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1.
Ecotoxicol Environ Saf ; 204: 110965, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32798747

RESUMO

Toxic and essential trace elements are associated with human fertility. However, limited studies have been conducted on the relationship between trace elements and in vitro fertilization (IVF) outcomes in the Chinese population. In this exploratory study, 103 couples who underwent IVF/intracytoplasmic sperm injection (ICSI) treatment in our reproductive center were recruited. Serum and follicular fluid (FF) samples and seminal plasma samples were collected from the female and male partners, respectively, on the day of oocyte retrieval. Concentrations of chromium (Cr), nickel (Ni), arsenic (As), selenium (Se), cadmium (Cd), and lead (Pb) in the specimens were measured by inductively coupled plasma-mass spectrometry. Generalized linear models were used to evaluate the associations of toxic and essential trace element levels with the intermediate parameters and outcomes of IVF at both the sex-specific and couple levels. The Cr level in the serum of the female partners was inversely associated with the count of mature oocytes retrieved (p for trend = 0.033). In terms of embryo development, As concentrations in female serum and FF were inversely associated with the probabilities to obtain good-quality cleavage embryos (p for trend < 0.01). There were significant correlations between follicular Se concentrations and seminal As concentrations and higher quality cleavage embryos (p for trend < 0.01). Moreover, a positive correlation was observed between the female serum Se concentrations and blastocyst formation (p for trend = 0.031). In contrast, a higher follicular Se level was negatively correlated with embryo development at the blastocyst stage (p for trend < 0.01). Regarding the clinical outcomes, a positive association of Se levels in seminal plasma and a negative association of follicular Cd levels was observed with the probabilities of pregnancy (p for trend = 0.006 and 0.035, respectively) and live birth (p for trend = 0.014 and 0.027, respectively). The results indicate that exposure to toxic elements (Cr, As and Cd) is associated with intermediate parameters and outcomes of IVF. Furthermore, male Se exposure may be related to better pregnancy outcomes.


Assuntos
Poluentes Ambientais/metabolismo , Líquido Folicular/química , Sêmen/química , Soro/química , Oligoelementos/metabolismo , Adulto , Poluentes Ambientais/sangue , Feminino , Fertilização In Vitro , Humanos , Masculino , Oligoelementos/sangue , Adulto Jovem
2.
Environ Toxicol ; 35(12): 1395-1405, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32790152

RESUMO

Per- and polyfluoroalkyl substances (PFAS), a class of environmental contaminants, have been detected in human placenta and cord blood. The mechanisms driving PFAS-induced effects on the placenta and adverse pregnancy outcomes are not well understood. This study investigated the impact of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and a replacement PFAS known as hexafluoropropylene oxide dimer acid (HFPO-DA, tradename GenX) on placental trophoblasts in vitro. Several key factors were addressed. First, PFAS levels in cell culture reagents at baseline were quantified. Second, the role of supplemental media serum in intracellular accumulation of PFAS in a human trophoblast (JEG3) cell line was established. Finally, the impact of PFAS on the expression of 96 genes involved in proper placental function in JEG3 cells was evaluated. The results revealed that serum-free media (SFM) contained no detectable PFAS. In contrast, fetal bovine serum-supplemented media (SSM) contained PFNA, PFUdA, PFTrDA, and 6:2 FTS, but these PFAS were not detected internally in cells. Intracellular accumulation following 24 hr treatments was significantly higher when cultured in SFM compared to SSM for PFOS and PFOA, but not HFPO-DA. Treatment with PFAS was associated with gene expression changes (n = 32) in pathways vital to placental function, including viability, syncytialization, inflammation, transport, and invasion/mesenchymal transition. Among the most robust PFAS-associated changes were those observed in the known apoptosis-related genes, BAD and BAX. These results suggest a complex relationship between PFAS, in vitro culture conditions, and altered expression of key genes necessary for proper placentation.


