Sample records for valve interstitial cell
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Duan, B; Kapetanovic, E; Hockaday, L A; Butcher, J T
2014-05-01
Tissue engineering has great potential to provide a functional de novo living valve replacement, capable of integration with host tissue and growth. Among various valve conduit fabrication techniques, three-dimensional (3-D) bioprinting enables deposition of cells and hydrogels into 3-D constructs with anatomical geometry and heterogeneous mechanical properties. Successful translation of this approach, however, is constrained by the dearth of printable and biocompatible hydrogel materials. Furthermore, it is not known how human valve cells respond to these printed environments. In this study, 3-D printable formulations of hybrid hydrogels are developed, based on methacrylated hyaluronic acid (Me-HA) and methacrylated gelatin (Me-Gel), and used to bioprint heart valve conduits containing encapsulated human aortic valvular interstitial cells (HAVIC). Increasing Me-Gel concentration resulted in lower stiffness and higher viscosity, facilitated cell spreading, and better maintained HAVIC fibroblastic phenotype. Bioprinting accuracy was dependent upon the relative concentrations of Me-Gel and Me-HA, but when optimized enabled the fabrication of a trileaflet valve shape accurate to the original design. HAVIC encapsulated within bioprinted heart valves maintained high viability, and remodeled the initial matrix by depositing collagen and glyosaminoglycans. These findings represent the first rational design of bioprinted trileaflet valve hydrogels that regulate encapsulated human VIC behavior. The use of anatomically accurate living valve scaffolds through bioprinting may accelerate understanding of physiological valve cell interactions and progress towards de novo living valve replacements. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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Osman, Narin; Grande-Allen, K Jane; Ballinger, Mandy L; Getachew, Robel; Marasco, Silvana; O'Brien, Kevin D; Little, Peter J
2013-01-01
Calcific aortic valve disease is a progressive condition that shares some common pathogenic features with atherosclerosis. Transforming growth factor-β1 is a recognized mediator of atherosclerosis and is expressed in aortic valve lesions. Transforming growth factorβ1 stimulates glycosaminoglycan elongation of proteoglycans that is associated with increased lipid binding. We investigated the presence of transforming growth factor-β1 and downstream signaling intermediates in diseased human aortic valves and the effects of activated transforming growth factor-β1 receptor signaling on aortic valve interstitial cell proteoglycan synthesis and lipid binding as a possible mechanism for the initiation of the early lesion of calcific aortic valve disease. Diseased human aortic valve leaflets demonstrated strong immunohistochemical staining for transforming growth factor-β1 and phosphorylated Smad2/3. In primary porcine aortic valve interstitial cells, Western blots showed that transforming growth factor-β1 stimulated phosphorylation in both the carboxy and linker regions of Smad2/3, which was inhibited by the transforming growth factor-β1 receptor inhibitor SB431542. Gel electrophoresis and size exclusion chromatography demonstrated that SB431542 decreased transforming growth factor-β1-mediated [(35)S]-sulfate incorporation into proteoglycans in a dose-dependent manner. Further, in proteoglycans derived from transforming growth factor-β1-treated valve interstitial cells, gel mobility shift assays demonstrated that inhibition of transforming growth factor-β1 receptor signaling resulted in decreased lipid binding. Classic transforming growth factor-β1 signaling is present in human aortic valves in vivo and contributes to the modification of proteoglycans expressed by valve interstitial cells in vitro. These findings suggest that transforming growth factor-β1 may promote increased low-density lipoprotein binding in the early phases of calcific aortic valve disease
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[Effect of rapamycin on proliferation of rat heart valve interstitial cells in vitro].
Tan, Yan; Wang, Ji-Ye; Yi, Ren-Liang; Qiu, Jian
2016-04-01
To investigate the effect of rapamycin on the proliferation of rat valvular interstitial cells in primary culture. The interstitial cells isolated from rat aortic valves were cultured and treated with rapamycin, and the cell growth and cell cycle changes were analyzed using MTT assay and flow cytometry, respectively. RT-PCR was used to detect mRNA expression levels of S6 and P70S6K in cells, and the protein expressions level of S6, P70S6K, P-S6, and P-P70S6K were detected using Western blotting. Rat aortic valvular interstitial cells was isolated successfully. The rapamycin-treated cells showed a suppressed proliferative activity (P<0.05), but the cell cycle distribution remained unaffected. Rapamycin treatment resulted in significantly decreased S6 and P70S6K protein phosphorylation level in the cells (P<0.05). The mechanism by which rapamycin inhibits the proliferation of valvular interstitial cells probably involves suppression of mTOR to lower S6 and P70S6K phosphorylation level but not direct regulation of the cell cycle.
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Santoro, Rosaria; Consolo, Filippo; Spiccia, Marco; Piola, Marco; Kassem, Samer; Prandi, Francesca; Vinci, Maria Cristina; Forti, Elisa; Polvani, Gianluca; Fiore, Gianfranco Beniamino; Soncini, Monica; Pesce, Maurizio
2016-02-01
Glutaraldehyde-fixed pericardium of animal origin is the elective material for the fabrication of bio-prosthetic valves for surgical replacement of insufficient/stenotic cardiac valves. However, the pericardial tissue employed to this aim undergoes severe calcification due to chronic inflammation resulting from a non-complete immunological compatibility of the animal-derived pericardial tissue resulting from failure to remove animal-derived xeno-antigens. In the mid/long-term, this leads to structural deterioration, mechanical failure, and prosthesis leaflets rupture, with consequent need for re-intervention. In the search for novel procedures to maximize biological compatibility of the pericardial tissue into immunocompetent background, we have recently devised a procedure to decellularize the human pericardium as an alternative to fixation with aldehydes. In the present contribution, we used this procedure to derive sheets of decellularized pig pericardium. The decellularized tissue was first tested for the presence of 1,3 α-galactose (αGal), one of the main xenoantigens involved in prosthetic valve rejection, as well as for mechanical tensile behavior and distensibility, and finally seeded with pig- and human-derived aortic valve interstitial cells. We demonstrate that the decellularization procedure removed the αGAL antigen, maintained the mechanical characteristics of the native pig pericardium, and ensured an efficient surface colonization of the tissue by animal- and human-derived aortic valve interstitial cells. This establishes, for the first time, the feasibility of fixative-free pericardial tissue seeding with valve competent cells for derivation of tissue engineered heart valve leaflets. © 2015 Wiley Periodicals, Inc.
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Duan, Bin; Yin, Ziying; Hockaday Kang, Laura; Magin, Richard L; Butcher, Jonathan T
2016-05-01
Calcific aortic valve disease (CAVD) progression is a highly dynamic process whereby normally fibroblastic valve interstitial cells (VIC) undergo osteogenic differentiation, maladaptive extracellular matrix (ECM) composition, structural remodeling, and tissue matrix stiffening. However, how VIC with different phenotypes dynamically affect matrix properties and how the altered matrix further affects VIC phenotypes in response to physiological and pathological conditions have not yet been determined. In this study, we develop 3D hydrogels with tunable matrix stiffness to investigate the dynamic interplay between VIC phenotypes and matrix biomechanics. We find that VIC populated within hydrogels with valve leaflet like stiffness differentiate towards myofibroblasts in osteogenic media, but surprisingly undergo osteogenic differentiation when cultured within lower initial stiffness hydrogels. VIC differentiation progressively stiffens the hydrogel microenvironment, which further upregulates both early and late osteogenic markers. These findings identify a dynamic positive feedback loop that governs acceleration of VIC calcification. Temporal stiffening of pathologically lower stiffness matrix back to normal level, or blocking the mechanosensitive RhoA/ROCK signaling pathway, delays the osteogenic differentiation process. Therefore, direct ECM biomechanical modulation can affect VIC phenotypes towards and against osteogenic differentiation in 3D culture. These findings highlight the importance of the homeostatic maintenance of matrix stiffness to restrict pathological VIC differentiation. We implement 3D hydrogels with tunable matrix stiffness to investigate the dynamic interaction between valve interstitial cells (VIC, major cell population in heart valve) and matrix biomechanics. This work focuses on how human VIC responses to changing 3D culture environments. Our findings identify a dynamic positive feedback loop that governs acceleration of VIC calcification, which
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The Effects of Combined Cyclic Stretch and Pressure on the Aortic Valve Interstitial Cell Phenotype
Thayer, Patrick; Balachandran, Kartik; Rathan, Swetha; Yap, Choon Hwai; Arjunon, Sivakkumar; Jo, Hanjoong; Yoganathan, Ajit P.
2017-01-01
Aortic valve interstitial cells (VIC) can exhibit phenotypic characteristics of fibroblasts, myofibroblasts, and smooth muscle cells. Others have proposed that valve cells become activated and exhibit myofibroblast or fibroblast characteristics during disease initiation and progression; however, the cues that modulate this phenotypic change remain unclear. We hypothesize that the mechanical forces experienced by the valve play a role in regulating the native phenotype of the valve and that altered mechanical forces result in an activated phenotype. Using a novel ex vivo cyclic stretch and pressure bioreactor, we subjected porcine aortic valve (AV) leaflets to combinations of normal and pathological stretch and pressure magnitudes. The myofibroblast markers α-SMA and Vimentin, along with the smooth muscle markers Calponin and Caldesmon, were analyzed using immunohistochemistry and immunoblotting. Tissue structure was analyzed using Movat’s pentachrome staining. We report that pathological stretch and pressure inhibited the contractile and possibly myofibroblast phenotypes as indicated by downregulation of the proteins α-SMA, Vimentin, and Calponin. In particular, Calponin downregulation implies depolymerization of actin filaments and possible conversion to a more synthetic (non-contractile) phenotype. This agreed well with the increase in spongiosa and fibrosa thickness observed under elevated pressure and stretch that are typically indicative of increased matrix synthesis. Our study therefore demonstrates how cyclic stretch and pressure may possibly act together to modulate the AVIC phenotype. PMID:21347552
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Zeng, Qingchun; Song, Rui; Fullerton, David A; Ao, Lihua; Zhai, Yufeng; Li, Suzhao; Ballak, Dov B; Cleveland, Joseph C; Reece, T Brett; McKinsey, Timothy A; Xu, Dingli; Dinarello, Charles A; Meng, Xianzhong
2017-02-14
Calcific aortic valve disease is a chronic inflammatory process, and aortic valve interstitial cells (AVICs) from diseased aortic valves express greater levels of osteogenic factors in response to proinflammatory stimulation. Here, we report that lower cellular levels of IL-37 in AVICs of diseased human aortic valves likely account for augmented expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphatase (ALP) following stimulation of Toll-like receptor (TLR) 2 or 4. Treatment of diseased AVICs with recombinant human IL-37 suppresses the levels of BMP-2 and ALP as well as calcium deposit formation. In mice, aortic valve thickening is observed when exposed to a TLR4 agonist or a high fat diet for a prolonged period; however, mice expressing human IL-37 exhibit significantly lower BMP-2 levels and less aortic valve thickening when subjected to the same regimens. A high fat diet in mice results in oxidized low-density lipoprotein (oxLDL) deposition in aortic valve leaflets. Moreover, the osteogenic responses in human AVICs induced by oxLDL are suppressed by recombinant IL-37. Mechanistically, reduced osteogenic responses to oxLDL in human AVICs are associated with the ability of IL-37 to inhibit NF-κB and ERK1/2. These findings suggest that augmented expression of osteogenic factors in AVICs of diseased aortic valves from humans is at least partly due to a relative IL-37 deficiency. Because recombinant IL-37 suppresses the osteogenic responses in human AVICs and alleviates aortic valve lesions in mice exposed to high fat diet or a proinflammatory stimulus, IL-37 has therapeutic potential for progressive calcific aortic valve disease.
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Zeng, Qingchun; Song, Rui; Fullerton, David A.; Ao, Lihua; Zhai, Yufeng; Li, Suzhao; Ballak, Dov B.; Cleveland, Joseph C.; Reece, T. Brett; McKinsey, Timothy A.; Xu, Dingli; Dinarello, Charles A.; Meng, Xianzhong
2017-01-01
Calcific aortic valve disease is a chronic inflammatory process, and aortic valve interstitial cells (AVICs) from diseased aortic valves express greater levels of osteogenic factors in response to proinflammatory stimulation. Here, we report that lower cellular levels of IL-37 in AVICs of diseased human aortic valves likely account for augmented expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphatase (ALP) following stimulation of Toll-like receptor (TLR) 2 or 4. Treatment of diseased AVICs with recombinant human IL-37 suppresses the levels of BMP-2 and ALP as well as calcium deposit formation. In mice, aortic valve thickening is observed when exposed to a TLR4 agonist or a high fat diet for a prolonged period; however, mice expressing human IL-37 exhibit significantly lower BMP-2 levels and less aortic valve thickening when subjected to the same regimens. A high fat diet in mice results in oxidized low-density lipoprotein (oxLDL) deposition in aortic valve leaflets. Moreover, the osteogenic responses in human AVICs induced by oxLDL are suppressed by recombinant IL-37. Mechanistically, reduced osteogenic responses to oxLDL in human AVICs are associated with the ability of IL-37 to inhibit NF-κB and ERK1/2. These findings suggest that augmented expression of osteogenic factors in AVICs of diseased aortic valves from humans is at least partly due to a relative IL-37 deficiency. Because recombinant IL-37 suppresses the osteogenic responses in human AVICs and alleviates aortic valve lesions in mice exposed to high fat diet or a proinflammatory stimulus, IL-37 has therapeutic potential for progressive calcific aortic valve disease. PMID:28137840
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Yao, Qingzhou; Song, Rui; Ao, Lihua; Cleveland, Joseph C; Fullerton, David A; Meng, Xianzhong
2017-06-01
Calcific aortic valve disease (CAVD) is a leading cardiovascular disorder in the elderly. Diseased aortic valves are characterized by sclerosis (fibrosis) and nodular calcification. Sclerosis, an early pathological change, is caused by aortic valve interstitial cell (AVIC) proliferation and overproduction of extracellular matrix (ECM) proteins. However, the mechanism of aortic valve sclerosis remains unclear. Recently, we observed that diseased human aortic valves overexpress growth factor neurotrophin 3 (NT3). In the present study, we tested the hypothesis that NT3 is a profibrogenic factor to human AVICs. AVICs isolated from normal human aortic valves were cultured in M199 growth medium and treated with recombinant human NT3 (0.10 µg/ml). An exposure to NT3 induced AVIC proliferation, upregulated the production of collagen and matrix metalloproteinase (MMP), and augmented collagen deposition. These changes were abolished by inhibition of the Trk receptors. NT3 induced Akt phosphorylation and increased cyclin D1 protein levels in a Trk receptor-dependent fashion. Inhibition of Akt abrogated the effect of NT3 on cyclin D1 production. Furthermore, inhibition of either Akt or cyclin D1 suppressed NT3-induced cellular proliferation and MMP-9 and collagen production, as well as collagen deposition. Thus, NT3 upregulates cellular proliferation, ECM protein production, and collagen deposition in human AVICs. It exerts these effects through the Trk-Akt-cyclin D1 cascade. NT3 is a profibrogenic mediator in human aortic valve, and overproduction of NT3 by aortic valve tissue may contribute to the mechanism of valvular sclerosis. Copyright © 2017 the American Physiological Society.
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Latif, Najma; Quillon, Alfred; Sarathchandra, Padmini; McCormack, Ann; Lozanoski, Alec; Yacoub, Magdi H.; Chester, Adrian H.
2015-01-01
Valve interstitial cells (VICs) are fibroblastic in nature however in culture it is widely accepted that they differentiate into a myofibroblastic phenotype. This study assessed a fibroblast culture media formulation for its ability to maintain the phenotype and function of VICs as in the intact healthy valve. Normal human VICs were cultured separately in standard DMEM and in fibroblast media consisting of FGF2 (10ng/ml), insulin (50ng/ml) and 2% FCS for at least a week. Cell morphology, aspect ratio, size, levels and distribution of protein expression, proliferation, cell cycle, contraction and migration were assessed. Some VICs and some valve endothelial cells expressed FGF2 in valve tissue and this expression was increased in calcified valves. VICs in DMEM exhibited large, spread cells whereas VICs in fibroblast media were smaller, elongated and spindly. Aspect ratio and size were both significantly higher in DMEM (p<0.01). The level of expression of α-SMA was significantly reduced in fibroblast media at day 2 after isolation (p<0.01) and the expression of α-SMA, SM22 and EDA-fibronectin was significantly reduced in fibroblast media at days 7 and 12 post-isolation (p<0.01). Expression of cytoskeletal proteins, bone marker proteins and extracellular matrix proteins was reduced in fibroblast media. Proliferation of VICs in fibroblast media was significantly reduced at weeks 1 (p<0.05) and 2 (p<0.01). Collagen gel contraction was significantly reduced in fibroblast media (p<0.05). VICs were found to have significantly fewer and smaller focal adhesions in fibroblast media (p<0.01) with significantly fewer supermature focal adhesions in fibroblast media (p<0.001). Ultrastructurally, VICs in fibroblast media resembled native VICs from intact valves. VICs in fibroblast media demonstrated a slower migratory ability after wounding at 72 hours (p<0.01). Treatment of human VICs with this fibroblast media formulation has the ability to maintain and to dedifferentiate the
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Perez, Jessica; Diaz, Nancy; Tandon, Ishita; Plate, Rachel; Martindale, Christopher; Balachandran, Kartik
2018-06-01
While the valvulopathic effects of serotonin (5HT) and angiotensin-II (Ang-II) individually are known, it was not clear how 5HT and Ang-II might interact, specifically in the context of the mechanobiological responses due to altered valve mechanics potentiated by these molecules. In this context, the hypothesis of this study was that increased serotonin levels would result in accelerated progression toward disease in the presence of angiotensin-II-induced hypertension. C57/BL6 J mice were divided into four groups and subcutaneously implanted with osmotic pumps containing: PBS (control), 5HT (2.5 ng/kg/min), Ang-II (400 ng/kg/min), and 5HT + Ang-II (combination). Blood pressure was monitored using the tail cuff method. Echocardiography was performed on the mice before surgery and every week thereafter to assess ejection fraction. After three weeks, the mice were sacrificed and their hearts excised, embedded and sectioned for analysis of the aortic valves via histology and immunohistochemistry. In separate experiments, porcine valve interstitial cells (VICs) were directly stimulated with 5HT (10 -7 M), Ang-II (100 nM) or both and assayed for cellular contractility, cytoskeletal organization and collagen remodeling. After three weeks, average systolic blood pressure was significantly increased in the 5HT, Ang-II and combination groups compared to control. Echocardiographic analysis demonstrated significantly reduced ejection fraction in Ang-II and the combination groups. H&E staining demonstrated thicker leaflets in the combination groups, suggesting a more aggressive remodeling process. Picrosirius red staining and image analysis suggested that the Ang-II and combination groups had the largest proportion of thicker collagen fibers. VIC orientation, cellular contractility and collagen gene expression was highest for the 5HT + Ang-II combination treatment compared to all other groups. Overall, our results suggest that 5HT and Ang-II interact to result in
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Bonetti, Antonella; Della Mora, Alberto; Contin, Magali; Gregoraci, Giorgia; Tubaro, Franco; Marchini, Maurizio; Ortolani, Fulvia
2017-01-01
Valve dystrophic calcification is a common disorder affecting normophosphatemic subjects. Here, cultured aortic valve interstitial cells (AVICs) were treated 3 to 28 days with phosphate (Pi) concentrations spanning the normal range in humans (0.8, 1.3, and 2.0 mM) alone or supplemented with proinflammatory stimuli to assess possible priming of dystrophic-like calcification. Compared with controls, spectrophotometric analyses revealed marked increases in calcium amounts and alkaline phosphatase activity for 2.0-mM-Pi-containing cultures, with enhancing by proinflammatory mediators. Ultrastructurally, AVICs treated with low/middle Pi concentrations showed an enormous endoplasmic reticulum (ER) enclosing organelle debris, so apparently executing a survival-related atypical macroautophagocytosis, consistently with ultracytochemical demonstration of ER-associated acid phosphatase activity and decreases in autophagosomes and immunodetectable MAP1LC3. In contrast, AVICs cultured at 2.0-mM Pi underwent mineralization due to intracellular release and peripheral layering of phospholipid-rich material acting as hydroxyapatite nucleator, as revealed by Cuprolinic Blue and von Kossa ultracytochemical reactions. Lack of immunoblotted caspase-3 cleaved form indicated apoptosis absence for all cultures. In conclusion, fates of cultured AVICs were crucially driven by Pi concentration, suggesting that serum Pi levels just below the upper limit of normophosphatemia in humans may represent a critical watershed between macroautophagy-associated cell restoring and procalcific cell death. PMID:28112549
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Aortic valve cell seeding into decellularized animal pericardium by perfusion-assisted bioreactor.
Amadeo, Francesco; Boschetti, Federica; Polvani, Gianluca; Banfi, Cristina; Pesce, Maurizio; Santoro, Rosaria
2018-04-27
Animal-derived pericardium is the elective tissue employed in manufacturing heart valve prostheses. The preparation of this tissue for biological valve production consists of fixation with aldehydes, which reduces, but not eliminates, the xenoantigens and the donor cellular material. As a consequence, especially in patients below 65-70 years of age, the employment of valve substitutes contaning pericardium is not indicated due to progressive calcification that causes tissue degeneration and recurrence of valve insufficiency. Decellularization with ionic or nonionic detergents has been proposed as an alternative procedure to prepare aldehyde- or xenoantigen-free pericardium for biological valve manufacturing. In the present contribution, we optimized a decellularization procedure that is permissive for seeding and culturing valve competent cells able to colonize and reconstitute a valve-like tissue. A high-efficiency cellularization was achieved by forcing cell penetration inside the pericardium matrix using a perfusion bioreactor. Because the decellularization procedure was found not to alter the collagen composition of the pericardial matrix and cells seeded in the tissue constructs consistently grew and acquired the phenotype of "quiescent" valve interstitial cells, our investigation sets a novel standard in pericardium application for tissue engineering of "living" valve implants. Copyright © 2018 John Wiley & Sons, Ltd.
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Gao, Li; Ji, Yue; Lu, Yan; Qiu, Ming; Shen, Yejiao; Wang, Yaqing; Kong, Xiangqing; Shao, Yongfeng; Sheng, Yanhui; Sun, Wei
2018-03-09
The most frequently used oral anti-coagulant warfarin has been implicated in inducing calcification of aortic valve interstitial cells (AVICs), whereas the mechanism is not fully understood. The low-level activation of p53 is found to be involved in osteogenic transdifferentiation and calcification of AVICs. Whether p53 participates in warfarin-induced AVIC calcification remains unknown. In this study, we investigated the role of low-level p53 overexpression in warfarin-induced porcine AVIC (pAVIC) calcification. Immunostaining, quantitative PCR, and Western blotting revealed that p53 was expressed in human and pAVICs and that p53 expression was slightly increased in calcific human aortic valves compared with non-calcific valves. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining indicated that apoptosis slightly increased in calcific aortic valves than in non-calcific valves. Warfarin treatment led to a low-level increase of p53 mRNA and protein in both pAVICs and mouse aortic valves. Low-level overexpression of p53 in pAVICs via an adenovirus vector did not affect pAVIC apoptosis but promoted warfarin-induced calcium deposition and expression of osteogenic markers. shRNA-mediated p53 knockdown attenuated the pAVIC calcium deposition and osteogenic marker expression. Moreover, ChIP and luciferase assays showed that p53 was recruited to the slug promoter and activated slug expression in calcific pAVICs. Of note, overexpression of Slug increased osteogenic marker Runx2 expression, but not pAVIC calcium deposition, and Slug knockdown attenuated pAVIC calcification and p53-mediated pAVIC calcium deposition and expression of osteogenic markers. In conclusion, we found that p53 plays an important role in warfarin induced pAVIC calcification, and increased slug transcription by p53 is required for p53-mediated pAVIC calcification. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
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Endothelial Progenitor Cells as a Sole Source for Ex Vivo Seeding of Tissue-Engineered Heart Valves
Mettler, Bret A.; Engelmayr, George C.; Aikawa, Elena; Bischoff, Joyce; Martin, David P.; Exarhopoulos, Alexis; Moses, Marsha A.; Schoen, Frederick J.; Sacks, Michael S.
2010-01-01
Purposes: We investigated whether circulating endothelial progenitor cells (EPCs) can be used as a cell source for the creation of a tissue-engineered heart valve (TEHV). Methods: Trileaflet valved conduits were fabricated using nonwoven polyglycolic acid/poly-4-hydroxybutyrate polymer. Ovine peripheral blood EPCs were dynamically seeded onto a valved conduit and incubated for 7, 14, and 21 days. Results: Before seeding, EPCs were shown to express CD31+, eNOS+, and VE-Cadherin+ but not α-smooth muscle actin. Histological analysis demonstrated relatively homogenous cellular ingrowth throughout the valved conduit. TEHV constructs revealed the presence of endothelial cell (EC) markers and α-smooth muscle actin+ cells comparable with native valves. Protein levels were comparable with native valves and exceeded those in unseeded controls. EPC-TEHV demonstrated a temporal pattern of matrix metalloproteinases-2/9 expression and tissue inhibitors of metalloproteinase activities comparable to that of native valves. Mechanical properties of EPC-TEHV demonstrated significantly greater stiffness than that of the unseeded scaffolds and native valves. Conclusions: Circulating EPC appears to have the potential to provide both interstitial and endothelial functions and could potentially serve as a single-cell source for construction of autologous heart valves. PMID:19698056
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Jahnavi, S; Saravanan, U; Arthi, N; Bhuvaneshwar, G S; Kumary, T V; Rajan, S; Verma, R S
2017-04-01
Major challenge in heart valve tissue engineering for paediatric patients is the development of an autologous valve with regenerative capacity. Hybrid tissue engineering approach is recently gaining popularity to design scaffolds with desired biological and mechanical properties that can remodel post implantation. In this study, we fabricated aligned nanofibrous Bio-Hybrid scaffold made of decellularized bovine pericardium: polycaprolactone-chitosan with optimized polymer thickness to yield the desired biological and mechanical properties. CD44 + , αSMA + , Vimentin + and CD105 - human valve interstitial cells were isolated and seeded on these Bio-Hybrid scaffolds. Subsequent biological evaluation revealed interstitial cell proliferation with dense extra cellular matrix deposition that indicated the viability for growth and proliferation of seeded cells on the scaffolds. Uniaxial mechanical tests along axial direction showed that the Bio-Hybrid scaffolds has at least 20 times the strength of the native valves and its stiffness is nearly 3 times more than that of native valves. Biaxial and uniaxial mechanical studies on valve interstitial cells cultured Bio-Hybrid scaffolds revealed that the response along the axial and circumferential direction was different, similar to native valves. Overall, our findings suggest that Bio-Hybrid scaffold is a promising material for future development of regenerative heart valve constructs in children. Copyright © 2016 Elsevier B.V. All rights reserved.
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Amyloid substance within stenotic aortic valves promotes mineralization.
Audet, Audrey; Côté, Nancy; Couture, Christian; Bossé, Yohan; Després, Jean-Pierre; Pibarot, Philippe; Mathieu, Patrick
2012-10-01
Accumulation of apolipoproteins may play an important role in the pathobiology of calcific aortic valve disease (CAVD). We aimed to explore the hypothesis that apolipoprotein-derived amyloid could play a role in the development of CAVD. In 70 explanted CAVD valves and 15 control non-calcified aortic valves, we assessed the presence of amyloid by using Congo red staining. Immunohistochemistry was performed to document the presence of apolipoprotein AI (Apo-AI). Apoptosis was documented by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) studies performed in control and CAVD valves. Control valves were free of amyloid. Deposition of amyloid was detected in all CAVD valves, and the amount was positively correlated with plasma high-density lipoprotein and Apo-AI levels. Apo-AI within CAVD valves co-localized with intense staining of fibrillar amyloid. In turn, deposition of amyloid co-localized with apoptosis near mineralized areas. Isolation of amyloid fibrils confirmed that Apo-AI is a major component of amyloid deposits in CAVD. In vitro, CAVD-derived amyloid extracts increased apoptosis and mineralization of isolated aortic valvular interstitial cells. Apo-AI is a major component of amyloid substance present within CAVD valves. Furthermore, amyloid deposits participate in mineralization in CAVD by promoting apoptosis of valvular interstitial cells. © 2012 Blackwell Publishing Ltd.
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Assessment of Parylene C Thin Films for Heart Valve Tissue Engineering
Marei, Isra; Chester, Adrian; Carubelli, Ivan; Prodromakis, Themistoklis; Trantidou, Tatiana
2015-01-01
Background: Scaffolds are a key component of tissue-engineered heart valves (TEHVs). Several approaches had been adopted in the design of scaffolds using both natural and synthetic resources. We have investigated the suitability of parylene C (PC), a vapor deposited polymeric material, for the use as a scaffold in TEHV. Aims: To evaluate the adsorption of extracellular matrix components onto plasma-activated PC and study the biocompatibility of PC by measuring cellular adhesion, viability, apoptosis, and phenotypic expression of valve endothelial and interstitial cells. Finally, the mechanical properties of PC were compared with those of native aortic valve cusp tissue. Methods: PC slides were plasma activated and then coated with gelatin, type I collagen, or fibronectin. Porcine pulmonary valve endothelial and interstitial cells were then grown on plasma oxidized PC with different types of coatings and their adhesion was observed after 20 h of incubation. Cell viability was tested using the MTS assay, and apoptosis was estimated using TUNEL staining. The mechanical properties of PC and valve tissue were measured using a Bose Mechanical Tester. Finally, cell-seeded PC films were exposed to pulsatile pressure and aortic shear stress, respectively, to test their durability in a dynamic environment. Results: Our findings show that collagen and fibronectin could bind to plasma oxidized PC. Both valve endothelial and interstitial cells adhered to protein-coated ECM. PC had a profile of mechanical stiffness and ultimate tensile strength that were comparable with or in excess of those seen in porcine aortic valve cusps. Cells were still attached to PC films after 3 days of exposure to up to 50 mmHg pulsatile pressure or aortic levels of shear stress. Conclusion: PC is a promising candidate for use as a scaffold in tissue engineering heart valves. Additional studies are required to determine both the durability and long-term performance of cell-seeded PC when in a
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Cushing, Melinda C.; Mariner, Peter D.; Liao, Jo-Tsu; Sims, Evan A.; Anseth, Kristi S.
2008-01-01
This study aimed to identify signaling pathways that oppose connective tissue fibrosis in the aortic valve. Using valvular interstitial cells (VICs) isolated from porcine aortic valve leaflets, we show that basic fibroblast growth factor (FGF-2) effectively blocks transforming growth factor-β1 (TGF-β1)-mediated myofibroblast activation. FGF-2 prevents the induction of α-smooth muscle actin (αSMA) expression and the exit of VICs from the cell cycle, both of which are hallmarks of myofibroblast activation. By blocking the activity of the Smad transcription factors that serve as the downstream nuclear effectors of TGF-β1, FGF-2 treatment inhibits fibrosis in VICs. Using an exogenous Smad-responsive transcriptional promoter reporter, we show that Smad activity is repressed by FGF-2, likely an effect of the fact that FGF-2 treatment prevents the nuclear localization of Smads in these cells. This appears to be a direct effect of FGF signaling through mitogen-activated protein kinase (MAPK) cascades as the treatment of VICs with the MAPK/extracellular regulated kinase (MEK) inhibitor U0126 acted to induce fibrosis and blocked the ability of FGF-2 to inhibit TGF-β1 signaling. Furthermore, FGF-2 treatment of VICs blocks the development of pathological contractile and calcifying phenotypes, suggesting that these pathways may be utilized in the engineering of effective treatments for valvular disease.—Cushing, M. C., Mariner, P. D., Liao, J. T., Sims, E. A., Anseth, K. S. Fibroblast growth factor represses Smad-mediated myofibroblast activation in aortic valvular interstitial cells. PMID:18218921
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Davari, Seyyed Ali; Masjedi, Shirin; Ferdous, Zannatul; Mukherjee, Dibyendu
2018-01-01
Calcific aortic valve disease (CAVD) is a major cardiovascular disorder caused by osteogenic differentiation of valvular interstitial cells (VICs) within aortic valves. Conventional methods like colorimetric assays and histology fail to detect small calcium depositions during in-vitro VIC cultures. Laser-induced breakdown spectroscopy (LIBS) is a robust analytical tool used for inorganic materials characterizations, but relatively new to biomedical applications. We employ LIBS, for the first time, for quantitative in-vitro detection of calcium depositions in VICs at various osteogenic differentiation stages. VICs isolated from porcine aortic valves were cultured in osteogenic media over various days. Colorimetric calcium assays based on arsenazo dye and Von Kossa staining measured the calcium depositions within VICs. Simultaneously, LIBS signatures for Ca I (422.67 nm) atomic emission lines were collected for estimating calcium depositions in lyophilized VIC samples. Our results indicate excellent linear correlation between the calcium assay and our LIBS measurements. Furthermore, unlike the assay results, the LIBS results could resolve calcium signals from cell samples with as early as 2 days of osteogenic culture. Quantitatively, the LIBS measurements establish the limit of detection for calcium content in VICs to be ∼0.17±0.04 μg which indicates a 5-fold improvement over calcium assay. Picture: Quantitative LIBS enables in-vitro analysis for early stage detection of calcium deposition within aortic valvular interstitial cells (VICs). © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Interstitial Cells: Regulators of Smooth Muscle Function
Sanders, Kenton M.; Ward, Sean M.; Koh, Sang Don
2014-01-01
Smooth muscles are complex tissues containing a variety of cells in addition to muscle cells. Interstitial cells of mesenchymal origin interact with and form electrical connectivity with smooth muscle cells in many organs, and these cells provide important regulatory functions. For example, in the gastrointestinal tract, interstitial cells of Cajal (ICC) and PDGFRα+ cells have been described, in detail, and represent distinct classes of cells with unique ultrastructure, molecular phenotypes, and functions. Smooth muscle cells are electrically coupled to ICC and PDGFRα+ cells, forming an integrated unit called the SIP syncytium. SIP cells express a variety of receptors and ion channels, and conductance changes in any type of SIP cell affect the excitability and responses of the syncytium. SIP cells are known to provide pacemaker activity, propagation pathways for slow waves, transduction of inputs from motor neurons, and mechanosensitivity. Loss of interstitial cells has been associated with motor disorders of the gut. Interstitial cells are also found in a variety of other smooth muscles; however, in most cases, the physiological and pathophysiological roles for these cells have not been clearly defined. This review describes structural, functional, and molecular features of interstitial cells and discusses their contributions in determining the behaviors of smooth muscle tissues. PMID:24987007
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Feng, Xiang; Li, Jian-ming; Liao, Xiao-bo; Hu, Ye-rong; Shang, Bao-peng; Zhang, Zhi-yuan; Yuan, Ling-qing; Xie, Hui; Sheng, Zhi-feng; Tang, Hao; Zhang, Wei; Gu, Lu; Zhou, Xin-min
2012-10-01
Aortic valve calcification (AVC) is an active process characterized by osteoblastic differentiation of the aortic valve interstitial cells (AVICs). Taurine is a free β-amino acid and plays important physiological roles including protective effect of cardiovascular events. To evaluate the possible role of taurine in AVC, we isolated human AVICs from patients with type A dissection without leaflet disease. We demonstrated that the cultured AVICs express SM α-actin, vimentin and taurine transporter (TAUT), but not CD31, SM-myosin or desmin. We also established the osteoblastic differentiation model of the AVICs induced by pro-calcific medium (PCM) containing β-glycerophosphate disodium, dexamethasone and ascorbic acid in vitro. The results showed that taurine attenuated the PCM-induced osteoblastic differentiation of AVICs by decreasing the alkaline phosphate (ALP) activity/expression and the expression of the core binding factor α1 (Cbfα1) in a dose-dependent manner (reaching the maximum protective effect at 10 mM), and taurine (10 mM) inhibited the mineralization level of AVICs in the form of calcium content significantly. Furthermore, taurine activated the extracellular signal-regulated protein kinase (ERK) pathway via TAUT, and the inhibitor of ERK (PD98059) abolished the effect of taurine on both ALP activity/expression and Cbfα1 expression. These results suggested that taurine could inhibit osteoblastic differentiation of AVIC via the ERK pathway.
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Recellularization of decellularized heart valves: Progress toward the tissue-engineered heart valve
VeDepo, Mitchell C; Detamore, Michael S; Hopkins, Richard A; Converse, Gabriel L
2017-01-01
The tissue-engineered heart valve portends a new era in the field of valve replacement. Decellularized heart valves are of great interest as a scaffold for the tissue-engineered heart valve due to their naturally bioactive composition, clinical relevance as a stand-alone implant, and partial recellularization in vivo. However, a significant challenge remains in realizing the tissue-engineered heart valve: assuring consistent recellularization of the entire valve leaflets by phenotypically appropriate cells. Many creative strategies have pursued complete biological valve recellularization; however, identifying the optimal recellularization method, including in situ or in vitro recellularization and chemical and/or mechanical conditioning, has proven difficult. Furthermore, while many studies have focused on individual parameters for increasing valve interstitial recellularization, a general understanding of the interacting dynamics is likely necessary to achieve success. Therefore, the purpose of this review is to explore and compare the various processing strategies used for the decellularization and subsequent recellularization of tissue-engineered heart valves. PMID:28890780
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The Significance of Interstitial Cells in Neurogastroenterology
Blair, Peter J; Rhee, Poong-Lyul; Sanders, Kenton M; Ward, Sean M
2014-01-01
Smooth muscle layers of the gastrointestinal tract consist of a heterogeneous population of cells that include enteric neurons, several classes of interstitial cells of mesenchymal origin, a variety of immune cells and smooth muscle cells (SMCs). Over the last number of years the complexity of the interactions between these cell types has begun to emerge. For example, interstitial cells, consisting of both interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor alpha-positive (PDGFRα+) cells generate pacemaker activity throughout the gastrointestinal (GI) tract and also transduce enteric motor nerve signals and mechanosensitivity to adjacent SMCs. ICC and PDGFRα+ cells are electrically coupled to SMCs possibly via gap junctions forming a multicellular functional syncytium termed the SIP syncytium. Cells that make up the SIP syncytium are highly specialized containing unique receptors, ion channels and intracellular signaling pathways that regulate the excitability of GI muscles. The unique role of these cells in coordinating GI motility is evident by the altered motility patterns in animal models where interstitial cell networks are disrupted. Although considerable advances have been made in recent years on our understanding of the roles of these cells within the SIP syncytium, the full physiological functions of these cells and the consequences of their disruption in GI muscles have not been clearly defined. This review gives a synopsis of the history of interstitial cell discovery and highlights recent advances in structural, molecular expression and functional roles of these cells in the GI tract. PMID:24948131
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Heart Valve Biomechanics and Underlying Mechanobiology
Ayoub, Salma; Ferrari, Giovanni; Gorman, Robert C.; Gorman, Joseph H.; Schoen, Frederick J.; Sacks, Michael S.
2017-01-01
Heart valves control unidirectional blood flow within the heart during the cardiac cycle. They have a remarkable ability to withstand the demanding mechanical environment of the heart, achieving lifetime durability by processes involving the ongoing remodeling of the extracellular matrix. The focus of this review is on heart valve functional physiology, with insights into the link between disease-induced alterations in valve geometry, tissue stress, and the subsequent cell mechanobiological responses and tissue remodeling. We begin with an overview of the fundamentals of heart valve physiology and the characteristics and functions of valve interstitial cells (VICs). We then provide an overview of current experimental and computational approaches that connect VIC mechanobiological response to organ- and tissue-level deformations and improve our understanding of the underlying functional physiology of heart valves. We conclude with a summary of future trends and offer an outlook for the future of heart valve mechanobiology, specifically, multiscale modeling approaches, and the potential directions and possible challenges of research development. PMID:27783858
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Xiao, Xiaoxiong; Zhou, Tingwen; Guo, Shichao; Guo, Chao; Zhang, Qiao; Dong, Nianguo; Wang, Yongjun
2017-09-15
Emerging evidences have indicated that long non-coding RNAs (lncRNAs) play vital roles in cardiovascular physiology and pathology. The lncRNA MALAT1, a highly abundant and conserved imprinted gene, has been implicated in many cardiovascular diseases. However, the function of MALAT1 in calcific aortic valve disease (CAVD) remains unknown. This study sought to document the function and underlying mechanism of MALAT1 in regulating CAVD. Protein level was determined by immunoblotting and immunofluorescence staining. MALAT1, miR-204 and mRNA expressions were detected by qRT-PCR. Mineralized bone matrix formation was assessed by Alizarin Red staining. The interaction between MALAT1 and miR-204 was studied using luciferase reporter assay, RNA pull-down assay and RNA-binding protein immunoprecipitation assay. Ectopic expression of MALAT1 was observed in calcific valves and after osteogenic induction in human aortic valve interstitial cells (VICs). In vitro experiments revealed that MALAT1 acted as a positive regulator of osteogenic differentiation by repressing miR-204 expression and activity and thereby promoting expression of osteoblast-specific markers, including alkaline phosphatase, mineralized bone matrix formation and osteocalcin. Mechanistically, we identified Smad4 as a direct target of miR-204. Importantly, MALAT1 could directly interact with miR-204 and overexpression of miR-204 efficiently reversed the upregulation of Smad4 induced by MALAT1. Thus, MALAT1 positively regulated the expression of Smad4 through sponging miR-204, and promoted osteogenic differentiation of VICs. Our study provides novel mechanistic insights into a critical role for lncRNA MALAT1 as a miRNA sponge in CAVD and sheds new light on lncRNA-directed diagnostics and therapeutics in CAVD. Copyright © 2017. Published by Elsevier B.V.
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Cells for tissue engineering of cardiac valves.
Jana, Soumen; Tranquillo, Robert T; Lerman, Amir
2016-10-01
Heart valve tissue engineering is a promising alternative to prostheses for the replacement of diseased or damaged heart valves, because tissue-engineered valves have the ability to remodel, regenerate and grow. To engineer heart valves, cells are harvested, seeded onto or into a three-dimensional (3D) matrix platform to generate a tissue-engineered construct in vitro, and then implanted into a patient's body. Successful engineering of heart valves requires a thorough understanding of the different types of cells that can be used to obtain the essential phenotypes that are expressed in native heart valves. This article reviews different cell types that have been used in heart valve engineering, cell sources for harvesting, phenotypic expression in constructs and suitability in heart valve tissue engineering. Natural and synthetic biomaterials that have been applied as scaffold systems or cell-delivery platforms are discussed with each cell type. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
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The mechanobiology of mitral valve function, degeneration, and repair
Richards, Jennifer M.; Farrar, Emily J.; Kornreich, Bruce G.; Moïse, N. Sydney; Butcher, Jonathan T.
2013-01-01
In degenerative valve disease, the highly organized mitral valve leaflet matrix stratification is progressively destroyed and replaced with proteoglycan rich, mechanically inadequate tissue. This is driven by the actions of originally quiescent valve interstitial cells that become active contractile and migratory myofibroblasts. While treatment for myxomatous mitral valve disease in humans ranges from repair to total replacement, therapies in dogs focus on treating the consequences of the resulting mitral regurgitation. The fundamental gap in our understanding is how the resident valve cells respond to altered mechanical signals to drive tissue remodeling. Despite the pathological similarities and high clinical occurrence, surprisingly little mechanistic insight has been gleaned from the dog. This review presents what is known about mitral valve mechanobiology from clinical, in vivo, and in vitro data. There are a number of experimental strategies already available to pursue this significant opportunity, but success requires the collaboration between veterinary clinicians, scientists, and engineers. PMID:22366572
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Aortic calcified particles modulate valvular endothelial and interstitial cells.
van Engeland, Nicole C A; Bertazzo, Sergio; Sarathchandra, Padmini; McCormack, Ann; Bouten, Carlijn V C; Yacoub, Magdi H; Chester, Adrian H; Latif, Najma
Normal and calcified human valve cusps, coronary arteries, and aortae harbor spherical calcium phosphate microparticles of identical composition and crystallinity, and their role remains unknown. The objective was to examine the direct effects of isolated calcified particles on human valvular cells. Calcified particles were isolated from healthy and diseased aortae, characterized, quantitated, and applied to valvular endothelial cells (VECs) and interstitial cells (VICs). Cell differentiation, viability, and proliferation were analyzed. Particles were heterogeneous, differing in size and shape, and were crystallized as calcium phosphate. Diseased donors had significantly more calcified particles compared to healthy donors (P<.05), but there were no differences between the composition of the particles from healthy and diseased donors. VECs treated with calcified particles showed a significant decrease in CD31 and VE-cadherin and an increase in von Willebrand factor expression, P<.05. There were significantly increased α-SMA and osteopontin in treated VICs (P<.05), significantly decreased VEC and VIC viability (P<.05), and significantly increased number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive VECs (P<.05) indicating apoptosis when treated with the calcified particles. Isolated calcified particles from human aortae are not innocent bystanders but induce a phenotypical and pathological change of VECs and VICs characteristic of activated and pathological cells. Therapy tailored to reduce these calcified particles should be investigated. Copyright © 2017 Elsevier Inc. All rights reserved.
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Miyamoto-Kikuta, Sachiko; Ezaki, Taichi; Komuro, Terumasa
2009-10-01
The guinea-pig ileocaecal junction including the valve was studied by immunohistochemistry to clarify the organization of the muscle bundles, the enteric nerves and the interstitial cells of Cajal (ICC). This region clearly exhibited characteristic features in the distribution patterns of ICC in a proximal to distal direction: (1) the thickened portion of the terminal ileum immediately adjacent to the ileocecal junction contained many ICC throughout the circular (ICC-CM) and longitudinal (ICC-LM) muscle layers, but ICC were few or absent in the rest of the ileum; (2) the ileal side of the valve contained ICC associated with the deep muscular plexus (ICC-DMP) as in the small intestine, whereas ICC-DMP were absent in the caecal side as in the caecum; (3) the valve contained many ICC-CM and ICC-LM in both the ileal and caecal sides; (4) many ICC associated with the myenteric plexus were observed in both the ileal and caecal sides of the valve, whereas they were only sparsely found in the caecum; (5) ICC were also observed around the submucosal plexus in a confined area of the terminal ileum and the ileocaecal valve. These observations provide morphological evidence that the terminal ileum and ileocaecal valve are specially equipped for their active involvement in the movement of the junctional area.
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Understanding Lymphatic Valve Function via Computational Modeling
NASA Astrophysics Data System (ADS)
Wolf, Ki; Nepiyushchikh, Zhanna; Razavi, Mohammad; Dixon, Brandon; Alexeev, Alexander
2017-11-01
The lymphatic system is a crucial part to the circulatory system with many important functions, such as transport of interstitial fluid, fatty acid, and immune cells. Lymphatic vessels' contractile walls and valves allow lymph flow against adverse pressure gradients and prevent back flow. Yet, the effect of lymphatic valves' geometric and mechanical properties to pumping performance and lymphatic dysfunctions like lymphedema is not well understood. Our coupled fluid-solid computational model based on lattice Boltzmann model and lattice spring model investigates the dynamics and effectiveness of lymphatic valves in resistance minimization, backflow prevention, and viscoelastic response under different geometric and mechanical properties, suggesting the range of lymphatic valve parameters with effective pumping performance. Our model also provides more physiologically relevant relations of the valve response under varied conditions to a lumped parameter model of the lymphatic system giving an integrative insight into lymphatic system performance, including its failure due to diseases. NSF CMMI-1635133.
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Side-Specific Endothelial-Dependent Regulation of Aortic Valve Calcification
Richards, Jennifer; El-Hamamsy, Ismail; Chen, Si; Sarang, Zubair; Sarathchandra, Padmini; Yacoub, Magdi H.; Chester, Adrian H.; Butcher, Jonathan T.
2014-01-01
Arterial endothelial cells maintain vascular homeostasis and vessel tone in part through the secretion of nitric oxide (NO). In this study, we determined how aortic valve endothelial cells (VEC) regulate aortic valve interstitial cell (VIC) phenotype and matrix calcification through NO. Using an anchored in vitro collagen hydrogel culture system, we demonstrate that three-dimensionally cultured porcine VIC do not calcify in osteogenic medium unless under mechanical stress. Co-culture with porcine VEC, however, significantly attenuated VIC calcification through inhibition of myofibroblastic activation, osteogenic differentiation, and calcium deposition. Incubation with the NO donor DETA-NO inhibited VIC osteogenic differentiation and matrix calcification, whereas incubation with the NO blocker l-NAME augmented calcification even in 3D VIC–VEC co-culture. Aortic VEC, but not VIC, expressed endothelial NO synthase (eNOS) in both porcine and human valves, which was reduced in osteogenic medium. eNOS expression was reduced in calcified human aortic valves in a side-specific manner. Porcine leaflets exposed to the soluble guanylyl cyclase inhibitor ODQ increased osteocalcin and α-smooth muscle actin expression. Finally, side-specific shear stress applied to porcine aortic valve leaflet endothelial surfaces increased cGMP production in VEC. Valve endothelial-derived NO is a natural inhibitor of the early phases of valve calcification and therefore may be an important regulator of valve homeostasis and pathology. PMID:23499458
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Pucéat, Michel
2013-04-01
The cardiac valves are targets of both congenital and acquired diseases. The formation of valves during embryogenesis (i.e., valvulogenesis) originates from endocardial cells lining the myocardium. These cells undergo an endothelial-mesenchymal transition, proliferate and migrate within an extracellular matrix. This leads to the formation of bilateral cardiac cushions in both the atrioventricular canal and the outflow tract. The embryonic origin of both the endocardium and prospective valve cells is still elusive. Endocardial and myocardial lineages are segregated early during embryogenesis and such a cell fate decision can be recapitulated in vitro by embryonic stem cells (ESC). Besides genetically modified mice and ex vivo heart explants, ESCs provide a cellular model to study the early steps of valve development and might constitute a human therapeutic cell source for decellularized tissue-engineered valves. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction. Copyright © 2012 Elsevier B.V. All rights reserved.
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Induced Autologous Stem Cell Transplantation for Treatment of Rabbit Renal Interstitial Fibrosis
Ruan, Guang-Ping; Xu, Fan; Li, Zi-An; Zhu, Guang-Xu; Pang, Rong-Qing; Wang, Jin-Xiang; Cai, Xue-Min; He, Jie; Yao, Xiang; Ruan, Guang-Hong; Xu, Xin-Ming; Pan, Xing-Hua
2013-01-01
Introduction Renal interstitial fibrosis (RIF) is a significant cause of end-stage renal failure. The goal of this study was to characterize the distribution of transplanted induced autologous stem cells in a rabbit model of renal interstitial fibrosis and evaluate its therapeutic efficacy for treatment of renal interstitial fibrosis. Methods A rabbit model of renal interstitial fibrosis was established. Autologous fibroblasts were cultured, induced and labeled with green fluorescent protein (GFP). These labeled stem cells were transplanted into the renal artery of model animals at 8 weeks. Results Eight weeks following transplantation of induced autologous stem cells, significant reductions (P < 0.05) were observed in serum creatinine (SCr) (14.8 ± 1.9 mmol/L to 10.1 ± 2.1 mmol/L) and blood urea nitrogen (BUN) (119 ± 22 µmol/L to 97 ± 13 µmol/L), indicating improvement in renal function. Conclusions We successfully established a rabbit model of renal interstitial fibrosis and demonstrated that transplantation of induced autologous stem cells can repair kidney damage within 8 weeks. The repair occurred by both inhibition of further development of renal interstitial fibrosis and partial reversal of pre-existing renal interstitial fibrosis. These beneficial effects lead to the development of normal tissue structure and improved renal function. PMID:24367598
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Interstitial flows promote an amoeboid cell phenotype and motility of breast cancer cells
NASA Astrophysics Data System (ADS)
Tung, Chih-Kuan; Huang, Yu Ling; Zheng, Angela; Wu, Mingming
2015-03-01
Lymph nodes, the drainage systems for interstitial flows, are clinically known to be the first metastatic sites of many cancer types including breast and prostate cancers. Here, we demonstrate that breast cancer cell morphology and motility is modulated by interstitial flows in a cell-ECM adhesion dependent manner. The average aspect ratios of the cells are significantly lower (or are more amoeboid like) in the presence of the flow in comparison to the case when the flow is absent. The addition of exogenous adhesion molecules within the extracellular matrix (type I collagen) enhances the overall aspect ratio (or are more mesenchymal like) of the cell population. Using measured cell trajectories, we find that the persistence of the amoeboid cells (aspect ratio less than 2.0) is shorter than that of mesenchymal cells. However, the maximum speed of the amoeboid cells is larger than that of mesenchymal cells. Together these findings provide the novel insight that interstitial flows promote amoeboid cell morphology and motility and highlight the plasticity of tumor cell motility in response to its biophysical environment. Supported by NIH Grant R21CA138366.
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Odelin, Gaëlle; Faure, Emilie; Coulpier, Fanny; Di Bonito, Maria; Bajolle, Fanny; Studer, Michèle; Avierinos, Jean-François; Charnay, Patrick; Topilko, Piotr; Zaffran, Stéphane
2018-01-03
Although cardiac neural crest cells are required at early stages of arterial valve development, their contribution during valvular leaflet maturation remains poorly understood. Here, we show in mouse that neural crest cells from pre-otic and post-otic regions make distinct contributions to the arterial valve leaflets. Genetic fate-mapping analysis of Krox20-expressing neural crest cells shows a large contribution to the borders and the interleaflet triangles of the arterial valves. Loss of Krox20 function results in hyperplastic aortic valve and partially penetrant bicuspid aortic valve formation. Similar defects are observed in neural crest Krox20 -deficient embryos. Genetic lineage tracing in Krox20 -/- mutant mice shows that endothelial-derived cells are normal, whereas neural crest-derived cells are abnormally increased in number and misplaced in the valve leaflets. In contrast, genetic ablation of Krox20 -expressing cells is not sufficient to cause an aortic valve defect, suggesting that adjacent cells can compensate this depletion. Our findings demonstrate a crucial role for Krox20 in arterial valve development and reveal that an excess of neural crest cells may be associated with bicuspid aortic valve. © 2018. Published by The Company of Biologists Ltd.
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3D Bioprinting of Heterogeneous Aortic Valve Conduits with Alginate/Gelatin Hydrogels
Duan, Bin; Hockaday, Laura A.; Kang, Kevin H.; Butcher, Jonathan T.
2013-01-01
Heart valve disease is a serious and growing public health problem for which prosthetic replacement is most commonly indicated. Current prosthetic devices are inadequate for younger adults and growing children. Tissue engineered living aortic valve conduits have potential for remodeling, regeneration, and growth, but fabricating natural anatomical complexity with cellular heterogeneity remain challenging. In the current study, we implement 3D bioprinting to fabricate living alginate/gelatin hydrogel valve conduits with anatomical architecture and direct incorporation of dual cell types in a regionally constrained manner. Encapsulated aortic root sinus smooth muscle cells (SMC) and aortic valve leaflet interstitial cells (VIC) were viable within alginate/gelatin hydrogel discs over 7 days in culture. Acellular 3D printed hydrogels exhibited reduced modulus, ultimate strength, and peak strain reducing slightly over 7-day culture, while the tensile biomechanics of cell-laden hydrogels were maintained. Aortic valve conduits were successfully bioprinted with direct encapsulation of SMC in the valve root and VIC in the leaflets. Both cell types were viable (81.4±3.4% for SMC and 83.2±4.0% for VIC) within 3D printed tissues. Encapsulated SMC expressed elevated alpha-smooth muscle actin when printed in stiff matrix, while VIC expressed elevated vimentin in soft matrix. These results demonstrate that anatomically complex, heterogeneously encapsulated aortic valve hydrogel conduits can be fabricated with 3D bioprinting. PMID:23015540
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Role of the testis interstitial compartment in spermatogonial stem cell function
Potter, Sarah J.; DeFalco, Tony
2017-01-01
Male fertility is maintained through intricate cellular and molecular interactions that ensure spermatogonial stem cells (SSCs) proceed in a step-wise differentiation process through spermatogenesis and spermiogenesis to produce sperm. SSCs lie within the seminiferous tubule compartment, which provides a nurturing environment for the development of sperm. Cells outside of the tubules, such as interstitial and peritubular cells, also help direct SSC activity. This review focuses on interstitial (interstitial macrophages, Leydig cells, and vasculature) and peritubular (peritubular macrophages, peritubular myoid cells) cells and their role in regulating SSC self-renewal and differentiation in mammals. Leydig cells, the major steroidogenic cells in the testis, influence SSCs through secreted factors, such as insulin growth factor 1 (IGF1) and colony stimulating factor 1 (CSF1). Macrophages interact with SSCs through various potential mechanisms, such as CSF1 and retinoic acid (RA), to induce proliferation or differentiation of SSCs, respectively. Vasculature influences SSC dynamics through CSF1, vascular endothelial growth factor (VEGF), and regulating oxygen levels. Lastly, peritubular myoid cells produce one of the most well-known factors that is required for SSC self-renewal, glial cell line derived neurotrophic factor (GDNF), as well as CSF1. Overall, SSC interactions with interstitial and peritubular cells are critical for SSC function and are an important underlying factor promoting male fertility. PMID:28115580
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Design and efficacy of a single-use bioreactor for heart valve tissue engineering.
Converse, Gabriel L; Buse, Eric E; Neill, Kari R; McFall, Christopher R; Lewis, Holley N; VeDepo, Mitchell C; Quinn, Rachael W; Hopkins, Richard A
2017-02-01
Heart valve tissue engineering offers the promise of improved treatments for congenital heart disorders; however, widespread clinical availability of a tissue engineered heart valve (TEHV) has been hindered by scientific and regulatory concerns, including the lack of a disposable, bioreactor system for nondestructive valve seeding and mechanical conditioning. Here we report the design for manufacture and the production of full scale, functional prototypes of such a system. To evaluate the efficacy of this bioreactor as a tool for seeding, ovine aortic valves were decellularized and subjected to seeding with human mesenchymal stem cells (hMSC). The effects of pulsatile conditioning using cyclic waveforms tuned to various negative and positive chamber pressures were evaluated, with respect to the seeding of cells on the decellularized leaflet and the infiltration of seeded cells into the interstitium of the leaflet. Infiltration of hMSCs into the aortic valve leaflet was observed following 72 h of conditioning under negative chamber pressure. Additional conditioning under positive pressure improved cellular infiltration, while retaining gene expression within the MSC-valve interstitial cell phenotype lineage. This protocol resulted in a subsurface pilot population of cells, not full tissue recellularization. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 249-259, 2017. © 2015 Wiley Periodicals, Inc.
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Deficiency of interstitial cells of Cajal in the small intestine of patients with Crohn's disease.
Porcher, Christophe; Baldo, Marjolaine; Henry, Monique; Orsoni, Pierre; Julé, Yvon; Ward, Sean M
2002-01-01
Interstitial cells of Cajal are critical for the generation of electrical slow waves that regulate the phasic contractile activity of the tunica muscularis of the GI tract. Under certain pathophysiological conditions loss of interstitial cells of Cajal may play a role in the generation of certain motility disorders. The aim of the present study was to determine if there is an abnormality in the density or distribution of interstitial cells of Cajal from patients with Crohn's disease. Small intestines from control subjects and patients with Crohn's disease were examined using immunohistochemistry and antibodies against the Kit receptor, which is expressed in interstitial cells of Cajal within the tunica muscularis of the GI tract. The density and distribution of interstitial cells of Cajal were assessed in the longitudinal and circular muscle layers and in the myenteric and deep muscular plexus regions of Crohn's and control tissues. Tissues from Crohn's disease patients showed an almost complete abolition of interstitial cells of Cajal within the longitudinal and circular muscle layers and a significant reduction in numbers at the level of the myenteric and deep muscular plexuses. In tissues from Crohn's disease patients, the density of interstitial cells of Cajal was reduced throughout the tunica muscularis in comparison to control small intestines. The disturbance of intestinal motility that occurs in patients with Crohn's disease may be a consequence of the loss of or defects in specific populations of interstitial cells of Cajal within the tunica muscularis.
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Fluid-Structure Model of Lymphatic Valve and Vessel
NASA Astrophysics Data System (ADS)
Wolf, Ki; Ballard, Matthew; Nepiyushchikh, Zhanna; Razavi, Mohammad; Dixon, Brandon; Alexeev, Alexander
The lymphatic system is a part of the circulatory system that performs a range of important functions such as transportation of interstitial fluid, fatty acid, and immune cells. The lymphatic vessels are composed of contractile walls to pump lymph against adverse pressure gradient and lymphatic valves that prevent back flow. Despite the importance of lymphatic system, the contribution of mechanical and geometric changes of lymphatic valves and vessels in pathologies of lymphatic dysfunction, such as lymphedema, is not well understood. We developed a coupled fluid-solid computational model to simultaneously simulate a lymphatic vessel, valve, and flow. A lattice Boltzmann model is used to represent the fluid component, while lattice spring model is used for the solid component of the lymphatic vessel, whose mechanical properties are derived experimentally. Behaviors such as lymph flow pattern and lymphatic valve performance against backflow and adverse pressure gradient under varied parameters of lymphatic valve and vessel geometry and mechanical properties are investigated to provide a better insight into the dynamics of lymphatic vessels, valves, and system and give insight into how they might fail in disease. NSF CMMI-1635133.
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Interstitial flow influences direction of tumor cell migration through competing mechanisms
Polacheck, William J.; Charest, Joseph L.; Kamm, Roger D.
2011-01-01
Interstitial flow is the convective transport of fluid through tissue extracellular matrix. This creeping fluid flow has been shown to affect the morphology and migration of cells such as fibroblasts, cancer cells, endothelial cells, and mesenchymal stem cells. A microfluidic cell culture system was designed to apply stable pressure gradients and fluid flow and allow direct visualization of transient responses of cells seeded in a 3D collagen type I scaffold. We used this system to examine the effects of interstitial flow on cancer cell morphology and migration and to extend previous studies showing that interstitial flow increases the metastatic potential of MDA-MB-435S melanoma cells [Shields J, et al. (2007) Cancer Cell 11:526–538]. Using a breast carcinoma line (MDA-MB-231) we also observed cell migration along streamlines in the presence of flow; however, we further demonstrated that the strength of the flow as well as the cell density determined directional bias of migration along the streamline. In particular, we found that cells either at high seeding density or with the CCR-7 receptor inhibited migration against, rather than with the flow. We provide further evidence that CCR7-dependent autologous chemotaxis is the mechanism that leads to migration with the flow, but also demonstrate a competing CCR7-independent mechanism that causes migration against the flow. Data from experiments investigating the effects of cell concentration, interstitial flow rate, receptor activity, and focal adhesion kinase phosphorylation support our hypothesis that the competing stimulus is integrin mediated. This mechanism may play an important role in development of metastatic disease. PMID:21690404
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Differentiating the aging of the mitral valve from human and canine myxomatous degeneration
Connell, Patrick S.; Han, Richard I.; Grande-Allen, K. Jane
2012-01-01
During the course of both canine and human aging, the mitral valve remodels in generally predictable ways. The connection between these aging changes and the morbidity and mortality that accompany pathologic conditions has not been made clear. By exploring work that has investigated the specific valvular changes in both age and disease, with respect to the cells and the extracellular matrix found within the mitral valve, heretofore unexplored connections between age and myxomatous valve disease can be found. This review addresses several studies that have been conducted to explore such age and disease related changes in extracellular matrix, valvular endothelial and interstitial cells, and valve innervation, and also reviews attempts to correlate aging and myxomatous disease. Such connections can highlight avenues for future research and help provide insight as to when an individual diverts from an aging pattern into a diseased pathway. Recognizing these patterns and opportunities could result in earlier intervention and the hope of reduced morbidity and mortality for patients. PMID:22364720
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A distinct type of cell in myocardium: interstitial Cajal-like cells (ICLCs)
Kostin, S; Popescu, L M
2009-01-01
Abstract The existence of a novel type of interstitial cells in the heart, interstitial Cajal-like cells (ICLCs), had been described for the first time in 2005. Their identification was mainly based on ultrastructural criteria: very long (tens up to hundreds of micrometres) and moniliform prolongations, which are extremely thin (less than 0.2 μm), below the resolving power of light microscopy. Myocardial ICLCs were also identified by methylene-blue vital staining, silver impregnation, and immunoreactivity for CD 34, vimentin, CD117/c-kit, etc. Although a series of studies provided evidence for the existence of ICLCs in human atria and rat ventricles, further investigations in other laboratories, using additional techniques, are required to substantiate the consistency of these findings. Here we provide further evidence for the existence of ICLCs in human and mammalian hearts (by transmission and scanning electron microscopy, as well as confocal laser scanning microscopy). Noteworthy, we confirm that ICLCs communicate with neighbouring cells via shedding (micro)vesicles. Although these so-called ICLCs represent a distinct type of cells, different from classical interstitial cells of Cajal, or fibroblasts, their role(s) in myocardium remain(s) to be established. Several hypotheses are proposed: (i) adult stromal (mesenchymal) stem cells, which might participate in cardiac repair/remodelling; (ii) intercellular signalling (e.g. via shedding microvesicles); (iii) chemo-mechanical transducers and (iv) players in pacemaking and/or arrhytmogenesis, and so on. PMID:19183408
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Pathology of myxomatous mitral valve disease in the dog.
Fox, Philip R
2012-03-01
Mitral valve competence requires complex interplay between structures that comprise the mitral apparatus - the mitral annulus, mitral valve leaflets, chordae tendineae, papillary muscles, and left atrial and left ventricular myocardium. Myxomatous mitral valve degeneration is prevalent in the canine, and most adult dogs develop some degree of mitral valve disease as they age, highlighting the apparent vulnerability of canine heart valves to injury. Myxomatous valvular remodeling is associated with characteristic histopathologic features. Changes include expansion of extracellular matrix with glycosaminoglycans and proteoglycans; valvular interstitial cell alteration; and attenuation or loss of the collagen-laden fibrosa layer. These lead to malformation of the mitral apparatus, biomechanical dysfunction, and mitral incompetence. Mitral regurgitation is the most common manifestation of myxomatous valve disease and in advanced stages, associated volume overload promotes progressive valvular regurgitation, left atrial and left ventricular remodeling, atrial tears, chordal rupture, and congestive heart failure. Future studies are necessary to identify clinical-pathologic correlates that track disease severity and progression, detect valve dysfunction, and facilitate risk stratification. It remains unresolved whether, or to what extent, the pathobiology of myxomatous mitral valve degeneration is the same between breeds of dogs, between canines and humans, and how these features are related to aging and genetics. Copyright © 2012 Elsevier B.V. All rights reserved.
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Benton, Julie A; DeForest, Cole A; Vivekanandan, Vani; Anseth, Kristi S
2009-11-01
The development of novel three-dimensional cell culture platforms for the culture of aortic valvular interstitial cells (VICs) has been fraught with many challenges. Although the most tunable, purely synthetic systems have not been successful at promoting cell survivability or function. On the other hand, entirely natural materials lack mechanical integrity. Here we explore a novel hybrid system consisting of gelatin macromers synthetically modified with methacrylate functionalities allowing for photoencapsulation of cells. Scanning electron microscopy observations show a microporous structure induced during polymerization within the hydrogel. This porous structure was tunable with polymerization rate and did not appear to have interconnected pores. Treatment with collagenase caused bulk erosion indicating enzymatic degradation controls the matrix remodeling. VICs, an important cell line for heart valve tissue engineering, were photoencapsulated and examined for cell-directed migration and differentiation. VICs were able to achieve their native morphology within 2 weeks of culture. The addition of the pro-fibrotic growth factor, transforming growth factor-beta1, accelerated this process and also was capable of inducing enhanced alpha-smooth muscle actin and collagen-1 expression, indicating a differentiation from quiescent fibroblasts to active myofibroblasts as demonstrated by quantitative real-time polymerase chain reaction and immunohistochemistry. Although these studies were limited to VICs, this novel hydrogel system may also be useful for studying other fibroblastic cell types.
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Design of a Cyclic Pressure Bioreactor for the Ex Vivo Study of Aortic Heart Valves
Schipke, Kimberly J.; Filip To, S. D.; Warnock, James N.
2011-01-01
The aortic valve, located between the left ventricle and the aorta, allows for unidirectional blood flow, preventing backflow into the ventricle. Aortic valve leaflets are composed of interstitial cells suspended within an extracellular matrix (ECM) and are lined with an endothelial cell monolayer. The valve withstands a harsh, dynamic environment and is constantly exposed to shear, flexion, tension, and compression. Research has shown calcific lesions in diseased valves occur in areas of high mechanical stress as a result of endothelial disruption or interstitial matrix damage1-3. Hence, it is not surprising that epidemiological studies have shown high blood pressure to be a leading risk factor in the onset of aortic valve disease4. The only treatment option currently available for valve disease is surgical replacement of the diseased valve with a bioprosthetic or mechanical valve5. Improved understanding of valve biology in response to physical stresses would help elucidate the mechanisms of valve pathogenesis. In turn, this could help in the development of non-invasive therapies such as pharmaceutical intervention or prevention. Several bioreactors have been previously developed to study the mechanobiology of native or engineered heart valves6-9. Pulsatile bioreactors have also been developed to study a range of tissues including cartilage10, bone11 and bladder12. The aim of this work was to develop a cyclic pressure system that could be used to elucidate the biological response of aortic valve leaflets to increased pressure loads. The system consisted of an acrylic chamber in which to place samples and produce cyclic pressure, viton diaphragm solenoid valves to control the timing of the pressure cycle, and a computer to control electrical devices. The pressure was monitored using a pressure transducer, and the signal was conditioned using a load cell conditioner. A LabVIEW program regulated the pressure using an analog device to pump compressed air into the
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Design of a cyclic pressure bioreactor for the ex vivo study of aortic heart valves.
Schipke, Kimberly J; To, S D Filip; Warnock, James N
2011-08-23
The aortic valve, located between the left ventricle and the aorta, allows for unidirectional blood flow, preventing backflow into the ventricle. Aortic valve leaflets are composed of interstitial cells suspended within an extracellular matrix (ECM) and are lined with an endothelial cell monolayer. The valve withstands a harsh, dynamic environment and is constantly exposed to shear, flexion, tension, and compression. Research has shown calcific lesions in diseased valves occur in areas of high mechanical stress as a result of endothelial disruption or interstitial matrix damage(1-3). Hence, it is not surprising that epidemiological studies have shown high blood pressure to be a leading risk factor in the onset of aortic valve disease(4). The only treatment option currently available for valve disease is surgical replacement of the diseased valve with a bioprosthetic or mechanical valve(5). Improved understanding of valve biology in response to physical stresses would help elucidate the mechanisms of valve pathogenesis. In turn, this could help in the development of non-invasive therapies such as pharmaceutical intervention or prevention. Several bioreactors have been previously developed to study the mechanobiology of native or engineered heart valves(6-9). Pulsatile bioreactors have also been developed to study a range of tissues including cartilage(10), bone(11) and bladder(12). The aim of this work was to develop a cyclic pressure system that could be used to elucidate the biological response of aortic valve leaflets to increased pressure loads. The system consisted of an acrylic chamber in which to place samples and produce cyclic pressure, viton diaphragm solenoid valves to control the timing of the pressure cycle, and a computer to control electrical devices. The pressure was monitored using a pressure transducer, and the signal was conditioned using a load cell conditioner. A LabVIEW program regulated the pressure using an analog device to pump compressed
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Valve Cap For An Electric Storage Cell
Verhoog, Roelof; Genton, Alain
2000-04-18
The valve cap for an electric storage cell includes a central annular valve seat (23) and a membrane (5) fixed by its peripheral edge and urged against the seat by a piston (10) bearing thereagainst by means of a spring (12), the rear end of said spring (12) bearing on the endwall (8) of a chamber (20) formed in the cap and containing the piston (10) and the spring. A vent (19) puts the chamber (20) into communication with the atmosphere. A central orifice (26, 28) through the piston (10) and the membrane (5), enables gas from within the cell to escape via the top vent (19) when the valve opens.
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Carrion, Katrina; Dyo, Jeffrey; Patel, Vishal; Sasik, Roman; Mohamed, Salah A; Hardiman, Gary; Nigam, Vishal
2014-01-01
Aortic valve calcification is a significant and serious clinical problem for which there are no effective medical treatments. Individuals born with bicuspid aortic valves, 1-2% of the population, are at the highest risk of developing aortic valve calcification. Aortic valve calcification involves increased expression of calcification and inflammatory genes. Bicuspid aortic valve leaflets experience increased biomechanical strain as compared to normal tricuspid aortic valves. The molecular pathogenesis involved in the calcification of BAVs are not well understood, especially the molecular response to mechanical stretch. HOTAIR is a long non-coding RNA (lncRNA) that has been implicated with cancer but has not been studied in cardiac disease. We have found that HOTAIR levels are decreased in BAVs and in human aortic interstitial cells (AVICs) exposed to cyclic stretch. Reducing HOTAIR levels via siRNA in AVICs results in increased expression of calcification genes. Our data suggest that β-catenin is a stretch responsive signaling pathway that represses HOTAIR. This is the first report demonstrating that HOTAIR is mechanoresponsive and repressed by WNT β-catenin signaling. These findings provide novel evidence that HOTAIR is involved in aortic valve calcification.
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The evaluation of interstitial Cajal cells distribution in non-tumoral colon disorders.
Becheanu, G; Manuc, M; Dumbravă, Mona; Herlea, V; Hortopan, Monica; Costache, Mariana
2008-01-01
Interstitial cells of Cajal (ICC) are pacemakers that generate electric waves recorded from the gut and are important for intestinal motility. The aim of the study was to evaluate the distribution of interstitial cells of Cajal in colon specimens from patients with idiopathic chronic pseudo-obstruction and other non-tumoral colon disorders as compared with samples from normal colon. The distribution pattern of ICC in the normal and pathological human colon was evaluated by immunohistochemistry using antibodies for CD117, CD34, and S-100. In two cases with intestinal chronic idiopathic pseudo-obstruction we found a diffuse or focal reducing number of Cajal cells, the loss of immunoreactivity for CD117 being correlated with loss of immunoreactivity for CD34 marker. Our study revealed that the number of interstitial cells of Cajal also decrease in colonic diverticular disease and Crohn disease (p<0.05), whereas the number of enteric neurones appears to be normal. These findings might explain some of the large bowel motor abnormalities known to occur in these disorders. Interstitial Cajal cells may play an important role in pathogenesis and staining for CD117 on transmural intestinal surgical biopsies could allow a more extensive diagnosis in evaluation of chronic intestinal pseudo-obstruction.
