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1.
Neurology ; 103(3): e209665, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39008782

RESUMO

BACKGROUND AND OBJECTIVES: Amyloid pathology, vascular disease pathology, and pathologies affecting the medial temporal lobe are associated with cognitive trajectories in older adults. However, only limited evidence exists on how these pathologies influence cognition in the oldest old. We evaluated whether amyloid burden, white matter hyperintensity (WMH) volume, and hippocampal volume (HV) are associated with cognitive level and decline in the oldest old. METHODS: This was a longitudinal, observational community-based cohort study. We included participants with 18F-florbetapir PET and MRI data from the 90+ Study. Amyloid load was measured using the standardized uptake value ratio in the precuneus/posterior cingulate with eroded white matter mask as reference. WMH volume was log-transformed. All imaging measures were standardized using sample means and SDs. HV and log-WMH volume were normalized by total intracranial volume using the residual approach. Global cognitive performance was measured by the Mini-Mental State Examination (MMSE) and modified MMSE (3MS) tests, repeated every 6 months. We used linear mixed-effects models with random intercepts; random slopes; and interaction between time, time squared, and imaging variables to estimate the associations of imaging variables with cognitive level and cognitive decline. Models were adjusted for demographics, APOE genotype, and health behaviors. RESULTS: The sample included 192 participants. The mean age was 92.9 years, 125 (65.1%) were female, 71 (37.0%) achieved a degree beyond college, and the median follow-up time was 3.0 years. A higher amyloid load was associated with a lower cognitive level (ßMMSE = -0.82, 95% CI -1.17 to -0.46; ß3MS = -2.77, 95% CI -3.69 to -1.84). A 1-SD decrease in HV was associated with a 0.70-point decrease in the MMSE score (95% CI -1.14 to -0.27) and a 2.27-point decrease in the 3MS score (95% CI -3.40 to -1.14). Clear nonlinear cognitive trajectories were detected. A higher amyloid burden and smaller HV were associated with faster cognitive decline. WMH volume was not significantly associated with cognitive level or decline. DISCUSSION: Amyloid burden and hippocampal atrophy are associated with both cognitive level and cognitive decline in the oldest old. Our findings shed light on how different pathologies contributed to driving cognitive function in the oldest old.


Assuntos
Disfunção Cognitiva , Hipocampo , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Substância Branca , Humanos , Feminino , Masculino , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Branca/metabolismo , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Hipocampo/metabolismo , Idoso de 80 Anos ou mais , Estudos Longitudinais , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Disfunção Cognitiva/metabolismo , Cognição/fisiologia , Estudos de Coortes , Tamanho do Órgão , Etilenoglicóis , Compostos de Anilina , Peptídeos beta-Amiloides/metabolismo , Amiloide/metabolismo
2.
Int J Biol Macromol ; 273(Pt 2): 133161, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38885863

RESUMO

Eucalyptus was pretreated with diethylene glycol catalyzed by 0.02 mol/L CrCl3 for 10 min, resulting in 91 % delignification and 98 % cellulose recovery, with trace fermentation inhibitors generated. After the mild pretreatment, the accessibility and affinity of cellulase to eucalyptus was enhanced, especially since enzyme adsorption rate increased by 1.6-fold. Therefore, glucose yield of pretreated eucalyptus was 7.9-fold higher than that of untreated eucalyptus after hydrolyzed 48 h, in which the maximum glucose concentration reached 62 g/L from eucalyptus by adding Tween 80. According to the characterization analysis, the structure of the eucalyptus lignin-carbohydrate complexes structure was destroyed during the pretreatment, while lignin fragments was likely reacted with diethylene glycol to form the stabilized aromatic ethers. Moreover, the extracted Deg-lignin exhibited better performances than commercial alkali lignin such as higher fluorescence intensity, less negative surface charge, and lower particle size. The mild pretreatment method with diethylene glycol and CrCl3 provided a promising approach for co-production of fermentable sugars and high activity lignin from lignocellulosic biomass.


Assuntos
Etilenoglicóis , Eucalyptus , Fermentação , Lignina , Eucalyptus/química , Lignina/química , Etilenoglicóis/química , Hidrólise , Glucose/metabolismo , Glucose/química , Açúcares/química , Açúcares/metabolismo , Celulase/metabolismo , Celulase/química , Biomassa
3.
Alzheimers Res Ther ; 16(1): 100, 2024 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711107

