Effect of small flow reversals on aerosol mixing in the alveolar region of the human lung

2004 ◽  
Vol 97 (6) ◽  
pp. 2083-2089 ◽  
Author(s):  
Chantal Darquenne ◽  
G. Kim Prisk
Keyword(s):  
Human Lung ◽  
Sudden Increase ◽  
Residual Volume ◽  
Research Aircraft ◽  
Residual Capacity ◽  
Small Flow ◽  
The One ◽  
High Degree ◽  
Flow Reversals

It has been suggested that irreversibility of alveolar flow combined with a stretched and folded pattern of streamlines can lead to a sudden increase in mixing in the lung. To determine whether this phenomenon is operative in the human lung in vivo, we performed a series of bolus studies with a protocol designed to induce complex folding patterns. Boli of 0.5- and 1-μm-diameter particles were inhaled at penetration volumes (Vp) of 300 and 1,200 ml in eight subjects during short periods of microgravity aboard the National Aeronautics and Space Administration Microgravity Research Aircraft. Inspiration was from residual volume to 1 liter above 1 G functional residual capacity. This was followed by a 10-s breathhold, during which up to seven 100-ml flow reversals (FR) were imposed at Vp = 300 ml and up to four 500-ml FR at Vp = 1,200 ml, and by an expiration to residual volume. Bolus dispersion and deposition were calculated from aerosol concentration and flow rate continuously monitored at the mouth. There was no significant increase in dispersion and deposition with increasing FR except for dispersion between 0 and 7 FR at Vp = 300 ml with 0.5-μm-diameter particles, and this increase was small. This suggested that either the phenomenon of stretch and fold did not occur within the number of FR we performed or that it had already occurred during the one breathing cycle included in the basic maneuver. We speculate that the phenomenon occurred during the basic maneuver, which is consistent with the high degree of dispersion and deposition observed previously in microgravity.

Deposition and dispersion of 1-μm aerosol boluses in the human lung: effect of micro- and hypergravity

1998 ◽  
Vol 85 (4) ◽  
pp. 1252-1259 ◽  
Author(s):  
Chantal Darquenne ◽  
John B. West ◽  
G. Kim Prisk
Keyword(s):  
Flow Rate ◽  
Functional Residual Capacity ◽  
Human Lung ◽  
Aerosol Concentration ◽  
Residual Volume ◽  
Parabolic Flights ◽  
Residual Capacity ◽  
Expired Gas

We performed bolus inhalations of 1-μm particles in four subjects on the ground (1 G) and during parabolic flights both in microgravity (μG) and in ∼1.6 G. Boluses of ∼70 ml were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 200 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The deposition, dispersion, and position of the bolus in the expired gas were calculated from these data. For Vp ≥400 ml, both deposition and dispersion increased with Vp and were strongly gravity dependent, with the greatest deposition and dispersion occurring for the largest G level. At Vp = 800 ml, deposition and dispersion increased from 33.9% and 319 ml in μG to 56.9% and 573 ml at ∼1.6 G, respectively ( P < 0.05). At each G level, the bolus was expired at a smaller volume than Vp, and this volume became smaller with increasing Vp. Although dispersion was lower in μG than in 1 G and ∼1.6 G, it still increased steadily with increasing Vp, showing that nongravitational ventilatory inhomogeneity is partly responsible for dispersion in the human lung.

scholarly journals Alterations in the Conserved SL1trans-Spliced Leader of Caenorhabditis elegansDemonstrate Flexibility in Length and Sequence Requirements In Vivo

1999 ◽  
Vol 19 (3) ◽  
pp. 1892-1900 ◽  
Author(s):  
Kimberly C. Ferguson ◽  
Joel H. Rothman
Keyword(s):  
Dna Sequences ◽  
Expression System ◽  
Leader Sequence ◽  
Critical Parameters ◽  
Spliced Leader ◽  
C Elegans ◽  
The One ◽  
High Degree ◽  
Sequence Requirements

