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[PMID]:28456646
[Au] Autor:Ng WY; Migotto A; Ferreira TS; Lopes LB
[Ad] Endereço:Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
[Ti] Título:Monoolein-alginate beads as a platform to promote adenosine cutaneous localization and wound healing.
[So] Source:Int J Biol Macromol;102:1104-1111, 2017 Sep.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Alginate beads containing the polar lipid monoolein were developed as a strategy to manage wet wounds by providing improved uptake of excess exudate while releasing adenosine locally for promotion of healing. To obtain monoolein-containing beads, the lipid was mixed with almond oil (2:1w/w), and emulsified within the alginate aqueous dispersion, followed by ionotropic gelation in CaCl solution. Compared to alginate-only, monoolein-alginate systems were 1.44-fold larger, their swelling ability was 1.40-fold higher and adenosine cumulative release was approximately 1.30-fold lower (at 24h). Monoolein-alginate beads were considered safe for topical application as demonstrated by the absence of changes on the viability of reconstructed skin equivalents compared to PBS. Smaller amounts of adenosine were delivered by the beads into and across damaged porcine skin (created by an incisional wound) compared to the drug aqueous solution, and cutaneous localization was favored. More specifically, the beads increased the viable skin layer/receptor phase delivery ratio by approximately 4-fold at 12h post-application. Considering the wide range of adenosine physiological effects and the importance of skin localization for its use in wound healing, these results demonstrate the potential of monoolein-containing beads for localized drug delivery and management of wet wounds.
[Mh] Termos MeSH primário: Adenosina/metabolismo
Alginatos/química
Portadores de Fármacos/química
Glicerídeos/química
Microesferas
Pele/metabolismo
Cicatrização/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adenosina/química
Adenosina/farmacologia
Animais
Liberação Controlada de Fármacos
Ácido Glucurônico/química
Ácidos Hexurônicos/química
Permeabilidade
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alginates); 0 (Drug Carriers); 0 (Glycerides); 0 (Hexuronic Acids); 8A5D83Q4RW (Glucuronic Acid); 8C3Z4148WZ (alginic acid); C4YAD5F5G6 (monoolein); K72T3FS567 (Adenosine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


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[PMID]:28450249
[Au] Autor:Kurt A; Toker OS; Tornuk F
[Ad] Endereço:Department of Food Engineering, Engineering Faculty, Ondokuz Mayis University, 55139, Samsun, Turkey; Department of Food Engineering, Engineering and Architecture Faculty, Bitlis Eren University, 13000 Bitlis, Turkey. Electronic address: abdullahkurt48@gmail.com.
[Ti] Título:Effect of xanthan and locust bean gum synergistic interaction on characteristics of biodegradable edible film.
[So] Source:Int J Biol Macromol;102:1035-1044, 2017 Sep.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The present study was aimed to use different combinations of xanthan (XG) and locust bean gum (LBG) in the biodegradable edible film preparation by benefitting from their synergistic interactions for the first time. Concentrations of LBG, XG and glycerol of the optimized film sample were found to be 89.6%, 10.4% and 20%, respectively. At the optimum point the WVP, TS, E% and EM values of film were found 0.22gmmh m kPa, 86.97MPa, 33.34% and 177.25MPa, respectively. The optimized film was characterized for its physical, thermal and structural behavior. The scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FTIR) analyses exhibited miscibility and presence of interaction between polymers. In conclusion, XG and LBG interaction was used successfully to get biodegradable films and coatings with improved characteristics.
