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[PMID]:28186768
[Au] Autor:Enright EF; Joyce SA; Gahan CG; Griffin BT
[Ad] Endereço:School of Pharmacy, ‡APC Microbiome Institute, §School of Biochemistry & Cell Biology, and ∥School of Microbiology, University College Cork , Cork, Ireland.
[Ti] Título:Impact of Gut Microbiota-Mediated Bile Acid Metabolism on the Solubilization Capacity of Bile Salt Micelles and Drug Solubility.
[So] Source:Mol Pharm;14(4):1251-1263, 2017 Apr 03.
[Is] ISSN:1543-8392
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In recent years, the gut microbiome has gained increasing appreciation as a determinant of the health status of the human host. Bile salts that are secreted into the intestine may be biotransformed by enzymes produced by the gut bacteria. To date, bile acid research at the host-microbe interface has primarily been directed toward effects on host metabolism. The aim of this work was to investigate the effect of changes in gut microbial bile acid metabolism on the solubilization capacity of bile salt micelles and consequently intraluminal drug solubility. First, the impact of bile acid metabolism, mediated in vivo by the microbial enzymes bile salt hydrolase (BSH) and 7α-dehydroxylase, on drug solubility was assessed by comparing the solubilization capacity of (a) conjugated vs deconjugated and (b) primary vs secondary bile salts. A series of poorly water-soluble drugs (PWSDs) were selected as model solutes on the basis of an increased tendency to associate with bile micelles. Subsequently, PWSD solubility and dissolution was evaluated in conventional biorelevant simulated intestinal fluid containing host-derived bile acids, as well as in media modified to contain microbial bile acid metabolites. The findings suggest that deconjugation of the bile acid steroidal core, as dictated by BSH activity, influences micellar solubilization capacity for some PWSDs; however, these differences appear to be relatively minor. In contrast, the extent of bile acid hydroxylation, regulated by microbial 7α-dehydroxylase, was found to significantly affect the solubilization capacity of bile salt micelles for all nine drugs studied (p < 0.05). Subsequent investigations in biorelevant media containing either the trihydroxy bile salt sodium taurocholate (TCA) or the dihydroxy bile salt sodium taurodeoxycholate (TDCA) revealed altered drug solubility and dissolution. Observed differences in biorelevant media appeared to be both drug- and amphiphile (bile salt/lecithin) concentration-dependent. Our studies herein indicate that bile acid modifications occurring at the host-microbe interface could lead to alterations in the capacity of intestinal bile salt micelles to solubilize drugs, providing impetus to consider the gut microbiota in the drug absorption process. In the clinical setting, disruption of the gut microbial ecosystem, through disease or antibiotic treatment, could transform the bile acid pool with potential implications for drug absorption and bioavailability.
[Mh] Termos MeSH primário: Ácidos e Sais Biliares/química
Bile/química
Microbioma Gastrointestinal/fisiologia
Preparações Farmacêuticas/química
[Mh] Termos MeSH secundário: Disponibilidade Biológica
Seres Humanos
Micelas
Solubilidade
Esteroides/química
Ácido Taurocólico/química
Ácido Taurodesoxicólico/química
Água/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bile Acids and Salts); 0 (Micelles); 0 (Pharmaceutical Preparations); 0 (Steroids); 059QF0KO0R (Water); 516-50-7 (Taurodeoxycholic Acid); 5E090O0G3Z (Taurocholic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170211
[St] Status:MEDLINE
[do] DOI:10.1021/acs.molpharmaceut.6b01155


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[PMID]:26349051
[Au] Autor:Aguirre TA; Rosa M; Coulter IS; Brayden DJ
[Ad] Endereço:UCD School of Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland; Sigmoid Pharma, Dublin City University, Invent Centre, Dublin 9, Ireland.
[Ti] Título:In vitro and in vivo preclinical evaluation of a minisphere emulsion-based formulation (SmPill®) of salmon calcitonin.
[So] Source:Eur J Pharm Sci;79:102-11, 2015 Nov 15.
