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1.
Leg Med (Tokyo) ; 47: 101780, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32882537

RESUMO

New psychoactive stimulants appeared in Hungary in 2010 as in several other European countries. We present our findings from cases where new psychoactive and conventional stimulants (we listed amphetamine, methamphetamine and MDMA as conventional drugs) have been detected in biological specimens between 2010 and 2019. MATERIALS: Biological samples (including urine, blood and body tissues), sent to the Department of Forensic Medicine, University of Pécs, South-West Hungary, in the period 2010-2019. METHOD: High performance liquid chromatography coupled with diode array detection (HPLC-DAD); supercritical fluid chromatography coupled to tandem mass spectrometry (SFC-MS/MS). RESULTS: During the nine-year period between 2010 and 2019, we found new stimulants in 973 (21.1%) cases, and conventional stimulants in 658 (14.2%) cases (out of 4604 analyses -100%- of samples sent to the laboratory for toxicology screening). 594 (12.9%) of all cases were post mortem analyses. The new drugs we've detected could be classified into three groups based on their chemical structure: cathinones (in 960 from our cases), substituted phenethylamines (8), and tryptamines (5). The most frequently identified new psychoactive stimulants were (in the order of decreasing frequency): pentedrone (262), mephedrone (188), N-ethylhexedrone (126), methylenedioxypyrovalerone (MDPV; 98), α-pyrrolidinopentiophenone (alpha-PVP; 93), 4-CMC (35). CONCLUSION: The new substances were detected in highest proportion in 2011; by 2018, the number of conventional drugs exceeded the new stimulants in our cases. According to the data of the Hungarian seizures, the decrease was predictable: from 2015, the seizures of traditional stimulants exceeded the seizures of new stimulants. In 2019 the new stimulants were dominated again among the detected substances in the samples.


Assuntos
Líquidos Corporais/química , Estimulantes do Sistema Nervoso Central/análise , Crime , Usuários de Drogas/estatística & dados numéricos , Drogas Ilícitas/análise , Psicotrópicos/análise , Detecção do Abuso de Substâncias/métodos , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Hungria/epidemiologia , Espectrometria de Massas em Tandem/métodos , Fatores de Tempo
2.
Indian J Ophthalmol ; 68(10): 2103-2106, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32971617

RESUMO

Purpose: The purpose of this study is to evaluate fluid droplet spray generation during phacoemulsification (PE), pars plana vitrectomy (PPV), and fragmatome lensectomy (FL) and assess factors affecting these. Methods: This is an experimental study. PE through 2.2 and 2.8 mm incisions was performed in six goat eyes and four simulator eyes using both continuous and interrupted ultrasound (U/S). PPV and FL were performed in three goat eyes. Generation of visible fluid droplet spray was analyzed from video recordings through the microscope camera and an external digital camera. Hydroxypropylmethylcellulose (HPMC) was applied over the incision site during PE and FL. Results: When PE was performed through both incision sizes, there was no visible fluid droplet spray if the phaco tip was centered in the incision, without sleeve compression. When there was phaco tip movement with the phaco sleeve sandwiched between the tip and the incision wall, there was visible fluid droplet spray generation. It was more difficult to induce fluid droplet spray with 2.8 mm incision, and spray was lesser with interrupted U/S. During PPV, there was no droplet spray. During FL, fluid droplet spray was only seen when U/S was delivered with the fragmatome tip close to the sclerotomy. HPMC impeded droplet spray. Conclusion: Fluid droplet generation during PE can be minimized to a large extent by keeping the phaco tip centered within the incision, avoiding sleeve compression. Smaller incision and continuous U/S were more prone to droplet generation. FL should be performed away from sclerotomy. HPMC over incision is recommended.


Assuntos
Betacoronavirus , Líquidos Corporais/química , Infecções por Coronavirus/epidemiologia , Complicações Intraoperatórias , Microbolhas , Facoemulsificação/instrumentação , Pneumonia Viral/epidemiologia , Vitrectomia/instrumentação , Experimentação Animal , Animais , Infecções por Coronavirus/prevenção & controle , Cabras , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Pandemias/prevenção & controle , Fotografação , Pneumonia Viral/prevenção & controle , Gravação em Vídeo
3.
Nat Commun ; 11(1): 4774, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963224