Assuntos
Ácidos Alcanossulfônicos/toxicidade , Caprilatos/toxicidade , Fluorcarbonetos/toxicidade , Expressão Gênica/efeitos dos fármacos , Placenta/efeitos dos fármacos , Soro/química , Trofoblastos/efeitos dos fármacos , Ácidos Alcanossulfônicos/sangue , Ácidos Alcanossulfônicos/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Bioacumulação/efeitos dos fármacos , Bioacumulação/genética , Caprilatos/sangue , Caprilatos/metabolismo , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Meios de Cultura Livres de Soro , Feminino , Fluorcarbonetos/sangue , Fluorcarbonetos/metabolismo , Humanos , Placenta/metabolismo , Gravidez , RNA Mensageiro/genética , Trofoblastos/metabolismo
3.
Environ Pollut ; 266(Pt 1): 115051, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32640408

RESUMO

Recent research suggests contaminants of emerging concern (CECs) are widespread and environmentally relevant concentrations can impact fishes. However, little is known about impacts of CECs to long-lived or rare species. The objective of this study was to characterize CEC concentrations in lake sturgeon (Acipenser fulvescens) serum and gametes. Blood serum was collected non-lethally from lake sturgeon at four lower Great Lakes basin sites: Detroit, upper Niagara, lower Niagara, and St. Lawrence rivers; additionally, gametes were collected from lake sturgeon in the St. Lawrence River. Samples were analyzed for pharmaceuticals and personal care products (PPCPs) and polybrominated diphenyl ethers (PBDEs). Overall, 44 different PPCPs were identified in serum and gamete samples across sites, with 22 PPCPs identified in at least 25% of serum samples and three PPCPs identified in 25% of gamete samples. PPCP concentrations in serum and gametes ranged from 0.00208 to 130 ppb and 0.00538-190 ppb, respectively. NMDS ordination revealed differences in the presence and concentrations of PPCPs in lake sturgeon serum across sites, however, N,N-diethyl-meta-toluamide (DEET), hydrocortisone, benztropine, and amitriptyline were detected in at least one serum sample at all sites. Additionally, DEET, 10-hydroxy-amitriptyline, and sertraline were detected in ≥25% of gamete samples collected from the St. Lawrence River. Twenty-six PBDE congeners were identified in 25% of serum samples and 24 were identified in 25% of gamete samples. PBDEs in serum were present across all sites and in gametes of St. Lawrence River lake sturgeon, and total PBDE concentrations in serum and gametes ranged from 0.184 to 12.7 ppb and 0.0826-0.44 ppb, respectively. Managers of lake sturgeon populations may need to consider the impacts of CECs if reproductive, developmental, behavioral, growth effects, or mortality are observed in the Great Lakes basin or other areas that are impacted by increased exposures to PPCPs and PBDEs.


Assuntos
Cosméticos , Poluentes Químicos da Água/análise , Animais , Monitoramento Ambiental , Peixes , Células Germinativas , Éteres Difenil Halogenados/análise , Lagos , Soro/química
4.
Nat Commun ; 11(1): 3186, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32581242

RESUMO

Mass spectrometry based metabolomics is a widely used approach in biomedical research. However, current methods coupling mass spectrometry with chromatography are time-consuming and not suitable for high-throughput analysis of thousands of samples. An alternative approach is flow-injection mass spectrometry (FI-MS) in which samples are directly injected to the ionization source. Here, we show that the sensitivity of Orbitrap FI-MS metabolomics methods is limited by ion competition effect. We describe an approach for overcoming this effect by analyzing the distribution of ion m/z values and computationally determining a series of optimal scan ranges. This enables reproducible detection of ~9,000 and ~10,000 m/z features in metabolomics and lipidomics analysis of serum samples, respectively, with a sample scan time of ~15 s and duty time of ~30 s; a ~50% increase versus current spectral-stitching FI-MS. This approach facilitates high-throughput metabolomics for a variety of applications, including biomarker discovery and functional genomics screens.