RESUMO

BACKGROUND: Retinal microvascular signs are accessible measures of early alterations in microvascular dysregulation and have been associated with dementia; it is unclear if they are associated with AD (Alzheimer's disease) pathogenesis as a potential mechanistic link. This study aimed to test the association of retinal microvascular abnormalities in mid and late life and late life cerebral amyloid. METHODS: Participants from the ARIC-PET (Atherosclerosis Risk in Communities-Positron Emission Tomography) study with a valid retinal measure (N = 285) were included. The associations of mid- and late-life retinal signs with late-life amyloid-ß (Aß) by florbetapir PET were tested. Two different measures of Aß burden were included: (1) elevated amyloid (SUVR > 1.2) and (2) continuous amyloid SUVR. The retinal measures' association with Aß burden was assessed using logistic and robust linear regression models. A newly created retinal score, incorporating multiple markers of retinal abnormalities, was also evaluated in association with greater Aß burden. RESULTS: Retinopathy in midlife (OR (95% CI) = 0.36 (0.08, 1.40)) was not significantly associated with elevated amyloid burden. In late life, retinopathy was associated with increased continuous amyloid standardized value uptake ratio (SUVR) (ß (95%CI) = 0.16 (0.02, 0.32)) but not elevated amyloid burden (OR (95%CI) = 2.37 (0.66, 9.88)) when accounting for demographic, genetic and clinical risk factors. A high retinal score in late life, indicating a higher burden of retinal abnormalities, was also significantly associated with increased continuous amyloid SUVR (ß (95% CI) = 0.16 (0.04, 0.32)) independent of vascular risk factors. CONCLUSIONS: Retinopathy in late life may be an easily obtainable marker to help evaluate the mechanistic vascular pathway between retinal measures and dementia, perhaps acting via AD pathogenesis. Well-powered future studies with a greater number of retinal features and other microvascular signs are needed to test these findings.


Assuntos
Peptídeos beta-Amiloides , Compostos de Anilina , Encéfalo , Tomografia por Emissão de Pósitrons , Vasos Retinianos , Humanos , Feminino , Masculino , Peptídeos beta-Amiloides/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Idoso , Pessoa de Meia-Idade , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Vasos Retinianos/diagnóstico por imagem , Doenças Retinianas/diagnóstico por imagem , Doenças Retinianas/metabolismo , Microvasos/diagnóstico por imagem , Microvasos/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Etilenoglicóis
4.
J Nucl Med ; 65(5): 781-787, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38575189

RESUMO

Amyloid-ß (Aß) accumulation in Alzheimer disease (AD) is typically measured using SUV ratio and the centiloid (CL) scale. The low spatial resolution of PET images is known to degrade quantitative metrics because of the partial-volume effect. This article examines the impact of spatial resolution, as determined by the reconstruction configuration, on the Aß PET quantitation in both cross-sectional and longitudinal data. Methods: The cross-sectional study involved 89 subjects with 20-min [18F]florbetapir scans generated on an mCT (44 Aß-negative [Aß-], 45 Aß-positive [Aß+]) using 69 reconstruction configurations, which varied in number of iteration updates, point-spread function, time-of-flight, and postreconstruction smoothing. The subjects were classified as Aß- or Aß+ visually. For each reconstruction, Aß CL was calculated using CapAIBL, and the spatial resolution was calculated as full width at half maximum (FWHM) using the barrel phantom method. The change in CLs and the effect size of the difference in CLs between Aß- and Aß+ groups with FWHM were examined. The longitudinal study involved 79 subjects (46 Aß-, 33 Aß+) with three 20-min [18F]flutemetamol scans generated on an mCT. The subjects were classified as Aß- or Aß+ using a cutoff CL of 20. All scans were reconstructed using low-, medium-, and high-resolution configurations, and Aß CLs were calculated using CapAIBL. Since linear Aß accumulation was assumed over a 10-y interval, for each reconstruction configuration, Aß accumulation rate differences (ARDs) between the second and first periods were calculated for all subjects. Zero ARD was used as a consistency metric. The number of Aß accumulators was also used to compare the sensitivity of CL across reconstruction configurations. Results: In the cross-sectional study, CLs in both the Aß- and the Aß+ groups were impacted by the FWHM of the reconstruction method. Without postreconstruction smoothing, Aß- CLs increased for a FWHM of 4.5 mm or more, whereas Aß+ CLs decreased across the FWHM range. High-resolution reconstructions provided the best statistical separation between groups. In the longitudinal study, the median ARD of low-resolution reconstructed data for the Aß- group was greater than zero whereas the ARDs of higher-resolution reconstructions were not significantly different from zero, indicating more consistent rate estimates in the higher-resolution reconstructions. Higher-resolution reconstructions identified 10 additional Aß accumulators in the Aß- group, resulting in a 22% increased group size compared with the low-resolution reconstructions. Higher-resolution reconstructions reduced the average CLs of the negative group by 12 points. Conclusion: High-resolution PET reconstructions, inherently less impacted by partial-volume effect, may improve Aß PET quantitation in both cross-sectional and longitudinal data. In the cross-sectional analysis, separation of CLs between Aß- and Aß+ cohorts increased with spatial resolution. Higher-resolution reconstructions also exhibited both improved consistency and improved sensitivity in measures of Aß accumulation. These features suggest that higher-resolution reconstructions may be advantageous in early-stage AD therapies.


