Pyrazolo-triazolo-pyrimidines as adenosine receptor antagonists: Effect of the N-5 bond type on the affinity and selectivity at the four adenosine receptor subtypes

In the last few years, many efforts have been made to search for potent and selective human A3 adenosine antagonists. In particular, one of the most promising human A3 adenosine receptor antagonists is represented by the pyrazolo-triazolo-pyrimidine family. This class of compounds has been strongly investigated from the point of view of structure-activity relationships. In particular, it has been observed that fundamental requisites for having both potency and selectivity at the human A3 adenosine receptors are the presence of a small substituent at the N8 position and an unsubstitued phenyl carbamoyl moiety at the N5 position. In this study, we report the role of the N5-bond type on the affinity and selectivity at the four adenosine receptor subtypes. The observed structure-activity relationships of this class of antagonists are also exhaustively rationalized using the recently published ligand-based homology modeling approach

Follow-up of atheroma burden with sequential whole body contrast enhanced MR angiography:a feasibility study

Assess the feasibility of whole body magnetic resonance angiography (WB-MRA) for monitoring global atheroma burden in a population with peripheral arterial disease (PAD). 50 consecutive patients with symptomatic PAD referred for clinically indicated MRA were recruited. Whole body MRA (WB-MRA) was performed at baseline, 6 months and 3 years. The vasculature was split into 31 anatomical arterial segments. Each segment was scored according to degree of luminal narrowing: 0 = normal, 1 = <50 %, 2 = 50–70 %, 3 = 71–99 %, 4 = vessel occlusion. The score from all assessable segments was summed, and then normalised to the number of assessable vessels. This normalised score was divided by four (the maximum vessel score) and multiplied by 100 to give a final standardised atheroma score (SAS) with a score of 0–100. Progression was assessed with repeat measure ANOVA. 36 patients were scanned at 0 and 6 months, with 26 patients scanned at the 3 years follow up. Only those who completed all three visits were included in the final analysis. Baseline atherosclerotic burden was high with a mean SAS of 15.7 ± 10.3. No significant progression was present at 6 months (mean SAS 16.4 ± 10.5, p = 0.67), however there was significant disease progression at 3 years (mean SAS 17.7 ± 11.5, p = 0.01). Those with atheroma progression at follow-up were less likely to be on statin therapy (79 vs 100 %, p = 0.04), and had significantly higher baseline SAS (17.6 ± 11.2 vs 10.7 ± 5.1, p = 0.043). Follow up of atheroma burden is possible with WB-MRA, which can successfully quantify and monitor atherosclerosis progression at 3 years follow-up

Cardiovascular imaging 2011 in the International Journal of Cardiovascular Imaging

Cardiovascular Aspects of Radiolog

Whole-body magnetic resonance angiography.

Vascular disease, whether it be atherosclerosis, inflammatory, or hereditary vasculitide, is a systemic disorder with disease in one territory predictive of disease in another. Despite this, current approaches focus on single-territory assessment ignoring the global burden of disease. Advances in MRI have enabled us to surmount previous limitations and expand our approach to such conditions with the ability to simultaneously assess the entirety of the arterial tree in a single examination, allowing a staging examination as it were, of the vascular health in its totality. This review will cover the acquisition technique, reporting, clinical utility, and current evidence base for such an approach

The value of systematic pattern analysis in FNAC of breast lesions: 225 cases with cytohistological correlation

Background : Fine needle aspiration cytology (FNAC) has a high rating in the assessment of breast lesions. Various methods have been used to diagnose cytology of breast lesions. Aims : Present study was undertaken to evaluate the feasibility of application of systematic pattern analysis based on morphology in diagnosing breast aspirates. Materials and Methods : This is a retrospective study of FNAC of the breast done over a period of 4 years in a tertiary care centre. A total of 225 cases of breast lesions for which FNAC was done with histological follow-up were included in the study. Breast aspirates were provisionally diagnosed based on systematic pattern analysis. Aspirates were grouped into six categories based on predominant cellular pattern, and correlation between cytological and histological diagnosis was assessed. Results : Application of pattern analysis on FNAC of breast lesions in our study had a sensitivity of 94.5%, specificity of 98%, diagnostic accuracy of 97%, positive predictive value of 95.8%, and negative predictive value of 97.4%. Conclusions : Systematic pattern analysis based on morphology of FNAC smears was found to be highly reliable and could be easily reproducible in the assessment of breast masses

GSTO1-1 plays a pro-inflammatory role in models of inflammation, colitis and obesity

Abstract Glutathione transferase Omega 1 (GSTO1-1) is an atypical GST reported to play a pro-inflammatory role in response to LPS. Here we show that genetic knockout of Gsto1 alters the response of mice to three distinct inflammatory disease models. GSTO1-1 deficiency ameliorates the inflammatory response stimulated by LPS and attenuates the inflammatory impact of a high fat diet on glucose tolerance and insulin resistance. In contrast, GSTO1-1 deficient mice show a more severe inflammatory response and increased escape of bacteria from the colon into the lymphatic system in a dextran sodium sulfate mediated model of inflammatory bowel disease. These responses are similar to those of TLR4 and MyD88 deficient mice in these models and confirm that GSTO1-1 is critical for a TLR4-like pro-inflammatory response in vivo. In wild-type mice, we show that a small molecule inhibitor that covalently binds in the active site of GSTO1-1 can be used to ameliorate the inflammatory response to LPS. Our findings demonstrate the potential therapeutic utility of GSTO1-1 inhibitors in the modulation of inflammation and suggest their possible application in the treatment of a range of inflammatory conditions