[Is] ISSN:1879-0720
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Salmon calcitonin (sCT, MW 3432Da) is a benchmark molecule for an oral peptide delivery system because it is degraded and has low intestinal epithelial permeability. Four dry emulsion minisphere prototypes (SmPill®) containing sCT were co-formulated with permeation enhancers (PEs): sodium taurodeoxycholate (NaTDC), sodium caprate (C10) or coco-glucoside (CG), or with a pH acidifier, citric acid (CA). Minispheres protected sCT from thermal degradation and the released sCT retained high bioactivity, as determined by cyclic AMP generation in T47D cells. Pre-minisphere emulsions of PEs combined with sCT increased absolute bioavailability (F) compared to native sCT following rat intra-jejunal (i.j.) and intra-colonic (i.c.) loop instillations, an effect that was more pronounced in colon. Minispheres corresponding to ~2000I.U. (~390µg) sCT/kg were instilled by i.j. or i.c. instillations and hypocalcaemia resulted from all prototypes. The absolute F (i.j.) of sCT was 11.0, 4.8, and 1.4% for minispheres containing NaTDC (10µmol/kg), CG (12µmol/kg) or CA (32µmol/kg) respectively. For i.c. instillations, the largest absolute F (22% in each case) was achieved for minispheres containing either C10 (284µmol/kg) or CG (12µmol/kg), whilst the absolute F was 8.2% for minispheres loaded with CA (32µmol/kg). In terms of relative F, the best data were obtained for minispheres containing NaTDC (i.j.), a 4-fold increase over sCT solution, and also for either C10 or CG (i.c.), where there was a 3-fold increase over sCT solution. Histology of instilled intestinal loops indicated that neither the minispheres nor components thereof caused major perturbation. In conclusion, selected SmPill® minisphere formulations may have the potential to be used as oral peptide delivery systems when delivered to jejunum or colon.
[Mh] Termos MeSH primário: Sistemas de Liberação de Medicamentos/métodos
[Mh] Termos MeSH secundário: Administração Oral
Animais
Disponibilidade Biológica
Calcitonina
Colo
Ácidos Decanoicos/administração & dosagem
Ácidos Decanoicos/farmacocinética
Emulsões
Técnicas In Vitro
Instilação de Medicamentos
Absorção Intestinal
Jejuno
Masculino
Microesferas
Ratos
Ratos Wistar
Ácido Taurodesoxicólico/administração & dosagem
Ácido Taurodesoxicólico/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Decanoic Acids); 0 (Emulsions); 4G9EDB6V73 (decanoic acid); 516-50-7 (Taurodeoxycholic Acid); 7SFC6U2VI5 (salmon calcitonin); 9007-12-9 (Calcitonin)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150909
[St] Status:MEDLINE


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[PMID]:26280129
[Au] Autor:Brighton CA; Rievaj J; Kuhre RE; Glass LL; Schoonjans K; Holst JJ; Gribble FM; Reimann F
[Ad] Endereço:University of Cambridge (C.A.B., J.R., L.L.G., F.M.G., F.R.), Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Novo Nordisk Foundati
[Ti] Título:Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein-Coupled Bile Acid Receptors.
[So] Source:Endocrinology;156(11):3961-70, 2015 Nov.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein-coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1-secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca(2+). In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca(2+) response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber-mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms.
[Mh] Termos MeSH primário: Ácidos e Sais Biliares/farmacologia
Células Enteroendócrinas/efeitos dos fármacos
Peptídeo 1 Semelhante ao Glucagon/secreção
Receptores Acoplados a Proteínas-G/metabolismo
[Mh] Termos MeSH secundário: Animais
Cálcio/metabolismo
Células Cultivadas
AMP Cíclico/metabolismo
Células Enteroendócrinas/metabolismo
Peptídeo 1 Semelhante ao Glucagon/metabolismo
Intestino Delgado/efeitos dos fármacos
Intestino Delgado/metabolismo
Espaço Intracelular/efeitos dos fármacos
Espaço Intracelular/metabolismo
Masculino
Camundongos Knockout
Camundongos Transgênicos
Microscopia de Fluorescência
Ratos Wistar
Receptores Acoplados a Proteínas-G/genética
Ácido Taurodesoxicólico/farmacologia
Ácido Taurolitocólico/farmacologia
Técnicas de Cultura de Tecidos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bile Acids and Salts); 0 (Gpbar1 protein, mouse); 0 (Receptors, G-Protein-Coupled); 516-50-7 (Taurodeoxycholic Acid); 516-90-5 (Taurolithocholic Acid); 89750-14-1 (Glucagon-Like Peptide 1); E0399OZS9N (Cyclic AMP); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:150818
[St] Status:MEDLINE
[do] DOI:10.1210/en.2015-1321


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[PMID]:26208104
[Au] Autor:James L; Yan K; Pence L; Simpson P; Bhattacharyya S; Gill P; Letzig L; Kearns G; Beger R
[Ad] Endereço:Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, United States of America; Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, United States of America.
