Academic literature on the topic 'Cell membranes Effect of drugs on'
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Journal articles on the topic "Cell membranes Effect of drugs on"
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Ramalho, Maria João, Stéphanie Andrade, Joana Angélica Loureiro, and Maria Carmo Pereira. "Interaction of Bortezomib with Cell Membranes Regulates Its Toxicity and Resistance to Therapy." Membranes 12, no. 9 (August 23, 2022): 823. http://dx.doi.org/10.3390/membranes12090823.
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Bortezomib (BTZ) is a potent proteasome inhibitor currently being used to treat multiple myeloma. However, its high toxicity and resistance to therapy severely limit the treatment outcomes. Drug–membrane interactions have a crucial role in drugs’ behavior in vivo, affecting their bioavailability and pharmacological activity. Additionally, drugs’ toxicity often occurs due to their effects on the cell membranes. Therefore, studying BTZ’s interactions with cell membranes may explain the limitations of its therapy. Due to the cell membranes’ complexity, lipid vesicles were proposed here as biomembrane models, focusing on the membrane’s main constituents. Two models with distinct composition and complexity were used, one composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and the other containing DMPC, cholesterol (Chol), and sphingomyelin (SM). BTZ’s interactions with the models were evaluated regarding the drugs’ lipophilicity, preferential location, and effects on the membrane’s physical state. The studies were conducted at different pH values (7.4 and 6.5) to mimic the normal blood circulation and the intestinal environment, respectively. BTZ revealed a high affinity for the membranes, which proved to be dependent on the drug-ionization state and the membrane complexity. Furthermore, BTZ’s interactions with the cell membranes was proven to induce changes in the membrane fluidity. This may be associated with its resistance to therapy, since the activity of efflux transmembrane proteins is dependent on the membrane’s fluidity.
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Kotyńska, Joanna, and Monika Naumowicz. "Effect of Selected Anionic and Cationic Drugs Affecting the Central Nervous System on Electrical Properties of Phosphatidylcholine Liposomes: Experiment and Theory." International Journal of Molecular Sciences 22, no. 5 (February 25, 2021): 2270. http://dx.doi.org/10.3390/ijms22052270.
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Interactions between phospholipid membranes and selected drugs affecting the central nervous system (CNS) were investigated. Small, unilamellar liposomes were used as biomimetic cell membrane models. Microelectrophoretic experiments on two-component liposomes were performed using the electrophoretic light scattering technique (ELS). The effect of both positively (perphenazine, PF) and negatively (barbituric acid, BA) charged drugs on zwitterionic L-α-phosphatidylcholine (PC) membranes were analyzed. Experimental membrane surface charge density (δ) data were determined as a function of pH. Quantitative descriptions of the adsorption equilibria formed due to the binding of solution ions to analyzed two-component membranes are presented. Binding constants of the solution ions with perphenazine and barbituric acid-modified membranes were determined. The results of our research show that both charged drugs change surface charge density values of phosphatidylcholine membranes. It can be concluded that perphenazine and barbituric acid are located near the membrane surface, interacting electrostatically with phosphatidylcholine polar heads.
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Aszalos, A., G. C. Yang, and M. M. Gottesman. "Depolymerization of microtubules increases the motional freedom of molecular probes in cellular plasma membranes." Journal of Cell Biology 100, no. 5 (May 1, 1985): 1357–62. http://dx.doi.org/10.1083/jcb.100.5.1357.
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Depolymerization of microtubules resulted in an increase in the motional freedom of molecular probes in the plasma membranes of Chinese hamster ovary cells expressed by the order parameter, S, measured with two different lipid-soluble spin label probes, 5-doxyl stearic acid and 16-doxyl methylstearate. Treatment with a variety of microtubule-depolymerizing agents, including Colcemid, colchicine, vinblastine, podophyllotoxin, and griseofulvin, all had similar effects on motional freedom of the probes whereas beta-lumicolchicine was inactive. Several independent lines of evidence suggest that these changes in motional freedom of the probes were not the direct result of the interaction of these relatively hydrophobic drugs with the plasma membrane: the effects of the drugs were not immediate; the dose response of the Colcemid effect was the same as the dose response for depolymerization of microtubules; taxol, which stabilizes microtubules but does not affect motional freedom in the membranes, blocked the effect of Colcemid on motional freedom; a mutant cell line which is resistant to colchicine because of reduced uptake of the drug showed no effects of colchicine on probe motional freedom; and a Colcemid-resistant mutant cell line with an altered beta-tubulin showed no effect of Colcemid on motional freedom in the membrane. These results support the hypothesis that microtubules might affect, directly or indirectly, plasma membrane functions.
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Torrisi, Cristina, Giuseppe Antonio Malfa, Rosaria Acquaviva, Francesco Castelli, and Maria Grazia Sarpietro. "Effect of Protocatechuic Acid Ethyl Ester on Biomembrane Models: Multilamellar Vesicles and Monolayers." Membranes 12, no. 3 (February 28, 2022): 283. http://dx.doi.org/10.3390/membranes12030283.
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The interactions of drugs with cell membranes are of primary importance for several processes involved in drugs activity. However, these interactions are very difficult to study due to the complexity of biological membranes. Lipid model membranes have been developed and used to gain insight into drug–membrane interactions. In this study, the interaction of protocatechuic acid ethyl ester, showing radical-scavenging activity, antimicrobial, antitumor and anti-inflammatory effects, with model membranes constituted by multilamellar vesicles and monolayers made of DMPC and DSPC, has been studied. Differential scanning calorimetry and Langmuir–Blodgett techniques have been used. Protocatechuic acid ethyl ester interacted both with MLV and monolayers. However, a stronger interaction of the drug with DMPC-based model membranes has been obtained. The finding of this study could help to understand the protocatechuic acid ethyl ester action mechanism.
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Tzoneva, Rumiana, Tihomira Stoyanova, Annett Petrich, Desislava Popova, Veselina Uzunova, Albena Momchilova, and Salvatore Chiantia. "Effect of Erufosine on Membrane Lipid Order in Breast Cancer Cell Models." Biomolecules 10, no. 5 (May 22, 2020): 802. http://dx.doi.org/10.3390/biom10050802.
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Alkylphospholipids are a novel class of antineoplastic drugs showing remarkable therapeutic potential. Among them, erufosine (EPC3) is a promising drug for the treatment of several types of tumors. While EPC3 is supposed to exert its function by interacting with lipid membranes, the exact molecular mechanisms involved are not known yet. In this work, we applied a combination of several fluorescence microscopy and analytical chemistry approaches (i.e., scanning fluorescence correlation spectroscopy, line-scan fluorescence correlation spectroscopy, generalized polarization imaging, as well as thin layer and gas chromatography) to quantify the effect of EPC3 in biophysical models of the plasma membrane, as well as in cancer cell lines. Our results indicate that EPC3 affects lipid–lipid interactions in cellular membranes by decreasing lipid packing and increasing membrane disorder and fluidity. As a consequence of these alterations in the lateral organization of lipid bilayers, the diffusive dynamics of membrane proteins are also significantly increased. Taken together, these findings suggest that the mechanism of action of EPC3 could be linked to its effects on fundamental biophysical properties of lipid membranes, as well as on lipid metabolism in cancer cells.
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Pérez-Isidoro, R., and M. Costas. "The effect of neuroleptic drugs on DPPC/sphingomyelin/cholesterol membranes." Chemistry and Physics of Lipids 229 (July 2020): 104913. http://dx.doi.org/10.1016/j.chemphyslip.2020.104913.
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Britt, Hannah M., Clara A. García-Herrero, Paul W. Denny, Jackie A. Mosely, and John M. Sanderson. "Lytic reactions of drugs with lipid membranes." Chemical Science 10, no. 3 (2019): 674–80. http://dx.doi.org/10.1039/c8sc04831b.
