Membrane proton transport mediated by phenylhydrazonopropanedinitriles

1988 ◽  
Vol 53 (1) ◽  
pp. 186-197
Author(s):  
Ľubomír Kluka ◽  
Ernest Šturdík ◽  
Štefan Baláž ◽  
Dušan Kordík ◽  
Michal Rosenberg ◽  
...  
Keyword(s):  
Proton Transport ◽  
Physicochemical Characteristics ◽  
Potassium Ions ◽  
Inner Mitochondrial Membrane ◽  
Compartment System ◽  
Sodium Potassium ◽  
System 1 ◽  
System Water

Some fundamental physicochemical characteristics as stability in solutions, solubility in various solvents and association constants describing equilibria with protons and potassium ions in aqueous solutions were determined for phenylhydrazonopropanedinitriles (PHPD). The effect of pH and sodium, potassium, calcium, and magnesium cations on the distribution of PHPD were examined in a two-compartment system 1-octanol-water. The transmembrane transfer of protons by PHPD causing a disturbance of the pH-gradient was verified in vitro using a model three-compartment system water-octanol-water, imitating the in vivo intracristal space-inner mitochondrial membrane – matrix system. Transfer of H+ ions mediated by PHPD in the system under study was found to be considerably faster when an exchange with K+ ions (ion-exchanging antiport H+/K+) was possible. A model was described indicating the reality of ion-exchanging antiport H+/Me+ mediated by PHPD on biomembranes which is in line with the chemiosmotic theory.

scholarly journals A simple method of suspending implant wear particles for more physiological modelling of cell-particle interactions in vitro

2021 ◽  
Author(s):  
Christine Poon
Keyword(s):  
Wear Debris ◽  
Culture Media ◽  
Polymeric Materials ◽  
Wear Particle ◽  
Physicochemical Characteristics ◽  
Wear Particles ◽  
Simple Method ◽  
Implant Wear

AbstractArthroplasty implants e.g. hip, knee, spinal disc sustain relatively high compressive loading and friction wear, which lead to the formation of wear particles or debris between articulating surfaces. Despite advances in orthopaedic materials and surface treatments, the production of wear debris from any part of a joint arthroplasty implant is currently unavoidable. Implant wear debris induces host immune responses and inflammation, which causes patient pain and ultimately implant failure through progressive inflammation-mediated osteolysis and implant loosening, where the severity and rate of periprosthetic osteolysis depends on the material and physicochemical characteristics of the wear particles. Evaluating the cytotoxicity of implant wear particles is important for regulatory approved clinical application of arthroplasty implants, as is the study of cell-particle response pathways. However, the wear particles of polymeric materials commonly used for arthroplasty implants tend to float when placed in culture media, which limits their contact with cell cultures. This study reports a simple means of suspending wear particles in liquid medium using sodium carboxymethyl cellulose (NaCMC) to provide a more realistic proxy of the interaction between cells and tissues to wear particles in vivo, which are free-floating in synovial fluid within the joint cavity. Low concentrations of NaCMC dissolved in culture medium were found to be effective for suspending polymeric wear particles. Such suspensions may be used as more physiologically-relevant means for testing cellular responses to implant wear debris, as well as studying the combinative effects of shear and wear particle abrasion on cells in a dynamic culture environments such as perfused tissue-on-chip devices.

pqsfinder web: G-quadruplex prediction using optimized pqsfinder algorithm

2019 ◽  
Vol 36 (8) ◽  
pp. 2584-2586 ◽  
Author(s):  
Dominika Labudová ◽  
Jiří Hon ◽  
Matej Lexa
Keyword(s):  
Sequence Analysis ◽  
Recursive Algorithm ◽  
Supplementary Information ◽  
Potassium Ions ◽  
Bioconductor Package ◽  
G Quadruplex ◽  
Weak Points ◽  
User Friendly

Abstract Motivation G-quadruplex is a DNA or RNA form in which four guanine-rich regions are held together by base pairing between guanine nucleotides in coordination with potassium ions. G-quadruplexes are increasingly seen as a biologically important component of genomes. Their detection in vivo is problematic; however, sequencing and spectrometric techniques exist for their in vitro detection. We previously devised the pqsfinder algorithm for PQS identification, implemented it in C++ and published as an R/Bioconductor package. We looked for ways to optimize pqsfinder for faster and user-friendly sequence analysis. Results We identified two weak points where pqsfinder could be optimized. We modified the internals of the recursive algorithm to avoid matching and scoring many sub-optimal PQS conformations that are later discarded. To accommodate the needs of a broader range of users, we created a website for submission of sequence analysis jobs that does not require knowledge of R to use pqsfinder. Availability and implementation https://pqsfinder.fi.muni.cz, https://bioconductor.org/packages/pqsfinder. Supplementary information Supplementary data are available at Bioinformatics online.