ABSTRACT Approximately 70% of mRNAs in Caenorhabditis elegansare trans spliced to conserved 21- to 23-nucleotide leader RNAs. While the function of SL1, the major C. elegans trans-spliced leader, is unknown, SL1 RNA, which contains this leader, is essential for embryogenesis. Efforts to characterize in vivo requirements of the SL1 leader sequence have been severely constrained by the essential role of the corresponding DNA sequences in SL1 RNA transcription. We devised a heterologous expression system that circumvents this problem, making it possible to probe the length and sequence requirements of the SL1 leader without interfering with its transcription. We report that expression of SL1 from a U2 snRNA promoter rescues mutants lacking the SL1-encoding genes and that the essential embryonic function of SL1 is retained when approximately one-third of the leader sequence and/or the length of the leader is significantly altered. In contrast, although all mutant SL1 RNAs were well expressed, more severe alterations eliminate this essential embryonic function. The one non-rescuing mutant leader tested was never detected on messages, demonstrating that part of the leader sequence is essential for trans splicing in vivo. Thus, in spite of the high degree of SL1 sequence conservation, its length, primary sequence, and composition are not critical parameters of its essential embryonic function. However, particular nucleotides in the leader are essential for the in vivo function of the SL1 RNA, perhaps for its assembly into a functional snRNP or for the trans-splicing reaction.

Three-dimensional reconstruction of the in vivo human diaphragm shape at different lung volumes

1994 ◽  
Vol 76 (2) ◽  
pp. 495-506 ◽  
Author(s):  
A. P. Gauthier ◽  
S. Verbanck ◽  
M. Estenne ◽  
C. Segebarth ◽  
P. T. Macklem ◽  
...  
Keyword(s):  
Total Lung Capacity ◽  
Three Dimensional ◽  
Residual Volume ◽  
Lung Volumes ◽  
Lung Inflation ◽  
Lung Capacity ◽  
Residual Capacity ◽  
Dimensional Shape ◽  
Three Dimensional Shape

The ability of the diaphragm to generate pressures at different lung volumes (VLs) in humans may be determined by the following factors: 1) its in vivo three-dimensional shape, radius of curvature, and tension according to Laplace law; 2) the relative degree to which it is apposed to the rib cage (i.e., zone of apposition) and lungs (i.e., diaphragm dome); and 3) its length-force properties. To gain more insight into these factors we have reconstructed from nuclear magnetic images the three-dimensional shape of the diaphragm of four normal subjects under supine relaxed conditions at four different VLs: residual volume, functional residual capacity, functional residual capacity plus one-half of the inspiratory capacity, and total lung capacity. Under our experimental conditions the shape of the diaphragm changes substantially in the anteroposterior plane but not in the coronal one. Multivariate regression analysis indicates that the zone of apposition is dependent on both diaphragm shortening and lower rib cage widening with lung inflation, although much more on the first of these two factors. Because of the changes in anteroposterior shape and expansion of the insertional origin at the costal margin with lung inflation, the data therefore suggest that the diaphragm may be more accurately modeled by a “widening piston” (Petroll's model) than a simple “piston in a cylinder” model. A significant portion of the muscular surface is lung apposed, suggesting that diaphragmatic force has radial vectors in the dome and vectors along the body axis in the zone of apposition. The muscular surface area of the diaphragm decreased linearly by approximately 41% with VL from residual volume to total lung capacity. Diaphragmatic fibers may shorten under physiological conditions more than any other skeletal muscle. The large changes in fiber length combined with limited shape changes with lung inflation suggest that the length-twitch force properties of the diaphragm may be the most important factor for the pressure-generating function of this respiratory muscle in response to bilateral phrenic shocks at different VLs.