Assuntos
Análise de Injeção de Fluxo/métodos , Espectrometria de Massas/métodos , Metabolômica/métodos , Linhagem Celular Tumoral , Análise de Injeção de Fluxo/normas , Ensaios de Triagem em Larga Escala , Humanos , Íons/química , Lipidômica/métodos , Espectrometria de Massas/normas , Metabolômica/normas , Soro/química , Soro/metabolismo
5.
J Vet Sci ; 21(3): e45, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32476319

RESUMO

BACKGROUND: Feline mammary carcinoma is the third most common cancer that affects female cats. OBJECTIVES: The purpose of this study was to screen differential serum proteins in feline and clarify the relationship between them and the occurrence of feline mammary carcinoma. METHODS: Chinese pastoral cats were used as experimental animals. Six serum samples from cats with mammary carcinoma (group T) and six serum samples from healthy cats (group C) were selected. Differential protein analysis was performed using a Label-free technique, while parallel reaction monitoring (PRM) was performed to verify the screened differential proteins. RESULTS: A total of 82 differential proteins were detected between group T and group C, of which 55 proteins were down regulated and 27 proteins were up regulated. Apolipoprotein A-I, Apolipoprotein A-II (ApoA-II), Apolipoprotein B (ApoB), Apolipoprotein C-III (ApoC-III), coagulation factor V, coagulation factor X, C1q, albumen (ALB) were all associated with the occurrence of feline mammary carcinoma. Differential proteins were involved in a total of 40 signaling pathways, among which the metabolic pathways associated with feline mammary carcinoma were the complement and coagulation cascade and cholesterol metabolism. According to the Label-free results, ApoB, ApoC-III, ApoA-II, FN1, an uncharacterized protein, and ALB were selected for PRM target verification. The results were consistent with the trend of the label-free. CONCLUSIONS: This experimen is the first to confirm ApoA-II and ApoB maybe new feline mammary carcinoma biomarkers and to analyze their mechanisms in the development of such carcinoma in feline.


Assuntos
Proteínas Sanguíneas/análise , Carcinoma/veterinária , Doenças do Gato/sangue , Neoplasias Mamárias Animais/sangue , Proteoma/análise , Animais , Carcinoma/sangue , Gatos , Feminino , Proteômica , Soro/química
6.
Anim Sci J ; 91(1): e13388, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578273

RESUMO

Serum-based biomarkers hold propitious applications for addressing livestock health, and management. However, discovery of protein biomarkers in complex biological fluids like serum is wholly intractable due to the large dynamic range of protein concentrations; that is, ˜10-12 high abundance proteins constitute >90% of the total protein content and effectively mask proteomic detection of low-abundance biomarkers. Toward addressing this limitation, we test a continuous elution size-based fractionation method, and two approaches that use affinity interaction-based separation of proteins in preparing bovine serum, and compare liquid chromatography tandem mass spectrometry protein identification to neat serum. Our results identify the high-abundance proteins in bovine serum, and demonstrate dynamic range compression and improved protein identification with the different enrichment methods. Although these findings indicate the highest protein number identified in bovine serum (445 proteins, all methods combined), and by any single sample processing method (312 proteins) to date, they still remain lower than levels deemed necessary for biomarker discovery. As such, this investigation revealed limitations to resolving the bovine serum proteome, and the need for species-specific tools for immunodepleting high-abundance proteins. In concert, this study represents a step toward advancing sample preparation methods for bovine serum biomarker identification.


Assuntos
Proteínas Sanguíneas/análise , Fracionamento Químico/métodos , Cromatografia Líquida/métodos , Proteoma/análise , Soro/química , Espectrometria de Massas em Tandem/métodos , Animais , Biomarcadores/sangue , Bovinos , Feminino , Manejo de Espécimes/métodos
7.
Complement Ther Med ; 51: 102453, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32507419

RESUMO

OBJECTIVES: There is a growing body of evidence supporting the role of whole-body cryostimulation (WBC) and sauna - bathing as treatments for relaxation, mental well-being and several health problems. Despite their polar opposite temperatures, both of these treatments come with a dose of similar health benefits. This study is designed to compare effects of WBC and sauna application on the athletes' response to exercise. DESIGN: The blood samples were collected from 10 professional cross-country skiers at four stages: before exercise, after exercise, at 1-h recovery and after 24 h of rest in sessions before and after 10 thermal treatments. Differential scanning calorimetry (DSC) was used to examine the process of serum denaturation. The parameters of endothermic transition were compared at various stages of each exercise session. RESULTS: Post-exercise changes in DSC profiles of athlete's blood serum are similar in character but clearly stronger in the session held after sauna treatments and slightly weaker after WBC than those in the session not preceded by treatments. These changes can be, at least in part, explained by the exercise induced increase in the concentration of oxidized albumin. A return of serum denaturation transition to pre-exercise shape has been observed within a few hours of rest. It suggests relatively quick restoration of a fraction of non-oxidized albumin molecules during the recovery period. CONCLUSIONS: An exercise performed by athletes after a series of sauna treatments leads to temporary greater modification of the blood serum proteome than the similar exercise during the session preceded by WBC treatments.