[Mh] Termos MeSH primário: Materiais Biocompatíveis/química
Galactanos/química
Mananas/química
Gomas Vegetais/química
Polissacarídeos Bacterianos/química
Embalagem de Produtos
[Mh] Termos MeSH secundário: Materiais Biocompatíveis/metabolismo
Composição de Medicamentos
Glicerol/química
Fenômenos Mecânicos
Permeabilidade
Reologia
Vapor
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biocompatible Materials); 0 (Galactans); 0 (Mannans); 0 (Plant Gums); 0 (Polysaccharides, Bacterial); 0 (Steam); PDC6A3C0OX (Glycerol); TTV12P4NEE (xanthan gum); V4716MY704 (locust bean gum)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:28450246
[Au] Autor:Günes S; Tihminlioglu F
[Ad] Endereço:Graduate Program of Biogineering, Izmir Institute of Technology, Izmir, 35430, Turkey.
[Ti] Título:Hypericum perforatum incorporated chitosan films as potential bioactive wound dressing material.
[So] Source:Int J Biol Macromol;102:933-943, 2017 Sep.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Recent studies in wound dressing applications offer new therapies and promote wound healing process. The aim of this study was to develop Hypericum perforatum (St John's Wort) oil incorporated chitosan films for wound dressing applications. H. perforatum oil as a potential therapeutic agent was encapsulated in chitosan film to achieve a better wound dressing material. Oil incorporated chitosan films were successfully prepared by solvent casting method in different oil concentrations (0.25-1.5%v/v). Water vapor permeability (WVP), mechanical test, swelling behavior and surface hydrophobicity were performed in order to characterize the prepared films. Antimicrobial test was performed by disc diffusion method and the growth inhibition effects of the films including different amount of H. perforatum oil were investigated on Escherichia coli and Staphylococcus aureus. WVP increased with oil incorporation and the highest value was obtained for 0.25% oil concentration.The highest strain value was obtained in 0.25% oil content films although tensile stress decreased with increasing oil content. H. perforatum oil incorporated films had antimicrobial effect on both microorganisms. Chitosan based films had no cytotoxic effects on NIH3T3fibroblast cells and provided a good surface for cell attachment and proliferation. The results showed that the H. perforatum incorporated chitosan films seems to be a potential and novel biomaterial for wound healing applications.
[Mh] Termos MeSH primário: Bandagens
Materiais Biocompatíveis/química
Materiais Biocompatíveis/farmacologia
Quitosana/química
Hypericum/química
Óleos Vegetais/química
Cicatrização
[Mh] Termos MeSH secundário: Animais
Anti-Infecciosos/química
Anti-Infecciosos/farmacologia
Bandagens/microbiologia
Adesão Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Fenômenos Mecânicos
Camundongos
Células NIH 3T3
Permeabilidade
Vapor
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Infective Agents); 0 (Biocompatible Materials); 0 (Plant Oils); 0 (Steam); 9012-76-4 (Chitosan)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:29267502
[Au] Autor:Liu C; Shui CL; Wang Q; Luo H; Gu CG
[Ad] Endereço:Department of Urology, The Second People's Hospital of Deyang City, Deyang, Sichuan Province, China.
[Ti] Título:Mechanism of hif-1α mediated hypoxia-induced permeability changes in bladder endothelial cells.
[So] Source:Braz J Med Biol Res;51(2):e6768, 2017 Dec 18.
[Is] ISSN:1414-431X
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:This study aimed to investigate the mechanism of hypoxia-inducible factor-1 alpha (HIF-1α) mediated hypoxia-induced permeability changes in bladder endothelial cells. Models of in vitro hypoxic cell culture of bladder cancer, bladder cancer cells with low HIF-1α expression and HIF-1α RNA interference (RNAi) expression vector were established. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to detect the expression of HIF-1α and vascular endothelial growth factor (VEGF) in each group. Bladder cell permeability was determined. Results showed that protein and mRNA expression of HIF-1α and VEGF at 3 and 12 h of hypoxia were significantly higher than normal control (P<0.05), and peaked at 12 h. HIF-1α and VEGF expression in the hypoxic group and hypoxic+3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) group were significantly higher than normal control (P<0.05), while expression in the hypoxic+YC-1 group was significantly lower than the hypoxic group (P<0.05). Bladder cell permeability in the hypoxic and hypoxic+YC-1 group were significantly increased compared to normal control (P<0.05), while in the hypoxic+YC-1 group was significantly decreased compared to the hypoxic group (P<0.05). Most of the cells in the stably transfected HIF-1α RNAi expression vector pcDNA6.2-GW/EmGFP-miR-siHIF-1α expressed green fluorescence protein (GFP) under fluorescence microscope. pcDNA6.2-GW/EmGFP-miR-siHIF-1α could significantly inhibit HIF-1α gene expression (P<0.05). HIF-1α and VEGF expression in the hypoxic group and siHIF-1α hypoxic group were significantly higher than normal group (P<0.05), while expression in the siHIF-1α hypoxic group was significantly lower than the hypoxic group (P<0.05). Findings suggest that HIF-1α is an important factor in the increase of bladder cancer cell permeability.