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Suwalsky, Mario, Pedro L. Hernández, Fernando Villena, and Carlos P. Sotomayor. "The Anticancer Drug Cytarabine Does not Interact with the Human Erythrocyte Membrane." Zeitschrift für Naturforschung C 58, no. 11-12 (December 1, 2003): 885–90. http://dx.doi.org/10.1515/znc-2003-11-1225.
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Abstract Cytarabine, an analog of deoxycytidine, is an important agent in the treatment of ovarian carcinoma, acute myeloid and lymphoblastic leukemia. Its mechanism of action has been attributed to an interference with DNA replication. The plasma membrane has received increasing attention as a possible target of antitumor drugs, where the drugs may act as growth factor antagonists and receptor blockers, interfere with mitogenic signal transduction or exert direct cytotoxic effects. Furthermore, it has been reported that drugs that exert their antiproliferative effect by interacting with DNA generally cause structural and functional membrane alterations which may be essential for growth inhibition by these agents. This paper describes the studies undertaken to determine the structural effects induced by cytarabine to cell membranes. The results showed that cytarabine, at a concentration about one thousand times higher than that found in plasma when it is therapeutically administered, did not induce significant structural perturbation in any of these systems. Therefore, it can be unambiguously concluded that this widely used anticancer drug does not interact at all with erythrocyte membranes.
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Rols, M. P., M. Golzio, B. Gabriel, and J. Teissié. "Factors Controlling Electropermeabilisation of Cell Membranes." Technology in Cancer Research & Treatment 1, no. 5 (October 2002): 319–27. http://dx.doi.org/10.1177/153303460200100502.
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Electric field pulses are a new approach for drug and gene delivery for cancer therapy. They induce a localized structural alteration of cell membranes. The associated physical mechanisms are well explained and can be safely controlled. A position dependent modulation of the membrane potential difference is induced when an electric field is applied to a cell. Electric field pulses with an overcritical intensity evoke a local membrane alteration. A free exchange of hydrophilic low molecular weight molecules takes place across the membrane. A leakage of cytosolic metabolites and a loading of polar drugs into the cytoplasm are obtained. The fraction of the cell surface which is competent for exchange is a function of the field intensity. The level of local exchange is strongly controlled by the pulse duration and the number of successive pulses. The permeabilised state is long lived. Its lifetime is under the control of the cumulated pulse duration. Cell viability can be preserved. Gene transfer is obtained but its mechanism is not a free diffusion. Plasmids are electrophoretically accumulated against the permeabilised cell surface and form aggregates due to the field effect. After the pulses, several steps follow: translocation to the cytoplasm, traffic to the nucleus and expression. Molecular structural and metabolic changes in cells remain mostly poorly understood. Nevertheless, while most studies were established on cells in culture ( in vitro), recent experiments show that similar effects are obtained on tissue ( in vivo). Transfer remains controlled by the physical parameters of the electrical treatment.
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Zhou, Yong, Elizabeth J. Dial, Rand Doyen, and Lenard M. Lichtenberger. "Effect of indomethacin on bile acid-phospholipid interactions: implication for small intestinal injury induced by nonsteroidal anti-inflammatory drugs." American Journal of Physiology-Gastrointestinal and Liver Physiology 298, no. 5 (May 2010): G722—G731. http://dx.doi.org/10.1152/ajpgi.00387.2009.
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The injurious effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in the small intestine was not appreciated until the widespread use of capsule endoscopy. Animal studies found that NSAID-induced small intestinal injury depends on the ability of these drugs to be secreted into the bile. Because the individual toxicity of amphiphilic bile acids and NSAIDs directly correlates with their interactions with phospholipid membranes, we propose that the presence of both NSAIDs and bile acids alters their individual physicochemical properties and enhances the disruptive effect on cell membranes and overall cytotoxicity. We utilized in vitro gastric AGS and intestinal IEC-6 cells and found that combinations of bile acid, deoxycholic acid (DC), taurodeoxycholic acid, glycodeoxycholic acid, and the NSAID indomethacin (Indo) significantly increased cell plasma membrane permeability and became more cytotoxic than these agents alone. We confirmed this finding by measuring liposome permeability and intramembrane packing in synthetic model membranes exposed to DC, Indo, or combinations of both agents. By measuring physicochemical parameters, such as fluorescence resonance energy transfer and membrane surface charge, we found that Indo associated with phosphatidylcholine and promoted the molecular aggregation of DC and potential formation of larger and isolated bile acid complexes within either biomembranes or bile acid-lipid mixed micelles, which leads to membrane disruption. In this study, we demonstrated increased cytotoxicity of combinations of bile acid and NSAID and provided a molecular mechanism for the observed toxicity. This mechanism potentially contributes to the NSAID-induced injury in the small bowel.
Dissertations / Theses on the topic "Cell membranes Effect of drugs on"
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Englund, Marita. "Effects of hypoxia and antiepileptic drugs on electrophysiological properties of CA1 neurons in hippocampus /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-237-8/.
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Dricu, Anica. "Role of dolichyl phosphate, N-linked glycosylation and cell membrane expression of insulin-like growth factor-1 receptor in maintenance of malignant cell growth /." Stockholm, 1997. http://diss.kib.ki.se/1997/91-628-2751-0.
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Boyd, Nolan Lee. "The effect of shear stress on caveolae formation and function in endothelial cells." Diss., Available online, Georgia Institute of Technology, 2004:, 2003. http://etd.gatech.edu/theses/available/etd-04082004-180030/unrestricted/boyd%5Fnolan%5Fl%5F200312%5Fphd.pdf.
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Meza, Benjamin. "The Effect of Cell Type on the Efficacy of CMV Antiviral Drugs." VCU Scholars Compass, 2008. http://scholarscompass.vcu.edu/etd/1567.
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Until recently, all in vitro drug susceptibility assays of cytomegalovirus (CMV) were performed in clinically irrelevant fibroblast cells. This study sought to test if drug susceptibility was affected by cell type. MRC-5 embryonic lung fibroblasts and ARPE-19 retinal pigmented epithelial cells were infected with BADrUL131-Y4 epithelial/fibroblast tropic virus under serial concentrations of ganciclovir (GCV) or maribavir (MBV). Virus was quantified using plaque reduction, GFP fluorescence, and yield reduction. Both drugs performed less efficiently in ARPE-19 cells. A cell type effect was observed for both plaque reduction and yield reduction assays with implications for the treatment of CMV retinitis as well as other manifestations of CMV Disease that involve non-fibroblast cell types.
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Chapman, Dail. "The Effect of Cholesterol on Small-Molecule Diffusion Through Liver Cell Membranes." Scholarship @ Claremont, 2013. http://scholarship.claremont.edu/scripps_theses/269.
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Cholesterol is an important component in maintaining the structure and dynamics of cell membranes. Dysregulation of cholesterol results in detrimental changes including decreased fluidity of the membrane and changes in membrane permeability. Because cholesterol is synthesized and regulated in the liver, many liver diseases are accompanied by dysregulation of cholesterol. And this dysregulation could alter transportation of small molecules through the cell membrane of such diseased cells. This study will focus on the diffusion of three small-molecule drugs through liver cell membranes with varying cholesterol concentration using a molecular dynamics approach. Results from this study could provide more detail about cholesterol’s effect on liver cell membrane permeability.
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Hartsel, Scott Clifton. "Effect of membrane supramolecular structure on the photoresponse and structural stability of bacteriorhodopsin /." The Ohio State University, 1985. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487260531954914.
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Almaawi, Abdulaziz. "Effect of acetaminophen and nonsteroidal anti-inflammatory drugs on gene expression of human mesenchymal stem cells." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114405.