STUDIES IN CONGENITAL GENERALIZED LIPODYSTROPHY

1973 ◽  
Vol 72 (3) ◽  
pp. 495-505 ◽  
Author(s):  
Oddmund Søvik ◽  
Svein Oseid
Keyword(s):  
Biological Activity ◽  
Insulin Response ◽  
Epididymal Adipose Tissue ◽  
Large Individual ◽  
Immunoreactive Insulin ◽  
List Type ◽  
Glucose Load ◽  
Congenital Generalized Lipodystrophy ◽  
The One

ABSTRACT The biological activity of plasma insulin from 4 cases of congenital generalized lipodystrophy has been studied, using rat diaphragm and epididymal adipose tissue in vivo. The results are compared with previous data on plasma immunoreactive insulin obtained in these patients. 2 of the 4 cases exhibited unusually high biological insulin activities during the fasting state as well as after an intravenous (iv) glucose load. In the fat pad assay activities as high as 10 000 μU insulin per ml were observed. During childhood the biological insulin activities were generally high, although there were large individual variations. However, in the one case studied after the age of puberty, the insulin response to a glucose load was negligible. Taken together, the biological and immunological activities observed strongly suggest the presence of pancreatic insulin in these patients. It appears that the circulating insulin has a fully biological activity. The decreasing insulin activities after cessation of growth are in agreement with the appearance of frank diabetes at this time.

El Prestige: comparativa de los regímenes internacionales de responsabilidad civil

2019 ◽  
Vol 37 (3) ◽  
pp. 31
Author(s):  
Raquel Fernández González ◽  
Marcos Íñigo Pérez Pérez
Keyword(s):  
Institutional Economics ◽  
Geographical Area ◽  
New Institutional Economics ◽  
Rigorous Analysis ◽  
Judicial Process ◽  
Main Research ◽  
Civil Responsibility ◽  
The One ◽  
High Degree ◽  
The Prestige

The return of institutions to the main research agenda has highlighted the importance of rules in economic analysis. The New Institutional Economics has allowed a better understanding of the case studies that concern different areas of knowledge, also the one concerning the management of natural resources. In this article, the institutional analysis focuses on the maritime domain, where two large civil liability regimes for pollution coexist (OPA 90-IMO), each in a different geographical area (United States - Europe). Therefore, a comparative analysis is made between the two large regimes of civil responsibility assignment applying them to the Prestige catastrophe. In this way, the allocation and distribution of responsibilities in the investigation and subsequent judicial process of the Prestige is compared with an alternative scenario in which the applicable compensation instruments are governed by the provisions of the Oil Polution Act of 1990 (OPA 90), in order to establish a rigorous analysis on the effects that the different norms can have in the same scenario. In the comparative established in the case of the Prestige, where the responsibilities were solved very slowly in a judicial process with high transaction costs, the application of rules governed by the OPA 90 would not count with such a high degree of imperfection. This is so, since by applying the preponderance of the evidence existing in OPA 90 there would be no mitigation for the presumed culprits. On the other hand, the agents involved in the sinking would not be limited only to the owner, but also that operators or shipowners would be responsible as well. In addition, the amount of compensation would increase when counting in the damage count the personal damages, the taxes without perceiving and the ecological damage caused in a broad sense, damages not computable in the IMO.

scholarly journals Precision radiogenomics: fusion biopsies to target tumour habitats in vivo

2021 ◽  
Author(s):  
Mireia Crispin-Ortuzar ◽  
Evis Sala
Keyword(s):  
Ovarian Cancer ◽  
Ct Scans ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
High Degree ◽  
Degree Of Heterogeneity

SummaryHigh-grade serous ovarian cancer lesions display a high degree of heterogeneity on CT scans. We have recently shown that regions with distinct imaging profiles can be accurately biopsied in vivo using a technique based on the fusion of CT and ultrasound scans.

scholarly journals POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ronggang Luo ◽  
Yi Zhuo ◽  
Quan Du ◽  
Rendong Xiao
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Cancer Tissues

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.