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Mixed germ cell-sex cord-stromal tumor with a concurrent interstitial cell tumor in a ferret
INOUE, Saki; YONEMARU, Kayoko; YANAI, Tokuma; SAKAI, Hiroki
2014-01-01
A 5-year-old male ferret presented with an enlarged canalicular testis in the left inguinal region. Microscopically, the enlarged testis consisted of a diffuse intimately admixed proliferation of c-kit-positive germ cell-like and Wilms tumor-1 protein-positive Sertoli cell-like components, but no Call-Exner body was detected. In addition, the compact proliferation of steroidogenic acute regulatory protein-intense positive interstitial cells was identified in a separate peripheral area of the mass. Based on histopathological and immunohistochemical findings, the tumor was diagnosed as a mixed germ cell-sex cord-stromal tumor with a concurrent interstitial cell tumor. PMID:25311985
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2014-01-01
Background Acute interstitial pneumonia is a rare interstitial lung disease that rapidly progresses to respiratory failure or death. Several studies showed that myofibroblast plays an important role in the evolution of diffuse alveolar damage, which is the typical feature of acute interstitial pneumonia. However, no evidence exists whether alveolar epithelial cells are an additional source of myofibroblasts via epithelial-mesenchymal transition in acute interstitial pneumonia. Case presentation In this report, we present a case of acute interstitial pneumonia in a previously healthy 28-year-old non-smoking woman. Chest high-resolution computed tomography scan showed bilateral and diffusely ground-glass opacification. The biopsy was performed on the fifth day of her hospitalization, and results showed manifestation of acute exudative phase of diffuse alveolar damage characterized by hyaline membrane formation. On the basis of the preliminary diagnosis of acute interstitial pneumonia, high-dose glucocorticoid was used. However, this drug showed poor clinical response and could improve the patient’s symptoms only during the early phase. The patient eventually died of respiratory dysfunction. Histological findings in autopsy were consistent with the late form of acute interstitial pneumonia. Conclusions The results in this study revealed that alveolar epithelial cells underwent epithelial-mesenchymal transition and may be an important origin of myofibroblasts in the progression of acute interstitial pneumonia. Conducting research on the transformation of alveolar epithelial cells into myofibroblasts in the lung tissue of patients with acute interstitial pneumonia may be beneficial for the treatment of this disease. However, to our knowledge, no research has been conducted on this topic. PMID:24755111
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Lauten, Alexander; Laube, Adrian; Schubert, Harald; Bischoff, Sabine; Nietzsche, Sandor; Horstkötter, Kim; Poudel-Bochmann, Bhawana; Franz, Marcus; Lichtenberg, Artur; Figulla, Hans R; Akhyari, Payam
2015-01-01
Caval valve implantation has been suggested for transcatheter treatment of severe tricuspid regurgitation (TR). Combining the interventional technique with the promising surgical experience with decellularized valves, we sought to evaluate the functional and structural outcome of decellularized pericardial tissue valves (dTVs) in the low-pressure venous circulation in a chronic model of TR. Sixteen pericardial tissue valves were heterotopically implanted in the inferior and superior vena cava in a sheep model (54-98 kg; median 74.5 kg, n = 8) of severe TR. The devices were assembled using self-expanding nitinol stents and bovine pericardia decellularized by a detergent-based protocol (group dTV; n = 8). Glutaraldehyde-fixed pericardial tissue valves served as control (GaTV, n = 8). After 6 months, device function and structural maturation were analyzed using echocardiographic, histologic, immunohistologic, and electron microscopic approaches. After implantation, cardiac output increased significantly from 3.7 ± 1.1 l/min to 4.8 ± 1.1 l/min (P < 0.05) and competent valve function was verified by angiography. At 6 months, angiographic and echocardiographic evaluation revealed moderate to severe regurgitation in all GaTV. In contrast, five of the eight dTVs functioned well with only minor regurgitation. In these animals, autopsy revealed preserved valve structure with tender leaflets without signs of thrombosis or calcification. Conversely, GaTV showed severe degeneration with large calcification areas. Microscopic and histologic analysis confirmed endothelial repopulation in both valve types. However, additional interstitial reseeding was observed in decellularized valves. In the venous circulation in severe TR, decellularized valves show superior functional performance compared to Ga-fixed tissue valves. Macroscopic and microscopic analyses suggest preserved structural integrity and advanced endothelial and interstitial repopulation with
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Bukowiecki, L.J.; Geloeen, A.; Collet, A.J.
1986-06-01
The mechanisms of brown adipocyte proliferation and differentiation during cold acclimation (and/or adaptation to hyperphagia) have been studied by quantitative photonic radioautography. (/sup 3/H)thymidine was injected to warm-acclimated (25/sup 0/C) rats and to animals exposed to 5/sup 0/C for 2 days. Samples of interscapular brown adipose tissue were collected for quantitative analysis of mitotic frequencies at various periods of time (4 h-15 days) after the injection of (/sup 3/H)thymidine, the rats being maintained at the temperatures to which they were initially exposed. It was found that cold exposure for 2 days markedly enhanced mitotic activity in endothelial cells, interstitial cells,more » and brown preadipocytes rather than in fully differentiated brown adipocytes. The total tissue labeling index (percent of labeled nuclei) increased approx.70 times over control values. The authors now report that cellular labeling progressively increased in mature brown adipocytes during cold acclimation, whereas it correspondingly decreased in interstitial cells and brown preadipocytes. This indicates that the sequence of events for cellular differentiation is interstitial cells ..-->.. brown preadipocytes ..-->.. mature brown adipocytes. Remarkable, labeling frequency did not change in endothelial cells during cold acclimation demonstrating that these cells cannot be considered as progenitors of brown adipocytes. It is suggested that brown adipocyte proliferation and differentiation from interstitial cells represent the fundamental phenomena explaining the enhanced capacity of cold-acclimated and/or hyperphagic rats to respond calorigenically to catecholamines.« less
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Straka, Frantisek; Schornik, David; Masin, Jaroslav; Filova, Elena; Mirejovsky, Tomas; Burdikova, Zuzana; Svindrych, Zdenek; Chlup, Hynek; Horny, Lukas; Daniel, Matej; Machac, Jiri; Skibová, Jelena; Pirk, Jan; Bacakova, Lucie
2018-04-01
The objective of our study was to compare the cellular and extracellular matrix (ECM) structure and the biomechanical properties of human pericardium (HP) with the normal human aortic heart valve (NAV). HP tissues (from 12 patients) and NAV samples (from 5 patients) were harvested during heart surgery. The main cells in HP were pericardial interstitial cells, which are fibroblast-like cells of mesenchymal origin similar to the valvular interstitial cells in NAV tissue. The ECM of HP had a statistically significantly (p < 0.001) higher collagen I content, a lower collagen III and elastin content, and a similar glycosaminoglycans (GAGs) content, in comparison with the NAV, as measured by ECM integrated density. However, the relative thickness of the main load-bearing structures of the two tissues, the dense part of fibrous HP (49 ± 2%) and the lamina fibrosa of NAV (47 ± 4%), was similar. In both tissues, the secant elastic modulus (Es) was significantly lower in the transversal direction (p < 0.05) than in the longitudinal direction. This proved that both tissues were anisotropic. No statistically significant differences in UTS (ultimate tensile strength) values and in calculated bending stiffness values in the longitudinal or transversal direction were found between HP and NAV. Our study confirms that HP has an advantageous ECM biopolymeric structure and has the biomechanical properties required for a tissue from which an autologous heart valve replacement may be constructed.
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Zhang, Xing; Xu, Bin; Puperi, Daniel S; Yonezawa, Aline L; Wu, Yan; Tseng, Hubert; Cuchiara, Maude L; West, Jennifer L; Grande-Allen, K Jane
2015-03-01
The development of advanced scaffolds that recapitulate the anisotropic mechanical behavior and biological functions of the extracellular matrix in leaflets would be transformative for heart valve tissue engineering. In this study, anisotropic mechanical properties were established in poly(ethylene glycol) (PEG) hydrogels by crosslinking stripes of 3.4 kDa PEG diacrylate (PEGDA) within 20 kDa PEGDA base hydrogels using a photolithographic patterning method. Varying the stripe width and spacing resulted in a tensile elastic modulus parallel to the stripes that was 4.1-6.8 times greater than that in the perpendicular direction, comparable to the degree of anisotropy between the circumferential and radial orientations in native valve leaflets. Biomimetic PEG-peptide hydrogels were prepared by tethering the cell-adhesive peptide RGDS and incorporating the collagenase-degradable peptide PQ (GGGPQG↓IWGQGK) into the polymer network. The specific amounts of RGDS and PEG-PQ within the resulting hydrogels influenced the elongation, de novo extracellular matrix deposition and hydrogel degradation behavior of encapsulated valvular interstitial cells (VICs). In addition, the morphology and activation of VICs grown atop PEG hydrogels could be modulated by controlling the concentration or micro-patterning profile of PEG-RGDS. These results are promising for the fabrication of PEG-based hydrogels using anatomically and biologically inspired scaffold design features for heart valve tissue engineering. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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Emmert, Maximilian Y; Weber, Benedikt; Behr, Luc; Sammut, Sebastien; Frauenfelder, Thomas; Wolint, Petra; Scherman, Jacques; Bettex, Dominique; Grünenfelder, Jürg; Falk, Volkmar; Hoerstrup, Simon P
2014-01-01
While transcatheter aortic valve implantation (TAVI) has rapidly evolved for the treatment of aortic valve disease, the currently used bioprostheses are prone to continuous calcific degeneration. Thus, autologous, cell-based, living, tissue-engineered heart valves (TEHVs) with regeneration potential have been suggested to overcome these limitations. We investigate the technical feasibility of combining the concept of TEHV with transapical implantation technology using a state-of-the-art transcatheter delivery system facilitating the exact anatomical position in the systemic circulation. Trileaflet TEHVs fabricated from biodegradable synthetic scaffolds were sewn onto self-expanding Nitinol stents seeded with autologous marrow stromal cells, crimped and transapically delivered into the orthotopic aortic valve position of adult sheep (n = 4) using the JenaValve transapical TAVI System (JenaValve, Munich, Germany). Delivery, positioning and functionality were assessed by angiography and echocardiography before the TEHV underwent post-mortem gross examination. For three-dimensional reconstruction of the stent position of the anatomically oriented system, a computed tomography analysis was performed post-mortem. Anatomically oriented, transapical delivery of marrow stromal cell-based TEHV into the orthotopic aortic valve position was successful in all animals (n = 4), with a duration from cell harvest to TEHV implantation of 101 ± 6 min. Fluoroscopy and echocardiography displayed sufficient positioning, thereby entirely excluding the native leaflets. There were no signs of coronary obstruction. All TEHV tolerated the loading pressure of the systemic circulation and no acute ruptures occurred. Animals displayed intact and mobile leaflets with an adequate functionality. The mean transvalvular gradient was 7.8 ± 0.9 mmHg, and the mean effective orifice area was 1.73 ± 0.02 cm(2). Paravalvular leakage was present in two animals, and central aortic regurgitation due to a
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Moreso, F; Seron, D; O'Valle, F; Ibernon, M; Gomà, M; Hueso, M; Cruzado, J M; Bestard, O; Duarte, V; del Moral, R García; Grinyó, J M
2007-12-01
Patients with a protocol renal allograft biopsy simultaneously displaying interstitial fibrosis/tubular atrophy (IF/TA) and subclinical rejection (SCR) have a shortened graft survival than patients with a normal biopsy, or with a biopsy only displaying IF/TA or SCR. The poor outcome of these patients could be related with a more severe inflammation. We evaluate the immunophenotype of infiltrating cells in these diagnostic categories. Nonexhausted paraffin blocks from protocol biopsies done during the first year were stained with anti-CD45, CD3, CD20, CD68 and CD15 monoclonal antibodies. Glomerular and interstitial positive cells were counted. C4d deposition in peritubular capillaries was evaluated. Histological diagnoses were: normal (n = 80), SCR (n = 17), IF/TA (n = 42) and IF/TA + SCR (n = 17). Only interstitial CD20 positive cells were significantly increased in patients displaying IF/TA + SCR; normal (137 +/- 117), SCR (202 +/- 145), IF/TA (208 +/- 151) and IF/TA + SCR (307 +/- 180 cells/mm(2)), p < 0.01. The proportion of biopsies displaying C4d deposition was not different among groups. The upper tertile of CD20 positive interstitial cells was associated with a decreased death-censored graft survival (relative risk: 3.01, 95% confidence interval: 1.23-7.35; p = 0.015). These data suggest that B-cell interstitial infiltrates are associated with histological damage and outcome, but do not distinguish whether these infiltrates were the cause or the consequence of chronic tubulo-interstitial damage.
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Connolly, Jeanne M.; Alferiev, Ivan; Clark-Gruel, Jocelyn N.; Eidelman, Naomi; Sacks, Michael; Palmatory, Elizabeth; Kronsteiner, Allyson; DeFelice, Suzanne; Xu, Jie; Ohri, Rachit; Narula, Navneet; Vyavahare, Narendra; Levy, Robert J.
2005-01-01
We investigated a novel polyepoxide crosslinker that was hypothesized to confer both material stabilization and calcification resistance when used to prepare bioprosthetic heart valves. Triglycidylamine (TGA) was synthesized via reacting epichlorhydrin and NH3. TGA was used to crosslink porcine aortic cusps, bovine pericardium, and type I collagen. Control materials were crosslinked with glutaraldehyde (Glut). TGA-pretreated materials had shrink temperatures comparable to Glut fixation. However, TGA crosslinking conferred significantly greater collagenase resistance than Glut pretreatment, and significantly improved biomechanical compliance. Sheep aortic valve interstitial cells grown on TGA-pretreated collagen did not calcify, whereas sheep aortic valve interstitial cells grown on control substrates calcified extensively. Rat subdermal implants (porcine aortic cusps/bovine pericardium) pretreated with TGA demonstrated significantly less calcification than Glut pretreated implants. Investigations of extracellular matrix proteins associated with calcification, matrix metalloproteinases (MMPs) 2 and 9, tenascin-C, and osteopontin, revealed that MMP-9 and tenascin-C demonstrated reduced expression both in vitro and in vivo with TGA crosslinking compared to controls, whereas osteopontin and MMP-2 expression were not affected. TGA pretreatment of heterograft biomaterials results in improved stability compared to Glut, confers biomechanical properties superior to Glut crosslinking, and demonstrates significant calcification resistance. PMID:15631995
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Deep wells integrated with microfluidic valves for stable docking and storage of cells.
Jang, Yun-Ho; Kwon, Cheong Hoon; Kim, Sang Bok; Selimović, Seila; Sim, Woo Young; Bae, Hojae; Khademhosseini, Ali
2011-02-01
In this paper, we describe a microfluidic mechanism that combines microfluidic valves and deep wells for cell localization and storage. Cells are first introduced into the device via externally controlled flow. Activating on-chip valves was used to interrupt the flow and to sediment the cells floating above the wells. Thus, valves could be used to localize the cells in the desired locations. We quantified the effect of valves in the cell storage process by comparing the total number of cells stored with and without valve activation. We hypothesized that in deep wells external flows generate low shear stress regions that enable stable, long-term docking of cells. To assess this hypothesis we conducted numerical calculations to understand the influence of well depth on the forces acting on cells. We verified those predictions experimentally by comparing the fraction of stored cells as a function of the well depth and input flow rate upon activation of the valves. As expected, upon reintroduction of the flow the cells in the deep wells were not moved whereas those in shallow wells were washed away. Taken together, our paper demonstrates that deep wells and valves can be combined to enable a broad range of cell studies. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Mizuno, Ryuichi; Asano, Koichiro; Mikami, Shuji; Nagata, Hirohiko; Kaneko, Gou; Oya, Mototsugu
2012-05-01
To elucidate the patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma, we reviewed seven cases of everolimus-induced interstitial lung disease. Seven patients with metastatic renal cell carcinoma, which continued to progress despite treatment with sunitinib or sorafenib, developed interstitial lung disease after treatment with everolimus. Chest X-ray demonstrated diffuse infiltrates in lung fields, and chest computed tomography showed bilateral reticular and ground-glass opacities. Serum levels of lactate dehydrogenase (7/7), C-reactive protein (6/7), pulmonary surfactant associated protein D (1/7) and Krebs von den Lungen 6 (5/7) were elevated. The bronchoalveolar lavage fluid obtained from four patients with Grade 3 interstitial lung disease showed lymphocytosis. The transbronchial lung biopsy specimens showed interstitial lymphocytic infiltration and septal thickening of alveolar walls. In two cases with mild interstitial lung disease, the everolimus therapy was successfully continued. In four cases with Grade 3 interstitial lung disease, the drug was discontinued and steroid therapy was initiated. Pulmonary symptoms and radiological abnormalities resolved within 2 months. Serum Krebs von den Lungen 6 was elevated compared with baseline in all cases with interstitial lung disease. Some patients who developed mild interstitial lung disease during everolimus treatment could continue to receive the treatment. Even when severe interstitial lung disease developed, withdrawal of the drug and short-term use of high-dose steroids resulted in rapid recovery. Prompt recognition of interstitial lung disease exacerbation as well as exclusion of progressive disease or infection is of primary importance.
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Hockaday, L A; Kang, K H; Colangelo, N W; Cheung, P Y C; Duan, B; Malone, E; Wu, J; Girardi, L N; Bonassar, L J; Lipson, H; Chu, C C; Butcher, J T
2013-01-01
The aortic valve exhibits complex three-dimensional (3D) anatomy and heterogeneity essential for long-term efficient biomechanical function. These are, however, challenging to mimic in de novo engineered living tissue valve strategies. We present a novel simultaneous 3D-printing/photocrosslinking technique for rapidly engineering complex, heterogeneous aortic valve scaffolds. Native anatomic and axisymmetric aortic valve geometries (root wall and tri-leaflets) with 12 to 22 mm inner diameters (ID) were 3D printed with poly-ethylene glycol-diacrylate (PEG-DA) hydrogels (700 or 8000 MW) supplemented with alginate. 3D printing geometric accuracy was quantified and compared using Micro-CT. Porcine aortic valve interstitial cells (PAVIC) seeded scaffolds were cultured for up to 21 days. Results showed that blended PEG-DA scaffolds could achieve over 10-fold range in elastic modulus (5.3±0.9 to 74.6±1.5 kPa). 3D printing times for valve conduits with mechanically contrasting hydrogels were optimized to 14 to 45 minutes, increasing linearly with conduit diameter. Larger printed valves had greater shape fidelity (93.3±2.6, 85.1±2.0, and 73.3±5.2% for 22, 17, and 12 mm ID porcine valves; 89.1±4.0, 84.1±5.6, and 66.6±5.2% for simplified valves). PAVIC seeded scaffolds maintained near 100% viability over 21 days. These results demonstrate that 3D hydrogel printing with controlled photocrosslinking can rapidly fabricate anatomical heterogeneous valve conduits that support cell engraftment. PMID:22914604
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Manipulation of valve composition to elucidate the role of collagen in aortic valve calcification
2014-01-01
Background Extracellular matrix (ECM) disarray is found in calcific aortic valvular disease (CAVD), yet much remains to be learned about the role of individual ECM components in valvular interstitial cell (VIC) function and dysfunction. Previous clinical analyses have shown that calcification is associated with decreased collagen content, while previous in vitro work has suggested that the presence of collagen attenuates the responsiveness of VICs to pro-calcific stimuli. The current study uses whole leaflet cultures to examine the contributions of endogenous collagen in regulating the phenotype and calcification of VICs. Methods A “top-down” approach was used to characterize changes in VIC phenotype in response to collagen alterations in the native 3D environment. Collagen-deficient leaflets were created via enzymatic treatment and cultured statically for six days in vitro. After culture, leaflets were harvested for analysis of DNA, proliferation, apoptosis, ECM composition, calcification, and gene/protein expression. Results In general, disruption of collagen was associated with increased expression of disease markers by VICs in whole organ leaflet culture. Compared to intact control leaflets, collagen-deficient leaflets demonstrated increased VIC proliferation and apoptosis, increased expression of disease-related markers such as alpha-smooth muscle actin, alkaline phosphatase, and osteocalcin, and an increase in calcification as evidenced by positive von Kossa staining. Conclusions These results indicate that disruption of the endogenous collagen structure in aortic valves is sufficient to stimulate pathological consequences in valve leaflet cultures, thereby highlighting the importance of collagen and the valve extracellular matrix in general in maintaining homeostasis of the valve phenotype. PMID:24581344
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Giant-cell interstitial pneumonia in a gas station worker.
Lee, S M; Moon, C H; Oh, Y B; Kim, H Y; Ahn, Y; Ko, E J; Joo, J E
1998-10-01
Giant-cell interstitial Pneumonia (GIP) is a very uncommon respiratory disease. The majority of cases of GIP are caused by exposure to cobalt, tungsten and other hard metals. In this report, we describe GIP in a patient who worked in gas station and dealt in propane gas vessels. He presented with clinical features of chronic interstitial lung disease and underwent an open lung biopsy that showed DIP-like reaction with large numbers of intra-alveolar macrophages and numerous large, multinucleated histiocytes which were admixed with the macrophages. Analysis of lung tissue for hard metals was done. Cobalt was the main component of detected hard metals. Corticosteroid therapy was started and he recovered fully.
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Huang, Siyao; Huang, Hsiao-Ying Shadow
2015-10-01
Heart valve leaflet collagen turnover and remodeling are innate to physiological homeostasis; valvular interstitial cells routinely catabolize damaged collagen and affect repair. Moreover, evidence indicates that leaflets can adapt to altered physiological (e.g. pregnancy) and pathological (e.g. hypertension) mechanical load states, tuning collagen structure and composition to changes in pressure and flow. However, while valvular interstitial cell-secreted matrix metalloproteinases are considered the primary effectors of collagen catabolism, the mechanisms by which damaged collagen fibers are selectively degraded remain unclear. Growing evidence suggests that the collagen fiber strain state plays a key role, with the strain-dependent configuration of the collagen molecules either masking or presenting proteolytic sites, thereby protecting or accelerating collagen proteolysis. In this study, the effects of equibiaxial strain state on collagen catabolism were investigated in porcine aortic valve and pulmonary valve tissues. Bacterial collagenase (0.2 and 0.5 mg/mL) was utilized to simulate endogenous matrix metalloproteinases, and biaxial stress relaxation and biochemical collagen concentration served as functional and compositional measures of collagen catabolism, respectively. At a collagenase concentration of 0.5 mg/mL, increasing the equibiaxial strain imposed during stress relaxation (0%, 37.5%, and 50%) yielded significantly lower median collagen concentrations in the aortic valve (p = 0.0231) and pulmonary valve (p = 0.0183), suggesting that relatively large strain magnitudes may enhance collagen catabolism. Collagen concentration decreases were paralleled by trends of accelerated normalized stress relaxation rate with equibiaxial strain in aortic valve tissues. Collectively, these in vitro results indicate that biaxial strain state is capable of affecting the susceptibility of valvular collagens to catabolism, providing a basis for further investigation of
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Ulcerative colitis: ultrastructure of interstitial cells in myenteric plexus.
Rumessen, J J; Vanderwinden, J-M; Horn, T
2010-10-01
Interstitial cells of Cajal (ICC) are key regulatory cells in the gut. In the colon of patients with severe ulcerative colitis (UC), myenteric ICC had myoid ultrastructural features and were in close contact with nerve terminals. In all patients as opposed to controls, some ICC profiles showed degenerative changes, such as lipid droplets and irregular vacuoles. Nerve terminals often appeared swollen and empty. Glial cells, muscle cells, and fibroblast-like cells (FLC) showed no alterations. FLC enclosed macrophages (MLC), which were in close contact with naked axon terminals. The organization and cytological changes may be of pathophysiological significance in patients with UC.
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Sekimoto, Yasuhito; Kato, Motoyasu; Shukuya, Takehiko; Koyama, Ryo; Nagaoka, Tetsutaro; Takahashi, Kazuhisa
2016-04-01
Bevacizumab is a monoclonal antibody targeting the vascular endothelial growth factor receptor and a key drug for advanced non-small cell lung cancer. There are few reports describing bevacizumab-induced chronic interstitial pneumonia. A 62-year-old man with advanced non-small cell lung cancer was admitted to our hospital with dyspnea. He previously received four courses of carboplatin plus paclitaxel with bevacizumab combination therapy and thereafter received four courses of maintenance bevacizumab monotherapy. A chest-computed tomography scan on admission revealed diffuse ground glass opacity. He had not received any other drugs and did not have pneumonia. Thus, he was diagnosed with bevacizumab-induced chronic interstitial pneumonia and was treated with a high dose of corticosteroids. After steroid treatment, his dyspnea and radiological findings improved. This case report is the first description of bevacizumab-induced chronic interstitial pneumonia during maintenance therapy in a patient with non-small cell lung cancer.
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Prediction of oxygen distribution in aortic valve leaflet considering diffusion and convection.
Wang, Ling; Korossis, Sotirios; Fisher, John; Ingham, Eileen; Jin, Zhongmin
2011-07-01
Oxygen supply and transport is an important consideration in the development of tissue engineered constructs. Previous studies from our group have focused on the effect of tissue thickness on the oxygen diffusion within a three-dimensional aortic valve leaflet model, and highlighted the necessity for additional transport mechanisms such as oxygen convection. The aims of this study were to investigate the effect of interstitial fluid flow within the aortic valve leaflet, induced by the cyclic loading of the leaflet, on oxygen transport. Indentation testing and finite element modelings were employed to derive the biphasic properties of the leaflet tissue. The biphasic properties were subsequently used in the computational modeling of oxygen convection in the leaflet, which was based on the effective interstitial fluid velocity and the tissue deformation. Subsequently, the oxygen profile was predicted within the valve leaflet model by solving the diffusion and convection equation simultaneously utilizing the finite difference method. The compression modulus (E) and hydraulic permeability were determined by adapting a finite element model to the experimental indentation test on valvular tissue, E = 0.05MPa, and k =2.0 mm4/Ns. Finite element model of oxygen convection in valvular tissue incorporating the predicted biphasic properties was developed and the interstitial fluid flow rate was calculated falling in range of 0.025-0.25 mm/s depending on the tissue depth. Oxygen distribution within valvular tissue was predicted using one-dimensional oxygen diffusion model taking into consider the interstitial fluid effect. It was found that convection did enhance the oxygen transport in valvular tissue by up to 68% increase in the minimum oxygen tension within the tissue, depending on the strain level of the tissue as reaction of the magnitude and frequencies of the cardiac loading. The effective interstitial fluid velocity was found to play an important role in enhancing the
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Abstract
Procedures for purification of Leydig cells have facilitated studies of their regulatory biology. A multistep procedure, that includes a filtration with nylon mesh (100 micron pore size) to separate interstitial cells from the seminiferous tubules, combining centr... -
Teaching a changing paradigm in physiology: a historical perspective on gut interstitial cells.
Drumm, Bernard T; Baker, Salah A
2017-03-01
The study and teaching of gastrointestinal (GI) physiology necessitates an understanding of the cellular basis of contractile and electrical coupling behaviors in the muscle layers that comprise the gut wall. Our knowledge of the cellular origin of GI motility has drastically changed over the last 100 yr. While the pacing and coordination of GI contraction was once thought to be solely attributable to smooth muscle cells, it is now widely accepted that the motility patterns observed in the GI tract exist as a result of a multicellular system, consisting of not only smooth muscle cells but also enteric neurons and distinct populations of specialized interstitial cells that all work in concert to ensure proper GI functions. In this historical perspective, we focus on the emerging role of interstitial cells in GI motility and examine the key discoveries and experiments that led to a major shift in a paradigm of GI physiology regarding the role of interstitial cells in modulating GI contractile patterns. A review of these now classic experiments and papers will enable students and educators to fully appreciate the complex, multicellular nature of GI muscles as well as impart lessons on how shifting paradigms in physiology are fueled by new technologies that lead to new emerging discoveries. Copyright © 2017 the American Physiological Society.
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Tien, Joe; Truslow, James G; Nelson, Celeste M
2012-01-01
This paper reports the effect of elevated pressure on the invasive phenotype of patterned three-dimensional (3D) aggregates of MDA-MB-231 human breast cancer cells. We found that the directionality of the interstitial pressure profile altered the frequency of invasion by cells located at the surface of an aggregate. In particular, application of pressure at one end of an aggregate suppressed invasion at the opposite end. Experimental alteration of the configuration of cell aggregates and computational modeling of the resulting flow and solute concentration profiles revealed that elevated pressure inhibited invasion by altering the chemical composition of the interstitial fluid near the surface of the aggregate. Our data reveal a link between hydrostatic pressure, interstitial convection, and invasion.
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Narang, Nikhil; Lang, Roberto M; Liarski, Vladimir M; Jeevanandam, Valluvan; Hofmann Bowman, Marion A
2017-01-01
A 55-year-old man with a history of erosive, seropositive rheumatoid arthritis (RA), and interstitial lung disease presented with shortness of breath. Echocardiography showed new-onset severe left ventricular (LV) dysfunction with an ejection fraction (EF) of 15% and moderately increased mean aortic valve gradient of 20 mmHg in a trileaflet aortic valve with severe sclero-calcific degeneration. Coronary angiography revealed no significant obstructive coronary disease. Invasive hemodynamic studies and dobutamine stress echocardiography were consistent with moderate aortic stenosis. Guideline directed medical therapy for heart failure with reduced EF was initiated; however, diuretics and neurohormonal blockade (beta-blocker and angiotensin receptor blocker) provided minimal improvement, and the patient remained functionally limited. Of interest, echocardiography performed 1 year prior to his presentation showed normal LV EF and mild aortic leaflet calcification with moderate stenosis, suggesting a rapid progressing of calcific aortic valve disease. Subsequently, the patient underwent surgical aortic valve replacement and demonstrated excellent postsurgical recovery of LV EF (55%). Calcific aortic valve disease is commonly associated with aging, bicuspid aortic valve, and chronic kidney disease. Pathophysiological mechanism for valvular calcification is incompletely understood but include osteogenic transformation of valvular interstitial cells mediated by local and systemic inflammatory processes. Several rheumatologic diseases including RA are associated with premature atherosclerosis and arterial calcification, and we speculated a similar role of RA accelerating calcific aortic valve disease. We present a case of accelerated aortic valve calcification with (only) moderate stenosis, complicated by a rapid decline in LV systolic performance. Guidelines for AVR in moderate stenosis without concomitant cardiac surgery are not well established, although it should be
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COX2 Inhibition Reduces Aortic Valve Calcification In Vivo
Wirrig, Elaine E.; Gomez, M. Victoria; Hinton, Robert B.; Yutzey, Katherine E.
2016-01-01
Objective Calcific aortic valve disease (CAVD) is a significant cause of morbidity and mortality, which affects approximately 1% of the US population and is characterized by calcific nodule formation and stenosis of the valve. Klotho-deficient mice were used to study the molecular mechanisms of CAVD as they develop robust aortic valve (AoV) calcification. Through microarray analysis of AoV tissues from klotho-deficient and wild type mice, increased expression of the gene encoding cyclooxygenase 2/COX2 (Ptgs2) was found. COX2 activity contributes to bone differentiation and homeostasis, thus the contribution of COX2 activity to AoV calcification was assessed. Approach and Results In klotho-deficient mice, COX2 expression is increased throughout regions of valve calcification and is induced in the valvular interstitial cells (VICs) prior to calcification formation. Similarly, COX2 expression is increased in human diseased AoVs. Treatment of cultured porcine aortic VICs with osteogenic media induces bone marker gene expression and calcification in vitro, which is blocked by inhibition of COX2 activity. In vivo, genetic loss of function of COX2 cyclooxygenase activity partially rescues AoV calcification in klotho-deficient mice. Moreover, pharmacologic inhibition of COX2 activity in klotho-deficient mice via celecoxib-containing diet reduces AoV calcification and blocks osteogenic gene expression. Conclusions COX2 expression is upregulated in CAVD and its activity contributes to osteogenic gene induction and valve calcification in vitro and in vivo. PMID:25722432
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2015-01-01
Hepatocellular carcinoma (HCC) is the most common form of liver cancer (~80%), and it is one of the few cancer types with rising incidence in the United States. This highly invasive cancer is very difficult to detect until its later stages, resulting in limited treatment options and low survival rates. There is a dearth of knowledge regarding the mechanisms associated with the effects of biomechanical forces such as interstitial fluid flow (IFF) on hepatocellular carcinoma invasion. We hypothesized that interstitial fluid flow enhanced hepatocellular carcinoma cell invasion through chemokine-mediated autologous chemotaxis. Utilizing a 3D in vitro invasion assay, we demonstrated that interstitial fluid flow promoted invasion of hepatocellular carcinoma derived cell lines. Furthermore, we showed that autologous chemotaxis influences this interstitial fluid flow-induced invasion of hepatocellular carcinoma derived cell lines via the C-X-C chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12) signaling axis. We also demonstrated that mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling affects interstitial fluid flow-induced invasion; however, this pathway was separate from CXCR4/CXCL12 signaling. This study demonstrates, for the first time, the potential role of interstitial fluid flow in hepatocellular carcinoma invasion. Uncovering the mechanisms that control hepatocellular carcinoma invasion will aid in enhancing current liver cancer therapies and provide better treatment options for patients. PMID:26560447
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Vossler, John D; Min Ju, Young; Williams, J Koudy; Goldstein, Steven; Hamlin, James; Lee, Sang Jin; Yoo, James J; Atala, Anthony
2015-09-03
The long term efficacy of tissue based heart valve grafts may be limited by progressive degeneration characterized by immune mediated inflammation and calcification. To avoid this degeneration, decellularized heart valves with functionalized surfaces capable of rapid in vivo endothelialization have been developed. The aim of this study is to examine the capacity of CD133 antibody-conjugated valve tissue to capture circulating endothelial progenitor cells (EPCs). Decellularized human pulmonary valve tissue was conjugated with CD133 antibody at varying concentrations and exposed to CD133 expressing NTERA-2 cl.D1 (NT2) cells in a microflow chamber. The amount of CD133 antibody conjugated on the valve tissue surface and the number of NT2 cells captured in the presence of shear stress was measured. Both the amount of CD133 antibody conjugated to the valve leaflet surface and the number of adherent NT2 cells increased as the concentration of CD133 antibody present in the surface immobilization procedure increased. The data presented in this study support the hypothesis that the rate of CD133(+) cell adhesion in the presence of shear stress to decellularized heart valve tissue functionalized by CD133 antibody conjugation increases as the quantity of CD133 antibody conjugated to the tissue surface increases.
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Gilloteaux, J
1975-08-27
Studies on the intrinsic innervation of the anterior byssal retractor muscle (ABRM) in Mytilus edulis L. were continued at the ultrastructural level. Electron micrographs show nerve processes ensheathed by glio-interstitial cells running between muscle fibers. The glio-interstitial cells may represent all the types of osmiophilic cells previously described by the light microscopic ZIO technique in the anterior byssal retractor muscle.
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Henry, M; Porcher, C; Julé, Y
1998-06-10
The aim of the present study was to describe the deep muscular plexus of the pig duodenum and to characterize its cellular components. Numerous nerve varicosities have been detected in the deep muscular plexus using anti-synaptophysin antibodies. Nerve fibres were also detected here in the outer circular muscle layer, whereas no nerve fibres were observed in the inner circular muscle layer. In the deep muscular plexus, nerve fibres projected to interstitial cells which were characterized at the ultrastructural level. The interstitial cells were of two kinds: the interstitial fibroblastic-like cells (FLC) and the interstitial dense cells (IDC), both of which were interposed between nerve fibres and smooth muscle cells. The FLC were characterized by their elongated bipolar shape, the lack of basal lamina, a well-developed endoplasmic reticulum, a Golgi apparatus, and intermediate filaments. They were closely apposed to axon terminals containing small clear synaptic vesicles and/or dense-cored vesicles. They were frequently connected to each other and to smooth muscle cells of the inner and outer circular layer by desmosomes and more rarely by gap junctions. The IDC are myoid-like cells. They had a stellate appearance and were characterized by a dense cell body, numerous caveolae, and a discontinuous basal lamina. The IDC were always closely apposed to nerve fibres and were connected to smooth muscle cells by desmosomes and small gap junctions. The present results show the unique pattern of cellular organization of the deep muscular plexus of the pig small intestine. They suggest that the interstitial cells in the deep muscular plexus are involved in the integration and transmission of nervous inputs from myenteric neurons to the inner and outer circular muscle layers. The clear-cut distinction observed here between the two types of interstitial cells (fibroblastic and myoid-like) suggests that the interstitial cells of each type may also be involved in some other
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Calcium responses in subserosal interstitial cells of the guinea-pig proximal colon.
Tamada, H; Hashitani, H
2014-01-01
In the subserosal layer between the longitudinal muscle layer and mesothelium, heterogeneous populations of interstitial cells are distributed. As the distribution of nerve elements in this layer is sparse as compared with the nerve plexus layer or tunica muscularis, there may be unique communication among subserosal interstitial cells (SSICs). This study aimed to explore functional properties of SSICs. In subserosal preparations of the guinea-pig proximal colon, changes in intracellular Ca(2+) ([Ca(2+) ]i ) were visualized using Fluo-4 Ca(2+) imaging. Immunohistochemistry was also performed to identify the SSICs exhibiting Ca(2+) transients. A majority of SSICs responded to adenosine triphosphate (ATP, 10 μM) by increasing [Ca(2+) ]i , but remained quiescent during the application of acetylcholine (10 μM). ATP-induced Ca(2+) responses were mimicked by adenosine 5'-diphosphate (10 μM), MRS2365 (10 nM) but not α, β-methylene ATP (10 μM) or uridine triphosphate (10 μM), and could be reproduced in Ca(2+) -free solution, suggesting that ATP acts via P2Y receptors, most likely P2Y1 subtype, but not P2X receptors. Live staining of the same preparations after Ca(2+) imaging indicated the ATP-sensitive SSICs were not positive for c-Kit antibody, a specific marker for gastrointestinal interstitial cells of Cajal (ICC). Immunohistochemistry identified vimentin (mesenchymal cell marker)+/Kit- and SK3 (fibroblast-like cell (FLC) marker)+/Kit- cells that had a similar morphology to the ATP-sensitive SSICs in Ca(2+) imaging. A majority of the SSICs in the guinea-pig proximal colon, presumably FLC, are capable of responding to ATP and thus may contribute to smooth muscle relaxation upon stimulation with ATP released from non-neuronal cells. © 2013 John Wiley & Sons Ltd.
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Epimorphin expression in interstitial pneumonia
Terasaki, Yasuhiro; Fukuda, Yuh; Suga, Moritaka; Ikeguchi, Naoki; Takeya, Motohiro
2005-01-01
Epimorphin modulates epithelial morphogenesis in embryonic mouse organs. We previously suggested that epimorphin contributes to repair of bleomycin-induced pulmonary fibrosis in mice via epithelium-mesenchyme interactions. To clarify the role of epimorphin in human lungs, we evaluated epimorphin expression and localization in normal lungs, lungs with nonspecific interstitial pneumonia (NSIP), and lungs with usual interstitial pneumonia (UIP); we also studied the effect of recombinant epimorphin on cultured human alveolar epithelial cells in vitro. Northern and Western blotting analyses revealed that epimorphin expression in NSIP samples were significantly higher than those in control lungs and lungs with UIP. Immunohistochemistry showed strong epimorphin expression in mesenchymal cells of early fibrotic lesions and localization of epimorphin protein on mesenchymal cells and extracellular matrix of early fibrotic lesions in the nonspecific interstitial pneumonia group. Double-labeled fluorescent images revealed expression of matrix metalloproteinase 2 in re-epithelialized cells overlying epimorphin-positive early fibrotic lesions. Immunohistochemistry and metalloproteinase activity assay demonstrated augmented expression of metalloproteinase induced by recombinant epimorphin in human alveolar epithelial cells. These findings suggest that epimorphin contributes to repair of pulmonary fibrosis in nonspecific interstitial pneumonia, perhaps partly by inducing expression of matrix metalloproteinase 2, which is an important proteolytic factor in lung remodeling. PMID:15651999
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Pfeil, Uwe; Bharathala, Subhashini; Murtaza, Ghulam; Mermer, Petra; Papadakis, Tamara; Boening, Andreas; Kummer, Wolfgang
2016-12-01
Heart valves are highly organized structures determining the direction of blood flow through the heart. Smooth muscle cells within the valve are thought to play an active role during the heart cycle, rather than being just passive flaps. The mature heart valve is composed of extracellular matrix (ECM), various differentiations of valvular interstitial cells (VIC), smooth muscle cells and overlying endothelium. VIC are important for maintaining the structural integrity of the valve, thereby affecting valve function and ECM remodelling. Accumulating evidence suggests an important role of calcitonin receptor-like receptor (CRL) signalling in preventing heart damage under several pathological conditions. Thus we investigate the existence of a putative CRL signalling system in mouse and human heart valves by real-time RT-PCR, laser-assisted microdissection, immunofluorescence and NADPH-diaphorase histochemistry. Mouse and human heart valves expressed mRNAs for the CRL ligands adrenomedullin (AM), adrenomedullin-2 (AM-2) and calcitonin gene-related peptide (CGRP) and for their receptor components, i.e., CRL and receptor-activity-modifying proteins 1-3. Immunofluorescence analysis revealed AM-, AM-2- and CRL-immunolabelling in endothelial cells and VIC, whereas CGRP immunoreactivity was restricted to nerve fibres and some endothelial cells. Nitric oxide synthase activity, as demonstrated by NADPH-diaphorase histochemistry, was shown mainly in valvular endothelial cells in mice, whereas in human aortic valves, VIC and smooth muscle cells were positive. Our results showed the presence of an intrinsic AM/AM-2/CGRP signalling system in murine and human heart valves with distinct cellular localization, suggesting its involvement in the regulation of valve stiffness and ECM production and turnover.
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Munjal, Charu; Opoka, Amy M.; Osinska, Hanna; James, Jeanne F.; Bressan, Giorgio M.; Hinton, Robert B.
2014-01-01
Aortic valve disease (AVD) is characterized by elastic fiber fragmentation (EFF), fibrosis and aberrant angiogenesis. Emilin1 is an elastin-binding glycoprotein that regulates elastogenesis and inhibits TGF-β signaling, but the role of Emilin1 in valve tissue is unknown. We tested the hypothesis that Emilin1 deficiency results in AVD, mediated by non-canonical (MAPK/phosphorylated Erk1 and Erk2) TGF-β dysregulation. Using histology, immunohistochemistry, electron microscopy, quantitative gene expression analysis, immunoblotting and echocardiography, we examined the effects of Emilin1 deficiency (Emilin1−/−) in mouse aortic valve tissue. Emilin1 deficiency results in early postnatal cell-matrix defects in aortic valve tissue, including EFF, that progress to latent AVD and premature death. The Emilin1−/− aortic valve displays early aberrant provisional angiogenesis and late neovascularization. In addition, Emilin1−/− aortic valves are characterized by early valve interstitial cell activation and proliferation and late myofibroblast-like cell activation and fibrosis. Interestingly, canonical TGF-β signaling (phosphorylated Smad2 and Smad3) is upregulated constitutively from birth to senescence, whereas non-canonical TGF-β signaling (phosphorylated Erk1 and Erk2) progressively increases over time. Emilin1 deficiency recapitulates human fibrotic AVD, and advanced disease is mediated by non-canonical (MAPK/phosphorylated Erk1 and Erk2) TGF-β activation. The early manifestation of EFF and aberrant angiogenesis suggests that these processes are crucial intermediate factors involved in disease progression and therefore might provide new therapeutic targets for human AVD. PMID:25056700
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Living nano-micro fibrous woven fabric/hydrogel composite scaffolds for heart valve engineering.
Wu, Shaohua; Duan, Bin; Qin, Xiaohong; Butcher, Jonathan T
2017-03-15
Regeneration and repair of injured or diseased heart valves remains a clinical challenge. Tissue engineering provides a promising treatment approach to facilitate living heart valve repair and regeneration. Three-dimensional (3D) biomimetic scaffolds that possess heterogeneous and anisotropic features that approximate those of native heart valve tissue are beneficial to the successful in vitro development of tissue engineered heart valves (TEHV). Here we report the development and characterization of a novel composite scaffold consisting of nano- and micro-scale fibrous woven fabrics and 3D hydrogels by using textile techniques combined with bioactive hydrogel formation. Embedded nano-micro fibrous scaffolds within hydrogel enhanced mechanical strength and physical structural anisotropy of the composite scaffold (similar to native aortic valve leaflets) and also reduced its compaction. We determined that the composite scaffolds supported the growth of human aortic valve interstitial cells (HAVIC), balanced the remodeling of heart valve ECM against shrinkage, and maintained better physiological fibroblastic phenotype in both normal and diseased HAVIC over single materials. These fabricated composite scaffolds enable the engineering of a living heart valve graft with improved anisotropic structure and tissue biomechanics important for maintaining valve cell phenotypes. Heart valve-related disease is an important clinical problem, with over 300,000 surgical repairs performed annually. Tissue engineering offers a promising strategy for heart valve repair and regeneration. In this study, we developed and tissue engineered living nano-micro fibrous woven fabric/hydrogel composite scaffolds by using textile technique combined with bioactive hydrogel formation. The novelty of our technique is that the composite scaffolds can mimic physical structure anisotropy and the mechanical strength of natural aortic valve leaflet. Moreover, the composite scaffolds prevented the
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Sickle cell anemia and mitral valve replacement. Case report.
Bomfim, V; Ribeiro, A; Gouvea, F; Pereira, J; Björk, V
1989-01-01
An 8-year-old black boy with sickle cell disease and severe hemolytic anemia crisis (95% hemoglobin S) also had mitral incompetence due to rheumatic valve disease. A 27 mm monostrut Björk-Shiley valve prosthesis was implanted after partial exchange transfusions had reduced the hemoglobin S to less than 40%. High-flow normothermic perfusion was used during extracorporeal circulation, with care taken to avoid hypoxia and acidosis. Postoperative recovery was uneventful.
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Canisso, I F; Coffee, L L; Ortved, K; Fubini, S L; Monteagudo, L V; Schlafer, D H; Gilbert, R O
2014-12-01
An 8-year-old, mixed breed, polled goat was presented for evaluation of male-like behaviour. Clinical findings included clitoromegaly, a heavily muscled neck, pronounced beard, and erect dorsal guard hairs, which are phenotypic characteristics commonly observed in intersex animals. Transrectal ultrasonography revealed the presence of two abdominal masses caudolateral to the uterine horns. Serum concentration of estradiol was elevated. Genetic evaluation was compatible with polled intersex syndrome defined by an XX karyotype without a Y chromosome or SRY gene. Based on gross and histologic evaluation, the abdominal masses were determined to be intra-abdominal testes, each of which was effaced by Sertoli cell and interstitial (Leydig) cell tumours. The Sertoli cell tumours (SCTs) represented two unique histologic patterns. Regardless of pattern, neoplastic Sertoli cells were consistently lipid laden and positive for vimentin. Interstitial cell tumours (ICTs) were negative for vimentin. Clinical and histopathologic findings suggest that prolonged exposure to steroids secreted by neoplastic Sertoli cells contributed to virilization. In addition, results from immunohistochemistry indicated that vimentin may be a valuable immunodiagnostic tool for differentiation between interstitial and Sertoli cell tumours in goats. © 2014 Blackwell Verlag GmbH.
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Gaylo, Alison; Schrock, Dillon C; Fernandes, Ninoshka R J; Fowell, Deborah J
2016-01-01
Effector T cells exit the inflamed vasculature into an environment shaped by tissue-specific structural configurations and inflammation-imposed extrinsic modifications. Once within interstitial spaces of non-lymphoid tissues, T cells migrate in an apparent random, non-directional, fashion. Efficient T cell scanning of the tissue environment is essential for successful location of infected target cells or encounter with antigen-presenting cells that activate the T cell's antimicrobial effector functions. The mechanisms of interstitial T cell motility and the environmental cues that may promote or hinder efficient tissue scanning are poorly understood. The extracellular matrix (ECM) appears to play an important scaffolding role in guidance of T cell migration and likely provides a platform for the display of chemotactic factors that may help to direct the positioning of T cells. Here, we discuss how intravital imaging has provided insight into the motility patterns and cellular machinery that facilitates T cell interstitial migration and the critical environmental factors that may optimize the efficiency of effector T cell scanning of the inflamed tissue. Specifically, we highlight the local micro-positioning cues T cells encounter as they migrate within inflamed tissues, from surrounding ECM and signaling molecules, as well as a requirement for appropriate long-range macro-positioning within distinct tissue compartments or at discrete foci of infection or tissue damage. The central nervous system (CNS) responds to injury and infection by extensively remodeling the ECM and with the de novo generation of a fibroblastic reticular network that likely influences T cell motility. We examine how inflammation-induced changes to the CNS landscape may regulate T cell tissue exploration and modulate function.
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Gaylo, Alison; Schrock, Dillon C.; Fernandes, Ninoshka R. J.; Fowell, Deborah J.
2016-01-01
Effector T cells exit the inflamed vasculature into an environment shaped by tissue-specific structural configurations and inflammation-imposed extrinsic modifications. Once within interstitial spaces of non-lymphoid tissues, T cells migrate in an apparent random, non-directional, fashion. Efficient T cell scanning of the tissue environment is essential for successful location of infected target cells or encounter with antigen-presenting cells that activate the T cell’s antimicrobial effector functions. The mechanisms of interstitial T cell motility and the environmental cues that may promote or hinder efficient tissue scanning are poorly understood. The extracellular matrix (ECM) appears to play an important scaffolding role in guidance of T cell migration and likely provides a platform for the display of chemotactic factors that may help to direct the positioning of T cells. Here, we discuss how intravital imaging has provided insight into the motility patterns and cellular machinery that facilitates T cell interstitial migration and the critical environmental factors that may optimize the efficiency of effector T cell scanning of the inflamed tissue. Specifically, we highlight the local micro-positioning cues T cells encounter as they migrate within inflamed tissues, from surrounding ECM and signaling molecules, as well as a requirement for appropriate long-range macro-positioning within distinct tissue compartments or at discrete foci of infection or tissue damage. The central nervous system (CNS) responds to injury and infection by extensively remodeling the ECM and with the de novo generation of a fibroblastic reticular network that likely influences T cell motility. We examine how inflammation-induced changes to the CNS landscape may regulate T cell tissue exploration and modulate function. PMID:27790220
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Yin, Dan-Dan; Luo, Jun-Hui; Zhao, Zhu-Ye; Liao, Ying-Jun; Li, Ying
2018-05-01
Renal interstitial fibrosis is a final pathway that is observed in various types of kidney diseases, including diabetic kidney disease (DKD). The present study investigated the effect of tranilast on renal interstitial fibrosis and the association between its role and mast cell infiltration in a rat model of DKD. A total of 30 healthy 6‑week‑old male Sprague‑Dawley rats were randomly divided into the following four groups: Normal control group; DKD model group; low‑dose tranilast group (200 mg/kg/day); and high‑dose tranilast group (400 mg/kg/day). The morphological alterations of tubulointerstitial fibrosis were evaluated by Masson's trichrome staining, while mast cell infiltration into the renal tubular interstitium was measured by toluidine blue staining and complement C3a receptor 1 (C3aR) immunohistochemical staining (IHC). The expression of fibronectin (FN), collagen I (Col‑I), stem cell factor (SCF) and proto‑oncogene c‑kit (c‑kit) was detected by IHC, western blotting and reverse transcription‑quantitative‑polymerase chain reaction. The results demonstrated that tubulointerstitial fibrosis and mast cell infiltration were observed in DKD model rats, and this was improved dose‑dependently in the tranilast treatment groups. The expression of FN, Col‑I, SCF and c‑kit mRNA and protein was upregulated in the tubulointerstitium of DKD model rats compared with the normal control rats, and tranilast inhibited the upregulated expression of these markers. Furthermore, the degree of SCF and c‑kit expression demonstrated a significant positive correlation with C3aR‑positive mast cells and the markers of renal interstitial fibrosis. The results of the present study indicate that mast cell infiltration may promote renal interstitial fibrosis via the SCF/c‑kit signaling pathway. Tranilast may prevent renal interstitial fibrosis through inhibition of mast cell infiltration mediated through the SCF/c-kit signaling pathway.
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Levay, Agata K; Peacock, Jacqueline D; Lu, Yinhui; Koch, Manuel; Hinton, Robert B; Kadler, Karl E; Lincoln, Joy
2008-10-24
Heart valve structures, derived from mesenchyme precursor cells, are composed of differentiated cell types and extracellular matrix arranged to facilitate valve function. Scleraxis (scx) is a transcription factor required for tendon cell differentiation and matrix organization. This study identified high levels of scx expression in remodeling heart valve structures at embryonic day 15.5 through postnatal stages using scx-GFP reporter mice and determined the in vivo function using mice null for scx. Scx(-/-) mice display significantly thickened heart valve structures from embryonic day 17.5, and valves from mutant mice show alterations in valve precursor cell differentiation and matrix organization. This is indicated by decreased expression of the tendon-related collagen type XIV, increased expression of cartilage-associated genes including sox9, as well as persistent expression of mesenchyme cell markers including msx1 and snai1. In addition, ultrastructure analysis reveals disarray of extracellular matrix and collagen fiber organization within the valve leaflet. Thickened valve structures and increased expression of matrix remodeling genes characteristic of human heart valve disease are observed in juvenile scx(-/-) mice. In addition, excessive collagen deposition in annular structures within the atrioventricular junction is observed. Collectively, our studies have identified an in vivo requirement for scx during valvulogenesis and demonstrate its role in cell lineage differentiation and matrix distribution in remodeling valve structures.
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Patel, Vishal; Carrion, Katrina; Hollands, Andrew; Hinton, Andrew; Gallegos, Thomas; Dyo, Jeffrey; Sasik, Roman; Leire, Emma; Hardiman, Gary; Mohamed, Salah A.; Nigam, Sanjay; King, Charles C.; Nizet, Victor; Nigam, Vishal
2015-01-01
Bicuspid aortic valves calcify at a significantly higher rate than normal aortic valves, a process that involves increased inflammation. Because we have previously found that bicuspid aortic valve experience greater stretch, we investigated the potential connection between stretch and inflammation in human aortic valve interstitial cells (AVICs). Microarray, quantitative PCR (qPCR), and protein assays performed on AVICs exposed to cyclic stretch showed that stretch was sufficient to increase expression of interleukin and metalloproteinase family members by more than 1.5-fold. Conditioned medium from stretched AVICs was sufficient to activate leukocytes. microRNA sequencing and qPCR experiments demonstrated that miR-148a-3p was repressed in both stretched AVICs (43% repression) and, as a clinical correlate, human bicuspid aortic valves (63% reduction). miR-148a-3p was found to be a novel repressor of IKBKB based on data from qPCR, luciferase, and Western blot experiments. Furthermore, increasing miR-148a-3p levels in AVICs was sufficient to decrease NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling and NF-κB target gene expression. Our data demonstrate that stretch-mediated activation of inflammatory pathways is at least partly the result of stretch-repression of miR-148a-3p and a consequent failure to repress IKBKB. To our knowledge, we are the first to report that cyclic stretch of human AVICs activates inflammatory genes in a tissue-autonomous manner via a microRNA that regulates a central inflammatory pathway.—Patel, V., Carrion, K., Hollands, A., Hinton, A., Gallegos, T., Dyo, J., Sasik, R., Leire, E., Hardiman, G., Mohamed, S. A., Nigam, S., King, C. C., Nizet, V., Nigam V. The stretch responsive microRNA miR-148a-3p is a novel repressor of IKBKB, NF-κB signaling, and inflammatory gene expression in human aortic valve cells. PMID:25630970
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Tamada, Hiromi; Kiyama, Hiroshi
2015-01-01
Interstitial cells of Cajal (ICC) are mesenchymal cells that are distributed along the gastrointestinal tract and function as pacemaker cells or intermediary cells between nerves and smooth muscle cells. ICC express a receptor tyrosine kinase c-Kit, which is an established marker for ICC. The c-kit gene is allelic with the murine white-spotting locus (W), and some ICC subsets were reported to be missing in heterozygous mutant W/Wv mice carrying W and Wv mutated alleles. In this study, the characterization of interstitial cells in the subserosal layer of W/Wv mice was analyzed by immunohistochemistry and electron microscopy. In the proximal and distal colon of W/Wv mutant mice, no c-Kit-positive cells were detected in the subserosal layer by immunohistochemistry. By electron microscopy, the interstitial cells, which were characterized by the existence of caveolae, abundant mitochondria and gap junctions, were observed in the W/Wv mutant colon. The morphological characteristics were comparable to those of the multipolar c-Kit positive ICC seen in the subserosa of proximal and distal colon of wild-type mice. Fibroblasts were also located in the same layers, but the morphology of the fibroblasts was distinguishable from that of ICC in wild type mice or of ICC-like cells in W/Wv mutant mice. Collectively, it is concluded that c-Kit-negative interstitial cells showing a typical ICC ultrastructure exist in the proximal and distal colon of W/Wv mutant mice. PMID:26727725
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Tamada, Hiromi; Kiyama, Hiroshi
2015-01-01
Interstitial cells of Cajal (ICC) are mesenchymal cells that are distributed along the gastrointestinal tract and function as pacemaker cells or intermediary cells between nerves and smooth muscle cells. ICC express a receptor tyrosine kinase c-Kit, which is an established marker for ICC. The c-kit gene is allelic with the murine white-spotting locus (W), and some ICC subsets were reported to be missing in heterozygous mutant W/Wv mice carrying W and Wv mutated alleles. In this study, the characterization of interstitial cells in the subserosal layer of W/Wv mice was analyzed by immunohistochemistry and electron microscopy. In the proximal and distal colon of W/Wv mutant mice, no c-Kit-positive cells were detected in the subserosal layer by immunohistochemistry. By electron microscopy, the interstitial cells, which were characterized by the existence of caveolae, abundant mitochondria and gap junctions, were observed in the W/Wv mutant colon.The morphological characteristics were comparable to those of the multipolar c-Kit positive ICC seen in the subserosa of proximal and distal colon of wild-type mice. Fibroblasts were also located in the same layers,but the morphology of the fibroblasts was distinguishable from that of ICC in wild type mice or of ICC-like cells in W/Wv mutant mice. Collectively, it is concluded that c-Kit-negative interstitial cells showing a typical ICC ultrastructure exist in the proximal and distal colon of W/Wv mutant mice.
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Tamaki, Tetsuro; Akatsuka, Akira; Ando, Kiyoshi; Nakamura, Yoshihiko; Matsuzawa, Hideyuki; Hotta, Tomomitsu; Roy, Roland R; Edgerton, V Reggie
2002-05-13
Putative myogenic and endothelial (myo-endothelial) cell progenitors were identified in the interstitial spaces of murine skeletal muscle by immunohistochemistry and immunoelectron microscopy using CD34 antigen. Enzymatically isolated cells were characterized by fluorescence-activated cell sorting on the basis of cell surface antigen expression, and were sorted as a CD34+ and CD45- fraction. Cells in this fraction were approximately 94% positive for Sca-1, and mostly negative (<3% positive) for CD14, 31, 49, 144, c-kit, and FLK-1. The CD34+/45- cells formed colonies in clonal cell cultures and colony-forming units displayed the potential to differentiate into adipocytes, endothelial, and myogenic cells. The CD34+/45- cells fully differentiated into vascular endothelial cells and skeletal muscle fibers in vivo after transplantation. Immediately after sorting, CD34+/45- cells expressed only c-met mRNA, and did not express any other myogenic cell-related markers such as MyoD, myf-5, myf-6, myogenin, M-cadherin, Pax-3, and Pax-7. However, after 3 d of culture, these cells expressed mRNA for all myogenic markers. CD34+/45- cells were distinct from satellite cells, as they expressed Bcrp1/ABCG2 gene mRNA (Zhou et al., 2001). These findings suggest that myo-endothelial progenitors reside in the interstitial spaces of mammalian skeletal muscles, and that they can potentially contribute to postnatal skeletal muscle growth.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Quake, Stephen R; Marcus, Joshua S; Hansen, Carl L
2015-01-13
Sieve valves for use in microfluidic device are provided. The valves are useful for impeding the flow of particles, such as chromatography beads or cells, in a microfluidic channel while allowing liquid solution to pass through the valve. The valves find particular use in making microfluidic chromatography modules.
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Yin, Zhongcheng; Zhou, Xudong; Li, Xiaoju; Xiao, Aiguo
2013-01-01
Interstitial fibrosis is regarded as the main pathway for the progression of chronic kidney disease (CKD) and is often associated with severe renal dysfunction. Stem cell-based therapies may provide alternative approaches for the treatment of CKD. Human amniotic fluid-derived stem cells (hAFSCs) are a novel stem cell population, which exhibit both embryonic and mesenchymal stem cell characteristics. Herein, the present study investigated whether the transplantation of hAFSCs into renal tissues could improve renal interstitial fibrosis in a murine model of unilateral ureteral obstruction (UUO). We showed that hAFSCs provided a protective effect and alleviated interstitial fibrosis as reflected by an increase in microvascular density; additionally, hAFSCs treatment beneficially modulated protein levels of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α (HIF-1α) and transforming growth factor-β1 (TGF-β1). Therefore, we hypothesize that hAFSCs could represent an alternative, readily available source of stem cells that can be applied for the treatment of renal interstitial fibrosis. PMID:23724119
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Tamada, Hiromi; Kiyama, Hiroshi
2015-01-01
Interstitial cells of Cajal (ICC) are mesenchymal cells that are distributed along the gastrointestinal tract and function as pacemaker cells or intermediary cells between nerves and smooth muscle cells. ICC express a receptor tyrosine kinase c-Kit, which is an established marker for ICC. The c-kit gene is allelic with the murine white-spotting locus (W), and some ICC subsets were reported to be missing in heterozygous mutant W/W(v) mice carrying W and W(v) mutated alleles. In this study, the characterization of interstitial cells in the subserosal layer of W/W(v) mice was analyzed by immunohistochemistry and electron microscopy. In the proximal and distal colon of W/W(v) mutant mice, no c-Kit-positive cells were detected in the subserosal layer by immunohistochemistry. By electron microscopy, the interstitial cells, which were characterized by the existence of caveolae, abundant mitochondria and gap junctions, were observed in the W/W(v) mutant colon. The morphological characteristics were comparable to those of the multipolar c-Kit positive ICC seen in the subserosa of proximal and distal colon of wild-type mice. Fibroblasts were also located in the same layers, but the morphology of the fibroblasts was distinguishable from that of ICC in wild type mice or of ICC-like cells in W/W(v) mutant mice. Collectively, it is concluded that c-Kit-negative interstitial cells showing a typical ICC ultrastructure exist in the proximal and distal colon of W/W(v) mutant mice.
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Interstitial inflammation in Alport syndrome.
Jedlicka, Jan; Soleiman, Afschin; Draganovici, Dan; Mandelbaum, Jana; Ziegler, Urs; Regele, Heinz; Wüthrich, Rudolf P; Gross, Oliver; Anders, Hans-Joachim; Segerer, Stephan
2010-04-01
The Alport syndrome is a hereditary glomerular disease linked to structural abnormalities of collagen IV. In a mouse model of Alport syndrome, the interstitial lymphocyte influx was important for disease progression. CXCR3 is a chemokine receptor involved in lymphocyte recruitment to the kidney. We hypothesized that CXCR3-positive T cells might be involved in human Alport syndrome. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded biopsies from 17 patients with Alport syndrome, 10 with immunoglobulin A (IgA) nephropathy, and 11 healthy donor kidneys. We investigated the expression of the alpha5 chain of collagen IV to confirm the morphologic diagnosis, the chemokine receptor CXCR3 and CD3-positive T cells. Alport syndrome biopsies demonstrated a complete loss of the alpha5 chain of collagen IV from the glomerular basement membrane and the morphologic features consistent with Alport syndrome on electron microscopy. A prominent number of CXCR3-positive cells were found in the tubulointerstitium. Most of the CXCR3-positive cells were CD3-positive T cells, demonstrated by double-labeling in selected biopsies. The number of CXCR3-positive cells in kidneys with Alport syndrome correlated with serum creatinine (P < .05) and with morphologic features of a progressive disease (eg, interstitial fibrosis, glomerulosclerosis, and tubular atrophy). The severity of interstitial CXCR3-positive cell influx was similar in Alport syndrome as compared to immunoglobulin A nephropathy. The noninflammatory glomerular lesion of Alport syndrome is associated with prominent interstitial accumulation of CD3- and CXCR3-positive lymphocytes. The degree of infiltration correlated with renal function. We speculate that targeting T lymphocytes, for example, by CXCR3 blocking agents, might be a novel approach to inhibit disease progression in patients with Alport syndrome. Copyright 2010 Elsevier Inc.
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Schmidt, Dörthe; Achermann, Josef; Odermatt, Bernhard; Breymann, Christian; Mol, Anita; Genoni, Michele; Zund, Gregor; Hoerstrup, Simon P
2007-09-11
A novel concept providing prenatally tissue engineered human autologous heart valves based on routinely obtained fetal amniotic fluid progenitors as single cell source is introduced. Fetal human amniotic progenitors were isolated from routinely sampled amniotic fluid and sorted using CD133 magnetic beads. After expansion and differentiation, cell phenotypes of CD133- and CD133+ cells were analyzed by immunohistochemistry and flowcytometry. After characterization, CD133- derived cells were seeded onto heart valve leaflet scaffolds (n=18) fabricated from rapidly biodegradable polymers, conditioned in a pulse duplicator system, and subsequently coated with CD133+ derived cells. After in vitro maturation, opening and closing behavior of leaflets was investigated. Neo-tissues were analyzed by histology, immunohistochemistry, and scanning electron microscopy (SEM). Extracellular matrix (ECM) elements and cell numbers were quantified biochemically. Mechanical properties were assessed by tensile testing. CD133- derived cells demonstrated characteristics of mesenchymal progenitors expressing CD44 and CD105. Differentiated CD133+ cells showed features of functional endothelial cells by eNOS and CD141 expression. Engineered heart valve leaflets demonstrated endothelialized tissue formation with production of ECM elements (GAG 80%, HYP 5%, cell number 100% of native values). SEM showed intact endothelial surfaces. Opening and closing behavior was sufficient under half of systemic conditions. The use of amniotic fluid as single cell source is a promising low-risk approach enabling the prenatal fabrication of heart valves ready to use at birth. These living replacements with the potential of growth, remodeling, and regeneration may realize the early repair of congenital malformations.
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Smoking-related interstitial lung diseases.
Caminati, A; Graziano, P; Sverzellati, N; Harari, S
2010-12-01
In pulmonary pathology, a wide spectrum of morphological changes is related to the consequences of smoking, and recognizing them on surgical specimens and on small transbronchial biopsies represents a challenge for the pathologist. Respiratory bronchiolitis, also referred to as smoker's bronchiolitis, is a common histologic feature found in the lung tissue of cigarette smokers. When identified as the sole histopathologic finding in the clinical setting of symptomatic interstitial lung disease, a diagnosis of respiratory bronchiolitis-interstitial lung disease is made. Since smoking is recognized to cause a variety of histologic patterns encompassing respiratory bronchiolitis, respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia and pulmonary Langerhans cell hystiocytosis, smoking-related interstitial lung disease may be a useful concept to keep in mind for the pathologists. The relationship of smoking with each of these entities has been largely established on the basis of epidemiologic evidence. Although they have been retained as distinct and separate conditions in various classifications of interstitial lung diseases, these entities share a number of clinical, radiologic, and pathologic features suggesting that they represent a spectrum of patterns of interstitial lung disease occurring in predisposed individuals who smoke. Evaluation of histologic features, particularly in surgical lung biopsy samples, is important in making the distinction between these disorders. However, even after tissue biopsy, it may sometimes be difficult to clearly separate these entities. Recently, respiratory bronchiolitis-interstitial lung disease with fibrosis has been described and postulated that this is a smoking-related condition distinct from fibrotic non-specific interstitial pneumonia.
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Hyperandrogenism from an ovarian interstitial-cell tumor in an alpaca.
Gilbert, Rosanne; Kutzler, Michelle; Valentine, Beth A; Semevolos, Stacy
2006-11-01
An 8-year-old intact female Huacaya alpaca (Lama pacos) was presented for recent development of male behavior. Serum testosterone concentration was determined to be 969.1 pg/ml by using radioimmunoassay, while the range in 33 healthy female adult intact alpacas was 11.7-62.1 pg/ml. An ovarian mass was suspected, and an exploratory laparotomy was performed. A tan mass was present on the left ovary. Histologically, the mass was composed of closely packed, plump, polygonal cells with central round nuclei with granular chromatin and abundant eosinophilic finely granular to vesiculate cytoplasm. An ovarian benign interstitial (Leydig) cell tumor was diagnosed.
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Interstitial cells of Cajal in chagasic megaesophagus.
de Lima, Marcus Aurelho; Cabrine-Santos, Marlene; Tavares, Marcelo Garcia; Gerolin, Gustavo Pacheco; Lages-Silva, Eliane; Ramirez, Luis Eduardo
2008-08-01
Chagasic visceromegalies are the most important digestive manifestations of Chagas disease and are characterized by motor disorders and dilation of organs such as esophagus and colon. One of the theories raised to explain the physiopathogenesis of chagasic megas is the plexus theory. Recent studies have shown a reduction of interstitial cells of Cajal (ICCs) in the colon of chagasic patients. These cells are present throughout the gastrointestinal tract and are considered to be pacemaker cells, that is, they are responsible for coordinating peristalsis and for mediating nerve impulses. In view of the lack of studies on these cells in megaesophagus and the previous observation of a reduction of ICCs in chagasic megacolons, we compared the distribution of ICCs in the esophagus of chagasic and nonchagasic patients to contribute to a better understanding of the physiopathogenesis of this esophageal disease. Esophageal biopsy samples from 10 chagasic and 5 nonchagasic patients were used. Cells were identified with the anti-CD117 antibody. The number of ICCs was quantified in longitudinal and circular muscle layers and myenteric plexus. The results were analyzed statistically by comparison of means. An intense reduction in the number of ICCs was observed in muscle layers and in the myenteric plexus of patients with megaesophagus. We conclude that there is an intense reduction of ICCs in the esophagus of chagasic patients when compared to nonchagasic patients, a finding supporting the important role of these cells in gastrointestinal tract motility. A deficiency in these cells might be implied in the genesis of megaesophagus.
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Jana, Soumen; Lerman, Amir
2015-12-01
Heart valve tissue engineering could be a possible solution for the limitations of mechanical and biological prostheses, which are commonly used for heart valve replacement. In tissue engineering, cells are seeded into a 3-dimensional platform, termed the scaffold, to make the engineered tissue construct. However, mimicking the mechanical and spatial heterogeneity of a heart valve structure in a fabricated scaffold with uniform cell distribution is daunting when approached conventionally. Bioprinting is an emerging technique that can produce biological products containing matrix and cells, together or separately with morphological, structural and mechanical diversity. This advance increases the possibility of fabricating the structure of a heart valve in vitro and using it as a functional tissue construct for implantation. This review describes the use of bioprinting technology in heart valve tissue engineering. Copyright © 2015 Elsevier Inc. All rights reserved.
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A significant negative correlation between testicular interstitial cell tumors and pituitary tumors in control male F344 rats has been reported associated with the number of animals per cage. Change in numbers of animals per cage may cause stress and increased serum corticosteroi...
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Geng, Jie-jie; Zhang, Kui; Chen, Li-na; Miao, Jin-lin; Yao, Meng; Ren, Ying; Fu, Zhi-guang; Chen, Zhi-nan; Zhu, Ping
2014-09-01
Lung interstitial fibrosis is a chronic lung disease, and few effective therapies are available to halt or reverse the progression of the disease. In murine and human lung fibrosis, the expression of CD147 is increased. However, the role of CD147 in lung fibrosis has not been identified, and it remains to be determined whether lung fibrosis would be improved by decreasing the expression of CD147. A murine bleomycin-induced lung interstitial fibrosis model was used in the experiments, and HAb18 mAbs and CsA were administered during the induction of lung fibrosis. In our study, we found that the HAb18 mAbs markedly reduced the collagen score and down-regulated M1 macrophages and Th17 cells. In vitro, flow cytometry analysis showed that M1 macrophages induced higher Th17 differentiation than M2 macrophages. After treatment with HAb18 mAbs or after reducing the expression of CD147 by lentivirus interference in M1 macrophages, the level of Th17 cells were significantly inhibited. In conclusion, HAb18 mAbs or CsA treatment ameliorates lung interstitial fibrosis. CD147 promoted M1 macrophage and induced the differentiation of Th17 cells in lung interstitial fibrosis, perhaps by regulating some cytokines such as IL-6, IL-1β, IL-12 and IL-23. These results indicated that CD147 may play an important role in the development of lung interstitial fibrosis. Copyright © 2014 Elsevier B.V. All rights reserved.
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The plasma membrane of myxosporidian valve cells: freeze fracture data.
Desportes-Livage, I; Nicolas, G
1990-01-01
Freeze fracturing of Myxosporidian spores reveals the occurrence of a continuous layer of transmembrane particles all over the surface area of the valve cells which form the spore envelope. These particles are densely packed all over the P face membrane. Due to their polygonal outline, their diameter (6-7 nm) and their central core, they resemble the particles forming the connections of gap junctions which metabolically couple the neighboring cells in animal tissues. In the present report, the role of the transmembrane particles is still hypothetical. However, they might represent a membrane structural specialization of the spores which are submitted to osmotic variations of the fluid external medium. Furthermore similar transmembrane particles are observed at the level of the septate junction which seals the valve cells. In this occurrence, they are arranged in a series of 40 double rows parallel to the suture of the spore envelope. These findings support the view that Myxosporidia are Metazoa and raise the problem of their origin.