RESUMO

Detection of microbial nucleic acids in body fluids has become the preferred method for rapid diagnosis of many infectious diseases. However, culture-based diagnostics that are time-consuming remain the gold standard approach in certain cases, such as sepsis. New culture-free methods are urgently needed. Here, we describe Single MOLecule Tethering or SMOLT, an amplification-free and purification-free molecular assay that can detect microorganisms in body fluids with high sensitivity without the need of culturing. The signal of SMOLT is generated by the displacement of micron-size beads tethered by DNA probes that are between 1 and 7 microns long. The molecular extension of thousands of DNA probes is determined with sub-micron precision using a robust and rapid optical approach. We demonstrate that SMOLT can detect nucleic acids directly in blood, urine and sputum at sub-femtomolar concentrations, and microorganisms in blood at 1 CFU mL-1 (colony forming unit per milliliter) threefold faster, with higher multiplexing capacity and with a more straight-forward protocol than amplified methodologies. SMOLT's clinical utility is further demonstrated by developing a multiplex assay for simultaneous detection of sepsis-causing Candida species directly in whole blood.


Assuntos
Líquidos Corporais/química , Técnicas de Diagnóstico Molecular/métodos , Ácidos Nucleicos/isolamento & purificação , Sepse/diagnóstico , Candida/genética , Candida/isolamento & purificação , Candidíase/diagnóstico , Contagem de Colônia Microbiana , Doenças Transmissíveis/diagnóstico , DNA/isolamento & purificação , Humanos , Ácidos Nucleicos/sangue , Ácidos Nucleicos/urina , Reação em Cadeia da Polimerase/métodos , RNA/isolamento & purificação , Sensibilidade e Especificidade , Sepse/microbiologia , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Urina
5.
Carbohydr Polym ; 237: 116174, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32241452

RESUMO

Hydroxyapatite-associated bacterial cellulose (BC/HA) is a promising composite for biomedical applications. However, this hybrid composite has some limitations due to its low in vivo degradability. The objective of this work was to oxidize BC and BC/HA composites for different time periods to produce 2,3 dialdehyde cellulose (DAC). The BC and oxidized BC (OxBC) membranes were mineralized to obtain the hybrid materials (BC/HA and OxBC/HA) and their physico-chemical, degradability, and bioactivity properties were studied. The results showed that OxBC/HA was more bioactive and degradable than BC/HA, which isa function of the degree of BC oxidation. High glucose levels in the BC degradation were observed as a function of oxidation degree, and other products, such as butyric acid and acetic acid resulted from DAC degradation. Therefore, this chemical modification reaction favors BC degradation, making it a good biodegradable and bioactive material with a potential for bone regeneration applications.


Assuntos
Celulose/química , Durapatita/química , Ácido Acético/química , Acetobacteraceae , Líquidos Corporais/química , Regeneração Óssea , Ácido Butírico/química , Glucose/química , Oxirredução , Engenharia Tecidual
6.
BMC Infect Dis ; 20(1): 301, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321418

RESUMO

BACKGROUND: In Ghana, pre-school-aged children (PSAC) are at risk of intestinal schistosomiasis and are living in need of praziquantel treatment. To better assess the infection burden within this vulnerable demographic group, we have provided a comparative assessment of the prevalence of Schistosoma mansoni in pre-school-aged children by urine circulating cathodic antigen (CCA) dipsticks, real-time PCR Taqman® faecal assays and Kato-Katz coproscopy. METHODS: In all, 190 pre-school-aged children were sampled from three endemic communities (viz. Tomefa, Torgahkope/Adakope, and Manheam) around Weija dam, Southern Ghana. Fresh stool and urine samples were collected from all participants for diagnosis. RESULTS: Among all the three communities, the urine-CCA assay recorded the highest prevalence values of 90.5% (95% CI 80.4-96.4), 87.9% (95% CI 76.7-95), and 81.2% (95% CI 69.9-89.6) in Tomefa, Torgahkope/Adakope, and Manheam respectively. Prevalence by real-time PCR was 50% (95% CI 35.5-64.5), 8% (95% CI 2.2-19.2) and 16.7% (95% CI 8.3-28.5), while by Kato-Katz was 55.6% (95% CI 42.5-68.1), 8.6% (95% CI 2.9-19) and 11.6% (95% CI 5.1-21.6) respectively. Children aged 1 year and over were found to be positive with the urine-CCA assay; by the ages of 3-4, over 50% were urine-CCA patent. The sensitivity and specificity of the POC-CCA dipsticks, when compared against the combined results of Kato-Katz/TaqMan results was found to be 84.1% (95% CI = 72.7-92.1) and 12.9% (95% CI = 6.6-22) respectively. CONCLUSIONS: We propose that the urine-CCA dipstick may be a useful rapid diagnostic tool to estimate the prevalence of intestinal schistosomiasis in PSAC, particularly in rapid identification of at-risk areas. However, our assessment has shown that it possible to record false positives when compared to combined Kato-Katz and qPCR results. To guide PSAC praziquantel treatment needs, we propose the urine CCA assay should be included in routine surveillance of intestinal schistosomiasis alongside other diagnostics such as Kato-Katz and urine filtration.


