Effects of Changing to Individually Ventilated Caging on Guinea Pigs (Cavia porcellus).

The goal of this study was to evaluate the effect of changing to IVC housing on guinea pigs by recording several physiologic parameters in guinea pigs housed sequentially in open-top cages (OTC) and IVC. To register heart rate and locomotor activity, 10 male Dunkin-Hartley guinea pigs implanted with telemetric transmitters were moved from OTC to new, freshly prepared OTC or IVC and subsequently monitored by telemetry during the 4 d after the first cage change. Body weight and food consumption were measured twice during the study. Comparison of data from OTC- and IVC-housed guinea pigs showed no relevant differences in heart rate (mean ± 1 SD; 213 ± 10 bpm and 207 ± 9 bpm, respectively) at any time point. In contrast, locomotor activity varied: whereas activity during the first 4 h after the change of cage type was greater in IVC-housed animals, that during the following 24 h was greater in OTC but was similar between groups thereafter. Animals housed in OTC consumed more food than did those in IVC and, under both conditions, consumption was statistically related to body weight changes. Together, these results show that a change to IVC housing induced only transient increases in locomotor activity in guinea pigs without a marked increase in heart rate but with a decrease in food consumption. Because decreased food consumption was the only stress-associated sign during the 4-d observation, longer studies are needed to ascertain the importance of this finding.

Role of computer-aided detection in very small screening detected invasive breast cancers.

This study aims to assess computer-aided detection (CAD) performance with full-field digital mammography (FFDM) in very small (equal to or less than 1 cm) invasive breast cancers. Sixty-eight invasive breast cancers less than or equal to 1 cm were retrospectively studied. All cases were detected with FFDM in women aged 49-69 years from our breast cancer screening program. Radiological characteristics of lesions following BI-RADS descriptors were recorded and compared with CAD sensitivity. Age, size, BI-RADS classification, breast density type, histological type of the neoplasm, and role of the CAD were also assessed. Per-study specificity and mass false-positive rate were determined by using 100 normal consecutive studies. Thirty-seven (54.4 %) masses, 17 (25 %) calcifications, 6 (8.8 %) masses with calcifications, 7 (10.3 %) architectural distortions, and 1 asymmetry (1.5 %) were found. CAD showed an overall sensitivity of 86.7 % (masses, 86.5 %; calcifications, 100 %; masses with calcifications, 100 %; and architectural distortion, 57.14 %), CAD failed to detect 9 out of 68 cases: 5 of 37 masses, 3 of 7 architectural distortions, and 1 of 1 asymmetry. Fifteen out of 37 masses were hyperdense, and all of them were detected by CAD. No association was seen among mass morphology or margins and detectability. Per-study specificity and CAD false-positive rate was 26 % and 1.76 false marks per study. In conclusion, CAD shows a high sensitivity and a low specificity. Lesion size, histology, and breast density do not influence sensitivity. Mammographic features, mass density, and thickness of the spicules in architectural distortions do influence.

Statins normalize vascular lysyl oxidase down-regulation induced by proatherogenic risk factors.

AIMS: Statins are lipid-lowering drugs widely used in the management of vascular diseases. Clinical and experimental evidence suggest that statins improve endothelial function by both cholesterol-lowering-dependent and -independent mechanisms. We have previously shown that endothelial dysfunction induced by risk factors and proinflammatory cytokines is associated with down-regulation of lysyl oxidase (LOX), a key enzyme modulating extracellular matrix maturation and vascular integrity. Our aim was to analyse whether statins could normalize LOX expression impaired by proatherogenic risk factors. METHODS AND RESULTS: We observed that pharmacological concentrations of statins (atorvastatin and simvastatin) modulated LOX transcriptional activity, counteracting the down-regulation of LOX (at the mRNA, protein, and activity level) caused by tumour necrosis factor-alpha (TNFalpha) in porcine, bovine, and human aortic endothelial cells. Geranylgeraniol but not farnesol reversed this effect, suggesting the involvement of geranylgeranylated proteins. In accordance, inhibitors of RhoA/Rho kinase also counteracted LOX down-regulation caused by TNFalpha, and over-expression of a RhoA dominant-negative mutant mimicked statin effects. Statins were also able to counteract the decrease in LOX expression produced by atherogenic concentrations of LDL by a similar mechanism and to partially prevent the increase in endothelial permeability elicited by these lipoproteins. Finally, in the in vivo porcine model of hypercholesterolaemia, we observed that statins abrogated the reduction of vascular LOX expression triggered by high plasma levels of LDL. CONCLUSION: These data indicate that statins normalize vascular LOX expression altered by atherogenic risk factors through a RhoA/Rho kinase-dependent mechanism. Thus, modulation of LOX by statins could contribute to vascular protection and to the cardiovascular risk reduction achieved by this therapy.

Pravastatin reduces thrombogenicity by mechanisms beyond plasma cholesterol lowering.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzymeA reductase are widely used in the management and prevention of cardiovascular disease. In addition to its major activity, plasma lipid lowering, statins have shown a wide spectrum of additional effects that may contribute to their benefits in the prevention of cardiovascular disease. Our objective was to study whether treatment with a statin, pravastatin, could reduce thrombosis triggered by damaged vessels without changing plasma cholesterol levels. A cholesterol-clamp animal model was developed by feeding swine for 100 days on an hypercholesterolemic (HL) diet; in the last 50 days, they were randomly assigned to receive either placebo (HLC) or pravastatin (5 mg . kg(-1) . day(-1)) (HLP) in addition to the hypercholesterolemic diet. A normocholesterolemic control group (NLC) was simultaneously studied. There were no significant differences in total cholesterol, LDL and HDL plasma levels between the two groups; however, mural thrombosis triggered by both an eroded and disrupted vessel wall was significantly inhibited by pravastatin (P<0.05). Axial dependence analysis of platelet deposition revealed that pravastatin treatment reduced the increase in platelet deposition associated to the shear rate increase at the stenosis. Additionally, pravastatin treatment significantly reduced platelet membrane RhoA expression (P<0.05) and vascular wall tissue factor (TF) protein expression (P<0.05). In addition to its lipid lowering effects, pravastatin can reduce blood thrombogenicity by mechanisms independent of plasma cholesterol lowering.