Assuntos
Atletas , Proteínas Sanguíneas/química , Crioterapia/métodos , Exercício Físico/fisiologia , Banho a Vapor/métodos , Adulto , Varredura Diferencial de Calorimetria , Humanos , Desnaturação Proteica , Proteoma/química , Soro/química , Esqui
8.
Curr Pharm Biotechnol ; 21(12): 1204-1212, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32297575

RESUMO

OBJECTIVES: To investigate the effect of Danggui-Shaoyao-San (DSS)-containing serum on the renal tubular Epithelial-Mesenchymal Transition (EMT) of Diabetic Nephropathy (DN) in high glucose- induced HK-2 cells and its mechanism. METHODS: 20 rats were randomly divided into four groups: blank control group, DSS low dose group (DSS-L), DSS middle dose group (DSS-M), and DSS high dose group (DSS-H). DSS was administrated to the corresponding group (7g/kg/d, 14g/kg/d and 21g/kg/d) for 7 consecutive days, and the same volume of saline was given to the blank control group by gavage. The rat drug-containing serum was successfully prepared. HK-2 cells were divided into five groups: blank control group, model group, DSS-L, DSS-M, DSS-H, according to the corresponding drug and dose of each treatment group. Protein and mRNA levels of Jagged1, Notch1, Hes5, Notch Intracellular Domain (NICD), E-cadherin, alpha- Smooth Muscle Actin (α-SMA) and vimentin at 24h, 48h and 72h were detected by Western Blot and RT-qPCR. RESULTS: The protein and mRNA levels of Jagged1, Notch1, Hes5, NICD, α-SMA and vimentin in the treatment groups were remarkably decreased compared with the model group (P<0.05), and the protein and mRNA levels of E-cadherin were notably increased (P<0.05) by Western Blot and RT-qPCR. CONCLUSION: Our results demonstrated that DSS could prevent DN by ameliorating renal tubular EMT through inhibition of the Notch signaling pathway.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Receptor Notch1/antagonistas & inibidores , Actinas/metabolismo , Animais , Antígenos CD/metabolismo , Caderinas/metabolismo , Linhagem Celular , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Células Epiteliais/metabolismo , Humanos , Proteína Jagged-1/metabolismo , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Masculino , Ratos Sprague-Dawley , Soro/química , Transdução de Sinais
9.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1440-1451, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32281359

RESUMO

The differences of transitional components and metabolic processes of Huatan Jiangqi Capsules(HTJQ) in rats under normal physiological and pathological conditions of COPD were analyzed by UPLC-Q-TOF-MS. The rat COPD model was established by passive smoking and intratracheal instillation of lipopolysaccharide. After the normal and COPD model rats were douched with HTJQ, the blood was collected from hepatic portal vein and the drug-containing serum samples were prepared by methanol precipitation of protein. Then, 10 batches of drug-containing serum samples of HTJQ were prepared and analyzed by UPLC serum fingerprint to evaluate the quality and stability of drug-containing serum samples. UPLC-Q-TOF-MS was used to collect the mass spectrometric information of the transitional components. Twenty-eight transitional components of HTJQ in normal rats and 25 transitional components of HTJQ in COPD model rats were identified by UPLC-Q-TOF-MS. Under pathological and physiological conditions, there were not only the same transitional components in rat serum, but also corresponding differences. Further studies showed that there were also differences in the metabolic process of transitional components between the two conditions. In normal rats, most of the metabolic types of transitional components were phase I reactions. In COPD model rats, phase Ⅰ reactions decreased and phase Ⅱ reactions increased correspondingly. With UPLC-Q-TOF-MS technology, the differences of transitional components and the metabolism process of HTJQ in rats under normal physiological and pathological conditions were analyzed. The results showed that types of transitional components and the activity of some metabolic enzymes would be changed in COPD pathological state, which would affect the metabolic process of bioactive components in vivo. It laid a foundation for further elucidating the metabolic process and pharmacodynamic substance basis of HTJQ.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Soro/química , Animais , Cápsulas , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Ratos
10.
Res Vet Sci ; 130: 59-67, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32145458

