An intra-aortic shunt prevents paralysis during aortic surgery in sheep

INTRODUCTION: Sheep are recommended by the United States Food and Drug Administration as a model for testing cardiovascular tissue, but are particularly prone to spinal cord ischemia and subsequent paralysis during aortic cross-clamping. METHODS: A shunt consisting of a 9 cm long phosphorylcholine coated 1/4 in. (i.d.) polyvinylchloride tube was inserted through the aortotomy into the aorta to provide blood flow across the operative site. Blood pressure and flow in the distal aorta were measured continuously with an indwelling femoral artery catheter and an ultrasonic aortic flow probe. The hemodynamic effects were measured in seven 45 to 55 kg Suffolk sheep. This shunt was then used to implant decellularized pulmonary artery patches into 25 animals. RESULTS: Occlusion of the aorta reduced the distal mean aortic pressure from 86.4 +/- 4.6 mmHg to 1.79 +/- 0.4 mmHg (P < 0.001) and opening the intra-aortic shunt restored the distal mean aortic pressure to 67.9 +/- 7.3 mmHg (P = 0.053). Blood flow in the distal aorta was 2.35 +/- 0.37 L/min at baseline and was reduced to -0.01 +/- 0.01 L/min (P < 0.001) with the aorta cross-clamped and returned to 2.49 +/- 0.36 L/min (P = 0.945) when the shunt was opened. Use of this shunt prevented hind leg paralysis in all 24 animals surviving the procedure. CONCLUSIONS: A simple intra-aortic shunt was effective in restoring blood pressure and flow in the aorta distal to the operative site and prevented hind leg paralysis associated with aortic clamping.     

NMR assessment of Me(2)SO in decellularized cryopreserved aortic valve conduits

INTRODUCTION: Decellularized cryopreserved allograft vascular tissue may provide a nonimmunogenic scaffold that is suitable for repopulation by cells from a variety of sources, conferring the potential for growth and repair. Although dimethyl sulfoxide (Me(2)SO) is generally regarded as a safe cryoprotectant, even low levels may alter function of repopulating cells. We investigated the residual concentration of Me(2)SO in the aqueous compartment of cryopreserved ovine aortic valve conduits following decellularization. MATERIALS AND METHODS: Aortic valve conduits from Suffolk sheep were cryopreserved in 1.1 M (7.5% vol/vol) Me(2)SO according to the protocol of our local tissue bank. Three aortic valve conduits were decellularized in a series of hypotonic and hypertonic Tris buffers. Tissue samples were taken at regular time intervals throughout the decellularization process and equilibrated in double distilled, deionized H(2)O for 28 days. Quantitative proton nuclear magnetic resonance spectroscopy was used to determine the residual Me(2)SO concentration in the equilibration solutions from which Me(2)SO tissue concentrations were calculated. RESULTS: After thawing, the mean Me(2)SO concentration in the valve conduit was 0.302 +/- 0.081 M. The decellularization process resulted in a stepwise reduction in the Me(2)SO concentration to less than 8.56 x 10(-5) +/- 9 x 10(-5) M (P = 0.02). The diffusion coefficient was 2.5 x 10(-6) cm(2)/s. CONCLUSIONS: Our study demonstrates that Me(2)SO is effectively washed out of the aortic valve conduit during decellularization, resulting in a final concentration that is several orders of magnitude less than Me(2)SO concentrations reported to alter cell function.     

Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications

Platelets have a central role in the development of arterial thrombosis and subsequent cardiovascular events. An appreciation of this complex process has made antiplatelet therapy the cornerstone of cardiovascular disease management. However, numerous patients will experience a recurrent atherothrombotic vascular event despite adequate antiplatelet therapy. Individual differences in the rate of platelet activation and reactivity markedly influence normal hemostasis and the pathological outcome of thrombosis. Such an individual variability is largely determined by environmental and genetic factors. These are known to either hamper platelets' response to agonists, and thereby mimic the pharmacological modulation of platelet function or mask therapy effect and sensitize platelets. In this article, we reviewed the antiplatelet mechanisms of aspirin and clopidogrel and the possible role of different polymorphisms, which may affect the efficacy of antiplatelet therapy. Heterogeneity in the way patients respond to aspirin and clopidogrel may in part reflect variation in cyclooxygenase (COX)-1, COX-2, glycoprotein (GP) Ib alpha, GP Ia/IIa, GP IIb/IIIa, UGT1A6*2, P2Y₁, P2Y₁₂, CYP2C9, CYP3A4 and CYP3A5 genotypes.     