Assuntos
Peptídeos beta-Amiloides , Etilenoglicóis , Processamento de Imagem Assistida por Computador , Tomografia por Emissão de Pósitrons , Humanos , Peptídeos beta-Amiloides/metabolismo , Estudos Transversais , Tomografia por Emissão de Pósitrons/métodos , Estudos Longitudinais , Masculino , Feminino , Idoso , Processamento de Imagem Assistida por Computador/métodos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Compostos de Anilina
5.
Chemosphere ; 358: 142084, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38642772

RESUMO

The widely-used surfactant Nonylphenol Ethoxylate (NPEO) produces endocrine-disrupting compounds during biodegradation, with these byproducts being more harmful than untreated NPEO. This study investigates the effectiveness of a Fluidized Bed Reactor (FBR) in reducing the production of 4-Nonylphenol (4-NP) during the biodegradation of NPEO. Two identical FBR filled with sand were used to assess the NPEO degradation and to enhance the microbial consortia capable of breaking down the complex byproducts, ethanol and fumarate were introduced as co-substrates. Our findings demonstrate the significant potential of the FBR, especially when coupled with fumarate, for enhancing the surfactant degradation. It outperforms the efficiency achieved with ethanol as the primary electron donor, albeit with a higher rate of byproduct production. Microbial community taxonomy and metabolic prediction revealed the high abundance of Geobacter (1.51-31.71%) and Methanobacterium (1.08-13.81%) in non-conductive sand. This may hint a new metabolic interaction and expand our understanding of Direct Interspecies Electron Transfer (DIET) in bioreactors applied to micropollutants degradation. Such an intricate relationship between facultative and anaerobes working together to simultaneously biodegrade the ethoxy and alkyl chains presents a new perspective on NPEO degradation and can potentially be extended to other micropollutants.


Assuntos
Biodegradação Ambiental , Reatores Biológicos , Etilenoglicóis , Reatores Biológicos/microbiologia , Etilenoglicóis/metabolismo , Etilenoglicóis/química , Fenóis/metabolismo , Tensoativos/metabolismo , Tensoativos/química , Disruptores Endócrinos/metabolismo , Consórcios Microbianos , Geobacter/metabolismo
6.
J Chromatogr A ; 1721: 464850, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38564932

RESUMO

The solvation parameter model uses five system independent descriptors to characterize compound properties defined as excess molar refraction, E, dipolarity/polarizability, S, hydrogen-bond acidity, A, hydrogen-bond basicity, B, and McGowan's characteristic volume, V, to model transfer properties between condensed phases. The V descriptor is assigned from structure. For compounds liquid at 20 °C the E descriptor can be assigned from the characteristic volume and its refractive index. The E descriptor for compounds solid at 20 °C and the S, A, and B descriptors are experimental properties traditionally assigned from chromatographic, liquid-liquid partition, and solubility measurements. In this report liquid-liquid partition constants in totally organic and aqueous biphasic systems are evaluated as a standalone technique for descriptor assignments. Using six totally organic biphasic systems the S, A, and B descriptors were assigned with an average absolute deviation (AAD) of about 0.04, 0.03, and 0.04, respectively, compared with the best estimate of the true descriptor values for 65 compounds. The E descriptor for compounds solid at 20 °C can only be estimated with an AAD of approximately 0.1. For six aqueous biphasic systems the B descriptor is assigned with a lower AAD of 0.028 and higher AAD of 0.08 and 0.05 for the S and A descriptors, respectively, than for the totally organic biphasic systems for compounds with a reliable value for the E descriptor. The preferred system for descriptor assignments utilizes both totally organic biphasic systems (heptane-1,1,1-trifluoroethanol, isopentyl ether-propylene carbonate, isopentyl ether-ethanolamine, heptane-ethylene glycol, heptane-formamide, and 1,2-dichloroethane-ethylene glycol) and aqueous biphasic systems (octanol-water, cyclohexane-water) with the possible substitution of some systems with alternative systems of similar selectivity. For 55 varied compounds this combination of eight organic and aqueous biphasic systems resulted in an AAD of approximately 0.03, 0.02, and 0.02 for the S, A, and B descriptors compared to the best estimate of the true descriptor value. For 30 compounds solid at 20 °C the AAD for the E descriptor of 0.11 is poorly assigned. The relative average absolute deviation in percent (RAAD) corresponds to 9.7 %, 3.1 %. 4.0 % and 8.3 % for E, S, A, and B, respectively, for the eight biphasic systems. Liquid-liquid partition is compared to reversed-phase liquid and gas chromatography as a standalone technique for descriptor assignments.