[Mh] Termos MeSH primário: Células Endoteliais/fisiologia
Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia
Hipóxia Tumoral/fisiologia
Neoplasias da Bexiga Urinária/metabolismo
Fator A de Crescimento do Endotélio Vascular/fisiologia
[Mh] Termos MeSH secundário: Animais
Western Blotting
Linhagem Celular Tumoral
Células Endoteliais/patologia
Regulação Neoplásica da Expressão Gênica/fisiologia
Subunidade alfa do Fator 1 Induzível por Hipóxia/análise
Permeabilidade
Interferência de RNA
Coelhos
Reação em Cadeia da Polimerase em Tempo Real
Neoplasias da Bexiga Urinária/genética
Neoplasias da Bexiga Urinária/patologia
Fator A de Crescimento do Endotélio Vascular/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (Vascular Endothelial Growth Factor A)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE


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[PMID]:28455168
[Au] Autor:Cummings CS; Fein K; Murata H; Ball RL; Russell AJ; Whitehead KA
[Ad] Endereço:Center for Polymer-based Protein Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, United States; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, United States.
[Ti] Título:ATRP-grown protein-polymer conjugates containing phenylpiperazine selectively enhance transepithelial protein transport.
[So] Source:J Control Release;255:270-278, 2017 Jun 10.
[Is] ISSN:1873-4995
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Despite its patient-friendliness, the oral route is not yet a viable strategy for the delivery of biomacromolecular therapeutics. This is, in part, due to the large size of proteins, which greatly limits their absorption across the intestinal epithelium. Although chemical permeation enhancers can improve macromolecular transport, their positive impact is often accompanied by toxicity. One element potentially contributing to this toxicity is the lack of co-localization of the enhancer with the protein drug, which can result in non-specific permeation of the intestine as well as enhancer overdosing in some areas due to non-uniform distribution. To circumvent these issues, this study describes a new way of increasing protein permeability via a polymer conjugation process that co-localizes permeation enhancer with the protein. Based on previous reports demonstrating the utility of 1-phenylpiperazine as an intestinal permeation enhancer, we synthesized protein-polymer conjugates with a phenylpiperazine-containing polymer using polymer-based protein engineering. A novel phenylpiperazine acrylamide monomer was synthesized and chain extended using atom transfer radical polymerization from the model protein bovine serum albumin (BSA). At non-cytotoxic doses, the protein-polymer conjugates induced a dose dependent reduction in the trans-epithelial electrical resistance of Caco-2 monolayers and an impressive ~30-fold increase in BSA permeability. Furthermore, this permeability increase was selective, as the permeability of the small molecule calcein co-incubated with the protein-polymer conjugate increased only 5-fold. Together, these data represent an important first step in the development of protein polymer conjugates that facilitate selective protein transport across membranes that are typically impermeable to macromolecules.
