Effects of the laryngeal jet on nano- and microparticle transport and deposition in an approximate model of the upper tracheobronchial airways

2008 ◽  
Vol 104 (6) ◽  
pp. 1761-1777 ◽  
Author(s):  
Jinxiang Xi ◽  
P. Worth Longest ◽  
Ted B. Martonen

The extent to which laryngeal-induced flow features penetrate into the upper tracheobronchial (TB) airways and their related impact on particle transport and deposition are not well understood. The objective of this study was to evaluate the effects of including the laryngeal jet on the behavior and fate of inhaled aerosols in an approximate model of the upper TB region. The upper TB model was based on a simplified numerical reproduction of a replica cast geometry used in previous in vitro deposition experiments that extended to the sixth respiratory generation along some paths. Simulations with and without an approximate larynx were performed. Particle sizes ranging from 2.5 nm to 12 μm were considered using a well-tested Lagrangian tracking model. The model larynx was observed to significantly affect flow dynamics, including a laryngeal jet skewed toward the right wall of the trachea and a significant reverse flow in the left region of the trachea. Inclusion of the laryngeal model increased the tracheal deposition of nano- and micrometer particles by factors ranging from 2 to 10 and significantly reduced deposition in the first three bronchi of the model. Considering localized conditions, inclusion of the laryngeal approximation decreased deposition at the main carina and produced a maximum in local surface deposition density in the lobar-to-segmental bifurcations (G2–G3) for both 40-nm and 4-μm aerosols. These findings corroborate previous experiments and highlight the need to include a laryngeal representation in future computational and in vitro models of the TB region.

2008 ◽  
Vol 295 (1) ◽  
pp. H297-H304 ◽  
Author(s):  
Liang Tang ◽  
Gyo-Seung Hwang ◽  
Hideki Hayashi ◽  
Juan Song ◽  
Masahiro Ogawa ◽  
...  

In vitro models of sustained monomorphic ventricular tachycardia (MVT) are rare and do not usually show spiral reentry on the epicardium. We hypothesized that MVT is associated with the spiral wave in the endocardium and that this stable reentrant propagation is supported by a persistently elevated intracellular calcium (Cai) transient at the core of the spiral wave. We performed dual optical mapping of transmembrane potential ( Vm) and Cai dynamics of the right ventricular (RV) endocardium in Langendorff-perfused rabbit hearts ( n = 12). Among 64 induced arrhythmias, 55% were sustained MVT (>10 min). Eighty percent of MVT showed stationary spiral waves (>10 cycles, cycle length: 128 ± 14.6 ms) in the endocardial mapped region, anchoring to the anatomic discontinuities. No reentry activity was observed in the epicardium. During reentry, the amplitudes of Vm and Cai signals were higher in the periphery and gradually decreased toward the core. At the core, maximal Vm and Cai amplitudes were 42.95 ± 5.89% and 43.95 ± 9.46%, respectively, of the control ( P < 0.001). However, the trough of the Vm and Cai signals at the core were higher than those in the periphery, indicating persistent Vm and Cai elevations during reentry. BAPTA-AM, a calcium chelator, significantly reduced the maximal Cai transient amplitude and prevented sustained MVT and spiral wave formation in the mapped region. These findings indicate that endocardial spiral waves often anchor to anatomic discontinuities causing stable MVT in normal rabbit ventricles. The spiral core is characterized by diminished Vm and Cai amplitudes and persistent Vm and Cai elevations during reentry.


2020 ◽  
Vol 72 (5) ◽  
pp. 665-683
Author(s):  
Outi Huttala ◽  
Jertta-Riina Sarkanen ◽  
Marika Mannerström ◽  
Tarja Toimela ◽  
Tuula Heinonen ◽  
...  

Abstract Inflammation has been proven significant factor in development of type 2 diabetes. So far, most of the adipose tissue related research has been performed in animals, mainly rodent models. The relevance of translation of animal results to humans is questionable. However, in vitro model with relevant human cell source, such as human adipose tissue stromal cells (hASC), can be developed and should be utilized for human adipose tissue research. We developed in vitro models of human adipose tissue utilizing hASC, endothelial cells and monocytes/macrophages. By isolating endothelial cells and macrophages from same adipose tissue as hASC, we were able to provide method for constructing personalized models of adipose tissue. With these models, we studied the effect of macrophages on adipogenesis and protein secretion, with and without vasculature. The models were analyzed for immunocytochemical markers, cell number, triglyceride accumulation and protein secretion. We found that lipid accumulation was greater in adipocytes in the presence of macrophages. Interferon gamma increased this difference between adipocyte culture and Adipocyte–Macrophage co-culture. Protein secretion was affected more by macrophages when vasculature was not present compared to the mild effect when vasculature was present. The vascularized adipose model with macrophages is valuable tool for human adipose tissue research, especially for the personalized medicine approaches; for choosing the right treatments and for studying rare medical conditions.


1997 ◽  
Vol 119 (1) ◽  
pp. 30-38 ◽  
Author(s):  
S. A. Jones ◽  
D. P. Giddens ◽  
F. Loth ◽  
C. K. Zarins ◽  
F. Kajiya ◽  
...  

