A Paclitaxel-Eluting Stent for the Prevention of Coronary Restenosis

Background Intimal hyperplasia and resulting restenosis limit the efficacy of coronary stenting. We studied a coronary stent coated with the antiproliferative agent paclitaxel as a means of preventing restenosis. Methods We conducted a multicenter, randomized, controlled, triple-blind study to evaluate the ability of a paclitaxel-eluting stent to inhibit restenosis. At three centers, 177 patients with discrete coronary lesions (<15 mm in length, 2.25 to 3.5 mm in diameter) underwent implantation of paclitaxel-eluting stents (low dose, 1.3 µg per square millimeter, or high dose, 3.1 µg per square millimeter) or control stents. Antiplatelet therapies included aspirin with ticlopidine (120 patients), clopidogrel (18 patients), or cilostazol (37 patients). Clinical follow-up was performed at one month and four to six months, and angiographic follow-up at four to six months. Results Technical success was achieved in 99 percent of the patients (176 of 177). At follow-up, the high-dose group, as compared with the control group, had significantly better results for the degree of stenosis (mean [±SD], 14±21 percent vs. 39±27 percent; P<0.001), late loss of luminal diameter (0.29±0.72 mm vs. 1.04±0.83 mm, P<0.001), and restenosis of more than 50 percent (4 percent vs. 27 percent, P<0.001). Intravascular ultrasound analysis demonstrated a dose-dependent reduction in the volume of intimal hyperplasia (31, 18, and 13 mm3, in the high-dose, low-dose, and control groups, respectively). There was a higher rate of major cardiac events in patients receiving cilostazol than in those receiving ticlopidine or clopidogrel. Among patients receiving ticlopidine or clopidogrel, event-free survival was 98 percent and 100 percent in the high-dose and control groups, respectively, at one month, and 96 percent in both at four to six months. Conclusions Paclitaxel-eluting stents used with conventional antiplatelet therapy effectively inhibit restenosis and neointimal hyperplasia, with a safety profile similar to that of standard stents.published_or_final_versio

Fluctuations, dissipation and the dynamical Casimir effect

Vacuum fluctuations provide a fundamental source of dissipation for systems coupled to quantum fields by radiation pressure. In the dynamical Casimir effect, accelerating neutral bodies in free space give rise to the emission of real photons while experiencing a damping force which plays the role of a radiation reaction force. Analog models where non-stationary conditions for the electromagnetic field simulate the presence of moving plates are currently under experimental investigation. A dissipative force might also appear in the case of uniform relative motion between two bodies, thus leading to a new kind of friction mechanism without mechanical contact. In this paper, we review recent advances on the dynamical Casimir and non-contact friction effects, highlighting their common physical origin.Comment: 39 pages, 4 figures. Review paper to appear in Lecture Notes in Physics, Volume on Casimir Physics, edited by Diego Dalvit, Peter Milonni, David Roberts, and Felipe da Rosa. Minor changes, a reference adde

Network analysis of human protein location

<p>Abstract</p> <p>Background</p> <p>Understanding cellular systems requires the knowledge of a protein's subcellular localization (SCL). Although experimental and predicted data for protein SCL are archived in various databases, SCL prediction remains a non-trivial problem in genome annotation. Current SCL prediction tools use amino-acid sequence features and text mining approaches. A comprehensive analysis of protein SCL in human PPI and metabolic networks for various subcellular compartments is necessary for developing a robust SCL prediction methodology.</p> <p>Results</p> <p>Based on protein-protein interaction (PPI) and metabolite-linked protein interaction (MLPI) networks of proteins, we have compared, contrasted and analysed the statistical properties across different subcellular compartments. We integrated PPI and metabolic datasets with SCL information of human proteins from LOCATE and GOA (Gene Ontology Annotation) and estimated three statistical properties: Chi-square (χ²) test, Paired Localisation Correlation Profile (PLCP) and network topological measures. For the PPI network, Pearson's chi-square test shows that for the same SCL category, twice as many interacting protein pairs are observed than estimated when compared to non-interacting protein pairs (χ²= 1270.19, <it>P-value </it>< 2.2 × 10^-16), whereas for MLPI, metabolite-linked protein pairs having the same SCL are observed 20% more than expected, compared to non-metabolite linked proteins (χ²= 110.02, <it>P-value </it>< 2.2 x10^-16). To address the issue of proteins with multiple SCLs, we have specifically used the PLCP (Pair Localization Correlation Profile) measure. PLCP analysis revealed that protein interactions are majorly restricted to the same SCL, though significant cross-compartment interactions are seen for nuclear proteins. Metabolite-linked protein pairs are restricted to specific compartments such as the mitochondrion (<it>P-value </it>< 6.0e-07), the lysosome (<it>P-value </it>< 4.7e-05) and the Golgi apparatus (<it>P-value </it>< 1.0e-15). These findings indicate that the metabolic network adds value to the information in the PPI network for the localisation process of proteins in human subcellular compartments.</p> <p>Conclusions</p> <p>The MLPI network differs significantly from the PPI network in its SCL distribution. The PPI network shows passive protein interaction, possibly due to its high false positive rate, across different subcellular compartments, which seem to be absent in the MLPI network, as the MLPI network has evolved to maintain high substrate specificity for proteins.</p