Assuntos
Éteres , Água , Etilenoglicóis , Heptanos/química , Hidrogênio , Água/química , Cicloexanos/química , Octanóis/química
7.
Arch Toxicol ; 98(6): 1771-1780, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38668861

RESUMO

2-Phenoxyethanol (PhE) is an aromatic glycol ether and is used in a variety of functions and applications, e.g., as preservative in pharmaceuticals, cosmetic and personal care products, as biocide in disinfectants (e.g. human hygiene), or as a solvent in formulations (e.g. coatings, functional fluids). Despite its widespread use, little is yet known on its biotransformation and toxicokinetics in humans. Therefore, a pilot study was conducted with oral administration of PhE (5 mg/kg body weight) to five volunteers. Blood and urine samples were collected and analyzed for PhE and three of its presumed metabolites up to 48 h post-exposure. Additionally, one volunteer was dermally exposed to PhE and monitored until 72 h post-exposure. PhE was rapidly resorbed following both oral and dermal application with tmax-levels in blood of about 1 h and 3 h, respectively. Metabolism of PhE was observed to be rather extensive with phenoxyacetic acid (PhAA) and 4-hydroxyphenoxyacetic acid (4-OH-PhAA) as the main metabolites found in blood and urine following oral and dermal exposure. PhE was excreted rapidly and efficiently via urine mostly in metabolized form: following oral exposure, on average 77% and 12% of the applied dose was excreted within 48 h as PhAA and 4-OH-PhAA, respectively. A similar metabolism pattern was observed following the single dermal exposure experiment. The obtained data on biotransformation and toxicokinetics of PhE in humans provide valuable information on this important chemical and will be highly useful for pharmacokinetic modelling and evaluation of human PhE exposure.


Assuntos
Biotransformação , Etilenoglicóis , Toxicocinética , Humanos , Administração Oral , Projetos Piloto , Etilenoglicóis/farmacocinética , Etilenoglicóis/toxicidade , Adulto , Masculino , Feminino , Administração Cutânea , Adulto Jovem
8.
Environ Sci Pollut Res Int ; 31(21): 30497-30508, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38607492

RESUMO

Detergents are highly produced pollutants with environmental problems like foam generation and toxic effects in biota. Nonylphenol ethoxylates (NPEs) are efficient, economical, and versatile surfactants, used in detergents for more than 40 years due to their detergency capacity. In the environment, NPE biodegrades into the metabolite nonylphenol (NP), classified as an endocrine disruptor. The identification and quantification of 4-NP in a designed detergent and 30 commercially available detergents were performed to prove the degradation of NPE into 4-NP during storage time. This investigation introduces the first evidence of NPE degradation during storage in commercially available detergents, demonstrating a novel exposure pathway in humans that has not been explored before, representing potential human health risks. Therefore, simple, easy, low-cost, and available approaches to remove and substitute NP is paramount. Alkyl polyglucoside (APG) was assessed as a substitute, and the feasibility of this substitution was proven according to physical and chemical properties, cleaning performance, and antimicrobial properties. NPE substitution in detergents is demonstrated as a viable strategy to minimize exposure risks in humans and the environment.


Assuntos
Detergentes , Detergentes/química , Etilenoglicóis/química , Fenóis , Tensoativos/química , Humanos , Disruptores Endócrinos/análise
10.
J Anal Toxicol ; 48(6): 419-428, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-38662393

RESUMO

2-Phenoxyethanol (PhE) is widely used as a preservative in consumer products such as cosmetics as well as at the workplace as a component of metal-working fluids and hydraulic fluids. Therefore, both industry workers and consumers may potentially be exposed to PhE. An analytical method for the quantification of PhE and three selected metabolites, namely phenoxyacetic acid (PhAA), 4-hydroxyphenoxyacetic acid (4-OH-PhAA), and 4-hydroxyphenoxyethanol (4-OH-PhE), in human urine and blood was developed and validated. The sample preparation includes enzymatic hydrolysis of urine samples or protein precipitation of blood samples, followed by liquid-liquid extraction and silylation of the target analytes. Analyses of the extracts were carried out by gas chromatography with tandem mass spectrometry (GC-MS-MS). 3,4-Hydroxyphenoxyethanol, a probably minor PhE metabolite, could not be reliably analyzed due to its instability. The limits of quantification (LOQ) of the analytes ranged between 0.5 and 6.1 µg/L and 2.0 and 3.9 µg/L in urine and blood, respectively. The method was successfully applied to spot urine samples of 50 individuals without occupational exposure to PhE and additionally to blood samples from seven volunteers. In urine, PhAA and 4-OH-PhAA could be quantified in all analyzed samples, whereas 4-OH-PhE and unchanged PhE were found in 36% and 32% of the samples, respectively. In blood, PhAA was also found in every sample in levels above the LOQ, whereas PhE itself was detected in three of seven samples only. Neither 4-OH-PhAA nor 4-OH-PhE was found in any of the analyzed blood samples. The developed method promises to be a valuable tool for PhE monitoring of urine and blood samples and may also enable an advanced investigation of PhE biotransformation pathways in humans.