[Mh] Termos MeSH primário: Piperazinas/administração & dosagem
Soroalbumina Bovina/administração & dosagem
[Mh] Termos MeSH secundário: Células CACO-2
Sobrevivência Celular/efeitos dos fármacos
Seres Humanos
Absorção Intestinal
Permeabilidade
Piperazinas/química
Polimerização
Transporte Proteico
Soroalbumina Bovina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Piperazines); 27432CM55Q (Serum Albumin, Bovine); J9225CBI7D (phenylpiperazine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:29442035
[Au] Autor:Incecayir T; Ilbasmis-Tamer S; Tirnaksiz F; Degim T
[Ti] Título:Assessment of the potential drug-drug interaction between carvedilol and clopidogrel mediated through intestinal P-glycoprotein.
[So] Source:Pharmazie;71(8):472-477, 2016 08 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The most widely prescribed oral antiplatelet agent, clopidogrel, shows high interindividual variability resulting in an increased risk of cardiovascular events in the patients with reduced platelet inhibition. The purpose of this study was to investigate the role of the P-glycoprotein (P-gp) efflux pump in limiting the intestinal permeability of clopidogrel and the effect of a ß-blocker, namely, carvedilol, on its intestinal transport. Effective permeabilities (Peff) of clopidogrel and carvedilol were investigated in the proximal jejunum and distal ileum of rats using an in situ intestinal perfusion model. Peff values of clopidogrel and carvedilol were found to be concentration dependent with decreased Peff values at the low perfusate concentrations. Coperfusion with the P-gp inhibitors verapamil (100 µM) and carvedilol (10 µM) significantly increased the Peff of clopidogrel in the jejunum (8.31±0.20 x 10-5 and 6.98±0.75 x 10-5 vs. 3.60±0.51 x 10-5, respectively) and ileum (9.08±2.19 x 10-5 and 8.35±1.58 x 10-5 vs. 3.85±0.15 x 10-5, respectively). However, at the highest concentration tested (30 µM), clopidogrel exhibited 3 and 1.4 times higher Peff than those of metoprolol, an FDA high permeability reference standard, in the jejunum and ileum, respectively. Overall, this study indicates that the efflux function appears not to have a significant impact on the in vivo intestinal absorption of clopidogrel due to the saturation of P-gp, suggesting no clinically relevant interaction between carvedilol and clopidogrel mediated through P-gp at intestinal level.
[Mh] Termos MeSH primário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/efeitos dos fármacos
Antagonistas Adrenérgicos beta/farmacologia
Carbazóis/farmacologia
Intestino Delgado/efeitos dos fármacos
Inibidores da Agregação de Plaquetas/farmacologia
Propanolaminas/farmacologia
Ticlopidina/análogos & derivados
[Mh] Termos MeSH secundário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores
Animais
Interações Medicamentosas
Absorção Intestinal/efeitos dos fármacos
Intestino Delgado/metabolismo
Masculino
Metoprolol/farmacologia
Perfusão
Permeabilidade/efeitos dos fármacos
Ratos
Ratos Wistar
Ticlopidina/farmacologia
Verapamil/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Adrenergic beta-Antagonists); 0 (Carbazoles); 0 (Platelet Aggregation Inhibitors); 0 (Propanolamines); 0K47UL67F2 (carvedilol); A74586SNO7 (clopidogrel); CJ0O37KU29 (Verapamil); GEB06NHM23 (Metoprolol); OM90ZUW7M1 (Ticlopidine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6059


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[PMID]:28468836
[Au] Autor:Yoshikado T; Toshimoto K; Nakada T; Ikejiri K; Kusuhara H; Maeda K; Sugiyama Y
[Ad] Endereço:Sugiyama Laboratory, RIKEN Innovation Center, RIKEN, Kanagawa, Japan (T.Y., K.T., Y.S.); DMPK Research Laboratories Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma, Saitama, Japan (T.N.); and Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Univer
[Ti] Título:Comparison of Methods for Estimating Unbound Intracellular-to-Medium Concentration Ratios in Rat and Human Hepatocytes Using Statins.
[So] Source:Drug Metab Dispos;45(7):779-789, 2017 Jul.