RESUMO

Folate (vitamin B9) and cobalamin (vitamin B12) play an important role in amino acid metabolism, nucleic acid synthesis, and methyl group transfer. Two intracellular enzymes, methionine synthase and methylmalonyl-CoA mutase, are folate and/or cobalamin-dependent, respectively. At the cellular level, a lack of folate and cobalamin leads to accumulation of serum homocysteine (HCY) and a lack of cobalamin leads to increased methylmalonic acid (MMA) concentrations. Altered serum HCY and MMA concentrations can influence amino acid metabolism and nucleic acid synthesis in pigs. Therefore, we aimed to evaluate serum folate, cobalamin, HCY, and MMA concentrations in postweaning pigs between 6 and 26 weeks of age. Serum samples from 12 pigs collected at week 6, 7, 8, 9, 10, 14, 18, 22, and 26 as part of an unrelated study were analyzed. Serum folate (p < .0001), cobalamin (p = .0001), HCY (p < .0001), and MMA (p < .0001) concentrations differed significantly during the postweaning period between 6 and 26 weeks of age; with significantly higher serum HCY (at weeks 6 and 7 compared to weeks 9, 14, 18, 22, and 26) and MMA concentrations (at weeks 6, 7, and 8 compared to weeks 14, 18, 22, and 26) and an overall decrease of serum MMA concentrations from week 6 to week 14 in the pigs studied. This study suggests age-dependent changes in intracellular folate- and cobalamin-dependent metabolites (i.e., HCY and MMA) in pigs between 6 and 26 weeks of age, possibly reflecting decreased availability of intracellular folate and/or cobalamin for amino acid metabolism, nucleic acid synthesis, and methyl group transfer.


Assuntos
Ácido Fólico/sangue , Soro/química , Sus scrofa/sangue , Vitamina B 12/sangue , Animais , Citoplasma/química , Homocisteína/sangue , Ácido Metilmalônico/sangue
11.
J Vis Exp ; (156)2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32150163

RESUMO

Mass spectrometry (MS) is a powerful tool in analytical chemistry because it provides very accurate information about molecules, such as mass-to-charge ratios (m/z), which are useful to deduce molecular weights and structures. While it is essentially a destructive analytical method, recent advancements in the ambient ionization technique have enabled us to acquire data while leaving tissue in a relatively intact state in terms of integrity. Probe electrospray ionization (PESI) is a so-called direct method because it does not require complex and time-consuming pretreatment of samples. A fine needle serves as a sample picker, as well as an ionization emitter. Based on the very sharp and fine property of the probe tip, destruction of the samples is minimal, allowing us to acquire the real-time molecular information from living things in situ. Herein, we introduce three applications of PESI-MS technique that will be useful for biomedical research and development. One involves the application to solid tissue, which is the basic application of this technique for the medical diagnosis. As this technique requires only 10 mg of the sample, it may be very useful in the routine clinical settings. The second application is for in vitro medical diagnostics where human blood serum is measured. The ability to measure fluid samples is also valuable in various biological experiments where a sufficient volume of sample for conventional analytical techniques cannot be provided. The third application leans toward the direct application of probe needles in living animals, where we can obtain real-time dynamics of metabolites or drugs in specific organs. In each application, we can infer the molecules that have been detected by MS or use artificial intelligence to obtain a medical diagnosis.


