrous tissue tended to be lower in current smokers (mean±SD, 57.7±10.5% versus 60.4±12.6%, p = 0.050) and fibro-fatty tissue was higher in current smokers (median[IQR], 9.6[6.0–13.7]% versus 8.6[5.8–12.2]%, p = 0.039). However, differences in percentage necrotic core and dense calcium could not be demonstrated. Also, no differences were found with regard to high-risk lesions.

Conclusions

An association between smoking and degree of coronary atherosclerosis was present in patients undergoing coronary angiography who presented with ACS. Although smoking was associated with higher fibro-fatty percentage, no associations could be demonstrated with percentage necrotic core, nor with VH-IVUS derived TCFA lesions. Since the magnitude of the differences in both degree and composition of atherosclerosis was modest, clinical relevance of the findings may be questioned.     

Liver-specific knockdown of JNK1 up-regulates proliferator-activated receptor gamma coactivator 1 beta and increases plasma triglyceride despite reduced glucose and insulin levels in diet-induced obese mice

The c-Jun N-terminal kinases (JNKs) have been implicated in the development of insulin resistance, diabetes, and obesity. Genetic disruption of JNK1, but not JNK2, improves insulin sensitivity in diet-induced obese (DIO) mice. We applied RNA interference to investigate the specific role of hepatic JNK1 in contributing to insulin resistance in DIO mice. Adenovirus-mediated delivery of JNK1 short-hairpin RNA (Ad-shJNK1) resulted in almost complete knockdown of hepatic JNK1 protein without affecting JNK1 protein in other tissues. Liver-specific knockdown of JNK1 resulted in significant reductions in circulating insulin and glucose levels, by 57 and 16%, respectively. At the molecular level, JNK1 knockdown mice had sustained and significant increase of hepatic Akt phosphorylation. Furthermore, knockdown of JNK1 enhanced insulin signaling in vitro. Unexpectedly, plasma triglyceride levels were robustly elevated upon hepatic JNK1 knockdown. Concomitantly, expression of proliferator-activated receptor gamma coactivator 1 beta, glucokinase, and microsomal triacylglycerol transfer protein was increased. Further gene expression analysis demonstrated that knockdown of JNK1 up-regulates the hepatic expression of clusters of genes in glycolysis and several genes in triglyceride synthesis pathways. Our results demonstrate that liver-specific knockdown of JNK1 lowers circulating glucose and insulin levels but increases triglyceride levels in DIO mice.     

Changes in clinical profile, treatment, and mortality in patients hospitalised for acute myocardial infarction between 1985 and 2008

Objectives

To quantify the impact of the implementation of treatment modalities into clinical practice since 1985, on outcome of patients with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI).

Methods

All consecutive patients admitted for STEMI or NSTEMI at the Thoraxcenter between 1985 and 2008 were included. Baseline characteristics, pharmacological and invasive treatment modalities, and survival status were collected. The study population was categorised in three groups of patients: those hospitalised between 1985–1990, 1990–2000, and 2000–2008.

Results

We identified 14,434 patients hospitalised for myocardial infarction (MI). Both STEMI and NSTEMI patients were increasingly treated with the current guideline based therapy. In STEMI, at 30 days following admission, cumulative mortality rate decreased from 17% in 1985–1990 to 13% in 1990–2000, and to 6% in 2000–2008. Adjusted 30-day and three-year mortality in the last period was 80% and 68% lower than in 1985, respectively. In NSTEMI, at 30 days following admission, cumulative mortality rate decreased from 6% in 1985–1990 to 4% in 1990–2000, and to 2% in 2000–2008. Adjusted 30-day and three-year mortality in the last period was 78% and 49% lower than in 1985, respectively. For patients admitted between 2000 and 2008, 3 year survival of STEMI and NSTEMI patients was 87% and 88%, respectively.

Conclusions

Our results indicate substantial improvements in acute- and long-term survival in patients hospitalised for MI, related to improved acute- as well as long-term treatment. Early medical evaluation in suspected MI and intensive early hospital treatment both remain warranted in the future.     

Synthesis and evaluation of urea-based indazoles as melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity

A series of urea-based N-1-(2-aminoethyl)-indazoles was synthesized and evaluated for melanin-concentrating hormone receptor 1 (MCHr1) antagonism in both binding and functional assays. Several compounds that acted as MCHr1 antagonists were identified, and optimization afforded a compound with excellent binding affinity, good functional potency, and oral efficacy in a chronic model for weight loss in diet-induced obese mice.     

Macrophyte communities in unimpacted European streams: variability in assemblage patterns, abundance and diversity

Macrophytes are an important component of aquatic ecosystems and are used widely within the Water Framework Directive (WFD) to establish ecological quality. In the present paper we investigated macrophyte community structure, i.e., composition, richness and diversity measures in 60 unimpacted stream and river sites throughout Europe. The objectives were to describe assemblage patterns in different types of streams and to assess the variability in various structural and ecological metrics within these types to provide a basis for an evaluation of their suitability in ecological quality assessment. Macrophyte assemblage patterns varied considerably among the main stream types. Moving from small-sized, shallow mountain streams to medium-sized, lowland streams there was a clear transition in species richness, diversity and community structure. There was especially a shift from a predominance of species-poor mosses and communities dominated by liverwort in the small-sized, shallow mountain streams to more species-rich communities dominated by vascular plants in the medium-sized, lowland streams. The macrophyte communities responded to most of the features underlying the typological framework defined in WFD. The present interpretation of the WFD typology may not, however, be adequate for an evaluation of stream quality based on macrophytes. First and most important, by using this typology we may overlook an important community type, which is characteristic of small-sized, relatively steep-gradient streams that are an intermediate type between the small-sized, shallow mountain streams and the medium-sized, lowland streams. Second, the variability in most of the calculated metrics was slightly higher when using the pre-defined typology. The consistency of these results should be investigated by analysing a larger number of sites. Particularly the need of re-defining the typology to improve the ability to detect impacts on streams and rivers from macrophyte assemblage patterns should be investigated. Electronic supplementary material Electronic supplementary material is available for this article at and accessible for authorised users.     

Macrophyte communities of European streams with altered physical habitat

The impact of altering hydro-morphology on three macrophyte community types was investigated at 107 European stream sites. Sites were surveyed using standard macrophyte and habitat survey techniques (Mean Trophic Rank Methodology and River Habitat Survey respectively). Principal Components Analysis shows the macrophyte community of upland streams live in a more structurally diverse physical habitat than lowland communities. Variables representing the homogeneity and diversity of the physical environment were used to successfully separate un-impacted from impacted sites, e.g. homogeneity of depth and substrate increased with decreasing quality class for lowland sites (ANOVA p < 0.05). Macrophyte attribute groups and structural metrics such as species richness were successfully linked to hydro-morphological variables indicative of impact. Most links were specific to each macrophyte community type, e.g., the attribute group liverworts, mosses and lichens decreased in abundance with increasing homogeneity of depth and decreasing substrate size at lowland sites but not at upland sites. Elodea canadensis, Sparganium emersum and Potamogeton crispus were indicative of impacted lowland sites. Many of the indicator species are also known to be tolerant to other forms of impact. The potential for a macrophyte tool indicative of hydro-morphological impact is discussed. It is concluded one could be constructed by combining indicator species and metrics such as species richness and evenness.