133 research outputs found
Medial Hypoxia and Adventitial Vasa Vasorum Remodeling in Human Ascending Aortic Aneurysm
Human ascending aortic aneurysms characteristically exhibit cystic medial degeneration of the aortic wall encompassing elastin degeneration, proteoglycan accumulation and smooth muscle cell loss. Most studies have focused on the aortic media and there is a limited understanding of the importance of the adventitial layer in the setting of human aneurysmal disease. We recently demonstrated that the adventitial ECM contains key angiogenic factors that are downregulated in aneurysmal aortic specimens. In this study, we investigated the adventitial microvascular network (vasa vasorum) of aneurysmal aortic specimens of different etiology and hypothesized that the vasa vasorum is disrupted in patients with ascending aortic aneurysm. Morphometric analyses of hematoxylin and eosin-stained human aortic cross-sections revealed evidence of vasa vasorum remodeling in aneurysmal specimens, including reduced density of vessels, increased lumen area and thickening of smooth muscle actin-positive layers. These alterations were inconsistently observed in specimens of bicuspid aortic valve (BAV)-associated aortopathy, while vasa vasorum remodeling was typically observed in aneurysms arising in patients with the morphologically normal tricuspid aortic valve (TAV). Gene expression of hypoxia-inducible factor 1α and its downstream targets, metallothionein 1A and the pro-angiogenic factor vascular endothelial growth factor, were down-regulated in the adventitia of aneurysmal specimens when compared with non-aneurysmal specimens, while the level of the anti-angiogenic factor thrombospondin-1 was elevated. Immunodetection of glucose transporter 1 (GLUT1), a marker of chronic tissue hypoxia, was minimal in non-aneurysmal medial specimens, and locally accumulated within regions of elastin degeneration, particularly in TAV-associated aneurysms. Quantification of GLUT1 revealed elevated levels in the aortic media of TAV-associated aneurysms when compared to non-aneurysmal counterparts. We detected evidence of chronic inflammation as infiltration of lymphoplasmacytic cells in aneurysmal specimens, with a higher prevalence of lymphoplasmacytic infiltrates in aneurysmal specimens from patients with TAV compared to that of patients with BAV. These data highlight differences in vasa vasorum remodeling and associated medial chronic hypoxia markers between aneurysms of different etiology. These aberrations could contribute to malnourishment of the aortic media and could conceivably participate in the pathogenesis of thoracic aortic aneurysm
Classification and Functional Characterization of Vasa Vasorum-Associated Perivascular Progenitor Cells in Human Aorta
In the microcirculation, pericytes are believed to function as mesenchymal stromal cells (MSCs). We hypothesized that the vasa vasorum harbor progenitor cells within the adventitia of human aorta. Pericytes, endothelial progenitor cells, and other cell subpopulations were detected among freshly isolated adventitial cells using flow cytometry. Purified cultured pericytes were enriched for the MSC markers CD105 and CD73 and depleted of the endothelial markers von Willebrand factor and CD31. Cultured pericytes were capable of smooth muscle lineage progression including inducible expression of smooth muscle myosin heavy chain, calponin, and α-smooth muscle actin, and adopted a spindle shape. Pericytes formed spheroids when cultured on Matrigel substrates and peripherally localized with branching endothelial cells in vitro. Our results indicate that the vasa vasorum form a progenitor cell niche distinct from other previously described progenitor populations in human adventitia. These findings could have important implications for understanding the complex pathophysiology of human aortic disease
Coarse Particulate Organic Matter Dynamics in Ephemeral Tributaries of a Central Appalachian Stream Network