Assuntos
Lipídeos/análise , Fígado/metabolismo , Soro/química , Manejo de Espécimes/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Animais , Humanos
12.
Food Chem ; 320: 126612, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32197124

RESUMO

In this work, in-syringe membrane solid-phase extraction (MSPE) device was fabricated for the on-site sampling of sulfamethoxazole (SMX) in food samples followed by solid-phase fluorescence spectra analysis. The samples and fluorescamine (FA) were added to a syringe for derivation. Then, the derivative of SMX was extracted by a membrane in the syringe SPE device. Subsequently, the derivative on the membrane was measured immediately without additional elution procedure. The method was successfully applied in plasma, milk, and egg samples for the trace SMX detection, with the recovery of 98%-102%, RSDs from 1% to 6%. Compared with liquid chromatography, direct detection of the concentrated analyte significantly improved the sensitivity. Moreover, fluorescamine made it unnecessary to separate SMX from the interference. Consequently, it was a time-saving, low-cost, and easy-operation method, which demonstrated the potential of in-syringe SPE as a promising candidate for on-site analysis.


Assuntos
Sulfametoxazol/análise , Animais , Galinhas , Cromatografia Líquida de Alta Pressão , Análise de Alimentos , Leite/química , Óvulo/química , Soro/química , Extração em Fase Sólida/instrumentação , Espectrometria de Fluorescência , Seringas , Fatores de Tempo
13.
J Pregnancy ; 2020: 1515321, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32148965

RESUMO

Hypertensive disorders of pregnancy (HDP) are the most common cardiometabolic complications of pregnancy, affecting nearly 10% of US pregnancies and contributing substantially to maternal and infant morbidity and mortality. In the US, women of African American race are at increased risk for HDP. Early biomarkers that reliably identify women at risk for HDP remain elusive, yet are essential for the early identification and targeting of interventions to improve maternal and infant outcomes. We employed high-resolution metabolomics (HRM) to identify metabolites and metabolic pathways that were altered in early (8-14 weeks) gestation serum samples of pregnant African American women who developed HDP after 20 weeks' gestation (n = 20)-either preeclampsia (PE; n = 11) or gestational hypertension (gHTN; n = 9)-compared to those who delivered full term without complications (n = 80). We found four metabolic pathways that were significantly (p < 0.05) altered in women who developed PE and five pathways that were significantly (p < 0.05) altered in women who developed gHTN compared to women who delivered full term without complications. We also found that four specific metabolites (p < 0.05) were distinctly upregulated (retinoate, kynurenine) or downregulated (SN-glycero-3-phosphocholine, 2'4'-dihydroxyacetophenone) in women who developed PE compared to gHTN. These findings support that there are systemic metabolic disruptions that are detectable in early pregnancy (8-14 weeks of gestation) among pregnant African American women who develop PE and gHTN. Furthermore, the early pregnancy metabolic disruptions associated with PE and gHTN are distinct, implying they are unique entities rather than conditions along a spectrum of the same disease process despite the common clinical feature of high blood pressure.


Assuntos
Hipertensão/diagnóstico , Complicações Cardiovasculares na Gravidez/diagnóstico , Soro/química , Adulto , Biomarcadores/sangue , Feminino , Humanos , Hipertensão/metabolismo , Masculino , Projetos Piloto , Gravidez , Complicações Cardiovasculares na Gravidez/metabolismo , Adulto Jovem
14.
Environ Health ; 19(1): 33, 2020 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-32169067

RESUMO

BACKGROUND: Exposures to perfluoroalkyl substances (PFAS) have shown positive associations with serum lipids in previous studies. While many studies on lipids investigated associations with perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), there are only a few studies regarding other PFAS, such as perfluorohexane sulfonic acid (PFHxS). The purpose of the current study is to investigate if associations with serum lipids were present, not only for serum PFOS and PFOA, but also for PFHxS, and if the associations with PFAS remained also in a comparison based only on residency in areas with contrasting exposure to PFAS. METHODS: 1945 adults aged 20-60 were included from Ronneby, Sweden, a municipality where one out of two waterworks had been heavily contaminated from aqueous fire-fighting foams, and from a nearby control area. The exposure was categorized based on either been living in areas with contrasting PFAS exposure or based on the actual serum PFAS measurements. Regression analyses of serum lipids were fitted against serum PFAS levels, percentile groups, smooth splines and between exposed and reference areas, adjusting for age, sex and BMI. RESULTS: Drinking water contamination caused high serum levels of PFOS (median 157 ng/ml) and PFHxS (median 136 ng/ml) and PFOA (median 8.6 ng/ml). These serum PFAS levels in the exposed groups were 5 to 100-fold higher than in the controls. In this population with mixed PFAS exposure, predominantly PFOS and PFHxS, PFAS exposure were positively associated with serum lipids. This was observed both when quantifying exposure as contrast between exposed and controls, and in terms of serum PFAS. Due to high correlations between each PFAS, we cannot separate them. CONCLUSIONS: In conclusion, the present study provides further evidence of a causal association between PFAS and serum lipids, especially for PFHxS.