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Ortega, Israel; Villanueva, Jesus A.; Wong, Donna H.; Cress, Amanda B.; Sokalska, Anna; Stanley, Scott D.
2012-01-01
Polycystic ovary syndrome is characterized by theca-interstitial hyperplasia and increased expression of steroidogenic genes, leading to excessive androgen production. Resveratrol, a natural polyphenol, promotes apoptosis and reduces rat theca-interstitial cell growth, in part by inhibiting the mevalonate pathway and decreasing the availability of substrates of isoprenylation [farnesyl-pyrophosphate (FPP) and geranylgeranyl-pyrophosphate (GGPP)]. This study evaluated the effect of resveratrol on rat theca-interstitial cell steroidogenesis. Because resveratrol may activate sirtuins, this study also investigated whether steroidogenesis was affected by sirtuin inhibitors (nicotinamide, sirtinol). Theca-interstitial cells were cultured with or without resveratrol (1–10 μm), GGPP (30 μm), FPP (30 μm), nicotinamide (1 mm), and/or sirtinol (10 μm). Resveratrol did not affect progesterone levels but reduced androgen production in a concentration-dependent fashion (androstenedione by up to 78% and androsterone by up to 76%). This inhibitory effect correlated with a decrease in mRNA expression of genes regulating androgen production, especially Cyp17a1 (by up to 73%). GGPP and FPP had no effect on androgen levels and Cyp17a1 mRNA levels and did not alter the effects induced by resveratrol. Similarly, sirtuin inhibitors did not reverse resveratrol-induced inhibition of steroidogenesis. However, resveratrol decreased activity of serine-threonine kinase/protein kinase B pathway, a cell-signaling pathway involved in ovarian steroidogenesis. The present findings indicate that resveratrol reduces androgen production primarily by inhibiting Cyp17a1 mRNA expression, and this inhibition may be mediated, in part, by blocking the activity of the serine-threonine kinase/protein kinase B pathway. These findings may be of clinical relevance to conditions associated with excessive production of androgens by theca cells, such as polycystic ovary syndrome. PMID:22719052
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Galli, Daniela; Manuguerra, Roberta; Monaco, Rodolfo; Manotti, Laura; Goldoni, Matteo; Becchi, Gabriella; Carubbi, Cecilia; Vignali, Giulia; Cucurachi, Nicola; Gherli, Tiziano; Nicolini, Francesco; Lorusso, Roberto; Vitale, Marco; Corradi, Domenico
2017-02-01
With age, aortic valve cusps undergo varying degrees of sclerosis which, sometimes, can progress to calcific aortic valve stenosis (AVS). To perform a retrospective clinico-pathologic investigation in patients with calcific AVS. We characterized and graded the structural remodeling in 236 aortic valves (200 tricuspid and 36 bicuspid) from patients with calcific AVS (148 males; average 72years); possible relationships between general/clinical/echocardiographic characteristics and the histopathologic changes were explored. Twenty autopsy aortic valves served as controls. In 40 cases, we also tested the immunohistochemical expression of metalloproteinases and cytokines, and characterized the inflammatory infiltrate. In 5 cases, we cultured cusp stem cells and explored their potential to differentiate into osteoblasts/adipocytes. AVS cusps showed structural remodeling as severe fibrosis (100%), calcific nodules (100%), neoangiogenesis (81%), inflammation (71%), bone metaplasia with or without hematopoiesis (6% and 53%, respectively), adipose metaplasia (16%), and cartilaginous metaplasia (7%). At multivariate analysis, AVS degree and interventricular septum thickness were the only predictors of remodeling (barring inflammation). All the tested metalloproteinases (except MMP-13) and cytokines were expressed in AVS cusps. Inflammation mainly consisted of B and T lymphocytes (CD4+/CD8+ cell ratio 3:1) and plasma cells. AVS changes were mostly different from typical atherosclerosis. Cultured mesenchymal cusp stem cells could differentiate into osteoblasts/adipocytes. Structural remodeling in AVS is peculiar and considerable, and is related to the severity of the disease. However, the different newly formed tissues-where "valvular interstitial cells" play a key role-and their well-known slow turnover suggest a reverse structural remodeling improbable. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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Yasuda, Yuichiro; Hattori, Yoshihiro; Tohnai, Rie; Ito, Shoichi; Kawa, Yoshitaka; Kono, Yuko; Urata, Yoshiko; Nogami, Munenobu; Takenaka, Daisuke; Negoro, Shunichi; Satouchi, Miyako
2018-01-01
The optimal chemotherapy regimen for non-small cell lung cancer patients with interstitial lung disease is unclear. We therefore investigated the safety and efficacy of carboplatin plus nab-paclitaxel as a first-line regimen for non-small cell lung cancer in patients with interstitial lung disease. We retrospectively reviewed advanced non-small cell lung cancer patients with interstitial lung disease who received carboplatin plus nab-paclitaxel as a first-line chemotherapy regimen at Hyogo Cancer Center between February 2013 and August 2016. interstitial lung disease was diagnosed according to the findings of pretreatment chest high-resolution computed tomography. Twelve patients were included (male, n = 11; female, n = 1). The overall response rate was 67% and the disease control rate was 100%. The median progression free survival was 5.1 months (95% CI: 2.9-8.3 months) and the median overall survival was 14.9 months (95% CI: 4.8-not reached). A chemotherapy-related acute exacerbation of interstitial lung disease was observed in one patient; the extent of this event was Grade 2. There were no treatment-related deaths. Carboplatin plus nab-paclitaxel, as a first-line chemotherapy regimen for non-small cell lung cancer, showed favorable efficacy and safety in patients with preexisting interstitial lung disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
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The interstitial stem cells in Hydractinia and their role in regeneration.
Gahan, James M; Bradshaw, Brian; Flici, Hakima; Frank, Uri
2016-10-01
Hydractinia species have been animal models in developmental biology and comparative immunology for over a century, but are having a renaissance due to the establishment of modern genetic and genomic tools by the growing community of researchers utilizing them. Hydractinia has a predictable and accessible life cycle and its stem cell system, known as interstitial- or i-cells has been a paradigm for animal stem cells since the late 1800s. In adult Hydractinia, i-cells continuously provide progenitors to sustain clonal growth, tissue homeostasis, sexual reproduction and regeneration. We review recent developments in stem cell and regeneration research centered on this animal. Hydractinia joins an established team of cnidarian genetic models in times of rapid progress in these disciplines. While each animal is particularly suited to specific experimental settings, jointly they can provide an integrative insight into the diversity of animal stem cell systems, how they drive regeneration, and how they evolved. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Papper, S
1980-01-01
There are many causes of interstitial nephritis other than pyelonephritis. The term interstitial nephritis does not connote a single etiologic or pathogenetic mechanism; it rather arbitrarily places together a wider variety of renal diseases that have a predilection for early and major involvement of the renal interstitium. The prototype of acute interstitial nephritis is acute pyelonephritis. In addition, there is a drug-related acute interstitial disease that is probably of immunological nature and usually reverses with discontinuance of the offending drug. Chronic interstitial nephritis includes many diverse illnesses. Nonobstructive pyelonephritis occurs but its prevalence is debated. Analgesic abuse nephropathy is not rare and is potentially reversible. Papillary necrosis has many causes and a wide spectrum of clinical presentations. Heavy metals, such as lead, cause interstitial nephritis. Balkan nephropathy occurs in an endemic area and although not bacterial in origin is of unknown cause.
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Sajisevi, Mirabelle; Rigual, Nestor R; Bellnier, David A.; Seshadri, Mukund
2014-01-01
Objective Photodynamic therapy (PDT) is a clinically approved minimally invasive treatment for cancer. In this preclinical study, using an imaging-guided approach, we examined the potential utility of PDT in the management of bulky squamous cell carcinomas (SCCs). Methods To mimic bulky oropharyngeal cancers seen in the clinical setting, intramuscular SCCs were established in six-to-eight week old female C3H mice. Animals were injected with the photosensitizer, 2-[hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH; 0.4 μmol/kg, i.v.) and tumors were illuminated 24 hours post injection with 665 nm light. PDT as a single treatment modality was administered by surface illumination or by interstitial placement of fibers (iPDT). Magnetic resonance imaging was used to guide treatment and assess tumor response to PDT along with correlative histopathologic assessment. Results Interstitial HPPH-PDT resulted in a marked change on T2 maps 24 hours post treatment compared to untreated controls or transcutaneous illumination. Corresponding apparent diffusion coefficient maps also showed hyperintense areas in tumors following iPDT suggestive of effective photodynamic cell kill. Histologic sections (H&E) confirmed presence of extensive tumor necrosis following iPDT. Conclusions These results highlight the potential utility of PDT in the treatment of bulky oropharyngeal cancers. The findings of our study also demonstrate the utility of MRI as a non-invasive tool for mapping of early tissue response to PDT. PMID:25750858
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Diffusion and interactions of interstitials in hard-sphere interstitial solid solutions
NASA Astrophysics Data System (ADS)
van der Meer, Berend; Lathouwers, Emma; Smallenburg, Frank; Filion, Laura
2017-12-01
Using computer simulations, we study the dynamics and interactions of interstitial particles in hard-sphere interstitial solid solutions. We calculate the free-energy barriers associated with their diffusion for a range of size ratios and densities. By applying classical transition state theory to these free-energy barriers, we predict the diffusion coefficients, which we find to be in good agreement with diffusion coefficients as measured using event-driven molecular dynamics simulations. These results highlight that transition state theory can capture the interstitial dynamics in the hard-sphere model system. Additionally, we quantify the interactions between the interstitials. We find that, apart from excluded volume interactions, the interstitial-interstitial interactions are almost ideal in our system. Lastly, we show that the interstitial diffusivity can be inferred from the large-particle fluctuations alone, thus providing an empirical relationship between the large-particle fluctuations and the interstitial diffusivity.
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Denosumab could be a Potential Inhibitor of Valvular Interstitial Cells Calcification in vitro.
Lerman, Daniel Alejandro; Prasad, Sai; Alotti, Nasri
2016-01-03
Denosumab is a fully human monoclonal antibody and novel antiresorptive agent that works by binding receptor activator of nuclear factor kappa-β ligand (RANKL) and inhibiting the signaling cascade that causes osteoclast maturation, activity, and survival. We aimed to elucidate the effect of Denosumab in the process of spontaneous and induced calcification in an in vitro porcine valvular interstitial cells (VICs) model. VICs were extracted from fresh porcine hearts by serial collagenase digestion. Spontaneous calcification of VICs was increased in vitro by adding Na 3 PO 4 (3 mM, pH 7.4) and different concentrations (0.1, 1 and 10 ng/ml) of transforming growth factor beta (TGFß). The degree of calcification before and after treatment with Denosumab was estimated by Alizarin Red staining for calcium deposition, and Sirius Red staining for collagen. Colorimetric techniques were used to determine calcium and collagen deposition quantitatively. For statistical analysis we used SPSS and Microsoft Office Excel 2013. Porcine aortic VICs in vitro were induced to calcify by the addition of either 3 mM Na 3 PO 4 , showing a 5.2 fold increase by 14 days (P<0.001), or 3 mM Na 3 PO 4 + 10 ng/ml of TGFβ, showing a 7 fold increase by Day 14 (P<0.001). Denosumab inhibited induced calcification by 3 mM Na 3 PO 4 and 3 mM Na 3 PO 4 with the addition of TGFß at either 0.1, 1 or 10 ng/ml to basal levels only at a concentration of 50 μg/ml (P<0.001). This study has proved that Denosumab could be a potential inhibitor of the calcification of VICs in vitro . A fuller understanding of the actions of Denosumab may identify a novel therapeutic strategy for clinical intervention against aortic valve calcification and aortic stenosis.
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Junquera, Concepción; Martínez-Ciriano, Carmen; Castiella, Tomás; Serrano, Pedro; Azanza, María Jesús; Ramón y Cajal Junquera, Santiago
2007-01-01
Abstract Santiago Ramón y Cajal discovered a new type of cell related to the myenteric plexus and also to the smooth muscle cells of the circular muscle layer of the intestine. Based on their morphology, relationships and staining characteristics, he considered these cells as primitive neurons. One century later, despite major improvements in cell biology, the interstitial cells of Cajal (ICCs) are still controversial for many researchers. The aim of study was to perform an immunohistochemical and ultrastructural characterization of the ICCs in the rabbit duo-denum. We have found interstitial cells that are positive for c-Kit, CD34 and nestin and are also positive for Ki67 protein, tightly associated with somatic cell proliferation. By means of electron microscopy, we describe ICCs around enteric ganglia. They present triangular or spindle forms and a very voluminous nucleus with scarce per-inuclear chromatin surrounded by a thin perinuclear cytoplasm that expands with long cytoplasmic processes. ICC processes penetrate among the smooth muscle cells and couple with the processes of other ICCs located in the connective tissue of the circular muscle layer and establish a three-dimensional network. Intercellular con-tacts by means of gap-like junctions are frequent. ICCs also establish gap-like junctions with smooth muscle cells. We also observe a population of interstitial cells of stellate morphology in the connective tissue that sur-rounds the muscle bundles in the circular muscle layer, usually close to nervous trunks. These cells establish different types of contacts with the muscle cells around them. In addition, the presence of a single cilium show-ing a structure 9 + 0 in an ICC is demonstrated for the first time. In conclusion, we report positive staining c-kit, CD34, nestin and Ki 67. ICCs fulfilled the usual transmission electron microscopy (TEM) criteria. A new ultrastructural characteristic of at least some ICCs is demonstrated: the presence of a single
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Zhao, Min; Davis, Linda S.; Blackwell, Timothy S.; Yull, Fiona; Breyer, Matthew D.; Hao, Chuan-Ming
2013-01-01
High salt diet induces renal medullary COX2 expression. Selective blockade of renal medullary COX2 activity in rats causes salt sensitive hypertension, suggesting a role for renal medullary COX2 in maintaining systemic sodium balance. The present study characterized the cellular location of COX2 induction in the kidney of mice following high salt diet and examined the role of NFκB in mediating this COX2 induction in response to increased dietary salt. High salt diet (8% NaCl) for 3 days markedly increased renal medullary COX2 expression in C57Bl/6J mice. Co-immunofluorescence using a COX2 antibody and antibodies against AQP2, ClC-K, AQP1 and CD31 showed that high salt diet-induced COX2 was selectively expressed in renal medullary interstitial cells. By using NFκB reporter transgenic mice, we observed a 7 fold increase of luciferase activity in the renal medulla of the NFκB-luciferase reporter mice following high salt diet, and a robust induction of EGFP expression mainly in renal medullary interstitial cells of the NFκB-EGFP reporter mice following high salt diet. Treating high salt diet fed C57Bl/6J mice with selective IκB kinase inhibitor IMD-0354 (8mg/kg bw) substantially suppressed COX2 induction in renal medulla, and also significantly reduced urinary PGE2. These data therefore suggest that renal medullary interstitial cell NFκB plays an important role in mediating renal medullary COX2 expression and promoting renal PGE2 synthesis in response to increased dietary sodium. PMID:23900806
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Interstitial cystitis - resources
Resources - interstitial cystitis ... The following organizations are good resources for information on interstitial cystitis : Interstitial Cystitis Association -- www.ichelp.org National Institute of Diabetes and Digestive and Kidney Diseases -- www. ...
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Mechanics of Fluid-Filled Interstitial Gaps. II. Gap Characteristics in Xenopus Embryonic Ectoderm.
Barua, Debanjan; Parent, Serge E; Winklbauer, Rudolf
2017-08-22
The ectoderm of the Xenopus embryo is permeated by a network of channels that appear in histological sections as interstitial gaps. We characterized this interstitial space by measuring gap sizes, angles formed between adjacent cells, and curvatures of cell surfaces at gaps. From these parameters, and from surface-tension values measured previously, we estimated the values of critical mechanical variables that determine gap sizes and shapes in the ectoderm, using a general model of interstitial gap mechanics. We concluded that gaps of 1-4 μm side length can be formed by the insertion of extracellular matrix fluid at three-cell junctions such that cell adhesion is locally disrupted and a tension difference between cell-cell contacts and the free cell surface at gaps of 0.003 mJ/m 2 is generated. Furthermore, a cell hydrostatic pressure of 16.8 ± 1.7 Pa and an interstitial pressure of 3.9 ± 3.6 Pa, relative to the central blastocoel cavity of the embryo, was found to be consistent with the observed gap size and shape distribution. Reduction of cell adhesion by the knockdown of C-cadherin increased gap volume while leaving intracellular and interstitial pressures essentially unchanged. In both normal and adhesion-reduced ectoderm, cortical tension of the free cell surfaces at gaps does not return to the high values characteristic of the free surface of the whole tissue. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.
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NASA Technical Reports Server (NTRS)
Ringel, S. A.; Chatterjee, B.
2004-01-01
Hydrogen passivation of heteroepitaxial InP solar cells is of recent interest for deactivation of dislocations and other defects caused by the cell/substrate lattice mismatch that currently limit the photovoltaic performance of these devices. In this paper we present strong evidence that, in addition to direct hydrogen-dislocation interactions, hydrogen forms complexes with the high concentration of interstitial Zn defects present within the p(+) Zn-doped emitter of MOCVD-grown heteroepitaxial InP devices, resulting in a dramatic increase of the forward bias turn-on voltage by as much as 280 mV, from 680 mV to 960 mV. This shift is reproducible and thermally reversible and no such effect is observed for either n(+)p structures or homoepitaxial p(+)n structures grown under identical conditions. A combination of photoluminescence (PL), electrochemical C-V dopant profiling, SIMS and I-V measurements were performed on a set of samples having undergone a matrix of hydrogenation and post-hydrogenation annealing conditions to investigate the source of this voltage enhancement and confirm the expected role of interstitial Zn and hydrogen. A precise correlation between all measurements is demonstrated which indicates that Zn interstitials within the p(+) emitter and their interaction with hydrogen are indeed responsible for this device behavior.
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Malik, Shabana T; Birch, Brian R; Voegeli, David; Fader, Mandy; Foria, Vipul; Cooper, Alan J; Walls, Andrew F; Lwaleed, Bashir A
2018-05-15
To identify the presence and geographical distribution of mast cell (MC) subtypes: MC T (tryptase positive-chymase negative) and MC TC (tryptase positive-chymase positive) in bladder tissue. Bladder tissue was obtained from patients with painful bladder syndrome/interstitial cystitis (n=14) and normal histology from University Hospital Southampton tissue bank. Sequential tissue slices were immunohistochemically stained for MC subtypes using anti-MC tryptase (for MC T and MC TC ) and anti-MC chymase (for MC TC ). Stained sections were photographed, and positively stained MCs were quantified using ImageJ. Data were analysed using descriptive statistics and individual paired t-tests. There was a significant difference in the density of MCs between each layer of the disease bladder, with the greatest accumulation within the detrusor (p<0.001). There was a significant increase in MC TC subtype in the lamina (p=0.009) in painful bladder syndrome/interstitial cystitis. Our results suggest that mastocytosis is present within all layers of disease bladder, especially the muscle layer. The varying increase in MC subtypes in the lamina and mucosa may explain the variability in painful bladder syndrome/interstitial cystitis symptoms. A high influx of MC TC in the mucosa of individuals who also had ulceration noted within their diagnostic notes may be of the Hunner's ulcer subclassification. These findings suggest a relationship between the pathogenesis of MC subtypes and the clinical presentation of painful bladder syndrome/interstitial cystitis. A cohort study would further elucidate the diagnostic and/or therapeutic potential of MCs in patients with painful bladder syndrome/interstitial cystitis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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49 CFR 236.383 - Valve locks, valves, and valve magnets.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false Valve locks, valves, and valve magnets. 236.383... Inspection and Tests § 236.383 Valve locks, valves, and valve magnets. Valve locks on valves of the non-cut-off type shall be tested at least once every three months, and valves and valve magnets shall be...
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[Modern Views on Children's Interstitial Lung Disease].
Boĭtsova, E V; Beliashova, M A; Ovsiannikov, D Iu
2015-01-01
Interstitial lung diseases (ILD, diffuse lung diseases) are a heterogeneous group of diseases in which a pathological process primarily involved alveoli and perialveolar interstitium, resulting in impaired gas exchange, restrictive changes of lung ventilation function and diffuse interstitial changes detectable by X-ray. Children's interstitial lung diseases is an topical problem ofpediatricpulmonoogy. The article presents current information about classification, epidemiology, clinical presentation, diagnostics, treatment and prognosis of these rare diseases. The article describes the differences in the structure, pathogenesis, detection of various histological changes in children's ILD compared with adult patients with ILD. Authors cite an instance of registers pediatric patients with ILD. The clinical semiotics of ILD, the possible results of objective research, the frequency of symptoms, the features of medical history, the changes detected on chest X-rays, CT semiotics described in detail. Particular attention was paid to interstitial lung diseases, occurring mainly in newborns and children during the first two years of life, such as congenital deficiencies of surfactant proteins, neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis. The diagnostic program for children's ILD, therapy options are presented in this article.
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He, Wenjuan; Zhang, Min; Zhao, Min; Davis, Linda S; Blackwell, Timothy S; Yull, Fiona; Breyer, Matthew D; Hao, Chuan-Ming
2014-02-01
High salt diet induces renal medullary cyclooxygenase 2 (COX2) expression. Selective blockade of renal medullary COX2 activity in rats causes salt-sensitive hypertension, suggesting a role for renal medullary COX2 in maintaining systemic sodium balance. The present study characterized the cellular location of COX2 induction in the kidney of mice following high salt diet and examined the role of NFκB in mediating this COX2 induction in response to increased dietary salt. High salt diet (8 % NaCl) for 3 days markedly increased renal medullary COX2 expression in C57Bl/6 J mice. Co-immunofluorescence using a COX2 antibody and antibodies against aquaporin-2, ClC-K, aquaporin-1, and CD31 showed that high salt diet-induced COX2 was selectively expressed in renal medullary interstitial cells. By using NFκB reporter transgenic mice, we observed a sevenfold increase of luciferase activity in the renal medulla of the NFκB-luciferase reporter mice following high salt diet, and a robust induction of enhanced green fluorescent protein (EGFP) expression mainly in renal medullary interstitial cells of the NFκB-EGFP reporter mice following high salt diet. Treating high salt diet-fed C57Bl/6 J mice with selective IκB kinase inhibitor IMD-0354 (8 mg/kg bw) substantially suppressed COX2 induction in renal medulla, and also significantly reduced urinary prostaglandin E2 (PGE2). These data therefore suggest that renal medullary interstitial cell NFκB plays an important role in mediating renal medullary COX2 expression and promoting renal PGE2 synthesis in response to increased dietary sodium.
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New insights into canted spiro carbon interstitial in graphite
NASA Astrophysics Data System (ADS)
EL-Barbary, A. A.
2017-12-01
The self-interstitial carbon is the key to radiation damage in graphite moderator nuclear reactor, so an understanding of its behavior is essential for plant safety and maximized reactor lifetime. The density functional theory is applied on four different graphite unit cells, starting from of 64 carbon atoms up to 256 carbon atoms, using AIMPRO code to obtain the energetic, athermal and mechanical properties of carbon interstitial in graphite. This study presents first principles calculations of the energy of formation that prove its high barrier to athermal diffusion (1.1 eV) and the consequent large critical shear stress (39 eV-50 eV) necessary to shear graphite planes in its presence. Also, for the first time, the gamma surface of graphite in two dimensions is calculated and found to yield the critical shear stress for perfect graphite. Finally, in contrast to the extensive literature describing the interstitial of carbon in graphite as spiro interstitial, in this work the ground state of interstitial carbon is found to be canted spiro interstitial.
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Cuy, Janet L; Beckstead, Benjamin L; Brown, Chad D; Hoffman, Allan S; Giachelli, Cecilia M
2003-11-01
Stable endothelialization of a tissue-engineered heart valve is essential for proper valve function, although adhesive characteristics of the native valve endothelial cell (VEC) have rarely been explored. This research evaluated VEC adhesive qualities and attempted to enhance VEC growth on the biopolymer chitosan, a novel tissue-engineering scaffold material with promising biological and chemical properties. Aortic VEC cultures were isolated and found to preferentially adhere to fibronectin, collagen types IV and I over laminin and osteopontin in a dose-dependent manner. Seeding of VEC onto comparison substrates revealed VEC growth and morphology to be preferential in the order: tissue culture polystyrene > gelatin, poly(DL-lactide-co-glycolide), chitosan > poly(hydroxy alkanoate). Adhesive protein precoating of chitosan did not significantly enhance VEC growth, despite equivalent protein adsorption as to polystyrene. Initial cell adhesion to protein-precoated chitosan, however, was higher than for polystyrene. Composite chitosan/collagen type IV films were investigated as an alternative to simple protein precoatings, and were shown to improve VEC growth and morphology over chitosan alone. These findings suggest potential manipulation of chitosan properties to improve amenability to valve tissue-engineering applications. Copyright 2003 Wiley Periodicals, Inc.
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Mazzia, C; Porcher, C; Julé, Y; Christen, M O; Henry, M
2000-05-01
C-kit immunocytochemistry was performed on ultrathin sections of human distal colon. Our attention was focused on relationships between c-kit immunoreactive interstitial cells (c-kit ICs) and muscular cells and nervous elements located in the external muscular layers of the colonic wall. C-kit ICs established membrane apposition with both nerve fibers and smooth muscle cells of, respectively, the longitudinal and circular muscle layers, the myenteric area, and the extremus submucosus plexus. C-kit ICs also surrounded the external submucosus plexus and established membrane appositions with nerve elements located inside the myenteric ganglia. These membrane appositions were observed either at the level of the c-kit IC bodies or at that of their cytoplasmic processes. In some cases, membrane appositions were observed concomitantly between the c-kit ICs, nerve fibers, and smooth muscle cells. In all the regions studied, the c-kit ICs were also found to be located in the close vicinity of blood vessels and to have established close contacts with non-immunoreactive fibroblast-like cells. The results of the present study shed essential light on the relationships of c-kit ICs with the neighboring muscle cells and nerve elements, and confirm that the intercalated c-kit ICs well fit with the so-called "interstitial cells of Cajal".
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Bioprosthetic Valve Fracture to Facilitate Transcatheter Valve-in-Valve Implantation.
Allen, Keith B; Chhatriwalla, Adnan K; Cohen, David J; Saxon, John T; Aggarwal, Sanjeev; Hart, Anthony; Baron, Suzanne; Davis, J Russell; Pak, Alex F; Dvir, Danny; Borkon, A Michael
2017-11-01
Valve-in-valve transcatheter aortic valve replacement is less effective in small surgical bioprostheses. We evaluated the feasibility of bioprosthetic valve fracture with a high-pressure balloon to facilitate valve-in-valve transcatheter aortic valve replacement. In vitro bench testing on aortic tissue valves was performed on 19-mm and 21-mm Mitroflow (Sorin, Milan, Italy), Magna and Magna Ease (Edwards Lifesciences, Irvine, CA), Trifecta and Biocor Epic (St. Jude Medical, Minneapolis, MN), and Hancock II and Mosaic (Medtronic, Minneapolis, MN). High-pressure balloons Tru Dilation, Atlas Gold, and Dorado (C.R. Bard, Murray Hill, NJ) were used to determine which valves could be fractured and at what pressure fracture occurred. Mitroflow, Magna, Magna Ease, Mosaic, and Biocor Epic surgical valves were successfully fractured using high-pressures balloon 1 mm larger than the labeled valve size whereas Trifecta and Hancock II surgical valves could not be fractured. Only the internal valve frame was fractured, and the sewing cuff was never disrupted. Manufacturer's rated burst pressures for balloons were exceeded, with fracture pressures ranging from 8 to 24 atmospheres depending on the surgical valve. Testing further demonstrated that fracture facilitated the expansion of previously constrained, underexpanded transcatheter valves (both balloon and self-expanding) to the manufacturer's recommended size. Bench testing demonstrates that the frame of most, but not all, bioprosthetic surgical aortic valves can be fractured using high-pressure balloons. The safety of bioprosthetic valve fracture to optimize valve-in-valve transcatheter aortic valve replacement in small surgical valves requires further clinical investigation. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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Do we understand any more about bladder interstitial cells?-ICI-RS 2013.
Kanai, Anthony; Fry, Christopher; Hanna-Mitchell, Ann; Birder, Lori; Zabbarova, Irina; Bijos, Dominika; Ikeda, Youko
2014-06-01
To present a brief review on discussions from "Do we understand any more about lower urinary tract interstitial cells?" session at the 2013 International Consultation on Incontinence-Research Society (ICI-RS) meeting in Bristol, UK. Discussion focused on bladder interstitial cell (IC) subtypes, their localization and characterization, and communication between themselves, the urothelium, and detrusor smooth muscle. The role of ICs in bladder pathologies and new methods for studying ICs were also addressed. ICs have been studied extensively in the lower urinary tract and have been characterized based on comparisons with ICs of Cajal in the gastro-intestinal tract. In fetal bladders it is believed that ICs drive intrinsic contractions to expel urine through the urachus. These contractions diminish postpartum as bladder innervation develops. Voiding in human neonates occurs when filling triggers a spinal cord reflex that contracts the detrusor; in rodents, maternal stimulation of the perineum triggers voiding. Following spinal cord injury, intrinsic contractions, and spinal micturition reflexes develop, similar to those seen during neonatal development. These enhanced contractions may stimulate nociceptive and mechanosensitive afferents contributing to neurogenic detrusor overactivity and incontinence. The IC-mediated activity is believed to be initiated in the lamina propria by responding to urothelial factors. These IC may act syncytially through gap junction coupling and modulate detrusor activity through unknown mechanisms. There has been a great deal of information discovered regarding bladder ICs, however, many of their (patho)physiological functions and mechanisms are still unclear and necessitates further research. Neurourol. Urodynam. 33:573-576, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.
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Whittlesey, Curtis C.
1985-01-01
An improved battery stack design for an electrochemical system having at least one cell from which a gas is generated and an electrolyte in communication with the cell is described. The improved battery stack design features means for defining a substantially closed compartment for containing the battery cells and at least a portion of the electrolyte for the system, and means in association with the compartment means for selectively venting gas from the interior of the compartment means in response to the level of the electrolyte within the compartment means. The venting means includes a relief valve having a float member which is actuated in response to the level of the electrolyte within the compartment means. This float member is adapted to close the relief valve when the level of the electrolyte is above a predetermined level and open the relief valve when the level of electrolyte is below this predetermined level.
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Li, Zhifang; Chen, Haiyu; Zhou, Feifan; Li, Hui; Chen, Wei R.
2015-01-01
Photothermal therapy is an effective means to induce tumor cell death, since tumor tissue is more sensitive to temperature increases than normal tissue. Biological responses depend on tissue temperature; target tissue temperature needs to be precisely measured and controlled to achieve desired thermal effects. In this work, a unique photoacoustic (PA) sensor is proposed for temperature measurement during interstitial laser phototherapy. A continuous-wave laser light and a pulsed laser light, for photothermal irradiation and photoacoustic temperature measurement, respectively, were delivered to the target tissue through a fiber coupler. During laser irradiation, the PA amplitude was measured. The Grüneisen parameter and the bioheat equation were used to determine the temperature in strategic positions in the target tissue. Our results demonstrate that the interstitial PA amplitude is a linear function of temperature in the range of 22 to 55 °C, as confirmed by thermocouple measurement. Furthermore, by choosing appropriate laser parameters, the maximum temperature surrounding the active diffuse fiber tip in tissue can be controlled in the range of 41 to 55 °C. Thus, this sensor could potentially be used for fast, accurate, and convenient three-dimensional temperature measurement, and for real-time feedback and control of interstitial laser phototherapy in cancer treatment. PMID:25756865
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Tissue engineering of heart valves: in vitro experiences.
Sodian, R; Hoerstrup, S P; Sperling, J S; Daebritz, S H; Martin, D P; Schoen, F J; Vacanti, J P; Mayer, J E
2000-07-01
Tissue engineering is a new approach, whereby techniques are being developed to transplant autologous cells onto biodegradable scaffolds to ultimately form new functional tissue in vitro and in vivo. Our laboratory has focused on the tissue engineering of heart valves, and we have fabricated a trileaflet heart valve scaffold from a biodegradable polymer, a polyhydroxyalkanoate. In this experiment we evaluated the suitability of this scaffold material as well as in vitro conditioning to create viable tissue for tissue engineering of a trileaflet heart valve. We constructed a biodegradable and biocompatible trileaflet heart valve scaffold from a porous polyhydroxyalkanoate (Meatabolix Inc, Cambridge, MA). The scaffold consisted of a cylindrical stent (1 x 15 x 20 mm inner diameter) and leaflets (0.3 mm thick), which were attached to the stent by thermal processing techniques. The porous heart valve scaffold (pore size 100 to 240 microm) was seeded with vascular cells grown and expanded from an ovine carotid artery and placed into a pulsatile flow bioreactor for 1, 4, and 8 days. Analysis of the engineered tissue included biochemical examination, enviromental scanning electron microscopy, and histology. It was possible to create a trileaflet heart valve scaffold from polyhydroxyalkanoate, which opened and closed synchronously in a pulsatile flow bioreactor. The cells grew into the pores and formed a confluent layer after incubation and pulsatile flow exposure. The cells were mostly viable and formed connective tissue between the inside and the outside of the porous heart valve scaffold. Additionally, we demonstrated cell proliferation (DNA assay) and the capacity to generate collagen as measured by hydroxyproline assay and movat-stained glycosaminoglycans under in vitro pulsatile flow conditions. Polyhydroxyalkanoates can be used to fabricate a porous, biodegradable heart valve scaffold. The cells appear to be viable and extracellular matrix formation was induced
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Loss of Axin2 results in impaired heart valve maturation and subsequent myxomatous valve disease.
Hulin, Alexia; Moore, Vicky; James, Jeanne M; Yutzey, Katherine E
2017-01-01
Myxomatous valve disease (MVD) is the most common aetiology of primary mitral regurgitation. Recent studies suggest that defects in heart valve development can lead to heart valve disease in adults. Wnt/β-catenin signalling is active during heart valve development and has been reported in human MVD. The consequences of increased Wnt/β-catenin signalling due to Axin2 deficiency in postnatal valve remodelling and pathogenesis of MVD were determined. To investigate the role of Wnt/β-catenin signalling, we analysed heart valves from mice deficient in Axin2 (KO), a negative regulator of Wnt/β-catenin signalling. Axin2 KO mice display enlarged mitral and aortic valves (AoV) after birth with increased Wnt/β-catenin signalling and cell proliferation, whereas Sox9 expression and collagen deposition are decreased. At 2 months in Axin2 KO mice, the valve extracellular matrix (ECM) is stratified but distal AoV leaflets remain thickened and develop aortic insufficiency. Progressive myxomatous degeneration is apparent at 4 months with extensive ECM remodelling and focal aggrecan-rich areas, along with increased BMP signalling. Infiltration of inflammatory cells is also observed in Axin2 KO AoV prior to ECM remodelling. Overall, these features are consistent with the progression of human MVD. Finally, Axin2 expression is decreased and Wnt/β-catenin signalling is increased in myxomatous mitral valves in a murine model of Marfan syndrome, supporting the importance of Wnt/β-catenin signalling in the development of MVD. Altogether, these data indicate that Axin2 limits Wnt/β-catenin signalling after birth and allows proper heart valve maturation. Moreover, dysregulation of Wnt/β-catenin signalling resulting from loss of Axin2 leads to progressive MVD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.
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Blood and interstitial flow in the hierarchical pore space architecture of bone tissue.
Cowin, Stephen C; Cardoso, Luis
2015-03-18
There are two main types of fluid in bone tissue, blood and interstitial fluid. The chemical composition of these fluids varies with time and location in bone. Blood arrives through the arterial system containing oxygen and other nutrients and the blood components depart via the venous system containing less oxygen and reduced nutrition. Within the bone, as within other tissues, substances pass from the blood through the arterial walls into the interstitial fluid. The movement of the interstitial fluid carries these substances to the cells within the bone and, at the same time, carries off the waste materials from the cells. Bone tissue would not live without these fluid movements. The development of a model for poroelastic materials with hierarchical pore space architecture for the description of blood flow and interstitial fluid flow in living bone tissue is reviewed. The model is applied to the problem of determining the exchange of pore fluid between the vascular porosity and the lacunar-canalicular porosity in bone tissue due to cyclic mechanical loading and blood pressure. These results are basic to the understanding of interstitial flow in bone tissue that, in turn, is basic to understanding of nutrient transport from the vasculature to the bone cells buried in the bone tissue and to the process of mechanotransduction by these cells. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Blood and Interstitial flow in the hierarchical pore space architecture of bone tissue
Cowin, Stephen C.; Cardoso, Luis
2015-01-01
There are two main types of fluid in bone tissue, blood and interstitial fluid. The chemical composition of these fluids varies with time and location in bone. Blood arrives through the arterial system containing oxygen and other nutrients and the blood components depart via the venous system containing less oxygen and reduced nutrition. Within the bone, as within other tissues, substances pass from the blood through the arterial walls into the interstitial fluid. The movement of the interstitial fluid carries these substances to the cells within the bone and, at the same time, carries off the waste materials from the cells. Bone tissue would not live without these fluid movements. The development of a model for poroelastic materials with hierarchical pore space architecture for the description of blood flow and interstitial fluid flow in living bone tissue is reviewed. The model is applied to the problem of determining the exchange of pore fluid between the vascular porosity and the lacunar-canalicular porosity in bone tissue due to cyclic mechanical loading and blood pressure. These results are basic to the understanding of interstitial flow in bone tissue that, in turn, is basic to understanding of nutrient transport from the vasculature to the bone cells buried in the bone tissue and to the process of mechanotransduction by these cells. PMID:25666410
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Mechanics of Fluid-Filled Interstitial Gaps. I. Modeling Gaps in a Compact Tissue.
Parent, Serge E; Barua, Debanjan; Winklbauer, Rudolf
2017-08-22
Fluid-filled interstitial gaps are a common feature of compact tissues held together by cell-cell adhesion. Although such gaps can in principle be the result of weak, incomplete cell attachment, adhesion is usually too strong for this to occur. Using a mechanical model of tissue cohesion, we show that, instead, a combination of local prevention of cell adhesion at three-cell junctions by fluidlike extracellular material and a reduction of cortical tension at the gap surface are sufficient to generate stable gaps. The size and shape of these interstitial gaps depends on the mechanical tensions between cells and at gap surfaces, and on the difference between intracellular and interstitial pressures that is related to the volume of the interstitial fluid. As a consequence of the dependence on tension/tension ratios, the presence of gaps does not depend on the absolute strength of cell adhesion, and similar gaps are predicted to occur in tissues of widely differing cohesion. Tissue mechanical parameters can also vary within and between cells of a given tissue, generating asymmetrical gaps. Within limits, these can be approximated by symmetrical gaps. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.
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Red cell distribution width in anemic patients undergoing transcatheter aortic valve implantation
Hellhammer, Katharina; Zeus, Tobias; Verde, Pablo E; Veulemanns, Verena; Kahlstadt, Lisa; Wolff, Georg; Erkens, Ralf; Westenfeld, Ralf; Navarese, Eliano P; Merx, Marc W; Rassaf, Tienush; Kelm, Malte
2016-01-01
AIM: To determine the impact of red blood cell distribution width on outcome in anemic patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: In a retrospective single center cohort study we determined the impact of baseline red cell distribution width (RDW) and anemia on outcome in 376 patients with aortic stenosis undergoing TAVI. All patients were discussed in the institutional heart team and declined for surgical aortic valve replacement due to high operative risk. Collected data included patient characteristics, imaging findings, periprocedural in hospital data, laboratory results and follow up data. Blood samples for hematology and biochemistry analysis were taken from every patient before and at fixed intervals up to 72 h after TAVI including blood count and creatinine. Descriptive statistics were used for patient’s characteristics. Kaplan-Meier survival curves were used for time to event outcomes. A recursive partitioning regression and classification was used to investigate the association between potential risk factors and outcome variables. RESULTS: Mean age in our study population was 81 ± 6.1 years. Anemia was prevalent in 63.6% (n = 239) of our patients. Age and creatinine were identified as risk factors for anemia. In our study population, anemia per se did influence 30-d mortality but did not predict longterm mortality. In contrast, a RDW > 14% showed to be highly predictable for a reduced short- and longterm survival in patients with aortic valve disease after TAVI procedure. CONCLUSION: Age and kidney function determine the degree of anemia. The anisocytosis of red blood cells in anemic patients supplements prognostic information in addition to that derived from the WHO-based definition of anemia. PMID:26981217
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Kalinina Ayuso, Viera; Scheerlinck, Laura M; de Boer, Joke H
2013-03-01
To assess the effect of Ahmed glaucoma valve implants on corneal endothelial cell density (ECD) in children with uveitic glaucoma. Cross-sectional study. setting: Institutional. patientpopulation: Eighty eyes from 42 patients diagnosed with uveitis before the age of 16. Twenty-eight eyes had an Ahmed glaucoma valve implant because of secondary glaucoma. Fifty-two eyes without an implant served as controls. intervention orobservationprocedure(s): Corneal ECD was examined cross-sectionally using a noncontact specular microscope. Univariate and multivariate generalized estimating equations analyses with correction for paired eyes were performed. mainoutcomemeasure(s): Correlation of ECD with the presence of an Ahmed glaucoma valve implant and with the time following implantation. ECD was significantly lower in the Ahmed glaucoma valve group than in controls (2359 and 3088 cells/mm(2), respectively; P < .001) following an average of 3.5 years after Ahmed glaucoma valve implantation. Presence of an Ahmed glaucoma valve implant, previous intraocular surgery, age, duration of uveitis, and history of corneal touch by the implant tube were all significantly associated with decreased ECD. Following a multivariate analysis, presence of an Ahmed glaucoma valve implant (B = -340; adjusted P < .011) and older age (B = -58; adjusted P = .005) remained independently associated with decreased ECD. Within the implant group, the age-adjusted time interval following Ahmed glaucoma valve implantation was highly correlated with decreased ECD (B = -558, P < .001). Ahmed glaucoma valve implants in children with uveitic glaucoma are independently associated with decreased ECD, and this effect is associated with the time interval following Ahmed glaucoma valve implantation. Copyright © 2013 Elsevier Inc. All rights reserved.
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Mkannez, Ghada; Gagné-Ouellet, Valérie; Nsaibia, Mohamed Jalloul; Boulanger, Marie-Chloé; Rosa, Mickael; Argaud, Deborah; Hadji, Fayez; Gaudreault, Nathalie; Rhéaume, Gabrielle; Bouchard, Luigi; Bossé, Yohan; Mathieu, Patrick
2018-05-02
Calcific aortic valve disease (CAVD) is characterized by the osteogenic transition of valve interstitial cells (VICs). In CAVD, lysophosphatidic acid (LysoPA), a lipid mediator with potent osteogenic activity, is produced in the aortic valve (AV) and is degraded by membrane-associated phospholipid phosphatases (PLPPs). We thus hypothesized that a dysregulation of PLPPs could participate to the osteogenic reprograming of VICs during CAVD. The expression of PLPPs was examined in human control and mineralized AVs and comprehensive analyses were performed to document the gene regulation and impact of PLPPs on the osteogenic transition of VICs. We found that PLPP3 gene and enzymatic activity were downregulated in mineralized AVs. Multidimensional gene profiling in 21 human AVs showed that expression of PLPP3 was inversely correlated with the level of 5-methylcytosine (5meC) located in an intronic mammalian interspersed repeat element (MIR). Bisulfite pyrosequencing in a larger series of 67 AVs confirmed that 5meC in intron 1 was increased by 2.2-fold in CAVD compared to control AVs. In isolated cells, epigenome editing with CRISPR-Cas9 system containing a deficient Cas9 fused with DNA methyltransferase (dCas9-DNMT) was used to increase 5meC in the intronic enhancer and showed that it reduced significantly the expression of PLPP3. Knockdown experiments showed that lower expression of PLPP3 in VICs promotes an osteogenic program. DNA methylation of a MIR-based enhancer downregulates the expression of PLPP3 and promotes the mineralization of the AV.
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Intraluminal valves: development, function and disease
Geng, Xin; Cha, Boksik; Mahamud, Md. Riaj
2017-01-01
ABSTRACT The circulatory system consists of the heart, blood vessels and lymphatic vessels, which function in parallel to provide nutrients and remove waste from the body. Vascular function depends on valves, which regulate unidirectional fluid flow against gravitational and pressure gradients. Severe valve disorders can cause mortality and some are associated with severe morbidity. Although cardiac valve defects can be treated by valve replacement surgery, no treatment is currently available for valve disorders of the veins and lymphatics. Thus, a better understanding of valves, their development and the progression of valve disease is warranted. In the past decade, molecules that are important for vascular function in humans have been identified, with mouse studies also providing new insights into valve formation and function. Intriguing similarities have recently emerged between the different types of valves concerning their molecular identity, architecture and development. Shear stress generated by fluid flow has also been shown to regulate endothelial cell identity in valves. Here, we review our current understanding of valve development with an emphasis on its mechanobiology and significance to human health, and highlight unanswered questions and translational opportunities. PMID:29125824
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Chhatriwalla, Adnan K; Allen, Keith B; Saxon, John T; Cohen, David J; Aggarwal, Sanjeev; Hart, Anthony J; Baron, Suzanne J; Dvir, Danny; Borkon, A Michael
2017-07-01
Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) may be less effective in small surgical valves because of patient/prosthesis mismatch. Bioprosthetic valve fracture (BVF) using a high-pressure balloon can be performed to facilitate VIV TAVR. We report data from 20 consecutive clinical cases in which BVF was successfully performed before or after VIV TAVR by inflation of a high-pressure balloon positioned across the valve ring during rapid ventricular pacing. Hemodynamic measurements and calculation of the valve effective orifice area were performed at baseline, immediately after VIV TAVR, and after BVF. BVF was successfully performed in 20 patients undergoing VIV TAVR with balloon-expandable (n=8) or self-expanding (n=12) transcatheter valves in Mitroflow, Carpentier-Edwards Perimount, Magna and Magna Ease, Biocor Epic and Biocor Epic Supra, and Mosaic surgical valves. Successful fracture was noted fluoroscopically when the waist of the balloon released and by a sudden drop in inflation pressure, often accompanied by an audible snap. BVF resulted in a reduction in the mean transvalvular gradient (from 20.5±7.4 to 6.7±3.7 mm Hg, P <0.001) and an increase in valve effective orifice area (from 1.0±0.4 to 1.8±0.6 cm 2 , P <0.001). No procedural complications were reported. BVF can be performed safely in small surgical valves to facilitate VIV TAVR with either balloon-expandable or self-expanding transcatheter valves and results in reduced residual transvalvular gradients and increased valve effective orifice area. © 2017 American Heart Association, Inc.
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Brody, Sarah; Anilkumar, Thapasimuthu; Liliensiek, Sara; Last, Julie A; Murphy, Christopher J; Pandit, Abhay
2006-02-01
A fully effective prosthetic heart valve has not yet been developed. A successful tissue-engineered valve prosthetic must contain a scaffold that fully supports valve endothelial cell function. Recently, topographic features of scaffolds have been shown to influence the behavior of a variety of cell types and should be considered in rational scaffold design and fabrication. The basement membrane of the aortic valve endothelium provides important parameters for tissue engineering scaffold design. This study presents a quantitative characterization of the topographic features of the native aortic valve endothelial basement membrane; topographical features were measured, and quantitative data were generated using scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), and light microscopy. Optimal conditions for basement membrane isolation were established. Histological, immunohistochemical, and TEM analyses following decellularization confirmed basement membrane integrity. SEM and AFM photomicrographs of isolated basement membrane were captured and quantitatively analyzed. The basement membrane of the aortic valve has a rich, felt-like, 3-D nanoscale topography, consisting of pores, fibers, and elevations. All features measured were in the sub-100 nm range. No statistical difference was found between the fibrosal and ventricular surfaces of the cusp. These data provide a rational starting point for the design of extracellular scaffolds with nanoscale topographic features that mimic those found in the native aortic heart valve basement membrane.
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BRODY, SARAH; ANILKUMAR, THAPASIMUTHU; LILIENSIEK, SARA; LAST, JULIE A.; MURPHY, CHRISTOPHER J.; PANDIT, ABHAY
2016-01-01
A fully effective prosthetic heart valve has not yet been developed. A successful tissue-engineered valve prosthetic must contain a scaffold that fully supports valve endothelial cell function. Recently, topographic features of scaffolds have been shown to influence the behavior of a variety of cell types and should be considered in rational scaffold design and fabrication. The basement membrane of the aortic valve endothelium provides important parameters for tissue engineering scaffold design. This study presents a quantitative characterization of the topographic features of the native aortic valve endothelial basement membrane; topographical features were measured, and quantitative data were generated using scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), and light microscopy. Optimal conditions for basement membrane isolation were established. Histological, immunohistochemical, and TEM analyses following decellularization confirmed basement membrane integrity. SEM and AFM photomicrographs of isolated basement membrane were captured and quantitatively analyzed. The basement membrane of the aortic valve has a rich, felt-like, 3-D nanoscale topography, consisting of pores, fibers, and elevations. All features measured were in the sub-100 nm range. No statistical difference was found between the fibrosal and ventricular surfaces of the cusp. These data provide a rational starting point for the design of extracellular scaffolds with nanoscale topographic features that mimic those found in the native aortic heart valve basement membrane. PMID:16548699
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FLUID MECHANICS OF ARTIFICIAL HEART VALVES
Dasi, Lakshmi P; Simon, Helene A; Sucosky, Philippe; Yoganathan, Ajit P
2009-01-01
SUMMARY 1. Artificial heart valves have been in use for over five decades to replace diseased heart valves. Since the first heart valve replacement performed with a caged-ball valve, more than 50 valve designs have been developed, differing principally in valve geometry, number of leaflets and material. To date, all artificial heart valves are plagued with complications associated with haemolysis, coagulation for mechanical heart valves and leaflet tearing for tissue-based valve prosthesis. For mechanical heart valves, these complications are believed to be associated with non-physiological blood flow patterns. 2. In the present review, we provide a bird’s-eye view of fluid mechanics for the major artificial heart valve types and highlight how the engineering approach has shaped this rapidly diversifying area of research. 3. Mechanical heart valve designs have evolved significantly, with the most recent designs providing relatively superior haemodynamics with very low aerodynamic resistance. However, high shearing of blood cells and platelets still pose significant design challenges and patients must undergo life-long anticoagulation therapy. Bioprosthetic or tissue valves do not require anticoagulants due to their distinct similarity to the native valve geometry and haemodynamics, but many of these valves fail structurally within the first 10–15 years of implantation. 4. These shortcomings have directed present and future research in three main directions in attempts to design superior artificial valves: (i) engineering living tissue heart valves; (ii) development of advanced computational tools; and (iii) blood experiments to establish the link between flow and blood damage. PMID:19220329
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Fluid mechanics of artificial heart valves.
Dasi, Lakshmi P; Simon, Helene A; Sucosky, Philippe; Yoganathan, Ajit P
2009-02-01
1. Artificial heart valves have been in use for over five decades to replace diseased heart valves. Since the first heart valve replacement performed with a caged-ball valve, more than 50 valve designs have been developed, differing principally in valve geometry, number of leaflets and material. To date, all artificial heart valves are plagued with complications associated with haemolysis, coagulation for mechanical heart valves and leaflet tearing for tissue-based valve prosthesis. For mechanical heart valves, these complications are believed to be associated with non-physiological blood flow patterns. 2. In the present review, we provide a bird's-eye view of fluid mechanics for the major artificial heart valve types and highlight how the engineering approach has shaped this rapidly diversifying area of research. 3. Mechanical heart valve designs have evolved significantly, with the most recent designs providing relatively superior haemodynamics with very low aerodynamic resistance. However, high shearing of blood cells and platelets still pose significant design challenges and patients must undergo life-long anticoagulation therapy. Bioprosthetic or tissue valves do not require anticoagulants due to their distinct similarity to the native valve geometry and haemodynamics, but many of these valves fail structurally within the first 10-15 years of implantation. 4. These shortcomings have directed present and future research in three main directions in attempts to design superior artificial valves: (i) engineering living tissue heart valves; (ii) development of advanced computational tools; and (iii) blood experiments to establish the link between flow and blood damage.
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Reul, Ross M.; Ramchandani, Mahesh K.; Reardon, Michael J.
2017-01-01
Surgical aortic valve replacement is the gold standard procedure to treat patients with severe, symptomatic aortic valve stenosis or insufficiency. Bioprosthetic valves are used for surgical aortic valve replacement with a much greater prevalence than mechanical valves. However, bioprosthetic valves may fail over time because of structural valve deterioration; this often requires intervention due to severe bioprosthetic valve stenosis or regurgitation or a combination of both. In select patients, transcatheter aortic valve replacement is an alternative to surgical aortic valve replacement. Transcatheter valve-in-valve (ViV) replacement is performed by implanting a transcatheter heart valve within a failing bioprosthetic valve. The transcatheter ViV operation is a less invasive procedure compared with reoperative surgical aortic valve replacement, but it has been associated with specific complications and requires extensive preoperative work-up and planning by the heart team. Data from experimental studies and analyses of results from clinical procedures have led to strategies to improve outcomes of these procedures. The type, size, and implant position of the transcatheter valve can be optimized for individual patients with knowledge of detailed dimensions of the surgical valve and radiographic and echocardiographic measurements of the patient's anatomy. Understanding the complexities of the ViV procedure can lead surgeons to make choices during the original surgical valve implantation that can make a future ViV operation more technically feasible years before it is required. PMID:29743998
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Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and ... is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among coal ...
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Characterization of small microfluidic valves for studies of mechanical properties of bacteria
Yang, Da; Greer, Clayton M.; Jones, Branndon P.; ...
2015-09-02
Lab-on-a-chip platforms present many new opportunities to study bacterial cells and cellular assemblies. Here, the authors describe a new platform that allows us to apply uniaxial stress to individual bacterial cells while observing the cell and its subcellular assemblies using a high resolution optical microscope. The microfluidic chip consists of arrays of miniature pressure actuated valves. By placing a bacterium under one of such valves and partially closing the valve by externally applied pressure, the cell can be deformed. Although large pressure actuated valves used in integrated fluidic circuits have been extensively studied previously, here the authors downsize those microfluidicmore » valves and use flow channels with rectangular cross-sections to maintain the bacteria in contact with cell culture medium during the experiments. The closure of these valves has not been characterized before. First, these valves are modeled using finite element analysis, and then compared the modeling results with the actual closing profiles of the valves, which is determined from absorption measurements. The measurements and modeling show with good agreement that the deflection of valves is a linear function of externally applied pressure and the deflection scales proportionally to the width of the flow channel. In addition to characterizing the valve, the authors show at a proof-of-principle level that it can be used to deform a bacterial cell at considerable magnitude. They found the largest deformations in 5 μm wide channels where the bacterial width and length increase by 1.6 and 1.25 times, respectively. Narrower and broader channels are less optimal for these studies. Finally, the platform presents a promising approach to probe, in a quantitative and systematic way, the mechanical properties of not only bacterial cells but possibly also yeast and other single-celled organisms.« less
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Lotfi, Shahram; Becker, Michael; Moza, Ajay; Autschbach, Rüdiger; Marx, Nikolaus; Schröder, Jörg
2017-09-10
Transcatheter aortic valve implantation has become an accepted treatment modality for inoperable or high-risk surgical patients with symptomatic severe aortic stenosis. We report the case of a 70-year-old white man who was treated for severe symptomatic aortic regurgitation using transcatheter aortic valve implantation from the apical approach. Because of recurrent cardiac decompensation 4 weeks after implantation he underwent the implantation of a left ventricular assist device system. A year later echocardiography showed a severe transvalvular central insufficiency. Our heart team decided to choose a valve-in-valve approach while reducing the flow rate of left ventricular assist device to minimum and pacing with a frequency of 140 beats/minute. There was an excellent result and our patient is doing well with no relevant insufficiency of the aortic valve at 12-month follow-up. This is the first report about a successful treatment of a stenotic JenaValve using a CoreValve Evolut R; the use of a CoreValve Evolut R prosthesis may be an optimal option for valve-in-valve procedures.
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Mitral valve disease—morphology and mechanisms
Levine, Robert A.; Hagége, Albert A.; Judge, Daniel P.; Padala, Muralidhar; Dal-Bianco, Jacob P.; Aikawa, Elena; Beaudoin, Jonathan; Bischoff, Joyce; Bouatia-Naji, Nabila; Bruneval, Patrick; Butcher, Jonathan T.; Carpentier, Alain; Chaput, Miguel; Chester, Adrian H.; Clusel, Catherine; Delling, Francesca N.; Dietz, Harry C.; Dina, Christian; Durst, Ronen; Fernandez-Friera, Leticia; Handschumacher, Mark D.; Jensen, Morten O.; Jeunemaitre, Xavier P.; Le Marec, Hervé; Le Tourneau, Thierry; Markwald, Roger R.; Mérot, Jean; Messas, Emmanuel; Milan, David P.; Neri, Tui; Norris, Russell A.; Peal, David; Perrocheau, Maelle; Probst, Vincent; Pucéat, Michael; Rosenthal, Nadia; Solis, Jorge; Schott, Jean-Jacques; Schwammenthal, Ehud; Slaugenhaupt, Susan A.; Song, Jae-Kwan; Yacoub, Magdi H.
2016-01-01
Mitral valve disease is a frequent cause of heart failure and death. Emerging evidence indicates that the mitral valve is not a passive structure, but—even in adult life—remains dynamic and accessible for treatment. This concept motivates efforts to reduce the clinical progression of mitral valve disease through early detection and modification of underlying mechanisms. Discoveries of genetic mutations causing mitral valve elongation and prolapse have revealed that growth factor signalling and cell migration pathways are regulated by structural molecules in ways that can be modified to limit progression from developmental defects to valve degeneration with clinical complications. Mitral valve enlargement can determine left ventricular outflow tract obstruction in hypertrophic cardiomyopathy, and might be stimulated by potentially modifiable biological valvular–ventricular interactions. Mitral valve plasticity also allows adaptive growth in response to ventricular remodelling. However, adverse cellular and mechanobiological processes create relative leaflet deficiency in the ischaemic setting, leading to mitral regurgitation with increased heart failure and mortality. Our approach, which bridges clinicians and basic scientists, enables the correlation of observed disease with cellular and molecular mechanisms, leading to the discovery of new opportunities for improving the natural history of mitral valve disease. PMID:26483167
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Conradi, Lenard; Kloth, Benjamin; Seiffert, Moritz; Schirmer, Johannes; Koschyk, Dietmar; Blankenberg, Stefan; Reichenspurner, Hermann; Diemert, Patrick; Treede, Hendrik
2014-12-01
Recently, the feasibility of valve-in-valve procedures using current first-generation transcatheter heart valves (THV) in cases of structural valve degeneration has been reported as an alternative to conventional open repeat valve replacement. By design, certain biological valve xenografts carry a high risk of coronary ostia occlusion due to lateral displacement of leaflets after valve-in-valve procedures. In the present report we aimed to prove feasibility and safety of transapical valve-in-valve implantation of the JenaValve THV in two cases of degenerated Mitroflow bioprostheses. We herein report two cases of successful transapical valve-in-valve procedures using a JenaValve THV implanted in Sorin Mitroflow bioprostheses for structural valve degeneration. Both patients were alive and in good clinical condition at 30 days from the procedure. However, increased transvalvular gradients were noted in both cases. Transcatheter valve-in-valve implantation of a JenaValve THV is a valid alternative for patients with degenerated Mitroflow bioprostheses of sufficient size and in the presence of short distances to the coronary ostia who are too ill for conventional repeat open heart surgery. Increased pressure gradients have to be expected and weighed against the disadvantages of other treatment options when planning such a procedure.
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The stem cell growth factor receptor KIT is not expressed on interstitial cells in bladder.
Gevaert, Thomas; Ridder, Dirk De; Vanstreels, Els; Daelemans, Dirk; Everaerts, Wouter; Aa, Frank Van Der; Pintelon, Isabel; Timmermans, Jean-Pierre; Roskams, Tania; Steiner, Clara; Neuhaus, Jochen
2017-06-01
The mast/stem cell growth factor receptor KIT has long been assumed to be a specific marker for interstitial cells of Cajal (ICC) in the bladder, with possible druggable perspectives. However, several authors have challenged the presence of KIT + ICC in recent years. The aim of this study was therefore to attempt to clarify the conflicting reports on KIT expression in the bladder of human beings, rat, mouse and guinea pig and to elucidate the possible role of antibody-related issues and interspecies differences in this matter. Fresh samples were obtained from human, rat, mouse and guinea pig cystectomies and processed for single/double immunohistochemistry/immunofluorescence. Specific antibodies against KIT, mast cell tryptase (MCT), anoctamin-1 (ANO1) and vimentin were used to characterize the cell types expressing KIT. Gut (jejunum) tissue was used as an external antibody control. Our results revealed KIT expression on mast cells but not on ICC in human, rat, mouse and guinea pig bladder. Parallel immunohistochemistry showed KIT expression on ICC in human, rat, mouse and guinea pig gut, which confirmed the selectivity of the KIT antibody clones. In conclusion, we have shown that KIT + cells in human, rat, mouse and guinea pig bladder are mast cells and not ICC. The present report is important as it opposes the idea that KIT + ICC are present in bladder. In this perspective, functional concepts of KIT + ICC being involved in sensory and/or motor aspects of bladder physiology should be revised. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
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Qu, Feini; Li, Qing; Wang, Xiao; Cao, Xuan; Zgonis, Miltiadis H; Esterhai, John L; Shenoy, Vivek B; Han, Lin; Mauck, Robert L
2018-02-19
Few regenerative approaches exist for the treatment of injuries to adult dense connective tissues. Compared to fetal tissues, adult connective tissues are hypocellular and show limited healing after injury. We hypothesized that robust repair can occur in fetal tissues with an immature extracellular matrix (ECM) that is conducive to cell migration, and that this process fails in adults due to the biophysical barriers imposed by the mature ECM. Using the knee meniscus as a platform, we evaluated the evolving micromechanics and microstructure of fetal and adult tissues, and interrogated the interstitial migratory capacity of adult meniscal cells through fetal and adult tissue microenvironments with or without partial enzymatic digestion. To integrate our findings, a computational model was implemented to determine how changing biophysical parameters impact cell migration through these dense networks. Our results show that the micromechanics and microstructure of the adult meniscus ECM sterically hinder cell mobility, and that modulation of these ECM attributes via an exogenous matrix-degrading enzyme permits migration through this otherwise impenetrable network. By addressing the inherent limitations to repair imposed by the mature ECM, these studies may define new clinical strategies to promote repair of damaged dense connective tissues in adults.
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Heart valve cardiomyocytes of mouse embryos express the serotonin transporter SERT
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pavone, Luigi Michele; Department of Biochemistry and Medical Biotechnologies, University of Naples Federico II, Naples; Spina, Anna
2008-12-12
Multiple evidence demonstrate a role for serotonin and its transporter SERT in heart valve development and disease. By utilizing a Cre/loxP system driven by SERT gene expression, we recently demonstrated a regionally restricted distribution of SERT-expressing cells in developing mouse heart. In order to characterize the cell types exhibiting SERT expression within the mouse heart valves at early developmental stages, in this study we performed immunohistochemistry for Islet1 (Isl1) and connexin-43 (Cx-43) on heart sections from SERT{sup Cre/+};ROSA26R embryos previously stained with X-gal. We observed the co-localization of LacZ staining with Isl1 labelling in the outflow tract, the right ventriclemore » and the conal region of E11.5 mouse heart. Cx-43 labelled cells co-localized with LacZ stained cells in the forming atrioventricular valves. These results demonstrate the cardiomyocyte phenotype of SERT-expressing cells in heart valves of the developing mouse heart, thus suggesting an active role of SERT in early heart valve development.« less
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Bergman, Ulf C.
1984-01-01
The safety valve contains a resilient gland to be held between a valve seat and a valve member and is secured to the valve member by a sleeve surrounding the end of the valve member adjacent to the valve seat. The sleeve is movable relative to the valve member through a limited axial distance and a gap exists between said valve member and said sleeve.
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Real-time 3D visualization of cellular rearrangements during cardiac valve formation
Pestel, Jenny; Ramadass, Radhan; Gauvrit, Sebastien; Helker, Christian; Herzog, Wiebke
2016-01-01
During cardiac valve development, the single-layered endocardial sheet at the atrioventricular canal (AVC) is remodeled into multilayered immature valve leaflets. Most of our knowledge about this process comes from examining fixed samples that do not allow a real-time appreciation of the intricacies of valve formation. Here, we exploit non-invasive in vivo imaging techniques to identify the dynamic cell behaviors that lead to the formation of the immature valve leaflets. We find that in zebrafish, the valve leaflets consist of two sets of endocardial cells at the luminal and abluminal side, which we refer to as luminal cells (LCs) and abluminal cells (ALCs), respectively. By analyzing cellular rearrangements during valve formation, we observed that the LCs and ALCs originate from the atrium and ventricle, respectively. Furthermore, we utilized Wnt/β-catenin and Notch signaling reporter lines to distinguish between the LCs and ALCs, and also found that cardiac contractility and/or blood flow is necessary for the endocardial expression of these signaling reporters. Thus, our 3D analyses of cardiac valve formation in zebrafish provide fundamental insights into the cellular rearrangements underlying this process. PMID:27302398
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Real-time 3D visualization of cellular rearrangements during cardiac valve formation.
Pestel, Jenny; Ramadass, Radhan; Gauvrit, Sebastien; Helker, Christian; Herzog, Wiebke; Stainier, Didier Y R
2016-06-15
During cardiac valve development, the single-layered endocardial sheet at the atrioventricular canal (AVC) is remodeled into multilayered immature valve leaflets. Most of our knowledge about this process comes from examining fixed samples that do not allow a real-time appreciation of the intricacies of valve formation. Here, we exploit non-invasive in vivo imaging techniques to identify the dynamic cell behaviors that lead to the formation of the immature valve leaflets. We find that in zebrafish, the valve leaflets consist of two sets of endocardial cells at the luminal and abluminal side, which we refer to as luminal cells (LCs) and abluminal cells (ALCs), respectively. By analyzing cellular rearrangements during valve formation, we observed that the LCs and ALCs originate from the atrium and ventricle, respectively. Furthermore, we utilized Wnt/β-catenin and Notch signaling reporter lines to distinguish between the LCs and ALCs, and also found that cardiac contractility and/or blood flow is necessary for the endocardial expression of these signaling reporters. Thus, our 3D analyses of cardiac valve formation in zebrafish provide fundamental insights into the cellular rearrangements underlying this process. © 2016. Published by The Company of Biologists Ltd.
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Fracturing mechanics before valve-in-valve therapy of small aortic bioprosthetic heart valves.
Johansen, Peter; Engholt, Henrik; Tang, Mariann; Nybo, Rasmus F; Rasmussen, Per D; Nielsen-Kudsk, Jens Erik
2017-10-13
Patients with degraded bioprosthetic heart valves (BHV) who are not candidates for valve replacement may benefit from transcatheter valve-in-valve (VIV) therapy. However, in smaller-sized surgical BHV the resultant orifice may become too narrow. To overcome this, the valve frame can be fractured by a high-pressure balloon prior to VIV. However, knowledge on fracture pressures and mechanics are prerequisites. The aim of this study was to identify the fracture pressures needed in BHV, and to describe the fracture mechanics. Commonly used BHV of small sizes were mounted on a high-pressure balloon situated in a biplane fluoroscopic system with a high-speed camera. The instant of fracture was captured along with the balloon pressure. The valves were inspected for material protrusion and later dissected for fracture zone investigation and description. The valves with a polymer frame fractured at a lower pressure (8-10 atm) than those with a metal stent (19-26 atm). None of the fractured valves had elements protruding. VIV procedures in small-sized BHV may be performed after prior fracture of the valve frame by high-pressure balloon dilatation. This study provides tentative guidelines for expected balloon sizes and pressures for valve fracturing.
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Vascularization of bioprosthetic valve material
NASA Astrophysics Data System (ADS)
Boughner, Derek R.; Dunmore-Buyze, Joy; Heenatigala, Dino; Lohmann, Tara; Ellis, Chris G.
1999-04-01
Cell membrane remnants represent a probable nucleation site for calcium deposition in bioprosthetic heart valves. Calcification is a primary failure mode of both bovine pericardial and porcine aortic heterograft bioprosthesis but the nonuniform pattern of calcium distribution within the tissue remains unexplained. Searching for a likely cellular source, we considered the possibility of a previously overlooked small blood vessel network. Using a videomicroscopy technique, we examined 5 matched pairs of porcine aortic and pulmonary valves and 14 samples from 6 bovine pericardia. Tissue was placed on a Leitz Metallux microscope and transilluminated with a 75 watt mercury lamp. Video images were obtained using a silicon intensified target camera equipped with a 431 nm interference filter to maximize contrast of red cells trapped in a capillary microvasculature. Video images were recorded for analysis on a Silicon Graphics Image Analysis work station equipped with a video frame grabber. For porcine valves, the technique demonstrated a vascular bed in the central spongiosa at cusp bases with vessel sizes from 6-80 micrometers . Bovine pericardium differed with a more uniform distribution of 7-100 micrometers vessels residing centrally. Thus, small blood vessel endothelial cells provide a potential explanation patterns of bioprosthetic calcification.
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Chen, Yu-Chih; Ingram, Patrick; Yoon, Euisik
2016-01-01
Cancer-stromal interaction is a critical process in tumorigenesis. Conventional dish-based co-culture assays simply mix two cell types in the same dish; thus, they are deficient in controlling cell locations and precisely tracking single cell behavior from heterogeneous cell populations. Microfluidic technology can provide a good spatial temporal control of microenvironments, but the control has been typically realized by using external pumps, making long-term cultures cumbersome and bulky. In this work, we present a cell-cell interaction microfluidic platform that can accurately control co-culture microenvironment by using a novel electrolytic cell isolation scheme without using any valves or pneumatic pumps. The proposed microfluidic platform can also precisely control the number of interacting cells and pairing ratios to emulate cancer niches. More than 80% of the chambers captured the desired number of cells. The duration of cell isolation can be adjusted by electrolytic bubble generation and removal. We verified that electrolytic process has a negligible effect on cell viability and proliferation in our platform. To the best of our knowledge, this work is the first attempt to incorporate electrolytic bubble generation as a cell isolation method in microfluidics. For proof of feasibility, we performed cell-cell interaction assays between prostate cancer (PC3) cells and myoblast (C2C12) cells. The preliminary results demonstrated the potential of using electrolysis for micro-environmental control during cell culture. Also, the ratio controlled cell-cell interaction assays was successfully performed showing that the cell pairing ratios of PC3 to C2C12 affected the proliferation rate of myoblast cells due to increased secretion of growth factors from prostate cancer cells. PMID:25118341
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Upton, Hubert Allen; Garcia, Pablo
1999-08-24
A check valve for use in a GDCS of a nuclear reactor and having a motor driven disk including a rotatable armature for rotating the check valve disk over its entire range of motion is described. In one embodiment, the check valve includes a valve body having a coolant flow channel extending therethrough. The coolant flow channel includes an inlet end and an outlet end. A valve body seat is located on an inner surface of the valve body. The check valve further includes a disk assembly, sometimes referred to as the motor driven disc, having a counterweight and a disk shaped valve. The disk valve includes a disk base having a seat for seating with the valve body seat. The disk assembly further includes a first hinge pin member which extends at least partially through the disk assembly and is engaged to the disk. The disk valve is rotatable relative to the first hinge pin member. The check valve also includes a motor having a stator frame with a stator bore therein. An armature is rotatably positioned within the stator bore and the armature is coupled to the disk valve to cause the disk valve to rotate about its full range of motion.
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Upton, H.A.; Garcia, P.
1999-08-24
A check valve for use in a GDCS of a nuclear reactor and having a motor driven disk including a rotatable armature for rotating the check valve disk over its entire range of motion is described. In one embodiment, the check valve includes a valve body having a coolant flow channel extending therethrough. The coolant flow channel includes an inlet end and an outlet end. A valve body seat is located on an inner surface of the valve body. The check valve further includes a disk assembly, sometimes referred to as the motor driven disc, having a counterweight and a disk shaped valve. The disk valve includes a disk base having a seat for seating with the valve body seat. The disk assembly further includes a first hinge pin member which extends at least partially through the disk assembly and is engaged to the disk. The disk valve is rotatable relative to the first hinge pin member. The check valve also includes a motor having a stator frame with a stator bore therein. An armature is rotatably positioned within the stator bore and the armature is coupled to the disk valve to cause the disk valve to rotate about its full range of motion. 5 figs.