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A major drawback of cartilage tissue engineering is that human mesenchymalStem cells (MSCs) from patients with osteoarthritis (OA) express high levels of type X collagen. Type X collagen is a marker of late stage chondrocyte hypertrophy, linked with endochondral ossification. Also, MSCs from OA patients express osteogenic marker genes such as alkaline phosphatase (ALK), bone sialoprotein (BSP), and osteocalcin (OC) as well as aggrecan (ACAN), a marker of chondrogenesis, but not type II collagen. OA patients, in an attempt to relieve pain and other symptoms, often take NSAIDs and pain relievers like acetaminophen. The aim of this present study was to determine how these drugs influence human MSC gene expression of different chondrogenic and osteogenic markers. MSCs isolated from the bone marrow of osteoarthritic patients or from normal donors were cultured in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) without or with Acetaminophen (Acet) or non-steroidal anti-inflammatory drugs (NSAIDs), Ibuprofen (Ibu), Diclofenac (Dic), Naproxen (Npx) and Celecoxib (Cele). After 3 days of culture, the cells were collected and gene expression was measured using quantitative PCR for type X collagen (COL10A1), aggrecan (ACAN) and type 1 collagen，as well as osteogenic marker genes such as alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OC) and Runt-related transcription factor 2 (RUNX2). Acet and Npx supplementation led to a significant increase in COL10A1 & RUNX2 expression when compared to control. Furthermore, with Ibu, Acet and Npx supplementation, aggrecan message levels were decreased. In contrast, addition of Cele significantly increased aggrecan gene expression. Finally, Ibu, Acet and Npx decreased type I collagen expression while Cele had a tendency to increase type I collagen expression. The present study showed that NSAIDs and Acet could affect Osteogenic and chondrogenic differentiation of human MSCs. These are features that could interfere with intervertebral disc (IVD) or cartilage repair. Thus, caution must be exercised when using MSCs from OA patients in biological repair of articular cartilage or disc.Un des principaux problèmes de l'ingénierie tissulaire du cartilage réside dans le fait que les cellules souches mésenchymateuses humaines (hCSMs) de patients osteoarthritiques (OA) expriment fortement le collagène de type X (Col X) qui est un marqueur de l'hypertrophie des chondrocvytes, hypertrophie qui est associée à l'ossification. Les hCSMs de patients OA expriment également des marqueurs de l'ostéogénèse tels que la phosphatase alcaline (ALK), une sialoprotéine de l'os (BSP) et l'ostéocalcine (OC), ainsi que l'aggrécane (AGG), un marqueur de la chondrogenèse. Dans le but de diminuer la douleur et autres symptômes reliés à leur maladie, les patients OA consomment des drogues anti-inflammatoires non-stéroïdiennes (NSAIDs). Le but de la présente étude était de déterminer si ces drogues pouvaient influencer l'expression de gènes associés à la chondrogenèse ou à l'ostéogénèse dans les hCSMs. Les CSMs isolées de la moelle osseuse de patients OA ou de donneurs normaux ont été cultivées dans du milieu Eagle modifié selon Dulbecco (DMEM) supplémenté avec 10% de sérum de veau fétal (SVF), sans ou avec Acétominophène (Acét), Ibuprofène (Ibu), Dichlorofenac (Dic), Naproxen (Npx) et Célécoxib (célé). L'expression des marqueurs ostéogéniques et du Col X a été mesurée par PCR quantitatif après 3 jours en culture. Les résultats montrent que l'Acét et le Npx induisaient significativement l'expression du Col X et diminuaient, tout comme l'Ibu, l'expression de l'AGG et du Col de type I (Col I). Cependant, Célé stimulait de façon significative l'expression de l'AGG et inhibait, mais de façon non significative, l'expression du Col I. En résumé, la présente étude montre que les NSAIDs peuvent moduler l'expression de gènes associés à l'ostéogénèse et à la chondrogenèse dans les hCSMs, indiquant qu'ils pourraient interférer dans la réparation du cartilage. L'utilisation de hCSMs de patients OA devrait donc être faite avec prudence pour la réparation biologique du cartilage articulaire et même du disque intervertébral.
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Wu, Diana. "Effect of membrane thickness and unsaturation on dye efflux rates induced by [delta]-Lysin from phosphatidylcholine vesicles /." Electronic version (PDF), 2005. http://dl.uncw.edu/etd/2005/wud/dianawu.pdf.
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Porter, Tyrone M. "An investigation of the synergy between ultrasound and membrane-disruptive polymers and its effect on cell membranes /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/8126.
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Liao, Ximan, and 廖喜漫. "A study of proteoglycan production during suppressed cell proliferation of a human colon carcinoma cell line." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1999. http://hub.hku.hk/bib/B3123897X.
Full textBooks on the topic "Cell membranes Effect of drugs on"
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Alcohol and biological membranes. New York: Guilford Press, 1985.
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C, Aloia Roland, Curtain Cyril C, and Gordon Larry M, eds. Drug and anesthetic effects on membrane structure and function. New York: Wiley-Liss, 1991.
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C, Srivastava R. Surface activity in drug action. Amsterdam: Elsevier, 2005.
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Kasumov, Kh M. Molekuli͡a︡rnyĭ mekhanizm vzaimodeĭstvii͡a︡ polienovykh antibiotikov s lipidnymi membranami. Baku: "Ėlm", 1986.
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Robert, Lu D., and Øie Svein, eds. Cellular drug delivery: Principles and practice. Totowa, N.J: Humana Press, 2004.
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Polivoda, B. I. Biofizicheskie aspekty radiat͡s︡ionnogo porazhenii͡a︡ biomembran. Moskva: Ėnergoatomizdat, 1990.
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Sungurov, A. I͡U. Radiobiologii͡a kletochnoĭ poverkhnosti. Moskva: Akademii͡a nauk SSSR, Vses. in-t nauch. i tekhn. informat͡sii, 1988.
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Ryskulova, S. T. Radiat͡s︡ionnai͡a︡ biologii͡a︡ plazmaticheskikh membran. Moskva: "Ėnergoatomizdat", 1986.
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International School of Electromagnetic Fields and Biomembranes (1st 1986 Pleven, Bulgaria). Electromagnetic fields and biomembranes. New York: Plenum Press, 1988.
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E, Steele Vernon, ed. Cellular and molecular targets for chemoprevention. Boca Raton, Fla: CRC Press, 1992.
Find full textBook chapters on the topic "Cell membranes Effect of drugs on"
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Kerkhove, E., V. Pennemans, and Q. Swennen. "Cadmium, Effect on Transport Across Cell Membranes." In Encyclopedia of Metalloproteins, 378–82. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4614-1533-6_29.
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Grady, Martha E., Russell J. Composto, and David M. Eckmann. "Cytoskeletal Perturbing Drugs and Their Effect on Cell Elasticity." In Mechanics of Biological Systems and Materials, Volume 6, 169–77. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-41351-8_24.
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Fedor, Medzihradsky. "Structure and Function of Cell Membranes, and Cellular Transport of Drugs." In Principles of Radiopharmacology, 197–223. Boca Raton: CRC Press, 2021. http://dx.doi.org/10.1201/9780429288760-13.
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Mason, R. Preston. "Molecular mechanisms underlying the effects of cholesterol on neuronal cell membrane function and drug-membrane interactions." In Lipids, health, and behavior., 127–38. Washington: American Psychological Association, 1997. http://dx.doi.org/10.1037/10259-007.
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Le, Fei, Peter Wilce, David Hume, and Brian Shanley. "Effect of Acute and Chronic Administration of Ethanol on c-fos Expression in Brain." In Alcohol, Cell Membranes, and Signal Transduction in Brain, 305–16. Boston, MA: Springer US, 1993. http://dx.doi.org/10.1007/978-1-4615-2470-0_28.
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Park, Sang-Hyun, Byung-Cheon Lee, Cheon-Joo Choi, Kwang-Sup Soh, and Pan Dong Ryu. "Effects of Cholinergic Drugs on Membrane Potential of Cells in Organ Surface Primo Nodes." In The Primo Vascular System, 251–61. New York, NY: Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4614-0601-3_35.
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Sultana, F., M. Vaughan, and M. Khandaker. "Effect of Fiber Architecture on the Cell Functions of Electrospun Fiber Membranes." In Mechanics of Biological Systems and Materials, Volume 6, 157–60. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-41351-8_22.
