Inertance Estimation in a Lumped-Parameter Hydraulic Simulator of Human Circulation

2013 ◽  
Vol 135 (6) ◽  
Author(s):  
Ettore Lanzarone ◽  
Fabrizio Ruggeri

Pulsatile mock loop systems are largely used to investigate the cardiovascular system in vitro. They consist of a pump, which replicates the heart, coupled with a lumped-parameter hydraulic afterload, which simulates vasculature. An accurate dimensioning of components is required for a reliable mimicking of the physiopathological behavior of the system. However, it is not possible to create a component for the afterload inertance, and inertance contributions are present in the entire circuit. Hence, in the literature, inertance is neglected or qualitatively evaluated. In this paper, we propose two quantitative methods (Maximum-likelihood estimation (MLE) and Bayesian estimation) for estimating afterload inertance based on observed pressure and flow waveforms. These methods are also applied to a real mock loop system. Results show that the system has an inertance comparable with the literature reference value of the entire systemic circulation, and that the expected variations over inlet average flow and pulse frequency are in general confirmed. Comparing the methods, the Bayesian approach results in higher and more stable estimations than the classical MLE.

2021 ◽  
pp. 039139882110130
Author(s):  
Guang-Mao Liu ◽  
Fu-Qing Jiang ◽  
Xiao-Han Yang ◽  
Run-Jie Wei ◽  
Sheng-Shou Hu

Blood flow inside the left ventricle (LV) is a concern for blood pump use and contributes to ventricle suction and thromboembolic events. However, few studies have examined blood flow inside the LV after a blood pump was implanted. In this study, in vitro experiments were conducted to emulate the intraventricular blood flow, such as blood flow velocity, the distribution of streamlines, vorticity and the standard deviation of velocity inside the LV during axial blood pump support. A silicone LV reconstructed from computerized tomography (CT) data of a heart failure patient was incorporated into a mock circulatory loop (MCL) to simulate human systemic circulation. Then, the blood flow inside the ventricle was examined by particle image velocimetry (PIV) equipment. The results showed that the operating conditions of the axial blood pump influenced flow patterns within the LV and areas of potential blood stasis, and the intraventricular swirling flow was altered with blood pump support. The presence of vorticity in the LV from the thoracic aorta to the heart apex can provide thorough washing of the LV cavity. The gradually extending stasis region in the central LV with increasing blood pump support is necessary to reduce the thrombosis potential in the LV.


Endocrinology ◽  
1997 ◽  
Vol 138 (3) ◽  
pp. 1224-1231 ◽  
Author(s):  
Ursula B. Kaiser ◽  
Andrzej Jakubowiak ◽  
Anna Steinberger ◽  
William W. Chin

Abstract The hypothalamic hormone, GnRH, is released and transported to the anterior pituitary in a pulsatile manner, where it binds to specific high-affinity receptors and regulates gonadotropin biosynthesis and secretion. The frequency of GnRH pulses changes under various physiological conditions, and varying GnRH pulse frequencies have been shown to regulate differentially the secretion of LH and FSH and the expression of the gonadotropin α, LHβ, and FSHβ subunit genes in vivo. We demonstrate differential effects of varying GnRH pulse frequency in vitro in superfused primary monolayer cultures of rat pituitary cells. Cells were treated with 10 nm GnRH pulses for 24 h at a frequency of every 0.5, 1, 2, or 4 h. α, LHβ, and FSHβ messenger RNA (mRNA) levels were increased by GnRH at all pulse frequencies. α and LHβ mRNA levels and LH secretion were stimulated to the greatest extent at a GnRH pulse frequency of every 30 min, whereas FSHβ mRNA levels and FSH secretion were stimulated maximally at a lower GnRH pulse frequency, every 2 h. GnRH receptor (GnRHR) mRNA levels also were increased by GnRH at all pulse frequencies and were stimulated maximally at a GnRH pulse frequency of every 30 min. Similar results were obtained when the dose of each pulse of GnRH was adjusted to maintain a constant total cumulative dose of GnRH over 24 h. These data show that gonadotropin subunit gene expression is regulated differentially by varying GnRH pulse frequencies in vitro, suggesting that the differential effects of varying GnRH pulse frequencies on gonadotropin subunit gene expression occur directly at the level of the pituitary. The pattern of regulation of GnRHR mRNA levels correlated with that of α and LHβ but was different from that of FSHβ. This suggests that α and LHβ mRNA levels are maximally stimulated when GnRHR levels are relatively high, whereas FSHβ mRNA levels are maximally stimulated at lower levels of GnRHR expression, and that the mechanism for differential regulation of the gonadotropins by varying pulse frequencies of GnRH may involve levels of GnRHR. Furthermore, these data suggest that the mechanisms whereby varying GnRH pulse frequencies stimulate α, LHβ, and GnRHR gene expression are similar, whereas the stimulation of FSHβ mRNA levels may be different.