Assuntos
Antígenos de Helmintos/urina , Testes Diagnósticos de Rotina/métodos , Fezes/parasitologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Esquistossomose mansoni/diagnóstico , Urinálise/métodos , Animais , Antígenos de Helmintos/análise , Bioensaio/métodos , Líquidos Corporais/química , Líquidos Corporais/imunologia , Líquidos Corporais/parasitologia , Pré-Escolar , Fezes/química , Feminino , Gana/epidemiologia , Humanos , Lactente , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Praziquantel/uso terapêutico , Prevalência , Schistosoma mansoni/genética , Schistosoma mansoni/imunologia , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/urina , Sensibilidade e Especificidade
7.
Environ Pollut ; 263(Pt B): 114440, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32244121

RESUMO

Tetrabromobisphenol-A (TBBPA) is an emerging organic pollutant and a commonly used brominated flame retardant that has received much attention owing to its toxicity. Although TBBPA is ubiquitously detected in atmospheric particulate matter and dust, few studies have investigated the sub-chronic inhalation exposure to TBBPA. To further understand the excretion characteristics and tissue accumulation of TBBPA after inhalation exposure, we used the rat model to conduct a sub-chronic inhalation exposure study. Male rats were administered with different doses of aerosol TBBPA (12.9, 54.6, 121.6, and 455.0 mg/m3). TBBPA was found in the excretion (feces and urine) and all the target tissues (lung, liver, heart, thymus gland, spleen, testicles, muscles, kidneys, brain and serum). Feces were the main route of excretion, which contributed 19.18% to 72.54% (urine <0.10%). TBBPA excretion through feces following inhalation administration was much higher than that following oral and dermal exposure, thereby indicating lower bioavailability of TBBPA under inhalation exposure. Liver and serum showed higher levels of TBBPA compared with those of other tissues, thereby suggesting tissue-specific accumulation of TBBPA in rats. Owing to the relative non-invasiveness of serum sampling and greatest TBBPA concentration among the tissues, serum is a suitable matrix for estimation of TBBPA bioaccumulation after inhalation exposure.


Assuntos
Líquidos Corporais/química , Retardadores de Chama , Bifenil Polibromatos/análise , Animais , Disponibilidade Biológica , Fezes/química , Exposição por Inalação , Masculino , Ratos
8.
PLoS One ; 15(4): e0230610, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32240188

RESUMO

BACKGROUND: The development of rK39-based immunochromatographic rapid diagnostic tests represents an important advance for serodiagnosis of visceral leishmaniasis, being cheap and easy to use at the point of care (POC). Although the use of rK39 have considerably improved the sensitivity and specificity of serological tests compared with total antigens, great variability in sensitivity and specificity was reported. This study aimed at the evaluation of "Kalazar Detect™ Rapid Test, Whole Blood" (Kalazar Detect RDT) for Visceral Leishmaniasis (VL) diagnosis using oral fluid, whole blood and serum specimens collected at different endemic areas of VL of Brazil. METHODOLOGY: To evaluate Kalazar Detect RDT, oral fluid, whole blood and serum specimens from 128 VL patients, 85 healthy individuals, 22 patients with possible cross-reactivity diseases and 20 VL/aids coinfected patients were collected and assayed at the POC. PRINCIPAL FINDINGS AND CONCLUSIONS: The performance of Kalazar Detect RDT in whole blood and serum was similar; however, using oral fluid, the sensitivity was low. Particularly in samples from the city of Natal, Rio Grande do Norte state in Northeastern Brazil, we observed low sensitivity, 80.0% (95% CI: 62.7-90.5), using whole blood and serum, and poor sensitivity, 43.3% (95% CI: 27.4-60.8) with oral fluid. Those values were much lower than in the other regions, where sensitivity ranged from 92.7-96.3% in whole blood and serum, and 80.0-88.9% in oral fluid. Besides, in VL/aids coinfected patients, lower sensitivity was achieved compared with VL patients. In samples from Natal, the sensitivity was 0.0% (95% CI: 0.0-49.0) and 25.0% (95% CI: 4.6-69.9), using oral fluid and serum/whole blood, respectively; in samples from the other regions, the sensitivity ranged from 40.0-63.6% and 80.0-81.8%, respectively. As for specificity, high values were observed across the fluids, 100.0% (95% CI: 96.5-100.0) in whole blood, 96.3% (95% CI: 90.8-98.5) in serum, and 95.3% (95% CI: 89.5-98.0) in oral fluid; across localities, specificity ranged from 85.7-100.0%. Serum samples sent by the collaborating centers to Instituto de Medicina Tropical (n = 250) were tested by Kalazar Detect RDT, Direct Agglutination Test, Indirect immunofluorescence assay, Enzyme-linked immunosorbent assay, and IT-Leish® RDT. The regional difference in the performance of rK39-based RDT and lower sensitivity in Leishmania/HIV coinfected patients raise concern on the routine use of these products for the diagnosis of VL.