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Négrier, Sylvie. "Antiangiogenic Drugs in Cancer Therapy: Effect on Advanced Renal Cell Carcinoma." In Molecular Mechanisms of Angiogenesis, 375–82. Paris: Springer Paris, 2014. http://dx.doi.org/10.1007/978-2-8178-0466-8_18.
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Biaglow, John E., Marie E. Varnes, Birgit Jacobson, and Herman D. Suit. "Effect of Calcium Channel Blocking Drugs on Tumor Cell Oxygen Utilization." In Oxygen Transport to Tissue VIII, 583–89. Boston, MA: Springer US, 1986. http://dx.doi.org/10.1007/978-1-4684-5188-7_71.
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Rossaro, L., S. R. Dowd, V. Simplaceanu, R. Naccarato, D. H. Van Thiel, and C. Ho. "Effect of FK 506 and Cyclosporins on Model Membranes Studied by Nuclear Magnetic Resonance Spectroscopy." In Drugs and the Liver: High Risk Patients and Transplantation, 177–84. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1994-8_29.
Full textConference papers on the topic "Cell membranes Effect of drugs on"
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Teo, Ka Yaw, and Bumsoo Han. "Freezing-Assisted Intracellular Drug Delivery to Multi-Drug Resistant Cancer Cells." In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-192373.
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The efficacy of chemotherapy is significantly impaired by multi-drug resistance (MDR) of cancer cells. The mechanism of MDR is associated with the overexpression of certain ATP-binding cassette protein transporters in plasma membranes. These transporters actively keep intracellular drug concentration below the cell-killing threshold by extruding cytotoxic drugs. Various strategies to overcome MDR have been proposed and have shown promising results at the laboratory level. However, pharmacokinetic alteration of co-administered anticancer agents reduces their clinical effectiveness. This leads to increased toxicity and undesirable side effects at effective concentrations [1]. Hence, a clinically feasible strategy to overcome the phenomenon of MDR is highly desired.
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Arena, Christopher B., Michael B. Sano, Marissa Nichole Rylander, and Rafael V. Davalos. "High Frequency Electroporation for Cancer Therapy." In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53626.
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Electroporation is a non-linear biophysical mechanism in which the application of an external pulsed electric field leads to an increase in the permeability of cellular membranes. The extent of electroporation is attributed to the induced buildup of charge across the membrane, and consequently, transmembrane potential (TMP). Increasing the TMP has been described to produce various permeabilizing effects, wherein the formation of hydrophilic, aqueous pores becomes energetically favorable [1]. If the pulse parameters are tuned such that the membrane defects are only temporary, and the cell remains viable, the process is termed reversible electroporation. As a cancer therapy, reversible electroporation has been employed to increase the cellular uptake of chemotherapeutic drugs. Irreversible electroporation (IRE) results when membrane defects are permanent, leading to cell death. Recently, IRE has been recognized as an independent means to destroy tumors without the use of adjuvant drugs and prior to the onset of thermal injury [2].
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Davalos, Rafael V., David M. Otten, Lluis M. Mir, and Boris Rubinsky. "A Feasibility Study for Imaging Tissue Electroporation With Electrical Impedance Tomography." In ASME 2002 International Mechanical Engineering Congress and Exposition. ASMEDC, 2002. http://dx.doi.org/10.1115/imece2002-33071.
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In tissue electroporation, electrodes are inserted around the targeted tissue and electrical pulses are applied to permeabilize the cell membrane to macromolecules such as gene constructs in genetic engineering or cancer treatment drugs [1, 2]. For a specific set of voltage parameters (e.g. pulse number, frequency, duration), the effect that the electric field has depends on the voltage gradients that develop across the individual cell [2].
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Tourlomousis, Filippos, and Robert C. Chang. "Computational Modeling of 3D Printed Tissue-on-a-Chip Microfluidic Devices as Drug Screening Platforms." In ASME 2014 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2014. http://dx.doi.org/10.1115/imece2014-38454.
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Physiological tissue-on-a-chip technology is enabled by adapting microfluidics to create micro scale drug screening platforms that replicate the complex drug transport and reaction processes in the human liver. The ability to incorporate three-dimensional (3d) tissue models using layered fabrication approaches into devices that can be perfused with drugs offer an optimal analog of the in vivo scenario. The dynamic nature of such in vitro metabolism models demands reliable numerical tools to determine the optimum tissue fabrication process, flow, material, and geometric parameters for the most effective metabolic conversion of the perfused drug into the liver microenvironment. Thus, in this modeling-based study, the authors focus on modeling of in vitro 3d microfluidic microanalytical microorgan devices (3MD), where the human liver analog is replicated by 3d cell encapsulated alginate hydrogel based tissue-engineered constructs. These biopolymer constructs are hosted in the chamber of the 3MD device serving as walls of the microfluidic array of channels through which a fluorescent drug substrate is perfused into the microfluidic printed channel walls at a specified volumetric flow rate assuring Stokes flow conditions (Re<<1). Due to the porous nature of the hydrogel walls, a metabolized drug product is collected as an effluent stream at the outlet port. A rigorous modeling approached aimed to capture both the macro and micro scale transport phenomena is presented. Initially, the Stokes Flow Equations (free flow regime) are solved in combination with the Brinkman Equations (porous flow regime) for the laminar velocity profile and wall shear stresses in the whole shear mediated flow regime. These equations are then coupled with the Convection-Diffusion Equation to yield the drug concentration profile by incorporating a reaction term described by the Michael-Menten Kinetics model. This effectively yields a convection-diffusion–cell kinetics model (steady state and transient), where for the prescribed process and material parameters, the drug concentration profile throughout the flow channels can be predicted. A key consideration that is addressed in this paper is the effect of cell mechanotransduction, where shear stresses imposed on the encapsulated cells alter the functional ability of the liver cell enzymes to metabolize the drug. Different cases are presented, where cells are incorporated into the geometric model either as voids that experience wall shear stress (WSS) around their membrane boundaries or as solid materials, with linear elastic properties. As a last step, transient simulations are implemented showing that there exists a tradeoff with respect the drug metabolized effluent product between the shear stresses required and the residence time needed for drug diffusion.
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Liu, Wing Kam, and Ashfaq Adnan. "Multiscale Modeling and Simulation for Nanodiamond-Based Therapeutic Delivery." In ASME 2010 First Global Congress on NanoEngineering for Medicine and Biology. ASMEDC, 2010. http://dx.doi.org/10.1115/nemb2010-13273.
