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[PMID]:29444114
[Au] Autor:Nielsen TRH; Fonvig CE; Dahl M; Mollerup PM; Lausten-Thomsen U; Pedersen O; Hansen T; Holm JC
[Ad] Endereço:The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark.
[Ti] Título:Childhood obesity treatment; Effects on BMI SDS, body composition, and fasting plasma lipid concentrations.
[So] Source:PLoS One;13(2):e0190576, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The body mass index (BMI) standard deviation score (SDS) may not adequately reflect changes in fat mass during childhood obesity treatment. This study aimed to investigate associations between BMI SDS, body composition, and fasting plasma lipid concentrations at baseline and during childhood obesity treatment. METHODS: 876 children and adolescents (498 girls) with overweight/obesity, median age 11.2 years (range 1.6-21.7), and median BMI SDS 2.8 (range 1.3-5.7) were enrolled in a multidisciplinary outpatient treatment program and followed for a median of 1.8 years (range 0.4-7.4). Height and weight, body composition measured by dual-energy X-ray absorptiometry, and fasting plasma lipid concentrations were assessed at baseline and at follow-up. Lipid concentrations (total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL, and triglycerides (TG)) were available in 469 individuals (264 girls). Linear regressions were performed to investigate the associations between BMI SDS, body composition indices, and lipid concentrations. RESULTS: At baseline, BMI SDS was negatively associated with concentrations of HDL (p = 6.7*10-4) and positively with TG (p = 9.7*10-6). Reductions in BMI SDS were associated with reductions in total body fat percentage (p<2*10-16) and percent truncal body fat (p<2*10-16). Furthermore, reductions in BMI SDS were associated with improvements in concentrations of TC, LDL, HDL, non-HDL, LDL/HDL-ratio, and TG (all p <0.0001). Changes in body fat percentage seemed to mediate the changes in plasma concentrations of TC, LDL, and non-HDL, but could not alone explain the changes in HDL, LDL/HDL-ratio or TG. Among 81 individuals with available lipid concentrations, who increased their BMI SDS, 61% improved their body composition, and 80% improved their lipid concentrations. CONCLUSION: Reductions in the degree of obesity during multidisciplinary childhood obesity treatment are accompanied by improvements in body composition and fasting plasma lipid concentrations. Even in individuals increasing their BMI SDS, body composition and lipid concentrations may improve.
[Mh] Termos MeSH primário: Composição Corporal
Índice de Massa Corporal
Lipídeos/sangue
Obesidade/terapia
[Mh] Termos MeSH secundário: Absorciometria de Fóton
Adolescente
Adulto
Criança
Pré-Escolar
Feminino
Seres Humanos
Lactente
Masculino
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Lipids)
[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:180215
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190576


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[PMID]:29200850
[Au] Autor:Aliu H; Rask C; Brimnes J; Andresen TL
[Ad] Endereço:Immunology Department, In vivo Biology Team, ALK Abelló A/S, Hørsholm.
[Ti] Título:Enhanced efficacy of sublingual immunotherapy by liposome-mediated delivery of allergen.
[So] Source:Int J Nanomedicine;12:8377-8388, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Immunotherapy by sublingual administration of allergens provides high patient compliance and has emerged as an alternative to subcutaneous immunotherapy for the treatment of IgE-associated allergic diseases. However, sublingual immunotherapy (SLIT) can cause adverse events. Development of allergen delivery systems enabling more efficient delivery and hence lower allergen load might reduce the adverse events. In the present study, we have investigated neutral and cationic liposomes as delivery systems of ovalbumin (OVA), as a model allergen, in an OVA-induced allergic airway inflammation model. We investigated the liposome carriers' ability to improve tolerance induction of antigens compared to the corresponding dose of free OVA. Mice were treated sublingually over 2 weeks with free or liposome encapsulated OVA followed by intraperitoneal injections and intranasal challenge. Mice sublingually treated with OVA-liposomes showed a significant reduction of airway eosinophilia and splenocyte proliferation in comparison to free OVA. A similar nonsignificant pattern was seen for OVA-specific IgE antibodies. In addition, reduced levels of interferon-γ and interleukin-5 were observed in spleen cell culture supernatants from OVA-liposome-treated mice compared to the sham-treated group. In conclusion, in vivo efficacy data showed that prophylactic SLIT with OVA-liposomes is significantly more effective in preventing allergic inflammation than the corresponding dose of free OVA.
[Mh] Termos MeSH primário: Alérgenos/administração & dosagem
Sistemas de Liberação de Medicamentos
Imunoterapia Sublingual
[Mh] Termos MeSH secundário: Alérgenos/imunologia
Animais
Citocinas/metabolismo
Ensaio de Imunoadsorção Enzimática
Feminino
Lipídeos/química
Lipossomos
Camundongos Endogâmicos BALB C
Ovalbumina/imunologia
Pneumonia/imunologia
Pneumonia/patologia
Pneumonia/prevenção & controle
Baço/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Allergens); 0 (Cytokines); 0 (Lipids); 0 (Liposomes); 9006-59-1 (Ovalbumin)
[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:171205
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S137033


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[PMID]:29185703
[Au] Autor:Hoffmann M; Auerbach D; Panter F; Hoffmann T; Dorrestein PC; Müller R
[Ad] Endereço:Department of Microbial Natural Products (MINS), Department of Microbial Natural Products (MINS), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI) and Institute for Pharmaceutical Biotechnology, Saarland University , 66123 Saarbrücken, G
[Ti] Título:Homospermidine Lipids: A Compound Class Specifically Formed during Fruiting Body Formation of Myxococcus xanthus DK1622.
[So] Source:ACS Chem Biol;13(1):273-280, 2018 01 19.
[Is] ISSN:1554-8937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The fascinating ability of myxobacteria to form multicellular spore filled fruiting bodies under starvation conditions was widely studied as a model for cooperative microbial behavior. The potential of a life cycle induced change of secondary metabolism, as a means to discover novel natural products, remains largely underexplored. We therefore studied the model organism Myxococcus xanthus DK1622 under submersed and solid cultivation conditions to find putatively life-cycle related compounds by applying statistical analysis on analytical data. Utilizing the advantageous characteristics of LC-MS, LC-MS/MS, and MALDI-MSI allowed the identification of compounds unambiguously associated with myxobacterial fruiting bodies. Our screening effort resulted in the purification and structure elucidation of a novel compound, the homospermidine lipid, from cultures that had undergone the fruiting process. A combination of molecular networking and targeted LC-MS/MS in conjunction with our in-house metabolomics database subsequently revealed alternative producers of the respective compound as well as a number of compounds belonging to the same structural class. Three further members of this compound class were isolated from an alternative producer and structurally elucidated by NMR. Insights into the biosynthesis of this novel compound class was gained by feeding of isotopically labeled substrates and in silico analysis.
[Mh] Termos MeSH primário: Lipídeos/química
Myxococcus xanthus/metabolismo
Espermidina/metabolismo
[Mh] Termos MeSH secundário: Estrutura Molecular
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Lipids); U87FK77H25 (Spermidine)
[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:171130
[St] Status:MEDLINE
[do] DOI:10.1021/acschembio.7b00816


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[PMID]:28465178
[Au] Autor:Das S; Ghosh S; De AK; Bera T
[Ad] Endereço:Laboratory of Nanomedicine, Division of Pharmaceutical Biotechnology, Department of Pharmaceutical Technology, Jadavpur University, 188 Raja S.C. Mallick Road, Kolkata, 700 032, W.B., India.
[Ti] Título:Oral delivery of ursolic acid-loaded nanostructured lipid carrier coated with chitosan oligosaccharides: Development, characterization, in vitro and in vivo assessment for the therapy of leishmaniasis.
[So] Source:Int J Biol Macromol;102:996-1008, 2017 Sep.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Visceral leishmaniasis (VL) is a life-threatening disease caused by Leishmania donovani due to uncontrolled parasitisation of liver, spleen, and bone marrow. Ursolic acid (UA), a promising anti-inflammatory, anti-bacterial and anti-diabetic drug used successfully for treatment of ailments. Development of new delivery system is extremely urgent for UA with better efficacy and fewer side effects. The aim of present research work was to formulate and evaluate the potential anti-leishmanial activity of UA loaded N-octyl-chitosan surface decorated nanostructured lipid carrier system (UA-NLC) for delivery to the macrophages for VL. UA-NLC were prepared and characterized for shape, size, fourier transforms scanning electron microscopy (FESEM), transmittance electron microscopy (TEM), entrapment efficiency and in vitro drug release. The results indicate that the formulated UA-NLC had nano size range (103.7±2.8nm to 143.0±3.8nm) with high drug loading capacity (12.05±0.54%) and entrapment efficiency (88.63±2.7%). Ex vivo drug uptake by macrophage was also evaluated. The UA-NLC was more effective against AG83 wild type (12 fold), SSG-R (4 fold), PMM-R (4 fold) and GE1 field isolated (3 fold) cellular amastigotes than its free form. In vivo study showed orally effective UA-NLC could suppress the parasite burden to 98.75%.
[Mh] Termos MeSH primário: Quitosana/química
Portadores de Fármacos/química
Leishmaniose/tratamento farmacológico
Lipídeos/química
Nanoestruturas/química
Triterpenos/química
Triterpenos/farmacologia
[Mh] Termos MeSH secundário: Administração Oral
Animais
Desenho de Drogas
Liberação Controlada de Fármacos
Feminino
Macrófagos/efeitos dos fármacos
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Oligossacarídeos/química
Triterpenos/administração & dosagem
Triterpenos/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Carriers); 0 (Lipids); 0 (Oligosaccharides); 0 (Triterpenes); 9012-76-4 (Chitosan); P3M2575F3F (ursolic acid)
[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:170504
[St] Status:MEDLINE


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[PMID]:29458544
[Au] Autor:Aguilar-Ayala DA; Cnockaert M; Vandamme P; Palomino JC; Martin A; Gonzalez-Y-Merchand J
[Ad] Endereço:2​Laboratory of Microbiology, Department of Biochemistry and Microbiology, Ghent University, Ghent 9000, Belgium.
[Ti] Título:Antimicrobial activity against Mycobacterium tuberculosis under in vitro lipid-rich dormancy conditions.
[So] Source:J Med Microbiol;67(3):282-285, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Although tuberculosis treatment is dependent on drug-susceptibility testing (DST) and molecular drug-resistance detection, treatment failure and relapse remain a challenge. This could be partially due to the emergence of antibiotic-tolerant dormant mycobacteria, where host lipids have been shown to play an important role. This study evaluated the susceptibility of Mycobacterium tuberculosis to two antibiotic combinations - rifampicin, moxifloxacin, amikacin and metronidazole (RIF-MXF-AMK-MTZ), and rifampicin, moxifloxacin, amikacin and pretomanid (RIF-MXF-AMK-PA) - in a lipid-rich dormancy model. Although their effectiveness in in vitro cultures with dextrose as a carbon source has been proved, we observed that none of the antibiotic mixtures were bactericidal in the presence of lipids. The presence of lipids may confer tolerance to M. tuberculosis against the mixture of antibiotics tested and such tolerance could be even higher during the dormant stages. The implementation of lipids in DST on clinical isolates could potentially lead to a better treatment strategy.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Lipídeos/farmacologia
Mycobacterium tuberculosis/efeitos dos fármacos
Mycobacterium tuberculosis/fisiologia
[Mh] Termos MeSH secundário: Amicacina/farmacologia
Antituberculosos/farmacologia
Tolerância a Medicamentos
Fluoroquinolonas/farmacologia
Aptidão Genética
Genótipo
Seres Humanos
Metabolismo dos Lipídeos
Testes de Sensibilidade Microbiana
Modelos Biológicos
Infecções por Micobactéria não Tuberculosa/microbiologia
Mycobacterium tuberculosis/genética
Mycobacterium tuberculosis/crescimento & desenvolvimento
Nitroimidazóis/farmacologia
Rifampina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo(2,1-b)(1,3)oxazine); 0 (Anti-Bacterial Agents); 0 (Antitubercular Agents); 0 (Fluoroquinolones); 0 (Lipids); 0 (Nitroimidazoles); 84319SGC3C (Amikacin); U188XYD42P (moxifloxacin); VJT6J7R4TR (Rifampin)
[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:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000681


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[PMID]:28457894
[Au] Autor:Zupancic O; Bernkop-Schnürch A
[Ad] Endereço:Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 80/82, Center for Chemistry and Biomedicine, 6020 Innsbruck, Austria.
[Ti] Título:Lipophilic peptide character - What oral barriers fear the most.
[So] Source:J Control Release;255:242-257, 2017 Jun 10.
[Is] ISSN:1873-4995
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Peptide therapeutics is currently one of the fastest growing markets worldwide and consequently convenient ways of administration for these drugs are highly on demand. In particular, oral dosage forms would be preferred. A relative large molecular weight and high hydrophilicity, however, result in comparatively very low oral bioavailability being in most cases below 1%. Lipid based formulations (LBF), in particular self-emulsifying drug delivery systems (SEDDS) and solid lipid nanoparticles (SLN) as well as liposomes are among the most promising tools for oral peptide delivery. Key to success in orally delivering peptides via LBF seems to be a sufficiently high lipophilic character of those therapeutic agents. Hence, different non-covalent and covalent peptide lipidization methods from drug delivery point of view are presented. On the one hand, among non-covalent lipidization methods hydrophobic ion pairing seems to be a promising way to sufficiently increase peptide lipophilicity providing high drug payloads in the lipid phase, a protective effect against presystemic metabolism via thiol-disulphide exchange reactions and proteolysis as well as an improved intestinal membrane permeability. On the other hand, covalent methods like conjugating fatty acids via amidation, esterification, reversible aqueous lipidization (REAL) and cyclization also show potential. The present review therefore describes those lipidization methods in detail and critically evaluates their contribution in successfully overcoming the oral barriers.
[Mh] Termos MeSH primário: Lipídeos/química
Peptídeos/química
[Mh] Termos MeSH secundário: Administração Oral
Animais
Sistemas de Liberação de Medicamentos
Seres Humanos
Absorção Intestinal
Peptídeos/administração & dosagem
Peptídeos/farmacocinética
Peptídeos/uso terapêutico
Proteólise
Vacinas
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Lipids); 0 (Peptides); 0 (Vaccines)
[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:170502
[St] Status:MEDLINE


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[PMID]:27778642
[Au] Autor:Garibay-Nieto N; Queipo-García G; Alvarez F; Bustos M; Villanueva E; Ramírez F; León M; Laresgoiti-Servitje E; Duggirala R; Macías T; Cuevas S; Jalife A; Fonseca-Sánchez M; Serratos F; López-Alvarenga JC
[Ad] Endereço:Children and Adolescent Obesity Clinic.
[Ti] Título:Effects of Conjugated Linoleic Acid and Metformin on Insulin Sensitivity in Obese Children: Randomized Clinical Trial.
[So] Source:J Clin Endocrinol Metab;102(1):132-140, 2017 Jan 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: Insulin resistance precedes metabolic syndrome abnormalities and may promote cardiovascular disease and type 2 diabetes in children with obesity. Results of lifestyle modification programs have been discouraging, and the use of adjuvant strategies has been necessary. Objective: This study aimed to evaluate the effects of metformin and conjugated linoleic acid (CLA) on insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp technique and insulin pathway expression molecules in muscle biopsies of children with obesity. Design: A randomized, double-blinded, placebo-controlled clinical trial was conducted. Setting: Children with obesity were randomly assigned to receive metformin, CLA, or placebo. Results: Intervention had a positive effect in all groups. For insulin sensitivity Rd value (mg/kg/min), there was a statistically significant difference between the CLA vs placebo (6.53 ± 2.54 vs 5.05 ± 1.46, P = 0.035). Insulinemia and homeostatic model assessment of insulin resistance significantly improved in the CLA group (P = 0.045). After analysis of covariance was performed and the influence of body mass index, age, Tanner stage, prescribed diet, and fitness achievement was controlled, a clinically relevant effect size on insulin sensitivity remained evident in the CLA group (37%) and exceeded lifestyle program benefits. Moreover, upregulated expression of the insulin receptor substrate 2 was evident in muscle biopsies of the CLA group. Conclusions: Improvement of insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp and IRS2 upregulation, favored patients treated with CLA.
[Mh] Termos MeSH primário: Doenças Cardiovasculares/prevenção & controle
Hipoglicemiantes/uso terapêutico
Resistência à Insulina
Ácidos Linoleicos Conjugados/uso terapêutico
Síndrome Metabólica/prevenção & controle
Metformina/uso terapêutico
Obesidade/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Biomarcadores/análise
Glicemia/análise
Composição Corporal
Criança
Método Duplo-Cego
Quimioterapia Combinada
Feminino
Seguimentos
Seres Humanos
Insulina/sangue
Lipídeos/análise
Masculino
Obesidade/complicações
Prognóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Biomarkers); 0 (Blood Glucose); 0 (Hypoglycemic Agents); 0 (Insulin); 0 (Linoleic Acids, Conjugated); 0 (Lipids); 9100L32L2N (Metformin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2016-2701


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[PMID]:29397594
[Au] Autor:Wang W; Shi LP; Shi L; Xu L
[Ad] Endereço:Department of Gastroenterology, National Center of Gerontology, Beijing Hospital, Beijing 100730, China.
[Ti] Título:[Efficacy of probiotics on the treatment of non-alcoholic fatty liver disease].
[So] Source:Zhonghua Nei Ke Za Zhi;57(2):101-106, 2018 Feb 01.
[Is] ISSN:0578-1426
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To study the clinical effect of probiotics in the treatment of non-alcoholic fatty liver disease (NAFLD). A total of 200 patients with NAFLD were randomly divided into 4 groups: control group (routine treatment group) and combined treatment group A, B and C. Each group had equal patients. The control group received orally polyene phosphatidylcholine capsules; whereas combined group A, B and C were given orally the live "combined and powder" , "two live combined and " , and the both probiotics respectively. The duration of treatment was 1 month. Laboratory parameters were evaluated before treatment and thirtieth day after treatment, including cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase (AST), fasting blood glucose (FPG), serum high molecular weight adiponectin (HMW-APN) and serum TNFα. Meanwhile the faece sample was collected for routine test and bacterial culture. Liver ultrasound scan was done in all patients. In terms of blood lipids and blood glucose, each group improved after treatment with significant differences ( 0.05) except for HDL-C. As for liver function, serum ALT and AST decreased after treatment in each group; especially in combined group C which were lower than those of control group [(33.7±7.6) U/L vs. (45.0±8.5) U/L; (22.0±1.6) U/L vs. (29.4±3.7) U/L; 0.05]. TNFα levels decreased after treatment in each group, in addition the values in combined group C was significantly lower than that of control group[(0.51±0.27) µg/L vs. (0.82±0.28) µg/L, 0.05]. Serum HMW-APN increased after treatment in each group, and the HMW-APN in combined C group was significantly higher than that of control group[(9.28±3.72) µg/L vs. (7.87±3.96)µg/L, 0.05]. (5) After treatment, all groups showed improvement of fatty liver by ultrasound, but the difference between groups was not statistically significant. (6) Compared with before treatment, fecal flora in combined groups was all reduced ( 0.01), but it was comparable before and after treatment in control group. Probiotics improve intestinal microecological system in NAFLD patients via inhibiting TNFα and enhancing adiponectin, possibly resulting in regulating blood glucose, lipid metabolism, and protecting liver injury from NAFLD.
[Mh] Termos MeSH primário: Hepatopatia Gordurosa não Alcoólica/metabolismo
Hepatopatia Gordurosa não Alcoólica/terapia
Probióticos
[Mh] Termos MeSH secundário: Adiponectina
Alanina Transaminase/sangue
Alanina Transaminase/efeitos dos fármacos
Aspartato Aminotransferases/sangue
Aspartato Aminotransferases/efeitos dos fármacos
Glicemia
Colesterol/sangue
LDL-Colesterol/efeitos dos fármacos
LDL-Colesterol/metabolismo
Seres Humanos
Metabolismo dos Lipídeos
Lipídeos
Probióticos/uso terapêutico
Triglicerídeos/sangue
Triglicerídeos/metabolismo
Fator de Necrose Tumoral alfa
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (ADIPOQ protein, human); 0 (Adiponectin); 0 (Blood Glucose); 0 (Cholesterol, LDL); 0 (Lipids); 0 (TNF protein, human); 0 (Triglycerides); 0 (Tumor Necrosis Factor-alpha); 97C5T2UQ7J (Cholesterol); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.6.1.2 (Alanine Transaminase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180206
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0578-1426.2018.02.004


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[PMID]:29348617
[Au] Autor:Miranda AM; Lasiecka ZM; Xu Y; Neufeld J; Shahriar S; Simoes S; Chan RB; Oliveira TG; Small SA; Di Paolo G
[Ad] Endereço:Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 10032, USA.
[Ti] Título:Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures.
[So] Source:Nat Commun;9(1):291, 2018 01 18.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Defects in endolysosomal and autophagic functions are increasingly viewed as key pathological features of neurodegenerative disorders. A master regulator of these functions is phosphatidylinositol-3-phosphate (PI3P), a phospholipid synthesized primarily by class III PI 3-kinase Vps34. Here we report that disruption of neuronal Vps34 function in vitro and in vivo impairs autophagy, lysosomal degradation as well as lipid metabolism, causing endolysosomal membrane damage. PI3P deficiency also promotes secretion of unique exosomes enriched for undigested lysosomal substrates, including amyloid precursor protein C-terminal fragments (APP-CTFs), specific sphingolipids, and the phospholipid bis(monoacylglycero)phosphate (BMP), which normally resides in the internal vesicles of endolysosomes. Secretion of these exosomes requires neutral sphingomyelinase 2 and sphingolipid synthesis. Our results reveal a homeostatic response counteracting lysosomal dysfunction via secretion of atypical exosomes eliminating lysosomal waste and define exosomal APP-CTFs and BMP as candidate biomarkers for endolysosomal dysfunction associated with neurodegenerative disorders.