Assuntos
Líquidos Corporais/química , Cromatografia de Afinidade/métodos , Testes Diagnósticos de Rotina/métodos , Leishmania/isolamento & purificação , Leishmaniose Visceral/diagnóstico , Proteínas de Protozoários/imunologia , Testes Sorológicos/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Lactente , Leishmaniose Visceral/sangue , Leishmaniose Visceral/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistemas Automatizados de Assistência Junto ao Leito , Adulto Jovem
9.
Artigo em Inglês | MEDLINE | ID: mdl-32247187

RESUMO

Different methods have been used for CYP3A phenotyping, such as probe drugs or the urinary index 6ß-hydroxycortisol/cortisol ratio (6ß-OHF:C). This work describes a simple and affordable method for the simultaneous determination of the endogenous compounds cortisol and 6ß-hydroxycortisol in urine using a background subtraction approach. The method was applied to investigate the CYP3A activity in HIV-infected pregnant women (n = 9) in the third trimester and postpartum periods. Also, the within-day variability in the 6ß-OHF:C index was also evaluated. The sample preparation consists of a pre-cleanup with acetonitrile followed by liquid-liquid extraction with ethyl acetate. The analytes were resolved by employing an Acquity UPLC®BEH C18 column with a mobile phase that consisted of a mixture of acetonitrile containing 0.1% formic acid and 0.1% formic acid in gradient mode. The method presented linearities of 1-1.000 ng/mL and 2-1.000 ng/mL for C and 6ß-OHF, respectively, and presented acceptable precision and accuracy. Qualitative and quantitative matrix effects tests were also performed. A high 6ß-OHF:C within-day variability was observed in both phases. In the third trimester period, the 6ß-OHF:C ranged from 2.57 to 51.69, with a mean ± standard deviation (SD) of 15.12 ± 5.41 (n = 9). Similar values were obtained in the postpartum period, with 6ß-OHF:C ranging from 3.48 to 44.54 with a mean ± SD of 14.37 ± 5.73 (n = 7). Even though the 6ß-OHF:C is a non-invasive index for CYP3A phenotyping, its use is susceptible to high within-day variability.


Assuntos
Citocromo P-450 CYP3A/classificação , Hidrocortisona/análogos & derivados , Hidrocortisona/urina , Adulto , Líquidos Corporais/química , Cromatografia Líquida de Alta Pressão , Feminino , Infecções por HIV , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/metabolismo , Limite de Detecção , Extração Líquido-Líquido , Fenótipo , Gravidez , Espectrometria de Massas em Tandem , Fatores de Tempo
10.
Mikrochim Acta ; 187(4): 208, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152752

RESUMO

A nanocurcumin (NCur)-VO2+ ensemble-based optical nanoprobe is proposed for monitoring of human serum albumin (HSA) and transferrin (TF) in biofluids of serum and urine. The determination strategy of HSA and TF is based on the decrease of the absorbance/color intensity of NCur in the presence of VO2+ due to the formation of NCur-VO2+ ensemble. This leads to aggregation of the NCur and the color change of solution from orange to pale pink. Upon addition of HSA or TF, release of VO2+ from NCur-VO2+ ensemble occurs due to their stronger binding affinities to VO2+ in competition with the NCur. This leads to deaggregation of the NCur and recovery of the decreased absorption/color intensity within a defined time range. The absorption changes at λ = 455 and the color of NCur solution can be monitored spectrophotometrically or visually by a smartphone camera, respectively. Under optimal conditions, the analytical signals increase linearly in the ranges 50-200 nM (LOD = 11 nM) and 20-140 nM (LOD = 8 nM) for HSA and TF, respectively. The difference in the different affinities between the HSA and the TF for binding to VO2+ produces the unique time profiles of each protein. Therefore, the simultaneous determination of HSA and TF is provided by using the least-square support-vector machine (LS-SVM) model. The good recoveries and small errors of predicted values suggest that the nanoprobe is capable to resolve binary mixtures of HSA and TF. The method was applied to the simultaneous determination of HSA and TF in serum and urine samples. Graphical abstract.