[Ti] Título:Comparison of Bile Acids and Acetaminophen Protein Adducts in Children and Adolescents with Acetaminophen Toxicity.
[So] Source:PLoS One;10(7):e0131010, 2015.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Metabolomics approaches have enabled the study of new mechanisms of liver injury in experimental models of drug toxicity. Disruption of bile acid homeostasis is a known mechanism of drug induced liver injury. The relationship of individual bile acids to indicators of oxidative drug metabolism (acetaminophen protein adducts) and liver injury was examined in children with acetaminophen overdose, hospitalized children with low dose exposure to acetaminophen, and children with no recent exposure to acetaminophen. Nine bile acids were quantified through targeted metabolomic analysis in the serum samples of the three groups. Bile acids were compared to serum levels of acetaminophen protein adducts and alanine aminotransferase. Glycodeoxycholic acid, taurodeoxycholic acid, and glycochenodeoxycholic acid were significantly increased in children with acetaminophen overdose compared to healthy controls. Among patients with acetaminophen overdose, bile acids were higher in subjects with acetaminophen protein adduct values > 1.0 nmol/mL and modest correlations were noted for three bile acids and acetaminophen protein adducts as follows: taurodeoxycholic acid (R=0.604; p<0.001), glycodeoxycholic acid (R=0.581; p<0.001), and glycochenodeoxycholic acid (R=0.571; p<0.001). Variability in bile acids was greater among hospitalized children receiving low doses of acetaminophen than in healthy children with no recent acetaminophen exposure. Compared to bile acids, acetaminophen protein adducts more accurately discriminated among children with acetaminophen overdose, children with low dose exposure to acetaminophen, and healthy control subjects. In children with acetaminophen overdose, elevations of conjugated bile acids were associated with specific indicators of acetaminophen metabolism and non-specific indicators of liver injury.
[Mh] Termos MeSH primário: Acetaminofen/envenenamento
Ácidos e Sais Biliares/sangue
Doença Hepática Induzida por Substâncias e Drogas/sangue
Overdose de Drogas/sangue
[Mh] Termos MeSH secundário: Acetaminofen/metabolismo
Adolescente
Alanina Transaminase/metabolismo
Biomarcadores/sangue
Doença Hepática Induzida por Substâncias e Drogas/diagnóstico
Criança
Pré-Escolar
Diagnóstico Diferencial
Overdose de Drogas/diagnóstico
Feminino
Ácido Glicoquenodesoxicólico/sangue
Ácido Glicodesoxicólico/sangue
Homeostase
Seres Humanos
Masculino
Metabolômica/métodos
Ligação Proteica
Sensibilidade e Especificidade
Ácido Taurodesoxicólico/sangue
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Bile Acids and Salts); 0 (Biomarkers); 360-65-6 (Glycodeoxycholic Acid); 362O9ITL9D (Acetaminophen); 516-50-7 (Taurodeoxycholic Acid); 640-79-9 (Glycochenodeoxycholic Acid); EC 2.6.1.2 (Alanine Transaminase)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150725
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0131010


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[PMID]:25881988
[Au] Autor:Sharma A; Agrawal H; Mullani N; Sandhu A; Singh MK; Chauhan MS; Singla SK; Palta P; Manik RS
[Ad] Endereço:Embryo Biotechnology Laboratory, Animal Biotechnology Centre, National Dairy Research Institute, Karnal, India.
[Ti] Título:Supplementation of tauroursodeoxycholic acid during IVC did not enhance in vitro development and quality of buffalo IVF embryos but combated endoplasmic reticulum stress.
[So] Source:Theriogenology;84(2):200-7, 2015 Jul 15.