Assuntos
Etilenoglicóis , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas em Tandem , Humanos , Reprodutibilidade dos Testes , Limite de Detecção , Extração Líquido-Líquido
11.
Urolithiasis ; 52(1): 52, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564033

RESUMO

Urolithiasis is a prevalent urological disorder that contributes significantly to global morbidity. This study aimed to assess the anti-urolithic effects of Cymbopogon proximus (Halfa Bar) and Petroselinum crispum (parsley) seed ethanolic extract /Gum Arabic (GA) emulsion, and its nanogel form against ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats. Rats were divided into four groups: group 1 served as the normal control, group 2 received EG with AC in drinking water for 14 days to induce urolithiasis, groups 3 and 4 were orally administered emulsion (600 mg/kg/day) and nanogel emulsion (600 mg/kg/day) for 7 days, followed by co-administration with EG and AC in drinking water for 14 days. Urolithiatic rats exhibited a significant decrease in urinary excreted magnesium, and non-enzymic antioxidant glutathione and catalase activity. Moreover, they showed an increase in oxalate crystal numbers and various urolithiasis promoters, including excreted calcium, oxalate, phosphate, and uric acid. Renal function parameters and lipid peroxidation were intensified. Treatment with either emulsion or nanogel emulsion significantly elevated urolithiasis inhibitors, excreted magnesium, glutathione levels, and catalase activities. Reduced oxalate crystal numbers, urolithiasis promoters' excretion, renal function parameters, and lipid peroxidation while improving histopathological changes. Moreover, it decreased renal crystal deposition score and the expression of Tumer necrosis factor-α (TNF-α) and cleaved caspase-3. Notably, nanogel emulsion showed superior effects compared to the emulsion. Cymbopogon proximus (C. proximus) and Petroselinum crispum (P. crispum) seed ethanolic extracts/GA nanogel emulsion demonstrated protective effects against ethylene glycol induced renal stones by mitigating kidney dysfunction, oxalate crystal formation, and histological alterations.


Assuntos
Cymbopogon , Água Potável , Cálculos Renais , Polietilenoglicóis , Polietilenoimina , Urolitíase , Animais , Ratos , Petroselinum , Cloreto de Amônio , Goma Arábica , Emulsões , Catalase , Magnésio , Nanogéis , Urolitíase/induzido quimicamente , Urolitíase/tratamento farmacológico , Urolitíase/prevenção & controle , Sementes , Antioxidantes/uso terapêutico , Etanol , Glutationa , Oxalatos , Etilenoglicóis , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
12.
Chemosphere ; 353: 141589, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38432465

RESUMO

A comparative toxicity of widely applied organic solvents (methanol, ethanol, n-propanol, i-propanol, n-butanol, 2-butanol, i-butanol, t-butanol, 3-methoxy-3-methylbutanol-1 (MMB), ethylene glycol, diethylene glycol, 2-methoxyethanol, 2-ethoxyethanol, glycerol, ethyl acetate, acetonitrile, benzene, dioxane, dimethylformamide, dimethylacetamide, dimethylsulfoxide, 2-pyrrolidone, and N-methyl-2-pyrrolidone) and surfactants (PEG 300, PEG 6000, Tween 20, Tween 80, miramistin, and Cremophor EL) was studied using a sea urchin embryo model. Sea urchin embryo morphological alterations caused by the tested chemicals were described. The tested molecules affected P. lividus embryo development in a concentration-dependent manner. The observed phenotypic anomalies ranged from developmental delay and retardation of plutei growth to formation of aberrant blastules and gastrules, cleavage alteration/arrest, and embryo mortality. Discernible morphological defects were found after embryo exposure with common pharmaceutical ingredients, such as glycerol, Tween 80, and Cremophor EL. In general, solvents were less toxic than surfactants. PEG 6000 PEG 300, DMSO, ethanol, and methanol were identified as the most tolerable compounds with minimum effective concentration (MEC) values of 3.0-7.92 mg/mL. Previously reported MEC value of Pluronic F127 (4.0 mg/mL) fell within the same concentration range. Toxic effects of methanol, ethanol, DMSO, 2-methoxyethanol, 2-ethoxyethanol, Tween 20, and Tween 80 on P. lividus embryos correlated well with their toxicity obtained using other cell and animal models. The sea urchin embryos could be considered as an appropriate test system for toxicity assessment of solvents and surfactants for their further application as solubilizers of hydrophobic molecules in conventional in vitro cell-based assays and in vivo mammalian models. Nevertheless, to avoid adverse effect of a solubilizing agent in ecotoxicological and biological experiments, the preliminary assessment of its toxicity on a chosen test model would be beneficial.