2006 ◽  
Vol 13 (6) ◽  
pp. 671-677 ◽  
Author(s):  
Robert Mabry ◽  
Kathleen Brasky ◽  
Robert Geiger ◽  
Ricardo Carrion ◽  
Gene B. Hubbard ◽  
...  

ABSTRACT Several strategies that target anthrax toxin are being developed as therapies for infection by Bacillus anthracis. Although the action of the tripartite anthrax toxin has been extensively studied in vitro, relatively little is known about the presence of toxins during an infection in vivo. We developed a series of sensitive sandwich enzyme-linked immunosorbent assays (ELISAs) for detection of both the protective antigen (PA) and lethal factor (LF) components of the anthrax exotoxin in serum. The assays utilize as capture agents an engineered high-affinity antibody to PA, a soluble form of the extracellular domain of the anthrax toxin receptor (ANTXR2/CMG2), or PA itself. Sandwich immunoassays were used to detect and quantify PA and LF in animals infected with the Ames or Vollum strains of anthrax spores. PA and LF were detected before and after signs of toxemia were observed, with increasing levels reported in the late stages of the infection. These results represent the detection of free PA and LF by ELISA in the systemic circulation of two animal models exposed to either of the two fully virulent strains of anthrax. Simple anthrax toxin detection ELISAs could prove useful in the evaluation of potential therapies and possibly as a clinical diagnostic to complement other strategies for the rapid identification of B. anthracis infection.


1990 ◽  
Vol 112 (1) ◽  
pp. 75-79 ◽  
Author(s):  
O. Lichtenstein ◽  
U. Dinnar

This study presents a simulated analysis of Phased Compression Cardiac Assist Device (PCCAD) and evaluation of its applicability as a non-invasive temporary assist for a failing heart. The new technique is based on the chest pump mechanism for blood flow augmentation during external massage by phased compression of the abdominal and thoracic cavities. A semi-closed hydraulic system to simulate the systemic circulation was constructed; the system includes a left ventricle which functions according to the Starling principle and a pneumatic system which controls the pressures applied to the thoracic and abdominal cavities, in complete synchronization with the beating normal or failing heart. The possibility of manipulating the three pumps in series (venous, heart, and arterial) has been checked, and the principal parameters which effect the efficiency of the PCCAD were evaluated. This in-vitro analysis shows the high potential of a non-invasive temporary cardiac assist device. It points to the necessary measures one has to take in order to achieve good synchronization and to interfere externally with the augmentation of cardiac output or with the augmentation of root aortic pressure.


2018 ◽  
Vol 12 (1) ◽  
pp. 638-646 ◽  
Author(s):  
Massimo Amato ◽  
Alfredo Iandolo ◽  
Giuseppe Pantaleo ◽  
Dina Abtellatif ◽  
Michele Simeone ◽  
...  

Aim: The aim of this study was to evaluate the efficacy of the IG-file, a new instrument designed for apical diameter gauging. Materials and Methods: After shaping with F1 Universal Protaper, 60 roots were randomly divided into two groups and assigned to two operators, One Expert in Endodontics (EO) and One Unexpert (UO). In each sample, after canal curvatures have been detected, the apical diameters were measured with the IG-file and the K-NiTi. The results were compared with the reference value obtained by retrograde apical gauging. The data were statistically analyzed. Results: Among 60 samples, 10% of errors were recorded when the IG-files were used; in the K-NiTi group the incorrect measurements were 70%. In both groups (expert and unexpert) the IG-file measurements were more accurate than the K-NiTi (90 vs 33 and 90 vs 26,7). The differences were statistically significant. In curved canals, the difference between measurement rates performed with both instruments was statistically significant (85,7% IG-file vs 28,6% K-NiTi) as well as for the samples without curvatures (92,3% IG file vs 30,8% NiTi file). In root canals without curvatures overestimation errors in K-NiTi file group are more frequent than underestimation errors. This difference was statistically significant. Conclusion: A proper gauging of the apical diameter has a key role in endodontic therapy; an incorrect measurement can lead to clinical failures. This “in vitro” study highlights that IG-file improves measurement accuracy independently from clinician experience. Furthermore, in curved canals, the IG-file is more accurate than K-NiTi.


