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Modelling and Simulation of Nanosystems for Delivering Drugs to the Brain
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
Tânia F. G. G. Cova, Sandra C.C. Nunes
In Ref. [14] the convention enhanced delivery (CED) of liposomes loaded with doxorubicin was studied through a multiphysics model applied to 3D brain tumour images obtained by magnetic resonance. The model examines the role of tumour and liposome properties (see Tables 1 and 2 in Ref. [14]) covering important steps such as the drug release from the liposomes, drug migration with interstitial fluid flow, diffusion in the interstitial space of tumour and the surrounding normal tissue, binding with proteins, drainage by blood and elimination due to metabolism and physical degradation. The numerical model divides the tumour and its surrounding normal tissue into three compartments: extracellular space, cell membrane and intracellular space. Among other assumptions, it considers that (i) brain tumour and surrounding normal tissue are porous media, (ii) drug delivery occurs under general conditions without the effect of the insertion of the catheter, which is (iii) considered to be located in the tumour centre without examining the impact of infusion location, and also (iv) the effect of cell density on convention enhanced delivery treatments can be disregarded. Simulation results showed that intracerebral infusion was effective in increasing the interstitial fluid velocity and inhibiting the fluid leakage from blood around the infusion site. The effect of each transport property on the delivery outcomes, allowing to establish and optimise the liposome properties and delivery regimen for enhancing treatment efficacy, was also illustrated.
Electrodiagnostic Studies
Published in Joseph D. Bronzino, Donald R. Peterson, Biomedical Engineering Fundamentals, 2019
e nerve and muscle cells are electrically “active.” In their “resting” state, the cell maintains a voltage dierence of 80 mV across the cell membrane, the intracellular being negative (Figure 46.1b-a). If the cell depolarizes, that is, the intracellular potential increases from −80 to −50 mV (Figure 46.1b-b), an action potential (AP) is generated. It begins by opening the voltage-dependent sodium channels in the membrane, causing a ux of sodium ions from the extracellular space to the intracellular space. e intracellular space becomes positive with respect to the extracellular space by roughly 30 mV (Figure 46.1b-c). e sodium channels then close while potassium channels open. e movement of potassium ions from the intracellular space to the extracellular space (Figure 46.1b-d) restores the cell to its normal state (Figure 46.1b-e). is event lasts for only a millisecond or two. e depolarization also spreads along the muscle or nerve ber, causing the propagation (or conduction) of the AP. e initial depolarization of the cell membrane to produce the AP occurs via the release of neurotransmitters such as acetylcholine. e cell membrane can also be depolarized by applying an external electrical or magnetic eld. is forms the basis for the nerve (or muscle) stimulation to perform conduction studies.
The Application of Pharmacokinetic Models to Predict Target Dose
Published in Rhoda G. M. Wang, James B. Knaak, Howard I. Maibach, Health Risk Assessment, 2017
Jerry N. Blancato, Kenneth B. Bishoff
The concepts discussed in the previous section can be mathematically expanded to result in a description of disposition into cellular regions which depends upon parameters which have more physiologic meaning than those enumerated in the previous equations. For this purpose, the organ of interest will be initially subcompartmentalized into three distinct regions: the capillary pool, the extravascular space, and the intracellular space. The blood in the capillary bed represents only a fraction of the total arterial flow to the organ; thus equilibrium with the arterial blood may not be rapidly reached. Over time, different capillaries in an organ are open. Usually not all are open at one time. As a result, not all the capillaries would be receiving the chemical from the arterial flow at any one time. Thus it is to be expected that at the first pass of arterial blood containing a toxin, only some capillaries would receive blood rich in toxin. Therefore if all of the capillaries were collectively sampled at that time, the concentration of toxin in the blood of the collective capillary sample would be less than the concentration in the arterial sample. For modeling purposes, the capillaries are assumed to be such a collective sample rather than just a sample of one individual capillary reaching instantaneous equilibrium with the artery that just supplied its blood. Toxin is then able to diffuse across the collective capillary membrane into the extracellular space and from there across the cell membrane into the intracellular space.