Assuntos
Líquidos Corporais/química , Nanopartículas/química , Albumina Sérica Humana/análise , Transferrina/análise , Curcumina/química , Humanos , Modelos Moleculares , Fenômenos Ópticos , Software , Espectrofotometria , Ultrassom , Vanadatos/química
11.
Subcell Biochem ; 94: 1-34, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189294

RESUMO

The coelomic cavity is part of the main body plan of annelids. This fluid filled space takes up a considerable volume of the body and serves as an important site of exchange of both metabolites and proteins. In addition to low molecular substances such as amino acids and glucose and lactate, the coelomic fluid contains different proteins that can arise through release from adjacent tissues (intestine) or from secretion by coelomic cells. In this chapter, we will review the current knowledge about the proteins in the annelid coelomic fluid. Given the number of more than 20,000 extant annelid species, existing studies are confined to a relatively few species. Most studies on the oligochaetes are confined to the earthworms-clearly because of their important role in soil biology. In the polychaetes (which might represent a paraphyletic group) on the other hand, studies have focused on a few species of the Nereidid family. The proteins present in the coelomic fluid serve different functions and these have been studied in different taxonomic groups. In oligochaetes, proteins involved antibacterial defense such as lysenin and fetidin have received much attention in past and ongoing studies. In polychaetes, in contrast, proteins involved in vitellogenesis and reproduction, and the vitellogenic function of coelomic cells have been investigated in more detail. The metal binding metallothioneins as well as antimicrobial peptides, have been investigated in both oligochaetes and polychaetes. In the light of the literature available, this review will focus on lipoproteins, especially vitellogenin, and proteins involved in defense reactions. Other annelid groups such as the Pogonophora, Echiura, and Sipuncula (now considered polychaetes), have not received much attention and therefore, this overview is far from being complete.


Assuntos
Anelídeos/anatomia & histologia , Anelídeos/química , Líquidos Corporais/química , Proteínas/metabolismo , Animais , Anelídeos/classificação , Oligoquetos/anatomia & histologia , Oligoquetos/química , Oligoquetos/metabolismo , Proteínas/classificação
12.
Parasit Vectors ; 13(1): 136, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171305

RESUMO

Hookworm infection is a major public health problem that threatens about 500 million people throughout tropical areas of the world. Adult hookworms survive for many years in the host intestine, where they suck blood, causing iron deficiency anemia and malnutrition. Numerous molecules, named excretory/secretory (ES) products, are secreted by hookworm adults and/or larvae to aid in parasite survival and pathobiology. Although the molecular cloning and characterization of hookworm ES products began 25 years ago, the biological role and molecular nature of many of them are still unclear. Hookworm ES products, with distinct structures and functions, have been linked to many essential events in the disease pathogenesis. These events include host invasion and tissue migration, parasite nourishment and reproduction, and immune modulation. Several of these products represent promising vaccine targets for controlling hookworm disease and therapeutic targets for many inflammatory diseases. This review aims to summarize our present knowledge about hookworm ES products, including their role in parasite biology, host-parasite interactions, and as vaccine and pharmaceutical targets and to identify research gaps and future research directions in this field.


Assuntos
Ancylostomatoidea/imunologia , Líquidos Corporais/imunologia , Infecções por Uncinaria/imunologia , Infecções por Uncinaria/parasitologia , Interações Hospedeiro-Parasita/imunologia , Ancylostoma , Ancylostomatoidea/metabolismo , Animais , Antioxidantes , Líquidos Corporais/química , Clonagem Molecular , Feminino , Proteínas de Helminto/imunologia , Infecções por Uncinaria/prevenção & controle , Infecções por Uncinaria/terapia , Humanos , Fatores Imunológicos , Masculino , Peptídeo Hidrolases , Inibidores de Proteases , Vacinas/imunologia
13.
Anal Bioanal Chem ; 412(7): 1469-1481, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32034456

RESUMO

Due to their omnipresence in consumer products, there is a growing concern about the potential effects of nanoparticles on human health. Toxicological assessment and NP end-product studies require proper quantification of these materials in biological fluids. However, their quantifications in these media require stable predispersed NP solutions in aqueous media to enable the fortification in the matrices of interest or the preparation of calibration standards. In this study, a sample preparation scheme was developed by studying various dispersion media (polyvinylpyrrolidone and polyethylene glycol) and sonication strategies (bath and ultrasonic probe) to ensure homogeneous dispersion of titanium dioxide nanoparticles. Optimization of the various parameters was performed using SRM NIST 1898 NP reference material, composed of rutile and anatase phases. Number-based size distribution for titanium dioxide NPs was determined by dynamic light scattering and single-particle inductively coupled plasma mass spectrometry to evaluate the procedure efficiency. Changes in mean size and most frequent size distribution were also studied to determine if the agglomeration of nanoparticles occurs at the various dispersion conditions tested. Among the different dispersion parameters tested herein, the use of polyvinylpyrrolidone combined with a sonication process generated by a probe leads to a significant improvement in terms of suspension efficiency and stability over 72 h. The dispersion efficiency of the proposed methodology was assessed by single-particle inductively coupled plasma mass spectrometry with spiked biological fluids such as urine and blood. Graphical abstract.


