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Transmembrane Potentials of Human Lymphocytes*
Published in Richard C. Niemtzow, Transmembrane Potentials and Characteristics of Immune and Tumor Cell, 2020
All living cells are bounded by a cytoplasmic membrane composed of a bilayer of phospholipid molecules sandwiched between a layer of protein molecules. This fluid network is essential for sustaining the integrity of the cell. By virtue of this membrane, an electrical potential exists between its exterior and interior surfaces, designated “transmembrane potential”, and is measured in units of millivolts. This single measurement represents important biophysical events occurring at the membrane. The membrane is constantly in fluid flux with respect to certain thermodynamic states proper to its specific metabolism and interfacial environment. The electrical potential develops as a result of ionic movements across the membrane and is actually equal to the net algebraic sum of positive and negative ions and organic molecular charges on both sides of the boundary membrane. Practically, the movements of sodium and potassium ions are the most significant determinants of resting and action potentials in neurons and muscle cells. The selectivity of the membrane is due to the presence of membrane channels which allow the diffusion of specific ions. Of interest to immunologists is the fact that membrane receptors for a specific immune cell ligand, when placed in a diffusion gradient of that ligand, will statistically cluster in such a manner that the spatial relationship of the membrane is suitable not only to the exchange of immune factors, but as a consequence of the change in membrane permeability, will produce an alteration in its electrical properties.
Oxygen Consumption
Published in Robert A. Greenwald, CRC Handbook of Methods for Oxygen Radical Research, 2018
The majority of laboratories, other than those with a demand for specialized applications, now use the Clark-type membrane-covered combination electrode. These electrodes are commercially available and are rather robust. They differ from the naked vibrating and rotating electrodes in that both cathode and anode are mounted in an epoxyresin moulding and are separated from the reaction system by an oxygen-permeable Teflon® or polyethylene membrane. The electrode tip is designed so as to trap KCl solution between the anode and the membrane (Figure 3). The diffusion gradient across the membrane is removed by continuous replacement of fluid at the surface, achieved by a magnetic stirrer and a suitably designed follower. The somewhat longer but generally acceptable response time of membrane covered electrodes (90% in 5 to 10 sec) is compensated for by increased convenience and a greatly decreased susceptibility to electrode poisoning.
Orthopaedic Implant–Associated Infections: Pathogenesis, Clinical Presentation and Management
Published in Huiliang Cao, Silver Nanoparticles for Antibacterial Devices, 2017
In addition to the inefficient elimination by phagocytes, biofilm bacteria are also resistant to most antibiotics (Costerton et al. 1999; Stewart and Costerton 2001). Even long-term antimicrobial therapy frequently fails (Brandt et al. 1997). Antimicrobial activity requires penetration into the biofilm matrix (Stewart et al. 2009). Antibiotics penetrate along a diffusion gradient. In addition, for most antibiotics, there are channels penetrating through the biofilm matrix (Hoiby et al. 2011). The biofilm can be considered as an extra compartment in the tissue. Thus, during antibiotic treatment, there is not only a concentration gradient of antibiotics from the bloodstream to the tissue but also delay of their accumulation. Assuming biofilms as a third compartment, there is an additional concentration gradient as well as a further delay in antibiotic accumulation. If an antibiotic with short half-life and limited penetration abilities is used to treat the biofilm infection, the antibiotic concentration may likely never reach sufficient levels.