Assuntos
Etilenoglicóis , Glicerol/análogos & derivados , Metanol , Polissorbatos , Animais , Polissorbatos/toxicidade , Glicerol/toxicidade , Dimetil Sulfóxido , Tensoativos/toxicidade , Solventes/toxicidade , Ouriços-do-Mar , Etanol/farmacologia , Excipientes/química , 1-Propanol , Embrião não Mamífero , Mamíferos , Polietilenoglicóis
13.
AAPS PharmSciTech ; 25(3): 54, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443653

RESUMO

Chrysin is a natural flavonoid with a wide range of bioactivities. Only a few investigations have assessed the analgesic activity of chrysin. The lipophilicity of chrysin reduces its aqueous solubility and bioavailability. Hence, self-nanoemulsifying drug delivery systems (SNEDDS) were designed to overcome this problem. Kollisolv GTA, Tween 80, and Transcutol HP were selected as oil, surfactant, and cosurfactant, respectively. SNEDDS A, B, and C were prepared, loaded with chrysin (0.1%w/w), and extensively evaluated. The optimized formula (B) encompasses 25% Kollisolv GTA, 18.75% Tween 80, and 56.25% Transcutol HP was further assessed. TEM, in vitro release, and biocompatibility towards the normal oral epithelial cell line (OEC) were estimated. Brain targeting and acetic acid-induced writhing in a mouse model were studied. After testing several adsorbents, powdered SNEDDS B was formulated and evaluated. The surfactant/cosurfactant (S/CoS) ratio of 1:3 w/w was appropriate for the preparation of SNEDDS. Formula B exhibited instant self-emulsification, spherical nanoscaled droplets of 155.4 ± 32.02 nm, and a zeta potential of - 12.5 ± 3.40 mV. The in vitro release proved the superiority of formula B over chrysin suspension (56.16 ± 10.23 and 9.26 ± 1.67%, respectively). The biocompatibility of formula B towards OEC was duplicated (5.69 ± 0.03 µg/mL). The nociceptive pain was mitigated by formula B more efficiently than chrysin suspension as the writhing numbers reduced from 8.33 ± 0.96 to 0 after 60 min of oral administration. Aerosil R972 was selected as an adsorbent, and its chemical compatibility was confirmed. In conclusion, our findings prove the therapeutic efficacy of chrysin self-nanoemulsion as a potential targeting platform to combat pain.


Assuntos
Etilenoglicóis , Flavonoides , Polissorbatos , Animais , Camundongos , Flavonoides/farmacologia , Tensoativos , Ouro
14.
Sci Total Environ ; 926: 171798, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38521252

RESUMO

In this study, a biological treatment process, which used a built-in ozonation bypass to achieve sludge reduction, was built to treat the industrial antifreeze production wastewater (mainly composed of ethylene glycol). The results indicated there is a positive correlation between ozone dosage and sludge reduction. At the laboratory level, the MLSS in the system can be stably controlled at around 3400 mg MLSS L-1 under the dosage of 0.18 g O3 g-1 MLSS. Ozonation can increase the compactness of sludge flocs (fractal dimension increased from 1.89 to 1.92). Ozone destroys microbial cell membranes and alters the structure of sludge flocs through direct oxidation through electrophilic reactions. It leads to the release of intracellular polysaccharides, proteins, and other biological macromolecules in microorganisms, thereby promoting the implicit growth of microbial populations. Some bacteria such as g_Pseudomonas, g_Gemmobacter, etc. have strong ethylene glycol degradation ability and tolerance to ozonation. The removal of ethylene glycol includes the glyoxylate cycle, glycine serine carbon cycle, and the glutamate-cysteine ligase pathway of assimilation. Gene KatG and gpx may be key factors in improving microbial tolerance to ozonation. The comprehensive evaluation from the perspectives of cost and carbon emission shows that choosing ozone cracking-implicit growth in wastewater treatment systems has significant cost advantages and application value.