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Characterization of lymphocyte populations in nonspecific interstitial pneumonia*
Keogh, Karina A; Limper, Andrew H
2005-01-01
Study objectives Nonspecific interstitial pneumonia (NSIP) has been identified as a distinct entity with a more favorable prognosis and better response to immunosuppressive therapies than usual interstitial pneumonia (UIP). However the inflammatory profile of NSIP has not been characterized. Design Using immunohistochemistry techniques on open lung biopsy specimens, the infiltrate in NSIP was characterized in terms of T and B cells, and macrophages, and the T cell population further identified as either CD4 (helper) or CD8 (suppressor-cytotoxic) T cells. The extent of Th1 and Th2 cytokine producing cells was determined and compared to specimens from patients with UIP. Results In ten NSIP tissue samples 41.4 ± 4% of mononuclear cells expressed CD3, 24.7 ± 1.8% CD4, 19.1 ± 2% CD8, 27.4 ± 3.9% CD20, and 14.3 ± 1.6% had CD68 expression. Mononuclear cells expressed INFγ 21.9 ± 1.9% of the time and IL-4 in 3.0 ± 1%. In contrast, biopsies from eight patients with UIP demonstrated substantially less cellular staining for either cytokine (INFγ; 4.6 ± 1.7% and IL-4; 0.6 ± 0.3%). Significant populations of CD20 positive B-cells were also identified. Conclusion The lymphocytic infiltrate in NSIP is characterized by an elevated CD4/CD8 T-cell ratio, and is predominantly of Th1 type, with additional populations rich in B-cells. Such features are consistent with the favorable clinical course observed in patients with NSIP compared to UIP. PMID:16287509
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Depolarizing Effects of Daikenchuto on Interstitial Cells of Cajal from Mouse Small Intestine
Kim, Hyungwoo; Kim, Hyun Jung; Yang, Dongki; Jung, Myeong Ho; Kim, Byung Joo
2017-01-01
Background: Daikenchuto (DKT; TJ-100, TU-100), a traditional herbal medicineis used in modern medicine to treat gastrointestinal (GI) functional disorders. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the GI tract and play important roles in the regulation of GI motility. Objective: The objective of this study was to investigate the effects of DKT on the pacemaker potentials (PPs) of cultured ICCs from murine small intestine. Materials and Methods: Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues. All experiments on ICCs were performed after 12 h of culture. The whole-cell patch-clamp configuration was used to record ICC PPs (current clamp mode). All experiments were performed at 30-32°C. Results: In current-clamp modeDKT depolarized and concentration-dependently decreased the amplitudes of PPs. Y25130 (a 5-HT3 receptor antagonist) or SB269970 (a 5-HT7 receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT4 receptor antagonist) did. Methoctramine (a muscarinic M2 receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-diphenylacetoxy-N-methylpiperidine methiodide (a muscarinic M3 receptor antagonist) facilitated blockade of DKT-induced PP depolarization. Pretreatment with an external Ca2+-free solution or thapsigargin abolished PPsand under these conditions, DKT did not induce PP depolarization. Furthermore Ginseng radix and Zingiberis rhizomes depolarized PPs, whereas Zanthoxyli fructus fruit (the third component of DKT) hyperpolarized PPs. Conclusion: These results suggest that DKT depolarizes ICC PPs in an internal or external Ca2+-dependent manner by stimulating 5-HT4 and M3 receptors. Furthermore, the authors suspect that the component in DKT largely responsible for depolarization is probably also a component of Ginseng radix and Zingiberis rhizomes. SUMMARY Daikenchuto (DKT) depolarized and concentration-dependently decreased the amplitudes of
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Depolarizing Effects of Daikenchuto on Interstitial Cells of Cajal from Mouse Small Intestine.
Kim, Hyungwoo; Kim, Hyun Jung; Yang, Dongki; Jung, Myeong Ho; Kim, Byung Joo
2017-01-01
Daikenchuto (DKT; TJ-100, TU-100), a traditional herbal medicineis used in modern medicine to treat gastrointestinal (GI) functional disorders. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the GI tract and play important roles in the regulation of GI motility. The objective of this study was to investigate the effects of DKT on the pacemaker potentials (PPs) of cultured ICCs from murine small intestine. Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues. All experiments on ICCs were performed after 12 h of culture. The whole-cell patch-clamp configuration was used to record ICC PPs (current clamp mode). All experiments were performed at 30-32°C. In current-clamp modeDKT depolarized and concentration-dependently decreased the amplitudes of PPs. Y25130 (a 5-HT 3 receptor antagonist) or SB269970 (a 5-HT 7 receptor antagonist) did not block DKT-induced PP depolarization, but RS39604 (a 5-HT 4 receptor antagonist) did. Methoctramine (a muscarinic M 2 receptor antagonist) failed to block DKT-induced PP depolarization, but pretreating 4-diphenylacetoxy-N-methylpiperidine methiodide (a muscarinic M 3 receptor antagonist) facilitated blockade of DKT-induced PP depolarization. Pretreatment with an external Ca 2+ -free solution or thapsigargin abolished PPsand under these conditions, DKT did not induce PP depolarization. Furthermore Ginseng radix and Zingiberis rhizomes depolarized PPs, whereas Zanthoxyli fructus fruit (the third component of DKT) hyperpolarized PPs. These results suggest that DKT depolarizes ICC PPs in an internal or external Ca 2+ -dependent manner by stimulating 5-HT 4 and M 3 receptors. Furthermore, the authors suspect that the component in DKT largely responsible for depolarization is probably also a component of Ginseng radix and Zingiberis rhizomes. Daikenchuto (DKT) depolarized and concentration-dependently decreased the amplitudes of pacemaker potentials (PPs)Y25130 (a 5-HT 3 receptor antagonist) or
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Fabricating microfluidic valve master molds in SU-8 photoresist
NASA Astrophysics Data System (ADS)
Dy, Aaron J.; Cosmanescu, Alin; Sluka, James; Glazier, James A.; Stupack, Dwayne; Amarie, Dragos
2014-05-01
Multilayer soft lithography has become a powerful tool in analytical chemistry, biochemistry, material and life sciences, and medical research. Complex fluidic micro-circuits require reliable components that integrate easily into microchips. We introduce two novel approaches to master mold fabrication for constructing in-line micro-valves using SU-8. Our fabrication techniques enable robust and versatile integration of many lab-on-a-chip functions including filters, mixers, pumps, stream focusing and cell-culture chambers, with in-line valves. SU-8 created more robust valve master molds than the conventional positive photoresists used in multilayer soft lithography, but maintained the advantages of biocompatibility and rapid prototyping. As an example, we used valve master molds made of SU-8 to fabricate PDMS chips capable of precisely controlling beads or cells in solution.
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Transcatheter Aortic Valve Replacement for Native Aortic Valve Regurgitation
Spina, Roberto; Anthony, Chris; Muller, David WM
2015-01-01
Transcatheter aortic valve replacement with either the balloon-expandable Edwards SAPIEN XT valve, or the self-expandable CoreValve prosthesis has become the established therapeutic modality for severe aortic valve stenosis in patients who are not deemed suitable for surgical intervention due to excessively high operative risk. Native aortic valve regurgitation, defined as primary aortic incompetence not associated with aortic stenosis or failed valve replacement, on the other hand, is still considered a relative contraindication for transcatheter aortic valve therapies, because of the absence of annular or leaflet calcification required for secure anchoring of the transcatheter heart valve. In addition, severe aortic regurgitation often coexists with aortic root or ascending aorta dilatation, the treatment of which mandates operative intervention. For these reasons, transcatheter aortic valve replacement has been only sporadically used to treat pure aortic incompetence, typically on a compassionate basis and in surgically inoperable patients. More recently, however, transcatheter aortic valve replacement for native aortic valve regurgitation has been trialled with newer-generation heart valves, with encouraging results, and new ancillary devices have emerged that are designed to stabilize the annulus–root complex. In this paper we review the clinical context, technical characteristics and outcomes associated with transcatheter treatment of native aortic valve regurgitation. PMID:29588674
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Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient.
Azar, Ibrahim; Esfandiarifard, Saghi; Sinai, Pedram; Wazir, Ali; Foulke, Llewellyn; Mehdi, Syed
2017-01-01
Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS), and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN), in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF) by either TKI (sunitinib and sorafenib) or antibodies (bevacizumab) suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.
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NASA Technical Reports Server (NTRS)
Wojciechowski, Bogdan V. (Inventor); Pegg, Robert J. (Inventor)
2003-01-01
A fast-acting valve includes an annular valve seat that defines an annular valve orifice between the edges of the annular valve seat, an annular valve plug sized to cover the valve orifice when the valve is closed, and a valve-plug holder for moving the annular valve plug on and off the annular valve seat. The use of an annular orifice reduces the characteristic distance between the edges of the valve seat. Rather than this distance being equal to the diameter of the orifice, as it is for a conventional circular orifice, the characteristic distance equals the distance between the inner and outer radii (for a circular annulus). The reduced characteristic distance greatly reduces the gap required between the annular valve plug and the annular valve seat for the valve to be fully open, thereby greatly reducing the required stroke and corresponding speed and acceleration of the annular valve plug. The use of a valve-plug holder that is under independent control to move the annular valve plug between its open and closed positions is important for achieving controllable fast operation of the valve.
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Computed Flow Through An Artificial Heart Valve
NASA Technical Reports Server (NTRS)
Rogers, Stewart E.; Kwak, Dochan; Kiris, Cetin; Chang, I-Dee
1994-01-01
Report discusses computations of blood flow through prosthetic tilting disk valve. Computational procedure developed in simulation used to design better artificial hearts and valves by reducing or eliminating following adverse flow characteristics: large pressure losses, which prevent hearts from working efficiently; separated and secondary flows, which causes clotting; and high turbulent shear stresses, which damages red blood cells. Report reiterates and expands upon part of NASA technical memorandum "Computed Flow Through an Artificial Heart and Valve" (ARC-12983). Also based partly on research described in "Numerical Simulation of Flow Through an Artificial Heart" (ARC-12478).
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Interstitial laser prostatectomy
NASA Astrophysics Data System (ADS)
Johnson, Douglas E.; Cromeens, Douglas M.; Price, Roger E.
1994-05-01
Interstitial laser coagulation of the canine prostate using the Sharplan interstitial thermal therapy fiber (Model 25432) was performed in 9 adult dogs and the subsequent gross and histopathologic changes occurring in the prostate were studied at intervals ranging from 1 hour to 5 weeks. A large well-demarcated area of acute coagulative necrosis developed around each fiber tract which in turn was surrounded by a prominent narrow zone of marked tissue disruption and an outer zone of hemorrhage. Liquefaction developed within the coagulative areas within 24 hours and by 4 days, each prostatic lobe contained an irregular cavity which became lined by normal-appearing transitional epithelium and that by 5 weeks, communicated with the prostatic urethra. These changes, similar to those reported following transurethral visual laser ablation of the prostate, suggest that interstitial laser thermal therapy may provide an alternative means for treating selected patients suffering from prostatic enlargement.
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Advances in the treatment of rheumatic interstitial lung disease.
Vassallo, Robert; Thomas, Charles F
2004-05-01
Interstitial lung disease frequently complicates the rheumatic diseases. The purpose of this review is to outline recent advances and current concepts regarding the management of these interstitial lung diseases. Several histologic lesions cause interstitial lung disease in rheumatic diseases, including nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing pneumonia, lymphocytic interstitial pneumonia, desquamative interstitial pneumonia, and acute interstitial pneumonia. Although the relative frequency of occurrence of these histopathologic lesions is not definitively established, it seems that nonspecific interstitial pneumonia accounts for a large proportion of rheumatic disease-associated interstitial lung diseases. Although usual interstitial pneumonia generally responds poorly to corticosteroid therapy, other forms of interstitial pneumonia are often steroid responsive and have a more favorable long-term prognosis. Pulmonary hypertension is increasingly recognized as a complication of these interstitial lung diseases. Treatment of pulmonary hypertension in these patients provides clinical benefit and may suppress pulmonary inflammation and fibrosis. Lung transplantation is a treatment option for selected patients with severe pulmonary involvement and limited life expectancy. Interstitial lung disease is common in the rheumatic diseases, may be caused by a variety of lesions that respond differently to treatment, and may lead to the development of pulmonary hypertension. Whether the prognosis of interstitial lung disease associated with rheumatic disease is similar to that associated with the idiopathic interstitial pneumonias is not known. Treatment of these interstitial lung diseases should take into account the specific histologic lesion, the activity of the underlying rheumatic disease, and associated pulmonary hypertension, if present. The diagnosis of a rheumatic disease is no longer an absolute contraindication to lung
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MacGrogan, Donal; D'Amato, Gaetano; Travisano, Stanislao; Martinez-Poveda, Beatriz; Luxán, Guillermo; Del Monte-Nieto, Gonzalo; Papoutsi, Tania; Sbroggio, Mauro; Bou, Vanesa; Gomez-Del Arco, Pablo; Gómez, Manuel Jose; Zhou, Bin; Redondo, Juan Miguel; Jiménez-Borreguero, Luis J; de la Pompa, José Luis
2016-05-13
The Notch signaling pathway is crucial for primitive cardiac valve formation by epithelial-mesenchymal transition, and NOTCH1 mutations cause bicuspid aortic valve; however, the temporal requirement for the various Notch ligands and receptors during valve ontogeny is poorly understood. The aim of this study is to determine the functional specificity of Notch in valve development. Using cardiac-specific conditional targeted mutant mice, we find that endothelial/endocardial deletion of Mib1-Dll4-Notch1 signaling, possibly favored by Manic-Fringe, is specifically required for cardiac epithelial-mesenchymal transition. Mice lacking endocardial Jag1, Notch1, or RBPJ displayed enlarged valve cusps, bicuspid aortic valve, and septal defects, indicating that endocardial Jag1 to Notch1 signaling is required for post-epithelial-mesenchymal transition valvulogenesis. Valve dysmorphology was associated with increased mesenchyme proliferation, indicating that Jag1-Notch1 signaling restricts mesenchyme cell proliferation non-cell autonomously. Gene profiling revealed upregulated Bmp signaling in Jag1-mutant valves, providing a molecular basis for the hyperproliferative phenotype. Significantly, the negative regulator of mesenchyme proliferation, Hbegf, was markedly reduced in Jag1-mutant valves. Hbegf expression in embryonic endocardial cells could be readily activated through a RBPJ-binding site, identifying Hbegf as an endocardial Notch target. Accordingly, addition of soluble heparin-binding EGF-like growth factor to Jag1-mutant outflow tract explant cultures rescued the hyperproliferative phenotype. During cardiac valve formation, Dll4-Notch1 signaling leads to epithelial-mesenchymal transition and cushion formation. Jag1-Notch1 signaling subsequently restrains Bmp-mediated valve mesenchyme proliferation by sustaining Hbegf-EGF receptor signaling. Our studies identify a mechanism of signaling cross talk during valve morphogenesis involved in the origin of congenital heart
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Characterization of the Tumor Secretome from Tumor Interstitial Fluid (TIF).
Gromov, Pavel; Gromova, Irina
2016-01-01
Tumor interstitial fluid (TIF) surrounds and perfuses bodily tumorigenic tissues and cells, and can accumulate by-products of tumors and stromal cells in a relatively local space. Interstitial fluid offers several important advantages for biomarker and therapeutic target discovery, especially for cancer. Here, we describe the most currently accepted method for recovering TIF from tumor and nonmalignant tissues that was initially performed using breast cancer tissue. TIF recovery is achieved by passive extraction of fluid from small, surgically dissected tissue specimens in phosphate-buffered saline. We also present protocols for hematoxylin and eosin (H&E) staining of snap-frozen and formalin-fixed, paraffin-embedded (FFPE) tumor sections and for proteomic profiling of TIF and matched tumor samples by high-resolution two-dimensional gel electrophoresis (2D-PAGE) to enable comparative analysis of tumor secretome and paired tumor tissue.
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Ahuja, Suchit; Dogra, Deepika; Stainier, Didier Y R; Reischauer, Sven
2016-04-01
The atrioventricular canal (AVC) connects the atrial and ventricular chambers of the heart and its formation is critical for the development of the cardiac valves, chamber septation and formation of the cardiac conduction system. Consequently, problems in AVC formation can lead to congenital defects ranging from cardiac arrhythmia to incomplete cardiac septation. While our knowledge about early heart tube formation is relatively comprehensive, much remains to be investigated about the genes that regulate AVC formation. Here we identify a new role for the basic helix-loop-helix factor Id4 in zebrafish AVC valve development and function. id4 is first expressed in the AVC endocardium and later becomes more highly expressed in the atrial chamber. TALEN induced inactivation of id4 causes retrograde blood flow at the AV canal under heat induced stress conditions, indicating defects in AV valve function. At the molecular level, we found that id4 inactivation causes misexpression of several genes important for AVC and AV valve formation including bmp4 and spp1. We further show that id4 appears to control the number of endocardial cells that contribute to the AV valves by regulating Wnt signaling in the developing AVC endocardium. Copyright © 2016 Elsevier Inc. All rights reserved.
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Tsujimura, Tohru; Makiishi-Shimobayashi, Chiaki; Lundkvist, Johan; Lendahl, Urban; Nakasho, Keiji; Sugihara, Ayako; Iwasaki, Teruo; Mano, Masayuki; Yamada, Naoko; Yamashita, Kunihiro; Toyosaka, Akihiro; Terada, Nobuyuki
2001-01-01
It has recently been proposed that gastrointestinal stromal tumors (GISTs) originate from stem cells that differentiate toward a phenotype of interstitial cells of Cajal (ICCs). Nestin is a newly identified intermediate filament protein, and is predominantly expressed in immature cells, such as neuroectodermal stem cells and skeletal muscle progenitor cells, and tumors originating from these cells. In this study, we examined, using immunohistochemistry, the nestin expression in GISTs and ICCs to clarify the origin of GISTs. Strong immunoreactivity for nestin was observed in all 18 GISTs, and its expression was confirmed by Western blot and Northern blot analyses. In contrast, three leiomyomas and a schwannoma that developed in the gastrointestinal tract showed no apparent immunoreactivity for nestin. Among 17 mesenchymal tumors (seven leiomyosarcomas, five malignant peripheral nerve sheath tumors, and five fibrosarcomas) that occurred in sites other than the gastrointestinal tract, only two malignant peripheral nerve sheath tumors were moderately immunoreactive for nestin. Furthermore, with fluorescence double immunostaining of the normal small intestine, nestin expression was demonstrated in ICCs. These results show that nestin may be a useful marker for diagnosis of GISTs, and support the current hypothesis that GISTs are tumors of stem cells that differentiate toward an ICC phenotype. PMID:11238030
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Bioprosthetic Valve Fracture During Valve-in-valve TAVR: Bench to Bedside
Saxon, John T; Allen, Keith B; Cohen, David J
2018-01-01
Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) has been established as a safe and effective means of treating failed surgical bioprosthetic valves (BPVs) in patients at high risk for complications related to reoperation. Patients who undergo VIV TAVR are at risk of patient–prosthesis mismatch, as the transcatheter heart valve (THV) is implanted within the ring of the existing BPV, limiting full expansion and reducing the maximum achievable effective orifice area of the THV. Importantly, patient–prosthesis mismatch and high residual transvalvular gradients are associated with reduced survival following VIV TAVR. Bioprosthetic valve fracture (BVF) is as a novel technique to address this problem. During BPV, a non-compliant valvuloplasty balloon is positioned within the BPV frame, and a highpressure balloon inflation is performed to fracture the surgical sewing ring of the BPV. This allows for further expansion of the BPV as well as the implanted THV, thus increasing the maximum effective orifice area that can be achieved after VIV TAVR. This review focuses on the current evidence base for BVF to facilitate VIV TAVR, including initial bench testing, procedural technique, clinical experience and future directions. PMID:29593832
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Bioprosthetic Valve Fracture During Valve-in-valve TAVR: Bench to Bedside.
Saxon, John T; Allen, Keith B; Cohen, David J; Chhatriwalla, Adnan K
2018-01-01
Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) has been established as a safe and effective means of treating failed surgical bioprosthetic valves (BPVs) in patients at high risk for complications related to reoperation. Patients who undergo VIV TAVR are at risk of patient-prosthesis mismatch, as the transcatheter heart valve (THV) is implanted within the ring of the existing BPV, limiting full expansion and reducing the maximum achievable effective orifice area of the THV. Importantly, patient-prosthesis mismatch and high residual transvalvular gradients are associated with reduced survival following VIV TAVR. Bioprosthetic valve fracture (BVF) is as a novel technique to address this problem. During BPV, a non-compliant valvuloplasty balloon is positioned within the BPV frame, and a highpressure balloon inflation is performed to fracture the surgical sewing ring of the BPV. This allows for further expansion of the BPV as well as the implanted THV, thus increasing the maximum effective orifice area that can be achieved after VIV TAVR. This review focuses on the current evidence base for BVF to facilitate VIV TAVR, including initial bench testing, procedural technique, clinical experience and future directions.
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Mitochondrial calcium handling within the interstitial cells of Cajal
Cheng, Leo K.
2014-01-01
The interstitial cells of Cajal (ICC) drive rhythmic pacemaking contractions in the gastrointestinal system. The ICC generate pacemaking signals by membrane depolarizations associated with the release of intracellular calcium (Ca2+) in the endoplasmic reticulum (ER) through inositol-trisphosphate (IP3) receptors (IP3R) and uptake by mitochondria (MT). This Ca2+ dynamic is hypothesized to generate pacemaking signals by calibrating ER Ca2+ store depletions and membrane depolarization with ER store-operated Ca2+ entry mechanisms. Using a biophysically based spatio-temporal model of integrated Ca2+ transport in the ICC, we determined the feasibility of ER depletion timescale correspondence with experimentally observed pacemaking frequencies while considering the impact of IP3R Ca2+ release and MT uptake on bulk cytosolic Ca2+ levels because persistent elevations of free intracellular Ca2+ are toxic to the cell. MT densities and distributions are varied in the model geometry to observe MT influence on free cytosolic Ca2+ and the resulting frequencies of ER Ca2+ store depletions, as well as the sarco-endoplasmic reticulum Ca2+ ATP-ase (SERCA) and IP3 agonist concentrations. Our simulations show that high MT densities observed in the ICC are more relevant to ER establishing Ca2+ depletion frequencies than protection of the cytosol from elevated free Ca2+, whereas the SERCA pump is more relevant to containing cytosolic Ca2+ elevations. Our results further suggest that the level of IP3 agonist stimulating ER Ca2+ release, subsequent MT uptake, and eventual activation of ER store-operated Ca2+ entry may determine frequencies of rhythmic pacemaking exhibited by the ICC across species and tissue types. PMID:24789203
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Ehrbar, Martin; Pérez-Pomares, José M.
2013-01-01
The non-muscular cells that populate the space found between cardiomyocyte fibers are known as ‘cardiac interstitial cells’ (CICs). CICs are heterogeneous in nature and include different cardiac progenitor/stem cells, cardiac fibroblasts and other cell types. Upon heart damage CICs soon respond by initiating a reparative response that transforms with time into extensive fibrosis and heart failure. Despite the biomedical relevance of CICs, controversy remains on the ontogenetic relationship existing between the different cell kinds homing at the cardiac interstitium, as well as on the molecular signals that regulate their differentiation, maturation, mutual interaction and role in adult cardiac homeostasis and disease. Our work focuses on the analysis of epicardial-derived cells, the first cell type that colonizes the cardiac interstitium. We present here a characterization and an experimental analysis of the differentiation potential and mobilization properties of a new cell line derived from mouse embryonic epicardium (EPIC). Our results indicate that these cells express some markers associated with cardiovascular stemness and retain part of the multipotent properties of embryonic epicardial derivatives, spontaneously differentiating into smooth muscle, and fibroblast/myofibroblast-like cells. Epicardium-derived cells are also shown to initiate a characteristic response to different growth factors, to display a characteristic proteolytic expression profile and to degrade biological matrices in 3D in vitro assays. Taken together, these data indicate that EPICs are relevant to the analysis of epicardial-derived CICs, and are a god model for the research on cardiac fibroblasts and the role these cells play in ventricular remodeling in both ischemic or non/ischemic myocardial disease. PMID:23349729
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Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions.
Cheung, Daniel Y; Duan, Bin; Butcher, Jonathan T
2015-01-01
Heart valve disease is an increasingly prevalent and clinically serious condition. There are no clinically effective biological diagnostics or treatment strategies. The only recourse available is replacement with a prosthetic valve, but the inability of these devices to grow or respond biologically to their environments necessitates multiple resizing surgeries and life-long coagulation treatment, especially in children. Tissue engineering has a unique opportunity to impact heart valve disease by providing a living valve conduit, capable of growth and biological integration. This review will cover current tissue engineering strategies in fabricating heart valves and their progress towards the clinic, including molded scaffolds using naturally derived or synthetic polymers, decellularization, electrospinning, 3D bioprinting, hybrid techniques, and in vivo engineering. Whereas much progress has been made to create functional living heart valves, a clinically viable product is not yet realized. The next leap in engineered living heart valves will require a deeper understanding of how the natural multi-scale structural and biological heterogeneity of the tissue ensures its efficient function. Related, improved fabrication strategies must be developed that can replicate this de novo complexity, which is likely instructive for appropriate cell differentiation and remodeling whether seeded with autologous stem cells in vitro or endogenously recruited cells.
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Current Progress in Tissue Engineering of Heart Valves: Multiscale Problems, Multiscale Solutions
Cheung, Daniel Y; Duan, Bin; Butcher, Jonathan T.
2016-01-01
Introduction Heart valve disease is an increasingly prevalent and clinically serious condition. There are no clinically effective biological diagnostics or treatment strategies. The only recourse available is replacement with a prosthetic valve, but the inability of these devices to grow or respond biologically to their environments necessitates multiple resizing surgeries and life-long coagulation treatment, especially in children. Tissue engineering has a unique opportunity to impact heart valve disease by providing a living valve conduit, capable of growth and biological integration. Areas covered This review will cover current tissue engineering strategies in fabricating heart valves and their progress towards the clinic, including molded scaffolds using naturally-derived or synthetic polymers, decellularization, electrospinning, 3D bioprinting, hybrid techniques, and in vivo engineering. Expert opinion While much progress has been made to create functional living heart valves, a clinically viable product is not yet realized. The next leap in engineered living heart valves will require a deeper understanding of how the natural multi-scale structural and biological heterogeneity of the tissue ensures its efficient function. Related, improved fabrication strategies must be developed that can replicate this de novo complexity, which is likely instructive for appropriate cell differentiation and remodeling whether seeded with autologous stem cells in vitro or endogenously recruited cells. PMID:26027436
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klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis
Steed, Emily; Faggianelli, Nathalie; Roth, Stéphane; Ramspacher, Caroline; Concordet, Jean-Paul; Vermot, Julien
2016-01-01
The heartbeat and blood flow signal to endocardial cell progenitors through mechanosensitive proteins that modulate the genetic program controlling heart valve morphogenesis. To date, the mechanism by which mechanical forces coordinate tissue morphogenesis is poorly understood. Here we use high-resolution imaging to uncover the coordinated cell behaviours leading to heart valve formation. We find that heart valves originate from progenitors located in the ventricle and atrium that generate the valve leaflets through a coordinated set of endocardial tissue movements. Gene profiling analyses and live imaging reveal that this reorganization is dependent on extracellular matrix proteins, in particular on the expression of fibronectin1b. We show that blood flow and klf2a, a major endocardial flow-responsive gene, control these cell behaviours and fibronectin1b synthesis. Our results uncover a unique multicellular layering process leading to leaflet formation and demonstrate that endocardial mechanotransduction and valve morphogenesis are coupled via cellular rearrangements mediated by fibronectin synthesis. PMID:27221222
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Multiple-Step Injection Molding for Fibrin-Based Tissue-Engineered Heart Valves
Weber, Miriam; Gonzalez de Torre, Israel; Moreira, Ricardo; Frese, Julia; Oedekoven, Caroline; Alonso, Matilde; Rodriguez Cabello, Carlos J.
2015-01-01
Heart valves are elaborate and highly heterogeneous structures of the circulatory system. Despite the well accepted relationship between the structural and mechanical anisotropy and the optimal function of the valves, most approaches to create tissue-engineered heart valves (TEHVs) do not try to mimic this complexity and rely on one homogenous combination of cells and materials for the whole construct. The aim of this study was to establish an easy and versatile method to introduce spatial diversity into a heart valve fibrin scaffold. We developed a multiple-step injection molding process that enables the fabrication of TEHVs with heterogeneous composition (cell/scaffold material) of wall and leaflets without the need of gluing or suturing components together, with the leaflets firmly connected to the wall. The integrity of the valves and their functionality was proved by either opening/closing cycles in a bioreactor (proof of principle without cells) or with continuous stimulation over 2 weeks. We demonstrated the potential of the method by the two-step molding of the wall and the leaflets containing different cell lines. Immunohistology after stimulation confirmed tissue formation and demonstrated the localization of the different cell types. Furthermore, we showed the proof of principle fabrication of valves using different materials for wall (fibrin) and leaflets (hybrid gel of fibrin/elastin-like recombinamer) and with layered leaflets. The method is easy to implement, does not require special facilities, and can be reproduced in any tissue-engineering lab. While it has been demonstrated here with fibrin, it can easily be extended to other hydrogels. PMID:25654448
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Multiple-Step Injection Molding for Fibrin-Based Tissue-Engineered Heart Valves.
Weber, Miriam; Gonzalez de Torre, Israel; Moreira, Ricardo; Frese, Julia; Oedekoven, Caroline; Alonso, Matilde; Rodriguez Cabello, Carlos J; Jockenhoevel, Stefan; Mela, Petra
2015-08-01
Heart valves are elaborate and highly heterogeneous structures of the circulatory system. Despite the well accepted relationship between the structural and mechanical anisotropy and the optimal function of the valves, most approaches to create tissue-engineered heart valves (TEHVs) do not try to mimic this complexity and rely on one homogenous combination of cells and materials for the whole construct. The aim of this study was to establish an easy and versatile method to introduce spatial diversity into a heart valve fibrin scaffold. We developed a multiple-step injection molding process that enables the fabrication of TEHVs with heterogeneous composition (cell/scaffold material) of wall and leaflets without the need of gluing or suturing components together, with the leaflets firmly connected to the wall. The integrity of the valves and their functionality was proved by either opening/closing cycles in a bioreactor (proof of principle without cells) or with continuous stimulation over 2 weeks. We demonstrated the potential of the method by the two-step molding of the wall and the leaflets containing different cell lines. Immunohistology after stimulation confirmed tissue formation and demonstrated the localization of the different cell types. Furthermore, we showed the proof of principle fabrication of valves using different materials for wall (fibrin) and leaflets (hybrid gel of fibrin/elastin-like recombinamer) and with layered leaflets. The method is easy to implement, does not require special facilities, and can be reproduced in any tissue-engineering lab. While it has been demonstrated here with fibrin, it can easily be extended to other hydrogels.
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Gas chromatograph sample-transfer valve
NASA Technical Reports Server (NTRS)
Wang, W. S.; Wright, H. W., Jr.
1971-01-01
Slide-type gate valve incorporates sampling volume and transfer passageway for guiding a metered quantity of gas from pressurized test cell to gas chromatograph. Gate is moved by pneumatic bellows-type actuator.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Moore, Wayne R.
A control valve includes a first conduit having a first inlet and a first outlet and defining a first passage; a second conduit having a second inlet and a second outlet and defining a second passage, the second conduit extending into the first passage such that the second inlet is located within the first passage; and a valve plate disposed pivotably within the first passage, the valve plate defining a valve plate surface. Pivoting of the valve plate within the first passage varies flow from the first inlet to the first outlet and the valve plate is pivotal between amore » first position and a second position such that in the first position the valve plate substantially prevents fluid communication between the first passage and the second passage and such that in the second position the valve plate permits fluid communication between the first passage and the second passage.« less
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Special functions of valve organs of blood-sucking female mosquitoes
NASA Astrophysics Data System (ADS)
Kim, Boheum; Lee, Sangjoon
2010-11-01
Food-feeding insects usually have valve organs to regulate the sucking flow effectively. Female mosquitoes sucking lots of blood instantaneously have a unique valve system between two pumping organs located in their head. The valve system seems to prevent reverse flow and to grind granule particles such as red blood cells. To understand the functional characteristics of this valve organ in detail, the volumetric flow rate passing through the valves and their interaction with the two-pumps need to be investigated. However, it is very difficult to observe the dynamic behaviors of pumping organs and valve system. In this study, the dynamic motions of valve organs of blood-sucking female mosquitoes were observed under in vivo condition using synchrotron X-ray micro imaging technique. X-ray micro computed tomography was also employed to examine the three-dimensional internal structure of the blood pumping system including valve organs.
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Protective role of Smad6 in inflammation-induced valvular cell calcification
Li, Xin; Lim, Jina J.; Lu, Jinxiu; Pedego, Taylor M.; Demer, Linda; Tintut, Yin
2016-01-01
Calcific aortic vascular and valvular disease (CAVD) is associated with hyperlipidemia, the effects of which occur through chronic inflammation. Evidence suggests that inhibitory small mothers against decapentaplegic (I-Smads; Smad6 and 7) regulate valve embryogenesis and may serve as a mitigating factor in CAVD. However, whether I-Smads regulate inflammation-induced calcific vasculopathy is not clear. Therefore, we investigated the role of I-Smads in atherosclerotic calcification. Results showed that expression of Smad6, but not Smad7, was reduced in aortic and valve tissues of hyperlipidemic compared with normolipemic mice, while expression of tumor necrosis factor alpha (TNF-a) was upregulated. To test whether the effects are in response to inflammatory cytokines, we isolated murine aortic valve leaflets and cultured valvular interstitial cells (mVIC) from the normolipemic mice. By immunochemistry, mVICs were strongly positive for vimentin, weakly positive for smooth muscle alpha actin, and negative for an endothelial cell marker. TNF-a upregulated alkaline phosphatase (ALP) activity and matrix mineralization in mVICs. By gene expression analysis, TNF-a significantly upregulated bone morphogenetic protein 2 (BMP-2) expression while downregulating Smad6 expression. Smad7 expression was not significantly affected. To further test the role of Smad6 on TNF-a-induced valvular cell calcification, we knocked down Smad6 expression using lentiviral transfection. In cells transfected with Smad6 shRNA, TNF-a further augmented ALP activity, expression of BMP-2, Wnt- and redox-regulated genes, and matrix mineralization compared with the control cells. These findings suggest that TNF-a induces valvular and vascular cell calcification, in part, by specifically reducing the expression of a BMP-2 signaling inhibitor, Smad6. PMID:25864564
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Accumulation of BDCA1⁺ dendritic cells in interstitial fibrotic lung diseases and Th2-high asthma.
Greer, Alexandra M; Matthay, Michael A; Kukreja, Jasleen; Bhakta, Nirav R; Nguyen, Christine P; Wolters, Paul J; Woodruff, Prescott G; Fahy, John V; Shin, Jeoung-Sook
2014-01-01
Dendritic cells (DCs) significantly contribute to the pathology of several mouse lung disease models. However, little is known of the contribution of DCs to human lung diseases. In this study, we examined infiltration with BDCA1⁺ DCs of human lungs in patients with interstitial lung diseases or asthma. Using flow cytometry, we found that these DCs increased by 5∼6 fold in the lungs of patients with idiopathic pulmonary fibrosis or hypersensitivity pneumonitis, which are both characterized by extensive fibrosis in parenchyma. The same DC subset also significantly increased in the lung parenchyma of patients with chronic obstructive pulmonary disease, although the degree of increase was relatively modest. By employing immunofluorescence microscopy using FcεRI and MHCII as the specific markers for BDCA1⁺ DCs, we found that the numbers of BDCA1⁺ DCs also significantly increased in the airway epithelium of Th2 inflammation-associated asthma. These findings suggest a potential contribution of BDCA1⁺ DCs in human lung diseases associated with interstitial fibrosis or Th2 airway inflammation.
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Nuclear radiation actuated valve
Christiansen, David W.; Schively, Dixon P.
1985-01-01
A nuclear radiation actuated valve for a nuclear reactor. The valve has a valve first part (such as a valve rod with piston) and a valve second part (such as a valve tube surrounding the valve rod, with the valve tube having side slots surrounding the piston). Both valve parts have known nuclear radiation swelling characteristics. The valve's first part is positioned to receive nuclear radiation from the nuclear reactor's fuel region. The valve's second part is positioned so that its nuclear radiation induced swelling is different from that of the valve's first part. The valve's second part also is positioned so that the valve's first and second parts create a valve orifice which changes in size due to the different nuclear radiation caused swelling of the valve's first part compared to the valve's second part. The valve may be used in a nuclear reactor's core coolant system.
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[Status of aortic valve reconstruction and Ross operation in aortic valve diseases].
Sievers, Hans H
2002-08-01
if these are progressive and combined with aortic insufficiency. ROSS-OPERATION: The Ross-Operation includes the replacement of the diseased aortic valve with the pulmonary autograft and reconstruction of the right ventricular outflow tract using a homograft. The hemodynamic results are excellent regarding the autograft and also the clinical results with very low thromboembolic risk and acceptable reoperation rate. This method is especially indicated for active young patients, women, who desire children, athletes and patients in general, who like to avoid long-term anticoagulation. In some cases the homograft may develop a dysfunction predominantly a pulmonary stenosis requiring reoperation. In the author's series of 245 Ross-operations in 12 years the homograft had to be replaced in 4 cases without letality. Innovative, decellularized homografts with the potential to repopulate with autologeous cells show promising results after 1 year of clinical implantation without signs of antibody development. Probably these tissue-engineered modification may improve the homograft results. The reconstructive techniques of the aortic valve and the Ross-operation have a certain risk of reoperation that must be weighed against the advantages of very low hospital and late valve related death, excellent hemodynamics, very low risk of macro- and microembolism as well as bleeding, lack of long-term anticoagulation and unrestricted life-style.
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Chylothorax in dermatomyositis complicated with interstitial pneumonia.
Isoda, Kentaro; Kiboshi, Takao; Shoda, Takeshi
2017-04-01
Chylothorax is a disease in which chyle leaks and accumulates in the thoracic cavity. Interstitial pneumonia and pneumomediastinum are common thoracic manifestations of dermatomyositis, but chylothorax complicated with dermatomyositis is not reported. We report a case of dermatomyositis with interstitial pneumonia complicated by chylothorax. A 77-year-old woman was diagnosed as dermatomyositis with Gottron's papules, skin ulcers, anti-MDA5 antibody and rapid progressive interstitial pneumonia. Treatment with betamethasone, tacrolimus and intravenous high-dose cyclophosphamide was initiated, and her skin symptoms and interstitial pneumonia improved once. However, right-sided chylothorax began to accumulate and gradually increase, and at the same time, her interstitial pneumonia began to exacerbate, and skin ulcers began to reappear on her fingers and auricles. Although her chylothorax improved by fasting and parenteral nutrition, she died due to further exacerbations of dermatomyositis and interstitial pneumonia in spite of steroid pulse therapy, increase in the betamethasone dosage, additional intravenous high-dose cyclophosphamide and plasma pheresis. An autopsy showed no lesions such as malignant tumors in the thoracic cavity. This is the first report of chylothorax complicated by dermatomyositis with interstitial pneumonia.
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Merryman, W. David; Lukoff, Howard D.; Long, Rebecca A.; Engelmayr, George C.; Hopkins, Richard A.; Sacks, Michael S.
2007-01-01
Background Phenotypically, the aortic valve interstitial cell (AVIC) is a dynamic myofibroblast, appearing contractile and activated in times of development, disease, and remodeling. The precise mechanism of phenotypic modulation is unclear, but it is speculated that both biomechanical and biochemical factors are influential. Therefore, we hypothesized that isolated and combined treatments of cyclic tension and TGF-β1 would alter the phenotype and subsequent collagen biosynthesis of AVICs in situ. Methods and Results Porcine aortic valve leaflets received 7 and 14 day treatments of 15% cyclic stretch (Tension), 0.5 ng/ml TGF-β1 (TGF), 15% cyclic stretch and 0.5 ng/ml TGF-β1 (Tension+TGF), or neither mechanical nor cytokine stimuli (Null). Tissues were homogenized and assayed for AVIC phenotype (smooth muscle α-actin (SMA)) and collagen biosynthesis (via heat shock protein 47 (Hsp47) which was further verified with type I collagen C-terminal propeptide (CICP)). At both 7 and 14 days, SMA, Hsp47, and CICP quantities were significantly greater (p<0.001) in the Tension+TGF group compared to all other groups. Additionally, Tension alone appeared to maintain SMA and Hsp47 levels that were measured at day 0, while TGF alone elicited an increase in SMA and Hsp47 compared to day 0 levels. Null treatment revealed diminished proteins at both time points. Conclusions Elevated TGF-β1 levels, in the presence of cyclic mechanical tension, resulted in synergistic increases in the contractile and biosynthetic proteins in AVICs. Since cyclic mechanical stimuli can never be relieved in vivo, the presence of TGF-β1 (possibly from infiltrating macrophages) may result in overly biosynthetic AVICs, leading to altered ECM architecture, compromised valve function, and ultimately degenerative valvular disease. PMID:17868877
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Valve thrombosis following transcatheter aortic valve implantation: a systematic review.
Córdoba-Soriano, Juan G; Puri, Rishi; Amat-Santos, Ignacio; Ribeiro, Henrique B; Abdul-Jawad Altisent, Omar; del Trigo, María; Paradis, Jean-Michel; Dumont, Eric; Urena, Marina; Rodés-Cabau, Josep
2015-03-01
Despite the rapid global uptake of transcatheter aortic valve implantation, valve trombosis has yet to be systematically evaluated in this field. The aim of this study was to determine the clinical characteristics, diagnostic criteria, and treatment outcomes of patients diagnosed with valve thrombosis following transcatheter aortic valve implantation through a systematic review of published data. Literature published between 2002 and 2012 on valve thrombosis as a complication of transcatheter aortic valve implantation was identified through a systematic electronic search. A total of 11 publications were identified, describing 16 patients (mean age, 80 [5] years, 65% men). All but 1 patient (94%) received a balloon-expandable valve. All patients received dual antiplatelet therapy immediately following the procedure and continued to take either mono- or dual antiplatelet therapy at the time of valve thrombosis diagnosis. Valve thrombosis was diagnosed at a median of 6 months post-procedure, with progressive dyspnea being the most common symptom. A significant increase in transvalvular gradient (from 10 [4] to 40 [12] mmHg) was the most common echocardiographic feature, in addition to leaflet thickening. Thrombus was not directly visualized with echocardiography. Three patients underwent valve explantation, and the remaining received warfarin, which effectively restored the mean transvalvular gradient to baseline within 2 months. Systemic embolism was not a feature of valve thrombosis post-transcatheter aortic valve implantation. Although a rare, yet likely under-reported complication of post-transcatheter aortic valve implantation, progressive dyspnea coupled with an increasing transvalvular gradient on echocardiography within the months following the intervention likely signifies valve thrombosis. While direct thrombus visualization appears difficult, prompt initiation of oral anticoagulation therapy effectively restores baseline valve function. Copyright © 2014
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Yamamoto, Yuzo; Okamoto, Isamu; Otsubo, Kohei; Iwama, Eiji; Hamada, Naoki; Harada, Taishi; Takayama, Koichi; Nakanishi, Yoichi
2015-10-01
Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib treatment. An 86-year-old woman with stage IV lung adenocarcinoma positive for rearrangement of ALK gene was treated with alectinib. On the 215th day after initiation of alectinib administration, she was admitted to our hospital with the symptom of progressive dyspnea. Computed tomography (CT) revealed diffuse ground glass opacities and consolidations in both lungs, and analysis of bronchoalveolar lavage fluid revealed pronounced lymphocytosis. There was no evidence of infection or other specific causes of her condition, and she was therefore diagnosed with interstitial lung disease induced by alectinib. Her CT findings and respiratory condition improved after steroid pulse therapy. As far as we are aware, this is the first reported case of alectinib-induced severe interstitial lung disease (ILD). We should be aware of the possibility of such a severe adverse event and should therefore carefully monitor patients treated with this drug.
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Treede, Hendrik; Rastan, Ardawan; Ferrari, Markus; Ensminger, Stephan; Figulla, Hans-Reiner; Mohr, Friedrich-Wilhelm
2012-09-01
The JenaValve is a next-generation TAVI device which consists of a well-proven porcine root valve mounted on a low-profile nitinol stent. Feeler guided positioning and clip fixation on the diseased leaflets allow for anatomically correct implantation of the device without rapid pacing. Safety and efficacy of transapical aortic valve implantation using the JenaValve were evaluated in a multicentre prospective study that showed good short and midterm results. The valve was CE-mark released in Europe in September 2011. A post-market registry ensures on-going and prospective data collection in "real-world" patients. The transfemoral JenaValve delivery system will be evaluated in a first-in-man study in the near future.
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Skoda, G.I.
1989-03-28
A depressurization valve for use in relieving completely the pressure in a simplified boiling water reactor is disclosed. The normally closed and sealed valve is provided with a valve body defining a conduit from an outlet of a manifold from the reactor through a valve seat. A closing valve disk is configured for fitting to the valve seat to normally close the valve. The seat below the disk is provided with a radially extending annulus extending a short distance into the aperture defined by the seat. The disk is correspondingly provided with a longitudinally extending annulus that extends downwardly through the aperture defined by the seat towards the high pressure side of the valve body. A ring shaped membrane is endlessly welded to the seat annulus and to the disk annulus. The membrane is conformed over the confronted surface of the seat and disk in a C-sectioned configuration to seal the depressurization valve against the possibility of weeping. The disk is held to the closed position by an elongate stem extending away from the high pressure side of the valve body. The stem has a flange configured integrally to the stem for bias by two springs. The first spring acts from a portion of the housing overlying the disk on the stem flange adjacent the disk. This spring urges the stem and attached disk away from the seat and thus will cause the valve to open at any pressure. A second spring-preferably of the Belleville variety-acts on a latch plate surrounding and freely moving relative to the end of the stem. This second spring overcomes the bias of the first spring and any pressure acting upon the disk. This Belleville spring maintains through its spring force the valve in the closed position. At the same time, the latch plate with its freedom of movement relative to the stem allows the stem to thermally expand during valve temperature excursion.
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Palm, Fredrik; Takahashi, Tomoko; Ikegami-Kawai, Mayumi; Friederich-Persson, Malou; Hansell, Peter
2017-01-01
The content of hyaluronan (HA) in the interstitium of the renal medulla changes in relation to body hydration status. We investigated if hormones of central importance for body fluid homeostasis affect HA production by renomedullary interstitial cells in culture (RMICs). Simultaneous treatment with vasopressin and angiotensin II (Ang II) reduced HA by 69%. No change occurred in the mRNA expressions of hyaluronan synthase 2 (HAS2) or hyaluronidases (Hyals), while Hyal activity in the supernatant increased by 67% and CD44 expression reduced by 42%. The autocoid endothelin (ET-1) at low concentrations (10−10 and 10−8 M) increased HA 3-fold. On the contrary, at a high concentration (10−6 M) ET-1 reduced HA by 47%. The ET-A receptor antagonist BQ123 not only reversed the reducing effect of high ET-1 on HA, but elevated it to the same level as low concentration ET-1, suggesting separate regulating roles for ET-A and ET-B receptors. This was corroborated by the addition of ET-B receptor antagonist BQ788 to low concentration ET-1, which abolished the HA increase. HAS2 and Hyal2 mRNA did not alter, while Hyal1 mRNA was increased at all ET-1 concentrations tested. Hyal activity was elevated the most by high ET-1 concentration, and blockade of ET-A receptors by BQ123 prevented about 30% of this response. The present study demonstrates an important regulatory influence of hormones involved in body fluid balance on HA handling by RMICs, thereby supporting the concept of a dynamic involvement of interstitial HA in renal fluid handling. PMID:29236055
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Interstitial granulomatous dermatitis with arthritis.
Long, D; Thiboutot, D M; Majeski, J T; Vasily, D B; Helm, K F
1996-06-01
Interstitial granulomatous dermatitis with arthritis is an uncommon systemic disorder involving the cutaneous and musculoskeletal systems. The eruption may mimic other dermatoses including granuloma annulare, erythema chronicum migrans, and the inflammatory stage of morphea. Key histopathologic characteristics, along with clinical correlation, allow accurate diagnosis. We describe the clinical, serologic, and histologic features in three patients with interstitial granulomatous dermatitis with arthritis. Skin biopsy specimens were examined and correlated with the clinical and laboratory findings. Erythematous, annular, indurated plaques on the extremities were present in two women. An erythematous, papular eruption on the head and neck was present in a third patient. All patients had myalgia and migratory polyarthralgias of the extremities along with various serologic abnormalities. Histologic examination revealed a dense lymphohistiocytic interstitial infiltrate involving primarily the reticular dermis. Foci of necrobiotic collagen were present. Vasculitis was absent. Interstitial granulomatous dermatitis with arthritis is unique multisystem disease with variable cutaneous expression. Abnormal serologic findings indicate a possible connection to collagen vascular disease.
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Van Dyke, W.J.
1992-04-07
A fast valve is disclosed that can close on the order of 7 milliseconds. It is closed by the force of a compressed air spring with the moving parts of the valve designed to be of very light weight and the valve gate being of wedge shaped with O-ring sealed faces to provide sealing contact without metal to metal contact. The combination of the O-ring seal and an air cushion create a soft final movement of the valve closure to prevent the fast air acting valve from having a harsh closing. 4 figs.
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Van Dyke, William J.
1992-01-01
A fast valve is disclosed that can close on the order of 7 milliseconds. It is closed by the force of a compressed air spring with the moving parts of the valve designed to be of very light weight and the valve gate being of wedge shaped with O-ring sealed faces to provide sealing contact without metal to metal contact. The combination of the O-ring seal and an air cushion create a soft final movement of the valve closure to prevent the fast air acting valve from having a harsh closing.
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NASA Technical Reports Server (NTRS)
Burgess, Robert K.; Yakos, David; Walthall, Bryan
2012-01-01
This invention utilizes a new method of opening and closing a ball valve. Instead of rotating the ball with a perpendicular stem (as is the case with standard ball valves), the ball is rotated around a fixed axis by two guide pins. This innovation eliminates the leak point that is present in all standard ball valves due to the penetration of an actuation stem through the valve body. The VOST (Venturi Off-Set-Technology) valve has been developed for commercial applications. The standard version of the valve consists of an off-set venturi flow path through the valve. This path is split at the narrowest portion of the venturi, allowing the section upstream from the venturi to be rotated. As this rotation takes place, the venturi becomes restricted as one face rotates with respect to the other, eventually closing off the flow path. A spring-loaded seal made of resilient material is embedded in the upstream face of the valve, making a leak-proof seal between the faces; thus a valve is formed. The spring-loaded lip seal is the only seal that can provide a class six, or bubble-tight, seal against the opposite face of the valve. Tearing action of the seal by high-velocity gas on this early design required relocation of the seal to the downstream face of the valve. In the stemless embodiment of this valve, inner and outer magnetic cartridges are employed to transfer mechanical torque from the outside of the valve to the inside without the use of a stem. This eliminates the leak path caused by the valve stems in standard valves because the stems penetrate through the bodies of these valves.
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Lung transplantation and interstitial lung disease.
Alalawi, Raed; Whelan, Timothy; Bajwa, Ravinder S; Hodges, Tony N
2005-09-01
Interstitial lung disease includes a heterogeneous group of disorders that leads to respiratory insufficiency and death in a significant number of patients. Lung transplantation is a therapeutic option in select candidates. The indications, transplant procedure options, and outcomes continue to evolve. Various recipient comorbidities influence the choice of procedure in patients with interstitial lung disease. Single lung transplants are used as the procedure of choice and bilateral transplants are reserved for patients with suppurative lung disease and patients with pulmonary hypertension. Issues unique to patients with interstitial lung disease affect the morbidity, mortality and recurrence of the disease. Lung transplantation is an effective therapy for respiratory failure in interstitial lung disease with survival following transplant being similar to that achieved in transplant recipients with other diseases.
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Tricuspid valve and percutaneous approach: No longer the forgotten valve!
Bouleti, Claire; Juliard, Jean-Michel; Himbert, Dominique; Iung, Bernard; Brochet, Eric; Urena, Marina; Dilly, Marie-Pierre; Ou, Phalla; Nataf, Patrick; Vahanian, Alec
2016-01-01
Tricuspid valve disease is mainly represented by tricuspid regurgitation (TR), which is a predictor of poor outcome. TR is usually secondary, caused by right ventricle pressure or volume overload, the leading cause being left-sided heart valve diseases. Tricuspid surgery for severe TR is recommended during left valve surgery, and consists of either a valve replacement or, most often, a tricuspid repair with or without prosthetic annuloplasty. When TR persists or worsens after left valvular surgery, redo isolated tricuspid surgery is associated with high mortality. In addition, a sizeable proportion of patients present with tricuspid surgery deterioration over time, and need a reintervention, which is associated with high morbi-mortality rates. In this context, and given the recent major breakthrough in the percutaneous treatment of aortic and mitral valve diseases, the tricuspid valve appears an appealing challenge, although it raises specific issues. The first applications of transcatheter techniques for tricuspid valve disease were valve-in-valve and valve-in-ring implantation for degenerated bioprosthesis or ring annuloplasty. Some concerns remain regarding prosthesis sizing, rapid ventricular pacing and the best approach, but these procedures appear to be safe and effective. More recently, bicuspidization using a transcatheter approach for the treatment of native tricuspid valve has been published, in two patients. Finally, other devices are in preclinical development. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
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Balance point characterization of interstitial fluid volume regulation.
Dongaonkar, R M; Laine, G A; Stewart, R H; Quick, C M
2009-07-01
The individual processes involved in interstitial fluid volume and protein regulation (microvascular filtration, lymphatic return, and interstitial storage) are relatively simple, yet their interaction is exceedingly complex. There is a notable lack of a first-order, algebraic formula that relates interstitial fluid pressure and protein to critical parameters commonly used to characterize the movement of interstitial fluid and protein. Therefore, the purpose of the present study is to develop a simple, transparent, and general algebraic approach that predicts interstitial fluid pressure (P(i)) and protein concentrations (C(i)) that takes into consideration all three processes. Eight standard equations characterizing fluid and protein flux were solved simultaneously to yield algebraic equations for P(i) and C(i) as functions of parameters characterizing microvascular, interstitial, and lymphatic function. Equilibrium values of P(i) and C(i) arise as balance points from the graphical intersection of transmicrovascular and lymph flows (analogous to Guyton's classical cardiac output-venous return curves). This approach goes beyond describing interstitial fluid balance in terms of conservation of mass by introducing the concept of inflow and outflow resistances. Algebraic solutions demonstrate that P(i) and C(i) result from a ratio of the microvascular filtration coefficient (1/inflow resistance) and effective lymphatic resistance (outflow resistance), and P(i) is unaffected by interstitial compliance. These simple algebraic solutions predict P(i) and C(i) that are consistent with reported measurements. The present work therefore presents a simple, transparent, and general balance point characterization of interstitial fluid balance resulting from the interaction of microvascular, interstitial, and lymphatic function.
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Skoda, George I.
1989-01-01
A depressurization valve for use in relieving completely the pressure in a simplified boiling water reactor is disclosed. The normally closed and sealed valve is provided with a valve body defining a conduit from an outlet of a manifold from the reactor through a valve seat. A closing valve disk is configured for fitting to the valve seat to normally close the valve. The seat below the disk is provided with a radially extending annulus extending a short distance into the aperture defined by the seat. The disk is correspondingly provided with a longitudinally extending annulus that extends downwardly through the aperture defined by the seat towards the high pressure side of the valve body. A ring shaped membrane is endlessly welded to the seat annulus and to the disk annulus. The membrane is conformed over the confronted surface of the seat and disk in a C-sectioned configuration to seal the depressurization valve against the possibility of weeping. The disk is held to the closed position by an elongate stem extending away from the high pressure side of the valve body. The stem has a flange configured integrally to the stem for bias by two springs. The first spring acts from a portion of the housing overlying the disk on the stem flange adjacent the disk. This spring urges the stem and attached disk away from the seat and thus will cause the valve to open at any pressure. A second spring--preferably of the Belleville variety--acts on a latch plate surrounding and freely moving relative to the end of the stem. This second spring overcomes the bias of the first spring and any pressure acting upon the disk. This Belleville spring maintains through its spring force the valve in the closed position. At the same time, the latch plate with its freedom of movement relative to the stem allows the stem to thermally expand during valve temperature excursion. The latch plate in surrounding the stem is limited in its outward movement by a boss attached to the stem at the end of
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TexMi: Development of Tissue-Engineered Textile-Reinforced Mitral Valve Prosthesis
Moreira, Ricardo; Gesche, Valentine N.; Hurtado-Aguilar, Luis G.; Schmitz-Rode, Thomas; Frese, Julia
2014-01-01
Mitral valve regurgitation together with aortic stenosis is the most common valvular heart disease in Europe and North America. Mechanical and biological prostheses available for mitral valve replacement have significant limitations such as the need of a long-term anticoagulation therapy and failure by calcifications. Both types are unable to remodel, self-repair, and adapt to the changing hemodynamic conditions. Moreover, they are mostly designed for the aortic position and do not reproduce the native annular-ventricular continuity, resulting in suboptimal hemodynamics, limited durability, and gradually decreasing ventricular pumping efficiency. A tissue-engineered heart valve specifically designed for the mitral position has the potential to overcome the limitations of the commercially available substitutes. For this purpose, we developed the TexMi, a living textile-reinforced mitral valve, which recapitulates the key elements of the native one: annulus, asymmetric leaflets (anterior and posterior), and chordae tendineae to maintain the native annular-ventricular continuity. The tissue-engineered valve is based on a composite scaffold consisting of the fibrin gel as a cell carrier and a textile tubular structure with the twofold task of defining the gross three-dimensional (3D) geometry of the valve and conferring mechanical stability. The TexMi valves were molded with ovine umbilical vein cells and stimulated under dynamic conditions for 21 days in a custom-made bioreactor. Histological and immunohistological stainings showed remarkable tissue development with abundant aligned collagen fibers and elastin deposition. No cell-mediated tissue contraction occurred. This study presents the proof-of-principle for the realization of a tissue-engineered mitral valve with a simple and reliable injection molding process readily adaptable to the patient's anatomy and pathological situation by producing a patient-specific rapid prototyped mold. PMID:24665896
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Populations of subplate and interstitial neurons in fetal and adult human telencephalon.
Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša
2010-10-01
In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular
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Dave, Maneesh; Hayashi, Yujiro; Gajdos, Gabriella B; Smyrk, Thomas C; Svingen, Phyllis A; Kvasha, Sergiy M; Lorincz, Andrea; Dong, Haidong; Faubion, William A; Ordog, Tamas
2015-05-01
After allogeneic transplantation, murine stem cells (SCs) for interstitial cells of Cajal (ICCs), electrical pacemaker, and neuromodulator cells of the gut, were incorporated into gastric ICC networks, indicating in vivo immunosuppression. Immunosuppression is characteristic of bone marrow- and other non-gut-derived mesenchymal stem cells (MSCs), which are emerging as potential therapeutic agents against autoimmune diseases, including inflammatory bowel disease. Therefore, we investigated whether gut-derived ICC-SCs could also mitigate experimental colitis and studied the mechanisms of ICC-SC-mediated immunosuppression in relation to MSC-induced pathways. Isolated ICC-SCs were studied by transcriptome profiling, cytokine assays, flow cytometry, mixed lymphocyte reaction, and T-cell proliferation assay. Mice with acute and chronic colitis induced by dextran sulfate sodium and T-cell transfer, respectively, were administered ICC-SCs intraperitoneally and evaluated for disease activity by clinical and pathological assessment and for ICC-SC homing by live imaging. Unlike strain-matched dermal fibroblasts, intraperitoneally administered ICC-SCs preferentially homed to the colon and reduced the severity of both acute and chronic colitis assessed by clinical and blind pathological scoring. ICC-SCs profoundly suppressed T-cell proliferation in vitro. Similar to MSCs, ICC-SCs strongly expressed cyclooxygenase 1/2 and basally secreted prostaglandin E2. Indomethacin, a cyclooxygenase inhibitor, countered the ICC-SC-mediated suppression of T-cell proliferation. In contrast, we found no role for regulatory T-cell-, programmed death receptor-, and transforming growth factor-β-mediated mechanisms reported in MSCs; and transcriptome profiling did not support a relationship between ICC-SCs and MSCs. Murine ICC-SCs belong to a class different from MSCs and potently mitigate experimental colitis via prostaglandin E2-mediated immunosuppression. Copyright © 2015 AGA Institute
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Kiffer, Micah S.; Tentarelli, Stephen Clyde
2016-02-09
Excess flow shutoff valve comprising a valve body, a valve plug, a partition, and an activation component where the valve plug, the partition, and activation component are disposed within the valve body. A suitable flow restriction is provided to create a pressure difference between the upstream end of the valve plug and the downstream end of the valve plug when fluid flows through the valve body. The pressure difference exceeds a target pressure difference needed to activate the activation component when fluid flow through the valve body is higher than a desired rate, and thereby closes the valve.
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Iwamoto, Ryo; Mine, Naoki; Kawaguchi, Taichiro; Minami, Seigo; Saeki, Kazuko; Mekada, Eisuke
2010-07-01
HB-EGF, a member of the EGF family of growth factors, plays an important role in cardiac valve development by suppressing mesenchymal cell proliferation. Here, we show that HB-EGF must interact with heparan sulfate proteoglycans (HSPGs) to properly function in this process. In developing valves, HB-EGF is synthesized in endocardial cells but accumulates in the mesenchyme by interacting with HSPGs. Disrupting the interaction between HB-EGF and HSPGs in an ex vivo model of endocardial cushion explants resulted in increased mesenchymal cell proliferation. Moreover, homozygous knock-in mice (HB(Delta)(hb/)(Delta)(hb)) expressing a mutant HB-EGF that cannot bind to HSPGs developed enlarged cardiac valves with hyperproliferation of mesenchymal cells; this resulted in a phenotype that resembled that of Hbegf-null mice. Interestingly, although Hbegf-null mice had abnormal heart chambers and lung alveoli, HB(Delta)(hb/)(Delta)(hb) mice did not exhibit these defects. These results indicate that interactions with HSPGs are essential for the function of HB-EGF, especially in cardiac valve development, in which HB-EGF suppresses mesenchymal cell proliferation.
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Zhang, Qing-Fang
2017-12-01
The effect of ulinastatin (UTI) on renal tubular epithelial apoptosis and interstitial fibrosis in rats with unilateral ureteral obstruction (UUO) was investigated. A total of 18 male Wistar rats were randomly divided into the following 3 groups: The Sham group (n=6), the UUO group (n=6), and the UTI group (n=6). In the UUO and UTI groups, the left ureter was ligated to establish a UUO model. Starting from day 1 after surgery, an intervention treatment was performed using normal saline (1 ml/kg/d) and UTI (40,000 unit/kg/d). On day 7 after surgery, 6 rats from each group were sacrificed. In the Sham group, the left ureter was only freed, not ligated; after 7 days of abdominal closure, all of the rats were sacrificed. Blood samples were collected prior to sacrificing the animals to measure the blood urea nitrogen (BUN) and serum creatinine (Scr). The incidence of renal interstitial lesions on the obstruction side was observed by hematoxylin and eosin, and Masson staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemical detection of apoptosis regulator Bax (Bax), apoptosis regulator Bcl‑2 (Bcl‑2) and caspase‑3 were performed to observe the presence of renal tubular epithelial cell apoptosis. The UTI did not have a significant influence on the mouse BUN and Scr levels in any of the groups (P>0.05). Compared with that in the Sham group, renal tissue injury in the UUO group was significantly aggravated with renal tubular dilation, epithelial cell atrophy, renal interstitial inflammatory cell infiltration and fibrous tissue hyperplasia (P<0.01). Furthermore, the renal tubular epithelial TUNEL+ cell number and Bax and caspase‑3 levels were increased, and the expression of Bcl‑2 was decreased (P<0.01). Following the UTI treatment, the renal interstitial injury at the obstruction side was significantly attenuated (P<0.05), the renal tubular epithelial TUNEL+ cell number, and Bax and caspase‑3 levels
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Sarmah, Swapnalee; Muralidharan, Pooja
2016-01-01
Fetal alcohol spectrum disorder (FASD), birth defects associated with ethanol exposure in utero, includes a wide spectrum of congenital heart defects (CHDs), the most prevalent of which are septal and conotruncal defects. Zebrafish FASD model was used to dissect the mechanisms underlying FASD-associated CHDs. Embryonic ethanol exposure (3–24 hours post fertilization) led to defects in atrio-ventricular (AV) valvulogenesis beginning around 37 hpf, a morphogenetic event that arises long after ethanol withdrawal. Valve leaflets of the control embryos comprised two layers of cells confined at the compact atrio-ventricular canal (AVC). Ethanol treated embryos had extended AVC and valve forming cells were found either as rows of cells spanning the AVC or as unorganized clusters near the AV boundary. Ethanol exposure reduced valve precursors at the AVC, but some ventricular cells in ethanol treated embryos exhibited few characteristics of valve precursors. Late staged larvae and juvenile fish exposed to ethanol during embryonic development had faulty AV valves. Examination of AVC morphogenesis regulatory networks revealed that early ethanol exposure disrupted the Bmp signaling gradient in the heart during valve formation. Bmp signaling was prominent at the AVC in controls, but ethanol-exposed embryos displayed active Bmp signaling throughout the ventricle. Ethanol exposure also led to mislocalization of Notch signaling cells in endocardium during AV valve formation. Normally, highly active Notch signaling cells were organized at the AVC. In ethanol-exposed embryos, highly active Notch signaling cells were dispersed throughout the ventricle. At later stages, ethanol-exposed embryos exhibited reduced Wnt/β-catenin activity at the AVC. We conclude that early embryonic ethanol exposure alters Bmp, Notch and other signaling activities during AVC differentiation leading to faulty valve morphogenesis and valve defects persist in juvenile fish. PMID:27556898
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Sarmah, Swapnalee; Muralidharan, Pooja; Marrs, James A
2016-01-01
Fetal alcohol spectrum disorder (FASD), birth defects associated with ethanol exposure in utero, includes a wide spectrum of congenital heart defects (CHDs), the most prevalent of which are septal and conotruncal defects. Zebrafish FASD model was used to dissect the mechanisms underlying FASD-associated CHDs. Embryonic ethanol exposure (3-24 hours post fertilization) led to defects in atrio-ventricular (AV) valvulogenesis beginning around 37 hpf, a morphogenetic event that arises long after ethanol withdrawal. Valve leaflets of the control embryos comprised two layers of cells confined at the compact atrio-ventricular canal (AVC). Ethanol treated embryos had extended AVC and valve forming cells were found either as rows of cells spanning the AVC or as unorganized clusters near the AV boundary. Ethanol exposure reduced valve precursors at the AVC, but some ventricular cells in ethanol treated embryos exhibited few characteristics of valve precursors. Late staged larvae and juvenile fish exposed to ethanol during embryonic development had faulty AV valves. Examination of AVC morphogenesis regulatory networks revealed that early ethanol exposure disrupted the Bmp signaling gradient in the heart during valve formation. Bmp signaling was prominent at the AVC in controls, but ethanol-exposed embryos displayed active Bmp signaling throughout the ventricle. Ethanol exposure also led to mislocalization of Notch signaling cells in endocardium during AV valve formation. Normally, highly active Notch signaling cells were organized at the AVC. In ethanol-exposed embryos, highly active Notch signaling cells were dispersed throughout the ventricle. At later stages, ethanol-exposed embryos exhibited reduced Wnt/β-catenin activity at the AVC. We conclude that early embryonic ethanol exposure alters Bmp, Notch and other signaling activities during AVC differentiation leading to faulty valve morphogenesis and valve defects persist in juvenile fish.
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Absence of posterior tricuspid valve leaflet and valve reconstruction
Komoda, Takeshi; Stamm, Christof; Fleck, Eckart; Hetzer, Roland
2012-01-01
We report a rare case of the absence of a posterior tricuspid valve leaflet. A male patient, aged 46, suffering from severe tricuspid valve regurgitation (TR) of unknown aetiology and atrial septal aneurysm was referred to our hospital for surgery. On surgical inspection, the posterior tricuspid valve leaflet and its subvalvular apparatus were completely absent and only the valve annulus was seen in the corresponding position. The anterior and septal leaflets were normal. We successfully reconstructed the tricuspid valve as follows: the head of an anterior papillary muscle was approximated to the ventricular septum (Sebening stitch). After the approximation of the centre of the tricuspid annulus of the anterior leaflet to the tricuspid annulus on the opposite side, a sizer of 29 mm in diameter was easily passed through the anterior orifice. The posterior orifice was closed with running sutures (posterior annulorrhaphy after Hetzer). Before these procedures, we attempted to reconstruct the tricuspid valve with a posterior annulorrhaphy alone; however, valve competence was insufficient. A Sebening stitch was necessary to improve the valve competence. Echocardiography showed TR grade 1 at the patient's discharge from hospital and TR grade 1 to 2 at the follow-up, 10 months after the operation. PMID:22419794
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Collins, Clinton; Klausner, Adam P; Herrick, Benjamin; Koo, Harry P; Miner, Amy S; Henderson, Scott C; Ratz, Paul H
2009-01-01
Interstitial cells of Cajal (ICCs) have been identified as pacemaker cells in the upper urinary tract and urethra, but the role of ICCs in the bladder remains to be determined. We tested the hypotheses that ICCs express cyclooxygenase (COX), and that COX products (prostaglandins), are the cause of spontaneous rhythmic contraction (SRC) of isolated strips of rabbit bladder free of urothelium. SRC was abolished by 10 μM indomethacin and ibuprofen (non-selective COX inhibitors). SRC was concentration-dependently inhibited by selective COX-1 (SC-560 and FR-122047) and COX-2 inhibitors (NS-398 and LM-1685), and by SC-51089, a selective antagonist for the PGE-2 receptor (EP) and ICI-192,605 and SQ-29,548, selective antagonists for thromboxane receptors (TP). The partial agonist/antagonist of the PGF-2α receptor (FP), AL-8810, inhibited SRC by ∼50%. Maximum inhibition was ∼90% by SC-51089, ∼80–85% by the COX inhibitors and ∼70% by TP receptor antagonists. In the presence of ibuprofen to abolish SRC, PGE-2, sulprostone, misoprostol, PGF-2α and U-46619 (thromboxane mimetic) caused rhythmic contractions that mimicked SRC. Fluorescence immunohistochemistry coupled with confocal laser scanning microscopy revealed that c-Kit and vimentin co-localized to interstitial cells surrounding detrusor smooth muscle bundles, indicating the presence of extensive ICCs in rabbit bladder. Co-localization of COX-1 and vimentin, and COX-2 and vimentin by ICCs supports the hypothesis that ICCs were the predominant cell type in rabbit bladder expressing both COX isoforms. These data together suggest that ICCs appear to be an important source of prostaglandins that likely play a role in regulation of SRC. Additional studies on prostaglandin-dependent SRC may generate opportunities for the application of novel treatments for disorders leading to overactive bladder. PMID:19243470
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[Percutaneously implantable aortic valve: the JenaValve concept evolution].
Figulla, Hans R; Ferrari, Markus
2006-10-01
Due to the increasing incidence of severe aortic stenosis in old and multimorbid patients, the percutaneous implantation of aortic valve-carrying stents has become an alternative to the surgical replacement of aortic valves. Starting in 1995, the authors developed a self-expanding stent which transferred the necessary forces for anchoring up to the aorta ascendens-a conception taken over from CoreValve. The further improvement of this idea over the past 11 years has led to a self-expanding, relatively short stent-valve system that is reliably positioned in the cusps of the old aortic valve and holds the old valve like a paper clip, thus transferring the holding forces physiologically. As compared to conventional systems, the sophisticated insertion catheter requires further chronic animal tests so as to represent a true alternative to the conventional surgical procedure.
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Protective Role of Smad6 in Inflammation-Induced Valvular Cell Calcification.
Li, Xin; Lim, Jina; Lu, Jinxiu; Pedego, Taylor M; Demer, Linda; Tintut, Yin
2015-10-01
Calcific aortic vascular and valvular disease (CAVD) is associated with hyperlipidemia, the effects of which occur through chronic inflammation. Evidence suggests that inhibitory small mothers against decapentaplegic (I-Smads; Smad6 and 7) regulate valve embryogenesis and may serve as a mitigating factor in CAVD. However, whether I-Smads regulate inflammation-induced calcific vasculopathy is not clear. Therefore, we investigated the role of I-Smads in atherosclerotic calcification. Results showed that expression of Smad6, but not Smad7, was reduced in aortic and valve tissues of hyperlipidemic compared with normolipemic mice, while expression of tumor necrosis factor alpha (TNF-α) was upregulated. To test whether the effects are in response to inflammatory cytokines, we isolated murine aortic valve leaflets and cultured valvular interstitial cells (mVIC) from the normolipemic mice. By immunochemistry, mVICs were strongly positive for vimentin, weakly positive for smooth muscle α actin, and negative for an endothelial cell marker. TNF-α upregulated alkaline phosphatase (ALP) activity and matrix mineralization in mVICs. By gene expression analysis, TNF-α significantly upregulated bone morphogenetic protein 2 (BMP-2) expression while downregulating Smad6 expression. Smad7 expression was not significantly affected. To further test the role of Smad6 on TNF-α-induced valvular cell calcification, we knocked down Smad6 expression using lentiviral transfection. In cells transfected with Smad6 shRNA, TNF-α further augmented ALP activity, expression of BMP-2, Wnt- and redox-regulated genes, and matrix mineralization compared with the control cells. These findings suggest that TNF-α induces valvular and vascular cell calcification, in part, by specifically reducing the expression of a BMP-2 signaling inhibitor, Smad6. © 2015 Wiley Periodicals, Inc.
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[Pannus Formation Two Years after Bioprosthetic Aortic Valve Implantation;Report of a Case].
Ono, Kimiyo; Kuroda, Hiroaki
2015-08-01
We report a case of early deterioration of the bioprosthetic aortic valve 23 months postoperatively. A 77-year-old man who had undergone aortic valve replacement with a 23-mm Epic valve( St. Jude Medical [SJM])presented to us after a syncopal episode. Echocardiography revealed severe aortic stenosis, and redo aortic valve replacement with a 21-mm SJM mechanical valve was performed. All 3 cusps of the tissue valve were thickened by fibrous pannus overgrowth. Neither calcification nor invasion of inflammatory cells was observed. The cause of pannus formation at such an early stage after implantation remains unknown.
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Disorders of interstitial cells of Cajal in a neonate with segmental dilatation of the intestine.