[Is] ISSN:1521-009X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:It is essential to estimate concentrations of unbound drugs inside the hepatocytes to predict hepatic clearance, efficacy, and toxicity of the drugs. The present study was undertaken to compare predictability of the unbound hepatocyte-to-medium concentration ratios (K ) by two methods based on the steady-state cell-to-medium total concentration ratios at 37°C and on ice (K ) and based on their initial uptake rates (K ). Poorly metabolized statins were used as test drugs because of their concentrative uptake via organic anion-transporting polypeptides. K values of these statins provided less interexperimental variation than the K values, because only data at longer time are required for K K values for pitavastatin, rosuvastatin, and pravastatin were 1.2- to 5.1-fold K in rat hepatocytes; K values in human hepatocytes also tended to be larger than corresponding K To explain these discrepancies, theoretical values of K and K were compared with true K (K ), considering the inside-negative membrane potential and ionization of the drugs in hepatocytes and medium. Membrane potentials were approximately -30 mV in human hepatocytes at 37°C and almost abolished on ice. Theoretical equations considering the membrane potentials indicate that K values for the statins are 0.85- to 1.2-fold K , whereas K values are 2.2- to 3.1-fold K , depending on the ratio of the passive permeability of the ionized to nonionized forms. In conclusion, K values of anions are similar to K when the inside-negative membrane potential is considered. This suggests that K is preferable for estimating the concentration of unbound drugs inside the hepatocytes.
[Mh] Termos MeSH primário: Hepatócitos/metabolismo
Inibidores de Hidroximetilglutaril-CoA Redutases/metabolismo
[Mh] Termos MeSH secundário: Animais
Transporte Biológico/fisiologia
Seres Humanos
Fígado/metabolismo
Masculino
Potenciais da Membrana/fisiologia
Transportadores de Ânions Orgânicos/metabolismo
Permeabilidade
Pravastatina/metabolismo
Quinolinas/metabolismo
Ratos
Ratos Sprague-Dawley
Rosuvastatina Cálcica/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (Organic Anion Transporters); 0 (Quinolines); 83MVU38M7Q (Rosuvastatin Calcium); KXO2KT9N0G (Pravastatin); M5681Q5F9P (pitavastatin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1124/dmd.116.074823


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[PMID]:29427588
[Au] Autor:Nishimura-Danjobara Y; Oyama K; Yokoigawa K; Oyama Y
[Ad] Endereço:Department of Food Science, Faculty of Bioscience and Bioindustry, Tokushima University, Tokushima 770-8513, Japan.
[Ti] Título:Hyperpolarization by N-(3-oxododecanoyl)-l-homoserine-lactone, a quorum sensing molecule, in rat thymic lymphocytes.
[So] Source:Chem Biol Interact;283:91-96, 2018 Mar 01.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:To study the adverse effects of N-(3-oxododecanoyl)-l-homoserine-lactone (ODHL), a quorum sensing molecule, on mammalian host cells, its effect on membrane potential was examined in rat thymic lymphocytes using flow cytometric techniques with a voltage-sensitive fluorescent probe. As 3-300 µM ODHL elicited hyperpolarization, it is likely that it increases membrane K permeability because hyperpolarization is directly linked to changing K gradient across membranes, but not Na and Cl gradients. ODHL did not increase intracellular Ca concentration. ODHL also produced a response in the presence of an intracellular Zn chelator. Thus, it is unlikely that intracellular Ca and Zn are attributed to the response. Quinine, a non-specific K channel blocker, greatly reduced hyperpolarization. However, because charybdotoxin, tetraethylammonium chloride, 4-aminopyridine, and glibenclamide did not affect it, it is pharmacologically hypothesized that Ca -activated K channels, voltage-gated K channels, and ATP-sensitive K channels are not involved in ODHL-induced hyperpolarization. Although the K channels responsible for ODHL-induced hyperpolarization have not been identified, it is suggested that ODHL can elicit hyperpolarization in mammalian host cells, disturbing cellular functions.