Evaluation of low molecular weight polyethylenimine-introduced chitosan for gene delivery to mesenchymal stem cells

2020 ◽  
Vol 10 (7) ◽  
pp. 1170-1176
Author(s):  
Minchen Liu ◽  
Yulan Hu ◽  
Yi Feng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
A549 Cells ◽  
Safety Evaluation ◽  
Physicochemical Characteristics ◽  
Hatching Rate

This study aimed to examine the transfection ability of polyethylenimine (PEI) (1800 Da)-grafted chitosan (10 kDa) (CP), a newly synthesized PEI derivative, in mesenchymal stem cells (MSCs). The safety evaluation of the complex/DNA was studied in vitro and in vivo. In addition, CP/pGL3 was applied to investigate the effects of transfection efficiency. In this study, CP/DNA can be formed with compatible physicochemical characteristics for gene delivery. CP cytotoxicity decreased in A549 cells. Moreover, a zebrafish embryo model was used for evaluating the safety in vivo. Compared to the PEI (25 kDa) group, the zebrafish hatching rate increased and the mortality rate decreased in the CP/DNA group, which provided an indication of the safety of CP. In comparison with chitosan (100 kDa)-PEI (1200 Da), CP's transfection efficiency was higher in both A549 cells and MSCs. This study aimed to lay the foundation for further applications of CP in gene delivery. Therefore, further gene therapy investigations of CP by using MSCs need to be performed.

scholarly journals Impact of Mucin on Drug Diffusion: Development of a Straightforward In Vitro Method for the Determination of Drug Diffusivity in the Presence of Mucin

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 168 ◽  
Author(s):  
Margherita Falavigna ◽  
Paul Stein ◽  
Gøril Flaten ◽  
Massimiliano di Cagno
Keyword(s):  
Drug Interaction ◽  
Drug Absorption ◽  
Cost Effective ◽  
Physicochemical Characteristics ◽  
In Vivo Studies ◽  
Phospholipid Vesicle ◽  
Mucus Layer ◽  
The Impact

Mucosal drug delivery accounts for various administration routes (i.e., oral, vaginal, ocular, pulmonary, etc.) and offers a vast surface for the permeation of drugs. However, the mucus layer which shields and lubricates all mucosal tissues can compromise drugs from reaching the epithelial site, thus affecting their absorption and therapeutic effect. Therefore, the effect of the mucus layer on drug absorption has to be evaluated early in the drug-development phase, prior to in vivo studies. For this reason, we developed a simple, cost-effective and reproducible method employing UV-visible localized spectroscopy for the assessment of the interaction between mucin and drugs with different physicochemical characteristics. The mucin–drug interaction was investigated by measuring the drug relative diffusivity (Drel) in the presence of mucin, and the method was validated by fitting experimental and mathematical data. In vitro permeability studies were also performed using the mucus-covered artificial permeation barrier (mucus–PVPA, Phospholipid Vesicle-based Permeation Assay) for comparison. The obtained results showed that the diffusion of drugs was hampered by the presence of mucin, especially at higher concentrations. This novel method proved to be suitable for the investigation on the extent of mucin–drug interaction and can be successfully used to assess the impact that the mucus layer has on drug absorption.

scholarly journals Regulation of the Mitochondrial BKCa Channel by the Citrus Flavonoid Naringenin as a Potential Means of Preventing Cell Damage

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3010 ◽  
Author(s):  
Anna Kicinska ◽  
Rafał P. Kampa ◽  
Jan Daniluk ◽  
Aleksandra Sek ◽  
Wieslawa Jarmuszkiewicz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Damage ◽  
Herbal Medicines ◽  
Pharmacological Action ◽  
Bkca Channel ◽  
Inner Mitochondrial Membrane ◽  
Beneficial Effects ◽  
Factor Α

Naringenin, a flavanone obtained from citrus fruits and present in many traditional Chinese herbal medicines, has been shown to have various beneficial effects on cells both in vitro and in vivo. Although the antioxidant activity of naringenin has long been believed to be crucial for its effects on cells, mitochondrial pathways (including mitochondrial ion channels) are emerging as potential targets for the specific pharmacological action of naringenin in cardioprotective strategies. In the present study, we describe interactions between the mitochondrial large-conductance calcium-regulated potassium channel (mitoBKCa channel) and naringenin. Using the patch-clamp method, we showed that 10 µM naringenin activated the mitoBKCa channel present in endothelial cells. In the presence of 30 µM Ca2+, the increase in the mitoBKCa channel probability of opening from approximately 0.25 to 0.50 at −40 mV was observed. In addition, regulation of the mitoBKCa channel by naringenin was dependent on the concentration of calcium ions. To confirm our data, physiological studies on the mitochondria were performed. An increase in oxygen consumption and a decrease in membrane potential was observed after naringenin treatment. In addition, contributions of the mitoBKCa channel to apoptosis and necrosis were investigated. Naringenin protected cells against damage induced by tumor necrosis factor α (TNF-α) in combination with cycloheximide. In this study, we demonstrated that the flavonoid naringenin can activate the mitoBKCa channel present in the inner mitochondrial membrane of endothelial cells. Our studies describing the regulation of the mitoBKCa channel by this natural, plant-derived substance may help to elucidate flavonoid-induced cytoprotective mechanisms.