Okada, Tadao; Sasaki, Fumiaki; Honda, Shohei; Cho, Kazutosi; Matsuno, Yoshihiro; Itoh, Tomoo; Kubota, Kanako C; Todo, Satoru
2010-06-01
Localized myopathy of the muscular layers may be an important factor contributing to segmental dilatation of the intestine (SDI). Only one report has described SDI of the jejunum in a neonate showing no abnormality of the interstitial cells of Cajal (ICC). The present report describes the very rare case of a neonatal girl with segmental dilatation of the distal duodenum and proximal jejunum with irregular arrangements of Auerbach's plexus and ICC and the successful surgical treatment of SDI. We review the literature on this type of relationship between abnormality of ICC and SDI and discuss the clinical features of this complication. Furthermore, the possible neuropathic cause of SDI complicated with disorders of ICC was explored in this report. Copyright 2010 Elsevier Inc. All rights reserved.
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Outcome of bioprosthetic valve replacement in dogs with tricuspid valve dysplasia.
Bristow, P; Sargent, J; Luis Fuentes, V; Brockman, D
2017-04-01
To describe the short-term and long-term outcome in dogs with tricuspid valve dysplasia undergoing tricuspid valve replacement under cardiopulmonary bypass. Data were collected from the hospital records of all dogs that had undergone tricuspid valve replacement under cardiopulmonary bypass between 2006 and 2012. Dogs were considered candidates for tricuspid valve replacement if they had severe tricuspid valve regurgitation associated with clinical signs of cardiac compromise. Nine dogs of six different breeds were presented. Median age was 13 months (range 7 to 61 months), median weight 26·5 kg (range 9·7 to 59 kg). Eight bovine pericardial valves and one porcine aortic valve were used. One non-fatal intraoperative complication occurred. Complications during hospitalisation occurred in six dogs, four of which were fatal. Of the five dogs discharged, one presented dead due to haemothorax after minor trauma seven days later. The four remaining dogs survived a median of 533 days; all of these dogs received a bovine pericardial valve. Based on our results, tricuspid valve replacement with bovine or porcine prosthetic valves is associated with a high incidence of complications. © 2017 British Small Animal Veterinary Association.
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Desmaze, C; Pirzio, L M; Blaise, R; Mondello, C; Giulotto, E; Murnane, J P; Sabatier, L
2004-01-01
Telomeric repeat sequences, located at the end of eukaryotic chromosomes, have been detected at intrachromosomal locations in many species. Large blocks of telomeric sequences are located near the centromeres in hamster cells, and have been reported to break spontaneously or after exposure to ionizing radiation, leading to chromosome aberrations. In human cells, interstitial telomeric sequences (ITS) can be composed of short tracts of telomeric repeats (less than twenty), or of longer stretches of exact and degenerated hexanucleotides, mainly localized at subtelomeres. In this paper, we analyzed the radiation sensitivity of a naturally occurring short ITS localized in 2q31 and we found that this region is not a hot spot of radiation-induced chromosome breaks. We then selected a human cell line in which approximately 800 bp of telomeric DNA had been introduced by transfection into an internal euchromatic chromosomal region in chromosome 4q. In parallel, a cell line containing the plasmid without telomeric sequences was also analyzed. Both regions containing the transfected plasmids showed a higher frequency of radiation-induced breaks than expected, indicating that the instability of the regions containing the transfected sequences is not due to the presence of telomeric sequences. Taken together, our data show that ITS themselves do not enhance the formation of radiation-induced chromosome rearrangements in these human cell lines. Copyright 2003 S. Karger AG, Basel
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The multiple faces of leukocyte interstitial migration
Lämmermann, Tim; Germain, Ronald N.
2014-01-01
Spatiotemporal control of leukocyte dynamics within tissues is critical for successful innate and adaptive immune responses. Homeostatic trafficking and coordinated infiltration into and within sites of inflammation and infection rely on signaling in response to extracellular cues that in turn controls a variety of intracellular protein networks regulating leukocyte motility, migration, chemotaxis, positioning, and cell–cell interaction. In contrast to mesenchymal cells, leukocytes migrate in an amoeboid fashion by rapid cycles of actin polymerization and actomyosin contraction, and their migration in tissues is generally referred to as low adhesive and nonproteolytic. The interplay of actin network expansion, contraction, and adhesion shapes the exact mode of amoeboid migration, and in this review, we explore how leukocyte subsets potentially harness the same basic biomechanical mechanisms in a cell-type-specific manner. Most of our detailed understanding of these processes derives from in vitro migration studies in three-dimensional gels and confined spaces that mimic geometrical aspects of physiological tissues. We summarize these in vitro results and then critically compare them to data from intravital imaging of leukocyte interstitial migration in mouse tissues. We outline the technical challenges of obtaining conclusive mechanistic results from intravital studies, discuss leukocyte migration strategies in vivo, and present examples of mode switching during physiological interstitial migration. These findings are also placed in the context of leukocyte migration defects in primary immunodeficiencies. This overview of both in vitro and in vivo studies highlights recent progress in understanding the molecular and biophysical mechanisms that shape robust leukocyte migration responses in physiologically complex and heterogeneous environments. PMID:24573488
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Sang, Stephane Leung Wai; Beute, Tyler; Heiser, John; Berkompas, Duane; Fanning, Justin; Merhi, William
2017-11-20
Transcatheter aortic valve replacement (TAVR) is used increasingly to treat bioprosthetic valve failure. A paucity of data exists regarding valve-in-valve (ViV) TAVR in degenerated Freestyle stentless bioprostheses (FSBs). This study sought to evaluate the feasibility and short-term outcomes of ViV TAVR in previously placed FSB. From October 2014 to September 2016, 22 patients at a single institution underwent ViV TAVR with a self-expanding transcatheter valve for a failing FSB. Patient baseline characteristics and clinical outcomes data were collected retrospectively and entered into a dedicated database. The mean patient age was 74 ± 9years, and the mean Society of Thoracic Surgeons' Risk score was 9.0 ± 7.4%. Ten patients presented with acute heart failure requiring urgent intervention. The most common mode of failure of the FSB was regurgitation caused by a flail or malcoapting leaflet. Seventeen (77%) patients had a modified subcoronary implantation, 3 (14%) had a full root replacement, and 2 (9%) had a root inclusion. Device success using a self-expanding transcatheter valve was 95%, all via transfemoral approach. The mean implant depth was 7 ± 3 mm. Thirty-day survival was 100%. No patient had more than mild paravalvular regurgitation at 30days, and the permanent pacemaker rate was 9%. The mean hospital stay after intervention was 5 ± 2days. ViV TAVR using a self-expanding transcatheter valve is safe, feasible, and can be used successfully to treat a failed FSB. Procedural challenges suggest referral to valve centers of excellence. Copyright © 2017 Elsevier Inc. All rights reserved.
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Jiao, Jiao; Tian, Weihua; Qiu, Ping; Norton, Elizabeth L; Wang, Michael M; Chen, Y Eugene; Yang, Bo
2018-03-12
The NOTCH1 gene mutation has been identified in bicuspid aortic valve patients. We developed an in vitro model with human induced pluripotent stem cells (iPSCs) to evaluate the role of NOTCH1 in smooth muscle and endothelial cell (EC) differentiation. The iPSCs were derived from a patient with a normal tricuspid aortic valve and aorta. The NOTCH1 gene was targeted in iPSCs with the Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 nuclease (Cas9) system. The NOTCH1 -/- (NOTCH1 homozygous knockout) and isogenic control iPSCs (wild type) were differentiated into neural crest stem cells (NCSCs) and into cardiovascular progenitor cells (CVPCs). The NCSCs were differentiated into smooth muscle cells (SMCs). The CVPCs were differentiated into ECs. The differentiations of SMCs and ECs were compared between NOTCH1 -/- and wild type cells. The expression of NCSC markers (SRY-related HMG-box 10 and transcription factor AP-2 alpha) was significantly lower in NOTCH1 -/- NCSCs than in wild type NCSCs. The SMCs derived from NOTCH1 -/- NCSCs showed immature morphology with smaller size and decreased expression of all SMC-specific contractile proteins. In NOTCH1 -/- CVPCs, the expression of ISL1, NKX2.5, and MYOCD was significantly lower than that in isogenic control CVPCs, indicating impaired differentiation from iPSCs to CVPCs. The NOTCH1 -/- ECs derived from CVPCs showed significantly lower expression of cluster of differentiation 105 and cluster of differentiation 31 mRNA and protein, indicating a defective differentiation process. NOTCH1 is critical in SMC and EC differentiation of iPSCs through NCSCs and CVPCs, respectively. NOTCH1 gene mutations might potentially contribute to the development of thoracic aortic aneurysms by affecting SMC differentiation in some patients with bicuspid aortic valve. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
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The closing behavior of mechanical aortic heart valve prostheses.
Lu, Po-Chien; Liu, Jia-Shing; Huang, Ren-Hong; Lo, Chi-Wen; Lai, Ho-Cheng; Hwang, Ned H C
2004-01-01
Mechanical artificial heart valves rely on reverse flow to close their leaflets. This mechanism creates regurgitation and water hammer effects that may form cavitations, damage blood cells, and cause thromboembolism. This study analyzes closing mechanisms of monoleaflet (Medtronic Hall 27), bileaflet (Carbo-Medics 27; St. Jude Medical 27; Duromedics 29), and trileaflet valves in a circulatory mock loop, including an aortic root with three sinuses. Downstream flow field velocity was measured via digital particle image velocimetry (DPIV). A high speed camera (PIVCAM 10-30 CCD video camera) tracked leaflet movement at 1000 frames/s. All valves open in 40-50 msec, but monoleaflet and bileaflet valves close in much less time (< 35 msec) than the trileaflet valve (>75 msec). During acceleration phase of systole, the monoleaflet forms a major and minor flow, the bileaflet has three jet flows, and the trileaflet produces a single central flow like physiologic valves. In deceleration phase, the aortic sinus vortices hinder monoleaflet and bileaflet valve closure until reverse flows and high negative transvalvular pressure push the leaflets rapidly for a hard closure. Conversely, the vortices help close the trileaflet valve more softly, probably causing less damage, lessening back flow, and providing a washing effect that may prevent thrombosis formation.
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NASA Technical Reports Server (NTRS)
Robbins, John S.
1988-01-01
Unit removed with minimal disturbance. Valve inlet and outlet ports adjacent to each other on same side of valve body. Ports inserted into special manifold on fluid line. Valve body attached to manifold by four bolts or, alternatively, by toggle clamps. Electromechanical actuator moves in direction parallel to fluid line to open and close valve. When necessary to clean valve, removed simply by opening bolts or toggle clamps. No need to move or separate ports of fluid line. Valve useful where disturbance of fluid line detrimental or where fast maintenance essential - in oil and chemical industries, automotive vehicles, aircraft, and powerplants.
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Herndon, Charles; Brown, Roger A.
2002-01-01
An apparatus and process for removing a ball valve is provided. The ball valve removal tool provides a handle sliding along the length of a shaft. One end of the shaft is secured within an interior cavity of a ball valve while the opposite end of the shaft defines a stop member. By providing a manual sliding force to the handle, the handle impacts the stop member and transmits the force to the ball valve. The direction of the force is along the shaft of the removal tool and disengages the ball valve from the ball valve housing.
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Dukas, Jr., Stephen J.
1990-01-01
A bellows sealed plug valve includes a valve body having an inlet passage and an outlet passage, a valve chamber between the inlet and outlet passages. A valve plug has substantially the same shape as the valve chamber and is rotatably disposed therein. A shaft is movable linearly in response to a signal from a valve actuator. A bellows is sealingly disposed between the valve chamber and the valve actuator and means are located between the bellows and the valve plug for converting linear movement of the shaft connected to the valve actuator to rotational movement of the plug. Various means are disclosed including helical thread mechanism, clevis mechanism and rack and pinion mechanism, all for converting linear motion to rotational motion.
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Check valve installation in pilot operated relief valve prevents reverse pressurization
NASA Technical Reports Server (NTRS)
Oswalt, L.
1966-01-01
Two check valves prevent reverse flow through pilot-operated relief valves of differential area piston design. Title valves control pressure flow to ensure that the piston dome pressure is always at least as great as the main relief valve discharge pressure.
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Pulmonary hypertension in patients with interstitial lung disease.
Karampitsakos, Theodoros; Tzouvelekis, Argyrios; Chrysikos, Serafeim; Bouros, Demosthenes; Tsangaris, Iraklis; Fares, Wassim H
2018-06-01
Interstitial lung diseases (ILDs) comprise a broad and heterogeneous group of more than two hundred diseases with common functional characteristics. Their diagnosis and management require a multidisciplinary approach. This multidisciplinary approach involves the assessment of comorbid conditions including pulmonary hypertension (PH) that exerts a dramatic impact on survival. The current World Health Organization (WHO) classification of PH encompasses many of the interstitial lung diseases into WHO Group 3, while sarcoidosis, Pulmonary Langerhans Cell Histiocytosis and lymphangioleiomyomatosis are placed into WHO Group 5 as diseases with unclear or multifactorial mechanisms. Connective tissue diseases could span any of the 5 WHO groups based on the primary phenotype into which they manifest. Interestingly, several challenging phenotypes present with features that overlap between two or more WHO PH groups. Currently, PH-specific treatment is recommended only for patients classified into WHO Group 1 PH. The lack of specific treatment for other groups, including PH in the setting of ILD, reflects the poor outcomes of these patients. Thus, identification of the optimal strategy for ILD patients with PH remains an amenable need. This review article provides a brief overview of biomarkers indicative of vascular remodeling in interstitial lung disease, summarizes the current state of knowledge regarding patients with PH and ILD and highlights future perspectives that remain to be addressed. Copyright © 2018 Elsevier Ltd. All rights reserved.
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Globe stability during simulated vitrectomy with valved and non-valved trocar cannulas
Abulon, Dina Joy; Charles, Martin; Charles, Daniel E
2015-01-01
Purpose To compare the effects of valved and non-valved cannulas on intraocular pressure (IOP), fluid leakage, and vitreous incarceration during simulated vitrectomy. Methods Three-port pars plana incisions were generated in six rubber eyes using 23-, 25-, and 27-gauge valved and non-valved trocar cannulas. The models were filled with air and IOP was measured. Similar procedures were followed for 36 acrylic eyes filled with saline solution. Vitreous incarceration was analyzed in eleven rabbit and twelve porcine cadaver eyes. Results In the air-filled model, IOP loss was 89%–94% when two non-valved cannulas were unoccupied versus 1%–5% when two valved cannulas were unoccupied. In the fluid-filled model, with non-valved cannulas, IOP dropped while fluid leaked from the open ports. With two open ports, the IOP dropped to 20%–30% of set infusion pressure, regardless of infusion pressure and IOP compensation. The IOP was maintained in valved cannulas when one or two ports were left open, regardless of IOP compensation settings. There was no or minimal fluid leakage through open ports at any infusion pressure. Direct microscopic analysis of rabbit eyes showed that vitreous incarceration was significantly greater with 23-gauge non-valved than valved cannulas (P<0.005), and endoscopy of porcine eyes showed that vitreous incarceration was significantly greater with 23-gauge (P<0.05) and 27-gauge (P<0.05) non-valved cannulas. External observation of rabbit eyes showed vitreous prolapse through non-valved, but not valved, cannulas. Conclusion Valved cannulas surpassed non-valved cannulas in maintaining IOP, preventing fluid leakage, and reducing vitreous incarceration during simulated vitrectomy. PMID:26445520
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Squamous cell carcinoma of the bladder mimicking interstitial cystitis and voiding dysfunction.
Prudnick, Colton; Morley, Chad; Shapiro, Robert; Zaslau, Stanley
2013-01-01
Squamous cell carcinoma (SCC) of the bladder is a relatively uncommon cause of bladder cancer accounting for <5% of bladder tumors in the western countries. SCC has a slight male predominance and tends to occur in the seventh decade of life. The main presenting symptom of SCC is hematuria, and development of this tumor in the western world is associated most closely with chronic indwelling catheters and spinal cord injuries. A 39-year-old Caucasian female presented with bladder and lower abdominal pain, urinary frequency, and nocturia which was originally believed to be interstitial cystitis (IC) but was later diagnosed as SCC of the bladder. Presentation of SCC without hematuria is an uncommon presentation, but the absence of this symptom should not lead a practitioner to exclude the diagnosis of SCC. This case is being reported in an attempt to explain the delay and difficulty of diagnosis. Background on the risk factors for SCC of the bladder and the typical presenting symptoms of bladder SCC and IC are also reviewed.
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Campante Teles, Rui; Costa, Cátia; Almeida, Manuel; Brito, João; Sondergaard, Lars; Neves, José P; Abecasis, João; M Gabriel, Henrique
2017-03-01
Transcatheter aortic valve implantation (TAVI) has become an important treatment in high surgical risk patients with severe aortic stenosis (AS), whose complications need to be managed promptly. The authors report the case of an 86-year-old woman presenting with severe symptomatic AS, rejected for surgery due to advanced age and comorbidities. The patient underwent a first TAVI, with implantation of a Medtronic CoreValve ® , which became dislodged and migrated to the ascending aorta. Due to the previous balloon valvuloplasty, the patient's AS became moderate, and her symptoms improved. After several months, she required another intervention, performed with a St. Jude Portico ® repositionable self-expanding transcatheter aortic valve. There was a good clinical response that was maintained at one-year follow-up. The use of a self-expanding transcatheter bioprosthesis with repositioning features is a solution in cases of valve dislocation to avoid suboptimal positioning of a second implant, especially when the two valves have to be positioned overlapping or partially overlapping each other. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.
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Nitric Oxide Synthase-3 Promotes Embryonic Development of Atrioventricular Valves
Liu, Yin; Lu, Xiangru; Xiang, Fu-Li; Lu, Man; Feng, Qingping
2013-01-01
Nitric oxide synthase-3 (NOS3) has recently been shown to promote endothelial-to-mesenchymal transition (EndMT) in the developing atrioventricular (AV) canal. The present study was aimed to investigate the role of NOS3 in embryonic development of AV valves. We hypothesized that NOS3 promotes embryonic development of AV valves via EndMT. To test this hypothesis, morphological and functional analysis of AV valves were performed in wild-type (WT) and NOS3−/− mice at postnatal day 0. Our data show that the overall size and length of mitral and tricuspid valves were decreased in NOS3−/− compared with WT mice. Echocardiographic assessment showed significant regurgitation of mitral and tricuspid valves during systole in NOS3−/− mice. These phenotypes were all rescued by cardiac specific NOS3 overexpression. To assess EndMT, immunostaining of Snail1 was performed in the embryonic heart. Both total mesenchymal and Snail1+ cells in the AV cushion were decreased in NOS3−/− compared with WT mice at E10.5 and E12.5, which was completely restored by cardiac specific NOS3 overexpression. In cultured embryonic hearts, NOS3 promoted transforming growth factor (TGFβ), bone morphogenetic protein (BMP2) and Snail1expression through cGMP. Furthermore, mesenchymal cell formation and migration from cultured AV cushion explants were decreased in the NOS3−/− compared with WT mice. We conclude that NOS3 promotes AV valve formation during embryonic heart development and deficiency in NOS3 results in AV valve insufficiency. PMID:24204893
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Shear-Sensitive Genes in Aortic Valve Endothelium
Fernández Esmerats, Joan; Heath, Jack
2016-01-01
Abstract Significance: Currently, calcific aortic valve disease (CAVD) is only treatable through surgical intervention because the specific mechanisms leading to the disease remain unclear. In this review, we explore the forces and structure of the valve, as well as the mechanosensors and downstream signaling in the valve endothelium known to contribute to inflammation and valve dysfunction. Recent Advances: While the valvular structure enables adaptation to dynamic hemodynamic forces, these are impaired during CAVD, resulting in pathological systemic changes. Mechanosensing mechanisms—proteins, sugars, and membrane structures—at the surface of the valve endothelial cell relay mechanical signals to the nucleus. As a result, a large number of mechanosensitive genes are transcribed to alter cellular phenotype and, ultimately, induce inflammation and CAVD. Transforming growth factor-β signaling and Wnt/β-catenin have been widely studied in this context. Importantly, NADPH oxidase and reactive oxygen species/reactive nitrogen species signaling has increasingly been recognized to play a key role in the cellular response to mechanical stimuli. In addition, a number of valvular microRNAs are mechanosensitive and may regulate the progression of CAVD. Critical Issues: While numerous pathways have been described in the pathology of CAVD, no treatment options are available to avoid surgery for advanced stenosis and calcification of the aortic valve. More work must be focused on this issue to lead to successful therapies for the disease. Future Directions: Ultimately, a more complete understanding of the mechanisms within the aortic valve endothelium will lead us to future therapies important for treatment of CAVD without the risks involved with valve replacement or repair. Antioxid. Redox Signal. 25, 401–414. PMID:26651130
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... valve . Learn about the different types of stenosis: Aortic stenosis Tricuspid stenosis Pulmonary stenosis Mitral stenosis Outlook for ... Disease "Innocent" Heart Murmur Problem: Valve Stenosis - Problem: Aortic Valve Stenosis - Problem: Mitral Valve Stenosis - Problem: Tricuspid Valve Stenosis - ...
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Tsao, D D; Wang, S G; Lynn, B D; Nagy, J I
2017-06-01
Gap junctions between cells in the pineal gland have been described ultrastructurally, but their connexin constituents have not been fully characterized. We used immunofluorescence in combination with markers of pineal cells to document the cellular localization of connexin43 (Cx43). Immunofluorescence labelling of Cx43 with several different antibodies was widely distributed throughout the pineal, whereas another connexin examined, connexin26, was not found in pineal but only in surrounding leptomeninges. Labelling apparently associated with plasma membranes was visualized either as fine Cx43-puncta (1-2 μm) or as unusually large pools of Cx43 ranging up to 4-7 μm in diameter or length. These puncta and pools were highly concentrated in perivascular spaces, where they were associated with numerous cells devoid of labelling for markers of pinealocytes (e.g. tryptophan hydroxylase and serotonin), and where they were minimally associated with blood vessels and lacked association with resident macrophages. Astrocytes labelled for glial fibrillary acidic protein were largely restricted to the anterior pole of the pineal gland, where they displayed only fine and sparse Cx43-puncta along their processes. Labelling for Cx43 was localized largely though not exclusively to the somata and long processes of a subpopulation of perivascular interstitial cells that were immunopositive for calbindin-D28K. These cells were often located among dense bundles or termination areas of sympathetic fibres labelled for tyrosine hydroxylase or serotonin. The results indicate that interstitial cells form abundant gap junctions composed of Cx43, and suggest that gap junction-mediated intracellular communication by these cells supports the activities of pinealocytes. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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Thompson, J.L.; Upton, H.A.
1999-04-27
Breaker valve assemblies for a simplified boiling water nuclear reactor are described. The breaker valve assembly, in one form, includes a valve body and a breaker valve. The valve body includes an interior chamber, and an inlet passage extends from the chamber and through an inlet opening to facilitate transporting particles from outside of the valve body to the interior chamber. The breaker valve is positioned in the chamber and is configured to substantially seal the inlet opening. Particularly, the breaker valve includes a disk which is sized to cover the inlet opening. The disk is movably coupled to the valve body and is configured to move substantially concentrically with respect to the valve opening between a first position, where the disk completely covers the inlet opening, and a second position, where the disk does not completely cover the inlet opening. 1 fig.
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Thompson, Jeffrey L.; Upton, Hubert Allen
1999-04-27
Breaker valve assemblies for a simplified boiling water nuclear reactor are described. The breaker valve assembly, in one form, includes a valve body and a breaker valve. The valve body includes an interior chamber, and an inlet passage extends from the chamber and through an inlet opening to facilitate transporting particles from outside of the valve body to the interior chamber. The breaker valve is positioned in the chamber and is configured to substantially seal the inlet opening. Particularly, the breaker valve includes a disk which is sized to cover the inlet opening. The disk is movably coupled to the valve body and is configured to move substantially concentrically with respect to the valve opening between a first position, where the disk completely covers the inlet opening, and a second position, where the disk does not completely cover the inlet opening.
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NASA Technical Reports Server (NTRS)
Macglashan, W. F., Jr.
1980-01-01
Zero-leakage valve has fluid-sealing diaphragm support and flat sievelike sealing surface. Diaphragm-support valve is easy to fabricate and requires minimum maintenance. Potential applications include isolation valve for waste systems and remote air-actuated valve. Device is also useful in controlling flow of liquid fluorine and corrosive fluids at high pressures.
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Wottke, Michael; Deutsch, Marcus-André; Krane, Markus; Piazza, Nicolo; Lange, Ruediger; Bleiziffer, Sabine
2015-01-01
Background Due to a considerable rise in bioprosthetic as opposed to mechanical valve implantations, an increase of patients presenting with failing bioprosthetic surgical valves in need of a reoperation is to be expected. Redo surgery may pose a high-risk procedure. Transcatheter aortic valve-in-valve implantation is an innovative, less-invasive treatment alternative for these patients. However, a comprehensive evaluation of the outcome of consecutive patients after a valve-in-valve TAVI [transcatheter aortic valve-in-surgical aortic valve (TAV-in-SAV)] as compared to a standard reoperation [surgical aortic valve redo-operation (SAV-in-SAV)] has not yet been performed. The goal of this study was to compare postoperative outcomes after TAV-in-SAV and SAV-in-SAV in a single center setting. Methods All SAV-in-SAV and TAV-in-SAV patients from January 2001 to October 2014 were retrospectively reviewed. Patients with previous mechanical or transcatheter valves, active endocarditis and concomitant cardiac procedures were excluded. Patient characteristics, preoperative data, post-procedural complications, and 30-day mortality were collected from a designated database. Mean values ± SD were calculated for all continuous variables. Counts and percentages were calculated for categorical variables. The Chi-square and Fisher exact tests were used to compare categorical variables. Continuous variables were compared using the t-test for independent samples. A 2-sided P value <0.05 was considered statistically significant. Results A total of 102 patients fulfilled the inclusion criteria, 50 patients (49%) underwent a transcatheter valve-in-valve procedure, while 52 patients (51%) underwent redo-surgery. Patients in the TAV-in-SAV group were significantly older, had a higher mean logistic EuroSCORE and exhibited a lower mean left ventricular ejection fraction than patients in the SAV-in-SAV group (78.1±6.7 vs. 66.2±13.1, P<0.001; 27.4±18.7 vs. 14.4±10, P<0.001; and 49.8±13
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Superhydrophobicity to minimize thrombogenic risk on mechanical heart valves
NASA Astrophysics Data System (ADS)
Bark, David; Vahabi, Hamed; Movafaghi, Sanli; Popat, Ketul; Kota, Arun K.; Dasi, Lakshmi Prasad
2017-11-01
A large number of prosthetic heart valves are implanted each year to treat heart valve disease, where half of the surgically replaced valves are mechanical heart valves (MHV)s. MHVs are at high risk for thrombosis and therefore require lifelong antithrombotic therapies, causing an increased bleeding risk that can lead to death. To alleviate this need, we investigate the potential of superhydrophobic surfaces in reducing the thrombotic risk. Particle imaging velocimetry and computational fluid dynamics are used to quantify shear stress in the presence of potential slip on the surface. Coagulation and cell adhesion are quantified by incubating blood under static conditions. We further evaluate a dynamic blood response in polydimethylsiloxane channels under complex shear conditions that mimic the hinge region of bileaflet mechanical heart valves, a region known to exhibit thrombosis. Overall, Shear stress is not reduced on a superhydrophobic bileaflet MHV. However, superhydrophobic surfaces significantly reduce the potential for platelet responses under static and dynamic blood flow conditions, a counterintuitive result when considering that hydrophobic surfaces are prone to protein and cell adhesion. The authors gratefully acknowledge funding from National Institutes of Health (NIH) under Award Number R01HL119824 and F32HL129730. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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Application of Hydrogels in Heart Valve Tissue Engineering
Zhang, Xing; Xu, Bin; Puperi, Daniel S.; Wu, Yan; West, Jennifer L.; Grande-Allen, K. Jane
2015-01-01
With an increasing number of patients requiring valve replacement, there is heightened interest in advancing heart valve tissue engineering (HVTE) to provide solutions to the many limitations of current surgical treatments. A variety of materials have been developed as scaffolds for HVTE including natural polymers, synthetic polymers, and decellularized valvular matrices. Among them, biocompatible hydrogels are generating growing interest. Natural hydrogels, such as collagen and fibrin, generally show good bioactivity, but poor mechanical durability. Synthetic hydrogels, on the other hand, have tunable mechanical properties; however, appropriate cell-matrix interactions are difficult to obtain. Moreover, hydrogels can be used as cell carriers when the cellular component is seeded into the polymer meshes or decellularized valve scaffolds. In this review, we discuss current research strategies for HVTE with an emphasis on hydrogel applications. The physicochemical properties and fabrication methods of these hydrogels, as well as their mechanical properties and bioactivities are described. Performance of some hydrogels including in vitro evaluation using bioreactors and in vivo tests in different animal models are also discussed. For future HVTE, it will be compelling to examine how hydrogels can be constructed from composite materials to replicate mechanical properties and mimic biological functions of the native heart valve. PMID:25955010
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Karakoyun, Süleyman; Ozan Gürsoy, Mustafa; Yesin, Mahmut; Kalçık, Macit; Astarcıoğlu, Mehmet Ali; Gündüz, Sabahattin; Emrah Oğuz, Ali; Çoban Kökten, Şermin; Nimet Karadayı, Ayşe; Tuncer, Altuğ; Köksal, Cengiz; Gökdeniz, Tayyar; Özkan, Mehmet
2016-01-01
Prosthetic valve dysfunction due to pannus formation is a rare but serious complication. Currently, limited data are available concerning the pathogenesis and immunohistochemical properties of pannus. The study aim was to investigate the morphological, histopathological and immunohistochemical characteristics of pannus formation in patients with prosthetic valve dysfunction. A total of 35 patients (10 males, 25 females; mean age 44 ± 16 years) who had undergone re-do valve surgery due to prosthetic valve obstruction was enrolled in the study. Immunohistochemical studies were aimed at evaluating the expression of alphasmooth muscle actin (α-SMA) and desmin in myofibroblasts and smooth muscle cells; epithelial membrane antigen (EMA) in epithelial cells; and CD34, Factor VIII and vascular endothelial growth factor (VEGF) in endothelial cells. Matrix metalloproteinases (MMPs) -2 and -9, and transforming growth factor-beta (TGF-β) were used to demonstrate cytokine release from macrophages, leukocytes, fibroblasts and myofibroblasts. Pannus appeared as a tough and thick tissue hyperplasia which began from outside the suture ring in the periannular region and extended to the inflow and outflow surfaces of the prosthetic valves. Histopathological analysis showed the pannus tissue to consist of chronic inflammatory cells (lymphocytes, plasma cells, macrophages and foreign body giant cells), spindle cells such as myofibroblasts, capillary blood vessels and endothelial cells laying down the lumens. Calcification was present in the pannus tissue of 19 explanted prostheses. Immunohistochemical studies revealed positive α-SMA expression in all patients, whereas 60.5% of patients were positive for desmin, 50% for EMA, 42.1% for VEGF, 39.5% for TBF-β, 42.1% for MMP-2, 86.8% for CD34, and 97.4% for Factor VIII. MMP-9 was negative in all patients. Pannus tissue appears to be formed as the result of a neointimal response in periannular regions of prosthetic valves that consist
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Moreira, Ricardo; Velz, Thaddaeus; Alves, Nuno; Gesche, Valentine N.; Malischewski, Axel; Schmitz-Rode, Thomas; Frese, Julia
2015-01-01
Transcatheter aortic valve implantation of (nonviable) bioprosthetic valves has been proven a valid alternative to conventional surgical implantation in patients at high or prohibitive mortality risk. In this study we present the in vitro proof-of-principle of a newly developed tissue-engineered heart valve for minimally invasive implantation, with the ultimate aim of adding the unique advantages of a living tissue with regeneration capabilities to the continuously developing transcatheter technologies. The tube-in-stent is a fibrin-based tissue-engineered valve with a tubular leaflet design. It consists of a tubular construct sewn into a self-expandable nitinol stent at three commissural attachment points and along a circumferential line so that it forms three coaptating leaflets by collapsing under diastolic back pressure. The tubular constructs were molded with fibrin and human umbilical vein cells. After 3 weeks of conditioning in a bioreactor, the valves were fully functional with unobstructed opening (systolic phase) and complete closure (diastolic phase). Tissue analysis showed a homogeneous cell distribution throughout the valve's thickness and deposition of collagen types I and III oriented along the longitudinal direction. Immunohistochemical staining against CD31 and scanning electron microscopy revealed a confluent endothelial cell layer on the surface of the valves. After harvesting, the valves underwent crimping for 20 min to simulate the catheter-based delivery. This procedure did not affect the valvular functionality in terms of orifice area during systole and complete closure during diastole. No influence on the extracellular matrix organization, as assessed by immunohistochemistry, nor on the mechanical properties was observed. These results show the potential of combining tissue engineering and minimally invasive implantation technology to obtain a living heart valve with a simple and robust tubular design for transcatheter delivery. The effect
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Hardee, Harry C.
1991-01-01
A rotary pneumatic valve which is thrust balanced and the pneumatic pressure developed produces only radial loads on the valve cylinder producing negligible resistance and thus minimal torque on the bearings of the valve. The valve is multiplexed such that at least two complete switching cycles occur for each revolution of the cylinder spindle.
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DeWall, Kevin G.; Watkins, John C; Nitzel, Michael E.
2006-08-29
Apparatus for actuating a valve includes a support frame and at least one valve driving linkage arm, one end of which is rotatably connected to a valve stem of the valve and the other end of which is rotatably connected to a screw block. A motor connected to the frame is operatively connected to a motor driven shaft which is in threaded screw driving relationship with the screw block. The motor rotates the motor driven shaft which drives translational movement of the screw block which drives rotatable movement of the valve driving linkage arm which drives translational movement of the valve stem. The valve actuator may further include a sensory control element disposed in operative relationship with the valve stem, the sensory control element being adapted to provide control over the position of the valve stem by at least sensing the travel and/or position of the valve stem.
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Liu, L J; Schlesinger, M
2015-09-07
A correct description of the hydraulic conductivity is essential for determining the actual tumor interstitial fluid pressure (TIFP) distribution. Traditionally, it has been assumed that the hydraulic conductivities both in a tumor and normal tissue are constant, and that a tumor has a much larger interstitial hydraulic conductivity than normal tissue. The abrupt transition of the hydraulic conductivity at the tumor surface leads to non-physical results (the hydraulic conductivity and the slope of the TIFP are not continuous at tumor surface). For the sake of simplicity and the need to represent reality, we focus our analysis on avascular or poorly vascularized tumors, which have a necrosis that is mostly in the center and vascularization that is mostly on the periphery. We suggest that there is an intermediary region between the tumor surface and normal tissue. Through this region, the interstitium (including the structure and composition of solid components and interstitial fluid) transitions from tumor to normal tissue. This process also causes the hydraulic conductivity to do the same. We introduce a continuous variation of the hydraulic conductivity, and show that the interstitial hydraulic conductivity in the intermediary region should be monotonically increasing up to the value of hydraulic conductivity in the normal tissue in order for the model to correspond to the actual TIFP distribution. The value of the hydraulic conductivity at the tumor surface should be the lowest in value. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Structural valve deterioration in a starr-edwards mitral caged-disk valve prosthesis.
Aoyagi, Shigeaki; Tayama, Kei-Ichiro; Okazaki, Teiji; Shintani, Yusuke; Kono, Michitaka; Wada, Kumiko; Kosuga, Ken-Ichi; Mori, Ryusuke; Tanaka, Hiroyuki
2013-01-01
The durability of the Starr-Edwards (SE) mitral caged-disk valve, model 6520, is not clearly known, and structural valve deterioration in the SE disk valve is very rare. Replacement of the SE mitral disk valve was performed in 7 patients 23-40 years after implantation. Macroscopic examination of the removed disk valves showed no structural abnormalities in 3 patients, in whom the disk valves were removed at <26 years after implantation. Localized disk wear was found at the sites where the disk abutted the struts of the cage, in disk valves excised >36 years after implantation in 4 patients. Disk fracture, a longitudinal split in the disk along its circumference at the site of incorporation of the titanium ring, was detected in the valves removed 36 and 40 years after implantation, respectively, and many cracks were also observed on the outflow aspect of the disk removed 40 years after implantation. Disk fracture and localized disk wear were found in the SE mitral disk valves implanted >36 years previously. The present results suggest that SE mitral caged-disk valves implanted >20 years previously should be carefully followed up, and that those implanted >30 years previously should be electively replaced with modern prosthetic valves
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Omatsu-Kanbe, Mariko; Nishino, Yuka; Nozuchi, Nozomi; Sugihara, Hiroyuki; Matsuura, Hiroshi
2014-01-01
Atypically-shaped cardiomyocytes (ACMs) constitute a novel subpopulation of beating heart cells found in the cultures of cardiac myocyte-removed crude fraction cells obtained from adult mouse cardiac ventricles. Although ~500 beating ACMs are observed under microscope in the cell cultures obtained from the hearts of either male or female mice, the origin of these cells in cardiac tissue has yet to be elucidated due to the lack of exclusive markers. In the present study, we demonstrate the efficacy of cellular prion protein (PrP) as a surface marker of ACMs. Cells expressing PrP at the plasma membrane in the culture of the crude fraction cells were found to develop into beating ACMs by themselves or fuse with each other to become larger multinuclear beating ACMs. Combining PrP with a cardiac-specific contractile protein cardiac troponin T (cTnT) allowed us to identify native ACMs in the mouse cardiac ventricles as either clustered or solitary cells. PrP- and cTnT-marked cells were also found in the adult, even aged, human cardiac ventricles. These findings suggest that interstitial cells marked by PrP and cTnT, native ACMs, exhibit life-long survival in the cardiac ventricles of both mice and humans. PMID:25466571
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Aortic valve repair leads to a low incidence of valve-related complications.
Aicher, Diana; Fries, Roland; Rodionycheva, Svetlana; Schmidt, Kathrin; Langer, Frank; Schäfers, Hans-Joachim
2010-01-01
Aortic valve replacement for aortic regurgitation (AR) has been established as a standard treatment but implies prosthesis-related complications. Aortic valve repair is an alternative approach, but its mid- to long-term results still need to be defined. Over a 12-year period, 640 patients underwent aortic valve repair for regurgitation of a unicuspid (n=21), bicuspid (n=205), tricuspid (n=411) or quadricuspid (n=3) aortic valve. The mechanism of regurgitation involved prolapse (n=469) or retraction (n=20) of the cusps, and dilatation of the root (n=323) or combined pathologies. Treatment consisted of cusp repair (n=529), root repair (n=323) or a combination of both (n=208). The patients were followed clinically and echocardiographically; follow-up was complete in 98.5% (cumulative follow-up: 3035 patient years). Hospital mortality was 3.4% in the total patient cohort and 0.8% for isolated aortic valve repair. The incidences of thrombo-embolism (0.2% per patient per year) and endocarditis (0.16%per patient per year) were low. Freedom from re-operation at 5 and 10 years was 88% and 81% in bicuspid and 97% and 93% in tricuspid aortic valves (p=0.0013). At re-operation, 13 out of 36 valves could be re-repaired. Freedom from valve replacement was 95% and 90% in bicuspid and 97% and 94% in tricuspid aortic valves (p=0.36). Freedom from all valve-related complications at 10 years was 88%. Reconstructive surgery of the aortic valve is feasible with low mortality in many individuals with aortic regurgitation. Freedom from valve-related complications after valve repair seems superior compared to available data on standard aortic valve replacement. Copyright 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
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Cho, Nakwon
1980-01-01
A positive acting valve suitable for operation in a corrosive environment is provided. The valve includes a hollow valve body defining an open-ended bore for receiving two, axially aligned, spaced-apart, cylindrical inserts. One insert, designated the seat insert, terminates inside the valve body in an annular face which lies within plane normal to the axis of the two inserts. An elastomeric O-ring seal is disposed in a groove extending about the annular face. The other insert, designated the wedge insert, terminates inside the valve body in at least two surfaces oppositely inclined with respect to each other and with respect to a plane normal to the axis of the two inserts. An elongated reciprocable gate, movable between the two inserts along a path normal to the axis of the two inserts, has a first flat face portion disposed adjacent and parallel to the annular face of the seat insert. The gate has a second face portion opposite to the first face portion provided with at least two oppositely inclined surfaces for mating with respective inclined surfaces of the wedge insert. An opening is provided through the gate which registers with a flow passage through the two inserts when the valve is open. Interaction of the respective inclined surfaces of the gate and wedge insert act to force the first flat face portion of the gate against the O-ring seal in the seat insert at the limits of gate displacement where it reaches its respective fully open and fully closed positions.
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Mendrinos, E; Dosso, A; Sommerhalder, J; Shaarawy, T
2009-09-01
To report corneal endothelial cell loss and in vivo visualization of the Ahmed glaucoma valve implant in eyes with refractory glaucoma. Ten eyes underwent Ahmed valve implant surgery and were followed-up for 12 months. Data collected included intraocular pressure (IOP), number of antiglaucoma medications and surgery-related complications. At 6 and 12 months postoperatively, the intracameral length of the drainage tube (ICL) and the distance between the tube and the cornea (T-C distance), and the iris (T-I distance) were assessed using anterior segment optical coherence tomography (AS-OCT). Heidelberg cornea tomograph II (HRT II) was used to measure the corneal endothelial cell density. Mean (+/-SEM) preoperative IOP was 29.5+/-4 mmHg. Mean postoperative IOP was 11.6+/-2 at 12 months (P<0.01). Over a 6-month period, mean corneal endothelial loss was 7.9%+/-2.5 in the central and 7.5%+/-2.4 in the peripheral cornea (P<0.01). There was no correlation between central or peripheral corneal endothelial cell loss and the T-C, T-I distance or the ICL of the tube. Corneal endothelial cell loss occurs following Ahmed valve implant surgery, this appears to be multifactorial. AS-OCT and HRT II are promising methods for the follow-up of patients with a glaucoma drainage device.
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Guggenheim, S. Frederic
1986-01-01
A multi-port fluid valve apparatus is used to control the flow of fluids through a plurality of valves and includes a web, which preferably is a stainless steel endless belt. The belt has an aperture therethrough and is progressed, under motor drive and control, so that its aperture is moved from one valve mechanism to another. Each of the valve mechanisms comprises a pair of valve blocks which are held in fluid-tight relationship against the belt. Each valve block consists of a block having a bore through which the fluid flows, a first seal surrounding the bore and a second seal surrounding the first seal, with the distance between the first and second seals being greater than the size of the belt aperture. In order to open a valve, the motor progresses the belt aperture to where it is aligned with the two bores of a pair of valve blocks, such alignment permitting a flow of the fluid through the valve. The valve is closed by movement of the belt aperture and its replacement, within the pair of valve blocks, by a solid portion of the belt.
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Koo, Euna B; Hou, Jing; Han, Ying; Keenan, Jeremy D; Stamper, Robert L; Jeng, Bennie H
2015-01-01
The aim of this study was to assess the effect of various tube parameters on corneal endothelial cell density (ECD) after insertion of Ahmed valves. Thirty-nine eyes of 33 patients with previous superotemporal (ST) Ahmed valve implantation and 20 eyes of 13 participants with previous uncomplicated phacoemulsification and intraocular lens implantation but no history of glaucoma surgery were evaluated. Various tube parameters were measured with anterior segment optical coherence tomography. ST, central, and inferonasal (IN) ECD and pachymetry were measured. Endothelial cell loss and corneal thickness in the ST cornea was compared with those in the IN cornea. The mean age of the operated patients was 58 ± 22 years, and the mean time since glaucoma surgery was 2.5 ± 2.6 years. Thirty-two of the 39 study eyes were pseudophakic. The ECD was significantly lower in the ST endothelium than in the IN endothelium in eyes with glaucoma tube surgery (P < 0.001), although this relative reduction in ST ECD was not greater than that seen in pseudophakic control eyes (P = 0.16). In univariate analysis, tube angle relative to the cornea and distance from the tip of the tube to the cornea were significant risk factors for decreased ST endothelial cell loss when assessed relative to the IN ECD (P = 0.01 and P = 0.02, respectively). In multivariate analysis, only the distance of the tube tip to the cornea remained significantly associated with ST endothelial cell loss. Although this was a retrospective study with inherent limitations, tubes that are closer to the cornea seem to lead to increased loss of adjacent endothelial cells.
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Nalluri, Nikhil; Atti, Varunsiri; Munir, Abdullah B; Karam, Boutros; Patel, Nileshkumar J; Kumar, Varun; Vemula, Praveen; Edla, Sushruth; Asti, Deepak; Paturu, Amrutha; Gayam, Sriramya; Spagnola, Jonathan; Barsoum, Emad; Maniatis, Gregory A; Tamburrino, Frank; Kandov, Ruben; Lafferty, James; Kliger, Chad
2018-05-20
Bioprosthetic (BP) valves have been increasingly used for aortic valve replacement over the last decade. Due to their limited durability, patients presenting with failed BP valves are rising. Valve in Valve - Transcatheter Aortic Valve Implantation (ViV-TAVI) emerged as an alternative to the gold standard redo-Surgical Aortic Valve Replacement (redo-SAVR). However, the utility of ViV-TAVI is poorly understood. A systematic electronic search of the scientific literature was done in PubMed, EMBASE, SCOPUS, Google Scholar, and ClinicalTrials.gov. Only studies which compared the safety and efficacy of ViV-TAVI and redo-SAVR head to head in failed BP valves were included. Six observational studies were eligible and included 594 patients, of whom 255 underwent ViV- TAVI and 339 underwent redo-SAVR. There was no significant difference between ViV-TAVI and redo- SAVR for procedural, 30 day and 1 year mortality rates. ViV-TAVI was associated with lower risk of permanent pacemaker implantation (PPI) (OR: 0.43, CI: 0.21-0.89; P = 0.02) and a trend toward increased risk of paravalvular leak (PVL) (OR: 5.45, CI: 0.94-31.58; P = 0.06). There was no significant difference for stroke, major bleeding, vascular complications and postprocedural aortic valvular gradients more than 20 mm-hg. Our results reiterate the safety and feasibility of ViV-TAVI for failed aortic BP valves in patients deemed to be at high risk for surgery. VIV-TAVI was associated with lower risk of permanent pacemaker implantation with a trend toward increased risk of paravalvular leak. © 2018, Wiley Periodicals, Inc.
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NASA Astrophysics Data System (ADS)
Mahmud, Md Arafat; Elumalai, Naveen Kumar; Upama, Mushfika Baishakhi; Wang, Dian; Gonçales, Vinicius R.; Wright, Matthew; Xu, Cheng; Haque, Faiazul; Uddin, Ashraf
2018-04-01
The current work reports the concurrent passivation of interstitial and oxygen vacancy mediated defect states in low temperature processed ZnO electron transport layer (ETL) via Ultraviolet-Ozone (UVO) treatment for fabricating highly efficient (maximum efficiency: 16.70%), triple cation based MA0.57FA0.38Rb0.05PbI3 (MA: methyl ammonium, FA: formamidinium, Rb: rubidium) perovskite solar cell (PSC). Under UV exposure, ozone decomposes to free atomic oxygen and intercalates into the interstitial and oxygen vacancy induced defect sites in the ZnO lattice matrix, which contributes to suppressed trap-assisted recombination phenomena in perovskite device. UVO treatment also reduces the content of functional hydroxyl group on ZnO surface, that increases the inter-particle connectivity and grain size of perovskite film on UVO treated ZnO ETL. Owing to this, the perovskite film atop UVO treated ZnO film exhibits reduced micro-strain and dislocation density values, which contribute to the enhanced photovoltaic performance of PSC with modified ZnO ETL. The modified PSCs exhibit higher recombination resistance (RRec) ∼40% compared to pristine ZnO ETL based control devices. Adding to the merit, the UVO treated ZnO PSC also demonstrates superior device stability, retaining about 88% of its initial PCE in the course of a month-long, systematic degradation study.
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Force measuring valve assemblies, systems including such valve assemblies and related methods
DeWall, Kevin George [Pocatello, ID; Garcia, Humberto Enrique [Idaho Falls, ID; McKellar, Michael George [Idaho Falls, ID
2012-04-17
Methods of evaluating a fluid condition may include stroking a valve member and measuring a force acting on the valve member during the stroke. Methods of evaluating a fluid condition may include measuring a force acting on a valve member in the presence of fluid flow over a period of time and evaluating at least one of the frequency of changes in the measured force over the period of time and the magnitude of the changes in the measured force over the period of time to identify the presence of an anomaly in a fluid flow and, optionally, its estimated location. Methods of evaluating a valve condition may include directing a fluid flow through a valve while stroking a valve member, measuring a force acting on the valve member during the stroke, and comparing the measured force to a reference force. Valve assemblies and related systems are also disclosed.
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Magnetically operated check valve
NASA Technical Reports Server (NTRS)
Morris, Brian G. (Inventor); Bozeman, Richard J., Jr. (Inventor)
1994-01-01
A magnetically operated check valve is disclosed. The valve is comprised of a valve body and a movable poppet disposed therein. A magnet attracts the poppet to hold the valve shut until the force of fluid flow through the valve overcomes the magnetic attraction and moves the poppet to an unseated, open position. The poppet and magnet are configured and disposed to trap a magnetically attracted particulate and prevent it from flowing to a valve seating region.
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Magnetically operated check valve
NASA Astrophysics Data System (ADS)
Morris, Brian G.; Bozeman, Richard J., Jr.
1994-06-01
A magnetically operated check valve is disclosed. The valve is comprised of a valve body and a movable poppet disposed therein. A magnet attracts the poppet to hold the valve shut until the force of fluid flow through the valve overcomes the magnetic attraction and moves the poppet to an unseated, open position. The poppet and magnet are configured and disposed to trap a magnetically attracted particulate and prevent it from flowing to a valve seating region.
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Pediatric Tubular Pulmonary Heart Valve from Decellularized Engineered Tissue Tubes
Reimer, Jay M.; Syedain, Zeeshan H.; Haynie, Bee H.T.; Tranquillo, Robert T.
2015-01-01
Pediatric patients account for a small portion of the heart valve replacements performed, but a pediatric pulmonary valve replacement with growth potential remains an unmet clinical need. Herein we report the first tubular heart valve made from two decellularized, engineered tissue tubes attached with absorbable sutures, which can meet this need, in principle. Engineered tissue tubes were fabricated by allowing ovine dermal fibroblasts to replace a sacrificial fibrin gel with an aligned, cell-produced collagenous matrix, which was subsequently decellularized. Previously, these engineered tubes became extensively recellularized following implantation into the sheep femoral artery. Thus, a tubular valve made from these tubes may be amenable to recellularization and, ideally, somatic growth. The suture line pattern generated three equi-spaced “leaflets” in the inner tube, which collapsed inward when exposed to back pressure, per tubular valve design. Valve testing was performed in a pulse duplicator system equipped with a secondary flow loop to allow for root distention. All tissue-engineered valves exhibited full leaflet opening and closing, minimal regurgitation (< 5%), and low systolic pressure gradients (< 2.5 mmHg) under pulmonary conditions. Valve performance was maintained under various trans-root pressure gradients and no tissue damage was evident after 2 million cycles of fatigue testing. PMID:26036175
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Wei, Ruihan; Parsons, Sean P; Huizinga, Jan D
2017-03-01
What is the central question of this study? What are the effects of interstitial cells of Cajal (ICC) network perturbations on intestinal pacemaker activity and motor patterns? What is the main finding and its importance? Two-dimensional modelling of the ICC pacemaker activity according to a phase model of weakly coupled oscillators showed that network properties (coupling strength between oscillators, frequency gradient and frequency noise) strongly influence pacemaker network activity and subsequent motor patterns. The model explains motor patterns observed in physiological conditions and provides predictions and testable hypotheses for effects of ICC loss and frequency modulation on the motor patterns. Interstitial cells of Cajal (ICC) are the pacemaker cells of gut motility and are associated with motility disorders. Interstitial cells of Cajal form a network, but the contributions of its network properties to gut physiology and dysfunction are poorly understood. We modelled an ICC network as a two-dimensional network of weakly coupled oscillators with a frequency gradient and showed changes over time in video and graphical formats. Model parameters were obtained from slow-wave-driven contraction patterns in the mouse intestine and pacemaker slow-wave activities from the cat intestine. Marked changes in propagating oscillation patterns (including changes from propagation to non-propagating) were observed by changing network parameters (coupling strength between oscillators, the frequency gradient and frequency noise), which affected synchronization, propagation velocity and occurrence of dislocations (termination of an oscillation). Complete uncoupling of a circumferential ring of oscillators caused the proximal and distal section to desynchronize, but complete synchronization was maintained with only a single oscillator connecting the sections with high enough coupling. The network of oscillators could withstand loss; even with 40% of oscillators lost randomly
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Bradley, Scott M
2013-10-01
The contents of this article were presented in the session "Aortic insufficiency in the teenager" at the congenital parallel symposium of the 2013 Society of Thoracic Surgeons (STS) annual meeting. The accompanying articles detail the approaches of aortic valve repair and the Ross procedure.(1,2) The current article focuses on prosthetic valve replacement. For many young patients requiring aortic valve surgery, either aortic valve repair or a Ross procedure provides a good option. The advantages include avoidance of anticoagulation and potential for growth. In other patients, a prosthetic valve is an appropriate alternative. This article discusses the current state of knowledge regarding mechanical and bioprosthetic valve prostheses and their specific advantages relative to valve repair or a Ross procedure. In current practice, young patients requiring aortic valve surgery frequently undergo valve replacement with a prosthetic valve. In STS adult cardiac database, among patients ≤30 years of age undergoing aortic valve surgery, 34% had placement of a mechanical valve, 51% had placement of a bioprosthetic valve, 9% had aortic valve repair, and 2% had a Ross procedure. In the STS congenital database, among patients 12 to 30 years of age undergoing aortic valve surgery, 21% had placement of a mechanical valve, 18% had placement of a bioprosthetic valve, 30% had aortic valve repair, and 24% had a Ross procedure. In the future, the balance among these options may be altered by design improvements in prosthetic valves, alternatives to warfarin, the development of new patch materials for valve repair, and techniques to avoid Ross autograft failure.
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Cardoso, Luis; Fritton, Susannah P.; Gailani, Gaffar; Benalla, Mohammed; Cowin, Stephen C.
2012-01-01
This contribution reviews recent research performed to assess the porosity and permeability of bone tissue with the objective of understanding interstitial fluid movement. Bone tissue mechanotransduction is considered to occur due to the passage of interstitial pore fluid adjacent to dendritic cell structures in the lacunar-canalicular porosity. The movement of interstitial fluid is also necessary for the nutrition of osteocytes. This review will focus on four topics related to improved assessment of bone interstitial fluid flow. First, the advantages and limitations of imaging technologies to visualize bone porosities and architecture at several length scales are summarized. Second, recent efforts to measure the vascular porosity and lacunar-canalicular microarchitecture are discussed. Third, studies associated with the measurement and estimation of the fluid pressure and permeability in the vascular and lacunar-canalicular domains are summarized. Fourth, the development of recent models to represent the interchange of fluids between the bone porosities is described. PMID:23174418
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NASA Technical Reports Server (NTRS)
Hawkins, S. F.; Overbey, C. W.
1980-01-01
Cellulose-sponge disk absorbs incoming water and expands with enough force to shut valve. When water recedes, valve opens by squeezing sponge dry to its original size. This direct mechanical action is considered more reliable than solenoid valve.
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Cockburn, James; Dooley, Maureen; Parker, Jessica; Hill, Andrew; Hutchinson, Nevil; de Belder, Adam; Trivedi, Uday; Hildick-Smith, David
2017-02-15
Redo surgery for degenerative bioprosthetic aortic valves is associated with significant morbidity and mortality. Report results of valve-in-valve therapy (ViV-TAVI) in failed supra-annular stentless Freedom Solo (FS) bioprostheses, which are the highest risk for coronary occlusion. Six patients with FS valves (mean age 78.5 years, 50% males). Five had valvular restenosis (peak gradient 87.2 mm Hg, valve area 0.63 cm 2 ), one had severe regurgitation (AR). Median time to failure was 7 years. Patients were high risk (mean STS/Logistic EuroScore 10.6 15.8, respectively). FS valves ranged from 21 to 25 mm. Successful ViV-TAVI was achieved in 4/6 patients (67%). Of the unsuccessful cases, (patient 1 and 2 of series) patient 1 underwent BAV with simultaneous aortography which revealed left main stem occlusion. The procedure was stopped and the patient went forward for repeat surgery. Patient 2 underwent successful ViV-TAVI with a 26-mm CoreValve with a guide catheter in the left main, but on removal coronary obstruction occurred, necessitating valve snaring into the aorta. Among the successful cases, (patients 3, 4, 5, 6) the TAVIs used were CoreValve Evolut R 23 mm (n = 3), and Lotus 23 mm (n = 1). In the successful cases the peak gradient fell from 83.0 to 38.3 mm Hg. No patient was left with >1+ AR. One patient had a stroke on Day 2, with full neurological recovery. Two patients underwent semi-elective pacing for LBBB and PR >280 ms. ViV-TAVI in stentless Freedom Solo valves is high risk. The risk of coronary occlusion is high. The smallest possible prosthesis (1:1 sizing) should be used, and strategies to protect the coronary vessels must be considered. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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Hundal, Rolv; Kessinger, Boyd A.; Parlak, Edward A.
1984-07-24
An overflow control valve for use in a liquid sodium coolant pump tank which valve can be extended to create a seal with the pump tank wall or retracted to break the seal thereby accommodating valve removal. An actuating shaft which controls valve disc position also has cams which bear on roller surfaces to force retraction of a sliding cylinder against spring tension to retract the cylinder from sealing contact with the pump tank.
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NASA Technical Reports Server (NTRS)
Horstman, Raymond H.
1992-01-01
Aerodynamic flow achieved by adding fixed fairings to butterfly valve. When valve fully open, fairings align with butterfly and reduce wake. Butterfly free to turn, so valve can be closed, while fairings remain fixed. Design reduces turbulence in flow of air in internal suction system. Valve aids in development of improved porous-surface boundary-layer control system to reduce aerodynamic drag. Applications primarily aerospace. System adapted to boundary-layer control on high-speed land vehicles.
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Mesofluidic two stage digital valve
Jansen, John F; Love, Lonnie J; Lind, Randall F; Richardson, Bradley S
2013-12-31
A mesofluidic scale digital valve system includes a first mesofluidic scale valve having a valve body including a bore, wherein the valve body is configured to cooperate with a solenoid disposed substantially adjacent to the valve body to translate a poppet carried within the bore. The mesofluidic scale digital valve system also includes a second mesofluidic scale valve disposed substantially perpendicular to the first mesofluidic scale valve. The mesofluidic scale digital valve system further includes a control element in communication with the solenoid, wherein the control element is configured to maintain the solenoid in an energized state for a fixed period of time to provide a desired flow rate through an orifice of the second mesofluidic valve.
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NASA Technical Reports Server (NTRS)
Addona, Brad; Eddleman, David
2015-01-01
A developmental Main Oxidizer Valve (MOV) was designed by NASA-MSFC using additive manufacturing processes. The MOV is a pneumatically actuated poppet valve to control the flow of liquid oxygen to an engine's injector. A compression spring is used to return the valve to the closed state when pneumatic pressure is removed from the valve. The valve internal parts are cylindrical in shape, which lends itself to traditional lathe and milling operations. However, the valve body represents a complicated shape and contains the majority of the mass of the valve. Additive manufacturing techniques were used to produce a part that optimized mass and allowed for design features not practical with traditional machining processes.
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Interstitial space and collagen alterations of the developing rat diaphragm
NASA Technical Reports Server (NTRS)
Gosselin, L. E.; Martinez, D. A.; Vailas, A. C.; Sieck, G. C.
1993-01-01
The effect of growth on the relative interstitial space [%total cross-sectional area (CSA)] and collagen content of the rat diaphragm muscle was examined at postnatal ages of 0, 7, 14, and 21 days as well as in adult males. The proportion of interstitial space relative to total muscle CSA was determined by computerized image analysis of lectin-stained cross sections of diaphragm muscle. To assess collagen content and extent of collagen maturation (i.e., cross-linking), high-pressure liquid chromatography analysis was used to measure hydroxyproline concentration and the nonreducible collagen cross-link hydroxylysylpyridinoline (HP), respectively. At birth, interstitial space accounted for approximately 47% of total diaphragm muscle CSA. During postnatal growth, the relative contribution of interstitial space decreased such that by adulthood the interstitial space accounted for approximately 18% of total muscle CSA. The change in relative interstitial space occurred without a concomitant change in hydroxyproline concentration. However, the concentration of HP markedly increased with age such that the adult diaphragm contained approximately 17 times more HP than at birth. These results indicate that during development the relative CSA occupied by interstitial space decreases as muscle fiber size increases. However, the reduction in relative interstitial space is not associated with a change in collagen concentration. Thus collagen density in the interstitial space may increase with age. It is possible that the observed changes in relative interstitial space and collagen influence the passive length-force properties of the diaphragm.
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Idiopathic Interstitial Pneumonias
... 50 More than 60% Pulmonary rehabilitation Lung transplantation Pirfenidone or nintedanib 50–70% die in 5 years. ... In This Article Generic Name Select Brand Names Pirfenidone ESBRIET nintedanib OFEV Interstitial Lung Diseases Overview of ...
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Yuzuriha, Shunsuke; Matsuo, Kiyoshi; Ban, Ryokuya; Yano, Shiharu; Moriizumi, Tetsuji
2012-01-01
Background: We previously reported that the supratarsal Mueller's muscle is innervated by both sympathetic efferent fibers and trigeminal proprioceptive afferent fibers, which function as mechanoreceptors-inducing reflexive contractions of both the levator and frontalis muscles. Controversy still persists regarding the role of the mechanoreceptors in Mueller's muscle; therefore, we clinically and histologically investigated Mueller's muscle. Methods: We evaluated the role of phenylephrine administration into the upper fornix in contraction of Mueller's smooth muscle fibers and how intraoperative stretching of Mueller's muscle alters the degree of eyelid retraction in 20 patients with aponeurotic blepharoptosis. In addition, we stained Mueller's muscle in 7 cadavers with antibodies against α-smooth muscle actin, S100, tyrosine hydroxylase, c-kit, and connexin 43. Results: Maximal eyelid retraction occurred approximately 3.8 minutes after administration of phenylephrine and prolonged eyelid retraction for at least 20 minutes after administration. Intraoperative stretching of Mueller's muscle increased eyelid retraction due to its reflexive contraction. The tyrosine hydroxylase antibody sparsely stained postganglionic sympathetic nerve fibers, whereas the S100 and c-kit antibodies densely stained the interstitial cells of Cajal (ICCs) among Mueller's smooth muscle fibers. A connexin 43 antibody failed to stain Mueller's muscle. Conclusions: A contractile network of ICCs may mediate neurotransmission within Mueller's multiunit smooth muscle fibers that are sparsely innervated by postganglionic sympathetic fibers. Interstitial cells of Cajal may also serve as mechanoreceptors that reflexively contract Mueller's smooth muscle fibers, forming intimate associations with intramuscular trigeminal proprioceptive fibers to induce reflexive contraction of the levator and frontalis muscles. PMID:22359687
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Wong, H-P; Mozdarani, H; Finnegan, C; McIlrath, J; Bryant, P E; Slijepcevic, P
2004-01-01
Interstitial telomeric sites (ITSs) in chromosomes from DNA repair-proficient mammalian cells are sensitive to both spontaneous and radiation-induced chromosome breakage. Exact mechanisms of this chromosome breakage sensitivity are not known. To investigate factors that predispose ITSs to chromosome breakage we used murine scid cells. These cells lack functional DNA-PKcs, an enzyme involved in the repair of DNA double-strand breaks. Interestingly, our results revealed lack of both spontaneous and radiation-induced chromosome breakage at ITSs found in scid chromosomes. Therefore, it is possible that increased sensitivity of ITSs to chromosome breakage is associated with the functional DNA double-strand break repair machinery. To investigate if this is the case we used scid cells in which DNA-PKcs deficiency was corrected. Our results revealed complete disappearance of ITSs in scid cells with functional DNA-PKcs, presumably through chromosome breakage at ITSs, but their unchanged frequency in positive and negative control cells. Therefore, our results indicate that the functional DNA double-strand break machinery is required for elevated sensitivity of ITSs to chromosome breakage. Interestingly, we observed significant differences in mitotic chromosome condensation between scid cells and their counterparts with restored DNA-PKcs activity suggesting that lack of functional DNA-PKcs may cause a defect in chromatin organization. Increased condensation of mitotic chromosomes in the scid background was also confirmed in vivo. Therefore, our results indicate a previously unanticipated role of DNA-PKcs in chromatin organisation, which could contribute to the lack of ITS sensitivity to chromosome breakage in murine scid cells. Copyright 2003 S. Karger AG, Basel
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Slow opening valve. [valve design for shuttle portable oxygen system
NASA Technical Reports Server (NTRS)
Drapeau, D. F. (Inventor)
1984-01-01
A valve control is described having a valve body with an actuator stem and a rotating handle connected to the actuator stem by a differential drive mechanism which, during uniform movement of the handle in one direction, initially opens the valve at a relatively slow rate and, thereafter, complete the valve movement at a substantially faster rate. A series of stop rings are received about the body in frictional abutting relationship and serially rotated by the handle to uniformly resist handle movement independently of the extent of handle movement.
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Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures
Park, Paul J.; Fuchs, Robert; Wei, Lai; Jorgensen, Brian G.; Redelman, Doug; Ward, Sean M.; Sanders, Kenton M.
2017-01-01
Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC), which serve as slow-wave electrical pacemakers for gastrointestinal (GI) smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes. In analyzing the transcriptome, we identified a unique set of ICC-restricted markers including transcription factors, epigenetic enzymes/regulators, growth factors, receptors, protein kinases/phosphatases, and ion channels/transporters. This analysis provides new and unique insights into the cellular and biological functions of ICC in GI physiology. Additionally, we constructed an interactive ICC genome browser (http://med.unr.edu/physio/transcriptome) based on the UCSC genome database. To our knowledge, this is the first online resource that provides a comprehensive library of all known genetic transcripts expressed in primary ICC. Our genome browser offers a new perspective into the alternative expression of genes in ICC and provides a valuable reference for future functional studies. PMID:28426719
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Native interstitial defects in ZnGeN2
NASA Astrophysics Data System (ADS)
Skachkov, Dmitry; Lambrecht, Walter R. L.
2017-10-01
A density functional study is presented of the interstitial Zni, Gei, and Ni in ZnGeN2. Corrections to the band gap are included by means of the LDA+U method. The Zn and Ge interstitials are both found to strongly prefer the larger octahedral site compared to the two types of tetrahedral sites. The Zn interstitial is found to be a shallow double donor, but it has higher energy than previously studied antisite defects. It has a resonance in the conduction band that is Zn-s like. The Ge interstitial is an even higher energy of formation defect and also behaves as a shallow double donor, but it also has a deep level in the gap corresponding to a Ge-s orbital character while the Ge-p forms a resonance in the conduction band. The nitrogen interstitial forms a split-interstitial configuration, as also occurs in GaN. Its electronic levels can be related to that of a N2 molecule. The defect levels in the gap correspond to the πg-like lowest unoccupied molecular orbital of the molecule, which here becomes filled with three electrons in the defect's neutral charge state. They are found to prefer a high-spin configuration in the q =+1 state. The corresponding transition levels are obtained and show that this is an amphoteric trap level occurring in +2 , +1 , 0, and -1 charge states. The two possible sites for this split interstitial, on top of Zn or on top of Ge, differ slightly in N2 bond length. While the Ni defects have the lowest formation energy among the interstitials, it is still higher than that of the antisites. Hence they are not expected to occur in sufficient concentration to affect the intrinsic Fermi level position. In particular, they do not contribute to the unintentional n -type background doping.
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NASA Technical Reports Server (NTRS)
Gonzalez, R.; Vandewalle, J.
1986-01-01
Redesigned actuator assembly weighs 50 percent less. Isolator valve operated by ac motor instead of usual dc solenoid. Valve weighs only 3 lb (1.4 kg). New valve functions with either two-phase or three-phase power. Developed for isolating fluids in propellant tanks, manifolds, and interconnecting lines of Space Shuttle reaction control and orbital maneuvering subsystems, valve suited to applications in which leakage must be kept to minimum at high pressure differences - in petroleum and chemical processing.
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Heart valve bioprosthesis durability: a challenge to the new generation of porcine valves.
Valente, M; Minarini, M; Maizza, A F; Bortolotti, U; Thiene, G
1992-01-01
Long-term experience with first generation porcine valve xenografts enabled identification of the major limitations to their durability: (1) prosthetic-ventricular mismatch due to the high profile of the stent in patients with mitral stenosis and a small left ventricle; (2) high-pressure fixation with loss of natural collagen crimping in the fibrosa, and wash-out of proteoglycans in the spongiosa; (3) xenograft tissue autolysis, due to the long interval between animal slaughter and aortic valve removal fixation; (4) muscle shelf in the right coronary cusp, which created a gradient and could undergo accelerated calcification and/or spontaneous perforation with time; (5) a flexible polypropylene stent, which could creep or even fracture with consequent inward bending of the stent; (6) progressive time-related dystrophic calcification; (7) host fibrous tissue ingrowth. An awareness of these limitations stimulated technical modifications, which frequently brought about distinct improvements: (1) the reduction of the stent profile eliminated the problem of mismatch, but resulted in a higher tendency towards cusp prolapse and earlier commissural tearing; (2) natural collagen waviness, proteoglycans and cusp extensibility were preserved by employing low or even zero pressure during the fixation process; (3) earlier valve fixation enabled preservation of cell integrity; (4) a new orifice for small valves was designed by replacing the right muscular cusp, thus achieving less gradient and avoiding muscle-shelf-related complications; (5) polypropylene was replaced by Delrin as stent material; (6) calcium-retarding agents like T6 and toluidine blue were applied during commercial processing and storage in order to mitigate tissue mineralization.(ABSTRACT TRUNCATED AT 250 WORDS)
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Brown, Stephen C; Cools, Bjorn; Gewillig, Marc
2016-09-01
Bioprosthetic valves degenerate over time. Transcatheter valve-in-valve procedures have become an attractive alternative to surgery. However, every valve increasingly diminishes the diameter of the valvar orifice. We report a 12-year-old female who had a previous transcatheter tricuspid valve-in-valve procedure; cracking the ring of a Carpentier Edwards Perimount valve by means of an ultrahigh pressure balloon allowed implantation of a further larger percutaneous valve. The advantage of this novel approach permits enlarging the inner valve diameter and may facilitate future interventions and prolong time to surgery. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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[Alternative treatments for interstitial cystitis].
Gamé, X; Bart, S; Castel-Lacanal, E; De Sèze, M; Karsenty, G; Labat, J-J; Rigaud, J; Scheiber-Nogueira, M C; Ruffion, A
2009-06-01
Interstitial cystitis is the first cause of bladder pain. In case of failure of the usual treatments, several other modalities have been proposed. These therapeutic modalities are posterior sacral root neuromodulation, posterior tibial nerve stimulation, vanilloid agent intravesical instillation, intradetrusor botulinum toxin injections and surgery. A certain efficiency of each of these treatments in the interstitial cystitis has been reported. However, the evaluation of these treatments is limited and the level of evidence is too low to propose these treatments in routine.
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Your heart has four valves. Normally, these valves open to let blood flow through or out of your heart, and then shut to keep it from flowing ... close tightly. It's one of the most common heart valve conditions. Sometimes it causes regurgitation. Stenosis - when ...
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Chen, Yei-Tsung; Wang, Juan; Wee, Abby S. Y.; Yong, Quek-Wei; Tay, Edgar Lik-Wui; Woo, Chin Cheng; Sorokin, Vitaly; Richards, Arthur Mark; Ling, Lieng-Hsi
2016-01-01
Myxomatous mitral valve prolapse (MMVP) and fibroelastic deficiency (FED) are two common variants of degenerative mitral valve disease (DMVD), which is a leading cause of mitral regurgitation worldwide. While pathohistological studies have revealed differences in extracellular matrix content in MMVP and FED, the molecular mechanisms underlying these two disease entities remain to be elucidated. By using surgically removed valvular specimens from MMVP and FED patients that were categorized on the basis of echocardiographic, clinical and operative findings, a cluster of microRNAs that expressed differentially were identified. The expressions of has-miR-500, -3174, -17, -1193, -646, -1273e, -4298, -203, -505, and -939 showed significant differences between MMVP and FED after applying Bonferroni correction (p < 0.002174). The possible involvement of microRNAs in the pathogenesis of DMVD were further suggested by the presences of in silico predicted target sites on a number of genes reported to be involved in extracellular matrix homeostasis and marker genes for cellular composition of mitral valves, including decorin (DCN), aggrecan (ACAN), fibromodulin (FMOD), α actin 2 (ACTA2), extracellular matrix protein 2 (ECM2), desmin (DES), endothelial cell specific molecule 1 (ESM1), and platelet/ endothelial cell adhesion molecule 1 (PECAM1), as well as inverse correlations of selected microRNA and mRNA expression in MMVP and FED groups. Our results provide evidence that distinct molecular mechanisms underlie MMVP and FED. Moreover, the microRNAs identified may be targets for the future development of diagnostic biomarkers and therapeutics. PMID:27213335
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Kearney, Sinéad M.; Kilcawley, Niamh A.; Early, Philip L.; Glynn, Macdara T.; Ducrée, Jens
2016-01-01
Here we present retrieval of Peripheral Blood Mononuclear Cells by density-gradient medium based centrifugation for subsequent analysis of the leukocytes on an integrated microfluidic “Lab-on-a-Disc” cartridge. Isolation of white blood cells constitutes a critical sample preparation step for many bioassays. Centrifugo-pneumatic siphon valves are particularly suited for blood processing as they function without need of surface treatment and are ‘low-pass’, i.e., holding at high centrifugation speeds and opening upon reduction of the spin rate. Both ‘hydrostatically’ and ‘hydrodynamically’ triggered centrifugo-pneumatic siphon valving schemes are presented. Firstly, the geometry of the pneumatic chamber of hydrostatically primed centrifugo-pneumatic siphon valves is optimised to enable smooth and uniform layering of blood on top of the density-gradient medium; this feature proves to be key for efficient Peripheral Blood Mononuclear Cell extraction. A theoretical analysis of hydrostatically primed valves is also presented which determines the optimum priming pressure for the individual valves. Next, ‘dual siphon’ configurations for both hydrostatically and hydrodynamically primed centrifugo-pneumatic siphon valves are introduced; here plasma and Peripheral Blood Mononuclear Cells are extracted through a distinct siphon valve. This work represents a first step towards enabling on disc multi-parameter analysis. Finally, the efficiency of Peripheral Blood Mononuclear Cells extraction in these structures is characterised using a simplified design. A microfluidic mechanism, which we termed phase switching, is identified which affects the efficiency of Peripheral Blood Mononuclear Cell extraction. PMID:27167376
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Knitting for heart valve tissue engineering
Ayad, Nadia; Wojciechowska, Dorota; Zielińska, Dorota; Struszczyk, Marcin H.; Latif, Najma; Yacoub, Magdi
Knitting is a versatile technology which offers a large portfolio of products and solutions of interest in heart valve (HV) tissue engineering (TE). One of the main advantages of knitting is its ability to construct complex shapes and structures by precisely assembling the yarns in the desired position. With this in mind, knitting could be employed to construct a HV scaffold that closely resembles the authentic valve. This has the potential to reproduce the anisotropic structure that is characteristic of the heart valve with the yarns, in particular the 3-layered architecture of the leaflets. These yarns can provide oriented growth of cells lengthwise and consequently enable the deposition of extracellular matrix (ECM) proteins in an oriented manner. This technique, therefore, has a potential to provide a functional knitted scaffold, but to achieve that textile engineers need to gain a basic understanding of structural and mechanical aspects of the heart valve and in addition, tissue engineers must acquire the knowledge of tools and capacities that are essential in knitting technology. The aim of this review is to provide a platform to consolidate these two fields as well as to enable an efficient communication and cooperation among these two research areas. PMID:29043276
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Late glaucoma after interstitial keratitis.