[Mh] Termos MeSH primário: 4-Butirolactona/análogos & derivados
Polaridade Celular/efeitos dos fármacos
Homosserina/análogos & derivados
Percepção de Quorum/efeitos dos fármacos
[Mh] Termos MeSH secundário: 4-Butirolactona/farmacologia
Animais
Cálcio/metabolismo
Charibdotoxina/farmacologia
Citometria de Fluxo
Glibureto/farmacologia
Homosserina/farmacologia
Canais KATP/metabolismo
Linfócitos/citologia
Linfócitos/efeitos dos fármacos
Linfócitos/metabolismo
Permeabilidade/efeitos dos fármacos
Potássio/metabolismo
Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo
Quinina/farmacologia
Ratos
Ratos Wistar
Timócitos/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (KATP Channels); 0 (N-(3-oxododecanoyl)homoserine lactone); 0 (Potassium Channels, Voltage-Gated); 115422-61-2 (Charybdotoxin); 6KA95X0IVO (Homoserine); A7V27PHC7A (Quinine); OL659KIY4X (4-Butyrolactone); RWP5GA015D (Potassium); SX6K58TVWC (Glyburide); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180211
[St] Status:MEDLINE


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[PMID]:28460485
[Au] Autor:Lv LX; Zhou ZX; Zhou Z; Zhang LJ; Yan R; Zhao Z; Yang LY; Bian XY; Jiang HY; Li YD; Sun YS; Xu QQ; Hu GL; Guan WJ; Li YQ
[Ad] Endereço:Institute of Pharmaceutical Biotechnology and College of Pharmaceutical Sciences, Zhejiang University, 310058 Hangzhou, China.
[Ti] Título:Hispidin induces autophagic and necrotic death in SGC-7901 gastric cancer cells through lysosomal membrane permeabilization by inhibiting tubulin polymerization.
[So] Source:Oncotarget;8(16):26992-27006, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hispidin and its derivatives are widely distributed in edible mushrooms. Hispidin is more cytotoxic to A549, SCL-1, Bel7402 and Capan-1 cancer cells than to MRC5 normal cells; by contrast, hispidin protects H9c2 cardiomyoblast cells from hydrogen peroxide-induced or doxorubicin-induced apoptosis. Consequently, further research on how hispidin affects normal and cancer cells may help treat cancer and reduce chemotherapy-induced side effects. This study showed that hispidin caused caspase-independent death in SGC-7901 cancer cells but not in GES-1 normal cells. Hispidin-induced increases in LC3-II occurred in SGC-7901 cells in a time independent manner. Cell death can be partially inhibited by treatment with ATG5 siRNA but not by autophagy or necroptosis inhibitors. Ultrastructural evidence indicated that hispidin-induced necrotic cell death involved autophagy. Hispidin-induced lysosomal membrane permeabilization (LMP) related to complex cell death occurred more drastically in SGC-7901 cells than in GES-1 cells. Ca2+ rather than cathepsins from LMP contributed more to cell death. Hispidin induced microtubule depolymerization, which can cause LMP, more drastically in SGC-7901 cells than in GES-1 cells. At 4.1 µM, hispidin promoted cell-free tubulin polymerization but at concentrations higher than 41 µM, hispidin inhibited polymerization. Hispidin did not bind to tubulin. Alterations in microtubule regulatory proteins, such as stathmin phosphorylation at Ser16, contributed to hispidin-induced SGC-7901 cell death. In conclusion, hispidin at concentrations higher than 41 µM may inhibit tubulin polymerization by modulating microtubule regulatory proteins, such as stathmin, causing LMP and complex SGC-7901 cell death. This mechanism suggests a promising novel treatment for human cancer.