Assuntos
Líquidos Corporais/química , Nanopartículas Metálicas/química , Titânio/química , Humanos , Nanopartículas Metálicas/normas , Padrões de Referência , Titânio/normas , Água
14.
Xenobiotica ; 50(8): 947-956, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32105166

RESUMO

Cenerimod is a sphingosine-1-phosphate 1 receptor modulator under development for treatment of systemic lupus erythematosus.This single-centre, open-label, single-dose study investigated the mass balance and excretion routes and aimed at identifying and quantifying cenerimod metabolites in plasma, urine, and faeces after oral administration of 2 mg/100 µCi (3.7 MBq) of 14C-cenerimod.Total mean cumulative recovery was 84% of the administered dose (58-100% in faeces and 4.6-12% in urine). In a 0-504 h cross-subject area under the curve plasma pool, cenerimod and two metabolites were detected accounting for 78, 6.0, and 4.9% of total radioactivity, respectively, i.e. no major metabolite was identified in plasma. Cenerimod was only detected in faeces and accounted for 17% of the radioactivity excreted in this matrix. The metabolite M32 was detected in both urine and faeces and represented 23% and 66% of radioactivity excreted in these matrices, respectively. Other metabolites of unknown structure were detected in small amounts. Overall, M32 and cenerimod accounted for 52% and 13%, respectively, of the total radioactivity recovered.Among the excreted metabolites, only the non-enzymatically formed M32 represented more than 25% of total drug-related material. Therefore, no pharmacokinetic drug-drug interaction studies are foreseen.


Assuntos
Oxidiazóis/farmacocinética , Propilenoglicóis/farmacocinética , Receptores de Esfingosina-1-Fosfato/antagonistas & inibidores , Administração Oral , Líquidos Corporais/química , Voluntários Saudáveis , Humanos , Oxidiazóis/administração & dosagem , Propilenoglicóis/administração & dosagem
15.
Ann Biol Clin (Paris) ; 78(1): 93-107, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32108587

RESUMO

The measurement performance of 13 biochemistry parameters (CEA, CA 19-9, amylase, lipase, sodium, potassium, chloride, creatinine, glucose, protein, albumin, LDH, triglycerides) was tested in a panel of biological fluids other than blood and urine (peritoneal, pleural, pancreatic fluids ...). Our protocol, based on a risk analysis, allowed us to justify our choices and compare the performance obtained with those of the serum or plasma matrix already validated. Thus, the coefficients of variation obtained in body fluids are comparable. The assessment of accuracy (spiking and dilution tests) shows the absence of bias, which is consistent with the absence of matrix effect. The linearity studied by dilution tests shows that the upper limits of the measurement interval communicated by the supplier are applicable to body fluids. The absence of contamination and stability have been also confirmed. All analytes are stable for 3 days at room temperature, 7 days between 2 and 8̊C, and 6 months at -20̊C; except LDH and lipase. For most analytes, at least one interference (hemolysis, icterus, lipemia) was found. Finally, a bibliographical study, confronted with the experience of prescribers, led us to define optimal thresholds to help interpret patients' results. In conclusion, this work has allowed us to validate analytical methods for body fluids testing after relying on their comparability to the blood matrix. We have also been able to adapt our practices and finally be accredited according to the standard NF IN ISO 15189.


Assuntos
Biomarcadores/análise , Líquidos Corporais/química , Técnicas de Laboratório Clínico , Albuminas/análise , Albuminas/metabolismo , Amilases/análise , Amilases/metabolismo , Biomarcadores/metabolismo , Líquidos Corporais/metabolismo , Antígeno CA-19-9/análise , Antígeno CA-19-9/metabolismo , Antígeno Carcinoembrionário/análise , Antígeno Carcinoembrionário/metabolismo , Cloretos/análise , Cloretos/metabolismo , Técnicas de Laboratório Clínico/métodos , Técnicas de Laboratório Clínico/normas , Creatinina/análise , Creatinina/metabolismo , Glucose/análise , Glucose/metabolismo , Humanos , L-Lactato Desidrogenase/análise , L-Lactato Desidrogenase/metabolismo , Lipase/análise , Lipase/metabolismo , Potássio/análise , Potássio/metabolismo , Proteínas/análise , Proteínas/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sódio/análise , Sódio/metabolismo , Temperatura , Triglicerídeos/análise , Triglicerídeos/metabolismo
16.
Int J Legal Med ; 134(2): 473-485, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31989244