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It has been demonstrated from recent research that nanodiamond(ND)-enabled drug delivery as cancer therapeutics represents an important component of optimized device functionality. The goal of the current research is to develop a multiscale modeling technique to understand the fundamental mechanism of a ND-based cancer therapeutic drug delivery system. The major components of the proposed device include nanodiamonds (ND), parylene buffer layer and doxorubicin (DOX) drugs, where DOX loaded self-assembled nanodiamonds are packed inside parylene capsule. The efficient functioning of the device is characterized by its ability to precisely detect targets (cancer cells) and then to release drugs at a controlled manner. The fundamental science issues concerning the development of the ND-based device includes (a) a precise identification of the equilibrium structure, surface electrostatics and self assembled morphology of nanodiamonds, (b) understanding of the drug/biomarker adsorption and desorption process to and from NDs, (c) rate of drug release through the parylene buffers, and finally, (d) device performance under physiological condition. In this study, we aim to systematically address these issues using a multscale computational framework. Specifically, the structure and electrostatics of the functionalized NDs are predicted by quantum scale calculation (Density Functional Tight Binding). The DFTB) study on smaller NDs suggests a facet dependent charge distributions on ND surfaces. Using the charges for smaller NDs (∼ valid for 1–3.3 nm dia ND), we then determined surface charges for larger (4–10 nm) truncated octahedral nanodiamonds (TOND). We found that the [100] face and the [111] face contain positively and negatively charged atoms, respectively. Employing this surface electrostatics of nanodiamonds, atomistic-scale simulations are performed to simulate the self-assembly process of the NDs and drug molecules in a solution as well as to evaluate nanoscale diffusion coefficient of DOX molecules. In order to quantify the nature of the aggregate morphology, a fractal analysis has been performed. The mass fractal dimensions for a variety of aggregate size have been obtained from molecular simulations assuming ‘diffusion-limited aggregation (DLA)’ process. Then, by considering the experimentally observed aggregate dimensions, by using DLA based fractal analysis and by utilizing Lagvankar-Gemmell Model for aggregate density, a continuum model for larger aggregates will be developed to characterize aggregate strengths and break-up mechanism, which in turn will help us to understand how aggregate size can be reduced. In this talk, an outline for this continuum model will be discussed. In addition, we have been performing molecular simulations on DOX-ND where multiple drug molecules are allowed to interact with a cluster of self-assembled nanodiamonds in pH controlled solution. The purpose of this study is to find the effect of solution pH on the loading and release of drug to and from nanodiamonds. Our initial results show that a higher pH is necessary to ensure drug release from nanodiamonds. Once we completely understand the essential physics of pH controlled drug loading and release, we plan to develop multiscale models of tumor nodules to represent them as a collection of individual tumor cells. Each cell will be then modeled as a deformable body comprised of three homogenous materials: cortex membrane, cytosol and nucleus. The cortex membrane and the cytosol will serve as a weak permeable medium where the absorption coefficients of the doxorubicin remain constant and obey Fick’s law. In this study, it will be assumed that drug release from the microdevice to its outer periphery will be governed by Fickian Diffusion. It will also be assumed that the complex flow of drug through the interstitial fluid of the body will be dictated by Darcy’s law. It will be assumed that the solute drug transport in these regions will be due to a combination of convection, diffusion, elimination in the intra- and extra-cellular space, receptive cell internalization and degradation. Results from this study will provide fundamental insight on the definitive targeting of infected cells and high resolution controlling of drug molecules.
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Wang, C. T., J. Y. Lee, J. C. Chen, Y. J. Shiao, and W. J. Tsai. "EFFECT OF TRIFLUOPERAZINE (TFP) ON HUMAN PLATELET MEMBRANE." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644816.
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TFP is a lipophilic antipsychotic drug. The drug will first encounter with cell membrane when adding it into a cell suspension. The effect of TFP on plasma membrane of the gel-filtered human platelet was investigated by : 1) scanning electron microscopy (SEM); 2) measuring theleakiness of marker enzymes and compound; 3) estimating its solubility in membrane. The cells were suspended in the modified Tyrode's buffer containing 0.1% dextrose, 0.2% of bovine serum albumin and without calcium. The SEM study showed that platelet changed shape from disc to ellipsoid in 10 μM TFP.,Increasingthe TFP concentration from 20 μM to 50 μM resulted in changing thecell from ellipsoid to sphere with a wavy surface. The drug did not cause any significant change in the cell volume. TFPof 70 μM caused platelet becoming a round ball shape with a spongy-like cell surface. 100 μM TFP caused more than 90% of cells to lyse and to agglutinate with each other. The time courseof morphological change of the TFP-affected platelets showed that the cellsswelled into irregular shape within 2 min. Apparent leakiness of serotonin was observed at 20 μM TFP, while the leakages of both lactate dehydrogenase and acid hydrolase were found at 40 μM TFP. The TFP uptake study showed that platelet was permeable to TFP by simple diffusion. The partition coefficient of TFP in platelet membrane was estimated to be 1 x 104. These results indicate that TFP molecules are solubilized in membrane. The extent in perturbation of the membrane structure depends on concentration of the drug used. (This research was supported by a grant from the National Science Council of the Republic of China.)
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Martin, Diana I., Elena N. Manaila, Mihaela I. Moisescu, Tudor D. Savopol, Eugenia A. Kovacs, Sabin A. Cinca, Constantin I. Matei, et al. "Radiation Interaction with Therapeutic Drugs and Cell Membranes." In SIXTH INTERNATIONAL CONFERENCE OF THE BALKAN PHYSICAL UNION. AIP, 2007. http://dx.doi.org/10.1063/1.2733557.
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Jayasuriya, A. Champa, Anthony Darr, and Nabil A. Ebraheim. "Chemotherapy Drug Encapsulated Poly(Lactic-Co-Glycolic Acid) Nanoparticles." In ASME 2006 International Mechanical Engineering Congress and Exposition. ASMEDC, 2006. http://dx.doi.org/10.1115/imece2006-14694.
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In order to exhibit pharmacological activity at the bone cancer site, high-dose chemotherapy drugs need to be used. This often causes toxicity and unfavorable systemic adverse effects leading to significant problems to the patient. Since nanoparticles are in subcellular size, they can effectively entered to the cell membrane that could result in higher cellular uptake. In this study, we report preparation and characterization of poly(lactic-co-glycolic acid) - PLGA nanoparticles, which encapsulated with chemotherapy drug cisplatin.
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Artmann, G., R. Grebe, H. Wolff, R. Degenhardt, and H. Schmid-SchÖnbein. "NOVEL TECHIQUES FOR QUANTIFICATION OF RBC-SHAPE (RS) AND SHEAR INDUCED RBC ELONGATION (SIRE): APPLICATION FOR ANALYSIS OF DRUG INDUCED ALTERATIONS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644217.
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In the past, red cell resting shape could only be assessed by subjective scaling, red cell deformability by a variety of rheological tests that are extremelydifficult to standardize and which all subject the RBC to high deforming forces. None of the latter have been accepted as reference in haematology, haemorheologyor pharmacology. A recent development from our group now allows objective, numerical analysis of red cell membrane curvature (i.e. the echinocytic or stomatocytic deviation from the discocytic resting shape) by a tangent count procedure in optical sections through freely suspended, randomly oriented RBC: (Grebe et al. Biorheology 22(6), 1985). Also, the deformation of point attached erythrocytes under the influence of extremely low shear stresses (0.05 Pa to 0.5 Pa, ARTOANN:Clin. Hemorheology 6, 1986), which are at least two orders of magnitude lower thanthat in any routinely available filtration method allows for the first time to model in vitro the extreme low flow states that occur in severe forms of haemodynamic insufficiency. These two methods in combination are ideally suited for routine tests of drug effects on normal human RBC: the drug action on RS can be monitored continuously during the action of drugs in the suspending medium; likewise, RISA can be recorded automatically on one population of adherent RBC while altering the composition and the drug concentration in the superfusate. The two methods were applied in combination to test rheological and membranological effects of two distinctly different compounds, namely Bencyclan (Bencylan-Hydrogen-Fumarate) and Vinpocitin (Aethyl vincamin) in normal cells and in cells after exposure to "stress conditions", i.e. hyperosmolarity and lactacidosis. Both olrugs given to n o r m a 1 RBC produce stomatocytosis in a done dependent fashion (1-100 uMolar). At shear stresses above o.6 Pa, the RISA is identical to controls, but is oxmsiderably less pronounced at lower shear stresses (T < 0.2 Pa). Thus, drugs of completely olifferent pharmacological action produce clear cut rheological effects on RBC in the micrcmolar concentration range; the combination of methods employed opens new possibilities for the systematic development of haemorheologically active drugs.Supported by DFG:Grant Gr 902/1-1
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Li, Jianbo, and Hao Lin. "The Effect of Electrical Conductivity on Pore Resistance and Electroporation." In ASME 2008 International Mechanical Engineering Congress and Exposition. ASMEDC, 2008. http://dx.doi.org/10.1115/imece2008-67773.