Assuntos
Ozônio , Purificação da Água , Águas Residuárias , Esgotos/microbiologia , Ozônio/química , Etilenoglicóis , Eliminação de Resíduos Líquidos/métodos
15.
Waste Manag ; 178: 351-361, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38430749

RESUMO

The traditional hydrometallurgy technology has been widely used to recover precious metals from electronic waste. However, such aqueous recycling systems often employ toxic/harsh chemicals, which may cause serious environmental problems. Herein, an efficient and environment-friendly method using a deep eutectic solvent (DES) mixed system of choline chloride-ethylene glycol-CuCl2·2H2O is developed for gold (Au) recovery from flexible printed circuit boards (FPCBs). The Au leaching and precipitation efficiency can reach approximately 100 % and 95.3 %, respectively, under optimized conditions. Kinetic results show that the Au leaching process follows a nucleation model, which is controlled by chemical surface reactions with an apparent activation energy of 80.29 kJ/mol. The present recycling system has a much higher selectivity for Au than for other base metals; the two-step recovery rate of Au can reach over 95 %, whereas those of copper and nickel are < 2 %. Hydrogen nuclear magnetic resonance spectroscopy (HNMR) and density functional theory (DFT) analyses confirm the formation of intermolecular hydrogen bonds in the DES mixed system, which increase the system melting and boiling points and facilitate the Au leaching process. The Au leaching system can be reused for several times, with the leaching efficiency remaining > 97 % after five cycles. Moreover, ethylene glycol (EG) and choline chloride (ChCl) act as aprotic solvents as well as coordinate with metals, decreasing the redox potential to shift the equilibrium to the leaching side. Overall, this research provides a theoretical and a practical basis for the recovery of metals from FPCBs.


Assuntos
Resíduo Eletrônico , Ouro , Ouro/química , Colina , Cobre/química , Reciclagem/métodos , Resíduo Eletrônico/análise , Etilenoglicóis
16.
Neuromolecular Med ; 26(1): 6, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504005

RESUMO

Familial Alzheimer's disease (AD) is a rare disease caused by autosomal-dominant mutations. APP (encoding amyloid precursor protein), PSEN1 (encoding presenilin 1), and PSEN2 (encoding presenilin 2) are the most common genes cause dominant inherited AD. This study aimed to demonstrate a Chinese early-onset AD pedigree presenting as progressive memory impairment, apraxia, visual-spatial disorders, psychobehavioral disorders, and personality changes with a novel APP gene mutation. The family contains four patients, three carries and three normal family members. The proband underwent brain magnetic resonance imaging (MRI), 18F-fludeoxyglucose positron emission tomography (18F-FDG-PET), cerebrospinal fluid amyloid detection, 18F-florbetapir (AV-45) Positron Emission Computed Tomography (PET) imaging, whole-exome sequencing and Sanger sequencing. Brain MRI images showed brain atrophy, especially in the entorhinal cortex, temporal hippocampus, and lateral ventricle dilation. The FDG-PET showed hypometabolism in the frontotemporal, parietal, and hippocampal regions. 18F-florbetapir (AV-45) PET imaging showed cerebral cortex Aß protein deposition. The cerebrospinal fluid amyloid protein test showed Aß42/Aß40 ratio decreases, pathological phosphor-tau level increases. Whole-exome sequencing detected a new missense mutation of codon 671 (M671L), which was a heterozygous A to T point mutation at position 2011 (c.2011A > T) in exon 16 of the amyloid precursor protein, resulting in the replacement of methionine to Leucine. The co-separation analysis was validated in this family. The mutation was found in 3 patients, 3 clinical normal members in the family, but not in the other 3 unaffected family members, 100 unrelated normal subjects, or 100 sporadic patients with AD. This mutation was probably pathogenic and novel in a Chinese Han family with early-onset AD.


Assuntos
Doença de Alzheimer , Compostos de Anilina , Etilenoglicóis , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Fluordesoxiglucose F18 , Mutação , China , Presenilina-1/genética , Peptídeos beta-Amiloides/metabolismo
17.
Clin Nucl Med ; 49(5): 486-488, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38465960

RESUMO

ABSTRACT: A 66-year-old man presented with multiple masses in different regions, including the left groin, back subcutaneous area, and lungs. Pathological examination confirmed localized amyloid deposits after 3 surgeries. Serum-free λ light chains were elevated. To evaluate systemic involvement, the patient underwent 18 F-Florbetapir PET/CT and 68 Ga-FAPI-04 PET/CT. Both scans showed increased uptake in multiple masses and nodules throughout the body. This report presents a rare case of light chain (AL) amyloidosis, primarily characterized by multiple localized tumor-like deposits with high activity on 18 F-Florbetapir PET/CT and 68 Ga-FAPI-04 PET/CT.