Author(s):  
Harmanpreet Singh ◽  
Pooja Jaiswal ◽  
Suksham Gupta ◽  
Simerjit Singh

  Objective: The current investigation deals with formulation and evaluation of fast disintegrating sublingual tablets of rizatriptan benzoate (RTB) to produce its intended therapeutic effect for acute treatment of migraine. When the drug is given by sublingual route, it overcomes the first pass metabolism and quick entry of drug in systemic circulation is obtained. It would result in fast pharmacological response hence faster relief from migraine which is an important criterion in migraine therapy.Methods: In this study, RTB sublingual tablets were prepared using direct compression process using various bioadhesive polymers such as sodium carboxymethyl cellulose, hydroxyl propyl methyl cellulose-K4M, and chitosan at various concentration ranging 0.5-5% w/w along with sodium starch glycolate (SSG) or cross carmellose sodium (CCS) as super disintegrants at different concentration ranging 2-8% w/w.Results: The tablets disintegrated quickly and dissolution tests conclude that RTB was released from the formulation within the compendial limits. The formulations batches (A8 and B8) containing 2% w/w chitosan along with 2% w/w SSG or CCS which disintegrate rapidly and show high dissolution and ex vivo permeation were selected as optimized formulations.Conclusion: The results obtained from the study showed that the bioavailability problem of the drug has been solved as the drug is given by sublingual route and it directly enters into systemic circulation. Furthermore, the formulation overcomes the problems associated with migraine attack as fast disintegrating technology is used.


2021 ◽  
Author(s):  
Emma V Troth ◽  
Dennis E Kyle

Naegleria fowleri is a pathogenic free-living amoeba that is commonly found in warm, freshwater and can cause a rapidly fulminant disease known as primary amoebic meningoencephalitis (PAM). New drugs are urgently needed to treat PAM, as the fatality rate is >97%. Until recently, few advances have been made in the discovery of new drugs for N. fowleri and one drawback is the lack of validated tools and methods to enhance drug discovery and diagnostics research. In this study we aimed to validate alternative methods to assess cell proliferation that are commonly used for other cell types and develop a novel drug screening assay to evaluate drug efficacy on N. fowleri replication. EdU (5-ethynyl-2´-deoxyuridine) is a pyrimidine analog of thymidine that can be used as a quantitative endpoint for cell proliferation. EdU incorporation is detected via a copper catalyzed click reaction with an Alexa Fluor linked azide. EdU incorporation in replicating N. fowleri was validated using fluorescence microscopy and quantitative methods for assessing EdU incorporation were developed by using an imaging flow cytometer. Currently used PAM therapeutics inhibited N. fowleri replication and EdU incorporation in vitro. EdA (5'ethynyl-2'-deoxyadenosine), an adenine analog, also was incorporated by N. fowleri, but was more cytotoxic than EdU. In summary, EdU incorporation could be used as a complimentary method for drug discovery for these neglected pathogens.


2021 ◽  
pp. 301-321
Author(s):  
Aleksey Domanov

This article attempts to identify the main assumptions, prerequisites and techniques of the methods developed by some modern statisticians on the basis of T. Bayes' theorem for the purposes of social variables interactions assessment. The author underlined several advantages of the given approach as compared to more traditional quantitative methods and highlighted key research areas subject to evaluation by Bayesian estimates. First of all, this approach is compatible with game and decision theory, event analysis, hidden Markov chains, prediction using neural networks and other predictive algorithms of artificial intelligence. The Bayesian approach differs significantly from traditional statistical methods (first of all, it is focused on finding the most probable, rather than the only true value of the feature coupling coefficient), hence a graphical interpretation was provided for such basic concepts and techniques as probabilistic inference, maximum likelihood estimation and Bayesian confidence network. The described tools were used to test the hypothesis about the impact of life quality decrease on rise in Euroscepticism of EU citizens. ANOVA and correlation analysis of 27 thousand people’s responses to Eurobarometer questions addressed in November-December 2019 attributed strong likelihood to this assumption. Moreover, Bayesian approach allowed for a probabilistic conclusion that this hypothesis is more plausible than the link between Euroscepticism and respondents’ current financial situation (explanatory power of comparison to the past is relatively greater).


ASAIO Journal ◽  
2005 ◽  
Vol 51 (2) ◽  
pp. 60A
Author(s):  
T Okahisa ◽  
H Okubo ◽  
D Ogawa ◽  
T Oda ◽  
T Motomura ◽  
...  

Nanomedicine ◽  
2021 ◽  
Author(s):  
Samrajya Lakshmi Yeruva ◽  
Prashant Kumar ◽  
Seetharam Deepa ◽  
Anand K Kondapi

Aim: We report here the development of tenofovir- and curcumin-loaded lactoferrin nanoparticles (TCNPs) as an HIV-microbicide. Materials & methods: TCNPs were subjected to various physicochemical characterization experiments, followed by in vitro and in vivo experiments to assess their efficacy. Results: TCNPs had a diameter of 74.31 ± 2.56 nm with a gross encapsulation of more than 61% for each drug. Nanoparticles were effective against HIV-1 replication, with an IC50 of 1.75 μM for curcumin and 2.8 μM for tenofovir. TCNPs provided drug release at the application site for up to 8–12 h, with minimal leakage into the systemic circulation. TCNPs showed spermicidal activity at ≥200 μM and induced minimal cytotoxicity and inflammation in the vaginal epithelium as revealed by histopathological and ELISA studies. Conclusion: We demonstrated that TCNPs could serve as a novel anti-HIV microbicidal agent in rats. [Formula: see text]


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