Headwater ephemeral tributaries are interfaces between uplands and downstream waters. Terrestrial coarse particulate organic matter (CPOM) is important in fueling aquatic ecosystems; however, the extent to which ephemeral tributaries are functionally connected to downstream waters through fluvial transport of CPOM has been little studied. Hydrology and deposition of leaf and wood, and surrogate transport (Ginkgo biloba leaves and wood dowels) were measured over monthâlong intervals through the winter and spring seasons (6 months) in 10 ephemeral tributaries (1.3â5.4 ha) in eastern Kentucky. Leaf deposition and surrogate transport varied over time, reflecting the seasonality of litterfall and runoff. Leaf deposition was higher in December than February and May but did not differ from January, March, and April. Mean percent of surrogate leaf transport from the ephemeral tributaries was highest in April (3.6% per day) and lowest in February (2.5%) and May (2%). Wood deposition and transport had similar patterns. No CPOM measures were related to flow frequency. Ephemeral tributaries were estimated to annually contribute 110.6 kg AFDM·kmâ1·yrâ1 of leaves to the downstream mainstem. Ephemeral tributaries are functionally connected to downstream waters through CPOM storage and subsequent release that is timed when CPOM is often limited in downstream waters
Mechanism of aortic medial matrix remodeling is distinct in patients with bicuspid aortic valve
ObjectivesPatients with bicuspid aortic valves (BAV) are predisposed to developing ascending thoracic aortic aneurysms (TAA) at an earlier age than patients who develop degenerative TAAs and have a tricuspid aortic valve (TAV). The hypothesis tested is that BAV-associated aortopathy is mediated by a mechanism of matrix remodeling that is distinct from that seen in TAAs of patients with tricuspid aortic valves.MethodsAortic specimens were collected during ascending aortic replacement, aortic valve replacement, and heart transplants from nonaneurysmal (NA) donors and recipients. Matrix architecture of the aortic media was assessed qualitatively using multiphoton microscopy followed by quantification of collagen and elastin fiber orientation. α-Elastin was determined and matrix maturity was assessed by quantifying immature and mature collagen and lysyl oxidase (Lox) expression and activity in aortic specimens. Matrix metalloproteinase-2/9 activity was quantified in aortic smooth muscle cells.ResultsElastin and collagen fibers were more highly aligned in BAV-NA and BAV-TAA cases than in TAV-TAA cases, whereas TAV-TAA cases were more disorganized than TAV-NA cases. α-Elastin content was unchanged. Immature collagen was reduced in BAV-NA and BAV-TAA cases when compared with TAV-NA and TAV-TAA cases. Mature collagen was elevated in TAV-TAA cases compared with TAV-NA and BAV-TAA cases. There was a trend toward elevated Lox gene expression and activity and matrix metalloproteinase-2/9 activity for TAV-TAA, BAV-NA, and BAV-TAA specimens.ConclusionsThe highly aligned matrix architecture in patients with BAVs indicates that wall remodeling is distinct from TAV-TAA. Altered matrix architecture and reduced collagen maturity suggest that the effector molecules mediating the remodeling of TAAs are different in BAV and TAV cases
Complex Calculations: How Drug Use During Pregnancy Becomes a Barrier to Prenatal Care
Pregnant women who use drugs are more likely to receive little or no prenatal care. This study sought to understand how drug use and factors associated with drug use influence womenâs prenatal care use. A total of 20 semi-structured interviews and 2 focus groups were conducted with a racially/ethnically diverse sample of low-income women using alcohol and drugs in a California county. Women using drugs attend and avoid prenatal care for reasons not connected to their drug use: concern for the health of their baby, social support, and extrinsic barriers such as health insurance and transportation. Drug use itself is a barrier for a few women. In addition to drug use, women experience multiple simultaneous risk factors. Both the drug use and the multiple simultaneous risk factors make resolving extrinsic barriers more difficult. Women also fear the effects of drug use on their babyâs health and fear being reported to Child Protective Services, each of which influence womenâs prenatal care use. Increasing the number of pregnant women who use drugs who receive prenatal care requires systems-level rather than only individual-level changes. These changes require a paradigm shift to viewing drug use in context of the person and society and acceptance of responsibility for unintended consequences of public health bureaucratic procedures and messages about effects of drug use during pregnancy
Secondary structure of rhBMP-2 in a protective biopolymeric carrier material