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Electroporation refers to the permeabilization of the cell membrane with one or multiple electric pulses. The reversible form of electroporation is widely applied for drug delivery, gene and cancer therapy, and stem cell research, among others; the irreversible form of electroporation is being explored for cancer treatment in a drug-free manner. In this work, an electroporation model is developed with particular focus on the prediction of pore resistance. The resulting formulation computes pore resistance as a function of pore size, and intracellular and extracellular conductivities, and avoids empirical or ad hoc specification of the conductivity of the pore-filling solution as practiced in previous works. Such a model is coupled at the whole cell level to investigate the effect of conductivity ratio on membrane permeabilization. The results reveal that the membrane achieves the maximum degree of permeabilization when the extracellular-to-intracellular conductivity ratio is around 0.5.
Reports on the topic "Cell membranes Effect of drugs on"
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Elmann, Anat, Orly Lazarov, Joel Kashman, and Rivka Ofir. therapeutic potential of a desert plant and its active compounds for Alzheimer's Disease. United States Department of Agriculture, March 2015. http://dx.doi.org/10.32747/2015.7597913.bard.
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We chose to focus our investigations on the effect of the active forms, TTF and AcA, rather than the whole (crude) extract. 1. To establish cultivation program designed to develop lead cultivar/s (which will be selected from the different Af accessions) with the highest yield of the active compounds TTF and/or achillolide A (AcA). These cultivar/s will be the source for the purification of large amounts of the active compounds when needed in the future for functional foods/drug development. This task was completed. 2. To determine the effect of the Af extract, TTF and AcA on neuronal vulnerability to oxidative stress in cultured neurons expressing FAD-linked mutants.Compounds were tested in N2a neuroblastoma cell line. In addition, we have tested the effects of TTF and AcA on signaling events promoted by H₂O₂ in astrocytes and by β-amyloid in neuronal N2a cells. 3. To determine the effect of the Af extract, TTF and AcA on neuropathology (amyloidosis and tau phosphorylation) in cultured neurons expressing FAD-linked mutants. 4. To determine the effect of A¦ extract, AcA and TTF on FAD-linked neuropathology (amyloidosis, tau phosphorylation and inflammation) in transgenic mice. 5. To examine whether A¦ extract, TTF and AcA can reverse behavioral deficits in APPswe/PS1DE9 mice, and affect learning and memory and cognitive performance in these FAD-linked transgenic mice. Background to the topic.Neuroinflammation, oxidative stress, glutamate toxicity and amyloid beta (Ab) toxicity are involved in the pathogenesis of Alzheimer's diseases. We have previously purified from Achilleafragrantissimatwo active compounds: a protective flavonoid named 3,5,4’-trihydroxy-6,7,3’-trimethoxyflavone (TTF, Fl-72/2) and an anti-inflammatory sesquiterpenelactone named achillolide A (AcA). Major conclusions, solutions, achievements. In this study we could show that TTF and AcA protected cultured astrocytes from H₂O₂ –induced cell death via interference with cell signaling events. TTF inhibited SAPK/JNK, ERK1/2, MEK1 and CREBphosphorylation, while AcA inhibited only ERK1/2 and MEK1 phosphorylation. In addition to its protective activities, TTF had also anti-inflammatory activities, and inhibited the LPS-elicited secretion of the proinflammatorycytokinesInterleukin 6 (IL-6) and IL-1b from cultured microglial cells. Moreover, TTF and AcA protected neuronal cells from glutamate and Abcytotoxicity by reducing the glutamate and amyloid beta induced levels of intracellular reactive oxygen species (ROS) and via interference with cell signaling events induced by Ab. These compounds also reduced amyloid precursor protein net processing in vitro and in vivo in a mouse model for Alzheimer’s disease and improvedperformance in the novel object recognition learning and memory task. Conclusion: TTF and AcA are potential candidates to be developed as drugs or food additives to prevent, postpone or ameliorate Alzheimer’s disease. Implications, both scientific and agricultural.The synthesis ofAcA and TTF is very complicated. Thus, the plant itself will be the source for the isolation of these compounds or their precursors for synthesis. Therefore, Achilleafragrantissima could be developed into a new crop with industrial potential for the Arava-Negev area in Israel, and will generate more working places in this region.
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Naim, Michael, Andrew Spielman, Shlomo Nir, and Ann Noble. Bitter Taste Transduction: Cellular Pathways, Inhibition and Implications for Human Acceptance of Agricultural Food Products. United States Department of Agriculture, February 2000. http://dx.doi.org/10.32747/2000.7695839.bard.
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Historically, the aversive response of humans and other mammals to bitter-taste substances has been useful for survival, since many toxic constituents taste bitter. Today, the range of foods available is more diverse. Many bitter foods are not only safe for consumption but contain bitter constituents that provide nutritional benefits. Despite this, these foods are often eliminated from our current diets because of their unacceptable bitterness. Extensive technology has been developed to remove or mask bitterness in foods, but a lack of understanding of the mechanisms of bitterness perception at the taste receptor level has prevented the development of inhibitors or efficient methods for reducing bitterness. In our original application we proposed to: (a) investigate the time course and effect of selected bitter tastants relevant to agricultural products on the formation of intracellular signal molecules (cAMP, IP3, Ca2+) in intact taste cells, in model cells and in membranes derived therefrom; (b) study the effect of specific bitter taste inhibitors on messenger formation and identify G-proteins that may be involved in tastant-induced bitter sensation; (c) investigate interactions and self-aggregation of bitter tastants within membranes; (d) study human sensory responses over time to these bitter-taste stimuli and inhibitors in order to validate the biochemical data. Quench-flow module (QFM) and fast pipetting system (FPS) allowed us to monitor fast release of the aforementioned signal molecules (cGMP, as a putative initial signal was substituted for Ca2+ ions) - using taste membranes and intact taste cells in a time range below 500 ms (real time of taste sensation) - in response to bitter-taste stimulation. Limonin (citrus) and catechin (wine) were found to reduce cellular cAMP and increase IP3 contents. Naringin (citrus) stimulated an IP3 increase whereas the cheese-derived bitter peptide cyclo(leu-Trp) reduced IP3 but significantly increased cAMP levels. Thus, specific transduction pathways were identified, the results support the notion of multiple transduction pathways for bitter taste and cross-talk between a few of those transduction pathways. Furthermore, amphipathic tastants permeate rapidly (within seconds) into liposomes and taste cells suggesting their availability for direct activation of signal transduction components by means of receptor-independent mechanisms within the time course of taste sensation. The activation of pigment movement and transduction pathways in frog melanophores by these tastants supports such mechanisms. Some bitter tastants, due to their amphipathic properties, permeated (or interacted with) into a bitter tastant inhibitor (specific phospholipid mixture) which apparently forms micelles. Thus, a mechanism via which this bitter taste inhibitor acts is proposed. Human sensory evaluation experiments humans performed according to their 6-n-propyl thiouracil (PROP) status (non-tasters, tasters, super-tasters), indicated differential perception of bitterness threshold and intensity of these bitter compounds by different individuals independent of PROP status. This suggests that natural products containing bitter compounds (e.g., naringin and limonin in citrus), are perceived very differently, and are in line with multiple transduction pathways suggested in the biochemical experiments. This project provides the first comprehensive effort to explore the molecular basis of bitter taste at the taste-cell level induced by economically important and agriculturally relevant food products. The findings, proposing a mechanism for bitter-taste inhibition by a bitter taste inhibitor (made up of food components) pave the way for the development of new, and perhaps more potent bitter-taste inhibitors which may eventually become economically relevant.
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Epel, Bernard, and Roger Beachy. Mechanisms of intra- and intercellular targeting and movement of tobacco mosaic virus. United States Department of Agriculture, November 2005. http://dx.doi.org/10.32747/2005.7695874.bard.