RESUMO

Biological traces found at crime scenes are analysed not only to genetically identify the donor(s) but also to determine the composition of the stain. For some cases, it is essential to associate a body fluid with a donor. Especially in mixed body fluid stains, but also in body fluid stains that appear to be single-source, this may be of importance. Linking a DNA profile (sub-source level) with evidence from a presumptive test or mRNA analysis (source level) is not straightforward. Our results support that associating donors and body fluids by means of comparing mixture ratios in RNA and DNA is not recommended. We introduce a set of 35 coding region SNPs (cSNPs) in body fluid-specific mRNA transcripts that represent a direct link between the body fluids and their donors. The discrimination power of the cSNPs was estimated based on allele frequencies calculated from a population sample (n = 188), and we investigated the practical application of the cSNPs in different scenarios. The results demonstrate that more cSNPs are needed to improve the discrimination power. However, the findings are promising as we were able to associate donors with body fluids in mixtures of different body fluids as well as in stains where both donors have contributed the same body fluid, e.g. a blood-blood mixture. In addition, the cSNP assay can be used for body fluid identification. The results of this proof-of-concept study support the use of cSNPs to assign body fluids to the respective donors.


Assuntos
Líquidos Corporais/química , Genética Forense/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/genética , Feminino , Humanos , Masculino , Estudo de Prova de Conceito , Análise de Sequência de DNA , Análise de Sequência de RNA
17.
Pharm Res ; 37(3): 42, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31989335

RESUMO

PURPOSE: The design of biorelevant conditions for in vitro evaluation of orally administered drug products is contingent on obtaining accurate values for physiologically relevant parameters such as pH, buffer capacity and bile salt concentrations in upper gastrointestinal fluids. METHODS: The impact of sample handling on the measurement of pH and buffer capacity of aspirates from the upper gastrointestinal tract was evaluated, with a focus on centrifugation and freeze-thaw cycling as factors that can influence results. Since bicarbonate is a key buffer system in the fasted state and is used to represent conditions in the upper intestine in vitro, variations on sample handling were also investigated for bicarbonate-based buffers prepared in the laboratory. RESULTS: Centrifugation and freezing significantly increase pH and decrease buffer capacity in samples obtained by aspiration from the upper gastrointestinal tract in the fasted state and in bicarbonate buffers prepared in vitro. Comparison of data suggested that the buffer system in the small intestine does not derive exclusively from bicarbonates. CONCLUSIONS: Measurement of both pH and buffer capacity immediately after aspiration are strongly recommended as "best practice" and should be adopted as the standard procedure for measuring pH and buffer capacity in aspirates from the gastrointestinal tract. Only data obtained in this way provide a valid basis for setting the physiological parameters in physiologically based pharmacokinetic models.


Assuntos
Bicarbonatos/química , Ácidos e Sais Biliares/química , Líquidos Corporais/química , Líquidos Corporais/metabolismo , Trato Gastrointestinal Superior/química , Trato Gastrointestinal Superior/metabolismo , Tampões (Química) , Famotidina/administração & dosagem , Famotidina/metabolismo , Absorção Gastrointestinal , Humanos , Concentração de Íons de Hidrogênio , Ibuprofeno/administração & dosagem , Ibuprofeno/metabolismo , Intestino Delgado , Sais/química , Estômago
18.
Food Chem ; 313: 126155, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31945701

RESUMO

The illegal use of ß-agonists often endangers animal-derived food safety. In this study, a selective detection method for ß-agonists in swine urine was established via the combination of polymeric ionic liquid-molecularly imprinted graphene oxide-miniaturized pipette tip solid-phase extraction and high-performance liquid chromatography. It is worth noting that this method relied mainly on the designed adsorbent, which presented a rich adsorption mechanism, fast mass transfer rate, and high selectivity, and was successfully utilized in the selective extraction of ß-agonists from swine urine samples. The proposed method has low LOD (0.20-0.56 ng/mL), high recovery (94.9-107.9%), and high reusability (4 times, 91.9-108.8%), which indicates its high potential as a selective, sensitive, accurate, and nonfatal method for monitoring the illegal use of ß-agonists in the livestock breeding stage.