[Is] ISSN:1879-3231
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Endoplasmic reticulum (ER) stress, a dysfunction in protein-folding capacity of ER, is involved in many pathologic and physiological responses including embryonic development. This study investigated the effect of supplementation of IVC medium with an ER stress inducer, tunicamycin (TM), and an inhibitor, tauroursodeoxycholic acid (TUDCA), on the developmental competence, apoptosis, and gene expression in buffalo embryos produced by IVF. Treatment of presumed zygotes with TM resulted in a significant (P < 0.01) decrease in the blastocyst rate, whereas TUDCA supplementation did not improve the blastocyst development rate. Further, presence of TUDCA could not ameliorate the adverse effects of TM in terms of the blastocyst rate in combined (TM + TUDCA) treatment. Tunicamycin treatment increased (P < 0.01) the apoptotic index and reduced the total cell number, whereas TUDCA did not affect them significantly. However, TUDCA reduced the extent of TM-mediated apoptosis during combined (TM + TUDCA) treatment. Tunicamycin treatment increased (P < 0.01) and TUDCA treatment decreased (P < 0.01) the expression level of ER chaperones, GRP78 and GRP94. In the combined TM + TUDCA treatment, TUDCA decreased their expression level compared to that in the controls. A similar pattern was observed in the case of proapoptotic gene BAX. We did not find any significant difference in the expression level of BCl-XL, BID, P53, and CASPASE 3 after TM and TUDCA supplementation. In conclusion, our study reported that TM induces ER stress in buffalo embryos produced in vitro resulting in a decrease in the blastocyst rate and an increase in the level of apoptosis and that these actions are mediated by modulating the expression of apoptosis-related genes and ER chaperones. Tauroursodeoxycholic acid did not improve the developmental potential of buffalo embryos; however, it attenuated the TM-induced apoptosis by downregulating BAX and ER chaperones.
[Mh] Termos MeSH primário: Búfalos/embriologia
Técnicas de Cultura Embrionária/veterinária
Desenvolvimento Embrionário/efeitos dos fármacos
Estresse do Retículo Endoplasmático/efeitos dos fármacos
Fertilização In Vitro/veterinária
Ácido Taurodesoxicólico/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Apoptose/genética
Blastocisto/efeitos dos fármacos
Blastocisto/fisiologia
Meios de Cultura
Técnicas de Cultura Embrionária/métodos
Expressão Gênica/efeitos dos fármacos
Proteínas de Choque Térmico
Chaperonas Moleculares/genética
Tunicamicina/farmacologia
Proteína X Associada a bcl-2/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Culture Media); 0 (Heat-Shock Proteins); 0 (Molecular Chaperones); 0 (bcl-2-Associated X Protein); 0 (molecular chaperone GRP78); 11089-65-9 (Tunicamycin); 516-50-7 (Taurodeoxycholic Acid)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:150605
[Lr] Data última revisão:
150605
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150418
[St] Status:MEDLINE


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[PMID]:25679293
[Au] Autor:Torcello-Gómez A; Fernández Fraguas C; Ridout MJ; Woodward NC; Wilde PJ; Foster TJ
[Ad] Endereço:Division of Food Sciences, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK. amelia.torcello_gomez@nottingham.ac.uk.
[Ti] Título:Effect of substituent pattern and molecular weight of cellulose ethers on interactions with different bile salts.
[So] Source:Food Funct;6(3):730-9, 2015 Mar.
[Is] ISSN:2042-650X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Some known mechanisms proposed for the reduction of blood cholesterol by dietary fibre are: binding with bile salts in the duodenum and prevention of lipid absorption, which can be partially related with the bile salt binding. In order to gain new insights into the mechanisms of the binding of dietary fibre to bile salts, the goal of this work is to study the main interactions between cellulose derivatives and two types of bile salts. Commercial cellulose ethers: methyl (MC), hydroxypropyl (HPC) and hydroxypropylmethyl cellulose (HPMC), have been chosen as dietary fibre due to their highly functional properties important in manufactured food products. Two types of bile salts: sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC), have been chosen to understand the effect of the bile salt type. Interactions in the bulk have been investigated by means of differential scanning calorimetry (DSC) and linear mechanical spectroscopy. Results show that both bile salts have inhibitory effects on the thermal structuring of cellulose ethers and this depends on the number and type of substitution in the derivatised celluloses, and is not dependent upon molecular weight. Concerning the bile salt type, the more hydrophobic bile salt (NaTDC) has greater effect on these interactions, suggesting more efficient adsorption onto cellulose ethers. These findings may have implications in the digestion of cellulose-stabilised food matrices, providing a springboard to develop new healthy cellulose-based food products with improved functional properties.