In-vivo velocity profiles were recorded with a 20 MHz, 80-channel pulsed Doppler ultrasound velocimeter in canine end-to-side ilio-femoral anastomotic grafts. The geometries were obtained from casts of the anastomotic region, and flow rates were measured with electromagnetic flow probes. Three cases reported here include a “standard” geometry, which was similar to previously studied in vitro models, a stenosed geometry, and a case with below average flow rate. Observed flow features include separation at the hood and toe, movement of the floor stagnation point, and skewed profiles in the proximal outflow segment. Out-of-plane curvature and lateral displacement of the anastomosis inlet appear to have a strong effect on the flow fields. In addition, compliance affects the instantaneous flow rates within the proximal and distal branches.


2018 ◽  
Vol 315 (2) ◽  
pp. F332-F335 ◽  
Author(s):  
Eryn E. Dixon ◽  
Owen M. Woodward

Novel technologies, new understanding of the basement membrane composition, and better comprehension of the embryonic development of the mammalian kidney have led to explosive growth in the use of three-dimensional in vitro models to study a range of human disease pathologies (Clevers H. Cell 165: 1586–1597, 2016; Shamir ER, Ewald AJ. Nat Rev Mol Cell Biol 15: 647–664, 2014). The development of these effective model systems represents a new tool to study the progressive cystogenesis of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is a prevalent and complex monogenetic disease, characterized by the pathological formation of fluid fill cysts in renal tissue (Grantham JJ, Mulamalla S, Swenson-Fields KI. Nat Rev Nephrol 7: 556–566, 2011; Takiar V, Caplan MJ. Biochim Biophys Acta 1812: 1337–1343, 2011). ADPKD cystogenesis is attributed to loss of function mutations in either PKD1 or PKD2, which encode for two transmembrane proteins, polycystin-1 and polycystin-2, and progresses with loss of both copies of either gene through a proposed two-hit mechanism with secondary somatic mutations (Delmas P, Padilla F, Osorio N, Coste B, Raoux M, Crest M. Biochem Biophys Res Commun 322: 1374–1383, 2004; Pei Y, Watnick T, He N, Wang K, Liang Y, Parfrey P, Germino G, St George-Hyslop P. Am Soc Nephrol 10: 1524–1529, 1999; Wu G, D’Agati V, Cai Y, Markowitz G, Park JH, Reynolds DM, Maeda Y, Le TC, Hou H Jr, Kucherlapati R, Edelmann W, Somlo S. Cell 93: 177–188, 1998). The exaggerated consequences of large fluid filled cysts result in fibrosis and nephron injury, leading initially to functional compensation but ultimately to dysfunction (Grantham JJ. Am J Kidney Dis 28: 788–803, 1996; Norman J. Biochim Biophys Acta 1812: 1327–1336, 2011; Song CJ, Zimmerman KA, Henke SJ, Yoder BK. Results Probl Cell Differ 60: 323–344, 2017). The complicated disease progression has scattered focus and resources across the spectrum of ADPKD research.


Author(s):  
Damian Muzzio ◽  
Maria L. Foglia ◽  
Martin F. Desimone ◽  
Marek Zygmunt

2016 ◽  
Vol 236 ◽  
pp. 10-25 ◽  
Author(s):  
Delyan P. Ivanov ◽  
Beth Coyle ◽  
David A. Walker ◽  
Anna M. Grabowska
Keyword(s):  

2014 ◽  
Vol 226 (06) ◽  
Author(s):  
D William ◽  
M Linnebacher ◽  
CF Classen

1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.


1997 ◽  
Vol 77 (02) ◽  
pp. 376-382 ◽  
Author(s):  
Bruce Lages ◽  
Harvey J Weiss

SummaryThe possible involvement of secreted platelet substances in agonist- induced [Ca2+]i increases was investigated by comparing these increases in aspirin-treated, fura-2-loaded normal platelets and platelets from patients with storage pool deficiencies (SPD). In the presence and absence of extracellular calcium, the [Ca2+]i response induced by 10 µM ADP, but not those induced by 0.1 unit/ml thrombin, 3.3 µM U46619, or 20 µM serotonin, was significantly greater in SPD platelets than in normal platelets, and was increased to the greatest extent in SPD patients with Hermansky-Pudlak syndrome (HPS), in whom the dense granule deficiencies are the most severe. Pre-incubation of SPD-HPS and normal platelets with 0.005-5 µM ADP produced a dose-dependent inhibition of the [Ca2+]i response induced by 10 µ M ADP, but did not alter the [Ca2+]i increases induced by thrombin or U46619. Within a limited range of ADP concentrations, the dose-inhibition curve of the [Ca2+]i response to 10 µM ADP was significantly shifted to the right in SPD-HPS platelets, indicating that pre-incubation with greater amounts of ADP were required to achieve the same extent of inhibition as in normal platelets. These results are consistent with a hypothesis that the smaller ADP-induced [Ca2+]i increases seen in normal platelets may result from prior interactions of dense granule ADP, released via leakage or low levels of activation, with membrane ADP receptors, causing receptor desensitization. Addition of apyrase to platelet-rich plasma prior to fura-2 loading increased the ADP-induced [Ca2+]i response in both normal and SPD-HPS platelets, suggesting that some release of ADP derived from both dense granule and non-granular sources occurs during in vitro fura-2 loading and platelet washing procedures. However, this [Ca2+]i response was also greater in SPD-HPS platelets when blood was collected with minimal manipulation directly into anticoagulant containing apyrase, raising the possibility that release of dense granule ADP resulting in receptor desensitization may also occur in vivo. Thus, in addition to enhancing platelet activation, dense granule ADP could also act to limit the ADP-mediated reactivity of platelets exposed in vivo to low levels of stimulation.


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