Efficient delivery of growth factors is one of the great challenges of tissue engineering. Polyelectrolyte multilayer films (PEM) made of biopolymers have recently emerged as an interesting carrier for delivering recombinant human bone morphogenetic protein 2 (rhBMP-2 noted here BMP-2) to cells in a matrix-bound manner. We recently showed that PEM made of poly(l-lysine) and hyaluronan (PLL/HA) can retain high and tunable quantities of BMP-2 and can deliver it to cells to induce their differentiation in osteoblasts. Here, we investigate quantitatively by Fourier transform infrared spectroscopy (FTIR) the secondary structure of BMP-2 in solution as well as trapped in a biopolymeric thin film. We reveal that the major structural elements of BMP-2 in solution are intramolecular ÎČ-sheets and unordered structures as well as α-helices. Furthermore, we studied the secondary structure of rhBMP-2 trapped in hydrated films and in dry films since drying is an important step for future applications of these bioactive films onto orthopedic biomaterials. We demonstrate that the structural elements were preserved when BMP-2 was trapped in the biopolymeric film in hydrated conditions and, to a lesser extent, in dry state. Importantly, its bioactivity was maintained after drying of the film. Our results appear highly promising for future applications of these films as coatings of biomedical materials, to deliver bioactive proteins while preserving their bioactivity upon storage in dry state.This work was supported by the French Ministry of Research through an ANR-EmergenceBIO grant (ANR-09-EBIO-012-01), by the European Commission (FP7 program) via a European Research Council starting grant (BIOMIM, GA 259370), and by GRAVIT (081012_FIBIOS). C.P. is grafetul to IUF for financial support
Complement C3 Deficiency Attenuates Chronic Hypoxia-Induced Pulmonary Hypertension in Mice
Background: Evidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension. Methodology/Principal Findings: Immunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3-/- hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3-/- mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3-/- mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3-/- mice. Conclusions: Herein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans. © 2011 Bauer et al
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1ÎČ, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1ÎČ innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.
Six-Coordinate Nitrito and Nitrato Complexes of Manganese Porphyrin
Reaction of small increments of NO2 gas with sublimed amorphous layers of Mn(II)(TPP) (TPP = meso-tetra-phenylporphyrinato dianion) in a vacuum cryostat leads to formation of the 5-coordinate monodentate nitrato complex Mn(III)(TPP)(η(1)-ONO2) (II). This transformation proceeds through the two distinct steps with initial formation of the five coordinate O-nitrito complex Mn(III)(TPP)(η(1)-ONO) (I) as demonstrated by the electronic absorption spectra and by FTIR spectra using differently labeled nitrogen dioxide. A plausible mechanism for the second stage of reaction is offered based on the spectral changes observed upon subsequent interaction of (15)NO2 and NO2 with the layered Mn(TPP). Low-temperature interaction of I and II with the vapors of various ligands L (L = O-, S-, and N-donors) leads to formation of the 6-coordinate O-nitrito Mn(III)(TPP)(L)(η(1)-ONO) and monodentate nitrato Mn(III)(TPP)(L)(η(1)-ONO2) complexes, respectively. Formation of the 6-coordinate O-nitrito complex is accompanied by the shifts of the Îœ(NâO) band to lower frequency and of the Îœ(N-O) band to higher frequency. The frequency difference between these bands ÎÎœ = Îœ(NâO) - Îœ(N-O) is a function of L and is smaller for the stronger bases. Reaction of excess NH3 with I leads to formation of Mn(TPP)(NH3)(η(1)-ONO) and of the cation [Mn(TPP)(NH3)2](+) plus ionic nitrite. The nitrito complexes are relatively unstable, but several of the nitrato species can be observed in the solid state at room temperature. For example, the tetrahydrofuran complex Mn(TPP)(THF)(η(1)-ONO2) is stable in the presence of THF vapors (âŒ5 mm), but it loses this ligand upon high vacuum pumping at RT. When L = dimethylsulfide (DMS), the nitrato complex is stable only to âŒ-30 °C. Reactions of II with the N-donor ligands NH3, pyridine, or 1-methylimidazole are more complex. With these ligands, the nitrato complexes Mn(III)(TPP)(L)(η(1)-ONO2) and the cationic complexes [Mn(TPP)(L)2](+) coexist in the layer at room temperature, the latter formed as a result of NO3(-) displacement when L is in excess