[Mh] Termos MeSH primário: Ácidos e Sais Biliares/química
Celulose/análogos & derivados
Fibras na Dieta/análise
Suplementos Nutricionais
Alimentos Fortificados
Derivados da Hipromelose/química
Metilcelulose/química
[Mh] Termos MeSH secundário: Adsorção
Ácidos e Sais Biliares/antagonistas & inibidores
Varredura Diferencial de Calorimetria
Configuração de Carboidratos
Celulose/química
Fenômenos Químicos
Módulo de Elasticidade
Aditivos Alimentares/química
Interações Hidrofóbicas e Hidrofílicas
Fenômenos Mecânicos
Peso Molecular
Reologia
Ácido Taurocólico/antagonistas & inibidores
Ácido Taurocólico/química
Ácido Taurodesoxicólico/antagonistas & inibidores
Ácido Taurodesoxicólico/química
Viscosidade
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bile Acids and Salts); 0 (Dietary Fiber); 0 (Food Additives); 3NXW29V3WO (Hypromellose Derivatives); 516-50-7 (Taurodeoxycholic Acid); 5E090O0G3Z (Taurocholic Acid); 9004-34-6 (Cellulose); 9004-67-5 (Methylcellulose); RFW2ET671P (hydroxypropylcellulose)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150214
[St] Status:MEDLINE
[do] DOI:10.1039/c5fo00099h


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[PMID]:25482338
[Au] Autor:Jin L; Boyd BJ; White PJ; Pennington MW; Norton RS; Nicolazzo JA
[Ad] Endereço:Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
[Ti] Título:Buccal mucosal delivery of a potent peptide leads to therapeutically-relevant plasma concentrations for the treatment of autoimmune diseases.
[So] Source:J Control Release;199:37-44, 2015 Feb 10.
[Is] ISSN:1873-4995
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Stichodactyla helianthus neurotoxin (ShK) is an immunomodulatory peptide currently under development for the treatment of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis by parenteral administration. To overcome the low patient compliance of conventional self-injections, we have investigated the potential of the buccal mucosa as an alternative delivery route for ShK both in vitro and in vivo. After application of fluorescent 5-Fam-ShK to untreated porcine buccal mucosa, there was no detectable peptide in the receptor chamber using an in vitro Ussing chamber model. However, the addition of the surfactants sodium taurodeoxycholate hydrate or cetrimide, and formulation of ShK in a chitosan mucoadhesive gel, led to 0.05-0.13% and 1.1% of the applied dose, respectively, appearing in the receptor chamber over 5h. Moreover, confocal microscopic studies demonstrated significantly enhanced buccal mucosal retention of the peptide (measured by mucosal fluorescence associated with 5-Fam-ShK) when enhancement strategies were employed. Administration of 5-Fam-ShK to mice (10mg/kg in a mucoadhesive chitosan-based gel (3%, w/v) with or without cetrimide (5%, w/w)) resulted in average plasma concentrations of 2.6-16.2nM between 2 and 6h, which were substantially higher than the pM concentrations required for therapeutic activity. This study demonstrated that the buccal mucosa is a promising administration route for the systemic delivery of ShK for the treatment of autoimmune diseases.
[Mh] Termos MeSH primário: Administração através da Mucosa
Doenças Autoimunes/tratamento farmacológico
Venenos de Cnidários/administração & dosagem
Venenos de Cnidários/uso terapêutico
Sistemas de Liberação de Medicamentos
Fatores Imunológicos/administração & dosagem
Fatores Imunológicos/uso terapêutico
Mucosa Bucal
Peptídeos/administração & dosagem
Peptídeos/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Doenças Autoimunes/sangue
Venenos de Cnidários/farmacocinética
Corantes Fluorescentes
Fatores Imunológicos/farmacocinética
Técnicas In Vitro
Camundongos
Peptídeos/farmacocinética
Padrões de Referência
Tensoativos/química
Tensoativos/farmacologia
Suínos
Ácido Taurodesoxicólico/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cnidarian Venoms); 0 (Fluorescent Dyes); 0 (Immunologic Factors); 0 (Peptides); 0 (Surface-Active Agents); 117860-13-6 (neurotoxin I, Stichodactyla helianthus); 516-50-7 (Taurodeoxycholic Acid)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:150127
[Lr] Data última revisão:
150127
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141209
[St] Status:MEDLINE


  8 / 402 MEDLINE  
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[PMID]:25227940
[Au] Autor:Liu Y; An H; Zhang J; Zhou H; Ren F; Hao Y
[Ad] Endereço:Key Laboratory of Functional Dairy, Co-constructed by Ministry of Education and Beijing Municipality, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing, China.