Grant, W M
1975-01-01
In a systematic study of 45 patients who had syphilitic interstitial keratitis early in life and, many years later, were discovered to have glaucoma, there was evidence of two different but equally common mechanisms. In one group of patients, a deep-chamber type of glaucoma was superimposed on old inflammatory changes, was characteristically refractory to medical treatment, but did well with filtering surgery. The other group of patients had reversible angle-closure glaucoma associated with anatomically small anterior segments, and typically responded well to iridectomy. The late, refractory, deep-chamber type of glaucoma may involve endothelialization and formation of glass membrane in the angle, as seen in one excised eye. Occurrence of the shallow-chamber, reversible angle-closure type of glaucoma after interstitial keratitis may be coincidental, since no other evidence supports the idea that small anterior segments might be particularly prevalent among patients who have had congenital syphilis or interstitial keratitis.
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Sarı, Cenk; Baştuğ, Serdal; Kasapkara, Hacı Ahmet; Durmaz, Tahir; Keleş, Telat; Akçay, Murat; Aslan, Abdullah Nabi; Bayram, Nihal Akar; Bozkurt, Engin
2015-01-01
Introduction Transcatheter aortic valve implantation for severe symptomatic aortic stenosis in patients with a previous mitral valve prosthesis is technically challenging, and pre-procedural comprehensive assessment of these patients before transcatheter aortic valve implantation is vital for an uncomplicated and successful procedure. Aim We want to share our experience with transcatheter aortic valve implantation in patients with a preexisting functional mitral valve prosthesis and describe a series of important technical and pre-procedural details. Material and methods At our center, 135 patients with symptomatic severe aortic stenosis were treated with transcatheter aortic valve implantation. Six of them with a preexisting mitral valve prosthesis received an Edwards SAPIEN XT valve through the transfemoral route. Results Transcatheter aortic valve implantation was performed successfully in all 6 patients without any deformation of the cobalt-chromium/steel stents of the aortic valve bioprosthesis. Also no distortion or malfunction in the mitral valve prosthesis was observed after the procedure. There were no complications during the hospitalization period. Post-procedural echocardiography revealed no or mild aortic paravalvular regurgitation and normal valve function in all the patients. In addition, serial echocardiographic examination demonstrated that both the stability and function of the aortic and mitral prosthetic valves were normal without any deterioration in the gradients and the degree of the regurgitation at long-term follow-ups. Conclusions Our experience confirms that transcatheter aortic valve implantation is technically feasible in patients with previous mitral valve replacement but comprehensive evaluation of patients by multimodal imaging techniques such as transesophageal echocardiography and multislice computed tomography is mandatory for a successful and safe procedure. PMID:26677380
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Neethling, W M; Papadimitriou, J M; Swarts, E; Hodge, A J
2000-06-01
Valve related factors and patient related factors are responsible for calcification of valvular bioprostheses. Recent studies showed different donor and recipient species have different influences on the total calcification rate of bioprostheses. This study was performed to evaluate and compare Kangaroo aortic valve leaflets with porcine aortic valve leaflets. Experimental design. Prospective study. Setting. Cardio-thoracic experimental research of a university department. Glutaraldehyde-fixed Kangaroo and porcine valve leaflets were evaluated in vitro according to valve geometry (internal diameter and leaflet thickness), morphology (light and electron microscopy) and tensile strength. In vivo evaluation consisted of implantation in a rat model for 8 weeks, Von Kossa stain for calcium and atomic absorption spectrophotometry for total extractable calcium content. Kangaroo valves indicated a smaller internal valve diameter as well as a thinner valve leaflet (p<0.01, ANOVA) at corresponding body weight, less proteoglycan spicules in the fibrosa, increased elasticity (p<0.05) and low calcification potential (p<0.01, confidence interval 95%). Kangaroo aortic valve leaflets have different valvular qualities compared to porcine valve tissue. Kangaroo valve leaflets are significantly superior to porcine valve leaflets as far as calcification is concerned. These results are encouraging and suggest further in vivo evaluation in a larger animal model before clinical application can be considered.
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... working correctly. Most valve replacements involve the aortic Tricuspid valve and mitral valves. The aortic valve separates ... where it shouldn’t. This is called incompetence, insufficiency or regurgitation. • Prolapse — mitral valve flaps don’t ...
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... and replacing it with a man-made or biological valve. Biological valves are made from pig, cow, or human ... the valve. Man-made valves last longer than biological valves and usually don’t have to be ...
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Valve repair in aortic regurgitation without root dilatation--aortic valve repair.
Lausberg, H F; Aicher, D; Kissinger, A; Langer, F; Fries, R; Schäfers, H-J
2006-02-01
Aortic valve repair was established in the context of aortic root remodeling. Variable results have been reported for isolated valve repair. We analyzed our experience with isolated valve repair and compared the results with those of aortic root remodeling. Between October 1995 and August 2003, isolated repair of the aortic valve was performed in 83 patients (REP), remodeling of the aortic valve in 175 patients (REMO). The demographics of the two groups were comparable (REP: mean age 54.4 +/- 20.7 yrs, male-female ratio 2.1 : 1; REMO: mean age 60.8 +/- 13.6 yrs, male-female ratio 2.4 : 1; p = ns). In both groups the number of bicuspid valves was comparable (REP: 41 %, REMO: 32 %; p = ns). All patients were followed by echocardiography for a cumulative follow-up of 8204 patient months (mean 32 +/- 23 months). Overall in-hospital mortality was 2.4 % in REP and 4.6 % in REMO ( p = 0.62). Systolic gradients were comparable in both groups (REP: 5.8 +/- 2.2, REMO: 6.5 +/- 3.1 mm Hg, p = 0.09). The mean degree of aortic regurgitation 12 months postoperatively was 0.8 +/- 0.7 after REP and 0.7 +/- 0.7 after REMO ( p = 0.29). Freedom from significant regurgitation (> or = II degrees ) after 5 years was 86 % in REP and 89 % in REMO ( p = 0.17). Freedom from re-operation after 5 years was 94.4 % in REP and 98.2 % in REMO ( p = 0.33). Aortic regurgitation without concomitant root dilatation can be treated effectively by aortic valve repair. The functional results are equivalent to those obtained with valve-preserving root replacement. Aortic valve repair appears to be an alternative to valve replacement in aortic regurgitation.
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Edwards, Daniel C; Gitman, Robert; May, Noah R; Amster, Melanie I
2017-01-01
A 71-year-old female presented with a large, protuberant abdominal mass, and was found to have both a left renal mass and a biopsy-proven neuroendocrine tumor of the ileocecal valve. Ultimately, right hemicolectomy revealed a well-differentiated and low-grade neuroendocrine tumor of the ileocecal valve, whereas left radical nephrectomy revealed a 23 cm × 22 cm × 15 cm renal cell carcinoma, chromophobe-type (RCC-CT) weighing 3564 g. RCC-CT represents a small portion of diagnosed RCC, and generally portends a more favorable prognosis than other variants. Modern reports of renal tumors exceeding 20 cm are exceedingly rare. In spite of massive size, favorable histology may allow for surgical cure. Copyright © 2016 Elsevier Inc. All rights reserved.
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Nitrergic signalling via interstitial cells of Cajal regulates motor activity in murine colon.
Lies, Barbara; Beck, Katharina; Keppler, Jonas; Saur, Dieter; Groneberg, Dieter; Friebe, Andreas
2015-10-15
In the enteric nervous systems, NO is released from nitrergic neurons as a major inhibitory neurotransmitter. NO acts via NO-sensitive guanylyl cyclase (NO-GC), which is found in different gastrointestinal (GI) cell types including smooth muscle cells (SMCs) and interstitial cells of Cajal (ICC). The precise mechanism of nitrergic signalling through these two cell types to regulate colonic spontaneous contractions is not fully understood yet. In the present study we investigated the impact of endogenous and exogenous NO on colonic contractile motor activity using mice lacking nitric oxide-sensitive guanylyl cyclase (NO-GC) globally and specifically in SMCs and ICC. Longitudinal smooth muscle of proximal colon from wild-type (WT) and knockout (KO) mouse strains exhibited spontaneous contractile activity ex vivo. WT and smooth muscle-specific guanylyl cyclase knockout (SMC-GCKO) colon showed an arrhythmic contractile activity with varying amplitudes and frequencies. In contrast, colon from global and ICC-specific guanylyl cyclase knockout (ICC-GCKO) animals showed a regular contractile rhythm with constant duration and amplitude of the rhythmic contractions. Nerve blockade (tetrodotoxin) or specific blockade of NO signalling (L-NAME, ODQ) did not significantly affect contractions of GCKO and ICC-GCKO colon whereas the arrhythmic contractile patterns of WT and SMC-GCKO colon were transformed into uniform motor patterns. In contrast, the response to electric field-stimulated neuronal NO release was similar in SMC-GCKO and global GCKO. In conclusion, our results indicate that basal enteric NO release acts via myenteric ICC to influence the generation of spontaneous contractions whereas the effects of elevated endogenous NO are mediated by SMCs in the murine proximal colon. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.
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NASA Technical Reports Server (NTRS)
Tervo, John N.
1992-01-01
Valve plate made to translate as well as rotate. Valve opened and closed by turning shaft and lever. Interactions among lever, spring, valve plate, and face seal cause plate to undergo combination of translation and rotation so valve plate clears seal during parts of opening and closing motions.
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Cinnamaldehyde impairs high glucose-induced hypertrophy in renal interstitial fibroblasts
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chao, Louis Kuoping; Chang, W.-T.; Shih, Y.-W.
2010-04-15
Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. To explore whether cinnamaldehyde was linked to altered high glucose (HG)-mediated renal tubulointerstitial fibrosis in diabetic nephropathy (DN), the molecular mechanisms of cinnamaldehyde responsible for inhibition of HG-induced hypertrophy in renal interstitial fibroblasts were examined. We found that cinnamaldehyde caused inhibition of HG-induced cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, cleaved poly(ADP-ribose) polymerase (PARP) protein expression, and mitochondrial cytochrome c release in HG or cinnamaldehyde treatments in these cells. HG-induced extracellular signal-regulatedmore » kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) (but not the Janus kinase 2/signal transducers and activators of transcription) activation was markedly blocked by cinnamaldehyde. The ability of cinnamaldehyde to inhibit HG-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of collagen IV, fibronectin, and alpha-smooth muscle actin (alpha-SMA). The results obtained in this study suggest that cinnamaldehyde treatment of renal interstitial fibroblasts that have been stimulated by HG reduces their ability to proliferate and hypertrophy through mechanisms that may be dependent on inactivation of the ERK/JNK/p38 MAPK pathway.« less
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Transapical JenaValve in a patient with mechanical mitral valve prosthesis.
O' Sullivan, Katie E; Casserly, Ivan; Hurley, John
2015-04-01
We report the first case of transcatheter aortic valve replacement implantation using JenaValve™ in a patient with mechanical mitral valve prosthesis. We believe that the design features of this valve may be particularly suited for use in this setting. © 2014 Wiley Periodicals, Inc.
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NASA Astrophysics Data System (ADS)
Kaiser, Alexander
2016-11-01
The mitral valve is one of four valves in the human heart. The valve opens to allow oxygenated blood from the lungs to fill the left ventricle, and closes when the ventricle contracts to prevent backflow. The valve is composed of two fibrous leaflets which hang from a ring. These leaflets are supported like a parachute by a system of strings called chordae tendineae. In this talk, I will describe a new computational model of the mitral valve. To generate geometry, general information comes from classical anatomy texts and the author's dissection of porcine hearts. An MRI image of a human heart is used to locate the tips of the papillary muscles, which anchor the chordae tendineae, in relation to the mitral ring. The initial configurations of the valve leaflets and chordae tendineae are found by solving solving an equilibrium elasticity problem. The valve is then simulated in fluid (blood) using the immersed boundary method over multiple heart cycles in a model valve tester. We aim to identify features and mechanisms that influence or control valve function. Support from National Science Foundation, Graduate Research Fellowship Program, Grant DGE 1342536.
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Magnetically operated check valve
NASA Astrophysics Data System (ADS)
Morris, Brian G.; Bozeman, Richard J., Jr.
1993-03-01
A magnetically operated check valve is disclosed having, in one aspect, a valve body and a movable poppet disposed therein. A magnet attracts the poppet to hold the valve shut until the force of fluid flow through the valve overcomes the magnetic attraction and moves the poppet to an unseated, open position. The poppet and magnet are configured and disposed to trap a magnetically attracted particulate and prevent it from flowing to a valve seating region.
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NASA Technical Reports Server (NTRS)
Perkins, Gerald S. (Inventor)
1979-01-01
A check valve which closes more rapidly to prevent wearing of the valve seat and of the valve member that seals thereagainst, including a solenoid or other actuator that aids the normal spring to quickly close the valve at approximately the time when downpath fluid flow would stop, the actuator then being deenergized. The control circuit that operates the actuator can include a pair of pressure sensors sensing pressure both upstream and downstream from the valve seat. Where the valve is utilized to control flow to or from a piston pump, energization of the actuator can be controlled by sensing when the pump piston reaches its extreme of travel.
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Sendo, Sho; Saegusa, Jun; Okano, Takaichi; Takahashi, Soshi; Akashi, Kengo; Morinobu, Akio
2017-12-01
SKG mice develop interstitial lung disease (ILD) resembling rheumatoid arthritis-associated ILD in humans. The aim of this study was to clarify the mechanism underlying the lung pathology by analyzing lung-infiltrating cells in SKG mice with ILD. We assessed the severity of zymosan A (ZyA)-induced ILD in SKG mice histologically, and we examined lung-infiltrating cells by flow cytometry. Total lung cells and isolated monocytic myeloid-derived suppressor cells (MDSCs) were cultured in vitro with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4. The proliferation of 5,6-carboxyfluorescein diacetate N-succinimidyl ester-labeled naive T cells cocultured with isolated CD11b+Gr-1 dim cells and MDSCs was evaluated by flow cytometry. CD11b+Gr-1 dim cells were adoptively transferred to ZyA-treated SKG mice. MDSCs, Th17 cells, and group 1 and 3 innate lymphoid cells (ILC1s and ILC3s) were increased in the lungs; the proportion of these cells varied with ILD severity. In this process, we found that a unique cell population, CD11b+Gr-1 dim cells, was expanded in the severely inflamed lungs. Approximately half of the CD11b+Gr-1 dim cells expressed CD11c. CD11b+Gr-1 dim cells were induced from monocytic MDSCs with GM-CSF in vitro and were considered tolerogenic because they suppressed T cell proliferation. These CD11b+Gr-1 dim cells have never been described previously, and we termed them CD11b+Gr-1 dim tolerogenic dendritic cell (DC)-like cells. Th17 cells, ILC1s, and ILC3s in the inflamed lung produced GM-CSF, which may have expanded CD11b+Gr-1 dim tolerogenic DC-like cells in vivo. Furthermore, adoptive transfer of CD11b+Gr-1 dim tolerogenic DC-like cells significantly suppressed progression of ILD in SKG mice. We identified unique suppressive myeloid cells that were differentiated from monocytic MDSCs in SKG mice with ILD, and we termed them CD11b+Gr-1 dim tolerogenic DC-like cells. © 2017, American College of Rheumatology.
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Double-orifice mitral valve associated with bicuspid aortic valve.
Khani, Mohammad; Rohani, Atoosheh
2017-06-01
Double-orifice mitral valve is a rare congenital anomaly that usually does not cause a significant hemodynamic effect. Double-orifice mitral valve and a bicuspid aortic valve were detected in a 54-year-old lady who presented with dyspnea on exertion for one year. This is a rare association. Three-dimensional echocardiography is helpful to determine the type of malformation. The patient had no significant mitral regurgitation or stenosis, but demonstrated moderate aortic stenosis. She is undergoing periodic monitoring.
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Valve-sparing aortic root replacement in bicuspid aortic valves: a reasonable option?
Aicher, Diana; Langer, Frank; Kissinger, Anke; Lausberg, Henning; Fries, Roland; Schäfers, Hans-Joachim
2004-11-01
Aortic dilatation occurs in many patients with bicuspid aortic valves. We have added root replacement using the remodeling technique originally designed for tricuspid aortic valves to bicuspid aortic valve repair for treatment of the dilated root. We compared the results of remodeling in bicuspid aortic valves with those in tricuspid aortic valves. From October 1995 through January 2004, 60 patients underwent root remodeling for bicuspid aortic valves (group A), and 130 patients underwent root remodeling for tricuspid aortic valves (group B). Correction of cusp prolapse was more often performed in group A (group A, 50/60; group B, 47/130; P < .0001). Transthoracic echocardiography was performed at 1 week, 6 and 12 months, and every year thereafter. Cumulative follow-up was 527 patient-years (mean, 2.9 +/- 2 years). No patient died in group A. Hospital mortality in group B was 5% (5/100; 95% confidence interval,1.6%-11.3%) after elective operations and 10% (3/30; 95% confidence interval, 2.1%-26.5%) after emergency operations. Mean systolic gradients were identical at 1 year (group A, 4.8 +/- 2.1 mm Hg; group B, 4.0 +/- 2 mm Hg) and 5 years (group A, 4.5 +/- 2.3 mm Hg; group B, 3.9 +/- 2.2 mm Hg). Freedom from aortic regurgitation of grade 2 or higher at 5 years was 96% in group A and 83% in group B ( P = .07), and freedom from reoperation at 5 years was 98% in group A and 98% in group B ( P = .73). Valve-sparing aortic replacement with root remodeling can be applied to aortic dilatation and a regurgitant bicuspid aortic valve. Hemodynamic function and valve stability of a repaired bicuspid aortic valve are comparable with those seen in cases of tricuspid anatomy.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
McKnight, Timothy E.; Johnson, Anthony; Moise, Kenneth J.
Valve implant systems positionable within a flow passage, the systems having an inlet, an outlet, and a remotely activatable valve between the inlet and outlet, with the valves being operable to provide intermittent occlusion of the flow path. A remote field is applied to provide thermal or magnetic activation of the valves.
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Oborny, Michael C.; Paul, Phillip H.; Hencken, Kenneth R.; Frye-Mason, Gregory C.; Manginell, Ronald P.
2001-01-01
A valve for controlling fluid flows. This valve, which includes both an actuation device and a valve body provides: the ability to incorporate both the actuation device and valve into a unitary structure that can be placed onto a microchip, the ability to generate higher actuation pressures and thus control higher fluid pressures than conventional microvalves, and a device that draws only microwatts of power. An electrokinetic pump that converts electric potential to hydraulic force is used to operate, or actuate, the valve.
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Williams, William R.
1979-01-01
The present invention is directed to a solids handling valve for use in combination with lock hoppers utilized for conveying pulverized coal to a coal gasifier. The valve comprises a fluid-actuated flow control piston disposed within a housing and provided with a tapered primary seal having a recessed seat on the housing and a radially expandable fluid-actuated secondary seal. The valve seals are highly resistive to corrosion, erosion and abrasion by the solids, liquids, and gases associated with the gasification process so as to minimize valve failure.
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Arkelyan, A.M.; Rickard, C.L.
1962-04-17
A gate valve for controlling the flow of fluid in separate concentric ducts or channels by means of a single valve is described. In one position, the valve sealing discs engage opposed sets of concentric ducts leading to the concentric pipes defining the flow channels to block flow therethrough. In another position, the discs are withdrawn from engagement with the opposed ducts and at the same time a bridging section is interposed therebetween to define concentric paths coextensive with and connecting the opposed ducts to facilitate flow therebetween. A wedge block arrangement is employed with each sealing disc to enable it to engage the ducts. The wedge block arrangement also facilitates unobstructcd withdrawal of the discs out of the intervening space between the sets of ducts. (AEC)
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Hellsten, Y; Nyberg, M; Mortensen, S P
2012-01-01
The regulation of blood flow to skeletal muscle involves a complex interaction between several locally formed vasodilators that are produced both in the skeletal muscle interstitium and intravascularly. The gas nitric oxide (NO) and the purines ATP and adenosine, are potent vasodilators that are formed by multiple cell types and released into the skeletal muscle interstitium and in plasma in response to muscle contraction. Cellular sources of ATP and NO in plasma are erythrocytes and endothelial cells, whereas interstitial sources are skeletal muscle cells and endothelial cells. Adenosine originates primarily from extracellular degradation of ATP. During exercise the concentrations of ATP and adenosine increase markedly in the interstitium with smaller increases occurring in plasma, and thus the interstitial concentration during exercise is severalfold higher than in plasma. The concentration of NO metabolites (NOx) in interstitium and plasma does not change during exercise and is similar in the two compartments. Adenosine and NO have been shown to contribute to exercise hyperaemia whereas the role of ATP remains unclear due to lack of specific purinergic receptor blockers. The relative role of intravascular versus interstitial vasodilators is not known but evidence suggests that both compartments are important. In cardiovascular disease, a reduced capacity to form adenosine in the muscle interstitium may be a contributing factor in increased peripheral vascular resistance. PMID:22733661
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Liquid rocket valve components
NASA Technical Reports Server (NTRS)
1973-01-01
A monograph on valves for use with liquid rocket propellant engines is presented. The configurations of the various types of valves are described and illustrated. Design criteria and recommended practices for the various valves are explained. Tables of data are included to show the chief features of valve components in use on operational vehicles.
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Valve assembly for internal combustion engine
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wakeman, R.J.; Shea, S.F.
1989-09-05
This patent describes an improvement in a valve assembly for an internal combustion engine of the type including a valve having a valve stem, a valve guideway for mounting this valve for reciprocal strokes between opened and seated position, and spring means for biasing the valve into the seated position. The improvement comprising a valve spool of greater cross-sectional diameter as compared to the valve stem, and a valve spool guideway within which the valve spool is movable during the strokes of the valve, an upper surface of the valve spool and a portion of the spool guideway collectively establishingmore » a damper chamber which varies in volume during the valve strokes. a feed passage for introducing oil into the damper chamber, and a bleed passage for discharging oil from the damper chamber. The bleed passages each laterally opening into the valve spool guideway.« less
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Cottle, Beverley J; Lewis, Fiona C; Shone, Victoria; Ellison-Hughes, Georgina M
2017-07-04
The development of cellular therapies to treat muscle wastage with disease or age is paramount. Resident muscle satellite cells are not currently regarded as a viable cell source due to their limited migration and growth capability ex vivo. This study investigated the potential of muscle-derived PW1 + /Pax7 - interstitial progenitor cells (PICs) as a source of tissue-specific stem/progenitor cells with stem cell properties and multipotency. Sca-1 + /PW1 + PICs were identified on tissue sections from hind limb muscle of 21-day-old mice, isolated by magnetic-activated cell sorting (MACS) technology and their phenotype and characteristics assessed over time in culture. Green fluorescent protein (GFP)-labelled PICs were used to determine multipotency in vivo in a tumour formation assay. Isolated PICs expressed markers of pluripotency (Oct3/4, Sox2, and Nanog), were clonogenic, and self-renewing with >60 population doublings, and a population doubling time of 15.8 ± 2.9 h. PICs demonstrated an ability to generate both striated and smooth muscle, whilst also displaying the potential to differentiate into cell types of the three germ layers both in vitro and in vivo. Moreover, PICs did not form tumours in vivo. These findings open new avenues for a variety of solid tissue engineering and regeneration approaches, utilising a single multipotent stem cell type isolated from an easily accessible source such as skeletal muscle.
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Transcatheter Aortic Valve Implantation: Experience with the CoreValve Device.
Asgar, Anita W; Bonan, Raoul
2012-01-01
The field of transcatheter aortic valve implantation has been rapidly evolving. The Medtronic CoreValve first emerged on the landscape in 2004 with initial first human studies, and it is currently being studied in the Pivotal US trial. This article details the current experience with the self-expanding aortic valve with a focus on clinical results and ongoing challenges. Copyright © 2012 Elsevier Inc. All rights reserved.
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Doody, Thomas J.
1978-08-22
A multiple-port valve assembly is designed to direct flow from a primary conduit into any one of a plurality of secondary conduits as well as to direct a reverse flow. The valve includes two mating hemispherical sockets that rotatably receive a spherical valve plug. The valve plug is attached to the primary conduit and includes diverging passageways from that conduit to a plurality of ports. Each of the ports is alignable wih one or more of a plurality of secondary conduits fitted into one of the hemispherical sockets. The other hemispherical socket includes a slot for the primary conduit such that the conduit's motion along that slot with rotation of the spherical plug about various axes will position the valve-plug ports in respect to the secondary conduits.
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Usnick, George B.; Ward, Gene T.; Blair, Henry O.; Roberts, James W.; Warner, Terry N.
1979-01-01
This invention is a novel valve of the slidable-gate type. The valve is designed especially for long-term use with highly abrasive slurries. The sealing surfaces of the gate are shielded by the valve seats when the valve is fully open or closed, and the gate-to-seat clearance is swept with an inflowing purge gas while the gate is in transit. A preferred form of the valve includes an annular valve body containing an annular seat assembly defining a flow channel. The seat assembly comprises a first seat ring which is slidably and sealably mounted in the body, and a second seat ring which is tightly fitted in the body. These rings cooperatively define an annular gap which, together with passages in the valve body, forms a guideway extending normal to the channel. A plate-type gate is mounted for reciprocation in the guideway between positions where a portion of the plate closes the channel and where a circular aperture in the gate is in register with the channel. The valve casing includes opposed chambers which extend outwardly from the body along the axis of the guideway to accommodate the end portions of the gate. The chambers are sealed from atmosphere; when the gate is in transit, purge gas is admitted to the chambers and flows inwardly through the gate-to-seat-ring, clearance, minimizing buildup of process solids therein. A shaft reciprocated by an external actuator extends into one of the sealed chambers through a shaft seal and is coupled to an end of the gate. Means are provided for adjusting the clearance between the first seat ring and the gate while the valve is in service.
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Solenoid Valve With Self-Compensation
NASA Technical Reports Server (NTRS)
Woeller, Fritz H.; Matsumoto, Yutaka
1987-01-01
New solenoid-operated miniature shutoff valve provides self-compensation of differential pressure forces that cause jamming or insufficient valve closure as in single-seal valves. Dual-seal valve is bidirectional. Valve simultaneously seals both inlet and outlet tubes by pressing single disk of silicone rubber against ends of both.
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CT in the diagnosis of interstitial lung disease
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bergin, C.J.; Mueller, N.L.
1985-09-01
The computed tomographic (CT) appearance of interstitial lung disease was assessed in 23 patients with known interstitial disease. These included seven patients with fibrosing alveolitis, six with silicosis, two with hypersensitivity pneumonitis, three with lymphangitic spread of tumor, two with sarcoidosis, one with rheumatoid lung disease, and two with neurofibromatosis. The CT appearance of the interstitial changes in the different disease entities was assessed. Nodules were a prominent CT feature in silicosis, sarcoidosis, and lymphangitic spread of malignancy. Distribution of nodules and associated interlobular septal thickening provided further distinguishing features in these diseases. Reticular densities were the predominant CT changemore » in fibrosing alveolitis, rheumatoid lung disease, and extrinsic allergic alveolitis. CT can be useful in the investigation of selected instances of interstitial pulmonary disease.« less
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Retinoic acid stimulates interstitial collagenase messenger ribonucleic acid in osteosarcoma cells
NASA Technical Reports Server (NTRS)
Connolly, T. J.; Clohisy, J. C.; Shilt, J. S.; Bergman, K. D.; Partridge, N. C.; Quinn, C. O.
1994-01-01
The rat osteoblastic osteosarcoma cell line UMR 106-01 secretes interstitial collagenase in response to retinoic acid (RA). The present study demonstrates by Northern blot analysis that RA causes an increase in collagenase messenger RNA (mRNA) at 6 h, which is maximal at 24 h (20.5 times basal) and declines toward basal level by 72 h. This stimulation is dose dependent, with a maximal response at 5 x 10(-7) M RA. Nuclear run-on assays show a greater than 20-fold increase in the rate of collagenase mRNA transcription between 12-24 h after RA treatment. Cycloheximide blocks RA stimulation of collagenase mRNA, demonstrating the need for de novo protein synthesis. RA not only causes an increase in collagenase secretion, but is known to decrease collagen synthesis in UMR 106-01 cells. In this study, the increase in collagenase mRNA is accompanied by a concomitant decrease in the level of alpha 1(I) procollagen mRNA, which is maximal at 24 h (70% decrease), with a return to near-control levels by 72 h. Nuclear run-on assays demonstrated that the decrease in alpha 1 (I) procollagen expression does not have a statistically significant transcriptional component. RA did not statistically decrease the stability of alpha 1 (I) procollagen mRNA (calculated t1/2 = 8.06 +/- 0.30 and 9.01 +/- 0.62 h in the presence and absence of RA, respectively). However, transcription and stability together probably contribute to the major decrease in stable alpha 1 (I) procollagen mRNA observed. Cycloheximide treatment inhibits basal level alpha 1 (I) procollagen mRNA accumulation, demonstrating the need for on-going protein synthesis to maintain basal expression of this gene.
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Study of multiple cycles valves
NASA Technical Reports Server (NTRS)
Wichmann, H.
1973-01-01
A discussion is presented regarding valves which can be cycled repeatedly and are available from industry for application in the inlet system for the Pioneer Venus Probe mass spectrometer. Both solenoid type and latching type valves are considered. The study is divided into two principal areas: (1) preparation of a valve specification reflecting the requirements of the inlet system cyclic valves for the Pioneer Venus Probe mass spectrometer and the submittal of this specification to potential valve suppliers for their response and proposal; (2) preparation of a design layout of an optimum cyclic valve meeting all of the valve specification requirements.
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Intraluminal fibrosis in interstitial lung disorders.
Basset, F.; Ferrans, V. J.; Soler, P.; Takemura, T.; Fukuda, Y.; Crystal, R. G.
1986-01-01
The histopathologic and ultrastructural features of intraluminal organizing and fibrotic changes were studied in open lung biopsies and autopsy specimens from 373 patients with interstitial lung disorders, including hypersensitivity pneumonitis (n = 44), idiopathic pulmonary fibrosis (n = 92), collagen-vascular diseases (n = 20), chronic eosinophilic pneumonia (n = 10), pulmonary histiocytosis X (n-90), pulmonary sarcoidosis (n = 62), pneumoconioses (n = 25), Legionnaire's disease (n = 5), drug- and toxin-induced pneumonitis (n = 4), radiation-induced pneumonitis (n = 2), lymphangioleiomyomatosis (n = 11), and chronic organizing pneumonia of unknown cause (n = 8). Three patterns of intraluminal organization and fibrosis were recognized: 1) intraluminal buds, which partially filled the alveoli, alveolar ducts and/or distal bronchioles; 2) obliterative changes, in which loose connective tissue masses obliterated the lumens of alveoli, alveolar ducts or distal bronchioles, and 3) mural incorporation of previously intraluminal connective tissue masses, which fused with alveolar, alveolar ductal, or bronchiolar structures and frequently became reepithelialized. All three patterns had common morphologic features, suggesting that, regardless of their severity, they resulted from a common pathogenetic mechanism, ie, the migration of activated connective tissue cells, through defects in the epithelial lining and its basement membrane, from the interstitial into the intraluminal compartment. Intraluminal buds were observed most frequently in hypersensitivity pneumonitis, chronic eosinophilic pneumonia, and organizing pneumonia of unknown cause. Mural incorporation and, to a lesser extent, obliterative changes were observed in most interstitial disorders and were very prominent in idiopathic pulmonary fibrosis. Mural incorporation and obliterative changes play an important role in pulmonary remodeling, especially when several adjacent alveoli and/or other air spaces are
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NASA Technical Reports Server (NTRS)
Morris, Brian G.; Bozeman, Richard J., Jr.
1994-01-01
Poppet in proposed check valve restored to closed condition by magnetic attraction instead of spring force. Oscillations suppressed, with consequent reduction of wear. Stationary magnetic disk mounted just upstream of poppet, also containing magnet. Valve body nonmagnetic. Forward pressure or flow would push poppet away from stationary magnetic disk so fluid flows easily around poppet. Stop in valve body prevents poppet from being swept away. When flow stopped or started to reverse, magnetic attraction draws poppet back to disk. Poppet then engages floating O-ring, thereby closing valve and preventing reverse flow. Floating O-ring facilitates sealing at low loads.
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Wilson, Carole L; Gough, Peter J; Chang, Cindy A; Chan, Christina K; Frey, Jeremy M; Liu, Yonggang; Braun, Kathleen R; Chin, Michael T; Wight, Thomas N; Raines, Elaine W
2013-01-01
Global inactivation of the metalloproteinase ADAM17 during mouse development results in perinatal lethality and abnormalities of the heart, including late embryonic cardiomegaly and thickened semilunar and atrioventricular valves. These defects have been attributed in part to a lack of ADAM17-mediated processing of HB-EGF, as absence of soluble HB-EGF results in similar phenotypes. Because valvular mesenchymal cells are largely derived from cardiac endothelial cells, we generated mice with a floxed Adam17 allele and crossed these animals with Tie2-Cre transgenics to focus on the role of endothelial ADAM17 in valvulogenesis. We find that although hearts from late-stage embryos with ablation of endothelial ADAM17 appear normal, an increase in valve size and cell number is evident, but only in the semilunar cusps. Unlike Hbegf(-/-) valves, ADAM17-null semilunar valves do not differ from controls in acute cell proliferation at embryonic day 14.5 (E14.5), suggesting compensatory processing of HB-EGF. However, levels of the proteoglycan versican are significantly reduced in mutant hearts early in valve remodeling (E12.5). After birth, aortic valve cusps from mutants are not only hyperplastic but also show expansion of the glycosaminoglycan-rich component, with the majority of adults exhibiting aberrant compartmentalization of versican and increased deposition of collagen. The inability of mutant outflow valve precursors to transition into fully mature cusps is associated with decreased postnatal viability, progressive cardiomegaly, and systolic dysfunction. Together, our data indicate that ADAM17 is required in valvular endothelial cells for regulating cell content as well as extracellular matrix composition and organization in semilunar valve remodeling and homeostasis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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Buch, W S; Pipkin, R D; Hancock, W D; Fogarty, T J
1975-11-01
From March 1971 through April 1975, one hundred twenty patients underwent mitral valve replacement with a Hancock "stabilized glutaraldehyde process" porcine aortic xenograft. A simultaneous canine experimental series was also carried out. In the clinical series, the early mortality was 8.3%. Actuarial analyses of all patients predicts survival at two years of 81.0% and at four years of 70.0%. The predicted survival for patients without coronary disease or prior prosthetic valve replacement is 87.5% at two years and 77.5% at four years. There were four thromboembolic episodes, a rate of 2.4% per patient-year. None were fatal. No valve failure were noted. Histologic examination and shrink temperature analysis of recovered valves show excellent tissue preservation at 40 months. The data indicate that the Hancock valve is durable, enjoys a low incidence of thromboembolism, and may be the valve of choice for mitral valve replacement.
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Anterior mitral valve aneurysm: a rare sequelae of aortic valve endocarditis.
Janardhanan, Rajesh; Kamal, Muhammad Umar; Riaz, Irbaz Bin; Smith, M Cristy
2016-03-01
SummaryIn intravenous drug abusers, infective endocarditis usually involves right-sided valves, with Staphylococcus aureus being the most common etiologic agent. We present a patient who is an intravenous drug abuser with left-sided (aortic valve) endocarditis caused by Enterococcus faecalis who subsequently developed an anterior mitral valve aneurysm, which is an exceedingly rare complication. A systematic literature search was conducted which identified only five reported cases in the literature of mitral valve aneurysmal rupture in the setting of E. faecalis endocarditis. Real-time 3D-transesophageal echocardiography was critical in making an accurate diagnosis leading to timely intervention. Early recognition of a mitral valve aneurysm (MVA) is important because it may rupture and produce catastrophic mitral regurgitation (MR) in an already seriously ill patient requiring emergency surgery, or it may be overlooked at the time of aortic valve replacement (AVR).Real-time 3D-transesophageal echocardiography (RT-3DTEE) is much more advanced and accurate than transthoracic echocardiography for the diagnosis and management of MVA. © 2016 The authors.
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Transcatheter Mitral Valve Replacement for Native and Failed Bioprosthetic Mitral Valves
Sarkar, Kunal; Reardon, Michael J.; Little, Stephen H.; Barker, Colin M.; Kleiman, Neal S.
2017-01-01
Transcatheter mitral valve replacement (TMVR) is a novel approach for treatment of severe mitral regurgitation. A number of TMVR devices are currently undergoing feasibility trials using both transseptal and transapical routes for device delivery. Overall experience worldwide is limited to fewer than 200 cases. At present, the 30-day mortality exceeds 30% and is attributable to both patient- and device-related factors. TMVR has been successfully used to treat patients with degenerative mitral stenosis (DMS) as well as failed mitral bioprosthesis and mitral repair using transcatheter mitral valve-in-valve (TMViV)/valve-in-ring (ViR) repair. These patients are currently treated with devices designed for transcatheter aortic valve replacement. Multicenter registries have been initiated to collect outcomes data on patients currently undergoing TMViV/ViR and TMVR for DMS and have confirmed the feasibility of TMVR in these patients. However, the high periprocedural and 30-day event rates underscore the need for further improvements in device design and multicenter randomized studies to delineate the role of these technologies in patients with mitral valve disease. PMID:29743999
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Fast acting multiple element valve
Yang, Jefferson Y. S.; Wada, James M.
1991-01-01
A plurality of slide valve elements having plural axial-spaced annular parts and an internal slide are inserted into a bulkhead in a fluid conduit from a downstream side of the bulkhead, locked in place by a bayonet coupling and set screw, and project through the bulkhead into the upstream conduit. Pneumatic lines connecting the slide valve element actuator to pilot valves are brought out the throat of the valve element to the downstream side. Pilot valves are radially spaced around the exterior of the valve to permit the pneumatic lines to be made identical, thereby to minimize adverse timing tolerances in operation due to pressure variations. Ring manifolds surround the valve adjacent respective pilot valve arrangements to further reduce adverse timing tolerances due to pressure variations, the manifolds being directly connected to the respective pilot valves. Position sensors are provided the valve element slides to signal the precise time at which a slide reaches or passes through a particular point in its stroke to initiate a calibrated timing function.
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NASA Technical Reports Server (NTRS)
Farner, Bruce
2013-01-01
A moveable valve for controlling flow of a pressurized working fluid was designed. This valve consists of a hollow, moveable floating piston pressed against a stationary solid seat, and can use the working fluid to seal the valve. This open/closed, novel valve is able to use metal-to-metal seats, without requiring seat sliding action; therefore there are no associated damaging effects. During use, existing standard high-pressure ball valve seats tend to become damaged during rotation of the ball. Additionally, forces acting on the ball and stem create large amounts of friction. The combination of these effects can lead to system failure. In an attempt to reduce damaging effects and seat failures, soft seats in the ball valve have been eliminated; however, the sliding action of the ball across the highly loaded seat still tends to scratch the seat, causing failure. Also, in order to operate, ball valves require the use of large actuators. Positioning the metal-to-metal seats requires more loading, which tends to increase the size of the required actuator, and can also lead to other failures in other areas such as the stem and bearing mechanisms, thus increasing cost and maintenance. This novel non-sliding seat surface valve allows metal-to-metal seats without the damaging effects that can lead to failure, and enables large seating forces without damaging the valve. Additionally, this valve design, even when used with large, high-pressure applications, does not require large conventional valve actuators and the valve stem itself is eliminated. Actuation is achieved with the use of a small, simple solenoid valve. This design also eliminates the need for many seals used with existing ball valve and globe valve designs, which commonly cause failure, too. This, coupled with the elimination of the valve stem and conventional valve actuator, improves valve reliability and seat life. Other mechanical liftoff seats have been designed; however, they have only resulted in
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Fast-acting valve and uses thereof
Meyer, J.A.
1980-05-16
A very fast acting valve capable of producing a very well-defined plug of gas suitable for filling a theta pinch vacuum vessel is given. The valve requires no springs, instead being stopped mainly by a nonlinear force. Thus, the valve is not subject to bouncing; and the ratio of the size of the valve housing to the size of the valve stem is smaller than it would be if springs were needed to stop the valve stem. Furthermore, the valve can be used for thousands of valve firings with no apparent valve damage.
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Fast-acting valve and uses thereof
Meyer, James A.
1982-01-01
A very fast acting valve capable of producing a very well-defined plug of gas suitable for filling a theta pinch vacuum vessel is given. The valve requires no springs, instead being stopped mainly by a nonlinear force. Thus, the valve is not subject to bouncing; and the ratio of the size of the valve housing to the size of the valve stem is smaller than it would be if springs were needed to stop the valve stem. Furthermore, the valve can be used for thousands of valve firings with no apparent valve damage.
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Evolution of anisotropy in bcc Fe distorted by interstitial boron
NASA Astrophysics Data System (ADS)
Gölden, Dominik; Zhang, Hongbin; Radulov, Iliya; Dirba, Imants; Komissinskiy, Philipp; Hildebrandt, Erwin; Alff, Lambert
2018-01-01
The evolution of magnetic anisotropy in bcc Fe as a function of interstitial boron atoms was investigated in thin films grown by molecular beam epitaxy. The thermodynamic nonequilibrium conditions during film growth allowed one to stabilize an interstitial boron content of about 14 at .% accompanied by lattice tetragonalization. The c /a ratio scaled linearly with the boron content up to a maximum value of 1.05 at 300 °C substrate growth temperature, with a room-temperature magnetization of. In contrast to nitrogen interstitials, the magnetic easy axis remained in-plane with an anisotropy of approximately -5.1 ×106erg /cm3 . Density functional theory calculations using the measured lattice parameters confirm this value and show that boron local ordering indeed favors in-plane magnetization. Given the increased temperature stability of boron interstitials as compared to nitrogen interstitials, this study will help to find possible ways to manipulate boron interstitials into a more favorable local order.
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Tao, Ende; Wan, Li; Wang, WenJun; Luo, YunLong; Zeng, JinFu; Wu, Xia
2017-01-01
Surgery remains the primary form of treatment for infective endocarditis (IE). However, it is not clear what type of prosthetic valve provides a better prognosis. We conducted a meta-analysis to compare the prognosis of infective endocarditis treated with biological valves to cases treated with mechanical valves. Pubmed, Embase and Cochrane databases were searched from January 1960 to November 2016.Randomized controlled trials, retrospective cohorts and prospective studies comparing outcomes between biological valve and mechanical valve management for infective endocarditis were analyzed. The Newcastle-Ottawa Scale(NOS) was used to evaluate the quality of the literature and extracted data, and Stata 12.0 software was used for the meta-analysis. A total of 11 publications were included; 10,754 cases were selected, involving 6776 cases of biological valves and 3,978 cases of mechanical valves. The all-cause mortality risk of the biological valve group was higher than that of the mechanical valve group (HR = 1.22, 95% CI 1.03 to 1.44, P = 0.023), as was early mortality (RR = 1.21, 95% CI 1.02 to 1.43, P = 0.033). The recurrence of endocarditis (HR = 1.75, 95% CI 1.26 to 2.42, P = 0.001), as well as the risk of reoperation (HR = 1.79, 95% CI 1.15 to 2.80, P = 0.010) were more likely to occur in the biological valve group. The incidence of postoperative embolism was less in the biological valve group than in the mechanical valve group, but this difference was not statistically significant (RR = 0.90, 95% CI 0.76 to 1.07, P = 0.245). For patients with prosthetic valve endocarditis (PVE), there was no significant difference in survival rates between the biological valve group and the mechanical valve group (HR = 0.91, 95% CI 0.68 to 1.21, P = 0.520). The results of our meta-analysis suggest that mechanical valves can provide a significantly better prognosis in patients with infective endocarditis. There were significant differences in the clinical features of patients
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Tao, Ende; Wan, Li; Wang, WenJun; Luo, YunLong; Zeng, JinFu; Wu, Xia
2017-01-01
Objective Surgery remains the primary form of treatment for infective endocarditis (IE). However, it is not clear what type of prosthetic valve provides a better prognosis. We conducted a meta-analysis to compare the prognosis of infective endocarditis treated with biological valves to cases treated with mechanical valves. Methods Pubmed, Embase and Cochrane databases were searched from January 1960 to November 2016.Randomized controlled trials, retrospective cohorts and prospective studies comparing outcomes between biological valve and mechanical valve management for infective endocarditis were analyzed. The Newcastle-Ottawa Scale(NOS) was used to evaluate the quality of the literature and extracted data, and Stata 12.0 software was used for the meta-analysis. Results A total of 11 publications were included; 10,754 cases were selected, involving 6776 cases of biological valves and 3,978 cases of mechanical valves. The all-cause mortality risk of the biological valve group was higher than that of the mechanical valve group (HR = 1.22, 95% CI 1.03 to 1.44, P = 0.023), as was early mortality (RR = 1.21, 95% CI 1.02 to 1.43, P = 0.033). The recurrence of endocarditis (HR = 1.75, 95% CI 1.26 to 2.42, P = 0.001), as well as the risk of reoperation (HR = 1.79, 95% CI 1.15 to 2.80, P = 0.010) were more likely to occur in the biological valve group. The incidence of postoperative embolism was less in the biological valve group than in the mechanical valve group, but this difference was not statistically significant (RR = 0.90, 95% CI 0.76 to 1.07, P = 0.245). For patients with prosthetic valve endocarditis (PVE), there was no significant difference in survival rates between the biological valve group and the mechanical valve group (HR = 0.91, 95% CI 0.68 to 1.21, P = 0.520). Conclusion The results of our meta-analysis suggest that mechanical valves can provide a significantly better prognosis in patients with infective endocarditis. There were significant differences in
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Heart valve surgery - series (image)
... heart valves are either natural (biologic) or artificial (mechanical). Natural valves are from human donors (cadavers), modified ... artificial valves will require anticoagulation. The advantage of mechanical valves is that they last longer-thus, the ...
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... called anticoagulants) for the rest of their lives. Biological valves are made from animal tissue (called a ... for valve replacement (called an autograft). Patients with biological valves usually do not need to take blood- ...
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Fluid mechanics of heart valves.
Yoganathan, Ajit P; He, Zhaoming; Casey Jones, S
2004-01-01
Valvular heart disease is a life-threatening disease that afflicts millions of people worldwide and leads to approximately 250,000 valve repairs and/or replacements each year. Malfunction of a native valve impairs its efficient fluid mechanic/hemodynamic performance. Artificial heart valves have been used since 1960 to replace diseased native valves and have saved millions of lives. Unfortunately, despite four decades of use, these devices are less than ideal and lead to many complications. Many of these complications/problems are directly related to the fluid mechanics associated with the various mechanical and bioprosthetic valve designs. This review focuses on the state-of-the-art experimental and computational fluid mechanics of native and prosthetic heart valves in current clinical use. The fluid dynamic performance characteristics of caged-ball, tilting-disc, bileaflet mechanical valves and porcine and pericardial stented and nonstented bioprostheic valves are reviewed. Other issues related to heart valve performance, such as biomaterials, solid mechanics, tissue mechanics, and durability, are not addressed in this review.
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Intelligent Flow Control Valve
NASA Technical Reports Server (NTRS)
Kelley, Anthony R (Inventor)
2015-01-01
The present invention is an intelligent flow control valve which may be inserted into the flow coming out of a pipe and activated to provide a method to stop, measure, and meter flow coming from the open or possibly broken pipe. The intelligent flow control valve may be used to stop the flow while repairs are made. Once repairs have been made, the valve may be removed or used as a control valve to meter the amount of flow from inside the pipe. With the addition of instrumentation, the valve may also be used as a variable area flow meter and flow controller programmed based upon flowing conditions. With robotic additions, the valve may be configured to crawl into a desired pipe location, anchor itself, and activate flow control or metering remotely.
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[Effect of CsA bleomycin-induced interstitial pulmonary disease in mice].
Ren, Ying; Yang, Hui; Zhu, Ping; Fan, Chun-mei; Wang, Yan-hong; Li, Jia; Liu, Hui
2012-03-01
To observe the therapeutic effect of cyclosporine A (CsA) on bleomycin (BLM) induced pulmonary fibrosis and to investigate its mechanism. One hundred and twenty C57BL/6 female mice were divided randomly into five groups: BLM model group, control saline group, CsA30 mg treatment group, CsA50 mg treatment group and control treatment group. Treatment groups and model groups were administrated BLM intratracheally to induce interstitial pulmonary disease model, with control saline group administrated with equal volume of normal saline instead. Mice in treatment groups were intraperitoneal injected with CsA, while control treatment group were injected with equal volume of normal saline instead. On the 4th, 7th and 14th day after administration, 8 mice of each group were sacrificed, and the peripheral blood was obtained to count total leucocytes with counting chamber and quantify CD4(+); T cells, CD14(+); monocytes and CD19(+); B cells by flow cytometry (FCM). Bronchoalveolar levage fluid was harvested for cell counting and Giemsa staining. Lung tissues were harvested for immunohistochemical staining and pathological examination. The quantity of total leucocyte was higher in BLM model group than those in control saline group.The proportion of CD14(+); T cells and CD19(+);B cells in BLM model group were increased markedly than those in control saline group on the 4th, 7th and 14th day post BLM. With CsA treatment, The proportion of CD14(+); T cells was lower than BLM model group at the same time point, especially on the 4th day. The proportion of CD19(+); B cells were significantly lower than those of BLM model group at the same time point(7 d, 14 d). The total and classification of cells of BLM model group were increased markedly than those in control saline group, and decreased obviously in the treatment groups at the same time point. Examination of lung tissues: With the prolonged time of BLM administration, it showed wider alveolar septum, more collagen deposition, as
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How to Make a Heart Valve: From Embryonic Development to Bioengineering of Living Valve Substitutes
MacGrogan, Donal; Luxán, Guillermo; Driessen-Mol, Anita; Bouten, Carlijn; Baaijens, Frank; de la Pompa, José Luis
2014-01-01
Cardiac valve disease is a significant cause of ill health and death worldwide, and valve replacement remains one of the most common cardiac interventions in high-income economies. Despite major advances in surgical treatment, long-term therapy remains inadequate because none of the current valve substitutes have the potential for remodeling, regeneration, and growth of native structures. Valve development is coordinated by a complex interplay of signaling pathways and environmental cues that cause disease when perturbed. Cardiac valves develop from endocardial cushions that become populated by valve precursor mesenchyme formed by an epithelial–mesenchymal transition (EMT). The mesenchymal precursors, subsequently, undergo directed growth, characterized by cellular compartmentalization and layering of a structured extracellular matrix (ECM). Knowledge gained from research into the development of cardiac valves is driving exploration into valve biomechanics and tissue engineering directed at creating novel valve substitutes endowed with native form and function. PMID:25368013
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Winston, John H.; Chen, Jinghong; Shi, Xuan-Zheng; Sarna, Sushil K.
2014-01-01
The initial hypothesis suggested that the interstitial cells of Cajal (ICC) played an essential role in mediating enteric neuronal input to smooth muscle cells. Much information for this hypothesis came from studies in W/Wv mice lacking ICC. However, mast cells, which play critical roles in regulating inflammation in their microenvironment, are also absent in W/Wv mice. We tested the hypothesis that the depletion of mast cells in W/Wv mice generates inflammation in fundus muscularis externa (ME) that impairs smooth muscle reactivity to Ach, independent of the depletion of ICC. We performed experiments on the fundus ME from wild type (WT) and W/Wv mice before and after reconstitution of mast cells by bone marrow transplant. We found that mast cell deficiency in W/Wv mice significantly increased COX-2 and iNOS expression and decreased smooth muscle reactivity to Ach. Mast cell reconstitution or concurrent blockade of COX-2 and iNOS restored smooth muscle contractility without affecting the suppression of c-kit in W/Wv mice. The expression of nNOS and ChAT were suppressed in W/Wv mice; mast cell reconstitution did not restore them. We conclude that innate inflammation induced by mast cell deficiency in W/Wv mice impairs smooth muscle contractility independent of ICC deficiency. The impairment of smooth muscle contractility and the suppression of the enzymes regulating the synthesis of Ach and NO in W/Wv mice need to be considered in evaluating the role of ICC in regulating smooth muscle and enteric neuronal function in W/Wv mice. PMID:24550836
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Sachithanandan, Anand; Nanjaiah, Prakash; Wright, Christine J; Rooney, Stephen J
2008-01-01
Homozygous sickle cell disease (SCD) presents a multitude of challenges in patients undergoing cardiac surgery with cardiopulmonary bypass. Special consideration must be made in such patients and routine practice modified to prevent hypoxia, hypothermia, acidaemia and low-flow states which may potentially trigger a fatal sickling crisis perioperatively. We discuss several perioperative management strategies including a preoperative exchange transfusion, high flow normothermic bypass and warm blood cardioplegia that was utilized in a woman with homozygous SCD who underwent a successful double valve procedure.
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Time scales of transient enhanced diffusion: Free and clustered interstitials
NASA Astrophysics Data System (ADS)
Cowern, N. E. B.; Huizing, H. G. A.; Stolk, P. A.; Visser, C. C. G.; de Kruif, R. C. M.; Kyllesbech Larsen, K.; Privitera, V.; Nanver, L. K.; Crans, W.
1996-12-01
Transient enhanced diffusion (TED) and electrical activation after nonamorphizing Si implantations into lightly B-doped Si multilayers shows two distinct timescales, each related to a different class of interstitial defect. At 700°C, ultrafast TED occurs within the first 15 s with a B diffusivity enhancement of > 2 × 10 5. Immobile clustered B is present at low concentration levels after the ultrafast transient and persists for an extended period (˜ 10 2-10 3 s). The later phase of TED exhibits a near-constant diffusivity enhancement of ≈ 1 × 10 4, consistent with interstitial injection controlled by dissolving {113} interstitial clusters. The relative contributions of the ultrafast and regular TED regimes to the final diffusive broadening of the B profile depends on the proportion of interstitials that escape capture by {113} clusters growing within the implant damage region upon annealing. Our results explain the ultrafast TED recently observed after medium-dose B implantation. In that case there are enough B atoms to trap a large proportion of interstitials in SiB clusters, and the remaining interstitials contribute to TED without passing through an intermediate {113} defect stage. The data on the ultrafast TED pulse allows us to extract lower limits for the diffusivities of the Si interstitial ( DI > 2 × 10 -10 cm 2s -1) and the B interstitial(cy) defect ( DBi > 2 × 10 -13 cm 2s -1) at 700°C.
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Hukkanen, V; Haarala, M; Nurmi, M; Klemi, P; Kiilholma, P
1996-01-01
Microbes may be involved in the pathogenesis of interstitial cystitis (IC). Adenoviruses and BK virus (BKV) can infect epithelial cells in urinary bladder and they are causative agents for hemorrhagic cystitis. We therefore studied the presence of adenovirus and BKV genomes in urinary bladder tissue specimens of patients with IC using polymerase chain reaction (PCR) and in situ hybridization (ISH). Controls were specimens from cases with transitional cell carcinoma of the bladder. Nucleic acids were extracted from paraffin sections of the bladder tissue for PCR. Primers detecting all adenovirus types were used. In situ hybridization was carried out for the paraffin sections using digoxigenin-labeled DNA probes for adenovirus and BKV. The adenovirus DNA PCR was able to detect one to two infected cells/specimen. All the seven IC cases studied and six controls were negative for adenovirus DNA by PCR and ISH. The ISH test for BKV genomes was also considered negative in IC cases and controls. The specimens which were negative in PCR tests yielded a signal with beta-globin primers, thus being amplifiable. We conclude that adenovirus and BKV do not play a major pathogenetic role in interstitial cystitis.
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Locking apparatus for gate valves
Fabyan, J.; Williams, C.W.
A locking apparatus for fluid operated valves having a piston connected to the valve actuator which moves in response to applied pressure within a cylinder housing having a cylinder head, a catch block is secured to the piston, and the cylinder head incorporates a catch pin. Pressure applied to the cylinder to open the valve moves the piston adjacent to the cylinder head where the catch pin automatically engages the catch block preventing further movement of the piston or premature closure of the valve. Application of pressure to the cylinder to close the valve, retracts the catch pin, allowing the valve to close. Included are one or more selector valves, for selecting pressure application to other apparatus depending on the gate valve position, open or closed, protecting such apparatus from damage due to premature closing caused by pressure loss or operational error.
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NASA Astrophysics Data System (ADS)
Hai, X.; Porcher, F.; Mayer, C.; Miraglia, S.
2018-02-01
Steady state and in-situ neutron powder diffraction on selected compositions of the magneto-caloric (La,Ce)(Fe,Si)13CxHy compounds has been used to locate the sites accommodated by the interstitial species and to reveal the structural modifications (breathing) that occur upon metal substitution and/or interstitial insertion. The latter type of measurement in which the sequential filling of interstitial sites is followed allows one to extract some useful hydrogenation kinetics data. This structural investigation has allowed to precise the deformations undergone by the complex metallic alloys La(Fe,Si)13 when subjected to light interstitial insertion or rare earth substitution at the cation site of the NaZn13-structure type. We attempt to correlate hydrogenation kinetics variations (depression or enhancement of the hydrogen absorption rate) with a particular inhomogeneous cell variation (breathing) and bonding of the NaZn13 structure-type.
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Analysis of Dissolved Organic Nutrients in the Interstitial Water of Natural Biofilms.
Tsuchiya, Yuki; Eda, Shima; Kiriyama, Chiho; Asada, Tomoya; Morisaki, Hisao
2016-07-01
In biofilms, the matrix of extracellular polymeric substances (EPSs) retains water in the interstitial region of the EPS. This interstitial water is the ambient environment for microorganisms in the biofilms. The nutrient condition in the interstitial water may affect microbial activity in the biofilms. In the present study, we measured the concentrations of dissolved organic nutrients, i.e., saccharides and proteins, contained in the interstitial water of biofilms formed on the stones. We also analyzed the molecular weight distribution, chemical species, and availability to bacteria of some saccharides in the interstitial water. Colorimetric assays showed that the concentrations of saccharides and proteins in the biofilm interstitial water were significantly higher (ca. 750 times) than those in the surrounding lake waters (p < 0.05). Chromatographic analyses demonstrated that the saccharides in the interstitial waters were mainly of low molecular-weight saccharides such as glucose and maltose, while proteins in the interstitial water were high molecular-weight proteins (over 7000 Da). Bacterial growth and production of EPS occurred simultaneously with the decrease in the low molecular-weight saccharide concentrations when a small portion of biofilm suspension was inoculated to the collected interstitial water, suggesting that the dissolved saccharides in the interstitial water support bacterial growth and formation of biofilms.
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Long life valve design concepts
NASA Technical Reports Server (NTRS)
Jones, J. R.; Hall, A. H., Jr.
1975-01-01
Valve concept evaluation, final candidate selection, design, manufacture, and demonstration testing of a pneumatically actuated 10-inch hybrid poppet butterfly shutoff valve are presented. Conclusions and recommendations regarding those valve characteristics and features which would serve to guide in the formulation of future valve procurements are discussed. The pertinent design goals were temperature range of plus 200 to minus 423 F, valve inlet pressure 35 psia, actuation pressure 750 psia, main seal leakage 3 x 0.00001 sccs at 35 psia valve inlet pressure, and a storage and operating life of 10 years. The valve was designed to be compatible with RP-1, propane, LH2, LO2, He, and N2.
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Integrated external and interstitial radiation therapy for primary carcinoma of the vagina
DOE Office of Scientific and Technical Information (OSTI.GOV)
Puthawala, A.; Syed, A.M.; Nalick, R.
1983-09-01
Twenty-seven patients with the diagnosis of primary carcinoma of the vagina were treated by definitive radiotherapy. Twenty-three patients received a combination of external and interstitial iridium-192 implant irradiation and four patients received only interstitial irradiation. Twenty-one patients had squamous cell carcinoma and six had adenocarcinoma. All patients were staged according to the FIGO classification. More than 70% of patients had relatively advanced local disease and conventional intracavitary irradiation was unsuitable. Local tumor control was observed in 85% (23 of 27 patients), and 56% of the patients remain alive and free of disease for a median follow-up period of 50 monthsmore » to a maximum follow-up period of 84 months. Fifteen percent of the patients suffered from treatment-related complications.« less
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Wu, Min; Frieboes, Hermann B.; McDougall, Steven R.; Chaplain, Mark A.J.; Cristini, Vittorio; Lowengrub, John
2013-01-01
The flow of interstitial fluid and the associated interstitial fluid pressure (IFP) in solid tumors and surrounding host tissues have been identified as critical elements in cancer growth and vascularization. Both experimental and theoretical studies have shown that tumors may present elevated IFP, which can be a formidable physical barrier for delivery of cell nutrients and small molecules into the tumor. Elevated IFP may also exacerbate gradients of biochemical signals such as angiogenic factors released by tumors into the surrounding tissues. These studies have helped to understand both biochemical signaling and treatment prognosis. Building upon previous work, here we develop a vascular tumor growth model by coupling a continuous growth model with a discrete angiogenesis model. We include fluid/oxygen extravasation as well as a continuous lymphatic field, and study the micro-environmental fluid dynamics and their effect on tumor growth by accounting for blood flow, transcapillary fluid flux, interstitial fluid flow, and lymphatic drainage. We thus elucidate further the non-trivial relationship between the key elements contributing to the effects of interstitial pressure in solid tumors. In particular, we study the effect of IFP on oxygen extravasation and show that small blood/lymphatic vessel resistance and collapse may contribute to lower transcapillary fluid/oxygen flux, thus decreasing the rate of tumor growth. We also investigate the effect of tumor vascular pathologies, including elevated vascular and interstitial hydraulic conductivities inside the tumor as well as diminished osmotic pressure differences, on the fluid flow across the tumor capillary bed, the lymphatic drainage, and the IFP. Our results reveal that elevated interstitial hydraulic conductivity together with poor lymphatic function is the root cause of the development of plateau profiles of the IFP in the tumor, which have been observed in experiments, and contributes to a more uniform
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The Double-Orifice Valve Technique to Treat Tricuspid Valve Incompetence.
Hetzer, Roland; Javier, Mariano; Delmo Walter, Eva Maria
2016-01-01
A straightforward tricuspid valve (TV) repair technique was used to treat either moderate or severe functional (normal valve with dilated annulus) or for primary/organic (Ebstein's anomaly, leaflet retraction/tethering and chordal malposition/tethering, with annular dilatation) TV incompetence, and its long-term outcome assessed. A double-orifice valve technique was employed in 91 patients (mean age 52.6 ± 23.2 years; median age 56 years; range: 0.6-82 years) with severe tricuspid regurgitation. Among the patients, three had post-transplant iatrogenic chordal rupture, five had infective endocarditis, 11 had mitral valve insufficiency, 23 had Ebstein's anomaly, and 47 had isolated severe TV incompetence. The basic principle was to reduce the distance between the coapting leaflets, wherein the most mobile leaflet could coapt to the opposite leaflet, by creating two orifices, ensuring valve competence. The TV repair was performed through a median sternotomy or right anterior thoracotomy in the fifth intercostal space under cardiopulmonary bypass. The degree and extent of creating a double-valve orifice was determined by considering the minimal body surface area (BSA)-related acceptable TV diameter. Repair was accomplished by passing pledgeted mattress sutures from the middle of the true anterior annulus to a spot on the opposite septal annulus, located approximately two-thirds of the length of the septal annulus to avoid injury to the bundle of His. The annular apposition divides the TV into a larger anterior and a smaller posterior orifices, enabling valve closure, on both sides. In adults, the diameter of the anterior valve orifice should be 23-25 mm, and the posterior orifice 15-18 mm; thus, the total valve orifice area is 5-6 cm2. In children, the total valve orifice should be a standard deviation of 1.7 mm for a BSA of <1. 0m2, and 1.5 mm for a BSA of >1.0m2. During a mean follow up of 8.7 ± 1.34 years (median 10 years; range: 1.5-25.9 years) there have been no
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Compact valve actuation mechanism
NASA Technical Reports Server (NTRS)
Brogdon, James William (Inventor); Gill, David Keith (Inventor)
2000-01-01
A valve actuation device. The device may include a free floating valve bridge movably supported within a cavity in the engine housing. The bridge may be provided with a cavity and an orifice arrangement for pumping gases entrained with lubricating fluid toward the piston stems as the bridge reciprocates back and forth. The device may also include a rocker arm that has a U-shaped cross-sectional shape for receiving at least a portion of the valve bridge, valve stem valve spring and spring retainer therein. The rocker arm may be provided with lubrication passages for directing lubrication to the point wherein it is pivotally affixed to the engine housing.
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Patzelt, Johannes; Zhang, Yingying; Magunia, Harry; Ulrich, Miriam; Jorbenadze, Rezo; Droppa, Michal; Zhang, Wenzhong; Lausberg, Henning; Walker, Tobias; Rosenberger, Peter; Seizer, Peter; Gawaz, Meinrad; Langer, Harald F
2017-08-01
Improved mitral valve leaflet coaptation with consecutive reduction of mitral regurgitation (MR) is a central goal of percutaneous mitral valve repair (PMVR) with the MitraClip® system. As influences of PMVR on mitral valve geometry have been suggested before, we examined the effect of the procedure on mitral annular size in relation to procedural outcome. Geometry of the mitral valve annulus was evaluated in 183 patients undergoing PMVR using echocardiography before and after the procedure and at follow-up. Mitral valve annular anterior-posterior (ap) diameter decreased from 34.0 ± 4.3 to 31.3 ± 4.9 mm (P < 0.001), and medio-lateral (ml) diameter from 33.2 ± 4.8 to 32.4 ± 4.9 mm (P < 0.001). Accordingly, we observed an increase in MV leaflet coaptation after PMVR. The reduction of mitral valve ap diameter showed a significant inverse correlation with residual MR. Importantly, the reduction of mitral valve ap diameter persisted at follow-up (31.3 ± 4.9 mm post PMVR, 28.4 ± 5.3 mm at follow-up). This study demonstrates mechanical approximation of both mitral valve annulus edges with improved mitral valve annular coaptation by PMVR using the MitraClip® system, which correlates with residual MR in patients with MR. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.
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Valve technology: A compilation
NASA Technical Reports Server (NTRS)
1971-01-01
A technical compilation on the types, applications and modifications to certain valves is presented. Data cover the following: (1) valves that feature automatic response to stimuli (thermal, electrical, fluid pressure, etc.), (2) modified valves changed by redesign of components to increase initial design effectiveness or give the item versatility beyond its basic design capability, and (3) special purpose valves with limited application as presented, but lending themselves to other uses with minor changes.
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Lung volumes and emphysema in smokers with interstitial lung abnormalities.
Washko, George R; Hunninghake, Gary M; Fernandez, Isis E; Nishino, Mizuki; Okajima, Yuka; Yamashiro, Tsuneo; Ross, James C; Estépar, Raúl San José; Lynch, David A; Brehm, John M; Andriole, Katherine P; Diaz, Alejandro A; Khorasani, Ramin; D'Aco, Katherine; Sciurba, Frank C; Silverman, Edwin K; Hatabu, Hiroto; Rosas, Ivan O
2011-03-10
Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema. Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; P<0.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of -950 Hounsfield units (-3%; 95% CI, -4 to -2; P<0.001) and -910 Hounsfield units (-10%; 95% CI, -12 to -8; P<0.001). As compared with participants without interstitial lung abnormalities, those with abnormalities were more likely to have a restrictive lung deficit (total lung capacity <80% of the predicted value; odds ratio, 2.3; 95% CI, 1.4 to 3.7; P<0.001) and were less likely to meet the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation
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Morais, António; Moura, M Conceição Souto; Cruz, M Rosa; Gomes, Isabel
2004-01-01
Nonspecific interstitial pneumonitis (NSIP) initially described by Katzenstein and Fiorelli in 1994, seems to be a distinct clinicopathologic entity among idiopathic interstitial pneumonitis (IIP). Besides different histologic features from other IIP, NSIP is characterized by a better long-term outcome, associated with a better steroids responsiveness than idiopathic pulmonar fibrosis (IPF), where usually were included. Thus, differentiating NSIP from other IIP, namely IPF is very significant, since it has important therapeutic and prognostic implications. NSIP encloses different pathologies, namely those with inflammatory predominance (cellular subtype) or fibrous predominance (fibrosing subtype). NSIP is reviewed and discussed by the authors, after two clinical cases description.
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The Melody® valve and Ensemble® delivery system for transcatheter pulmonary valve replacement
McElhinney, Doff B; Hennesen, Jill T
2013-01-01
The Melody® transcatheter pulmonary valve (TPV) is a percutaneous valve system designed for the treatment of obstruction and/or regurgitation of prosthetic conduits placed between the right ventricle and pulmonary arteries in patients with congenital heart disease. In 2000, Melody TPV became the first transcatheter valve implanted in a human; in 2006 it became the first transcatheter valve commercially available anywhere in the world; and in 2010 it was launched as the first commercially available transcatheter valve in the United States. In this review, we present the clinical background against which the Melody valve was developed and implemented, introduce the rationale for and challenges of transcatheter valve technology for this population, outline the history and technical details of its development and use, and summarize currently available data concerning the performance of the device. PMID:23834411
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Chen, Zhe (Jay); Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder
2011-01-01
Previous studies have shown that the procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations depends strongly on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al. (Int. J. Radiat. Oncol. Biol. Phys. 41, 1069–1077–1998) was used to characterize the edema evolutions observed previously during clinical PIB for prostate cancer. The concept of biologically effective dose (BED), taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not taken into account appropriately, can increase the cell survival and decrease the probability of local control of PIB. The edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life for radioactive decay and decreasing energy of the photons energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days
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Garg, Aatish; Parashar, Akhil; Agarwal, Shikhar; Aksoy, Olcay; Hammadah, Muhammad; Poddar, Kanhaiya Lal; Puri, Rishi; Svensson, Lars G; Krishnaswamy, Amar; Tuzcu, E Murat; Kapadia, Samir R
2015-02-15
The SAPIEN-XT is a newer generation balloon-expandable valve created of cobalt chromium frame, as opposed to the stainless steel frame used in the older generation SAPIEN valve. We sought to determine if there was difference in acute recoil between the two valves. All patients who underwent transfemoral-transcatheter aortic valve replacement using the SAPIEN-XT valve at the Cleveland Clinic were included. Recoil was measured using biplane cine-angiographic image analysis of valve deployment. Acute recoil was defined as [(valve diameter at maximal balloon inflation) - (valve diameter after deflation)]/valve diameter at maximal balloon inflation (reported as percentage). Patients undergoing SAPIEN valve implantation were used as the comparison group. Among the 23 mm valves, the mean (standard deviation-SD) acute recoil was 2.77% (1.14) for the SAPIEN valve as compared to 3.75% (1.52) for the SAPIEN XT valve (P = 0.04). Among the 26 mm valves, the mean (SD) acute recoil was 2.85% (1.4) for the SAPIEN valve as compared to 4.32% (1.63) for the SAPIEN XT valve (P = 0.01). Multivariable linear regression analysis demonstrated significantly greater adjusted recoil in the SAPIEN XT valves as compared to the SAPIEN valves by 1.43% [(95% CI: 0.69-2.17), P < 0.001]. However, the residual peak gradient was less for SAPIEN XT compared to SAPIEN valves [18.86 mm Hg versus 23.53 mm Hg (P = 0.01)]. Additionally, no difference in paravalvular leak was noted between the two valve types (P = 0.78). The SAPIEN XT valves had significantly greater acute recoil after deployment compared to the SAPIEN valves. Implications of this difference in acute recoil on valve performance need to be investigated in future studies. © 2014 Wiley Periodicals, Inc.
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Peirce, E J; Breed, W G
1990-05-01
The organization of testicular interstitial tissue of the spinifex hopping mouse, Notomys alexis differs from that of other rodents. It comprises between 10.3% and 17.3% (average 15.0%) of the total testicular volume, and is variable in its organization both at different locations within the testis of the one animal and among different individuals. Abundant, closely packed Leydig cells are usually present; however, in some regions large, thick-walled blood vessels and extensive peritubular lymphatic spaces, often lacking an endothelium adjacent to the Leydig cells, are also prominent. The Leydig cells in contact with the large blood vessels and lymphatics, unlike those in regions where lymph is sparse, are not densely packed and sometimes contain numerous lipid droplets. Ultrastructure of Leydig cells is typical of steroid-producing cells; however, mitochondria are often extremely large, unusual in shape or bizarrely arranged in relation to one another. Also electron-dense bodies displaying a paracrystalline-like internal structure of parallel, electron-dense filaments arranged in a lattice pattern occur in the cytoplasm of many cells. The significance of these unusual ultrastructural features and the organization of the interstitial tissue remain to be determined conclusively, but may relate to steroid synthesis, secretion and uptake.