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To cause disease, plant viruses must replicate and spread locally and systemically within the host. Cell-to-cell virus spread is mediated by virus-encoded movement proteins (MPs), which modify the structure and function of plasmodesmata (Pd), trans-wall co-axial membranous tunnels that interconnect the cytoplasm of neighboring cells. Tobacco mosaic virus (TMV) employ a single MP for cell- cell spread and for which CP is not required. The PIs, Beachy (USA) and Epel (Israel) and co-workers, developed new tools and approaches for study of the mechanism of spread of TMV that lead to a partial identification and molecular characterization of the cellular machinery involved in the trafficking process. Original research objectives: Based on our data and those of others, we proposed a working model of plant viral spread. Our model stated that MPᵀᴹⱽ, an integral ER membrane protein with its C-terminus exposed to the cytoplasm (Reichel and Beachy, 1998), alters the Pd SEL, causes the Pd cytoplasmic annulus to dilate (Wolf et al., 1989), allowing ER to glide through Pd and that this gliding is cytoskeleton mediated. The model claimed that in absence of MP, the ER in Pd (the desmotubule) is stationary, i.e. does not move through the Pd. Based on this model we designed a series of experiments to test the following questions: -Does MP potentiate ER movement through the Pd? - In the presence of MP, is there communication between adjacent cells via ER lumen? -Does MP potentiate the movement of cytoskeletal elements cell to cell? -Is MP required for cell-to-cell movement of ER membranes between cells in sink tissue? -Is the binding in situ of MP to RNA specific to vRNA sequences or is it nonspecific as measured in vitro? And if specific: -What sequences of RNA are involved in binding to MP? And finally, what host proteins are associated with MP during intracellular targeting to various subcellular targets and what if any post-translational modifications occur to MP, other than phosphorylation (Kawakami et al., 1999)? Major conclusions, solutions and achievements. A new quantitative tool was developed to measure the "coefficient of conductivity" of Pd to cytoplasmic soluble proteins. Employing this tool, we measured changes in Pd conductivity in epidermal cells of sink and source leaves of wild-type and transgenic Nicotiana benthamiana (N. benthamiana) plants expressing MPᵀᴹⱽ incubated both in dark and light and at 16 and 25 ᵒC (Liarzi and Epel, 2005 (appendix 1). To test our model we measured the effect of the presence of MP on cell-to-cell spread of a cytoplasmic fluorescent probe, of two ER intrinsic membrane protein-probes and two ER lumen protein-probes fused to GFP. The effect of a mutant virus that is incapable of cell-to-cell spread on the spread of these probes was also determined. Our data shows that MP reduces SEL for cytoplasmic molecules, dilates the desmotubule allowing cell-cell diffusion of proteins via the desmotubule lumen and reduces the rate of spread of the ER membrane probes. Replicase was shown to enhance cell-cell spread. The data are not in support of the proposed model and have led us to propose a new model for virus cell-cell spread: this model proposes that MP, an integral ER membrane protein, forms a MP:vRNAER complex and that this ER-membrane complex diffuses in the lipid milieu of the ER into the desmotubule (the ER within the Pd), and spreads cell to cell by simple diffusion in the ER/desmotubule membrane; the driving force for spread is the chemical potential gradient between an infected cell and contingent non-infected neighbors. Our data also suggests that the virus replicase has a function in altering the Pd conductivity. Transgenic plant lines that express the MP gene of the Cg tobamovirus fused to YFP under the control the ecdysone receptor and methoxyfenocide ligand were generated by the Beachy group and the expression pattern and the timing and targeting patterns were determined. A vector expressing this MPs was also developed for use by the Epel lab . The transgenic lines are being used to identify and isolate host genes that are required for cell-to-cell movement of TMV/tobamoviruses. This line is now being grown and to be employed in proteomic studies which will commence November 2005. T-DNA insertion mutagenesis is being developed to identify and isolate host genes required for cell-to-cell movement of TMV.
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Blumwald, Eduardo, and Avi Sadka. Citric acid metabolism and mobilization in citrus fruit. United States Department of Agriculture, October 2007. http://dx.doi.org/10.32747/2007.7587732.bard.
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Accumulation of citric acid is a major determinant of maturity and fruit quality in citrus. Many citrus varieties accumulate citric acid in concentrations that exceed market desires, reducing grower income and consumer satisfaction. Citrate is accumulated in the vacuole of the juice sac cell, a process that requires both metabolic changes and transport across cellular membranes, in particular, the mitochondrial and the vacuolar (tonoplast) membranes. Although the accumulation of citrate in the vacuoles of juice cells has been clearly demonstrated, the mechanisms for vacuolar citrate homeostasis and the components controlling citrate metabolism and transport are still unknown. Previous results in the PIs’ laboratories have indicated that the expression of a large number of a large number of proteins is enhanced during fruit development, and that the regulation of sugar and acid content in fruits is correlated with the differential expression of a large number of proteins that could play significant roles in fruit acid accumulation and/or regulation of acid content. The objectives of this proposal are: i) the characterization of transporters that mediate the transport of citrate and determine their role in uptake/retrieval in juice sac cells; ii) the study of citric acid metabolism, in particular the effect of arsenical compounds affecting citric acid levels and mobilization; and iii) the development of a citrus fruit proteomics platform to identify and characterize key processes associated with fruit development in general and sugar and acid accumulation in particular. The understanding of the cellular processes that determine the citrate content in citrus fruits will contribute to the development of tools aimed at the enhancement of citrus fruit quality. Our efforts resulted in the identification, cloning and characterization of CsCit1 (Citrus sinensis citrate transporter 1) from Navel oranges (Citrus sinesins cv Washington). Higher levels of CsCit1 transcripts were detected at later stages of fruit development that coincided with the decrease in the juice cell citrate concentrations (Shimada et al., 2006). Our functional analysis revealed that CsCit1 mediates the vacuolar efflux of citrate and that the CsCit1 operates as an electroneutral 1CitrateH2-/2H+ symporter. Our results supported the notion that it is the low permeable citrateH2 - the anion that establishes the buffer capacity of the fruit and determines its overall acidity. On the other hand, it is the more permeable form, CitrateH2-, which is being exported into the cytosol during maturation and controls the citrate catabolism in the juice cells. Our Mass-Spectrometry-based proteomics efforts (using MALDI-TOF-TOF and LC2- MS-MS) identified a large number of fruit juice sac cell proteins and established comparisons of protein synthesis patterns during fruit development. So far, we have identified over 1,500 fruit specific proteins that play roles in sugar metabolism, citric acid cycle, signaling, transport, processing, etc., and organized these proteins into 84 known biosynthetic pathways (Katz et al. 2007). This data is now being integrated in a public database and will serve as a valuable tool for the scientific community in general and fruit scientists in particular. Using molecular, biochemical and physiological approaches we have identified factors affecting the activity of aconitase, which catalyze the first step of citrate catabolism (Shlizerman et al., 2007). Iron limitation specifically reduced the activity of the cytosolic, but not the mitochondrial, aconitase, increasing the acid level in the fruit. Citramalate (a natural compound in the juice) also inhibits the activity of aconitase, and it plays a major role in acid accumulation during the first half of fruit development. On the other hand, arsenite induced increased levels of aconitase, decreasing fruit acidity. We have initiated studies aimed at the identification of the citramalate biosynthetic pathway and the role(s) of isopropylmalate synthase in this pathway. These studies, especially those involved aconitase inhibition by citramalate, are aimed at the development of tools to control fruit acidity, particularly in those cases where acid level declines below the desired threshold. Our work has significant implications both scientifically and practically and is directly aimed at the improvement of fruit quality through the improvement of existing pre- and post-harvest fruit treatments.
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Mevarech, Moshe, Jeremy Bruenn, and Yigal Koltin. Virus Encoded Toxin of the Corn Smut Ustilago Maydis - Isolation of Receptors and Mapping Functional Domains. United States Department of Agriculture, September 1995. http://dx.doi.org/10.32747/1995.7613022.bard.
