Effect of anticoagulation upon nephron obstruction in experimental acute ischaemic renal failure. A morphological study

Ischaemic-reperfusion injury as a model of acute renal failure (ARF) results in increased macromolecular permeability, tubular obstruction, and renal oedema. To investigate the role for coagulation in this model, anticoagulated and saline-pretreated rats were subjected to 60 min unilateral renal artery occlusion (RAO). After 15 min of reflow, specimens were collected for electron and light microscopic examination. Morphometry was employed to study podocyte changes and Bowman's space dilatation as measures of increased permeability and tubular obstruction, respectively. After 15 min of reflow, Bowman's space increased significantly and the podocytes were markedly widened and flattened. Rats pretreated with heparin or warfarin showed less widening of Bowman's space than saline-treated rats, whereas no significant difference was seen regarding the podocyte changes. In saline-treated rats, fibrin-positive material was seen in the tubules but not in the urine sediments collected after 90 min of reflow, either due to fibrinolysis or poor urinary elimination. The results suggest that anticoagulation does not preclude the glomerular sieving of macromolecules, but seems to reduce tubular obstruction, probably by preventing conversion of filtered fibrinogen into fibrin

Antonio Gramsci and 'the international': past, present and future

There is no abstract, but this is a representative paragraph from the introduction:'Accordingly, this chapter focuses on four key themes: (1) Gramsci as an avowedly ‘international’ theorist which does not require his concepts to be ‘scaled-up’ from the ‘national’ to ‘the international’ due to his inherent interest in the intertwining of the relations of force across different territorial and geographic scales of uneven development; (2) the ‘passive revolutionary’ road to capitalism related to struggles between class forces from above and below that combine elements of ‘revolution’ and ‘restoration’ in constituting and/or restructuring capitalist social relations of production; (3) the contemporary period of a globalizing world economy linked to the transnational expansion of capitalist class fractions and the implications for labor; and (4) the nature of, and conflicts accompanying, the current period of crisis since the Great Recession (2007 onward) in which the authoritarian dynamics of neoliberalization have come to the fore in repressing anti-capitalist social movements. It is then argued, in conclusion, that a critical, Gramsci-inspired approach has profound political consequences, for it enables us to appreciate the imperative of rethinking alternatives to the current world order during the current plight of capitalist crisis.

Large-scale gene-centric analysis identifies novel variants for coronary artery disease.

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in 3c2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10(-33); LPA:p<10(-19); 1p13.3:p<10(-17)) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5 710(-7)). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06-1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other 3c4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity\u200a=\u200a0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes