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1.
Phys Chem Chem Phys ; 26(3): 2657-2665, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38174429

RESUMO

The supramolecular and mesoscopic architectures of lead-saponified linseed oil, used by painters since the Renaissance, have been characterised and linked to their rheological properties. The multi-scale organization of saponified oils has been demonstrated by SAXS (Small Angle X-ray Scattering), FF-TEM (Freeze-Fracture Transmission Electron Microscopy) and DIC (Differential Interference Contrast): some of the lead soaps (formed when the oil is heated in the presence of PbO) are organized into microscopic lamellar domains, distributed in a continuous matrix made up of unorganized species (partially saponified triglycerides, glycerol, remaining soaps, etc.). The concentration of lead soaps in the oil controls the average size and interaction between the lamellar domains. Linseed oil + PbO 17 mol% is viscous and consists of aggregates of lamellar domains isolated within the continuous unorganized matrix. In contrast, in linseed oil + PbO 50 mol%, the domains are homogeneously dispersed and form what can be described as a three-dimensional network, giving the system viscoelastic properties.

2.
Nucleic Acids Res ; 51(14): 7496-7519, 2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37283053

RESUMO

Modified nucleotides in non-coding RNAs, such as tRNAs and snRNAs, represent an important layer of gene expression regulation through their ability to fine-tune mRNA maturation and translation. Dysregulation of such modifications and the enzymes installing them have been linked to various human pathologies including neurodevelopmental disorders and cancers. Several methyltransferases (MTases) are regulated allosterically by human TRMT112 (Trm112 in Saccharomyces cerevisiae), but the interactome of this regulator and targets of its interacting MTases remain incompletely characterized. Here, we have investigated the interaction network of human TRMT112 in intact cells and identify three poorly characterized putative MTases (TRMT11, THUMPD3 and THUMPD2) as direct partners. We demonstrate that these three proteins are active N2-methylguanosine (m2G) MTases and that TRMT11 and THUMPD3 methylate positions 10 and 6 of tRNAs, respectively. For THUMPD2, we discovered that it directly associates with the U6 snRNA, a core component of the catalytic spliceosome, and is required for the formation of m2G, the last 'orphan' modification in U6 snRNA. Furthermore, our data reveal the combined importance of TRMT11 and THUMPD3 for optimal protein synthesis and cell proliferation as well as a role for THUMPD2 in fine-tuning pre-mRNA splicing.


Assuntos
Precursores de RNA , Proteínas de Saccharomyces cerevisiae , Humanos , Precursores de RNA/genética , Precursores de RNA/metabolismo , Splicing de RNA , Spliceossomos/metabolismo , RNA Nuclear Pequeno/genética , RNA Nuclear Pequeno/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proliferação de Células/genética , Biossíntese de Proteínas , Metiltransferases/genética , tRNA Metiltransferases/genética , Proteínas de Saccharomyces cerevisiae/genética
3.
J Ophthalmol ; 2022: 6605771, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211596

RESUMO

Purpose: To evaluate risk factors associated with keratoconus in a monocentric cross-sectional case-control study. Methods: This observational study occurred from June 2019 to February 2021 in a university hospital (France). The case group consisted of 195 patients with keratoconus in at least one eye who were followed up by a corneal specialist. The control group consisted of 195 patients without any evidence of keratoconus on slit-lamp examination and corneal topography, who were matched 1 : 1 to controls by age and sex. Data were collected by a self-completed paper questionnaire before the consultation, and a multivariate logistic regression was performed. Results: Multivariate analysis revealed significant associations of keratoconus with family history (odds ratio [OR] = 22.2, p < 0.001), rubbing eyes (OR = 10.9, p < 0.001), allergy (any kind) (OR = 3.80, p < 0.001), smoking exposure (OR = 2.08, p=0.017), and dry eyes (OR = 1.77, p=0.045f). The worst eye was associated with the more rubbed eye (p < 0.001) and the more pressed eye during the night according to sleeping position (p < 0.041). Conclusion: This study confirmed the association between keratoconus and eye rubbing, family history, and allergy. It highlighted the role of pressure on the eyes during sleep. Other less known risk factors such as dry eyes and smoking exposure should be explored in future studies.

4.
Sci Rep ; 11(1): 14205, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244531

RESUMO

Mistletoe (Viscum album L.) is used in German-speaking European countries in the field of integrative oncology linking conventional and complementary medicine therapies to improve quality of life. Various companies sell extracts, fermented or not, for injection by subcutaneous or intra-tumoral route with a regulatory status of anthroposophic medicinal products (European Medicinal Agency (EMA) assessment status). These companies as well as anthroposophical physicians argue that complex matrices composed of many molecules in mixture are necessary for activity and that the host tree of the mistletoe parasitic plant is the main determining factor for this matrix composition. The critical point is that parenteral devices of European mistletoe extracts do not have a standard chemical composition regulated by EMA quality guidelines, because they are not drugs, regulatory speaking. However, the mechanism of mistletoe's anticancer activity and its effectiveness in treating and supporting cancer patients are not fully understood. Because of this lack of transparency and knowledge regarding the matrix chemical composition, we undertook an untargeted metabolomics study of several mistletoe extracts to explore and compare their fingerprints by LC-(HR)MS(/MS) and 1H-NMR. Unexpectedly, we showed that the composition was primarily driven by the manufacturer/preparation method rather than the different host trees. This differential composition may cause differences in immunostimulating and anti-cancer activities of the different commercially available mistletoe extracts as illustrated by structure-activity relationships based on LC-MS/MS and 1H-NMR identifications completed by docking experiments. In conclusion, in order to move towards an evidence-based medicine use of mistletoe, it is a priority to bring rigor and quality, chemically speaking.

5.
Nat Genet ; 53(2): 215-229, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33526924

RESUMO

Naive epiblast and embryonic stem cells (ESCs) give rise to all cells of adults. Such developmental plasticity is associated with genome hypomethylation. Here, we show that LIF-Stat3 signaling induces genomic hypomethylation via metabolic reconfiguration. Stat3-/- ESCs show decreased α-ketoglutarate production from glutamine, leading to increased Dnmt3a and Dnmt3b expression and DNA methylation. Notably, genome methylation is dynamically controlled through modulation of α-ketoglutarate availability or Stat3 activation in mitochondria. Alpha-ketoglutarate links metabolism to the epigenome by reducing the expression of Otx2 and its targets Dnmt3a and Dnmt3b. Genetic inactivation of Otx2 or Dnmt3a and Dnmt3b results in genomic hypomethylation even in the absence of active LIF-Stat3. Stat3-/- ESCs show increased methylation at imprinting control regions and altered expression of cognate transcripts. Single-cell analyses of Stat3-/- embryos confirmed the dysregulated expression of Otx2, Dnmt3a and Dnmt3b as well as imprinted genes. Several cancers display Stat3 overactivation and abnormal DNA methylation; therefore, the molecular module that we describe might be exploited under pathological conditions.


Assuntos
Blastocisto/fisiologia , Metilação de DNA/fisiologia , Células-Tronco Embrionárias/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA Metiltransferase 3A , Células-Tronco Embrionárias/fisiologia , Regulação da Expressão Gênica , Histonas/metabolismo , Ácidos Cetoglutáricos/metabolismo , Fator Inibidor de Leucemia/metabolismo , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fatores de Transcrição Otx/genética , Fatores de Transcrição Otx/metabolismo , Células-Tronco Pluripotentes/metabolismo , Regiões Promotoras Genéticas , Fator de Transcrição STAT3/genética , DNA Metiltransferase 3B
6.
J Nat Prod ; 83(10): 3069-3079, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33016067

RESUMO

A unique collection of 292 extracts from 107 New Caledonian Euphorbiaceae species sensu lato was profiled by LC-MS2 and the metabolite content organized by molecular networking. Based on the assumption that taxon-specific molecules are more likely to be structurally novel, taxonomic data were mapped on spectral networks to detect genus-specific clusters. Using this approach, a group of compounds unique to the genus Austrobuxus was highlighted. The subsequent MS-guided purification of the fruit EtOAc extract of Austrobuxus carunculatus led to the isolation of 13 new monolactone and "norditerpene" picrotoxanes (2-14), along with the known tutin (1). The structures of the new compounds were elucidated by HRESIMS and NMR spectroscopic data analysis, and the absolute configurations of compounds 1, 3, 7, 11, 12, and 14 were determined by single-crystal X-ray diffraction analysis. The relative and absolute configurations of compounds 4 and 5 were ascertained by chemical transformation of compound 3. The absolute configurations of other members of the series have been proposed on the basis of biogenetic considerations and specific rotation values of similar sign and magnitude. Compounds 1-14 were evaluated for their antiproliferative activities against HCT116 colon, U87-MG glioblastoma, and A549 lung human cancer cell lines. Compounds bearing an acyl chain at C-2 (i.e., 2, 4, and 13) showed IC50 values in the micromolar range for the three cell lines used.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Euphorbiaceae/química , Euphorbiaceae/classificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Classificação , Diterpenos , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Redes e Vias Metabólicas , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade , Difração de Raios X
7.
Cornea ; 39(12): 1473-1479, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32969859

RESUMO

PURPOSE: To assess the keratoconus (KC) prevalence among first-degree relatives of affected subjects. METHODS: We performed large epidemiological, prospective, and observational cohort, which took place in the French KC National Reference Centre, in Bordeaux. We studied data from 94 unrelated patients with KC and at least 2 first-degree relatives assessable. Each subject had a thorough ocular examination including visual acuity, refraction, slitlamp biomicroscopy, indirect ophthalmoscopy, keratometry, corneal topography and tomographer (Topographic Modeling System; Tomey Corporation, Japan; and Galilei G4, Ziemer, Switzerland, respectively), pachymetry, and biomechanical properties of cornea (Ocular Response Analyzer; Reichert, Depew, NY). Additional data were collected about atopy, smoking, and eye-rubbing habits. KC prevalence, multivariate analysis, and familial correlation analysis have been studied. RESULTS: Of the 221 relatives, 9.05% (n = 20) had clinically manifest KC, and 15.4% (n = 31) had subclinical KC. The prevalence of KC was estimated equal to 0.14 [95% confidence interval (CI), 0.07-0.22] among parents, 0.03 (95% CI, 0-0.10) among offspring, and 0.10 (95% CI, 0.04-0.20) among siblings. In multivariable analysis, age and eye-rubbing were associated with an increased risk of KC. The familial correlation of KC among probands' first-degree relatives was estimated at 0.55 among parents, 0.29 among offspring, and 0.49 among siblings. CONCLUSIONS: Being a first-degree relative of a subject with KC remains a risk factor for developing KC. This should be taken into account especially when screening for KC in pediatric patients, for refractive surgery candidates, and for patients being evaluated for cataract surgery.


Assuntos
Saúde da Família/estatística & dados numéricos , Ceratocone/epidemiologia , Adolescente , Adulto , Criança , Paquimetria Corneana , Topografia da Córnea , Feminino , França/epidemiologia , Humanos , Ceratocone/diagnóstico , Ceratocone/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oftalmoscopia , Prevalência , Estudos Prospectivos , Fatores de Risco , Microscopia com Lâmpada de Fenda , Acuidade Visual/fisiologia , Adulto Jovem
8.
Nat Commun ; 11(1): 1344, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32165618

RESUMO

The intestinal microbiota modulates host physiology and gene expression via mechanisms that are not fully understood. Here we examine whether host epitranscriptomic marks are affected by the gut microbiota. We use methylated RNA-immunoprecipitation and sequencing (MeRIP-seq) to identify N6-methyladenosine (m6A) modifications in mRNA of mice carrying conventional, modified, or no microbiota. We find that variations in the gut microbiota correlate with m6A modifications in the cecum, and to a lesser extent in the liver, affecting pathways related to metabolism, inflammation and antimicrobial responses. We analyze expression levels of several known writer and eraser enzymes, and find that the methyltransferase Mettl16 is downregulated in absence of a microbiota, and one of its target mRNAs, encoding S-adenosylmethionine synthase Mat2a, is less methylated. We furthermore show that Akkermansia muciniphila and Lactobacillus plantarum affect specific m6A modifications in mono-associated mice. Our results highlight epitranscriptomic modifications as an additional level of interaction between commensal bacteria and their host.


Assuntos
Adenosina/análogos & derivados , Ceco/metabolismo , Microbioma Gastrointestinal , Fígado/metabolismo , Adenosina/metabolismo , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Ceco/microbiologia , Feminino , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcriptoma
9.
J Phys Chem Lett ; 10(15): 4192-4196, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31305079

RESUMO

We report the successful one-pot synthesis of adenosine mono-, di-, and triphosphate in the confined space of a mordenite zeolite. This is also the first report of ATP synthesized onto a porous mineral surface. The results revealed a plausible prebiotic route to ribonucleotides and highlighted the contribution of microporous minerals in the origins of life.


Assuntos
Difosfato de Adenosina/síntese química , Monofosfato de Adenosina/síntese química , Trifosfato de Adenosina/síntese química , Silicatos de Alumínio/química , Nanopartículas/química , Técnicas de Síntese em Fase Sólida/métodos , Zeolitas/química , Adenina/química , Organofosfatos/química , Origem da Vida , Porosidade , Ribose/química , Propriedades de Superfície , Termodinâmica , Fatores de Tempo
10.
J Refract Surg ; 34(10): 664-670, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30296327

RESUMO

PURPOSE: To compare posterior corneal features and their discriminating power for differentiating normal corneas from subclinical keratoconus using the Placido dual-Scheimpflug analyzer. METHODS: Patients were retrospectively included in the study. The preoperative normal right eyes of 79 patients imaged with a Placido dual-Scheimpflug system and with a stable postoperative LASIK follow-up of a minimum of 36 months were included in the normal group and were compared to 39 contralateral topographically normal eyes with clinically evident keratoconus in the fellow eye. The posterior surface variables measured were categorized according to the feature of the corneal shape they were characterizing (curvature, elevation, asymmetry, and eccentricity) and compared between the two groups using the Student's two-sample t test. The discriminating ability of the posterior surface variables was compared by receiver operator characteristics curves. RESULTS: Variables that related to asymmetry and elevation of the posterior surface were statistically significantly different between groups (P < .05), whereas eccentricity and curvature-related parameters were not. Receiver operator characteristics curves analysis showed that the maximum posterior elevation over the best-fit toric and aspheric surface reference shape had the highest discriminating ability for distinguishing normal corneas from subclinical keratoconus, with an area under the curve of 0.877, followed by the asphericity asymmetry index, with an area under the curve of 0.871, and posterior inferior-superior value, with an area under the curve of 0.851. CONCLUSIONS: Posterior cornea measured with a dual-Scheimpflug analyzer provides useful parameters for differentiating normal corneas from subclinical keratoconus. Of the posterior surface parameters, asymmetry and elevation seem to be the most sensitive shape modifications for differentiating both populations. [J Refract Surg. 2018;34(10):664-670.].


Assuntos
Córnea/anatomia & histologia , Córnea/patologia , Técnicas de Diagnóstico Oftalmológico , Ceratocone/diagnóstico , Adulto , Paquimetria Corneana , Topografia da Córnea , Dilatação Patológica/diagnóstico , Dilatação Patológica/cirurgia , Feminino , Humanos , Ceratocone/cirurgia , Ceratomileuse Assistida por Excimer Laser In Situ , Lasers de Excimer/uso terapêutico , Masculino , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
11.
J Cataract Refract Surg ; 44(1): 103-105, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29502596

RESUMO

A 39-year-old woman presented with an early posterior vitreous detachment (PVD) after the implantation of an Implantable Collamer Lens phakic intraocular lens (pIOL). The patient detected PVD, noticing metamorphopsia early after surgery; it was confirmed with optical coherence tomography 5 days postoperatively. She was examined by a retinal expert, and no retinal tears were found. However, 15 days postoperatively, the patient had a retinal tear; 38 days later, a retinal detachment (RD) occurred despite treatment with argon laser photocoagulation. Prompt treatment and adequate patient cooperation achieved a final good uncorrected distance visual acuity (20/20). To our knowledge, this is the first description of the whole sequence involving early PVD leading to RD after pIOL implantation. This case highlights the importance of a fundus examination before and after surgery and of informing patients about the small chance of RD and visual symptoms.


Assuntos
Implante de Lente Intraocular/efeitos adversos , Lentes Intraoculares Fácicas/efeitos adversos , Descolamento Retiniano/etiologia , Descolamento do Vítreo/etiologia , Doença Aguda , Adulto , Crioterapia , Tamponamento Interno , Feminino , Humanos , Descolamento Retiniano/diagnóstico por imagem , Descolamento Retiniano/cirurgia , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia , Descolamento do Vítreo/diagnóstico por imagem , Descolamento do Vítreo/cirurgia
12.
Phytochem Anal ; 28(6): 512-520, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28626912

RESUMO

INTRODUCTION: Acetogenins are plant polyketides known to be cytotoxic and proposed as antitumor candidates. They are also suspected to be alimentary neurotoxins. Their occurrence as complex mixtures renders their dereplication and structural identification difficult using liquid chromatography coupled to tandem mass spectrometry and efforts are required to improve the methodology. OBJECTIVE: To develop a supercritical fluid chromatography (SFC) high-resolution tandem mass spectrometry method, involving lithium post-column cationisation, for the structural characterisation of Annonaceous acetogenins in crude extracts. METHODOLOGY: The seeds of Annona muricata L. were extracted with methanol. Supercritical fluid chromatography of the extract, using a 2-ethylpyridine stationary phase column, was monitored using a high-resolution quadrupole time-of-flight mass spectrometer. Lithium iodide was added post-column in the make-up solvent. For comparison, the same extract was analysed using high-pressure liquid chromatography coupled to the same mass spectrometer, with a column based on solid core particles. RESULTS: Sensitivity was similar for both HPLC and SFC approaches. Retention behaviour and fragmentation pathways of three different isomer groups are described. A previously unknown group of acetogenins was also evidenced for the first time. CONCLUSION: The use of SFC-MS/MS allows the reduction of the time of analysis, of environmental impact and an increase in the chromatographic resolution, compared to liquid chromatography. This new methodology enlightened a new group of acetogenins, isomers of montanacin-D. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Acetogeninas/química , Annona/química , Cromatografia com Fluido Supercrítico/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Limite de Detecção , Sensibilidade e Especificidade , Fatores de Tempo
13.
Sci Rep ; 7: 46658, 2017 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-28436449

RESUMO

Nonalcoholic steatohepatitis (NASH) is a condition which can progress to cirrhosis and hepatocellular carcinoma. Markers for NASH diagnosis are still lacking. We performed a comprehensive lipidomic analysis on human liver biopsies including normal liver, nonalcoholic fatty liver and NASH. Random forests-based machine learning approach allowed characterizing a signature of 32 lipids discriminating NASH with 100% sensitivity and specificity. Furthermore, we validated this signature in an independent group of NASH patients. Then, metabolism dysregulations were investigated in both patients and murine models. Alterations of elongase and desaturase activities were observed along the fatty acid synthesis pathway. The decreased activity of the desaturase FADS1 appeared as a bottleneck, leading upstream to an accumulation of fatty acids and downstream to a deficiency of long-chain fatty acids resulting to impaired phospholipid synthesis. In NASH, mass spectrometry imaging on tissue section revealed the spreading into the hepatic parenchyma of selectively accumulated fatty acids. Such lipids constituted a highly toxic mixture to human hepatocytes. In conclusion, this study characterized a specific and sensitive lipid signature of NASH and positioned FADS1 as a significant player in accumulating toxic lipids during NASH progression.


Assuntos
Carcinoma Hepatocelular/metabolismo , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Acetiltransferases/metabolismo , Adulto , Animais , Carcinoma Hepatocelular/patologia , Células Cultivadas , Dessaturase de Ácido Graxo Delta-5 , Progressão da Doença , Ácidos Graxos Dessaturases/metabolismo , Elongases de Ácidos Graxos , Ácidos Graxos/metabolismo , Feminino , Células Hep G2 , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Metabolismo dos Lipídeos , Lipídeos/análise , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Masculino , Metabolômica/métodos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia
14.
J Cataract Refract Surg ; 43(12): 1582-1590, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29335104

RESUMO

PURPOSE: To assess the quality of life in French keratoconus patients. SETTING: Fifty-seven Keratoconus National Reference Centers across France. DESIGN: Prospective case series. METHODS: Patients completed the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) and a French validated questionnaire on disability and dependency from February to June 2012 when they came for an ophthalmic examination at 57 participating centers across France. An ocular examination including refraction, corneal topography, pachymetry, and slitlamp biomicroscopy was performed. The composite or global NEI VFQ-25 score and the proportion of patients who were dependent (defined by the difficulties with activities of daily living) because of keratoconus were the main evaluation criteria in this study. RESULTS: The study comprised 550 keratoconus patients. Women, corrected distance visual acuity worse than 20/40, steep keratometry higher than 52.0 diopters, history of surgery (corneal transplant, intrastromal corneal ring segments, or corneal crosslinking), and more severe keratoconus according to the Amsler-Krumeich classification were associated with an increasingly negative impact on quality of life (overall scores are significantly lower). Moreover, 4.9% of participants reported having changed their jobs because of keratoconus and 7.8% received keratoconus-related disability. Sixty-nine (12.5%) patients reported having difficulties with activities of daily living and are considered dependent. CONCLUSION: Keratoconus was associated with a significant reduction in quality of life but it did not result in social exclusion.


Assuntos
Ceratocone , Qualidade de Vida , Atividades Cotidianas , França , Humanos , Ceratocone/cirurgia , Estudos Prospectivos , Próteses e Implantes , Visão Ocular , Acuidade Visual
15.
J Enzyme Inhib Med Chem ; 31(6): 1277-85, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26681513

RESUMO

The synthesis of 14-(aryl)-14H-naphto[2,1-b]pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-yl) acetamidoximes 2a-e has been accomplished by reaction of 2-acetonitrile derivatives 1a-e with hydroxylamine. Cyclocondensation reaction of precursors 2a-e with some elctrophilic species such as ethylorthoformate, acetic anhydride, and methyl-acetoacetate provided the new oxadiazole derivatives 3a-e, 4a-e, and 5a-e, respectively. On the other hand, the reaction of precursors 2a-e with 2-chloropropanoyl chloride afforded the new acetimidamides 6a-e which evolve under reflux of toluene to the new oxadiazoles 7a-e. The synthetic compounds were screened for their anti-xanthine oxidase, anti-soybean lipoxygenase, and cytotoxic activities. Moderate to weak xanthine oxidase and soybean lipoxygenase inhibitions were obtained but significant cytotoxic activities were noted. The most cytotoxic activities were recorded mainly (i) 5a was the most active (IC50 = 4.0 µM) and selective against MCF-7 and (ii) 2a was cytotoxic against the four cell lines with selectivity for MCF-7 and OVCAR-3 (IC50 = 17 and 12 µM, respectively) while 2e is highly selective against OVCAR-3 (IC50 = 10 µM).


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Glycine max/enzimologia , Lipoxigenase/efeitos dos fármacos , Pirimidinas/síntese química , Pirimidinas/farmacologia , Xantina Oxidase/antagonistas & inibidores , Antineoplásicos/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/química , Humanos , Espectroscopia de Prótons por Ressonância Magnética , Pirimidinas/química , Espectrometria de Massas por Ionização por Electrospray
16.
J Cataract Refract Surg ; 41(8): 1588-93, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26432114

RESUMO

PURPOSE: To evaluate the safety and efficacy of wavefront-guided laser in situ keratomileusis (LASIK) for the correction of low to high myopia and myopic astigmatism using data derived from a new-generation Hartmann-Shack aberrometer. SETTING: Refractive Surgery Unit, Bordeaux Hospital University, France. DESIGN: Retrospective case series. METHODS: This retrospective study analyzed the initial group of eyes treated with wavefront-guided LASIK for myopia and myopic astigmatism using the Visx S4IR excimer laser and wavefront data derived from a new Hartmann-Shack aberrometer (iDesign Advanced Wavescan aberrometer). Refractive (refraction and refractive accuracy) and visual outcomes (uncorrected [UDVA] and corrected [CDVA] distance visual acuities) were recorded 3 months postoperatively. RESULTS: The study included 100 eyes of 50 consecutively treated patients. The mean decimal UDVA improved from 0.1 ± 0.1 (SD) preoperatively to 1.1 ± 0.15 postoperatively (P < .01). A monocular UDVA of 20/16, 20/20, and 20/25 were achieved in 76.6%, 94.4%, and 96.6% of eyes, respectively. The postoperative manifest spherical equivalent was within ±0.5 diopter in all eyes. No eye lost 2 or more lines of CDVA, and 29.2% of the eyes gained 1 or more lines of CDVA. CONCLUSION: Wavefront-guided LASIK performed using data derived from the new Hartmann-Shack aberrometer was safe, effective, and predictable for treating myopia and myopic astigmatism. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.


Assuntos
Aberrometria/métodos , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Lasers de Excimer/uso terapêutico , Miopia/cirurgia , Adulto , Substância Própria/fisiopatologia , Substância Própria/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miopia/fisiopatologia , Refração Ocular/fisiologia , Estudos Retrospectivos , Retalhos Cirúrgicos , Acuidade Visual/fisiologia , Adulto Jovem
17.
Anal Bioanal Chem ; 407(17): 5133-42, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25822159

RESUMO

For the most effective analytical strategies, development and validation include optimization of such analytical variables as resolution, detectability, sensitivity, simplicity, cost effectiveness, flexibility, and speed. However, other aspects concerning operator safety and environmental impact are not considered at the same level. The result has been many unintended negative effects of analytical methods developed to investigate different kinds of sample, especially hydrophobic compounds that generate a large amount of chemical waste and have a strong negative environmental impact. In this context, quantification of tocopherols and tocotrienols, i.e. the vitamin E family, is usually achieved by normal-phase liquid chromatography using large volumes of toxic organic solvents, or reversed-phase liquid chromatography using a high percentage of methanol for elution. We propose here a "greener" analytical strategy, including the hyphenation of supercritical-fluid chromatography, using CO2 and ethanol as mobile phase, NH2 as stationary phase, and mass spectrometry for the detection and quantification of vitamin E congeners in soybean oil. An atmospheric-pressure photoionization (APPI) source seemed significantly more sensitive and robust than electrospray or atmospheric-pressure chemical ionization (APCI). This method led to shortened analysis time (less than 5 min) and was revealed to be as sensitive as more traditional approaches, with limits of detection and quantification in the tens of µg L(-1).


Assuntos
Cromatografia com Fluido Supercrítico/métodos , Espectrometria de Massas/métodos , Óleo de Soja/química , Tocoferóis/análise , Tocotrienóis/análise , Química Verde/métodos , Limite de Detecção , Reprodutibilidade dos Testes , Tocoferóis/isolamento & purificação , Tocotrienóis/isolamento & purificação
18.
J Refract Surg ; 30(9): 610-5, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25250416

RESUMO

PURPOSE: To evaluate the short-term aberrometric outcomes of wavefront-guided LASIK for the correction of low to moderate myopia and myopic astigmatism using a new generation aberrometer (iDesign System; Abbott Medical Optics, Inc., Santa Ana, CA). METHODS: Charts of 92 eyes of 46 patients successively treated by wavefront-guided LASIK for myopia and/or myopic astigmatism were retrospectively reviewed at 3 months postoperatively. Aberrometric analysis of the wavefront errors was performed for a 6-mm pupil diameter to investigate the surgical induction of the total higher-order aberrations (HOAs), spherical aberrations Z41, and coma-like aberrations Z3 . Additionally, correlations between the magnitude of aberrations induced with the level of achieved correction and the preoperative amount of aberrations were tested. RESULTS: A minimal but statistically significant induction in all of the aberrations tested was observed at 3 months postoperatively (P < .01), with an increase (calculated for a 6-mm pupil) of +0.12 + 0.2, +0.06 + 0.1, and 0.05 + 0.1 pm in the root mean square (RMS) total HOA, RMS spherical aberration Z41, and RMS coma Z31, respectively. The postoperative change in aberrations was poorly correlated with both the level of achieved myopic correction for all of the aberrations tested (r < 0.3; P < .001) and the preoperative level of spherical aberrations (r = 0.3; P < .05) and coma (r = 0.46; P < .05). CONCLUSIONS: Wavefront-guided LASIK using the new generation Hartmann-Shack aberrometer allows a minimal induction of HOAs regardless of the level of myopic correction achieved or the preoperative magnitude of aberrations.


Assuntos
Aberrometria/instrumentação , Aberrações de Frente de Onda da Córnea/fisiopatologia , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Lasers de Excimer/uso terapêutico , Miopia/cirurgia , Adulto , Astigmatismo/fisiopatologia , Astigmatismo/cirurgia , Córnea/fisiopatologia , Córnea/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miopia/fisiopatologia , Estudos Retrospectivos , Acuidade Visual/fisiologia , Adulto Jovem
19.
Anal Bioanal Chem ; 406(20): 4861-74, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24952904

RESUMO

Cytochromes P450 (CYPs) play critical roles in oxidative metabolism of many endogenous and exogenous compounds. Protein expression levels of CYPs in liver provide relevant information for a better understanding of the importance of CYPs in pharmacology and toxicology. This work aimed at establishing a simple method to quantify six CYPs (CYP3A4, CYP3A5, CYP1A2, CYP2D6, CYP2C9, and CYP2J2) in various biological samples without isotopic labeling. The biological matrix was spiked with the standard peptides prior to the digestion step to realize a label-free quantification by mass spectrometry. The method was validated and applied to quantify these six isoforms in both human liver microsomes and mitochondria, but also in recombinant expression systems such as baculosomes and the HepG2 cell line. The results showed intra-assay and interassay accuracy and precision within 16 % and 5 %, respectively, at the low quality control level, and demonstrated the advantages of the method in terms of reproducibility and cost.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Microssomos Hepáticos/enzimologia , Mitocôndrias Hepáticas/enzimologia , Fragmentos de Peptídeos/análise , Proteínas Recombinantes/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Cisteína/química , Células Hep G2 , Humanos , Isoenzimas
20.
Artigo em Inglês | MEDLINE | ID: mdl-25707130

RESUMO

Monoterpenes are the main class of biogenic volatile organic compounds. They promptly react with oxygen and nitrogen species, leading to the formation of secondary aerosols. The determination of their physicochemical properties, such as their ionization energies (IEs), is crucial to understand better their reactivity. We previously introduced a modified atmospheric pressure photoionization source coupled to a tunable vacuum ultraviolet source at the SOLEIL synchrotron radiation facility. Here, this set-up is employed to determine IEs of ten monoterpenes with a good precision (±50 meV) and a small sample consumption limited to 10 µg.


Assuntos
Monoterpenos/química , Pressão Atmosférica , Cicloexenos/química , Limoneno , Espectrometria de Massas/métodos , Síncrotrons , Terpenos/química , Raios Ultravioleta , Vácuo
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