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Technical pitfalls and tips for the valve-in-valve procedure
2017-01-01
Transcatheter aortic valve implantation (TAVI) has emerged as a viable treatment modality for patients with severe aortic valve stenosis and multiple co-morbidities. More recent indications include the use of transcatheter heart valves (THV) to treat degenerated bioprosthetic surgical heart valves (SHV), which are failing due to stenosis or regurgitation. Valve-in-valve (VIV) procedures in the aortic position have been performed with a variety of THV devices, although the balloon-expandable SAPIEN valve platform (Edwards Lifesciences Ltd, Irvine, CA, USA) and self-expandable CoreValve platform (Medtronic Inc., MN, USA) have been used in majority of the patients. VIV treatment is appealing as it is less invasive than conventional surgery but optimal patient selection is vital to avoid complications such as malposition, residual high gradients and coronary obstruction. To minimize the risk of complications, thorough procedural planning is critical. The first step is identification of the degenerated SHV, including its model, size, fluoroscopic appearance. Although label size and stent internal diameter (ID) are provided by the manufacturer, it is important to note the true ID. The true ID is the ID of a SHV after the leaflets are mounted and helps determine the optimal size of THV. The second step is to determine the type and size of the THV. Although this is determined in the majority of the cases by user preference, in certain situations one THV may be more suitable than another. As the procedure is performed under fluoroscopy, the third step is to become familiarized with the fluoroscopic appearance of both the SHV and THV. This helps to determine the landmarks for optimal positioning, which in turn determines the gradients and fixation. The fourth step is to assess the risk of coronary obstruction. This is performed with either aortic root angiography or ECG-gated computerised tomography (CT). Finally, the route of approach must be carefully planned. Once these
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Valve stem and packing assembly
Wordin, John J.
1991-01-01
A valve stem and packing assembly is provided in which a rotatable valve stem includes a first tractrix surface for sliding contact with a stem packing and also includes a second tractrix surface for sliding contact with a bonnet. Force is applied by means of a spring, gland flange, and gland on the stem packing so the stem packing seals to the valve stem and bonnet. This configuration serves to create and maintain a reliable seal between the stem packing and the valve stem. The bonnet includes a second complementary tractrix surface for contacting the second sliding tractrix surface, the combination serving as a journal bearing for the entire valve stem and packing assembly. The journal bearing so configured is known as a Schiele's pivot. The Schiele's pivot also serves to maintain proper alignment of the valve stem with respect to the bonnet. Vertical wear between the surfaces of the Schiele's pivot is uniform at all points of contact between the second sliding tractrix surface and the second complementary tractrix surface of a bonnet. The valve stem is connected to a valve plug by means of a slip joint. The valve is opened and closed by rotating the valve stem. The slip joint compensates for wear on the Schiele's pivot and on the valve plug. A ledge is provided on the valve bonnet for the retaining nut to bear against. The ledge prevents overtightening of the retaining nut and the resulting excessive friction between stem and stem packing.
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Valve stem and packing assembly
Wordin, J.J.
1991-09-03
A valve stem and packing assembly is provided in which a rotatable valve stem includes a first tractrix surface for sliding contact with a stem packing and also includes a second tractrix surface for sliding contact with a bonnet. Force is applied by means of a spring, gland flange, and gland on the stem packing so the stem packing seals to the valve stem and bonnet. This configuration serves to create and maintain a reliable seal between the stem packing and the valve stem. The bonnet includes a second complementary tractrix surface for contacting the second sliding tractrix surface, the combination serving as a journal bearing for the entire valve stem and packing assembly. The journal bearing so configured is known as a Schiele's pivot. The Schiele's pivot also serves to maintain proper alignment of the valve stem with respect to the bonnet. Vertical wear between the surfaces of the Schiele's pivot is uniform at all points of contact between the second sliding tractrix surface and the second complementary tractrix surface of a bonnet. The valve stem is connected to a valve plug by means of a slip joint. The valve is opened and closed by rotating the valve stem. The slip joint compensates for wear on the Schiele's pivot and on the valve plug. A ledge is provided on the valve bonnet for the retaining nut to bear against. The ledge prevents over tightening of the retaining nut and the resulting excessive friction between stem and stem packing. 2 figures.
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NASA Technical Reports Server (NTRS)
Tucker, Curtis E., Jr.; Sherrit, Stewart
2011-01-01
For commercial, military, and aerospace applications, low-cost, small, reliable, and lightweight gas and liquid hermetically sealed valves with post initiation on/off capability are highly desirable for pressurized systems. Applications include remote fire suppression, single-use system-pressurization systems, spacecraft propellant systems, and in situ instruments. Current pyrotechnic- activated rupture disk hermetic valves were designed for physically larger systems and are heavy and integrate poorly with portable equipment, aircraft, and small spacecraft and instrument systems. Additionally, current pyrotechnically activated systems impart high g-force shock loads to surrounding components and structures, which increase the risk of damage and can require additional mitigation. The disclosed mechanism addresses the need for producing a hermetically sealed micro-isolation valve for low and high pressure for commercial, aerospace, and spacecraft applications. High-precision electrical discharge machining (EDM) parts allow for the machining of mated parts with gaps less than a thousandth of an inch. These high-precision parts are used to support against pressure and extrusion, a thin hermetically welded diaphragm. This diaphragm ruptures from a pressure differential when the support is removed and/or when the plunger is forced against the diaphragm. With the addition of conventional seals to the plunger and a two-way actuator, a derivative of this design would allow nonhermetic use as an on/off or metering valve after the initial rupturing of the hermetic sealing disk. In addition, in a single-use hermetically sealed isolation valve, the valve can be activated without the use of potential leak-inducing valve body penetrations. One implementation of this technology is a high-pressure, high-flow-rate rupture valve that is self-rupturing, which is advantageous for high-pressure applications such as gas isolation valves. Once initiated, this technology is self
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Kogon, Brian; Mori, Makoto; Alsoufi, Bahaaldin; Kanter, Kirk; Oster, Matt
2015-06-01
Pulmonary valve disruption in patients with tetralogy of Fallot and congenital pulmonary stenosis often results in pulmonary insufficiency, right ventricular dilation, and tricuspid valve regurgitation. Management of functional tricuspid regurgitation at the time of subsequent pulmonary valve replacement remains controversial. Our aims were to (1) analyze tricuspid valve function after pulmonary valve replacement through midterm follow-up and (2) determine the benefits, if any, of concomitant tricuspid annuloplasty. Thirty-five patients with tetralogy of Fallot or congenital pulmonary stenosis were analyzed. All patients had been palliated in childhood by disrupting the pulmonary valve, and all patients had at least moderate tricuspid valve regurgitation at the time of subsequent pulmonary valve replacement. Preoperative and serial postoperative echocardiograms were analyzed. Pulmonary and tricuspid regurgitation, along with right ventricular dilation and dysfunction were scored as 0 (none), 1 (mild), 2 (moderate), and 3 (severe). Right ventricular volume and area were also calculated. Comparisons were made between patients who underwent pulmonary valve replacement alone and those who underwent concomitant tricuspid valve annuloplasty. At 1 month after pulmonary valve replacement, there were significant reductions in pulmonary valve regurgitation (mean 3 vs 0.39, p < 0.0001), tricuspid valve regurgitation (mean 2.33 vs 1.3, p < 0.0001), and in right ventricular dilation, volume, and area. There was no difference in the degree of tricuspid regurgitation 1 month postoperatively between patients who underwent concomitant tricuspid annuloplasty and those who underwent pulmonary valve replacement alone (mean 1.31 vs 1.29, p = 0.81). However, at latest follow-up (mean 7.0 ± 2.8 years), the degree of tricuspid regurgitation was significantly higher in the concomitant annuloplasty group (mean 1.87 vs 1.12, p = 0.005). In patients with at least moderate tricuspid valve
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NASA Technical Reports Server (NTRS)
McCormack, Kenneth J. (Inventor)
2016-01-01
A cryogenic cam butterfly valve has a body that includes an axially extending fluid conduit formed there through. A disc lug is connected to a back side of a valve disc and has a circular bore that receives and is larger than a cam of a cam shaft. The valve disc is rotatable for a quarter turn within the body about a lug axis that is offset from the shaft axis. Actuating the cam shaft in the closing rotational direction first causes the camming side of the cam of the cam shaft to rotate the disc lug and the valve disc a quarter turn from the open position to the closed position. Further actuating causes the camming side of the cam shaft to translate the valve disc into sealed contact with the valve seat. Opening rotational direction of the cam shaft reverses these motions.
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Interstitial pneumonitis after acetylene welding: a case report.
Brvar, Miran
2014-01-01
Acetylene is a colorless gas commonly used for welding. It acts mainly as a simple asphyxiant. In this paper, however, we present a patient who developed a severe interstitial pneumonitis after acetylene exposure during aluminum welding. A 44-year old man was welding with acetylene, argon and aluminum electrode sticks in a non-ventilated aluminum tank for 2 h. Four hours after welding dyspnea appeared and 22 h later he was admitted at the Emergency Department due to severe respiratory insufficiency with pO2 = 6.7 kPa. Chest X-ray showed diffuse interstitial infiltration. Pulmonary function and gas diffusion tests revealed a severe restriction (55% of predictive volume) and impaired diffusion capacity (47% of predicted capacity). Toxic interstitial pneumonitis was diagnosed and high-dose systemic corticosteroid methylprednisolone and inhalatory corticosteroid fluticasone therapy was started. Computed Tomography (CT) of the lungs showed a diffuse patchy ground-glass opacity with no signs of small airway disease associated with interstitial pneumonitis. Corticosteroid therapy was continued for the next 8 weeks gradually reducing the doses. The patient's follow-up did not show any deterioration of respiratory function. In conclusion, acetylene welding might result in severe toxic interstitial pneumonitis that improves after an early systemic and inhalatory corticosteroid therapy.
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Juthier, Francis; Vincentelli, André; Gaudric, Julien; Corseaux, Delphine; Fouquet, Olivier; Calet, Christine; Le Tourneau, Thierry; Soenen, Valérie; Zawadzki, Christophe; Fabre, Olivier; Susen, Sophie; Prat, Alain; Jude, Brigitte
2006-04-01
Autologous recellularization of decellularized heart valve scaffolds is a promising challenge in the field of tissue-engineered heart valves and could be boosted by bone marrow progenitor cell mobilization. The aim of this study was to examine the spontaneous in vivo recolonization potential of xenogeneic decellularized heart valves in a lamb model and the effects of granulocyte colony-stimulating factor mobilization of bone marrow cells on this process. Decellularized porcine aortic valves were implanted in 12 lambs. Six lambs received granulocyte colony-stimulating factor (10 microg x kg(-1) x d(-1) for 7 days, granulocyte colony-stimulating factor group), and 6 received no granulocyte colony-stimulating factor (control group). Additionally, nondecellularized porcine valves were implanted in 5 lambs (xenograft group). Angiographic and histologic evaluation was performed at 3, 6, 8, and 16 weeks. Few macroscopic modifications of leaflets and the aortic wall were observed in the control group, whereas progressive shrinkage and thickening of the leaflets appeared in the granulocyte colony-stimulating factor and xenograft groups. In the 3 groups progressive ovine cell infiltration (fluorescence in situ hybridization) was observed in the leaflets and in the adventitia and the intima of the aortic wall but not in the media. Neointimal proliferation of alpha-actin-positive cells, inflammatory infiltration, adventitial neovascularization, and calcifications were more important in the xenograft and the granulocyte colony-stimulating factor groups than in the control group. Continuous re-endothelialization appeared only in the control group. Decellularized xenogeneic heart valve scaffolds allowed partial autologous recellularization. Granulocyte colony-stimulating factor led to accelerated heart valve deterioration similar to that observed in nondecellularized xenogeneic cardiac bioprostheses.
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Ciani, Cesare; Doty, Stephen B.; Fritton, Susannah P.
2014-01-01
Bone interstitial fluid flow is thought to play a fundamental role in the mechanical stimulation of bone cells, either via shear stresses or cytoskeletal deformations. Recent evidence indicates that osteocytes are surrounded by a fiber matrix that may be involved in the mechanotransduction of external stimuli as well as in nutrient exchange. In our previous tracer studies designed to map how different-sized molecules travel through the bone porosities, we found that injected ferritin was confined to blood vessels and did not pass into the mineralized matrix. However, other investigators have shown that ferritin forms halo-shaped labeling that enters the mineralized matrix around blood vessels. This labeling is widely used to explain normal interstitial fluid movement in bone; in particular, it is said to demonstrate bulk centrifugal interstitial fluid movement away from a highly pressurized vascular porosity. In addition, appositional ferritin fronts are said to demonstrate centrifugal interstitial fluid movement from the medullary canal to the periosteal surface. The purpose of this study was to investigate the conflicting ferritin labeling results by evaluating the role of different histological processes in the formation of ferritin “halos.” Ferritin was injected into the rat vasculature and allowed to circulate for 5 min. Samples obtained from tibiae were reacted for different times with Perl's reagent and then were either paraffin-embedded or sectioned with a cryostat. Halo-like labeling surrounding vascular pores was found in all groups, ranging from 1.2–3.9% for the samples treated with the shortest histological processes (unembedded, frozen sections) to 5.6–15% for the samples treated with the longest histological processes (paraffin-embedded sections). These results indicate that different histological processing methods are able to create ferritin “halos,” with some processing methods allowing more redistribution of the ferritin tracer than
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Ciani, Cesare; Doty, Stephen B; Fritton, Susannah P
2005-09-01
Bone interstitial fluid flow is thought to play a fundamental role in the mechanical stimulation of bone cells, either via shear stresses or cytoskeletal deformations. Recent evidence indicates that osteocytes are surrounded by a fiber matrix that may be involved in the mechanotransduction of external stimuli as well as in nutrient exchange. In our previous tracer studies designed to map how different-sized molecules travel through the bone porosities, we found that injected ferritin was confined to blood vessels and did not pass into the mineralized matrix. However, other investigators have shown that ferritin forms halo-shaped labeling that enters the mineralized matrix around blood vessels. This labeling is widely used to explain normal interstitial fluid movement in bone; in particular, it is said to demonstrate bulk centrifugal interstitial fluid movement away from a highly pressurized vascular porosity. In addition, appositional ferritin fronts are said to demonstrate centrifugal interstitial fluid movement from the medullary canal to the periosteal surface. The purpose of this study was to investigate the conflicting ferritin labeling results by evaluating the role of different histological processes in the formation of ferritin "halos." Ferritin was injected into the rat vasculature and allowed to circulate for 5 min. Samples obtained from tibiae were reacted for different times with Perl's reagent and then were either paraffin-embedded or sectioned with a cryostat. Halo-like labeling surrounding vascular pores was found in all groups, ranging from 1.2-3.9% for the samples treated with the shortest histological processes (unembedded, frozen sections) to 5.6-15% for the samples treated with the longest histological processes (paraffin-embedded sections). These results indicate that different histological processing methods are able to create ferritin "halos," with some processing methods allowing more redistribution of the ferritin tracer than others. Based
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Slide valve apparatus for internal combustion engine
DOE Office of Scientific and Technical Information (OSTI.GOV)
Taylor, B.A.; McMahan, T.O.
This patent describes an internal combustion engine including a combustion cylinder having an opening at one end thereof, a piston mounted within the cylinder for coaxial reciprocable movement, a driven crankshaft, and a connecting rod connecting the crankshaft to the cylinder for linear reciprocable movement of the piston in response to the rotary movement of the crankshaft, a valve apparatus comprising: (a) a valve chamber extending longitudinally across and in fluid communication with the opening in the cylinder, (b) an intake valve plate having a longitudinal axis mounted within the valve chamber for slidable, reciprocable, longitudinal movement, (c) an exhaustmore » valve plate having a longitudinal axis mounted within the valve chamber alongside the intake valve plate for slidable, reciprocable, longitudinal movement and parallel to the longitudinal axis of the intake valve plate, (d) each of the valve plates having a plurality of longitudinally spaced valve ports therein, the valve ports comprising movable intake valve ports in the intake valve plate and movable exhaust valve ports in the exhaust valve plate, (e) the valve chamber comprising a planar wall on the opposite side of the valve plates from the cylinder opening and having a plurality of fixed valve ports therethrough. The fixed valve ports being equal in number and substantially equal in size and spacing as the movable intake and exhaust valve ports, whereby the movable intake valve ports are adapted to register with their corresponding fixed valve ports when the intake valve plate is in its intake operative position for opening fluid communication between the cylinder and the corresponding fixed valve ports.« less
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NASA Technical Reports Server (NTRS)
Burley, Richard K.; Guirguis, Kamal S.
1991-01-01
Simple, cheap device locks valve stem so its setting cannot be changed by unauthorized people. Device covers valve stem; cover locked in place with standard padlock. Valve lock made of PVC pipe and packing band. Shears, drill or punch, and forming rod only tools needed.
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NASA Technical Reports Server (NTRS)
Srinivasan, K. V.
1986-01-01
The design and development of a large diameter high pressure quick acting propulsion valve and valve actuator is described. The valve is the heart of a major test facility dedicated to conducting full scale performance tests of aircraft landing systems. The valve opens in less than 300 milliseconds releasing a 46-centimeter- (18-in.-) diameter water jet and closes in 300 milliseconds. The four main components of the valve, i.e., valve body, safety shutter, high speed shutter, and pneumatic-hydraulic actuator, are discussed. This valve is unique and may have other aerospace and industrial applications.
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NASA Technical Reports Server (NTRS)
Srinivasan, K. V.
1986-01-01
This paper describes the design and development of a large diameter high pressure quick acting propulsion valve and valve actuator. The valve is the heart of a major test facility dedicated to conducting full scale performance tests of aircraft landing gear systems. The valve opens in less than 300 milliseconds releasing a 46 cm (18 in) diameter water jet and closes in 300 milliseconds. The four main components of the valve, i.e., valve body, safety shutter, high speed shutter, and pneumatic-hydraulic actuator, are discussed. This valve is unique and may have other aerospace and industrial applications.
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van Gorp, Maarten J; van der Graaf, Yolanda; de Mol, Bas A J M; Bakker, Chris J G; Witkamp, Theo D; Ramos, Lino M P; Mali, Willem P T M
2004-03-01
To assess the relationship between heart valve history and susceptibility artifacts at magnetic resonance (MR) imaging of the brain in patients with Björk-Shiley convexoconcave (BSCC) valves. MR images of the brain were obtained in 58 patients with prosthetic heart valves: 20 patients had BSCC valve replacements, and 38 had other types of heart valves. Two experienced neuroradiologists determined the presence or absence of susceptibility artifacts in a consensus reading. Artifacts were defined as characteristic black spots that were visible on T2*-weighted gradient-echo MR images. The statuses of the 20 explanted BSCC valves-specifically, whether they were intact or had an outlet strut fracture (OSF) or a single-leg fracture (SLF)-had been determined earlier. Number of artifacts seen at brain MR imaging was correlated with explanted valve status, and differences were analyzed with nonparametric statistical tests. Significantly more patients with BSCC valves (17 [85%] of 20 patients) than patients with other types of prosthetic valves (18 [47%] of 38 patients) had susceptibility artifacts at MR imaging (P =.005). BSCC valve OSFs were associated with a significantly higher number of artifacts than were intact BSCC valves (P =.01). No significant relationship between SLF and number of artifacts was observed. Susceptibility artifacts at brain MR imaging are not restricted to patients with BSCC valves. These artifacts can be seen on images obtained in patients with various other types of fractured and intact prosthetic heart valves. Copyright RSNA, 2004
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9. BUTTERFLY VALVE CONTROL DIABLO POWERHOUSE. BUTTERFLY VALVES WERE MANUFACTURED ...
9. BUTTERFLY VALVE CONTROL DIABLO POWERHOUSE. BUTTERFLY VALVES WERE MANUFACTURED BY THE PELTON WATER WHEEL COMPANY IN 1931, 1989. - Skagit Power Development, Diablo Powerhouse, On Skagit River, 6.1 miles upstream from Newhalem, Newhalem, Whatcom County, WA
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Pregnancy-induced remodeling of heart valves.
Pierlot, Caitlin M; Moeller, Andrew D; Lee, J Michael; Wells, Sarah M
2015-11-01
Recent studies have demonstrated remodeling of aortic and mitral valves leaflets under the volume loading and cardiac expansion of pregnancy. Those valves' leaflets enlarge with altered collagen fiber architecture, content, and cross-linking and biphasic changes (decreases, then increases) in extensibility during gestation. This study extends our analyses to right-sided valves, with additional compositional measurements for all valves. Valve leaflets were harvested from nonpregnant heifers and pregnant cows. Leaflet structure was characterized by leaflet dimensions, and ECM composition was determined using standard biochemical assays. Histological studies assessed changes in cellular and ECM components. Leaflet mechanical properties were assessed using equibiaxial mechanical testing. Collagen thermal stability and cross-linking were assessed using denaturation and hydrothermal isometric tension tests. Pulmonary and tricuspid leaflet areas increased during pregnancy by 35 and 55%, respectively. Leaflet thickness increased by 20% only in the pulmonary valve and largely in the fibrosa (30% thickening). Collagen crimp length was reduced in both the tricuspid (61%) and pulmonary (42%) valves, with loss of crimped area in the pulmonary valve. Thermomechanics showed decreased collagen thermal stability with surprisingly maintained cross-link maturity. The pulmonary leaflet exhibited the biphasic change in extensibility seen in left side valves, whereas the tricuspid leaflet mechanics remained largely unchanged throughout pregnancy. The tricuspid valve exhibits a remodeling response during pregnancy that is significantly diminished from the other three valves. All valves of the heart remodel in pregnancy in a manner distinct from cardiac pathology, with much similarity valve to valve, but with interesting valve-specific responses in the aortic and tricuspid valves. Copyright © 2015 the American Physiological Society.
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Self-compensating solenoid valve
NASA Technical Reports Server (NTRS)
Woeller, Fritz H. (Inventor); Matsumoto, Yutaka (Inventor)
1987-01-01
A solenoid valve is described in which both an inlet and an outlet of the valve are sealed when the valve is closed. This double seal compensates for leakage at either the inlet or the outlet by making the other seal more effective in response to the leakage and allows the reversal of the flow direction by simply switching the inlet and outlet connections. The solenoid valve has a valve chamber within the valve body. Inlet and outlet tubes extend through a plate into the chamber. A movable core in the chamber extends into the solenoid coil. The distal end of the core has a silicone rubber plug. Other than when the solenoid is energized, the compressed spring biases the core downward so that the surface of the plug is in sealing engagement with the ends of the tubes. A leak at either end increases the pressure in the chamber, resulting in increased sealing force of the plug.
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Aydin, Unal; Gul, Mehmet; Aslan, Serkan; Akkaya, Emre; Yildirim, Aydin
2015-04-28
Transcatheter valve implantation is a novel interventional technique, which was developed as an alternative therapy for surgical aortic valve replacement in inoperable patients with severe aortic stenosis. Despite limited experience in using transcatheter valve implantation for mitral and aortic regurgitation, transapical transcatheter aortic valve implantation and valve-in-valve implantation for degenerated mitral valve bioprosthesis can be performed in high-risk patients who are not candidates for conventional replacement surgery. In this case, we present the simultaneous transcatheter valve implantation via transapical approach for both degenerated bioprosthetic mitral valve with severe regurgitation and pure severe aortic regurgitation.
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Fischer, Harry C.
1977-01-01
This invention is a reversing valve having an inlet, an outlet, and an inlet-outlet port. The valve is designed to respond to the introduction of relatively high-pressure fluid at its inlet or, alternatively, of lower-pressure fluid at its inlet-outlet port. The valve includes an axially slidable assembly which is spring-biased to a position where it isolates the inlet and connects the inlet-outlet port to the outlet. The admission of high-pressure fluid to the inlet displaces the slidable assembly to a position where the outlet is isolated and the inlet is connected to the inlet-outlet port. The valve is designed to minimize pressure drops and leakage. It is of a reliable and comparatively simple design.
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Intravesical NGF Antisense Therapy Using Lipid Nanoparticle for Interstitial Cystitis
2015-10-01
intravesical botulinum toxin type A injec- tions plus hydrodistention with hydrodis- tention alone for the treatment of refractory interstitial cystitis/ painful ...SUPPLEMENTARY NOTES 14. ABSTRACT Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating disorder characterized by persistent pelvic pain ...from an animal efficacy experiment conducted during the previous period. The project is ongoing. 15. SUBJECT TERMS Interstitial cystitis/ painful
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Anterior urethral valve associated with posterior urethral valves.
Kajbafzadeh, A M; Jangouk, P; Ahmadi Yazdi, C
2005-12-01
The association of anterior urethral valve (AUV) with posterior urethral valve (PUV) is rare. A 7-month-old infant was presented at a district hospital with episodes of acute pyelonephritis. He was treated medically and a voiding cystourethrogram (VCUG) confirmed bilateral vesico-urethral reflux. The presence of concomitant AUV and PUV was not recognized. He underwent several surgical procedures, which failed. He had reflux recurrence following two antireflux procedures. He had urinary retention after each operation, which was managed by vesicostomy and perineal urethrostomy. At the age of 3.5 years, he was referred to our paediatric urology clinic. Noticing the AUV and PUV in the past VCUG, the valves were fulgurated. Urodynamic study before and 3 months after valve ablation showed a high voiding pressure. VCUG 6 months following ablation showed no reflux, but several uroflowmetric studies showed a staccato and interrupted pattern. Empirical treatment with an alpha-blocker was started. One year after treatment, a repeat VCUG showed no reflux. Uroflowmetry and urodynamic studies returned to normal. The perineal urethrostomy was closed. The child was asymptomatic after 9 months of follow up.
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Transcatheter aortic valve implantation in patients with bicuspid aortic valve stenosis.
Wijesinghe, Namal; Ye, Jian; Rodés-Cabau, Josep; Cheung, Anson; Velianou, James L; Natarajan, Madhu K; Dumont, Eric; Nietlispach, Fabian; Gurvitch, Ronen; Wood, David A; Tay, Edgar; Webb, John G
2010-11-01
We evaluated transcatheter aortic valve implantation (TAVI) in high-risk patients with bicuspid aortic valve (BAV) stenosis. TAVI shows promise in the treatment of severe stenosis of triscupid aortic valves, especially in high-risk patients. However, BAV stenosis has been considered a contraindication to TAVI. Eleven patients (age 52 to 90 years) with symptomatic severe BAV stenosis underwent TAVI at 3 Canadian tertiary hospitals between May 2006 and April 2010. All patients were considered high risk for surgical aortic valve replacement. Edwards-SAPIEN transcatheter heart valves (Edwards Lifesciences, Inc., Irvine, California) were used. Transfemoral or transapical access was selected, depending on the adequacy of femoral access. Access was transfemoral in 7 patients and transapical in 4 patients. There were no intraprocedural complications. Significant symptomatic and hemodynamic improvement was observed in 10 of 11 patients. Baseline aortic valve area of 0.65 ± 0.17 cm(2) and mean transaortic pressure gradient of 41 ± 22.4 mm Hg were improved to 1.45 ± 0.3 cm(2) and 13.4 ± 5.7 mm Hg, respectively. Two patients had moderate perivalvular leaks. At the 30-day follow-up there were 2 deaths due to multisystem failure in 2 transapical patients. In 1 patient an undersized, suboptimally positioned, unstable valve required late conversion to open surgery. TAVI in selected high-risk patients with severe BAV stenosis can be successfully performed with acceptable clinical outcomes but will require further evaluation. Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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Systolic Anterior Motion of the Mitral Valve after Mitral Valve Repair
Sternik, Leonid; Zehr, Kenton J.
2005-01-01
Factors predisposing patients to systolic anterior motion of the mitral valve (SAM) with left ventricular outflow tract (LVOT) obstruction after mitral valve repair are the presence of a myxomatous mitral valve with redundant leaflets, a nondilated hyperdynamic left ventricle, and a short distance between the mitral valve coaptation point and the ventricular septum after repair. From December 1999 through March 2000, we used our surgical method in 6 patients with severely myxomatous regurgitant mitral valves who were at risk of developing SAM. Leaflets were markedly redundant in all 6. Left ventricular function was hyperdynamic in 4 patients and normal in 2. Triangular or quadrangular resection of the midportion of the posterior leaflet and posterior band annuloplasty were performed. To prevent SAM and LVOT obstruction, extra, posteriorly directed, mid-posterior-leaflet secondary chordae tendineae, which would otherwise have been resected, were transferred to the underside of the middle of the mid-anterior leaflet with a small piece of associated valve as an anchoring pledget. This kept the redundant anterior leaflet edge, which extended below the coaptation point, away from the LVOT. No post-repair SAM or LVOT obstruction was observed on intraoperative or discharge echocardiography. All patients had no or trivial residual mitral regurgitation. We conclude that extra chordae tendineae, when available, can be used in mitral valve repair to tether the redundant anterior leaflet and thus prevent it from flipping into the LVOT. This will theoretically prevent SAM and LVOT obstruction in patients with risk factors for SAM. PMID:15902821
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Wen, Qing; Wang, Yuqian; Tang, Jixin; Cheng, C Yan; Liu, Yi-Xun
2016-01-01
Sertoli cells play a significant role in regulating fetal testis compartmentalization to generate testis cords and interstitium during development. The Sertoli cell Wilms' tumor 1 (Wt1) gene, which encodes ~24 zinc finger-containing transcription factors, is known to play a crucial role in fetal testis cord assembly and maintenance. However, whether Wt1 regulates fetal testis compartmentalization by modulating the development of peritubular myoid cells (PMCs) and/or fetal Leydig cells (FLCs) remains unknown. Using a Wt1-/flox; Amh-Cre mouse model by deleting Wt1 in Sertoli cells (Wt1SC-cKO) at embryonic day 14.5 (E14.5), Wt1 was found to regulate PMC and FLC development. Wt1 deletion in fetal testis Sertoli cells caused aberrant differentiation and proliferation of PMCs, FLCs and interstitial progenitor cells from embryo to newborn, leading to abnormal fetal testis interstitial development. Specifically, the expression of PMC marker genes α-Sma, Myh11 and Des, and interstitial progenitor cell marker gene Vcam1 were down-regulated, whereas FLC marker genes StAR, Cyp11a1, Cyp17a1 and Hsd3b1 were up-regulated, in neonatal Wt1SC-cKO testes. The ratio of PMC:FLC were also reduced in Wt1SC-cKO testes, concomitant with a down-regulation of Notch signaling molecules Jag 1, Notch 2, Notch 3, and Hes1 in neonatal Wt1SC-cKO testes, illustrating changes in the differentiation status of FLC from their interstitial progenitor cells during fetal testis development. In summary, Wt1 regulates the development of FLC and interstitial progenitor cell lineages through Notch signaling, and it also plays a role in PMC development. Collectively, these effects confer fetal testis compartmentalization.
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Hanson, Clark L.
1984-01-10
A valve is provided for protecting the high vacuum of a particle accelera in the event of air leakage, wherein the valve provides an axially symmetrical passage to avoid disturbance of the partical beam during normal operation, and yet enables very rapid and tight closure of the beam-carrying pipe in the event of air leakage. The valve includes a ball member (30) which can rotate between a first position wherein a bore (32) in the member is aligned with the beam pipe, and a second position out of line with the pipe. A seal member (38) is flexibly sealed to the pipe, and has a seal end which can move tightly against the ball member after the bore has rotated out of line with the pipe, to thereby assure that the seal member does not retard rapid rotation of the ball valve member. The ball valve member can be rapidly rotated by a conductive arm (40) fixed to it and which is rotated by the discharge of a capacitor bank through coils (44, 45) located adjacent to the arm.
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Interstitial protein alterations in rabbit vocal fold with scar.
Thibeault, Susan L; Bless, Diane M; Gray, Steven D
2003-09-01
Fibrous and interstitial proteins compose the extracellular matrix of the vocal fold lamina propria and account for its biomechanic properties. Vocal fold scarring is characterized by altered biomechanical properties, which create dysphonia. Although alterations of the fibrous proteins have been confirmed in the rabbit vocal fold scar, interstitial proteins, which are known to be important in wound repair, have not been investigated to date. Using a rabbit model, interstitial proteins decorin, fibromodulin, and fibronectin were examined immunohistologically, two months postinduction of vocal fold scar by means of forcep biopsy. Significantly decreased decorin and fibromodulin with significantly increased fibronectin characterized scarred vocal fold tissue. The implications of altered interstitial proteins levels and their affect on the fibrous proteins will be discussed in relation to increased vocal fold stiffness and viscosity, which characterizes vocal fold scar.
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Roles of interstitial fluid pH in diabetes mellitus: Glycolysis and mitochondrial function
Marunaka, Yoshinori
2015-01-01
The pH of body fluids is one the most important key factors regulating various cell function such as enzyme activity and protein-protein interaction via modification of its binding affinity. Therefore, to keep cell function normal, the pH of body fluids is maintained constant by various systems. Insulin resistance is one of the most important, serious factors making the body condition worse in diabetes mellitus. I have recently found that the pH of body (interstitial) fluids is lower in diabetes mellitus than that in non-diabetic control, and that the lowered pH is one of the causes producing insulin resistance. In this review article, I introduce importance of body (interstitial) fluid pH in regulation of body function, evidence on abnormal regulation of body fluid pH in diabetes mellitus, and relationship between the body fluid pH and insulin resistance. Further, this review proposes perspective therapies on the basis of regulation of body fluid pH including propolis (honeybee product) diet. PMID:25685283
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Annihilating vacancies via dynamic reflection and emission of interstitials in nano-crystal tungsten
NASA Astrophysics Data System (ADS)
Li, Xiangyan; Duan, Guohua; Xu, Yichun; Zhang, Yange; Liu, Wei; Liu, C. S.; Liang, Yunfeng; Chen, Jun-Ling; Luo, G.-N.
2017-11-01
Radiation damage not only seriously degrades the mechanical properties of tungsten (W) but also enhances hydrogen retention in the material. Introducing a large amount of defect sinks, e.g. grain boundaries (GBs) is an effective method for improving radiation-resistance of W. However, the mechanism by which the vacancies are dynamically annihilated at long timescale in nano-crystal W is still not clear. The dynamic picture for eliminating vacancies with single interstitials and small interstitial-clusters has been investigated by combining molecular dynamics, molecular statics and object Kinetic Monte Carlo methods. On one hand, the annihilation of bulk vacancies was enhanced due to the reflection of an interstitial-cluster of parallel ≤ft< 1 1 1 \\right> crowdions by the GB. The interstitial-cluster was observed to be reflected back into the grain interior when approaching a locally dense GB region. Near this region, the energy landscape for the interstitial was featured by a shoulder, different to the decreasing energy landscape of the interstitial near a locally loose region as indicative of the sink role of the GB. The bulk vacancy on the reflection path was annihilated. On the other hand, the dynamic interstitial emission efficiently anneals bulk vacancies. The single interstitial trapped at the GB firstly moved along the GB quickly and clustered to be the di-interstitial therein, reducing its mobility to a value comparable to that that for bulk vacancy diffusion. Then, the bulk vacancy was recombined via the coupled motion of the di-interstitial along the GB, the diffusion of the vacancy towards the GB and the accompanying interstitial emission. These results suggest that GBs play an efficient role in improving radiation-tolerance of nano-crystal W via reflecting highly-mobile interstitials and interstitial-clusters into the bulk and annihilating bulk vacancies, and via complex coupling of in-boundary interstitial diffusion, clustering of the interstitial
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[Airway-centered interstitial fibrosis related to exposure to fumes from cleaning products].
Serrano, Mario; Molina-Molina, María; Ramírez, José; Sánchez, Marcelo; Xaubet, Antoni
2006-10-01
Airway-centered interstitial fibrosis is a little known clinical entity that has only recently been described in the literature. Its pathology is characterized by bronchial fibrosis and localized interstitial pulmonary fibrosis around the airways. The disease has been associated with inhalation of a variety of substances, environmental or occupational, organic or inorganic. Clinical signs, radiographic manifestations, and lung function in patients with airway-centered interstitial fibrosis are similar to those of patients with idiopathic interstitial pneumonia. We describe a case of airway-centered interstitial fibrosis related to exposure to fumes from cleaning products.
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Downhole surge valve for earth boring apparatus
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, D.W.
1990-05-29
This patent describes a boring tool assembly having an underground percussion mole boring tool powered by a working fluid, the tool being driven through the earth by a rigid drill string pushed by a drilling frame, and a downhole valve assembly fixed between the downhole end of the drill string and the too, the improved downhole valve assembly. It comprises: a valve spool having an open first end, a closed second end and a peripheral sidewall, an axial bore extending partly through the valve spool from the open first end; a radial passage adjacent the closed second and of themore » valve spool, the radial passage extending radially from the valve spool axial bore through the valve spool peripheral sidewall; an axial groove in the peripheral sidewall of the valve spool; a valve body having a first end, a second end and a peripheral sidewall, an axial bore extending through the valve body, the valve spool extending through the valve body axial bore so that the second end of the valve body is adjacent the closed second end of the valve spool, the valve spool being axially moveable within the valve body axial bore; an axial slot; a free-floating key element; a valve housing; and seal means.« less
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Yokohori, Naoko; Sato, Akitoshi; Hasegawa, Mizue; Katsura, Hideki; Hiroshima, Kenzo; Takemura, Tamiko
2017-01-01
Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus involved in the pathogenesis of adult T-cell leukemia (ATL) and HTVL-1-associated bronchioloalveolar disorder (HABA). The clinical and pathological findings of HABA have been characterized as either a diffuse panbronchiolitis (DPB) pattern or idiopathic interstitial pneumonia (IIP) pattern. Treatments for HABA include corticosteroids for the IIP pattern and erythromycin for the DPB pattern. We herein report a case of HABA-associated unclassifiable interstitial pneumonia that improved with combined therapy with pirfenidone and erythromycin. This is the first report on the effectiveness of combined therapy with pirfenidone and erythromycin for HABA. PMID:28050003
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Xiao, Xia; Du, Chunyang; Yan, Zhe; Shi, Yonghong; Duan, Huijun; Ren, Yunzhuo
2017-01-01
Inflammation plays a crucial role in renal interstitial fibrosis, the pathway of chronic kidney diseases. Necroptosis is a novel form of regulated cell death, which plays a potential role in inflammation and renal diseases. The small molecule necrostatin-1 (Nec-1) is a specific inhibitor of necroptosis. This study was aimed at determining the role of necroptosis, RIP1/RIP3/mixed lineage kinase domain-like (MLKL) signaling pathway, in renal inflammation and interstitial fibrosis related to primitive tubulointerstitial injury. It was also aimed at evaluating the effect of Nec-1 in renal fibrosis induced by unilateral ureteral obstruction (UUO). Renal histology, immunohistochemistry, western blot, and real-time polymerase chain reaction were performed using UUO C57BL/6J mice model. Moreover, we tested whether Nec-1 was renal-protective in the interstitial fibrosis kidney. Mice were exposed to UUO and injected intraperitoneal with Nec-1 or vehicle. The levels of RIP1/RIP3/MLKL protein and mRNA were increased in the obstructed kidneys 7 days after UUO; this was accompanied by changes in renal pathological lesions. Renal histological examination showed lesser renal damage in Nec-1-treated UUO mice. Renal inflammation, assessed by tumor necrosis factor-α, interleukin-1β, and monocyte chemotactic protein-1 was markedly attenuated by Nec-1. Furthermore, Nec-1 treatment also significantly reduced TGF-β and α-smooth muscle actin, indicating lesser renal interstitial fibrosis. These findings suggest that the participation of necroptosis in UUO is partly demonstrated. And necroptosis inhibition may have a potential role in the treatment of diseases with increased inflammatory response and interstitial fibrosis in renal. © 2017 S. Karger AG, Basel.
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Update of transcatheter valve treatment
Liu, Xian-bao; Wang, Jian-an
2013-01-01
Transcatheter valve implantation or repair has been a very promising approach for the treatment of valvular heart diseases since transcatheter aortic valve implantation (TAVI) was successfully performed in 2002. Great achievements have been made in this field (especially TAVI and transcatheter mitral valve repair—MitraClip system) in recent years. Evidence from clinical trials or registry studies has proved that transcatheter valve treatment for valvular heart diseases is safe and effective in surgical high-risk or inoperable patients. As the evidence accumulates, transcatheter valve treatment might be an alterative surgery for younger patients with surgically low or intermediate risk valvular heart diseases in the near future. In this paper, the updates on transcatheter valve treatment are reviewed. PMID:23897785
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Pressure control valve. [inflating flexible bladders
NASA Technical Reports Server (NTRS)
Lambson, K. H. (Inventor)
1980-01-01
A control valve is provided which is adapted to be connected between a pressure source, such as a vacuum pump, and a pressure vessel so as to control the pressure in the vessel. The valve comprises a housing having a longitudinal bore which is connected between the pump and vessel, and a transversely movable valve body which controls the air flow through an air inlet in the housing. The valve body includes cylindrical and conical shaped portions which cooperate with reciprocally shaped portions of the housing to provide flow control. A filter in the air inlet removes foreign matter from the air. The bottom end of the valve body is screwed into the valve housing control knob formed integrally with the valve body and controls translation of the valve body, and the opening and closing of the valve.
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"Bail out" procedures for malpositioning of aortic valve prosthesis (CoreValve).
Vavouranakis, Manolis; Vrachatis, Dimitrios A; Toutouzas, Konstantinos P; Chrysohoou, Christina; Stefanadis, Christodoulos
2010-11-05
Two techniques for correcting malpositioning occurring during percutaneous aortic valve replacement (PAVR) with the CoreValve ReValving™ System are described in this article. The "Removing and Reinserting Technique" was used in 2 patients, in whom the prosthesis was positioned too high. The "Snare Technique" was used in 1 patient, in whom the prosthesis was implanted too low. In all patients the aortic valve prosthesis was successfully re-implanted. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.
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Modro, S. Michael; Ougouag, Abderrafi M.
2005-09-20
A passively actuated valve for isolating a high pressure zone from a low pressure zone and discontinuing the isolation when the pressure in the high pressure zone drops below a preset threshold. If the pressure in the high pressure zone drops below the preset threshold, the valve opens and allows flow from the high pressure zone to the low pressure zone. The valve remains open allowing pressure equalization and back-flow should a pressure inversion between the two pressure zone occur.
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Interstitial lung disease associated with Equine Infectious Anemia Virus infection in horses
2013-01-01
EIA (Equine Infectious Anemia) is a blood-borne disease primarily transmitted by haematophagous insects or needle punctures. Other routes of transmission have been poorly explored. We evaluated the potential of EIAV (Equine Infectious Anemia Virus) to induce pulmonary lesions in naturally infected equids. Lungs from 77 EIAV seropositive horses have been collected in Romania and France. Three types of lesions have been scored on paraffin-embedded lungs: lymphocyte infiltration, bronchiolar inflammation, and thickness of the alveolar septa. Expression of the p26 EIAV capsid (CA) protein has been evaluated by immunostaining. Compared to EIAV-negative horses, 52% of the EIAV-positive horses displayed a mild inflammation around the bronchioles, 22% had a moderate inflammation with inflammatory cells inside the wall and epithelial bronchiolar hyperplasia and 6.5% had a moderate to severe inflammation, with destruction of the bronchiolar epithelium and accumulation of smooth muscle cells within the pulmonary parenchyma. Changes in the thickness of the alveolar septa were also present. Expression of EIAV capsid has been evidenced in macrophages, endothelial as well as in alveolar and bronchiolar epithelial cells, as determined by their morphology and localization. To summarize, we found lesions of interstitial lung disease similar to that observed during other lentiviral infections such as FIV in cats, SRLV in sheep and goats or HIV in children. The presence of EIAV capsid in lung epithelial cells suggests that EIAV might be responsible for the broncho-interstitial damages observed. PMID:24289102
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Interstitial lung disease associated with Equine Infectious Anemia Virus infection in horses.
Bolfa, Pompei; Nolf, Marie; Cadoré, Jean-Luc; Catoi, Cornel; Archer, Fabienne; Dolmazon, Christine; Mornex, Jean-François; Leroux, Caroline
2013-12-01
EIA (Equine Infectious Anemia) is a blood-borne disease primarily transmitted by haematophagous insects or needle punctures. Other routes of transmission have been poorly explored. We evaluated the potential of EIAV (Equine Infectious Anemia Virus) to induce pulmonary lesions in naturally infected equids. Lungs from 77 EIAV seropositive horses have been collected in Romania and France. Three types of lesions have been scored on paraffin-embedded lungs: lymphocyte infiltration, bronchiolar inflammation, and thickness of the alveolar septa. Expression of the p26 EIAV capsid (CA) protein has been evaluated by immunostaining. Compared to EIAV-negative horses, 52% of the EIAV-positive horses displayed a mild inflammation around the bronchioles, 22% had a moderate inflammation with inflammatory cells inside the wall and epithelial bronchiolar hyperplasia and 6.5% had a moderate to severe inflammation, with destruction of the bronchiolar epithelium and accumulation of smooth muscle cells within the pulmonary parenchyma. Changes in the thickness of the alveolar septa were also present. Expression of EIAV capsid has been evidenced in macrophages, endothelial as well as in alveolar and bronchiolar epithelial cells, as determined by their morphology and localization. To summarize, we found lesions of interstitial lung disease similar to that observed during other lentiviral infections such as FIV in cats, SRLV in sheep and goats or HIV in children. The presence of EIAV capsid in lung epithelial cells suggests that EIAV might be responsible for the broncho-interstitial damages observed.
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Gong, Yaoyao; Huang, Lei; Cheng, Wenfang; Li, Xueliang; Lu, Jia; Lin, Lin; Si, Xinmin
2014-01-01
Interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal (GI) tract and loss of ICC is associated with many GI motility disorders. Previous studies have shown that ICC have the capacity to regenerate or restore, and several growth factors are critical to their growth, maintenance or regeneration. The present study aimed to investigate the roles of interleukin-9 (IL-9) in the growth, maintenance and pacemaker functions of cultured ICC. Here, we report that IL-9 promotes proliferation of ICC, and culturing ICC with IL-9 enhances cholecystokinin-8-induced Ca²⁺ transients, which is probably caused by facilitating maintenance of ICC functions under culture condition. We also show co-localizations of cholecystokinin-1 receptor and IL-9 receptor with c-kit by double-immunohistochemical labeling. In conclusion, IL-9 can promote ICC growth and help maintain ICC functions; IL-9 probably performs its functions via IL-9 receptors on ICC.
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... valve syndrome . What happens during MVP? Watch an animation of mitral valve prolapse When the heart pumps ( ... our brochures Popular Articles 1 Understanding Blood Pressure Readings 2 Sodium and Salt 3 Heart Attack Symptoms ...
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... with an artificial valve (this is called the Ross Procedure). This procedure may be useful for people ... valve that does not close all the way will allow blood to leak backwards. This is called ...
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Jeffrey Gutterman; A. J. Lasley
2008-08-31
Many approaches exist to enable advanced mode, low temperature combustion systems for diesel engines - such as premixed charge compression ignition (PCCI), Homogeneous Charge Compression Ignition (HCCI) or other HCCI-like combustion modes. The fuel properties and the quantity, distribution and temperature profile of air, fuel and residual fraction in the cylinder can have a marked effect on the heat release rate and combustion phasing. Figure 1 shows that a systems approach is required for HCCI-like combustion. While the exact requirements remain unclear (and will vary depending on fuel, engine size and application), some form of substantially variable valve actuation ismore » a likely element in such a system. Variable valve actuation, for both intake and exhaust valve events, is a potent tool for controlling the parameters that are critical to HCCI-like combustion and expanding its operational range. Additionally, VVA can be used to optimize the combustion process as well as exhaust temperatures and impact the after treatment system requirements and its associated cost. Delphi Corporation has major manufacturing and product development and applied R&D expertise in the valve train area. Historical R&D experience includes the development of fully variable electro-hydraulic valve train on research engines as well as several generations of mechanical VVA for gasoline systems. This experience has enabled us to evaluate various implementations and determine the strengths and weaknesses of each. While a fully variable electro-hydraulic valve train system might be the 'ideal' solution technically for maximum flexibility in the timing and control of the valve events, its complexity, associated costs, and high power consumption make its implementation on low cost high volume applications unlikely. Conversely, a simple mechanical system might be a low cost solution but not deliver the flexibility required for HCCI operation. After modeling more than 200 variations of the
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NASA Technical Reports Server (NTRS)
Kelley, Anthony R. (Inventor); Lindner, Jeffrey L. (Inventor)
2014-01-01
The present invention is a space vehicle valve system which controls the internal pressure of a space vehicle and the flow rate of purged gases at a given internal pressure and aperture site. A plurality of quasi-unique variable dimension peaked valve structures cover the purge apertures on a space vehicle. Interchangeable sheet guards configured to cover valve apertures on the peaked valve structure contain a pressure-activated surface on the inner surface. Sheet guards move outwardly from the peaked valve structure when in structural contact with a purge gas stream flowing through the apertures on the space vehicle. Changing the properties of the sheet guards changes the response of the sheet guards at a given internal pressure, providing control of the flow rate at a given aperture site.
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Fry, W.A.
1962-05-29
A valve for high vacuum applications such as the CStellarator where chamber pressures as low as 2 x 10/sup -10/ mm Hg are necessary is designed with a line-of-sight path through the valve for visual inspection of the contents of reactants in such chambers. The valve comprises a turnable resilient metal ball having an aperture therethrough, means for selectively turning the ball to rotate the axis of its line-of-sight path, and soft, deformable opposing orifices that are movable relatively toward said ball to seal with opposite ball surfaces upon said movement of said axis of said line-of-sight path. The valve also includes a bellows seal connected between said orifices and internal actuating means that eliminates the requirement for gasketed turnable valve closing stems. (AEC)
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Fluid Dynamics of the Heart and its Valves
NASA Astrophysics Data System (ADS)
Peskin, Charles S.
1997-11-01
The fluid dynamics of the heart involve the interaction of blood, a viscous incompressible fluid, with the flexible, elastic, fiber-reinforced heart valve leaflets that are immersed in that fluid. Neither the fluid motion nor the valve leaflet motion are known in advance: both must be computed simultaneously by solving their coupled equations of motion. This can be done by the immersed boundary method(Peskin CS and McQueen DM: A general method for the computer simulation of biological systems interacting with fluids. In: Biological Fluid Dynamics (Ellington CP and Pedley TJ, eds.), The Company of Biologists Limited, Cambridge UK, 1995, pp. 265-276.), which can be extended to incorporate the contractile fiber architecture of the muscular heart walls as well as the valve leaflets and the blood. In this way we arrive at a three-dimensional computer model of the heart(Peskin CS and McQueen DM: Fluid dynamics of the heart and its valves. In: Case Studies in Mathematical Modeling: Ecology, Physiology, and Cell Biology (Othmer HG, Adler FR, Lewis MA, and Dallon JC, eds.), Prentice-Hall, Englewood Cliffs NJ, 1996, pp. 309-337.), which can be used as a test chamber for the design of prosthetic cardiac valves, and also to study the function of the heart in health and in disease. Numerical solutions of the equations of cardiac fluid dynamics obtained by the immersed boundary method will be presented in the form of a video animation of the beating heart.
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All metal valve structure for gas systems
Baker, Ray W.; Pawlak, Donald A.; Ramey, Alford J.
1984-11-13
A valve assembly with a resilient metal seat member is disclosed for providing a gas-tight seal in a gas handling system. The valve assembly also includes a valve element for sealing against the valve seat member; and an actuating means for operating the valve element. The valve seat member is a one-piece stainless steel ring having a central valve port and peripheral mounting flange, and an annular corrugation in between. A groove between the first and second ridges serves as a flexure zone during operation of the valve member and thus provides the seating pressure between the inner ridge or valve seat and the valve element. The outer annular ridge has a diameter less than said valve element to limit the seating motion of the valve element, preventing non-elastic deformation of the seat member.
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All-metal valve structure for gas systems
Baker, R.W.; Pawlak, D.A.; Ramey, A.J.
1982-06-10
A valve assembly with a resilient metal seat member is disclosed for providing a gas-tight seal in a gas handling system. The valve assembly also includes a valve element for sealing against the valve seat member; and an actuating means for operating the valve element. The valve seat member is a one-piece stainless steel ring having a central valve port and peripheral mounting flange, and an annular corrugation in between. A groove between the first and second ridges serves as a flexure zone during operation of the valve member and thus provides the seating pressure between the inner ridge or valve seat and the valve element. The outer annular ridge has a diameter less than said valve element to limit the seating motion of the valve element, preventing non-elastic deformation of the seat member.
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Microblower assisted barometric valve
Rossabi, Joseph; Hyde, Warren K.; Riha, Brian D.; Jackson, Dennis G.; Sappington, Frank
2005-12-06
A gas exchange apparatus is provided which provides for both passive fluid flow and blower associated fluid flow through a barometric valve. A battery powered blower is provided which allows for operation of the barometric valve during times when the barometric valve would otherwise be closed, and provides for enhanced volume of gas exchange.
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Liquid rocket valve assemblies
NASA Technical Reports Server (NTRS)
1973-01-01
The design and operating characteristics of valve assemblies used in liquid propellant rocket engines are discussed. The subjects considered are as follows: (1) valve selection parameters, (2) major design aspects, (3) design integration of valve subassemblies, and (4) assembly of components and functional tests. Information is provided on engine, stage, and spacecraft checkout procedures.
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The pathological features of idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas.
Kojima, Yoko; Okudela, Koji; Matsumura, Mai; Omori, Takahiro; Baba, Tomohisa; Sekine, Akimasa; Woo, Tetsukan; Umeda, Shigeaki; Takemura, Tamiko; Mitsui, Hideaki; Suzuki, Takehisa; Tateishi, Yoko; Iwasawa, Tae; Arai, Hiromasa; Tajiri, Michihiko; Ogura, Takashi; Kameda, Yoichi; Masuda, Munetaka; Ohashi, Kenich
2017-03-01
To investigate the pathological features of idiopathic interstitial pneumonia (IIP)-associated pulmonary adenocarcinoma. Surgically resected adenocarcinomas associated with IIP (the IIP group) and adenocarcinomas without IIP (the non-IIP group) were subjected to analysis. Adenocarcinomas in the IIP group were subdivided into two groups: one group included tumours connected to bronchiolar metaplasia in honeycomb lesions (the H-IIP group), and the other included tumours unrelated to honeycomb lesions (the NH-IIP group). Histomorphological appearance and immunohistochemical expression were compared among the H-IIP group, the NH-IIP group, and the non-IIP group. Most of the tumour cells in the H-IIP group had a tall, columnar shape that showed similar features to proximal bronchial epithelium, whereas tumour cells in the NH-IIP group and the non-IIP group had a club-like shape that showed similar features to respiratory bronchiolar/alveolar epithelium. Adenocarcinomas in the H-IIP group tended to be negative for thyroid transcription factor-1 (TTF-1) and positive for hepatocyte nuclear factor-4α (HNF-4α). The frequency of EGFR mutations was significantly lower in adenocarcinomas in the H-IIP group, although the frequencies of KRAS and ALK mutations did not differ among the three groups. Idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas, especially those arising from honeycomb lesions, have distinct pathological features. © 2016 John Wiley & Sons Ltd.
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Aerosol penetration through respirator exhalation valves.
Bellin, P; Hinds, W C
1990-10-01
Exhalation valves are a critical component of industrial respirators. They are designed to permit minimal inward leakage of air contaminants during inhalation and provide low resistance during exhalation. Under normal conditions, penetration of aerosol through exhalation valves is minimal. The exhalation valve is, however, a vulnerable component of a respirator and under actual working conditions may become dirty or damaged to the point of causing significant leakage. Aerosol penetration was measured for normal exhalation valves and valves compromised by paint or fine copper wires on the valve seat. Penetration increased with increasing wire diameter. A wire 250 microns in diameter allowed greater than 1% penetration into the mask cavity. Dirt or paint accumulated on the exhalation valve allowed a similar level of penetration. Work rate had little effect on observed penetration. Penetration decreased significantly with increasing aerosol particle size. The amount of material on the valve or valve seat necessary for significant (greater than 0.5%) inward leakage in a half-mask respirator could be readily observed by careful inspection of the exhalation valve and its seat in good lighting conditions.
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Spool-Valve Pressure-Difference Regulator
NASA Technical Reports Server (NTRS)
Grasso, A. P.
1983-01-01
Valves maintain preset pressure difference between gas flows. Two spool valves connected by shaft move back and forth in response to changes in pressure in oxygen and hydrogen chambers. Spool-valve assembly acts to restore pressures to preset difference. By eliminating diaphragms, pressure exerted directly on external end of spool valve; however, forces and therefore sensitivity of assembly are reduced.
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Fujita, Buntaro; Scholtz, Smita; Ensminger, Stephan
2016-04-01
Coronary obstruction during transcatheter aortic valve implantation is a potentially life-threatening complication. Most of the widely used transcatheter heart valves require a certain distance between the basal aortic annular plane and the origins of the coronary arteries. We report the case of a successful valve-in-valve procedure with an Edwards SAPIEN XT valve into a JenaValve as a bail-out procedure in a patient with a low originating left coronary artery and a heavily calcified aorta. © 2015 Wiley Periodicals, Inc.
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Mechanisms of mechanical heart valve cavitation: investigation using a tilting disk valve model.
He, Z; Xi, B; Zhu, K; Hwang, N H
2001-09-01
The induction of mechanical heart valve (MHV) cavitation was investigated using a 27 mm Medtronic Hall (MH27) tilting disk valve. The MH27 valve was mounted in the mitral position of a simulating pulse flow system, and stroboscopic lighting used to visualize cavitation bubbles on the occluder inflow surface at the instant of valve closure. MHV cavitation was monitored using a digital camera with 0.04 mm/pixel resolution sufficient to render the tiny bubbles clearly visible on the computer monitor screen. Cavitation on MH27 valve was classified as five types according to the time, site and shape of the cavitation bubbles. Valve cavitation occurred at the instant of occluder impact with the valve seat at closing. The impact motion was subdivided into three temporal phases: (i) squeezing flow; (ii) elastic collision; and (iii) leaflet rebound. MHV cavitation caused by vortices was found to be initiated by the squeezing jet and/or by the transvalvular leakage jets. By using a tension wave which swept across the occluder surface immediately upon elastic impact, nuclei in the vortex core were expanded to form cavitation bubbles. Analysis of the shape and location of the cavitation bubbles permitted a better understanding of MHV cavitation mechanisms, based on the fluid dynamics of jet vortex and tension wave propagations.
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NASA Astrophysics Data System (ADS)
(Jay Chen, Zhe; Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder
2011-08-01
Previous studies have shown that procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations strongly depends on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al (1998 Int. J. Radiat. Oncol. Biol. Phys. 41 1069-77) was used to characterize the edema evolutions previously observed during clinical PIB for prostate cancer. The concept of biologically effective dose, taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not appropriately taken into account, can increase the cell survival and decrease the probability of local control of PIB. The magnitude of an edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life of radioactive decay and decreasing photon energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days) is longer than
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[New toxicity of fotemustine: diffuse interstitial lung disease].
Bertrand, M; Wémeau-Stervinou, L; Gauthier, S; Auffret, M; Mortier, L
2012-04-01
Fotemustine is an alkylating cytostatic drug belonging to the nitrosourea family and is used in particular in the treatment of disseminated malignant melanoma. Herein, we report a case of interstitial lung disease associated with fotemustine. An 81-year-old man treated with fotemustine for metastatic melanoma presented acute interstitial lung disease 20 days after a fourth course of fotemustine monotherapy. The condition regressed spontaneously, with the patient returning to the clinical, radiological and blood gas status that had preceded fotemustine treatment. After other potential aetiologies had been ruled out, acute fotemustine-induced lung toxicity was considered and this treatment was definitively withdrawn. Other cytostatic agents belonging to the nitrosourea family can cause similar pictures, with a number of cases of interstitial lung disease thus being ascribed to fotemustine and dacarbazine. To our knowledge, this is the first case of interstitial lung disease induced by fotemustine monotherapy. This diagnosis should be considered where respiratory signs appear in melanoma patients undergoing fotemustine treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
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Mechanisms of leading edge protrusion in interstitial migration
Wilson, Kerry; Lewalle, Alexandre; Fritzsche, Marco; Thorogate, Richard; Duke, Tom; Charras, Guillaume
2013-01-01
While the molecular and biophysical mechanisms underlying cell protrusion on two-dimensional substrates are well understood, our knowledge of the actin structures driving protrusion in three-dimensional environments is poor, despite relevance to inflammation, development and cancer. Here we report that, during chemotactic migration through microchannels with 5 μm × 5 μm cross-sections, HL60 neutrophil-like cells assemble an actin-rich slab filling the whole channel cross-section at their front. This leading edge comprises two distinct F-actin networks: an adherent network that polymerizes perpendicular to cell-wall interfaces and a ‘free’ network that grows from the free membrane at the cell front. Each network is polymerized by a distinct nucleator and, due to their geometrical arrangement, the networks interact mechanically. On the basis of our experimental data, we propose that, during interstitial migration, medial growth of the adherent network compresses the free network preventing its retrograde movement and enabling new polymerization to be converted into forward protrusion. PMID:24305616
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Effects of lubiprostone on pacemaker activity of interstitial cells of cajal from the mouse colon.
Jiao, Han-Yi; Kim, Dong Hyun; Ki, Jung Suk; Ryu, Kwon Ho; Choi, Seok; Jun, Jae Yeoul
2014-08-01
Lubiprostone is a chloride (Cl(-)) channel activator derived from prostaglandin E1 and used for managing constipation. In addition, lubiprostone affects the activity of gastrointestinal smooth muscles. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow-wave activity in smooth muscles. We studied the effects of lubiprostone on the pacemaker potentials of colonic ICCs. We used the whole-cell patch-clamp technique to determine the pacemaker activity in cultured colonic ICCs obtained from mice. Lubiprostone hyperpolarized the membrane and inhibited the generation of pacemaker potentials. Prostanoid EP1, EP2, EP3, and EP4 antagonists (SC-19220, PF-04418948, 6-methoxypyridine-2-boronc acid N-phenyldiethanolamine ester, and GW627368, respectively) did not block the response to lubiprostone. L-NG-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) did not block the response to lubiprostone. In addition, tetraethylammonium (TEA, a voltage-dependent potassium [K(+)] channel blocker) and apamin (a calcium [Ca(2+)]-dependent K(+) channel blocker) did not block the response to lubiprostone. However, glibenclamide (an ATP-sensitive K(+) channel blocker) blocked the response to lubiprostone. Similar to lubiprostone, pinacidil (an opener of ATP-sensitive K(+) channel) hyperpolarized the membrane and inhibited the generation of pacemaker potentials, and these effects were inhibited by glibenclamide. These results suggest that lubiprostone can modulate the pacemaker potentials of colonic ICCs via activation of ATP-sensitive K(+) channel through a prostanoid EP receptor-independent mechanism.
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Effects of Lubiprostone on Pacemaker Activity of Interstitial Cells of Cajal from the Mouse Colon
Jiao, Han-Yi; Kim, Dong Hyun; Ki, Jung Suk; Ryu, Kwon Ho; Choi, Seok
2014-01-01
Lubiprostone is a chloride (Cl-) channel activator derived from prostaglandin E1 and used for managing constipation. In addition, lubiprostone affects the activity of gastrointestinal smooth muscles. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow-wave activity in smooth muscles. We studied the effects of lubiprostone on the pacemaker potentials of colonic ICCs. We used the whole-cell patch-clamp technique to determine the pacemaker activity in cultured colonic ICCs obtained from mice. Lubiprostone hyperpolarized the membrane and inhibited the generation of pacemaker potentials. Prostanoid EP1, EP2, EP3, and EP4 antagonists (SC-19220, PF-04418948, 6-methoxypyridine-2-boronc acid N-phenyldiethanolamine ester, and GW627368, respectively) did not block the response to lubiprostone. L-NG-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) did not block the response to lubiprostone. In addition, tetraethylammonium (TEA, a voltage-dependent potassium [K+] channel blocker) and apamin (a calcium [Ca2+]-dependent K+ channel blocker) did not block the response to lubiprostone. However, glibenclamide (an ATP-sensitive K+ channel blocker) blocked the response to lubiprostone. Similar to lubiprostone, pinacidil (an opener of ATP-sensitive K+ channel) hyperpolarized the membrane and inhibited the generation of pacemaker potentials, and these effects were inhibited by glibenclamide. These results suggest that lubiprostone can modulate the pacemaker potentials of colonic ICCs via activation of ATP-sensitive K+ channel through a prostanoid EP receptor-independent mechanism. PMID:25177167
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De Gaetano, Francesco; Serrani, Marta; Bagnoli, Paola; Brubert, Jacob; Stasiak, Joanna; Moggridge, Geoff D.; Costantino, Maria Laura
2016-01-01
Introduction Only mechanical and biological heart valve prostheses are currently commercially available. The former show longer durability but require anticoagulant therapy, the latter display better fluid dynamic behaviour but do not have adequate durability. New Polymeric Heart Valves (PHVs) could potentially combine the haemodynamic properties of biological valves with the durability of mechanical valves. This work presents a hydrodynamic evaluation of two groups of newly developed supra-annular tri-leaflet prosthetic heart valves made from styrenic block copolymers (SBC): Poli-Valves. Methods Two types of Poli-Valves made of SBC differing in polystyrene fraction content were tested under continuous and pulsatile flow conditions as prescribed by ISO 5840 Standard. An ad - hoc designed pulse duplicator allowed the valve prototypes to be tested at different flow rates and frequencies. Pressure and flow were recorded; pressure drops, effective orifice area (EOA), and regurgitant volume were computed to assess the valve’s behaviour. Results Both types Poli-Valves met the minimum requirements in terms of regurgitation and EOA as specified by ISO 5840 Standard. Results were compared with five mechanical heart valves (MHVs) and five tissue heart valves (THVs), currently available on the market. Conclusion Based on these results, polymeric heart valves based on styrenic block copolymers, as Poli-Valves are, can be considered as promising alternative for heart valve replacement in near future. PMID:26689146
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De Gaetano, Francesco; Serrani, Marta; Bagnoli, Paola; Brubert, Jacob; Stasiak, Joanna; Moggridge, Geoff D; Costantino, Maria Laura
2015-11-01
Only mechanical and biological heart valve prostheses are currently commercially available. The former show longer durability but require anticoagulant therapy; the latter display better fluid dynamic behavior but do not have adequate durability. New Polymeric Heart Valves (PHVs) could potentially combine the hemodynamic properties of biological valves with the durability of mechanical valves. This work presents a hydrodynamic evaluation of 2 groups of newly developed supra-annular, trileaflet prosthetic heart valves made from styrenic block copolymers (SBC): Poli-Valves. 2 types of Poli-Valves made of SBC and differing in polystyrene fraction content were tested under continuous and pulsatile flow conditions as prescribed by ISO 5840 Standard. A pulse duplicator designed ad hoc allowed the valve prototypes to be tested at different flow rates and frequencies. Pressure and flow were recorded; pressure drops, effective orifice area (EOA), and regurgitant volume were computed to assess the behavior of the valve. Both types of Poli-Valves met the minimum requirements in terms of regurgitation and EOA as specified by the ISO 5840 Standard. Results were compared with 5 mechanical heart valves (MHVs) and 5 tissue heart valves (THVs), currently available on the market. Based on these results, PHVs based on styrenic block copolymers, as are Poli-Valves, can be considered a promising alternative for heart valve replacement in the near future.
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Low energy high pressure miniature screw valve
Fischer, Gary J [Sandia Park, NM; Spletzer, Barry L [Albuquerque, NM
2006-12-12
A low energy high pressure screw valve having a valve body having an upper portion and a lower portion, said lower portion of said valve body defining an inlet flow passage and an outlet flow passage traversing said valve body to a valve seat, said upper portion of said valve body defining a cavity at said valve seat, a diaphragm restricting flow between said upper portion of said valve body and said lower portion, said diaphragm capable of engaging said valve seat to restrict fluid communication between said inlet passage and said outlet passage, a plunger within said cavity supporting said diaphragm, said plunger being capable of engaging said diaphragm with said valve seat at said inlet and outlet fluid passages, said plunger being in point contact with a drive screw having threads engaged with opposing threads within said upper portion of said valve body such engagement allowing motion of said drive screw within said valve body.
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Mitral valve surgery - minimally invasive
... flow. Your valve has developed an infection (infectious endocarditis). You have severe mitral valve prolapse that is ... function. Damage to your heart valve from infection (endocarditis). A minimally invasive procedure has many benefits. There ...
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Code of Federal Regulations, 2010 CFR
2010-10-01
... PIPELINE Design Requirements § 195.116 Valves. Each valve installed in a pipeline system must comply with the following: (a) The valve must be of a sound engineering design. (b) Materials subject to the...
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So, Keum Young; Kim, Sang Hun; Sohn, Hong Moon; Choi, Soo Jin; Parajuli, Shankar Prasad; Choi, Seok; Yeum, Cheol Ho; Yoon, Pyung Jin; Jun, Jae Yeoul
2009-05-31
We studied the effect of carbachol on pacemaker currents in cultured interstitial cells of Cajal (ICC) from the mouse small intestine by muscarinic stimulation using a whole cell patch clamp technique and Ca2+-imaging. ICC generated periodic pacemaker potentials in the current-clamp mode and generated spontaneous inward pacemaker currents at a holding potential of-70 mV. Exposure to carbachol depolarized the membrane and produced tonic inward pacemaker currents with a decrease in the frequency and amplitude of the pacemaker currents. The effects of carbachol were blocked by 1-dimethyl-4-diphenylacetoxypiperidinium, a muscarinic M(3) receptor antagonist, but not by methotramine, a muscarinic M(2) receptor antagonist. Intracellular GDP-beta-S suppressed the carbachol-induced effects. Carbachol-induced effects were blocked by external Na+-free solution and by flufenamic acid, a non-selective cation channel blocker, and in the presence of thapsigargin, a Ca2+-ATPase inhibitor in the endoplasmic reticulum. However, carbachol still produced tonic inward pacemaker currents with the removal of external Ca2+. In recording of intracellular Ca2+ concentrations using fluo 3-AM dye, carbachol increased intracellular Ca2+ concentrations with increasing of Ca2+ oscillations. These results suggest that carbachol modulates the pacemaker activity of ICC through the activation of non-selective cation channels via muscarinic M(3) receptors by a G-protein dependent intracellular Ca2+ release mechanism.
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Solenoid valve performance characteristics studied
NASA Technical Reports Server (NTRS)
Abe, J. T.; Blackburn, S.
1970-01-01
Current and voltage waveforms of a solenoid coil are recorded as the valve opens and closes. Analysis of the waveforms with respect to time and the phase of the valve cycle accurately describes valve performance.
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100. INTERIOR OF SKID 9A: VENT VALVE AND RELIEF VALVE ...
100. INTERIOR OF SKID 9A: VENT VALVE AND RELIEF VALVE FOR RAPID-LOAD LIQUID OXYGEN TANK - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA
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Thermostatic Valves Containing Silicone-Oil Actuators
NASA Technical Reports Server (NTRS)
Bhandari, Pradeep; Birur, Gajanana C.; Bame, David P.; Karlmann, Paul B.; Prina, Mauro; Young, William; Fisher, Richard
2009-01-01
Flow-splitting and flow-mixing thermally actuated spool valves have been developed for controlling flows of a heat-transfer fluid in a temperature-regulation system aboard the Mars Science Laboratory (MSL) rover. Valves like these could also be useful in terrestrial temperature-regulation systems, including automobile air-conditioning systems and general refrigeration systems. These valves are required to provide smoother actuation over a wider temperature range than the flow-splitting, thermally actuated spool valves used in the Mars Explorer Rover (MER). Also, whereas the MER valves are unstable (tending to oscillate) in certain transition temperature ranges, these valves are required not to oscillate. The MER valves are actuated by thermal expansion of a wax against spring-loaded piston rods (as in common automotive thermostats). The MSL valves contain similar actuators that utilize thermal expansion of a silicone oil, because silicone-oil actuators were found to afford greater and more nearly linear displacements, needed for smoother actuation, over the required wider temperature range. The MSL valves also feature improved spool designs that reflect greater understanding of fluid dynamics, consideration of pressure drops in valves, and a requirement for balancing of pressures in different flow branches.
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Brain interstitial fluid TNF-α after subarachnoid hemorrhage
Hanafy, Khalid A.; Grobelny, Bartosz; Fernandez, Luis; Kurtz, Pedro; Connolly, ES; Mayer, Stephan A.; Schindler, Christian; Badjatia, Neeraj
2010-01-01
Objective: TNF-α is an inflammatory cytokine that plays a central role in promoting the cascade of events leading to an inflammatory response. Recent studies have suggested that TNF-α may play a key role in the formation and rupture of cerebral aneurysms, and that the underlying cerebral inflammatory response is a major determinate of outcome following subrarachnoid hemorrhage (SAH). Methods: We studied 14 comatose SAH patients who underwent multimodality neuromonitoring with intracranial pressure (ICP) and cerebral microdialysis as part of their clinical care. Continuous physiological variables were time-locked every 8 hours and recorded at the same point that brain interstitial fluid TNF-α was measured in brain microdialysis samples. Significant associations were determined using generalized estimation equations. Results: Each patient had a mean of 9 brain tissue TNF-α measurements obtained over an average of 72 hours of monitoring. TNF-α levels rose progressively over time. Predictors of elevated brain interstitial TNF-α included higher brain interstitial fluid glucose levels (β=0.066, P<0.02), intraventricular hemorrhage (β=0.085, P<0.021), and aneurysm size >6 mm (β=0.14, p<0.001). There was no relationship between TNF-α levels and the burden of cisternal SAH; concurrent measurements of serum glucose, or lactate-pyruvate ratio. Interpretation: Brain interstitial TNF-α levels are elevated after SAH, and are associated with large aneurysm size, the burden of intraventricular blood, and elevation brain interstitial glucose levels. PMID:20110094
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Options for Heart Valve Replacement
... which may include human or animal donor tissue) Ross Procedure — “Borrowing” your healthy valve and moving it ... Considerations for Surgery Medications Valve Repair Valve Replacement - Ross Procedure - Newer Surgery Options - What is TAVR? - Types ...