Assuntos
Amiloidose , Etilenoglicóis , Amiloidose de Cadeia Leve de Imunoglobulina , Masculino , Humanos , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Amiloidose/diagnóstico por imagem , Compostos de Anilina , Radioisótopos de Gálio , Fluordesoxiglucose F18
18.
Biosens Bioelectron ; 252: 116151, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38402725

RESUMO

Perylene diimide (PDI) is a readily reducible electron-deficient dye that exhibits strong photoluminescent properties, providing new opportunities for synthesizing novel electrochemiluminescence (ECL) emitters. In this study, ethylene glycol (EG) was used to induce the self-assembly of PDI supramolecules for the preparation of ultrathin EG-PDI nanosheets characterized by low crystallinity and weak stacking interaction. Notably, EG-PDI integrates luminescent and catalytic functions into one device, accelerating the interfacial electron transfer and the faster charge transfer kinetics of EG-PDI with K2S2O8. Furthermore, the narrow band gap of EG-PDI facilitates its excitation at an ultra-low potential (-0.3 V). To improve the efficiency of tumor marker analysis, multifunctional Au nanostars (ANS) was introduced both as an energy acceptor of the ECL system and a probe for the photothermal system. Dual-mode immunoassay have demonstrated superior analytical performance in detecting alpha-fetoprotein (AFP), meeting the requirements of modern clinical diagnostics in resource-limited environments.


Assuntos
Técnicas Biossensoriais , Imidas , Perileno/análogos & derivados , Imunoensaio , Etilenoglicóis
19.
Biomed Pharmacother ; 172: 116252, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325265

RESUMO

PURPOSE: Type 2 diabetes mellitus (T2DM) is associated with a greater risk of Alzheimer's disease. Synaptic impairment and protein aggregates have been reported in the brains of T2DM models. Here, we assessed whether neurodegenerative changes in synaptic vesicle 2 A (SV2A), γ-aminobutyric acid type A (GABAA) receptor, amyloid-ß, tau and receptor for advanced glycosylation end product (RAGE) can be detected in vivo in T2DM rats. METHODS: Positron emission tomography (PET) using [18F]SDM-8 (SV2A), [18F]flumazenil (GABAA receptor), [18F]florbetapir (amyloid-ß), [18F]PM-PBB3 (tau), and [18F]FPS-ZM1 (RAGE) was carried out in 12-month-old diabetic Zucker diabetic fatty (ZDF) and SpragueDawley (SD) rats. Immunofluorescence staining, Thioflavin S staining, proteomic profiling and pathway analysis were performed on the brain tissues of ZDF and SD rats. RESULTS: Reduced cortical [18F]SDM-8 uptake and cortical and hippocampal [18F]flumazenil uptake were observed in 12-month-old ZDF rats compared to SD rats. The regional uptake of [18F]florbetapir and [18F]PM-PBB3 was comparable in the brains of 12-month-old ZDF and SD rats. Immunofluorescence staining revealed Thioflavin S-negative, phospho-tau-positive inclusions in the cortex and hypothalamus in the brains of ZDF rats and the absence of amyloid-beta deposits. The level of GABAA receptors was lower in the cortex of ZDF rats than SD rats. Proteomic analysis further demonstrated that, compared with SD rats, synaptic-related proteins and pathways were downregulated in the hippocampus of ZDF rats. CONCLUSION: These findings provide in vivo evidence for regional reductions in SV2A and GABAA receptor levels in the brains of aged T2DM ZDF rats.


Assuntos
Compostos de Anilina , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Etilenoglicóis , Radioisótopos de Flúor , Piridinas , Pirrolidinas , Ratos , Animais , Flumazenil/metabolismo , Receptores de GABA-A/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Vesículas Sinápticas/metabolismo , Proteômica , Ratos Zucker , Tomografia por Emissão de Pósitrons/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Ácido gama-Aminobutírico/metabolismo
20.
Chemosphere ; 352: 141377, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38346514

RESUMO

In recent years, emerging pollutants, including nonylphenol (NP) and nonylphenol ethoxylate (NPE), have become a prominent topic. These substances are also classified as persistent organic pollutants. NP significantly affects the hormone secretion of organisms and exhibits neurotoxicity, which can affect the human hippocampus. Therefore, various countries are paying increased attention to NP regulation. NPEs are precursors of NPs and are widely used in the manufacture of various detergents and lubricants. NPEs can easily decompose into NPs, which possess strong biological and environmental toxicity. This review primarily addresses the distribution, toxicity mechanisms and performance, degradation technologies, management policies, and green alternative reagents of NPs and NPEs. Traditional treatment measures have been unable to completely remove NP from wastewater. With the progressively tightening management and regulatory policies, identifying proficient and convenient treatment methods and a sustainable substitute reagent with comparable product effectiveness is crucial.


Assuntos
Fenóis , Poluentes Químicos da Água , Humanos , Fenóis/toxicidade , Etilenoglicóis/toxicidade , Águas Residuárias , Poluentes Químicos da Água/análise
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