[Mh] Termos MeSH primário: Autofagia/efeitos dos fármacos
Membranas Intracelulares/efeitos dos fármacos
Lisossomos/metabolismo
Multimerização Proteica/efeitos dos fármacos
Pironas/farmacologia
Tubulina (Proteína)/metabolismo
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Caspases/metabolismo
Morte Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Seres Humanos
Microtúbulos/química
Microtúbulos/metabolismo
Óxido Nítrico/biossíntese
Permeabilidade
Fosforilação
Estatmina/metabolismo
Tubulina (Proteína)/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pyrones); 0 (STMN1 protein, human); 0 (Stathmin); 0 (Tubulin); 31C4KY9ESH (Nitric Oxide); EC 3.4.22.- (Caspases); SSJ18CG55E (hispidin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15935


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[PMID]:29342216
[Au] Autor:Narayanaswamy VP; Giatpaiboon SA; Uhrig J; Orwin P; Wiesmann W; Baker SM; Townsend SM
[Ad] Endereço:Synedgen, Inc., Claremont, California, United States of America.
[Ti] Título:In Vitro activity of novel glycopolymer against clinical isolates of multidrug-resistant Staphylococcus aureus.
[So] Source:PLoS One;13(1):e0191522, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The incidence of multidrug-resistant (MDR) organisms, including methicillin-resistant Staphylococcus aureus (MRSA), is a serious threat to public health. Progress in developing new therapeutics is being outpaced by antibiotic resistance development, and alternative agents that rapidly permeabilize bacteria hold tremendous potential for treating MDR infections. A new class of glycopolymers includes polycationic poly-N (acetyl, arginyl) glucosamine (PAAG) is under development as an alternative to traditional antibiotic strategies to treat MRSA infections. This study demonstrates the antibacterial activity of PAAG against clinical isolates of methicillin and mupirocin-resistant Staphylococcus aureus. Multidrug-resistant S. aureus was rapidly killed by PAAG, which completely eradicated 88% (15/17) of all tested strains (6-log reduction in CFU) in ≤ 12-hours at doses that are non-toxic to mammalian cells. PAAG also sensitized all the clinical MRSA strains (17/17) to oxacillin as demonstrated by the observed reduction in the oxacillin MIC to below the antibiotic resistance breakpoint. The effect of PAAG and standard antibiotics including vancomycin, oxacillin, mupirocin and bacitracin on MRSA permeability was studied by measuring propidium iodide (PI) uptake by bacterial cells. Antimicrobial resistance studies showed that S. aureus developed resistance to PAAG at a rate slower than to mupirocin but similar to bacitracin. PAAG was observed to resensitize drug-resistant S. aureus strains sampled from passage 13 and 20 of the multi-passage resistance study, reducing MICs of mupirocin and bacitracin below their clinical sensitivity breakpoints. This class of bacterial permeabilizing glycopolymers may provide a new tool in the battle against multidrug-resistant bacteria.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Glucosamina/análogos & derivados
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
Polímeros/farmacologia
Polissacarídeos/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/química
Farmacorresistência Bacteriana Múltipla
Glucosamina/química
Glucosamina/farmacologia
Glicosídeos
Seres Humanos
Técnicas In Vitro
Resistência a Meticilina
Staphylococcus aureus Resistente à Meticilina/isolamento & purificação
Staphylococcus aureus Resistente à Meticilina/metabolismo
Testes de Sensibilidade Microbiana
Mupirocina/farmacologia
Permeabilidade/efeitos dos fármacos
Polímeros/química
Polissacarídeos/química
Propídio/farmacocinética
Infecções Estafilocócicas/tratamento farmacológico
Infecções Estafilocócicas/microbiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Glycosides); 0 (Polymers); 0 (Polysaccharides); 0 (pinocembrin 7-O-apiosyl(1-5)apiosyl(1-2)glucopyranoside); 0 (poly-N (acetyl, arginyl)glucosamine); 36015-30-2 (Propidium); D0GX863OA5 (Mupirocin); N08U5BOQ1K (Glucosamine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191522



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