Pre-exercise hypohydration prevalence in soccer players: A quantitative systematic review.
Published in European Journal of Sport Science, 2020
L. Chapelle, B. Tassignon, N. Rommers, E. Mertens, P. Mullie, P. Clarys
Hypohydration, defined as a decrease in total body water content due to a mismatch between fluid intake and fluid floss, is known to decrease plasma volume and increase plasma osmotic pressure (Kenefick & Cheuvront, 2016). Although the increased plasma osmotic pressure mobilises fluid from the intracellular space into the extracellular space, this amount of fluid is not sufficient to restore plasma volume completely (Kenefick & Cheuvront, 2016; Oppliger & Bartok, 2002). As a consequence, skin blood flow and the sweating response will decrease during exercise thereby increasing body core temperature and thermoregulatory strain since the ability to transfer heat from the exercising muscles to the skin surface is impaired (Kenefick & Cheuvront, 2016). The decreased plasma volume also results in a decreased cardiac output and increased heart rate during exercise leading to a higher physiological strain (Kenefick & Cheuvront, 2016; Oppliger & Bartok, 2002; Sawka et al., 2007). In hot and humid environments, the presence of hypohydration exacerbates the thermoregulatory strain since the body’s potential to dissipate heat is further diminished. This diminished potential is due to a decreased heat loss capacity and a greater dependence on sweating for evaporative cooling (Sawka et al., 2007).
Mechanical filtration of the cerebrospinal fluid: procedures, systems, and applications
Published in Expert Review of Medical Devices, 2023
The central nervous system (CNS) compartments are the parenchyma of the brain and spinal cord, including the intracellular space with the intracellular fluids (ICF) and the extracellular space with the interstitial fluid (ISF), and the cerebrospinal fluid (CSF) space. The tissues of the CNS are separated from the systemic circulation by the blood–brain barrier (BBB) and blood–CSF barrier (BCSFB). These barriers protect the CNS from endogenous and exogenous compounds present in the systemic circulation and are essential to ensure the proper function of the CNS. In contrast to the BCSFB and BBB, the CSF and the ISF are not tightly separated. Even large molecules up to the size of albumin can move from/to the ISF and the CSF [1].
Theory of fast field-cycling NMR relaxometry of liquid systems undergoing chemical exchange
Published in Molecular Physics, 2018
Pascal H. Fries, Elie Belorizky
The influence of the acquisition delay on the best fit values of residence times and intrinsic relaxation times is illustrated now by simulating a very-low-field FFC-MRI investigation of a tumour tissue of a mouse leg [14]. Indeed, prototypes of FFC-MRI scanners and FFC-NMR relaxometers operating down to 2 are under development within the framework of the European project IDentIFY. In a tissue, at a given relaxation field , a water molecule basically goes back and forth between the intracellular space with intrinsic longitudinal time during a residence time and the extracellular space with intrinsic longitudinal time during a residence time . The population fractions are assumed to be and since , denoted as in Ref. [14], ranges between 0.14 and 0.30. Since the intracellular lifetime ranges between 0.48 and 1.44 s, we assume = 800 ms and = 200 ms. Below 0.2 mT, according to Figure 4 of Ref. [14] and to Fig. S2 of the related Supporting Information, and are expected to be of the order of a few tens and a few hundreds of ms, respectively. For simulation purpose, at = 10 , we take extrapolated values = 20 ms and = 400 ms. The initial proton magnetisation is assumed to have the equilibrium value in the polarisation field = 100 mT. The acquisition field is = 60 mT, in which the estimates of the intrinsic relaxation times are = 150 ms and = 2000 ms. Finally, the acquisition delay has a typical value = 20 ms as in an MRI scanner built by Lurie et al. [2,7–9]. Thus, is not negligible with respect to both and .