Assuntos
Agonistas Adrenérgicos beta/urina , Extração em Fase Sólida/métodos , Drogas Veterinárias/urina , Adsorção , Animais , Líquidos Corporais/química , Cruzamento , Cromatografia Líquida de Alta Pressão/métodos , Clembuterol/urina , Controle de Medicamentos e Entorpecentes , Grafite/química , Análise de Perigos e Pontos Críticos de Controle , Isoproterenol/análogos & derivados , Isoproterenol/urina , Impressão Molecular , Nanoestruturas/química , Extração em Fase Sólida/instrumentação , Suínos
19.
J Anim Sci ; 98(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31910258

RESUMO

Phytogenic actives (PA) are plant-derived natural bioactive compounds that may promote livestock health and well-being, as well as improve growth performance and production efficiency. The current study aims to evaluate their effects on sows and their offspring. Eighty-one hyperprolific sows (up to parity 7) were assigned to 3 experimental treatments. Control sows were offered a nonsupplemented diet during gestation and lactation, and treated sows were fed the control diet supplemented with 1 g/kg of a blend of PA (BPA) in lactation (L) or during gestation and lactation (GL). An evaluation was made of placental and milk maternal transfer of these BPA and colostrum-milk features, sows and piglets antioxidant status, reproductive performance (litter size), body weight (BW) changes, weaning-estrus interval, and litter performance. Finally, piglet´s jejunum gene expression was measured. The BPA supplementation during gestation (GL) increased the number of piglets born alive (P = 0.020) and reduced (P < 0.05) the newborn piglets BW, while there were no differences among treatments on the suckling (day 20) and weaned (day 7) piglets BW (P > 0.05). Dietary phytogenic volatile compounds reached GL placental fluid, and milk of L and GL sows (P < 0.05). Moreover, colostrum protein in GL and milk fat content in L and GL were increased (P < 0.05). Milk of GL showed inhibitory activity against Bacillus subtilis and Staphylococcus aureus (P < 0.05). Antioxidant status of GL sows showed an enhanced (P < 0.05) of catalase (CAT) and total antioxidant capacity levels at early gestation (day 35), whereas higher levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes at late gestation (day 110). Likewise, GL newborn piglets showed higher CAT levels, whereas both CAT and SOD levels in suckling piglets, as well as CAT, SOD, and GSH-Px in weaned piglets, were increased in L and GL (P < 0.05). Jejunum messenger ribonucleic acid abundance of suckling piglets in L and GL groups showed overexpression of barrier function MUC2, digestive enzyme IDO, and immune response PPARGC-α, TNF-α, TGF-ß1, and IL-10 genes (P < 0.05). In conclusion, dietary BPA supplementation in hyperprolific sows increased the litter size (born alive) and improved the composition and bioactivity of colostrum and milk, besides, modified the antioxidant status of sows and their offspring, as well as the suckling piglets gut health gene expression. Several BPA volatile compounds were prenatal and postnatal maternally transferred (placental fluid and milk).


Assuntos
Ração Animal , Colostro/química , Suplementos Nutricionais , Leite/química , Suínos/fisiologia , Ração Animal/análise , Animais , Animais Recém-Nascidos/fisiologia , Animais Lactentes/fisiologia , Antioxidantes/análise , Líquidos Corporais/química , Catalase/metabolismo , Colostro/metabolismo , Dieta/veterinária , Feminino , Expressão Gênica , Glutationa Peroxidase/metabolismo , Jejuno/enzimologia , Jejuno/metabolismo , Lactação/fisiologia , Tamanho da Ninhada de Vivíparos , Leite/metabolismo , Paridade , Gravidez , Desmame
20.
Methods Mol Biol ; 2102: 163-176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31989554

RESUMO

Two-dimensional difference gel electrophoresis (2D-DIGE) remains to be one of the most popular and versatile methods of protein separation among many proteomics technologies. Similar to traditional two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), the proteins are separated based on their charges and molecular weight by 2D-DIGE. Different from 2D-PAGE, proteins are pre-labeled with different fluorescent dyes, and different protein samples are run in one gel by this method. Therefore, 2D-DIGE not only carries the advantages of 2D-PAGE but also eliminates gel-to-gel variation and achieves high resolution, sensitivity, and reproducibility.


Assuntos
Proteoma/análise , Proteômica/métodos , Eletroforese em Gel Diferencial Bidimensional/métodos , Líquidos Corporais/química , Células Cultivadas , Eletroforese em Gel de Poliacrilamida , Corantes Fluorescentes , Humanos , Proteínas/análise , Proteínas/isolamento & purificação , Reprodutibilidade dos Testes , Fluxo de Trabalho
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