vProtein: Identifying Optimal Amino Acid Complements from Plant-Based Foods

Background: Indispensible amino acids (IAAs) are used by the body in different proportions. Most animal-based foods provide these IAAs in roughly the needed proportions, but many plant-based foods provide different proportions of IAAs. To explore how these plant-based foods can be better used in human nutrition, we have created the computational tool vProtein to identify optimal food complements to satisfy human protein needs. Methods: vProtein uses 1251 plant-based foods listed in the United States Department of Agriculture standard release 22 database to determine the quantity of each food or pair of foods required to satisfy human IAA needs as determined by the 2005 daily recommended intake. The quantity of food in a pair is found using a linear programming approach that minimizes total calories, total excess IAAs, or the total weight of the combination. Results: For single foods, vProtein identifies foods with particularly balanced IAA patterns such as wheat germ, quinoa, and cauliflower. vProtein also identifies foods with particularly unbalanced IAA patterns such as macadamia nuts, degermed corn products, and wakame seaweed. Although less useful alone, some unbalanced foods provide unusually good complements, such as Brazil nuts to legumes. Interestingly, vProtein finds no statistically significant bias toward grain/ legume pairings for protein complementation. These analyses suggest that pairings of plant-based foods should be based on the individual foods themselves instead of based on broader food group-food group pairings. Overall, the most efficien

African Rice (Oryza glaberrima Steud.): Lost Crop of the Enslaved Africans Discovered in Suriname1

African Rice (Oryza glaberrimaSteud.): Lost Crop of the Enslaved Africans Discovered in Suriname. African rice (Oryza glaberrima Steud.) was introduced to the Americas during the slave trade years and grown by enslaved Africans for decades before mechanical milling devices facilitated the shift towards Asian rice (O. sativa L.). Literature suggests that African rice is still grown in Guyana and French Guiana, but the most recent herbarium voucher dates from 1938. In this paper, evidence is presented that O. glaberrima is still grown by Saramaccan Maroons both for food and ritual uses. Saramaccan informants claim their forefathers collected their first “black rice” from a mysterious wild rice swamp and cultivated these seeds afterwards. Unmilled spikelets (grains with their husk still attached) are sold in small quantities for ancestor offerings, and even exported to the Netherlands to be used by Maroon immigrants. Little is known of the evolution of O. glaberrima, before and after domestication. Therefore, more research is needed on the different varieties of rice and other “lost crops” grown by these descendants of enslaved Africans who escaped from plantations in the 17th and 18th centuries and maintained much of their African cultural heritage in the deep rainforest

Intimal Hyperplasia in Balloon Dilated Coronary Arteries is Reduced by Local Delivery of the NO Donor, SIN-1 Via a cGMP-Dependent Pathway

<p>Abstract</p> <p>Background</p> <p>To elucidate the mechanism by which local delivery of 3-morpholino-sydnonimine (SIN-1) affects intimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA).</p> <p>Methods</p> <p>Porcine coronary arteries were treated with PTCA and immediately afterwards locally treated for 5 minutes, with a selective cytosolic guanylate cyclase inhibitor, 1 H-(1,2,4)oxadiazole(4,3-alpha)quinoxaline-1-one (ODQ) + SIN-1 or only SIN-1 using a drug delivery-balloon. Arteries were angiographically depicted, morphologically evaluated and analyzed after one and eight weeks for actin, myosin and intermediate filaments (IF) and nitric oxide synthase (NOS) contents.</p> <p>Results</p> <p>Luminal diameter after PCI in arteries treated with SIN-1 alone and corrected for age-growth was significantly larger as compared to ODQ + SIN-1 or to controls (p < 0.01). IF/actin ratio after one week in SIN-1 treated segments was not different compared to untreated segments, but was significantly reduced compared to ODQ + SIN-1 treated vessels (p < 0.05). Expression of endothelial NADPH diaphorase activity was significantly lower in untreated segments and in SIN-1 treated segments compared to controls and SIN-1 + ODQ treated arteries (p < 0.01). Restenosis index (p < 0.01) and intimal hyperplasia (p < 0.01) were significantly reduced while the residual lumen was increased (p < 0.01) in SIN-1 segments compared to controls and ODQ + SIN-1 treated vessels.</p> <p>Conclusions</p> <p>After PTCA local delivery of high concentrations of the NO donor SIN-1 for 5 minutes inhibited injury induced neointimal hyperplasia. This favorable effect was abolished by inhibition of guanylyl cyclase indicating mediation of a cyclic guanosine 3',5'-monophosphate (cGMP)-dependent pathway. The momentary events at the time of injury play crucial role in the ensuring development of intimal hyperplasia.</p