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Ustilago maydis is a fungal pathogen of maize. Some strains of U. maydis encode secreted polypeptide toxins capable of killing other susceptible strains of U. maydis. Resistance to the toxins is conferred by recessive nuclear genes. The toxins are encoded by genomic segments of resident double-strande RNA viruses. The best characterized toxin, KP6, is composed of two polypeptides, a and b, which are not covalently linked. It is encoded by P6M2 dsRNA, which has been cloned, sequenced and expressed in a variety of systems. In this study we have shown that the toxin acts on the membranes of sensitive cells and that both polypeptides are required for toxin activity. The toxin has been shown to function by creating new pores in the cell membrane and disrupting ion fluxes. The experiments performed on artificial phospholipid bilayers indicated that KP6 forms large voltage-independent, cation-selective channels. Experiments leading to the resolution of structure-function relationship of the toxin by in vitro analysis have been initiated. During the course of this research the collaboration also yielded X-ray diffracion data of the crystallized a polypeptide. The effect of the toxin on the pathogen has been shown to be receptor-mediated. A potential receptor protein, identified in membrane fractions of sensitive cells, was subjected to tryptic hydrolysis followed by amino-acid analysis. The peptides obtained were used to isolate a cDNA fragment by reverse PCR, which showed 30% sequence homology to the human HLA protein. Analysis of other toxins secreted by U. maydis, KP1 and KP4, have demonstrated that, unlike KP6, they are composed of a single polypeptide. Finally, KP6 has been expressed in transgenic tobacco plants, indicating that accurate processing by Kex2p-like activity occurs in plants as well. Using tobacco as a model system, we determined that active antifungal toxins can be synthesized and targeted to the outside of transgenic plant cells. If this methodology can be applied to other agronomically crop species, then U. maydis toxins may provide a novel means for biological control of pathogenic fungi.
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Lichter, Amnon, Joseph L. Smilanick, Dennis A. Margosan, and Susan Lurie. Ethanol for postharvest decay control of table grapes: application and mode of action. United States Department of Agriculture, July 2005. http://dx.doi.org/10.32747/2005.7587217.bard.
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Original objectives: Dipping of table grapes in ethanol was determined to be an effective measure to control postharvest gray mold infection caused by Botrytis cinerea. Our objectives were to study the effects of ethanol on B.cinerea and table grapes and to conduct research that will facilitate the implementation of this treatment. Background: Botrytis cinerea is known as the major pathogen of table grapes in cold storage. To date, the only commercial technology to control it relied on sulfur dioxide (SO₂) implemented by either fumigation of storage facilities or from slow release generator pads which are positioned directly over the fruits. This treatment is very effective but it has several drawbacks such as aftertaste, bleaching and hypersensitivity to humans which took it out of the GRAS list of compounds and warranted further seek for alternatives. Prior to this research ethanol was shown to control several pathogens in different commodities including table grapes and B. cinerea. Hence it seemed to be a simple and promising technology which could offer a true alternative for storage of table grapes. Further research was however required to answer some practical and theoretical questions which remained unanswered. Major conclusions, solutions, achievements: In this research project we have shown convincingly that 30% ethanol is sufficient to prevent germination of B. cinerea and kill the spores. In a comparative study it was shown that Alternaria alternata is also rather sensitive but Rhizopus stolonifer and Aspergillus niger are less sensitive to ethanol. Consequently, ethanol protected the grapes from decay but did not have a significant effect on occurrence of mycotoxigenic Aspergillus species which are present on the surface of the berry. B. cinerea responded to ethanol or heat treatments by inducing sporulation and transient expression of the heat shock protein HSP104. Similar responses were not detected in grape berries. It was also shown that application of ethanol to berries did not induce subsequent resistance and actually the berries were slightly more susceptible to infection. The heat dose required to kill the spores was determined and it was proven that a combination of heat and ethanol allowed reduction of both the ethanol and heat dose. Ethanol and heat did not reduce the amount or appearance of the wax layers which are an essential component of the external protection of the berry. The ethanol and acetaldehyde content increased after treatment and during storage but the content was much lower than the natural ethanol content in other fruits. The efficacy of ethanol applied before harvest was similar to that of the biological control agent, Metschnikowia fructicola, Finally, the performance of ethanol could be improved synergistically by packaging the bunches in modified atmosphere films which prevent the accumulation of free water. Implications, both scientific and agricultural: It was shown that the major mode of action of ethanol is mediated by its lethal effect on fungal inoculum. Because ethanol acts mainly on the cell membranes, it was possible to enhance its effect by lowering the concentration and elevating the temperature of the treatment. Another important development was the continuous protection of the treated bunches by modified atmosphere that can solve the problem of secondary or internal infection. From the practical standpoint, a variety of means were offered to enhance the effect of the treatment and to offer a viable alternative to SO2 which could be instantly adopted by the industry with a special benefit to growers of organic grapes.
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Chou, Roger, Jesse Wagner, Azrah Y. Ahmed, Ian Blazina, Erika Brodt, David I. Buckley, Tamara P. Cheney, et al. Treatments for Acute Pain: A Systematic Review. Agency for Healthcare Research and Quality (AHRQ), December 2020. http://dx.doi.org/10.23970/ahrqepccer240.
Full textAbstract:
Objectives. To evaluate the effectiveness and comparative effectiveness of opioid, nonopioid pharmacologic, and nonpharmacologic therapy in patients with specific types of acute pain, including effects on pain, function, quality of life, adverse events, and long-term use of opioids. Data sources. Electronic databases (Ovid® MEDLINE®, PsycINFO®, Embase®, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews) to August 2020, reference lists, and a Federal Register notice. Review methods. Using predefined criteria and dual review, we selected randomized controlled trials (RCTs) of outpatient therapies for eight acute pain conditions: low back pain, neck pain, other musculoskeletal pain, neuropathic pain, postoperative pain following discharge, dental pain (surgical or nonsurgical), pain due to kidney stones, and pain due to sickle cell disease. Meta-analyses were conducted on pharmacologic therapy for dental pain and kidney stone pain, and likelihood of repeat or rescue medication use and adverse events. The magnitude of effects was classified as small, moderate, or large using previously defined criteria, and strength of evidence was assessed. Results. One hundred eighty-three RCTs on the comparative effectiveness of therapies for acute pain were included. Opioid therapy was probably less effective than nonsteroidal anti-inflammatory drugs (NSAIDs) for surgical dental pain and kidney stones, and might be similarly effective as NSAIDs for low back pain. Opioids and NSAIDs were more effective than acetaminophen for surgical dental pain, but opioids were less effective than acetaminophen for kidney stone pain. For postoperative pain, opioids were associated with increased likelihood of repeat or rescue analgesic use, but effects on pain intensity were inconsistent. Being prescribed an opioid for acute low back pain or postoperative pain was associated with increased likelihood of use of opioids at long-term followup versus not being prescribed, based on observational studies. Heat therapy was probably effective for acute low back pain, spinal manipulation might be effective for acute back pain with radiculopathy, acupressure might be effective for acute musculoskeletal pain, an opioid might be effective for acute neuropathic pain, massage might be effective for some types of postoperative pain, and a cervical collar or exercise might be effective for acute neck pain with radiculopathy. Most studies had methodological limitations. Effect sizes were primarily small to moderate for pain, the most commonly evaluated outcome. Opioids were associated with increased risk of short-term adverse events versus NSAIDs or acetaminophen, including any adverse event, nausea, dizziness, and somnolence. Serious adverse events were uncommon for all interventions, but studies were not designed to assess risk of overdose, opioid use disorder, or long-term harms. Evidence on how benefits or harms varied in subgroups was lacking. Conclusions. Opioid therapy was associated with decreased or similar effectiveness as an NSAID for some acute pain conditions, but with increased risk of short-term adverse events. Evidence on nonpharmacological therapies was limited, but heat therapy, spinal manipulation, massage, acupuncture, acupressure, a cervical collar, and exercise were effective for specific acute pain conditions. Research is needed to determine the comparative effectiveness of therapies for sickle cell pain, acute neuropathic pain, neck pain, and management of postoperative pain following discharge; effects of therapies for acute pain on non-pain outcomes; effects of therapies on long-term outcomes, including long-term opioid use; and how benefits and harms of therapies vary in subgroups.