Selected abstracts from the Breastfeeding and Feminism International Conference 2016
Table of contents A1. Infant feeding and poverty: a public health perspective in a global context Lisa H. Amir A2. Mothersâ experiences with galactagogues for lactation: an exploratory cross sectional study Alessandra Bazzano, Shelley Thibeau, Katherine P. Theall A3. The motherhood journey and breastfeeding: from self-efficacy to resilience and social stigma Anna Blair, Karin Cadwell A4. Breastfeeding as an evolutionary adaptive behavior Emily A. Bronson A5. Conflict-of-interest in public health policy: as real as that logo on your website Elizabeth C. Brooks A6. Co-opting sisterhood and motherhood: behind the scenes of Similacâs aggressive social media campaigns Jodine Chase A7. The exclusion of women from the definition of exclusive breastfeeding Ellen Chetwynd, Rebecca Costello, Kathryn Wouk A8. Healthy maternity policies in the workplace: a state health departmentâs experience with the âBring Your Infant to Workâ program Lindsey Dermid-Gray A9. Implications for a paradigm shift: factors related to breastfeeding among African American women Stephanie Devane-Johnson, Cheryl Woods Giscombe, Miriam Labbok A10. Social experiences of breastfeeding: building bridges between research and policy: an ESRC-funded seminar series in the UK Sally Dowling A11. Managerâs perspectives of lactation breaks Melanie Fraser A12. The challenging second night: a dialogue from two perspectives Jane Grassley, Deborah McCarter-Spaulding, Becky Spencer A13. The role of lactation consultants in two council breastfeeding services in Melbourne, Australia â some preliminary impressions Jennifer Hocking, Pranee Liamputtong A14. Integrating social marketing and community engagement concepts in community breastfeeding programs Sheree H. Keitt, Harumi Reis-Reilly A15. What happens before and after the maternity stay? Creating a community-wide Ten Steps approach Miriam Labbok A16. #RVABREASTFEEDS: cultivating a breastfeeding-friendly community Leslie Lytle A17. Public health vs. free trade: a longitudinal analysis of a global policy to protect breastfeeding Mary Ann Merz A18. Legislative advocacy and grassroots organizing for improved breastfeeding laws in Virginia Kate Noon A19. Breastfeeding and the rights of incarcerated women Krista M Olson A20. Barriers and support for Puerto Rican breastfeeding working mothers Ana M. Parrilla-RodrĂguez, JosĂ© J. GorrĂn-Peralta Melissa Pellicier, Zeleida M. VĂĄzquez-Rivera A21. Pumping at work: a daily struggle for Puerto Rican breastfeeding mothers in spite of the law Melissa Pellicier A22. âI saw a wrong and I wanted to stand up for what I thought was right:â a narrative study on becoming a breastfeeding activist Jennifer L. Pemberton A23. Peer breastfeeding support: advocacy and action Catherine McEvilly Pestl A24. Good intentions: a study of breastfeeding intention and postpartum realities among first-time Central Brooklyn mothers Jennifer Pierre, Philip Noyes, Khushbu Srivastava, Sharon Marshall-Taylor A25. Women describing the infant feeding choice: the impact of the WIC breastfeeding classes on infant feeding practices in Ionia, Michigan Jennifer Proto, Sarah Hyland Laurie Brinks A26. Local and state programs and national partnership to reduce disparities through community breastfeeding support Harumi Reis-Reilly, Martelle Esposito, Megan Phillippi A27. Beyond black breastfeeding week: instagram image content analysis for #blackwomendobreastfeed/#bwdbf Cynthia L. Sears, Delores James, Cedric Harville, Kristina Carswell A28. Stakeholder views of breastfeeding education in the K-12 environment: a review of the literature Nicola Singletary, L. Suzanne Goodell, April Fogleman A29. âThe Breastfeeding Transitionâ: a framework for explaining changes in global breastfeeding rates as related to large-scale forces shaping the status of women Paige Hall Smith A30. Breastfeeding, contraception, and ethics, oh my! Advocacy and informed decision-making in the post-partum period Alison M. Stuebe, Amy G. Bryant, Anne Drapkin Lyerly A31. A hard dayâs night: juggling nighttime breastfeeding, sleep, and work Cecilia Tomori A32. Empowering change in Indian country through breastfeeding education Amanda L. Watkins, Joan E. Dodgson A33. Servants and âLittle Mothersâ take charge: work, class, and breastfeeding rates in the early 20th-century U.S. Jacqueline H. Wol
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