[Mh] Termos MeSH primário: Precursor de Proteína beta-Amiloide/metabolismo
Exossomos/metabolismo
Lipídeos/análise
Lisossomos/metabolismo
Neurônios/metabolismo
[Mh] Termos MeSH secundário: Precursor de Proteína beta-Amiloide/química
Animais
Autofagia/genética
Biomarcadores/metabolismo
Linhagem Celular Tumoral
Classe III de Fosfatidilinositol 3-Quinases/genética
Classe III de Fosfatidilinositol 3-Quinases/metabolismo
Células HEK293
Seres Humanos
Lisofosfolipídeos/metabolismo
Camundongos Endogâmicos C57BL
Camundongos Knockout
Monoglicerídeos/metabolismo
Doenças Neurodegenerativas/diagnóstico
Doenças Neurodegenerativas/metabolismo
Fragmentos de Peptídeos/metabolismo
Fosfatos de Fosfatidilinositol/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amyloid beta-Protein Precursor); 0 (Biomarkers); 0 (Lipids); 0 (Lysophospholipids); 0 (Monoglycerides); 0 (Peptide Fragments); 0 (Phosphatidylinositol Phosphates); 0 (bis(monoacylglyceryl)phosphate); 0 (phosphatidylinositol 3-phosphate); EC 2.7.1.137 (Class III Phosphatidylinositol 3-Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02533-w


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[PMID]:29200853
[Au] Autor:Briot T; Roger E; Lautram N; Verger A; Clavreul A; Lagarce F
[Ad] Endereço:Micro & Nanomédecines Translationelles - MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, MINT IBS-CHU.
[Ti] Título:Development and in vitro evaluations of new decitabine nanocarriers for the treatment of acute myeloid leukemia.
[So] Source:Int J Nanomedicine;12:8427-8442, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Decitabine is a hydrophilic drug that acts by hypomethylating DNA. Decitabine is used in Europe for the treatment of acute myeloid leukemia (AML) in patients aged ≥65 years. However, it can only be administered intravenously due to very low oral bioavailability and a large distribution volume. Oral administration would allow outpatient treatment, improving quality of life and reducing treatment costs. The present study proposes to develop lipid nanocapsules (LNCs), originally designed for lipophilic drugs, to encapsulate decitabine. Two different formulations of LNCs were designed: LNCs based on a high proportion of Transcutol HP (THP-LNCs) and LNCs associated with a mixture of Transcutol HP and Tween 80 (THP-T80-LNCs). The second formulation had a diameter of 26.5±0.5 nm, high encapsulation efficiency (>85%), and a drug payload of 472±64 µg/mL. Decitabine-loaded THP-T80-LNC cytotoxicity was evaluated on two AML cell lines depending on their decitabine resistance: HEL (not resistant) and HL-60 (resistant). The permeability of decitabine-loaded THP-T80-LNCs was also evaluated on Caco-2 cell monolayers. Decitabine cytotoxicity against HEL and HL-60 was higher when decitabine was loaded in THP-T80-LNCs than when free. Apparent permeability on Caco-2 cell monolayers was also increased, suggesting a potentially useful formulation to increase the oral bioavailability of decitabine.
[Mh] Termos MeSH primário: Azacitidina/análogos & derivados
Portadores de Fármacos/química
Leucemia Mieloide Aguda/tratamento farmacológico
Nanocápsulas/administração & dosagem
[Mh] Termos MeSH secundário: Administração Oral
Antimetabólitos Antineoplásicos/administração & dosagem
Antimetabólitos Antineoplásicos/farmacocinética
Azacitidina/administração & dosagem
Azacitidina/farmacocinética
Disponibilidade Biológica
Células CACO-2
Linhagem Celular Tumoral
Portadores de Fármacos/administração & dosagem
Liberação Controlada de Fármacos
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Estabilidade de Medicamentos
Etilenoglicóis/química
Seres Humanos
Lipídeos/química
Nanocápsulas/química
Polissorbatos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimetabolites, Antineoplastic); 0 (Drug Carriers); 0 (Ethylene Glycols); 0 (Lipids); 0 (Nanocapsules); 0 (Polysorbates); 776B62CQ27 (decitabine); A1A1I8X02B (carbitol); M801H13NRU (Azacitidine)
[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:171205
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S147659



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