Sugar Overconsumption during Adolescence Selectively Alters Motivation and Reward Function in Adult Rats

International audienceBACKGROUND:There has been a dramatic escalation in sugar intake in the last few decades, most strikingly observed in the adolescent population. Sugar overconsumption has been associated with several adverse health consequences, including obesity and diabetes. Very little is known, however, about the impact of sugar overconsumption on mental health in general, and on reward-related behavioral disorders in particular. This study examined in rats the effects of unlimited access to sucrose during adolescence on the motivation for natural and pharmacological rewards in adulthood.METHODOLOGY/PRINCIPAL FINDINGS:Adolescent rats had free access to 5% sucrose or water from postnatal day 30 to 46. The control group had access to water only. In adulthood, rats were tested for self-administration of saccharin (sweet), maltodextrin (non-sweet), and cocaine (a potent drug of abuse) using fixed- and progressive-ratio schedules, and a concentration-response curve for each substance. Adult rats, exposed or not exposed to sucrose, were tested for saccharin self-administration later in life to verify the specificity of adolescence for the sugar effects. Sugar overconsumption during adolescence, but not during adulthood, reduced the subsequent motivation for saccharin and maltodextrin, but not cocaine. This selective decrease in motivation is more likely due to changes in brain reward processing than changes in gustatory perception.CONCLUSIONS/SIGNIFICANCE:Sugar overconsumption induces a developmental stage-specific chronic depression in reward processing that may contribute to an increase in the vulnerability to reward-related psychiatric disorders

History Shaped the Geographic Distribution of Genomic Admixture on the Island of Puerto Rico

Contemporary genetic variation among Latin Americans human groups reflects population migrations shaped by complex historical, social and economic factors. Consequently, admixture patterns may vary by geographic regions ranging from countries to neighborhoods. We examined the geographic variation of admixture across the island of Puerto Rico and the degree to which it could be explained by historic and social events. We analyzed a census-based sample of 642 Puerto Rican individuals that were genotyped for 93 ancestry informative markers (AIMs) to estimate African, European and Native American ancestry. Socioeconomic status (SES) data and geographic location were obtained for each individual. There was significant geographic variation of ancestry across the island. In particular, African ancestry demonstrated a decreasing East to West gradient that was partially explained by historical factors linked to the colonial sugar plantation system. SES also demonstrated a parallel decreasing cline from East to West. However, at a local level, SES and African ancestry were negatively correlated. European ancestry was strongly negatively correlated with African ancestry and therefore showed patterns complementary to African ancestry. By contrast, Native American ancestry showed little variation across the island and across individuals and appears to have played little social role historically. The observed geographic distributions of SES and genetic variation relate to historical social events and mating patterns, and have substantial implications for the design of studies in the recently admixed Puerto Rican population. More generally, our results demonstrate the importance of incorporating social and geographic data with genetics when studying contemporary admixed populations

Genetic Ancestry, Social Classification, and Racial Inequalities in Blood Pressure in Southeastern Puerto Rico

The role of race in human genetics and biomedical research is among the most contested issues in science. Much debate centers on the relative importance of genetic versus sociocultural factors in explaining racial inequalities in health. However, few studies integrate genetic and sociocultural data to test competing explanations directly.We draw on ethnographic, epidemiologic, and genetic data collected in Southeastern Puerto Rico to isolate two distinct variables for which race is often used as a proxy: genetic ancestry versus social classification. We show that color, an aspect of social classification based on the culturally defined meaning of race in Puerto Rico, better predicts blood pressure than does a genetic-based estimate of continental ancestry. We also find that incorporating sociocultural variables reveals a new and significant association between a candidate gene polymorphism for hypertension (alpha(2C) adrenergic receptor deletion) and blood pressure.This study addresses the recognized need to measure both genetic and sociocultural factors in research on racial inequalities in health. Our preliminary results provide the most direct evidence to date that previously reported associations between genetic ancestry and health may be attributable to sociocultural factors related to race and racism, rather than to functional genetic differences between racially defined groups. Our results also imply that including sociocultural variables in future research may improve our ability to detect significant allele-phenotype associations. Thus, measuring sociocultural factors related to race may both empower future genetic association studies and help to clarify the biological consequences of social inequalities