DECREASED ALDOSTERONE PRODUCTION BY RAT ADRENAL TISSUE IN VITRO DUE TO TREATMENT WITH 9α-FLUOROCORTISOL, DEXAMETHASONE AND ADRENOCORTICOTROPHIN IN VIVO

1970 ◽  
Vol 63 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Jürg Müller
Keyword(s):  
Sodium Intake ◽  
Sodium Balance ◽  
Potassium Ions ◽  
Aldosterone Secretion ◽  
Deficient Diet ◽  
Adrenal Tissue ◽  
Aldosterone Production ◽  
Unknown Control

ABSTRACT Quartered adrenal glands of rats treated with 9α-fluorocortisol, dexamethasone or adrenocorticotrophin (ACTH) for two weeks were found to produce 70–90% less aldosterone in vitro than the adrenal tissue of untreated animals. The same fractional decreases in aldosterone production were observed when the adrenal tissue was incubated under basal conditions or was stimulated by serotonin, potassium ions or ACTH. In rats kept on a sodium-deficient diet, treatment with dexamethasone and ACTH, respectively, impaired aldosterone production to the same extent as in rats on a normal sodium intake, whereas treatment with 9α-fluorocortisol was almost completely ineffective. These results indicate that inhibition of aldosterone secretion by an exogenous mineralocorticosteroid is mediated by changes in sodium balance. On the other hand, high levels of exogenous or endogenous glucocorticosteroids apparently decrease aldosterone production by a yet unknown control mechanism which is independent of sodium intake.

scholarly journals Celecoxib confinement within mesoporous silicon for enhanced oral bioavailability

2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Feng Wang ◽  
Timothy J. Barnes ◽  
Clive A. Prestidge
Keyword(s):  
Physicochemical Characteristics ◽  
In Vitro Dissolution ◽  
Absolute Bioavailability ◽  
Dissolution Behavior ◽  
Pharmacokinetic Parameters ◽  
Mesoporous Silicon ◽  
Silicon Matrix ◽  
Oxidized Porous Silicon

AbstractWe investigate the physicochemical characteristics of celecoxib (CEL) entrapped within particles of an oxidized porous silicon matrix (pSiox); determine the oral dose response of CEL compared to pure drug and innovator formulation; develop in vivo-in vitro correlation (IVIVC). CEL was loaded into a pSiox matrix by solvent partitioning, with the physical state of the CEL characterized by FTIR, DSC, TGA and XRD, and correlated with in vitro dissolution behavior. Single dose pharmacokinetic parameters of orally dosed CEL were determined in fasted rats for aqueous suspensions of pure CEL, Celebrexr and CEL-pSiox microparticles. Physicochemical testing of CEL-pSiox formulation confirmed the entrapment of CEL within porous nanostructure in an amorphous or non-crystalline form. CEL-pSiox demonstrated superior pharmacokinetics compared with CEL particles or Celebrexr, i.e. increased absolute bioavailability (96.2% vs. 65.2% vs. 88.1%), increased C

scholarly journals The role of endoplasmic reticulum in in vivo cancer FDG kinetics

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252422
Author(s):  
Sara Sommariva ◽  
Mara Scussolini ◽  
Vanessa Cossu ◽  
Cecilia Marini ◽  
Gianmario Sambuceti ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cancer Metabolism ◽  
Cultured Cells ◽  
Accumulation Rate ◽  
Compartment Model ◽  
Compartment System ◽  
Positron Emission Tomography Scanner ◽  
Three Compartment Model

A recent result obtained by means of an in vitro experiment with cancer cultured cells has configured the endoplasmic reticulum as the preferential site for the accumulation of 2-deoxy-2-[18F]fluoro-D-glucose (FDG). Such a result is coherent with cell biochemistry and is made more significant by the fact that the reticular accumulation rate of FDG is dependent upon extracellular glucose availability. The objective of the present paper is to confirm in vivo the result obtained in vitro concerning the crucial role played by the endoplasmic reticulum in FDG cancer metabolism. This study utilizes data acquired by means of a Positron Emission Tomography scanner for small animals in the case of CT26 models of cancer tissues. The recorded concentration images are interpreted within the framework of a three-compartment model for FDG kinetics, which explicitly assumes that the endoplasmic reticulum is the dephosphorylation site for FDG in cancer cells. The numerical reduction of the compartmental model is performed by means of a regularized Gauss-Newton algorithm for numerical optimization. This analysis shows that the proposed three-compartment model equals the performance of a standard Sokoloff’s two-compartment system in fitting the data. However, it provides estimates of some of the parameters, such as the phosphorylation rate of FDG, more consistent with prior biochemical information. These results are made more solid from a computational viewpoint by proving the identifiability and by performing a sensitivity analysis of the proposed compartment model.

Sign in / Sign up

Export Citation Format

Share Document