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Neuromuscular Physiology
Published in Michael H. Stone, Timothy J. Suchomel, W. Guy Hornsby, John P. Wagle, Aaron J. Cunanan, Strength and Conditioning in Sports, 2023
Michael H. Stone, Timothy J. Suchomel, W. Guy Hornsby, John P. Wagle, Aaron J. Cunanan
Some anions such as chloride (Cl–) diffuse through the neurolemma relatively easily and are not dependent on a pump. This results in [Cl–] being largely determined by electrical potential, as Cl– is repelled by the negative anions inside of the cell. The result is a high concentration (≈103 mEq/L) on the outside of the cell. Because of this mechanism, the role of Cl– in the maintenance of the RMP is passive. However, the duration and magnitude of an action potential can be affected by the movement of Cl– anions. Typically, other ions are affected in the same way as Na+, K+, and Cl–. However, the concentrations and the permeability of the neurolemma to these ions is small, thus the RMP is little affected. The most important role for these additional ions, particularly Ca++ and Mg++, is in their effect on the membrane permeability of other ions. For example, Ca++ may affect the distribution of electrons on proteins and alter the atomic/intra-molecular bond angles potentially modifying the structural conformation of the pore/channel proteins, creating differences in membrane permeability to specific ions (86). Permeability is also affected by membrane composition. For example, alterations in the cholesterol content of the neurolemma can alter its permeability to most ions (15).
Bioavailability and Granule Properties
Published in Dilip M. Parikh, Handbook of Pharmaceutical Granulation Technology, 2021
The Biopharmaceutics Classification System (BCS) is a drug development tool that allows estimation of the contribution of three fundamental factors including dissolution, solubility, and intestinal permeability, which govern the rate and extent of drug absorption from solid oral dosage forms [13]. Permeability is referred to as the ability of the drug molecule to permeate through a membrane into the systemic circulation.
Recent in vitro Models for the Blood-Brain Barrier
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
João Basso, Maria Mendes, Maria Ferreira, João Sousa, Alberto Pais, Carla Vitorino
Passive transport (diffusion) across the barrier can be quantified pertaining to the permeability coefficient (cm/s). The permeability coefficient is a common measure which is independent of the microdevice design, thus being an acceptable parameter for model comparison. However, it should be noted that other modes of transport than diffusion or active transport may also contribute to the measurement of the permeability coefficient. For this reason, it is necessary to control the solute concentration and the pressure in the microchannels during the experiments. Fluorescent compounds (which should be inert and without affecting the physiology and function of the BBB) are a good approach to confirm the barrier integrity [23, 50–53].
A review of nanocarrier-mediated drug delivery systems for posterior segment eye disease: challenges analysis and recent advances
Published in Journal of Drug Targeting, 2021
Rui Wang, Yuan Gao, Anchang Liu, Guangxi Zhai
Transporters are a key factor determining cell permeability and may influence drug pharmacokinetics. ATP-binding cassette (ABC) proteins, such as P-glycoprotein (P-gp/MDR1), multidrug resistance-associated proteins (MRP) and breast cancer resistance protein (BCRP), are regarded as the efflux pump for ocular drug delivery. It is worth noting that transporter expression and substrate recognition may differ among species. For instance, the expression and activity of MDR1 transporter were confirmed in rabbit corneal epithelium [26], but not in human corneal epithelium [26,27]. In addition, the expression of MRP3 and BCRP was detected in a human cornea model, whereas no functional expression was found in rabbit and porcine cornea. Therefore, data obtained using animal models should be used with caution to predict human transport rates. The efflux pump mentioned above has been confirmed to exist in human BAB and BRB. The efflux transporters can effectively limit drug accumulation in RPE. The MRP transporters appear to have a very important role in RPE permeability [28].
Nutrition Provides the Essential Foundation for Optimizing Mental Health
Published in Evidence-Based Practice in Child and Adolescent Mental Health, 2021
Julia J. Rucklidge, Jeanette M. Johnstone, Bonnie J. Kaplan
Another possible contributor to nutrient depletion of crops is the heavy use of glyphosate, an herbicide and principal ingredient of Roundup®. Glyphosate, initially patented in the United States in 1964 as a descaling agent to get rid of mineral deposits in pipes and boilers, is now applied to crops to kill weeds. A 2019 study showed that glyphosate disturbs the human blood-brain barrier, making it more permeable (Martinez & Al-Ahmad, 2019). Permeability means that some molecules that the blood-brain barrier intended to exclude might be able to pass through, causing adverse effects in the brain. It is also relevant that while there is still debate on the topic, concerns have been raised about whether glyphosate can make dietary minerals like iron, manganese, and nickel less available for the body to absorb (Zobiole et al., 2010) as well as decreasing soil health (Kanissery et al., 2019), factors that could also affect plant nutrient density.
Role of gut microbiota in regulating gastrointestinal dysfunction and motor symptoms in a mouse model of Parkinson’s disease
Published in Gut Microbes, 2021
Yogesh Bhattarai, Jie Si, Meng Pu, Owen A. Ross, Pamela J. McLean, Lisa Till, William Moor, Madhusudan Grover, Karunya K. Kandimalla, Kara G. Margolis, Gianrico Farrugia, Purna C. Kashyap
In vivo permeability was measured using the method described previously.32 Briefly, on the day of measurement mice were fasted for 2 h then given a 200 µl oral gavage containing 100 mg/mL creatinine, 60 mg/mL FITC-4 kDa Dextran, and 40 mg/mL of rhodamine B isothiocyanate-70 kDa dextran (Sigma) to allow assessment of pore (radius 2.6 Å), leak (radius 13 Å) and unrestricted (radius 64 Å) barrier pathways, respectively.32 Mice were fasted for additional 2 h after which food was replaced. Five hours post-gavage, the intracardiac puncture was performed to harvest blood and collect serum samples. Serum samples were sent to the Mayo Clinic Immunochemical core for creatinine analysis while fluorescence for FITC and RITC was measured using a Synergy Mx (BioTek) at excitation wavelengths of 485 and 553 nm and emission wavelengths of 528 and 627 nm respectively. These were converted into absolute concentrations using standard curves.