Toxicokinetic and Genotoxicity Study of NNK in Male Sprague-Dawley Rats Following Nose-Only Inhalation Exposure, Intraperitoneal Injection, and Oral Gavage

2021 ◽  
Author(s):  
Shu-Chieh Hu ◽  
Matthew S Bryant ◽  
Estatira Sepehr ◽  
Hyun-Ki Kang ◽  
Raul Trbojevich ◽  
...  
Keyword(s):  
Human Lung ◽  
Inhalation Exposure ◽  
Systemic Exposure ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Sd Rats ◽  
New Information ◽  
Sprague Dawley Rats ◽  
Tissue Specimens

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5x10−5, 5x10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 hour. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal (IP) injection and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated timepoints and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 hours post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the toxicokinetics and genotoxicity of NNK.

scholarly journals The One-Year In Vivo Comparison of Lithium Disilicate and Zirconium Dioxide Inlays

Materials ◽  
2021 ◽  
Vol 14 (11) ◽  
pp. 3102
Author(s):  
Rini Behera ◽  
Lora Mishra ◽  
Darshan Devang Divakar ◽  
Abdulaziz A. Al-Kheraif ◽  
Naomi Ranjan Singh ◽  
...  
Keyword(s):  
Zirconium Dioxide ◽  
Clinical Performance ◽  
Lithium Disilicate ◽  
Study Groups ◽  
Resin Cement ◽  
Internal Surfaces ◽  
Colour Match ◽  
One Year ◽  
The One

The objective of the present study was to evaluate the one-year clinical performance of lithium disilicate (LD) and zirconium dioxide (ZrO2) class II inlay restorations. Thirty healthy individuals who met the inclusion criteria were enrolled for the study. The patients were randomly divided into two study groups (n = 15): LD (IPS e.max press) and ZrO2 (Dentcare Zirconia). In the ZrO2 group, the internal surfaces of the inlays were sandblasted and silanized with Monobond N (Ivoclar, Leichsteistein, Germany). In the LD group, the internal surfaces of the inlays were etched with 5% hydrofluoric acid. The ceramic inlays were cemented with self-cure resin cement (Multilink N). Clinical examinations were performed using modified United State Public Health Codes and Criteria (USPHS) after 2 weeks, 4 weeks, 6 months and 1 year. The one-year survival rate was evaluated. In total, one failure was observed in the ZrO2 group. The survival probability after 1 year for the ZrO2 inlays was 93%, and for the LD inlays was 100%, which was statistically insignificant. The differences between both groups for most USPHS criteria (except for colour match) were statistically insignificant. Within the imitations of the present study, the lithium disilicate- and zirconia dioxide-based inlays exhibited comparable clinical performances. However, the colour and translucency match was superior for the lithium disilicate restorations.

scholarly journals Formulation and Mathematical Optimization of Controlled Release Calcium Alginate Micro Pellets of Frusemide

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Amitava Ghosh ◽  
Prithviraj Chakraborty
Keyword(s):  
Sodium Alginate ◽  
Calcium Alginate ◽  
Mathematical Optimization ◽  
Extended Period ◽  
Cost Effective ◽  
Polynomial Equation ◽  
Chronic Hypertension ◽  
Order Polynomial ◽  
High Degree

Objective. Frusemide loaded calcium alginate micropellets, an oral microparticulate delivery system, was statistically optimized exhibiting prolonged therapeutic action minimizing its adverse effects.Methods. Ionotropic Gelation technique was adopted employing 32Factorial designs and keeping the entire process free from organic solvents. Physicochemical and the release characteristics of the prepared formulations were studied, keeping variations only in sodium alginate (primary polymer) and Acrycoat E30D (copolymer) dispersion.Result. Sodium alginate was predominant over Acrycoat E30D in all batches. Nonadditives or interaction was observed to be insignificant. Multiple regressions produced second-order polynomial equation, and the predictive results obtained were validated with high degree of correlation. Thein vivostudy applauded that optimized calcium alginate micropellets of frusemide can produce a much greater diuretic effect over an extended period of 24 hours.Conclusion. This study reveals that the potential of a single dose of the mathematically optimized micro pellets of frusemide formulation is sufficient in the management of peripheral edema and ascites in congestive heart failure and as well in the treatment of chronic hypertension, leading to better patient compliance, and can be produced with minimum experimentation and time, proving far more cost-effective formulation than the conventional methods of formulating dosage forms.

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