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Damage-Free Relief-Valve Disassembly
NASA Technical Reports Server (NTRS)
Haselmaier, H.
1986-01-01
Tool safely disassembles relief valves without damage to sensitive parts. Relief-valve disassembly tool used to extract valve nozzle from its housing. Holding device on tool grops nozzle. When user strikes hammer against impact disk, holding device pulls nozzle from press fit. Previously, nozzle dislodged by striking spindle above it, but practice often damaged retaining screw. New tool removes nozzle directly. With minor modifications, tool adapted to valves from different manufacturers.
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Transcatheter mitral valve repair in osteogenesis imperfecta associated mitral valve regurgitation.
van der Kley, Frank; Delgado, Victoria; Ajmone Marsan, Nina; Schalij, Martin J
2014-08-01
Osteogenesis imperfecta is associated with increased prevalence of significant mitral valve regurgitation. Surgical mitral valve repair and replacement are feasible but are associated with increased risk of bleeding and dehiscence of implanted valves may occur more frequently. The present case report describes the outcomes of transcatheter mitral valve repair in a patient with osteogenesis imperfecta. A 60 year-old patient with osteogenesis imperfecta and associated symptomatic moderate to severe mitral regurgitation underwent transthoracic echocardiography which showed a nondilated left ventricle with preserved systolic function and moderate to severe mitral regurgitation. On transoesophageal echocardiography the regurgitant jet originated between the anterolateral scallops of the anterior and posterior leaflets (A1-P1). Considering the comorbidities associated with osteogenesis imperfecta the patient was accepted for transcatheter mitral valve repair using the Mitraclip device (Abbott vascular, Menlo, CA). Under fluoroscopy and 3D transoesophageal echocardiography guidance, a Mitraclip device was implanted between the anterolateral and central scallops with significant reduction of mitral regurgitation. The postoperative evolution was uneventful. At one month follow-up, transthoracic echocardiography showed a stable position of the Mitraclip device with no mitral regurgitation. Transcatheter mitral valve repair is feasible and safe in patients with osteogenesis imperfecta and associated symptomatic significant mitral regurgitation. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
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Aortic valve replacement for papillary fibroelastoma.
Arikan, Ali Ahmet; Omay, Oğuz; Aydın, Fatih; Kanko, Muhip; Gür, Sibel; Derviş, Emir; Yılmaz, Cansu Eda; Müezzinoğlu, Bahar
2017-06-01
Surgery is indicated for symptomatic patients with papillary fibroelastomas (PFE) on the aortic valve. The valve is commonly spared during tumor excision. Rarely, aortic valve replacement (AVR) is needed. We present a case requiring AVR for an aortic valve PFE and review the literature to determine the risk factors for failure of aortic valve-sparing techniques in patients with PFE. © 2017 Wiley Periodicals, Inc.
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46 CFR 56.20-9 - Valve construction.
Code of Federal Regulations, 2011 CFR
2011-10-01
...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...
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46 CFR 56.20-9 - Valve construction.
Code of Federal Regulations, 2013 CFR
2013-10-01
...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...
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46 CFR 56.20-9 - Valve construction.
Code of Federal Regulations, 2012 CFR
2012-10-01
...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...
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46 CFR 56.20-9 - Valve construction.
Code of Federal Regulations, 2014 CFR
2014-10-01
...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...
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Palestini, Paola; Calvi, Chiara; Conforti, Elena; Daffara, Rossella; Botto, Laura; Miserocchi, Giuseppe
2003-10-01
We evaluated in anesthetized rabbits the compositional changes of plasmalemmal lipid microdomains from lung tissue samples after inducing pulmonary interstitial edema (0.5 ml/kg for 3 h, leading to approximately 5% increase in extravascular water). Lipid microdomains (lipid rafts and caveolae) were present in the detergent-resistant fraction (DRF) obtained after discontinuous sucrose density gradient. DRF was enriched in caveolin-1, flotillin, aquaporin-1, GM1, cholesterol, sphingomyelin, and phosphatidylserine, and their contents significantly increased in interstitial edema. The higher DRF content in caveolin, flotillin, and aquaporin-1 and of the ganglioside GM1 suggests an increase both in caveolar domains and in lipid rafts, respectively. Compositional changes could be ascribed to endothelial and epithelial cells that provide most of plasma membrane surface area in the air-blood barrier. Alterations in lipid components in the plasma membrane may reflect rearrangement of floating lipid platforms within the membrane and/or lipid translocation from intracellular stores. Lipid traffic could be stimulated by the marked increase in hydraulic interstitial pressure after initial water accumulation, from approximately -10 to 5 cmH2O, due to the low compliance of the pulmonary tissue, in particular in the basement membranes and in the interfibrillar substance. Compositional changes in lipid microdomains represent a sign of cellular activation and suggest the potential role of mechanotransduction in response to developing interstitial edema.
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Inverse spin-valve effect in nanoscale Si-based spin-valve devices
NASA Astrophysics Data System (ADS)
Hiep, Duong Dinh; Tanaka, Masaaki; Hai, Pham Nam
2017-12-01
We investigated the spin-valve effect in nano-scale silicon (Si)-based spin-valve devices using a Fe/MgO/Ge spin injector/detector deposited on Si by molecular beam epitaxy. For a device with a 20 nm Si channel, we observed clear magnetoresistance up to 3% at low temperature when a magnetic field was applied in the film plane along the Si channel transport direction. A large spin-dependent output voltage of 20 mV was observed at a bias voltage of 0.9 V at 15 K, which is among the highest values in lateral spin-valve devices reported so far. Furthermore, we observed that the sign of the spin-valve effect is reversed at low temperatures, suggesting the possibility of a spin-blockade effect of defect states in the MgO/Ge tunneling barrier.
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Valve malfunction detection apparatus
NASA Astrophysics Data System (ADS)
Burley, Richard K.
1993-07-01
A detection system is provided for sensing a malfunction of a valve having an outlet connected to an end of a first pipe through which pressurized fluid may be flowed in a downstream direction away from the valve. The system includes a bypass pipe connected at its opposite ends to the first pipe and operative to bypass a portion of the fluid flow therethrough around a predetermined section thereof. A housing is interiorly divided by a flexible diaphragm into first and second opposite chambers which are respectively communicated with the first pipe section and the bypass pipe, the diaphragm being spring-biased toward the second chamber. The diaphragm housing cooperates with check valves and orifices connected in the two pipes to create and maintain a negative pressure in the first pipe section in response to closure of the valve during pressurized flow through the first pipe. A pressure switch senses the negative pressure and transmits a signal indicative thereof to a computer. Upon cessation of the signal while the valve is still closed, the computer responsively generates a signal indicating that the valve, or another portion of the detection system, is leaking.
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Valve malfunction detection apparatus
NASA Technical Reports Server (NTRS)
Burley, Richard K. (Inventor)
1993-01-01
A detection system is provided for sensing a malfunction of a valve having an outlet connected to an end of a first pipe through which pressurized fluid may be flowed in a downstream direction away from the valve. The system includes a bypass pipe connected at its opposite ends to the first pipe and operative to bypass a portion of the fluid flow therethrough around a predetermined section thereof. A housing is interiorly divided by a flexible diaphragm into first and second opposite chambers which are respectively communicated with the first pipe section and the bypass pipe, the diaphragm being spring-biased toward the second chamber. The diaphragm housing cooperates with check valves and orifices connected in the two pipes to create and maintain a negative pressure in the first pipe section in response to closure of the valve during pressurized flow through the first pipe. A pressure switch senses the negative pressure and transmits a signal indicative thereof to a computer. Upon cessation of the signal while the valve is still closed, the computer responsively generates a signal indicating that the valve, or another portion of the detection system, is leaking.
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The effect of lymphatic valve morphology on fluid transport
NASA Astrophysics Data System (ADS)
Alexeev, Alexander; Ballard, Matthew; Nepiyushchikh, Zhanna; Dixon, Brandon
2016-11-01
The lymphatic vasculature is present in nearly all invertebrate tissue, and is essential in the transport of fluid and particles such as immune cells, antigens, proteins and lipids from the tissue to lymph nodes and to the venous circulation. Lymphatic vessels are made of up a series of contractile units that work together in harmony as "micro hearts" to pump fluid against a pressure gradient. Lymphatic valves are critical to this functionality, as they open and close with the oscillating pressure gradients from contractions, thus allowing flow in only one direction and leading to a net pumping effect. We use a hybrid lattice-Boltzmann lattice spring model which captures fluid-solid interactions through two-way coupling between a viscous fluid and lymphatic valves in a section of a lymphatic vessel to study the dynamics of lymphatic valves and their effect on fluid transport. Further, we investigate the effect of variations in valve geometry and material properties on fluid pumping. This work helps to increase our understanding of the mechanisms of lymphatic fluid transport, which has implications in a variety of pathologies, including cancer metastasis, autoimmunity, atherosclerosis and obesity. Support from NSF CMMI 1635133 is gratefully acknowledged.
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Electro-Mechanical Coaxial Valve
NASA Technical Reports Server (NTRS)
Patterson, Paul R (Inventor)
2004-01-01
Coaxial valves usually contain only one moving part. It has not been easy, then, to provide for electric motor actuation. Many actuators being proposed involve designs which lead to bulky packages. The key facing those improving coaxial valves is the provision of suitable linear actuation. The valve herein indudes a valve housing with a flow channel there-through. Arranged in the flow channel is a closing body. In alignment with the closing body is a ball screw actuator which includes a ball nut and a cylindrical screw. The ball nut sounds a threaded portion of the cylindrical screw. The cylindrical screw is provided with a passageway there-through through which fluid flows. The cylindrical screw is disposed in the flow channel to become a control tube adapted to move toward and away from the valve seat. To rotate the ball nut an actuating drive is employed driven by a stepper motor.
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Valve for controlling solids flow
Feldman, David K.
1980-01-01
A fluidized solids control valve is disclosed that is particularly well adapted for use with a flow of coal or char that includes both large particles and fines. The particles may or may not be fluidized at various times during the operation. The valve includes a tubular body that terminates in a valve seat covered by a normally closed closure plate. The valve body at the seat and the closure plate is provided with aligned longitudinal slots that receive a pivotally supported key plate. The key plate is positionable by an operator in inserted, intermediate and retracted positions respecting the longitudinal slot in the valve body. The key plate normally closes the slot within the closure plate but is shaped and aligned obliquely to the longitudinal slot within the valve body to provide progressively increasing slot openings between the inserted and retracted positions. Transfer members are provided between the operator, key plate and closure plate to move the closure plate into an open position only when the key plate is retracted from the longitudinal slot within the valve body.
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Optothermally actuated capillary burst valve
NASA Astrophysics Data System (ADS)
Eriksen, Johan; Bilenberg, Brian; Kristensen, Anders; Marie, Rodolphe
2017-04-01
We demonstrate the optothermal actuation of individual capillary burst valves in an all-polymer microfluidic device. The capillary burst valves are realised in a planar design by introducing a fluidic constriction in a microfluidic channel of constant depth. We show that a capillary burst valve can be burst by raising the temperature due to the temperature dependence of the fluid surface tension. We address individual valves by using a local heating platform based on a thin film of near infrared absorber dye embedded in the lid used to seal the microfluidic device [L. H. Thamdrup et al., Nano Lett. 10, 826-832 (2010)]. An individual valve is burst by focusing the laser in its vicinity. We demonstrate the capture of single polystyrene 7 μm beads in the constriction triggered by the bursting of the valve.
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SLM Produced Hermetically Sealed Isolation Valve
NASA Technical Reports Server (NTRS)
Richard, James
2014-01-01
Marshall Space Flight Center (MSFC) has developed a valve concept to replace traditional pyrotechnic-driven isolation valves. This paper will describe the valve design and development process. The valve design uses a stem/wedge to support a disk inside the valve. That disk hermetically seals the pressurized fluids. A release mechanism holds the stem/wedge and a large spring in place. When required to open, a solenoid is energized and pulls the release mechanism allowing the spring to pull the stem/wedge away from the disk. Now the disk is unsupported and the pressure ruptures the disk allowing flow to the outlet of the valve. This paper will provide details of this design, describe the development testing, and show the results from the valve level tests performed. Also, a trade study is presented to show the advantages of this design to a conventional pyrotechnic-based valve.
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SLM Produced Hermetically Sealed Isolation Valve
NASA Technical Reports Server (NTRS)
Richard, James A.
2014-01-01
Marshall Space Flight Center (MSFC) has developed a valve concept to replace traditional pyrotechnic driven isolation valves. This paper will describe the valve design and development process. The valve design uses a stem/wedge to support a disk inside the valve. That disk hermetically seals the pressurized fluids. A release mechanism holds the stem/wedge and a large spring in place. When required to open, a solenoid is energized and pulls the release mechanism allowing the spring to pull the stem/wedge away from the disk. Now the disk is unsupported and the pressure ruptures the disk allowing flow to the outlet of the valve. This paper will provide details of this design, describe the development testing, and show the results from the valve level tests performed. Also, a trade study is presented to show the advantages of this design to a conventional pyrotechnic based valve.
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Brun, Klaus; Gernentz, Ryan S.
2010-07-27
A method and system for fine-tuning the motion of suction or discharge valves associated with cylinders of a reciprocating gas compressor, such as the large compressors used for natural gas transmission. The valve's primary driving force is conventional, but the valve also uses an electromagnetic coil to sense position of the plate (or other plugging element) and to provide an opposing force prior to impact.
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Mitral valve-sparing procedures and prosthetic heart valve failure: A case report
Khan, Nasir A; Butany, Jagdish; Leong, Shaun W; Rao, Vivek; Cusimano, Robert J; Ross, Heather J
2009-01-01
Prosthetic heart valve dysfunction due to thrombus or pannus formation can be a life-threatening complication. The present report describes a 47-year-old woman who developed valvular cardiomyopathy after chorda-sparing mitral valve replacement, and subsequently underwent heart transplantation for progressive heart failure. The explanted mitral valve prosthesis showed significant thrombus and pannus leading to reduced leaflet mobility and valvular stenosis. The present report illustrates the role of the subvalvular apparatus and pannus in prosthesis dysfunction. PMID:19279993
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Edemagenic gain and interstitial fluid volume regulation.
Dongaonkar, R M; Quick, C M; Stewart, R H; Drake, R E; Cox, C S; Laine, G A
2008-02-01
Under physiological conditions, interstitial fluid volume is tightly regulated by balancing microvascular filtration and lymphatic return to the central venous circulation. Even though microvascular filtration and lymphatic return are governed by conservation of mass, their interaction can result in exceedingly complex behavior. Without making simplifying assumptions, investigators must solve the fluid balance equations numerically, which limits the generality of the results. We thus made critical simplifying assumptions to develop a simple solution to the standard fluid balance equations that is expressed as an algebraic formula. Using a classical approach to describe systems with negative feedback, we formulated our solution as a "gain" relating the change in interstitial fluid volume to a change in effective microvascular driving pressure. The resulting "edemagenic gain" is a function of microvascular filtration coefficient (K(f)), effective lymphatic resistance (R(L)), and interstitial compliance (C). This formulation suggests two types of gain: "multivariate" dependent on C, R(L), and K(f), and "compliance-dominated" approximately equal to C. The latter forms a basis of a novel method to estimate C without measuring interstitial fluid pressure. Data from ovine experiments illustrate how edemagenic gain is altered with pulmonary edema induced by venous hypertension, histamine, and endotoxin. Reformulation of the classical equations governing fluid balance in terms of edemagenic gain thus yields new insight into the factors affecting an organ's susceptibility to edema.
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NASA Technical Reports Server (NTRS)
1973-01-01
The development of and operational programs for effective use in design are presented for liquid rocket pressure regulators, relief valves, check valves, burst disks, and explosive valves. A review of the total design problem is presented, and design elements are identified which are involved in successful design. Current technology pertaining to these elements is also described. Design criteria are presented which state what rule or standard must be imposed on each essential design element to assure successful design. These criteria serve as a checklist of rules for a project manager to use in guiding a design or in assessing its adequacy. Recommended practices are included which state how to satisfy each of the criteria.
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Simple Check Valves for Microfluidic Devices
NASA Technical Reports Server (NTRS)
Willis, Peter A.; Greer, Harold F.; Smith, J. Anthony
2010-01-01
A simple design concept for check valves has been adopted for microfluidic devices that consist mostly of (1) deformable fluorocarbon polymer membranes sandwiched between (2) borosilicate float glass wafers into which channels, valve seats, and holes have been etched. The first microfluidic devices in which these check valves are intended to be used are micro-capillary electrophoresis (microCE) devices undergoing development for use on Mars in detecting compounds indicative of life. In this application, it will be necessary to store some liquid samples in reservoirs in the devices for subsequent laboratory analysis, and check valves are needed to prevent cross-contamination of the samples. The simple check-valve design concept is also applicable to other microfluidic devices and to fluidic devices in general. These check valves are simplified microscopic versions of conventional rubber- flap check valves that are parts of numerous industrial and consumer products. These check valves are fabricated, not as separate components, but as integral parts of microfluidic devices. A check valve according to this concept consists of suitably shaped portions of a deformable membrane and the two glass wafers between which the membrane is sandwiched (see figure). The valve flap is formed by making an approximately semicircular cut in the membrane. The flap is centered over a hole in the lower glass wafer, through which hole the liquid in question is intended to flow upward into a wider hole, channel, or reservoir in the upper glass wafer. The radius of the cut exceeds the radius of the hole by an amount large enough to prevent settling of the flap into the hole. As in a conventional rubber-flap check valve, back pressure in the liquid pushes the flap against the valve seat (in this case, the valve seat is the adjacent surface of the lower glass wafer), thereby forming a seal that prevents backflow.
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Wong, Sui-To; Wen, Eleanor; Fong, Dawson
2013-08-01
Malfunction of a Codman Hakim programmable valve due to jamming of its programmable component may necessitate shunt revision. The authors report a method for programming jammed Codman Hakim programmable valves by using a Strata II magnet and additional neodymium magnets. The programming method was derived after studying a jammed valve in the laboratory that was explanted from an 10-year-old boy with a history of fourth ventricle ependymoma. Programming the explanted valve with a Codman programmer failed, but rotating a Strata II magnet above the valve resulted in rotation of the spiral cam in the valve. It was found that the Strata II magnet could be used to program the jammed valve by rotating the magnet 90° or multiples of 90° above the valve. The strength of the magnetic field of the Strata II magnet was able to be increased by putting neodymium magnets on it. The programming method was then successfully used in a patient with a jammed Codman Hakim programmable valve. After successful programming using this method, clinical and radiological follow-up of the patient was advised.
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Alskaf, Ebraham; McConkey, Hannah; Laskar, Nabila; Kardos, Attila
2016-06-20
The Medtronic ATS Open Pivot mechanical valve has been successfully used in heart valve surgery for more than two decades. We present the case of a patient who, 19 years following a tricuspid valve replacement with an ATS prosthesis as part of a triple valve operation following infective endocarditis, developed severe tricuspid regurgitation due to pannus formation.
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Darwazah, Ahmad K
2012-06-29
Prosthetic valve dysfunction at aortic position is commonly caused by pannus formation. The exact etiology is not known. It arises from ventricular aspect of the prosthesis encroaching its leaflets causing stenosis or it may remain localized causing left ventricular outflow tract obstruction without affecting valve function.The difference in location entails different approaches in management. Such a pathology requires surgical excision of the pannus with or without valve re-replacement.A recurrent pannus was observed in a female patient who needed repeated surgical intervention to excise a localized pannus without re-replacement of a well functioning prosthetic valve.Management of our case presents several questions, whether recurrence of pannus is caused by sparing the prosthetic valve, is it simply an exaggeration of an inflammatory healing process in certain individuals or is it ideal to re-replace the valve despite a well preserved function.
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Analysis of Complex Valve and Feed Systems
NASA Technical Reports Server (NTRS)
Ahuja, Vineet; Hosangadi, Ashvin; Shipman, Jeremy; Cavallo, Peter; Dash, Sanford
2007-01-01
A numerical framework for analysis of complex valve systems supports testing of propulsive systems by simulating key valve and control system components in the test loop. In particular, it is designed to enhance the analysis capability in terms of identifying system transients and quantifying the valve response to these transients. This system has analysis capability for simulating valve motion in complex systems operating in diverse flow regimes ranging from compressible gases to cryogenic liquids. A key feature is the hybrid, unstructured framework with sub-models for grid movement and phase change including cryogenic cavitations. The multi-element unstructured framework offers improved predictions of valve performance characteristics under steady conditions for structurally complex valves such as pressure regulator valve. Unsteady simulations of valve motion using this computational approach have been carried out for various valves in operation at Stennis Space Center such as the split-body valve and the 10-in. (approx.25.4-cm) LOX (liquid oxygen) valve and the 4-in. (approx.10 cm) Y-pattern valve (liquid nitrogen). Such simulations make use of variable grid topologies, thereby permitting solution accuracy and resolving important flow physics in the seat region of the moving valve. An advantage to this software includes possible reduction in testing costs incurred due to disruptions relating to unexpected flow transients or functioning of valve/flow control systems. Prediction of the flow anomalies leading to system vibrations, flow resonance, and valve stall can help in valve scheduling and significantly reduce the need for activation tests. This framework has been evaluated for its ability to predict performance metrics like flow coefficient for cavitating venturis and valve coefficient curves, and could be a valuable tool in predicting and understanding anomalous behavior of system components at rocket propulsion testing and design sites.
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Architecture of interstitial nodal spaces in the rodent renal inner medulla.
Gilbert, Rebecca L; Pannabecker, Thomas L
2013-09-01
Every collecting duct (CD) of the rat inner medulla is uniformly surrounded by about four abutting ascending vasa recta (AVR) running parallel to it. One or two ascending thin limbs (ATLs) lie between and parallel to each abutting AVR pair, opposite the CD. These structures form boundaries of axially running interstitial compartments. Viewed in transverse sections, these compartments appear as four interstitial nodal spaces (INSs) positioned symmetrically around each CD. The axially running compartments are segmented by interstitial cells spaced at regular intervals. The pairing of ATLs and CDs bounded by an abundant supply of AVR carrying reabsorbed water, NaCl, and urea make a strong argument that the mixing of NaCl and urea within the INSs and countercurrent flows play a critical role in generating the inner medullary osmotic gradient. The results of this study fully support that hypothesis. We quantified interactions of all structures comprising INSs along the corticopapillary axis for two rodent species, the Munich-Wistar rat and the kangaroo rat. The results showed remarkable similarities in the configurations of INSs, suggesting that the structural arrangement of INSs is a highly conserved architecture that plays a fundamental role in renal function. The number density of INSs along the corticopapillary axis directly correlated with a loop population that declines exponentially with distance below the outer medullary-inner medullary boundary. The axial configurations were consistent with discrete association between near-bend loop segments and INSs and with upper loop segments lying distant from INSs.
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High speed exhaust gas recirculation valve
Fensom, Rod; Kidder, David J.
2005-01-18
In order to minimize pollutants such as Nox, internal combustion engines typically include an exhaust gas recirculation (EGR) valve that can be used to redirect a portion of exhaust gases to an intake conduit, such as an intake manifold, so that the redirected exhaust gases will be recycled. It is desirable to have an EGR valve with fast-acting capabilities, and it is also desirable to have the EGR valve take up as little space as possible. An exhaust gas recirculation valve is provided that includes an exhaust passage tube, a valve element pivotally mounted within the exhaust passage tube, a linear actuator; and a gear train. The gear train includes a rack gear operatively connected to the linear actuator, and at least one rotatable gear meshing with the rack gear and operatively connected to the valve element to cause rotation of the valve element upon actuation of the linear actuator. The apparatus provides a highly compact package having a high-speed valve actuation capability.
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Boudjemline, Younes
2018-01-01
To describe a new modification, the one-step procedure, that allows interventionists to pre-stent and implant a Melody valve simultaneously. Percutaneous pulmonary valve implantation (PPVI) is the standard of care for managing patients with dysfunctional right ventricular outflow tract, and the approach is standardized. Patients undergoing PPVI using the one-step procedure were identified in our database. Procedural data and radiation exposure were compared to those in a matched group of patients who underwent PPVI using the conventional two-step procedure. Between January 2016 and January 2017, PPVI was performed in 27 patients (median age/range, 19.1/10-55 years) using the one-step procedure involving manual crimping of one to three bare metal stents over the Melody valve. The stent and Melody valve were delivered successfully using the Ensemble delivery system. No complications occurred. All patients had excellent hemodynamic results (median/range post-PPVI right ventricular to pulmonary artery gradient, 9/0-20 mmHg). Valve function was excellent. Median procedural and fluoroscopic times were 56 and 10.2 min, respectively, which significantly differed from those of the two-step procedure group. Similarly, the dose area product (DAP), and radiation time were statistically lower in the one-step group than in the two-step group (P < 0.001 for all variables). After a median follow-up of 8 months (range, 3-14.7), no patient underwent reintervention, and no device dysfunction was observed. The one-step procedure is a safe modification that allows interventionists to prestent and implants the Melody valve simultaneously. It significantly reduces procedural and fluoroscopic times, and radiation exposure. © 2017 Wiley Periodicals, Inc.
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Interstitial Fluid Flow and Drug Delivery in Vascularized Tumors: A Computational Model
Welter, Michael; Rieger, Heiko
2013-01-01
Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider–with the help of a theoretical model–the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various
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Interstitial fluid flow and drug delivery in vascularized tumors: a computational model.
Welter, Michael; Rieger, Heiko
2013-01-01
Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider-with the help of a theoretical model-the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various
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Moche, Jason A; Cohen, Justin C; Pearlman, Steven J
2013-07-01
The objective of this work was to explore the utility of axial computed tomography (CT) imaging to objectively define a narrow internal nasal valve, and compare those findings with clinical examination and patient complaint. Retrospective review from a single facial plastic surgery center. We reviewed 40 consecutive patients evaluated for either sinusitis or nasal airway obstruction for which a CT scan was obtained at a single radiology institution. Thirty-six complete office records were examined for the presence of clinical internal valve narrowing and complaints of nasal obstruction. In total, 72 internal nasal valves were analyzed using axial plane CT and measurements were compared to clinical findings and presence of airway obstruction. Measured valve areas for clinically normal internal nasal valves averaged 0.47 cm(2) vs 0.28 cm(2) for clinically narrow valves, a decrease of 40.4%. In unobstructed nasal airways the valve area averaged 0.51 cm(2) vs 0.38 cm(2) in obstructed airways, a difference of 25.5%. A radiographically measured valve area of <0.30 cm(2) suggests clinical narrowing with a sensitivity of 71.4%, specificity of 88.9%, positive predictive value of 62.5%, and negative predictive value of 92.3%. Using standard axial CT imaging we describe an objective method of radiographically evaluating the nasal valve, demonstrating strong correlation with physical examination and patient complaint. Additionally, radiographic valve areas can be used to screen for clinically narrow nasal valves with good sensitivity and specificity, providing a novel straightforward method for nasal valve assessment. © 2012 ARS-AAOA, LLC.
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Mechanical valve replacement in congenital heart disease.
Fiane, A E; Lindberg, H L; Saatvedt, K; Svennevig, J L
1996-05-01
Mechanical valves are the prosthesis of choice in valve replacement in children. However, the problem of somatic growth leading to patient-valve mismatch remains present, and the appropriate anticoagulation regimen remains controversial. We present our experience of valve replacement in a young population over 20 years. Between 1972 and 1992, 48 patients (34 males and 14 females), mean age 11.2 years (range 0.4-27.4 years), underwent mechanical valve replacement at our institution. Aortic valve replacement was performed in 28 patients (58.3%), mitral valve replacement in 13 (27.1%), tricuspid valve replacement in six (12.5%) and pulmonary valve replacement in one patient (2.1%). The prostheses used were: St. Jude Medical (n = 2), Björk-Shiley (n = 14), Medtronic Hall (n = 16), Duromedics (n = 2) and CarboMedics (n = 14). Early mortality was 14.3%, 10.7% for aortic valve replacement and 30.8% for mitral valve replacement. Mean follow up for all patients was 8.3 years (range 0-22 years), with a total of 398 patient-years. Seven patients died during the follow up (17.1%). Survival after 10 years, including operative mortality, was 81% for aortic valve replacement, 33% for mitral valve replacement, 83% for tricuspid valve replacement and 100% for pulmonary valve replacement. All patients were anticoagulated with warfarin. In eight patients (16.7%) an antiplatelet drug (aspirin or dipyridamole) was added. Major events included paravalvular leak in six patients (1.5%/pty), valve thrombosis in five (mitral position in two, tricuspid in three) (1.3%/pty) and endocarditis in one patient (0.3%/pty). Minor thromboembolic events occurred in three patients (0.8%/pty) and minor hemorrhagic events in three (0.8%/pty). No patients developed hemolytic anemia and there was no case of structural failure. In our experience, mechanical prostheses in congenital heart disease were associated with significant morbidity and mortality, however long term survival after aortic valve
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Lee, Candice Y; Wong, Joshua K; Ross, Ronald E; Liu, David C; Khabbaz, Kamal R; Martellaro, Angelo J; Gorea, Heather R; Sauer, Jude S; Knight, Peter A
Prostheses attachment is critical in aortic valve replacement surgery, yet reliable prosthetic security remains a challenge. Accurate techniques to analyze prosthetic fixation pressures may enable the use of fewer sutures while reducing the risk of paravalvular leaks (PVL). Customized digital thin film pressure transducers were sutured between aortic annulus models and 21-mm bioprosthetic valves with 15 × 4-mm, 12 × 4-mm, or 9 × 6-mm-wide pledgeted mattress sutures. Simulating open and minimally invasive access, 4 surgeons, blinded to data acquisition, each secured 12 valves using manual knot-tying (hand-tied [HT] or knot-pusher [KP]) or automated titanium fasteners (TFs). Real-time pressure measurements and times were recorded. Two-dimensional (2D) and 3D pressure maps were generated for all valves. Pressures less than 80 mm Hg were considered at risk for PVL. Pressures under each knot (intrasuture) fell less than 80 mm Hg for 12 of 144 manual knots (5/144 HT, 7/144 KP) versus 0 of 288 TF (P < 0.001). Pressures outside adjacent sutures (extrasuture) were less than 80 mm Hg in 10 of 60 HT, zero of 60 KP, and zero of 120 TF sites for 15 × 4-mm valves; 17 of 48 HT, 25 of 48 KP, and 12 of 96 TF for 12 × 4-mm valves; and 15 of 36 HT, 17 of 36 KP, and 9 and 72 TF for 9 × 6-mm valves; P < 0.001 all manual versus TF. Annular areas with pressures less than 80 mm Hg ranged from 0% of the sewing-ring area (all open TF) to 31% (12 × 4 mm, KP). The average time per manual knot, 46 seconds (HT, 31 seconds; KP, 61 seconds), was greater than TF, 14 seconds (P < 0.005). Reduced operative times and PVL risk would fortify the advantages of surgical aortic valve replacement. This research encourages continued exploration of technical factors in optimizing prosthetic valve security.
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Investigations of lymphatic drainage from the interstitial space
NASA Astrophysics Data System (ADS)
Jayathungage Don, Tharanga; Richard Clarke Collaboration; John Cater Collaboration; Vinod Suresh Collaboration
2017-11-01
The lymphatic system is a highly complex biological system that facilitates the drainage of excess fluid in body tissues. In addition, it is an integral part of the immunological control system. Understanding the mechanisms of fluid absorption from the interstitial space and flow through the initial lymphatics is important to treat several pathological conditions. The main focus of this study is to computationally model the lymphatic drainage from the interstitial space. The model has been developed to consider a 3D lymphatic network and uses biological data to inform the creation of realistic geometries for the lymphatic capillary networks. We approximate the interstitial space as a porous region and the lymphatic vessel walls as permeable surfaces. The dynamics of the flow is approximated by Darcy's law in the interstitium and the Navier-Stokes equations in the lymphatic capillary lumen. The proposed model examines lymph drainage as a function of pressure gradient. In addition, we have examined the effects of interstitial and lymphatic wall permeabilities on the lymph drainage and the solute transportation in the model. The computational results are in accordance with the available experimental measurements.
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FLUID PRESSURE AND CAM OPERATED VACUUM VALVE
Batzer, T.H.
1963-11-26
An ultra-high vacuum valve that is bakable, reusable, and capable of being quickly opened and closed is described. A translationally movable valve gate having an annular ridge is adapted to contact an annular soft metal gasket disposed at the valve seat such that the soft metal gasket extends beyond the annular ridge on all sides. The valve gate is closed, by first laterally aligning the valve gate with the valve seat and then bringing the valve gate and valve seat into seating contact by the translational movement of a ramp-like wedging means that engages similar ramp-like stractures at the base of the valve gate to force the valve gate into essentially pressureless contact with the annular soft metal gasket. This gasket is then pressurized from beneath by a fluid thereby effecting a vacuura tight seal between the gasket and the ridge. (AEC)
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Kwon, Yong Hwan; Kim, Nayoung; Nam, Ryoung Hee; Park, Ji Hyun; Lee, Sun Min; Kim, Sung Kook; Lee, Hye Seung; Kim, Yong Sung; Lee, Dong Ho
2017-01-01
The gastric accommodation reflex is an important mechanism in gastric physiology. However, the aging-associated structural and functional changes in gastric relaxation have not yet been established. Thus, we evaluated the molecular changes of interstitial cell of Cajal (ICC) and neuronal nitric oxide synthase (nNOS) and the function changes in the corpus of F344 rats at different ages (6-, 31-, 74-wk and 2-yr). The proportion of the c-Kit-positive area in the submucosal border (SMB) and myenteric plexus (MP) layer was significantly lower in the older rats, as indicated by immunohistochemistry. The density of the nNOS-positive immunoreactive area also decreased with age in the SMB, circular muscle (CM), and MP. Similarly, the percent of nNOS-positive neuronal cells per total neuronal cells and the proportion of nNOS immunoreactive area of MP also decreased in aged rats. In addition, the mRNA and protein expression of c-Kit and nNOS significantly decreased with age. Expression of stem cell factor (SCF) and the pan-neuronal marker PGP 9.5 mRNA was significantly lower in the older rats than in the younger rats. Barostat studies showed no difference depending on age. Instead, the change of volume was significantly decreased by L-NG63-nitroarginine methyl ester in the 2-yr-old rats compared with the 6-wk-old rats (P = 0.003). Taken together, the quantitative and molecular nNOS changes in the stomach might play a role in the decrease of gastric accommodation with age. PMID:28045993
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Loger, K; Engel, A; Haupt, J; Lima de Miranda, R; Lutter, G; Quandt, E
2016-03-01
Heart valves are constantly exposed to high dynamic loading and are prone to degeneration. Therefore, it is a challenge to develop a durable heart valve substitute. A promising approach in heart valve engineering is the development of hybrid scaffolds which are composed of a mechanically strong inorganic mesh enclosed by valvular tissue. In order to engineer an efficient, durable and very thin heart valve for transcatheter implantations, we developed a fabrication process for microstructured heart valve leaflets made from a nickel-titanium (NiTi) thin film shape memory alloy. To examine the capability of microstructured NiTi thin film as a matrix scaffold for tissue engineered hybrid heart valves, leaflets were successfully seeded with smooth muscle cells (SMCs). In vitro pulsatile hydrodynamic testing of the NiTi thin film valve leaflets demonstrated that the SMC layer significantly improved the diastolic sufficiency of the microstructured leaflets, without affecting the systolic efficiency. Compared to an established porcine reference valve model, magnetron sputtered NiTi thin film material demonstrated its suitability for hybrid tissue engineered heart valves.
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Blaedel, K.L.
1983-11-03
An apparatus for metering fluids at high pressures of about 20,000 to 60,000 psi is disclosed. The apparatus includes first and second plates which are positioned adjacent each other to form a valve chamber. The plates are made of materials which have substantially equal elastic properties. One plate has a planar surface area, and the other a recessed surface area defined by periphery and central lips. When the two plates are positioned in adjacent contacting relationship, a valve chamber is formed between the planar surface area and the recessed surface area. Fluid is introduced into the chamber and exits therefrom when a deformation occurs at positions where they no longer form a valve seat. This permits the metering of fluids at high pressures and at slow variable rates. Fluid then exits from the chamber until an applied external force becomes large enough to bring the valve seats back into contact.
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Blaedel, Kenneth L.
1985-01-01
An apparatus for metering fluids at high pressures of about 20,000 to 60,000 psi is disclosed. The apparatus includes first and second plates which are positioned adjacent each other to form a valve chamber. The plates are made of materials which have substantially equal elastic properties. One plate has a planar surface area, and the other a recessed surface area defined by periphery and central lips. When the two plates are positioned in adjacent contacting relationship, a valve chamber is formed between the planar surface area and the recessed surface area. Fluid is introduced into the chamber and exits therefrom when a deformation occurs at positions where they no longer form a valve seat. This permits the metering of fluids at high pressures and at slow variable rates. Fluid then exits from the chamber until an applied external force becomes large enough to bring the valve seats back into contact.
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Amstrup Funder, Jonas; Christian Danielsen, Carl; Baandrup, Ulrik; Martin Bibby, Bo; Carl Andelius, Ted; Toft Brøndum, Emil; Wang, Tobias; Michael Hasenkam, J
2017-01-01
Heart valves which exist naturally in an extreme-pressure system must have evolved in a way to resist the stresses of high pressure. Giraffes are interesting as they naturally have a blood pressure twice that of humans. Thus, knowledge regarding giraffe heart valves may aid in developing techniques to design improved pressure-resistant biological heart valves. Heart valves from 12 giraffes and 10 calves were explanted and subjected to either biomechanical or morphological examinations. Strips from the heart valves were subjected to cyclic loading tests, followed by failure tests. Thickness measurements and analyses of elastin and collagen content were also made. Valve specimens were stained with hematoxylin and eosin, elastic van Gieson stain, Masson's trichrome and Fraser-Lendrum stain, as well as immunohistochemical reactions for morphological examinations. The aortic valve was shown to be 70% (95% CI 42-103%) stronger in the giraffe than in its bovine counterpart (p <0.001). No significant difference was found between mitral or pulmonary valves. After normalization for collagen, no significant differences were found in strength between species. The giraffe aortic valve was found to be significantly stiffer than the bovine aortic valve (p <0.001), with no significant difference between mitral and pulmonary valves. On a dry weight basis, the aortic (10.9%), pulmonary (4.3%), and mitral valves (9.6%) of giraffes contained significantly more collagen than those of calves. The elastin contents of the pulmonary valves (2.5%) and aortic valves (1.5%) were also higher in giraffes. The greater strength of the giraffe aortic valve is most likely due to a compact collagen construction. Both, collagen and elastin contents were higher in giraffes than in calves, which would make giraffe valves more resistant to the high-pressure forces. However, collagen also stiffens and thickens the valves. The mitral leaflets showed similar (but mostly insignificant) trends in strength
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An overview of interstitial brachytherapy and hyperthermia
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brandt, B.B.; Harney, J.
Interstitial thermoradiotherapy, an experimental cancer treatment that combines interstitial radiation implants (brachytherapy) and interstitial hyperthermia, is in the early stages of investigation. In accordance with the procedure used in a current national trial protocol, a 60-minute hyperthermia treatment is administered after catheters are placed into the tumor area while the patient is under general anesthesia. This is immediately followed by loading of radioactive Iridium-192 seeds into the catheters for a defined period of time. Once the prescribed radiation dose is delivered, the radioactive sources are removed and a second, 60-minute hyperthermia treatment is administered. Clinical trials with hyperthermia in combinationmore » with radiation have increased in recent years. Nurses caring for these patients need to become more knowledgeable about this investigational therapy. This paper provides an overview of the biologic rationale for this therapy, as well as a description of the delivery method and clinical application. Specific related nursing interventions are defined in a nursing protocol.23 references.« less
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Malate valves: Old shuttles with new perspectives.
Selinski, Jennifer; Scheibe, Renate
2018-06-22
Malate valves act as powerful systems for balancing the ATP/NAD(P)H ratio required in various subcellular compartments in plant cells. As components of malate valves, isoforms of malate dehydrogenases (MDHs) and dicarboxylate translocators catalyze the reversible interconversion of malate and oxaloacetate and their transport. Depending on the coenzyme specificity of the MDH isoforms, either NADH or NADPH can be transported indirectly. Arabidopsis thaliana possesses nine genes encoding MDH isoenzymes: Activities of NAD-dependent MDHs have been detected in mitochondria, peroxisomes, cytosol and plastids, respectively. In addition, chloroplasts possess a NADP-dependent MDH isoform. The NADP-MDH as part of the "light malate valve" plays an important role as a poising mechanism to adjust the ATP/NADPH ratio in the stroma. Its activity is strictly regulated by post-translational redox-modification mediated via the ferredoxin-thioredoxin system and fine control via the NADP + /NADP(H) ratio, thereby maintaining redox homeostasis under changing conditions. In contrast, the plastid NAD-MDH ("dark malate valve") is constitutively active and its lack leads to failure in early embryo development. While redox regulation of the main cytosolic MDH isoform has been shown, the knowledge about regulation of the other two cytosolic MDHs as well as NAD-MDH isoforms from peroxisomes and mitochondria is still lacking. Knockout mutants lacking the isoforms from chloroplasts, mitochondria, and peroxisomes have been characterized, but not much is known about cytosolic NAD-MDH isoforms and their role in planta. This review updates the current knowledge on MDH isoforms and the shuttle systems for intercompartmental dicarboxylate exchange focusing on the various metabolic functions of these valves. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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Cavitation guide for control valves
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tullis, J.P.
1993-04-01
This guide teaches the basic fundamentals of cavitation to provide the reader with an understanding of what causes cavitation, when it occurs, and the potential problems cavitation can cause to a valve and piping system. The document provides guidelines for understanding how to reduce the cavitation and/or select control valves for a cavitating system. The guide provides a method for predicting the cavitation intensity of control valves, and how the effect of cavitation on a system will vary with valve type, valve function, valve size, operating pressure, duration of operation and details of the piping installation. The guide defines sixmore » cavitation limits identifying cavitation intensities ranging from inception to the maximum intensity possible. The intensity of the cavitation at each limit Is described, including a brief discussion of how each level of cavitation influences the valve and system. Examples are included to demonstrate how to apply the method, including making both size and pressure scale effects corrections. Methods of controlling cavitation are discussed providing information on various techniques which can be used to design a new system or modify an existing one so it can operate at a desired level of cavitation.« less
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2012-01-01
Prosthetic valve dysfunction at aortic position is commonly caused by pannus formation. The exact etiology is not known. It arises from ventricular aspect of the prosthesis encroaching its leaflets causing stenosis or it may remain localized causing left ventricular outflow tract obstruction without affecting valve function. The difference in location entails different approaches in management. Such a pathology requires surgical excision of the pannus with or without valve re-replacement. A recurrent pannus was observed in a female patient who needed repeated surgical intervention to excise a localized pannus without re-replacement of a well functioning prosthetic valve. Management of our case presents several questions, whether recurrence of pannus is caused by sparing the prosthetic valve, is it simply an exaggeration of an inflammatory healing process in certain individuals or is it ideal to re-replace the valve despite a well preserved function. PMID:22747790
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Vafaee, Tayyebeh; Thomas, Daniel; Desai, Amisha; Jennings, Louise M.; Berry, Helen; Rooney, Paul; Kearney, John; Fisher, John
2017-01-01
Abstract The clinical use of decellularized cardiac valve allografts is increasing. Long‐term data will be required to determine whether they outperform conventional cryopreserved allografts. Valves decellularized using different processes may show varied long‐term outcomes. It is therefore important to understand the effects of specific decellularization technologies on the characteristics of donor heart valves. Human cryopreserved aortic and pulmonary valved conduits were decellularized using hypotonic buffer, 0.1% (w/v) sodium dodecyl sulfate and nuclease digestion. The decellularized tissues were compared to cellular cryopreserved valve tissues using histology, immunohistochemistry, quantitation of total deoxyribose nucleic acid, collagen and glycosaminoglycan content, in vitro cytotoxicity assays, uniaxial tensile testing and subcutaneous implantation in mice. The decellularized tissues showed no histological evidence of cells or cell remnants and >97% deoxyribose nucleic acid removal in all regions (arterial wall, muscle, leaflet and junction). The decellularized tissues retained collagen IV and von Willebrand factor staining with some loss of fibronectin, laminin and chondroitin sulfate staining. There was an absence of major histocompatibility complex Class I staining in decellularized pulmonary valve tissues, with only residual staining in isolated areas of decellularized aortic valve tissues. The collagen content of the tissues was not decreased following decellularization however the glycosaminoglycan content was reduced. Only moderate changes in the maximum load to failure of the tissues were recorded postdecellularization. The decellularized tissues were noncytotoxic in vitro, and were biocompatible in vivo in a mouse subcutaneous implant model. The decellularization process will now be translated into a good manufacturing practices‐compatible process for donor cryopreserved valves with a view to future clinical use. Copyright © 2016 The Authors
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Interstitial lung disease - adults - discharge
... lung disease Pulmonary alveolar proteinosis Rheumatoid lung disease Sarcoidosis Patient Instructions Eating extra calories when sick - adults ... team. Related MedlinePlus Health Topics Interstitial Lung Diseases Sarcoidosis Browse the Encyclopedia A.D.A.M., Inc. ...
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Use of anoctamin 1 (ANO1) to evaluate interstitial cells of Cajal in Hirschsprung's disease.
Coyle, David; Kelly, Danielle A M; O'Donnell, Anne Marie; Gillick, John; Puri, Prem
2016-02-01
Interstitial cells of Cajal (ICCs) are pacemaker cells involved in facilitating neurotransmission and the generation of slow electrical waves necessary for colonic peristalsis. Their distribution has been found to be abnormal in the aganglionic and ganglionic colon in Hirschsprung's disease (HSCR) using c-kit-labelling. Anoctamin-1 (ANO1) is a Ca(2+)-activated Cl(-) channel thought to be specifically expressed on ICCs. Unlike c-kit, it plays a key role in ICC pacemaker activity. We aimed to investigate the utility of ANO1 in evaluating the colonic ICC network in HSCR. We collected full-length pull-through specimens from children with HSCR (n = 10). Control colon specimens were collected at colostomy closure in children with anorectal malformation (n = 6). The distribution of ANO1 and c-kit expression was evaluated using immunofluorescence and confocal microscopy. ANO1 expression was quantified using Western blot analysis. ANO1 was not expressed on 23 % of c-kit immuno-positive cells in the circular muscle; however, 100 % of ANO1-positive ICCs were c-kit positive. The distribution of ANO1-positive ICCs was sparse in aganglionic colon, with a modest reduction in ICCs seen in the ganglionic colon in HSCR compared to controls (p = 0.044). ANO1 protein expression was reduced in aganglionic colon but similar in ganglionic colon relative to controls. ANO1 is preferential to c-kit in evaluating the ICC network in HSCR due to its specificity and functional importance. Abnormal distribution of ANO1-positive ICCs in the ganglionic colon in HSCR may contribute to persistent bowel symptoms in some patients after pull-through surgery.
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NASA Technical Reports Server (NTRS)
Goetz, C.; Ingle, W. M. (Inventor)
1980-01-01
A ball valve particularly suited for use in the handling of highly corrosive fluids is described. It is characterized by a valve housing formed of communicating segments of quartz tubing, a pair of communicating sockets disposed in coaxial alignment with selected segments of tubing for establishing a pair of inlet ports communicating with a common outlet port, a ball formed of quartz material supported for displacement between the sockets and configured to be received alternately thereby, and a valve actuator including a rod attached to the ball for selectively displacing the ball relative to each of the sockets for controlling fluid flow through the inlet ports.
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Tomii, Keisuke; Kato, Terufumi; Takahashi, Masashi; Noma, Satoshi; Kobashi, Yoichiro; Enatsu, Sotaro; Okubo, Sumiko; Kobayashi, Noriko; Kudoh, Shoji
2017-04-01
Interstitial lung disease (ILD) is important drug related toxicity because it commonly forced to discontinue the treatment. To characterize the prevalence and patterns of pemetrexed induced ILD, an independent ILD advisory board composed of external experts performed reassessment of ILD in two post marketing surveillance (PMS) studies for malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC). ILD incidences were originally 1.6% and 2.6% in 903 MPM and 683 NSCLC patients in safety analyses, respectively. Based on the reassessment by the board, the incidence was 1.1% MPM and 1.8% NSCLC. Common possible risk factors of ILD in MPM and NSCLC patients were male gender, 60 years or older age, and pre-existing ILD. Asbestosis in MPM, and smoking history in NSCLC are also considered as risk, respectively. In terms of computed tomography (CT) pattern, 7 of 10 cases in MPM patients had acute interstitial pneumonia pattern, which four were fatal. Eight of the 12 NSCLC patients had diffuse grand glass opacity, which all had recovered. Onset of ILD in MPM varied between the first and the fifth courses of pemetrexed treatment, and the latest onset was 48 days after the last administration. For NSCLC, it was between the second and the ninth course, 7 and 56 days after the last administration. The risk of pemetrexed-related ILD is similar level as other anti-cancer drugs under clinical settings. Careful observations continuously during and at least for 2 months after the last administration of pemetrexed are advised. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Code of Federal Regulations, 2011 CFR
2011-01-01
... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Oil valves. 125.137 Section 125.137....137 Oil valves. (a) Each oil valve must— (1) Comply with § 125.155; (2) Have positive stops or... the valve. (b) The closing of an oil shutoff means must not prevent feathering the propeller, unless...
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Code of Federal Regulations, 2010 CFR
2010-01-01
... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Oil valves. 125.137 Section 125.137....137 Oil valves. (a) Each oil valve must— (1) Comply with § 125.155; (2) Have positive stops or... the valve. (b) The closing of an oil shutoff means must not prevent feathering the propeller, unless...
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Code of Federal Regulations, 2012 CFR
2012-01-01
... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Oil valves. 125.137 Section 125.137....137 Oil valves. (a) Each oil valve must— (1) Comply with § 125.155; (2) Have positive stops or... the valve. (b) The closing of an oil shutoff means must not prevent feathering the propeller, unless...
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Code of Federal Regulations, 2014 CFR
2014-01-01
... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Oil valves. 125.137 Section 125.137....137 Oil valves. (a) Each oil valve must— (1) Comply with § 125.155; (2) Have positive stops or... the valve. (b) The closing of an oil shutoff means must not prevent feathering the propeller, unless...
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Code of Federal Regulations, 2013 CFR
2013-01-01
... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Oil valves. 125.137 Section 125.137....137 Oil valves. (a) Each oil valve must— (1) Comply with § 125.155; (2) Have positive stops or... the valve. (b) The closing of an oil shutoff means must not prevent feathering the propeller, unless...
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Double-reed exhaust valve engine
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bennett, Charles L.
An engine based on a reciprocating piston engine that extracts work from pressurized working fluid. The engine includes a double reed outlet valve for controlling the flow of low-pressure working fluid out of the engine. The double reed provides a stronger force resisting closure of the outlet valve than the force tending to open the outlet valve. The double reed valve enables engine operation at relatively higher torque and lower efficiency at low speed, with lower torque, but higher efficiency at high speed.
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Miniature piezo electric vacuum inlet valve
Keville, Robert F.; Dietrich, Daniel D.
1998-03-24
A miniature piezo electric vacuum inlet valve having a fast pulse rate and is battery operated with variable flow capability. The low power (<1.6 watts), high pulse rate (<2 milliseconds), variable flow inlet valve is utilized for mass spectroscopic applications or other applications where pulsed or continuous flow conditions are needed. The inlet valve also has a very minimal dead volume of less than 0.01 std/cc. The valve can utilize, for example, a 12 Vdc input/750 Vdc, 3 mA output power supply compared to conventional piezo electric valves which require preloading of the crystal drive mechanism and 120 Vac, thus the valve of the present invention is smaller by a factor of three.
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Dual-Valve and Counter-Flow Surface Plasmon Resonance.
Wang, Xiaoying; Zhou, Feimeng
2018-04-17
Two six-port injector valves and one selector valve commonly used in flow injection analysis are combined with a surface plasmon resonance (SPR) instrument wherein solutions introduced from the two inlets counter-flow inside the flow cell. The system is versatile as the same or different solutions can be rapidly and repeatedly introduced to the two fluidic channels in series or in parallel. Unlike most commercial SPR instruments employing a single injector valve, solutions separately injected from the two injector valves can be readily exchanged (<1 s) between the two channels. This new method, referred to as the alternate injection mode, not only saves analysis time but also facilitates efficient and facile surface reactions for ligand immobilization and prevents immobilized species from desorbing. These advantages are demonstrated with the measurements of binding of acetazolamide (222.2 Da) to histidine-tagged human carbonic anhydrase II (his-tagged HCA). Amine-containing residues of his-tagged HCA molecules tethered at Ni-nitrilotriacetic acid (NTA) sensors were rapidly cross-linked to the underlying carboxymethylated dextran. The higher ligand densities and more stable surfaces are essential for SPR detection of small molecule binding. In a different application, microglobulin solutions of increasing concentrations were introduced for continuous binding to the preimmobilized antibody. The kinetic and affinity measurements can be conducted without performing repeated dissociation and surface regeneration reactions.
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A review of state-of-the-art numerical methods for simulating flow through mechanical heart valves.
Sotiropoulos, Fotis; Borazjani, Iman
2009-03-01
In nearly half of the heart valve replacement surgeries performed annually, surgeons prefer to implant bileaflet mechanical heart valves (BMHV) because of their durability and long life span. All current BMHV designs, however, are prone to thromboembolic complications and implant recipients need to be on a life-long anticoagulant medication regiment. Non-physiologic flow patterns and turbulence generated by the valve leaflets are believed to be the major culprit for the increased risk of thromboembolism in BMHV implant recipients. In this paper, we review recent advances in developing predictive fluid-structure interaction (FSI) algorithms that can simulate BMHV flows at physiologic conditions and at resolution sufficiently fine to start probing the links between hemodynamics and blood-cell damage. Numerical simulations have provided the first glimpse into the complex hemodynamic environment experienced by blood cells downstream of the valve leaflets and successfully resolved for the first time the experimentally observed explosive transition to a turbulent-like state at the start of the decelerating flow phase. The simulations have also resolved a number of subtle features of experimentally observed valve kinematics, such as the asymmetric opening and closing of the leaflets and the leaflet rebound during closing. The paper also discusses a future research agenda toward developing a powerful patient-specific computational framework for optimizing valve design and implantation in a virtual surgery environment.
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A review of state-of-the-art numerical methods for simulating flow through mechanical heart valves
Borazjani, Iman
2009-01-01
In nearly half of the heart valve replacement surgeries performed annually, surgeons prefer to implant bileaflet mechanical heart valves (BMHV) because of their durability and long life span. All current BMHV designs, however, are prone to thromboembolic complications and implant recipients need to be on a life-long anticoagulant medication regiment. Non-physiologic flow patterns and turbulence generated by the valve leaflets are believed to be the major culprit for the increased risk of thromboembolism in BMHV implant recipients. In this paper, we review recent advances in developing predictive fluid–structure interaction (FSI) algorithms that can simulate BMHV flows at physiologic conditions and at resolution sufficiently fine to start probing the links between hemodynamics and blood-cell damage. Numerical simulations have provided the first glimpse into the complex hemodynamic environment experienced by blood cells downstream of the valve leaflets and successfully resolved for the first time the experimentally observed explosive transition to a turbulent-like state at the start of the decelerating flow phase. The simulations have also resolved a number of subtle features of experimentally observed valve kinematics, such as the asymmetric opening and closing of the leaflets and the leaflet rebound during closing. The paper also discusses a future research agenda toward developing a powerful patient-specific computational framework for optimizing valve design and implantation in a virtual surgery environment. PMID:19194734
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Hashitani, Hikaru; Suzuki, Hikaru
2007-01-01
Interstitial cells of Cajal-like cells (ICC-LCs) in the urethra may act as electrical pacemakers of spontaneous contractions. However, their properties in situ and their interaction with neighbouring urethral smooth muscle cells (USMCs) remain to be elucidated. To further explore the physiological role of ICC-LCs, spontaneous changes in [Ca2+]i (Ca2+ transients) were visualized in fluo-4 loaded preparations of rabbit urethral smooth muscle. ICC-LCs were sparsely distributed, rather than forming an extensive network. Ca2+ transients in ICC-LCs had a lower frequency and a longer half-width than those of USMCs. ICC-LCs often exhibited Ca2+ transients synchronously with each other, but did not often show a close temporal relationship with Ca2+ transients in USMCs. Nicardipine (1 μm) suppressed Ca2+ transients in USMCs but not in ICC-LCs. Ca2+ transients in ICC-LCs were abolished by cyclopiazonic acid (10 μm), ryanodine (50 μm) and caffeine (10 mm) or by removing extracellular Ca2+, and inhibited by 2-aminoethoxydiphenyl borate (50 μm) and 3-morpholino-sydnonimine (SIN-1; 10 μm), but facilitated by increasing extracellular Ca2+ or phenylephrine (1–10 μm). These results indicated that Ca2+ transients in urethral ICC-LCs in situ rely on both Ca2+ release from intracellular Ca2+ stores and Ca2+ influx through non-L-type Ca2+ channel pathways. ICC-LCs may not act as a coordinated pacemaker electrical network as do ICC in the gastrointestinal (GI) tract. Rather they may randomly increase excitability of USMCs to maintain the tone of urethral smooth muscles. PMID:17615099
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Laparoscopic management of interstitial pregnancy with automatic stapler
Ahsan Akhtar, Muhammad; Izzat, Feras; Keay, Stephen D
2012-01-01
A 36-year-old woman was referred by general practitioner to the early pregnancy unit with pelvic pain in her seventh week of pregnancy. She had a transvaginal ultrasound. Unruptured live twin tubal ectopic pregnancy was diagnosed on. Diagnostic laparoscopy revealed an unruptured left interstitial ectopic pregnancy. The interstitial tubal pregnancy was removed by laparoscopic automatic stapler with minimal blood loss. The patient had an uneventful recovery to health. PMID:23093504
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Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin
Liu, Qingdu; Binns, Thomas C.; Davidoff, Olena; Kapitsinou, Pinelopi P.; Pfaff, Andrew S.; Olauson, Hannes; Fogo, Agnes B.; Fong, Guo-Hua; Gross, Kenneth W.
2016-01-01
Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear. Here we targeted the PHD/HIF-2/EPO axis in FOXD1 stroma-derived renal interstitial cells and examined the role of individual PHDs in REPC pool size regulation and renal EPO output. Renal interstitial cells with EPO-producing capacity were entirely derived from FOXD1-expressing stroma, and Phd2 inactivation alone induced renal Epo in a limited number of renal interstitial cells. EPO induction was submaximal, as hypoxia or pharmacologic PHD inhibition further increased the REPC fraction among Phd2–/– renal interstitial cells. Moreover, Phd1 and Phd3 were differentially expressed in renal interstitium, and heterozygous deficiency for Phd1 and Phd3 increased REPC numbers in Phd2–/– mice. We propose that FOXD1 lineage renal interstitial cells consist of distinct subpopulations that differ in their responsiveness to Phd2 inactivation and thus regulation of HIF-2 activity and EPO production under hypoxia or conditions of pharmacologic or genetic PHD inactivation. PMID:27088801
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Saravanaperumal, Siva Arumugam; Gibbons, Simon J; Malysz, John; Sha, Lei; Linden, David R; Szurszewski, Joseph H; Farrugia, Gianrico
2018-01-01
What is the central question of this study? The aim was to investigate the roles of extracellular chloride in electrical slow waves and resting membrane potential of mouse jejunal smooth muscle by replacing chloride with the impermeant anions gluconate and isethionate. What is the main finding and its importance? The main finding was that in smooth muscle cells, the resting Cl - conductance is low, whereas transmembrane Cl - movement in interstitial cells of Cajal (ICCs) is a major contributor to the shape of electrical slow waves. Furthermore, the data confirm that ICCs set the smooth muscle membrane potential and that altering Cl - homeostasis in ICCs can alter the smooth muscle membrane potential. Intracellular Cl - homeostasis is regulated by anion-permeable channels and transporters and contributes to excitability of many cell types, including smooth muscle and interstitial cells of Cajal (ICCs). Our aims were to investigate the effects on electrical activity in mouse jejunal muscle strips of replacing extracellular Cl - (Cl - o ) with the impermeant anions gluconate and isethionate. On reducing Cl - o , effects were observed on electrical slow waves, with small effects on smooth muscle membrane voltage (E m ). Restoration of Cl - hyperpolarized smooth muscle E m proportional to the change in Cl - o concentration. Replacement of 90% of Cl - o with gluconate reversibly abolished slow waves in five of nine preparations. Slow waves were maintained in isethionate. Gluconate and isethionate substitution had similar concentration-dependent effects on peak amplitude, frequency, width at half peak amplitude, rise time and decay time of residual slow waves. Gluconate reduced free ionized Ca 2+ in Krebs solutions to 0.13 mm. In Krebs solutions containing normal Cl - and 0.13 mm free Ca 2+ , slow wave frequency was lower, width at half peak amplitude was smaller, and decay time was faster. The transient hyperpolarization following restoration of Cl - o was not observed
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Noninvasive valve monitor using alternating electromagnetic field
Eissenberg, David M.; Haynes, Howard D.; Casada, Donald A.
1993-01-01
One or more electrical coils are carefully located on the outside of a valve body. An alternating current passing through the coil(s) results in an alternating electromagnetic field being transmitted into the valve body and valve internals. The electromagnetic field varies in intensity and polarity in the valve. As the position of a valve internal part is changed, the electromagnetic field throughout the valve body and its internals is altered. A passive receiver coil carefully located on the outside of the valve body detects the intensity of the electromagnetic field at that location as an induced electrical voltage in the coil. With the change in position of the valve internal part, there is a corresponding change in the induced voltage as a result of the alteration in the alternating electromagnetic field at that location. Changes in the voltage provide an indication of the position and motion of valve internals.
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Noninvasive valve monitor using alternating electromagnetic field
Eissenberg, D.M.; Haynes, H.D.; Casada, D.A.
1993-03-16
One or more electrical coils are carefully located on the outside of a valve body. An alternating current passing through the coil(s) results in an alternating electromagnetic field being transmitted into the valve body and valve internals. The electromagnetic field varies in intensity and polarity in the valve. As the position of a valve internal part is changed, the electromagnetic field throughout the valve body and its internals is altered. A passive receiver coil carefully located on the outside of the valve body detects the intensity of the electromagnetic field at that location as an induced electrical voltage in the coil. With the change in position of the valve internal part, there is a corresponding change in the induced voltage as a result of the alteration in the alternating electromagnetic field at that location. Changes in the voltage provide an indication of the position and motion of valve internals.
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Triple valve surgery: a 25-year experience.
Yilmaz, Mustafa; Ozkan, Murat; Böke, Erkmen
2004-09-01
Surgical treatment of rheumatic valvular disease still constitutes a significant number of cardiac operations in developing countries. Despite improvements in myocardial protection and cardiopulmonary bypass techniques, triple valve operations (aortic, mitral and tricuspid valves) are still challenging because of longer duration of cardiopulmonary bypass and higher degree of myocardial decompensation. This study was instituted in order to assess results of triple valve surgery. Between 1977 and 2002, 34 patients underwent triple valve surgery in our clinic by the same surgeon (EB). Eleven patients underwent triple valve replacement (32.4%) and 23 underwent tricuspid valve annuloplasty with aortic and mitral valve replacements (67.6%). There was no significant difference between the two groups of patients who underwent triple valve replacement and aortic and mitral valve replacement with tricuspid valve annuloplasty. There were 4 hospital deaths (11.8%) occurring within 30 days. The duration of follow-up for 30 survivors ranged from 6 to 202 months (mean 97 months). The actuarial survival rates were 85%, 72%, and 48% at 5, 10, and 15 years respectively. Actuarial freedom from reoperation rates at 5, 10, and 15 years was 86.3%, 71.9%, and 51.2%, respectively. Freedom from cerebral thromboembolism and anticoagulation-related hemorrhage rates, expressed in actuarial terms was 75.9% and 62.9% at 5 and 10 years. Major cerebral complications occurred in 10 of the 30 patients. We prefer replacing, if repairing is not possible, the tricuspid valve, with a bileaflet mechanical prosthesis in a patient with valve replacement of the left heart who will be anticoagulated in order to avoid unfavorable properties of bioprosthesis like degeneration and of old generation mechanical prosthesis like thrombosis and poor hemodynamic function. In recent years, results of triple valve surgery either with tricuspid valve conservation or valve replacement in suitable cases have become
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Xu, Tong-yi; Zhang, Zhi-gang; Li, Xin; Han, Lin; Xu, Zhi-yun
2014-01-01
Background Since 2000, transcatheter pulmonary valve replacement has steadily advanced. However, the available prosthetic valves are restricted to bioprosthesis which have defects like poor durability. Polymeric heart valve is thought as a promising alternative to bioprosthesis. In this study, we introduced a novel polymeric transcatheter pulmonary valve and evaluated its feasibility and safety in sheep by a hybrid approach. Methods We designed a novel polymeric trileaflet transcatheter pulmonary valve with a balloon-expandable stent, and the valve leaflets were made of 0.1-mm expanded polytetrafluoroethylene (ePTFE) coated with phosphorylcholine. We chose glutaraldehyde-treated bovine pericardium valves as control. Pulmonary valve stents were implanted in situ by a hybrid transapical approach in 10 healthy sheep (8 for polymeric valve and 2 for bovine pericardium valve), weighing an average of 22.5±2.0 kg. Angiography and cardiac catheter examination were performed after implantation to assess immediate valvular functionality. After 4-week follow-up, angiography, echocardiography, computed tomography, and cardiac catheter examination were used to assess early valvular function. One randomly selected sheep with polymeric valve was euthanized and the explanted valved stent was analyzed macroscopically and microscopically. Findings Implantation was successful in 9 sheep. Angiography at implantation showed all 9 prosthetic valves demonstrated orthotopic position and normal functionality. All 9 sheep survived at 4-week follow-up. Four-week follow-up revealed no evidence of valve stent dislocation or deformation and normal valvular and cardiac functionality. The cardiac catheter examination showed the peak-peak transvalvular pressure gradient of the polymeric valves was 11.9±5.0 mmHg, while that of two bovine pericardium valves were 11 and 17 mmHg. Gross morphology demonstrated good opening and closure characteristics. No thrombus or calcification was seen
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Desai, Ravi R.; Vargas Abello, Lina Maria; Klein, Allan L.; Marwick, Thomas H.; Krasuski, Richard A.; Ye, Ying; Nowicki, Edward R.; Rajeswaran, Jeevanantham; Blackstone, Eugene H.; Pettersson, Gösta B.
2014-01-01
Objectives To study the effect of mitral valve repair with or without concomitant tricuspid valve repair on functional tricuspid regurgitation and right ventricular function. Methods From 2001 to 2007, 1833 patients with degenerative mitral valve disease, a structurally normal tricuspid valve, and no coronary artery disease underwent mitral valve repair, and 67 underwent concomitant tricuspid valve repair. Right ventricular function (myocardial performance index and tricuspid annular plane systolic excursion) was measured before and after surgery using transthoracic echocardiography for randomly selected patients with tricuspid regurgitation grade 0, 1+, and 2+(100 patients for each grade) and 93 with grade 3+/4+, 393 patients in total. Results In patients with mild (<3+) preoperative tricuspid regurgitation, mitral valve repair alone was associated with reduced tricuspid regurgitation and mild worsening of right ventricular function. Tricuspid regurgitation of 2+or greater developed in fewer than 20%, and right ventricular function had improved, but not to preoperative levels, at 3 years. In patients with severe (3+/4+) preoperative tricuspid regurgitation, mitral valve repair alone reduced tricuspid regurgitation and improved right ventricular function; however, tricuspid regurgitation of 2+ or greater returned and right ventricular function worsened toward preoperative levels within 3 years. Concomitant tricuspid valve repair effectively eliminated severe tricuspid regurgitation and improved right ventricular function. Also, over time, tricuspid regurgitation did not return and right ventricular function continued to improve to levels comparable to that of patients with lower grades of preoperative tricuspid regurgitation. Conclusions In patients with mitral valve disease and severe tricuspid regurgitation, mitral valve repair alone was associated with improved tricuspid regurgitation and right ventricular function. However, the improvements were incomplete and
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Influence of dislocation strain fields on the diffusion of interstitial iron impurities in silicon
NASA Astrophysics Data System (ADS)
Ziebarth, Benedikt; Mrovec, Matous; Elsässer, Christian; Gumbsch, Peter
2015-09-01
The efficiency of silicon (Si)-based solar cells is strongly affected by crystal defects and impurities. Metallic impurities, in particular interstitial iron (Fe) atoms, cause large electric losses because they act as recombination centers for photogenerated charge carriers. Here, we present a systematic first-principles density functional theory (DFT) study focusing on the influence of hydrostatic, uniaxial, and shear strains on the thermodynamic stability and the diffusivity of Fe impurities in crystalline Si. Our calculations show that the formation energy of neutral Fe interstitials in tetrahedral interstitial sites is almost unaffected by uniform deformations of the Si crystal up to strains of 5%. In contrast, the migration barrier varies significantly with strain, especially for hydrostatic deformation. In order to determine effective diffusion coefficients for different strain states, a kinetic Monte Carlo (kMC) model was set up based on the activation energy barriers and frequency factors obtained from the DFT simulations. By using the strain dependence of the migration barrier, we examined the migration of Fe interstitials in the vicinity of perfect 1 /2 <110 > screw and 60∘ mixed dislocations, and 1 /6 <112 > 90∘ and 30∘ partial dislocations. While the strain field of the perfect screw dislocation always enhances the local Fe diffusion, the existence of tensile and compressive regions around the 60∘ mixed dislocation results in a strong anisotropic diffusion profile with significantly faster and slower diffusivities on its tensile and compressive sides. The influences of the partial dislocations are qualitatively similar to that of the 60∘ mixed dislocation.
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Zimmern, P E; Laub, D; Leach, G E
1995-07-01
Fluorescein angiography has been used in the study of bleeding vessels, neovascularity, tumors and ischemic tissues in a variety of disorders. This pilot study was designed to evaluate the feasibility, safety and relevance of this interesting technology for the evaluation of bladder wall vessels in patients with interstitial cystitis and bladder cancer. Five patients with National Institutes of Health defined interstitial cystitis symptoms and 10 with bladder cancer were studied during cytoscopy while they were under general anesthesia. A yellow-green barrier filter (520 nm.) was placed over the cystoscope eyepiece and a blue exciter filter (465 nm.) was attached to the light source. Patients received a 5 ml. bolus of 10% fluorescein intravenously. After hydrodistension, glomerulations in interstitial cystitis patients were more prominent with fluorescein angiography and occurred in the venule phase. Areas of papillary transitional cell tumor and carcinoma in situ developed a brilliant yellow-green fluorescence. Adjacent normal urothelium was nonfluorescent and provided a contrasting dark background facilitating the detection of all lesions. No allergic reaction or other adverse effect related to the fluorescein injection was observed. These unique observations in a limited number of patients suggest that fluorescein angiography of the bladder is a safe and simple procedure. This preliminary report underscores the relevance of fluorescein angiography in the detection of bladder tumor and offers a new approach to the evaluation of bladder wall vessels in interstitial cystitis patients.
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[Transcatheter aortic valve replacement].
Sawa, Yoshiki
2014-07-01
While transcatheter aortic valve replacement( TAVR) has spread rapidly all over the world for highrisk patients with severe aortic stenosis (AS), SAPIEN XT was approved in Japan in October 2013. Since that, approximately 400 TAVR cases were performed in Japan. In our institute, we have performed 164 cases since first case in Japan in 2009 and have achieved satisfactory early results(30-day mortality:1.2%). At the same time, however, simultaneously various TAVR-related complications including a paravalvular leak, stroke, vascular complications, and coronary obstruction were observed. A reduction in the incidence and severity of these complications had led technical improvements in various new devices(2nd generation TAVR device such as the SAPIEN 3, ACURATE, and JenaValve) and in implantation techniques including repositioning/recapturing features, paravalvular sealing technologies, and prevention of coronary obstruction. Furthermore, there is also increasing experience with special indications for TAVR such as pure aortic valve insufficiency or valve-in-valve techniques. Currently, an increasing number of publications of midterm results demonstrate good prosthetic valve function and durability, with good quality of life and low morbidity after TAVR. There are also some randomized trials such as PARTNER 2 or SURTAVI to investigate potential benefits of TAVR for intermediate-risk patients. These improvements in the TAVR devices promises the expansion of TAVR towards the treatment of lower-risk patients in the near future.
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Coxiella burnetii, a hidden pathogen in interstitial lung disease?
Melenotte, Cléa; Izaaryene, Jalal-Jean; Gomez, Carine; Delord, Marion; Prudent, Elsa; Lepidi, Hubert; Mediannikov, Oleg; Lacoste, Marion; Djossou, Felix; Mania, Alexandre; Bernard, Noelle; Huchot, Eric; Mège, Jean-Louis; Brégeon, Fabienne; Raoult, Didier
2018-04-06
We report 7 patients with interstitial lung disease (ILD) on CT-scan reviewing. C. burnetii was diagnosed in situ in one lung biopsy performed. All patients had advanced interstitial lung fibrosis and persistent C. burnetii infection. Q fever may be a cofactor of ILD, especially in endemic areas.