[Ti] Título:Functional role of tlyC1 encoding a hemolysin-like protein from Bifidobacterium longum BBMN68 in bile tolerance.
[So] Source:FEMS Microbiol Lett;360(2):167-73, 2014 Nov.
[Is] ISSN:1574-6968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Bifidobacteria are normal inhabitants of the human gut, and members of which are generally considered to be probiotic. Before exerting their beneficial properties, they must survive and persist in the physiological concentrations (0.05-2%) of bile in the gut. In this work, the functional role of tlyC1 encoding a hemolysin-like protein from Bifidobacterium longum BBMN68 in bile tolerance was tested. Analysis using the program TMHMM and homologous alignment indicated that TlyC1 is a nontransporter membrane protein and is conserved in many bifidobacteria. Heterologous expression of tlyC1 in Lactococcus lactis NZ9000 was shown to confer 45-fold higher tolerance to 0.15% ox-bile. Notably, the recombinant strains showed threefold higher survival when exposed to sublethal concentration of TCA and TDCA, while no significant change was observed when exposed to GCA and GDCA. Furthermore, real-time quantitative PCR demonstrated that the transcription of tlyC1 was up-regulated c. 2.5- and 2.7-fold in B. longum BBMN68 exposed to sublethal concentration of TCA and TDCA, while no significant change was observed with GCA and GDCA challenges. This study indicated that tlyC1 was specifically induced by tauroconjugates, which provided enhanced resistance to sodium taurocholate and sodium taurodeoxycholate.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Bifidobacterium/efeitos dos fármacos
Bifidobacterium/fisiologia
Tolerância a Medicamentos
Proteínas de Membrana/metabolismo
Ácido Taurocólico/toxicidade
Ácido Taurodesoxicólico/toxicidade
[Mh] Termos MeSH secundário: Bifidobacterium/metabolismo
Expressão Gênica
Perfilação da Expressão Gênica
Seres Humanos
Lactococcus lactis/efeitos dos fármacos
Lactococcus lactis/genética
Viabilidade Microbiana/efeitos dos fármacos
Reação em Cadeia da Polimerase em Tempo Real
Proteínas Recombinantes/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Membrane Proteins); 0 (Recombinant Proteins); 516-50-7 (Taurodeoxycholic Acid); 5E090O0G3Z (Taurocholic Acid)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:141124
[Lr] Data última revisão:
141124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140918
[St] Status:MEDLINE
[do] DOI:10.1111/1574-6968.12601


  9 / 402 MEDLINE  
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[PMID]:24836923
[Au] Autor:Pucci C; Tardani F; La Mesa C
[Ad] Endereço:Department of Chemistry, Cannizzaro Building, La Sapienza University , P.le A. Moro 5, I-00185 Rome, Italy.
[Ti] Título:Formation and properties of gels based on lipo-plexes.
[So] Source:J Phys Chem B;118(23):6107-16, 2014 Jun 12.
[Is] ISSN:1520-5207
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Aqueous systems containing sodium taurodeoxycholate and, eventually, soybean lecithin were investigated. Depending on the relative amounts of two such species, molecular, micellar, vesicular, liquid crystalline, and solid phases were formed. In the presence of bovine serum albumin, micellar and vesicular systems form lipo-plexes. The latter self-organize into gels, depending on composition and thermal treatments. According to scanning electron microscopy, vesicle-based gels obtained from lipo-plexes form sponge-like entities, whereas micelle-based ones self-arrange in fibrous organizations. Gels are characterized by a significant viscoelasticity in a wide temperature and frequency range. Rheological data were interpreted by assuming strict relations between the system response and the self-organization of the lipo-plexes into gels. It was inferred that differences in the gel properties depend on the different self-assembly modes of the aggregates formed by the mentioned lipo-plexes. Use of the above systems in biomedical applications, mostly in the preparation of matrices requiring the use of smart and biocompatible gels, is suggested.