PLGA Nanoparticles Stabilized with Cationic Surfactant: Safety Studies and Application in Oral Delivery of Paclitaxel to Treat Chemical-Induced Breast Cancer in Rat

Purpose  

This study was carried out to formulate poly(lactide-co-glycolide) (PLGA) nanoparticles using a quaternary ammonium salt didodecyl dimethylammonium bromide (DMAB) and checking their utility to deliver paclitaxel by oral route.     

Reliability and Validity of Assessing User Satisfaction With Web-Based Health Interventions

BackgroundThe perspective of users should be taken into account in the evaluation of Web-based health interventions. Assessing the users’ satisfaction with the intervention they receive could enhance the evidence for the intervention effects. Thus, there is a need for valid and reliable measures to assess satisfaction with Web-based health interventions.ObjectiveThe objective of this study was to analyze the reliability, factorial structure, and construct validity of the Client Satisfaction Questionnaire adapted to Internet-based interventions (CSQ-I).MethodsThe psychometric quality of the CSQ-I was analyzed in user samples from 2 separate randomized controlled trials evaluating Web-based health interventions, one from a depression prevention intervention (sample 1, N=174) and the other from a stress management intervention (sample 2, N=111). At first, the underlying measurement model of the CSQ-I was analyzed to determine the internal consistency. The factorial structure of the scale and the measurement invariance across groups were tested by multigroup confirmatory factor analyses. Additionally, the construct validity of the scale was examined by comparing satisfaction scores with the primary clinical outcome.ResultsMultigroup confirmatory analyses on the scale yielded a one-factorial structure with a good fit (root-mean-square error of approximation =.09, comparative fit index =.96, standardized root-mean-square residual =.05) that showed partial strong invariance across the 2 samples. The scale showed very good reliability, indicated by McDonald omegas of .95 in sample 1 and .93 in sample 2. Significant correlations with change in depressive symptoms (r=−.35, P<.001) and perceived stress (r=−.48, P<.001) demonstrated the construct validity of the scale.ConclusionsThe proven internal consistency, factorial structure, and construct validity of the CSQ-I indicate a good overall psychometric quality of the measure to assess the user’s general satisfaction with Web-based interventions for depression and stress management. Multigroup analyses indicate its robustness across different samples. Thus, the CSQ-I seems to be a suitable measure to consider the user’s perspective in the overall evaluation of Web-based health interventions.     

Expression of the Proto-oncogene c-myc in Human Stenotic Aortocoronary Bypass Grafts

Proliferation and differentiation of vascular smooth muscle cells (VSMC) are central events in vascular pathobiology and play a major role in the development of stenotic and restenotic lesions [15, 27]. The proto-oncogene c-myc and other early cell cycle-regulating genes have been implicated in the induction of cell proliferation and differentiation under diverse pathophysiological conditions [11, 13]. In the present study we analyzed c-myc mRNAexpression by indirect nonradioactive in situ hybridization technique (NISH) in human stenotic venous bypass grafts (n = 32) retrieved during re-do operations of coronary artery disease and compared the results with 28 native veins (vena saphena magna) from the same patients.Stenotic bypass grafts showed enhanced c-myc expression located predominantly in VSMCin the media and neointima (severity score: ++–+++, 32/32 stenotic veins). In native veins we observed only low levels of – c-myc mRNA(severity score: +, 28/28 native veins), all signals were restricted to endothelial cells of either the innermost intimal layer or of the vasa vasorum.Our in situ hybridization studies demonstrate enhanced mRNAexpression of the proto-oncogene c-myc in stenotic venous bypass grafts. These results suggest that – in analogy to other pathophysiological conditions – c-myc exerts essential regulatory functions in cellular events operative during the initiation and progression of venous bypass graft disease.