Cryoablation as a first-line therapy for atrial fibrillation: current status and future prospects
Published in Expert Review of Medical Devices, 2022
Jason G. Andrade, Marc W. Deyell, Marc Dubuc, Laurent Macle
In contrast to radiofrequency energy, lesion formation with cryothermal ablation occurs through convective cooling. This tissue injury occurs through a combination of freezing-induced cellular injury and ischemic cell death due to microcirculatory failure [32]. Freezing induction results in progressive retardation of cellular metabolism, resulting in the loss of ion pump transport and induction of a more acidic intracellular environment [33]. Continued cooling leads to the formation of extracellular ice, generating hypertonia and a compensatory egress of water from the intracellular space [34]. This osmotic gradient precipitates a diffusion gradient resulting in the movement of hydrogen ions out of the cell and migration of solute ions into the cell, further reducing intracellular pH. This leads to enzyme impairment, protein damage, mitochondrial injury, and plasma membrane injury [34]. Subsequent to the freezing phase is coalescence of the intracellular and extracellular ice crystals. This coalescence augments the osmotic damage, and generates shear forces that further disrupt cellular architecture [35]. Rewarming-induced restoration of the microcirculation leads to vascular obliteration and microthrombi formation, extending the tissue destruction through ischemic cellular necrosis [36]. Reactive inflammation followed by replacement fibrosis constitutes the final phase, resulting in a mature lesion with a dense well-circumscribed central region of cold-induced fibrosis surrounded by a narrow border of cellular death due to microvascular injury and apoptosis [37].
The Mucosally-Adherent Rectal Microbiota Contains Features Unique to Alcohol-Related Cirrhosis
Published in Gut Microbes, 2021
Ting-Chin David Shen, Scott G. Daniel, Shivali Patel, Emily Kaplan, Lillian Phung, Kaylin Lemelle-Thomas, Lillian Chau, Lindsay Herman, Calvin Trisolini, Aimee Stonelake, Emily Toal, Vandana Khungar, Kyle Bittinger, K. Rajender Reddy, Gary D. Wu
There are limitations to our study. It was conducted at a single medical center in the Northeastern US with a limited sample size. Whether our findings can be generalized to the cirrhosis population at large in the US and worldwide will require further studies with larger sample sizes and a more heterogeneous study population. Additionally, our cirrhosis cohort consisted mostly of Child-Pugh Class B (CPS range 6–11, mean 7.67), with MELD score range 7–26 (mean 14.74). Thus, it is uncertain whether the findings can be extended to more severe liver diseases with higher CPS and MELD scores. We were unable to detect an association between dysbiosis and severity of liver disease potentially due to this limitation. Furthermore, although we hypothesized that ethanol and its metabolites are likely exerting greater effects at the mucosal surface due to diffusion gradient, we do not have correlative data between plasma, mucosal, and luminal levels of ethanol and its metabolites.
Anti-inflammatory flurbiprofen nasal powders for nose-to-brain delivery in Alzheimer’s disease
Published in Journal of Drug Targeting, 2019
Laura Tiozzo Fasiolo, Michele Dario Manniello, Fabrizio Bortolotti, Francesca Buttini, Alessandra Rossi, Fabio Sonvico, Paolo Colombo, Georgia Valsami, Gaia Colombo, Paola Russo
We have recently reviewed the nasal powders as dosage forms, underlining indisputable advantages compared to liquids from the biopharmaceutical and stability perspectives [22]. In particular, powders enhance the transport of the drug across the nasal barrier. After prompt drug dissolution in the fluid lining the nasal mucosa, a saturation concentration sustains the diffusion gradient across the tissue [23,24]. This is the target product profile for powder deposition in the nasal cavity when the CNS is the drug action site [25,26]. A nasal powder formulation of flurbiprofen aiming to increase the drug disposition into the brain [15] requires the construction of microparticles to be actively or passively deposited into the nose for a prompt drug release. Therefore, the aim of this research was to study flurbiprofen nasal powder formulations effective for nasal deposition and drug transport to brain through nasal mucosa. Flurbiprofen microparticles useful for nasal powder delivery were constructed. Using a powder technology typical for the manufacturing of microparticles for inhalation, the flurbiprofen API was transformed into micronized particles by spray drying [27]. By employing the drug in acid form or its sodium salt, microparticles were prepared with or without excipients, using two lab scale spray drying equipment and different operating conditions. The obtained nasal powders were characterised in vitro, and the ex vivo drug transport was assessed. The final nasal product construction and in vivo evaluation will be described in a subsequent paper.