[Mh] Termos MeSH primário: Géis/química
Géis/síntese química
Lecitinas/química
Proteínas de Plantas/química
Ácido Taurodesoxicólico/química
[Mh] Termos MeSH secundário: Animais
Bovinos
Difusão
Cinética
Micelas
Microscopia Eletrônica de Varredura
Soroalbumina Bovina/química
Feijão de Soja
Temperatura Ambiente
Substâncias Viscoelásticas/síntese química
Substâncias Viscoelásticas/química
Água/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Gels); 0 (Lecithins); 0 (Micelles); 0 (Plant Proteins); 0 (Viscoelastic Substances); 059QF0KO0R (Water); 27432CM55Q (Serum Albumin, Bovine); 516-50-7 (Taurodeoxycholic Acid)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140520
[St] Status:MEDLINE
[do] DOI:10.1021/jp5023086


  10 / 402 MEDLINE  
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[PMID]:24695629
[Au] Autor:Yoon SB; Choi SA; Sim BW; Kim JS; Mun SE; Jeong PS; Yang HJ; Lee Y; Park YH; Song BS; Kim YH; Jeong KJ; Huh JW; Lee SR; Kim SU; Chang KT
[Ad] Endereço:National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do, Republic of Korea Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea.
[Ti] Título:Developmental competence of bovine early embryos depends on the coupled response between oxidative and endoplasmic reticulum stress.
[So] Source:Biol Reprod;90(5):104, 2014 May.
[Is] ISSN:1529-7268
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The stress produced by the coupling of reactive oxygen species (ROS) and endoplasmic reticulum (ER) has been explored extensively, but little is known regarding their roles in the early development of mammalian embryos. Here, we demonstrated that the early development of in vitro-produced (IVP) bovine embryos was governed by the cooperative action between ROS and ER stress. Compared with the tension produced by 5% O2, 20% O2 significantly decreased the blastocyst formation rate and cell survival, which was accompanied by increases in ROS and in levels of sXBP-1 transcript, which is an ER stress indicator. In addition, treatment with glutathione (GSH), a ROS scavenger, decreased ROS levels, which resulted in increased blastocyst formation and cell survival rates. Importantly, levels of sXBP-1 and ER stress-associated transcripts were reduced by GSH treatment in developing bovine embryos. Consistent with this observation, tauroursodeoxycholate (TUDCA), an ER stress inhibitor, improved blastocyst developmental rate, trophectoderm proportion, and cell survival. Moreover, ROS and sXBP-1 transcript levels were markedly decreased by supplementation with TUDCA, suggesting a possible mechanism governing the mutual regulation between ROS and ER stress. Interestingly, knockdown of XBP-1 transcripts resulted in both elevation of ROS and decrease of antioxidant transcripts, which ultimately reduced in vitro developmental competence of bovine embryos. Based on these results, in vitro developmental competence of IVP bovine embryos was highly dependent on the coupled response between oxidative and ER stresses. These results increase our understanding of the mechanism(s) governing early embryonic development and may improve strategies for the generation of IVP embryos with high developmental competence.
[Mh] Termos MeSH primário: Apoptose/fisiologia
Bovinos/embriologia
Embrião de Mamíferos/fisiologia
Desenvolvimento Embrionário/fisiologia
Estresse do Retículo Endoplasmático/fisiologia
[Mh] Termos MeSH secundário: Animais
Western Blotting/veterinária
Feminino
Glutationa/farmacologia
Marcação In Situ das Extremidades Cortadas/veterinária
Microscopia de Fluorescência/veterinária
Gravidez
RNA Interferente Pequeno/farmacologia
Espécies Reativas de Oxigênio/metabolismo
Ácido Taurodesoxicólico/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Small Interfering); 0 (Reactive Oxygen Species); 516-50-7 (Taurodeoxycholic Acid); GAN16C9B8O (Glutathione)
[Em] Mês de entrada:1501
[Cu] Atualização por classe:140526
[Lr] Data última revisão:
140526
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140404
[St] Status:MEDLINE
[do] DOI:10.1095/biolreprod.113.113480



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