Assuntos
Ácidos Alcanossulfônicos/sangue , Caprilatos/sangue , Fluorcarbonetos/sangue , Lipídeos/sangue , Ácidos Sulfônicos/sangue , Poluentes Químicos da Água/sangue , Qualidade da Água , Adulto , Água Potável/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Soro/química , Suécia , Adulto Jovem
15.
Biochem Biophys Res Commun ; 526(1): 267-272, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32209261

RESUMO

Charcoal-stripped fetal bovine serum (CS-FBS) is frequently used in studies on hormone-responsive cancers to provide hormone-free cell culture conditions. CS-FBS may influence the growth of cancer cells; however, the underlying mechanisms remain unclear. In this study, we aimed to clarify the effects of CS-FBS on distinct subtypes of breast cancer cells. We found that the crucial oncoprotein c-Myc was significantly inhibited in estrogen receptor alpha (ER-α)-positive breast cancer cells when cultured in CS-FBS-supplemented medium, but it was not suppressed in ER-α-negative cells. The addition of 17ß-estradiol (E2) to CS-FBS-supplemented medium rescued the CS-FBS-induced inhibition of c-Myc, while treatment with 5α-dihydrotestosterone (DHT) suppressed c-Myc expression. Our data demonstrated that CS-FBS may impede the growth of ER-α-positive breast cancer cells via c-Myc inhibition, and this was possibly due to the removal of estrogen. These results highlighted that the core drivers of c-Myc expression were subtype-specific depending on the distinct cell context and special caution should be exercised when using CS-FBS in studies of hormone-responsive cancer cells.


Assuntos
Neoplasias da Mama/patologia , Carvão Vegetal/farmacologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Soro/química , Animais , Neoplasias da Mama/genética , Bovinos , Linhagem Celular Tumoral , Di-Hidrotestosterona/farmacologia , Células Epiteliais/metabolismo , Estradiol/farmacologia , Receptor alfa de Estrogênio/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Receptores Androgênicos/metabolismo , Transcrição Genética/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
16.
PLoS One ; 15(3): e0229873, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32134971

RESUMO

BACKGROUND: The clinical value of therapeutic drug monitoring can be increased most significantly by integrating assay results into clinical pharmacokinetic models for optimal dosing. The correct weighting in the modeling process is 1/variance, therefore, knowledge of the standard deviations (SD) of each measured concentration is important. Because bioanalytical methods are heteroscedastic, the concentration-SD relationship must be modeled using assay error equations (AEE). We describe a methodology of establishing AEE's for liquid chromatography-tandem mass spectrometry (LC-MS/MS) drug assays using carbamazepine, fluconazole, lamotrigine and levetiracetam as model analytes. METHODS: Following method validation, three independent experiments were conducted to develop AEE's using various least squares linear or nonlinear, and median-based linear regression techniques. SD's were determined from zero concentration to the high end of the assayed range. In each experiment, precision profiles of 6 ("small" sample sets) or 20 ("large" sample sets) out of 24 independent, spiked specimens were evaluated. Combinatorial calculations were performed to attain the most suitable regression approach. The final AEE's were developed by combining the SD's of the assay results, established in 24 specimens/spiking level and using all spiking levels, into a single precision profile. The effects of gross hyperbilirubinemia, hemolysis and lipemia as laboratory interferences were investigated. RESULTS: Precision profiles were best characterized by linear regression when 20 spiking levels, each having 24 specimens and obtained by performing 3 independent experiments, were combined. Theil's regression with the Siegel estimator was the most consistent and robust in providing acceptable agreement between measured and predicted SD's, including SD's below the lower limit of quantification. CONCLUSIONS: In the framework of precision pharmacotherapy, establishing the AEE of assayed drugs is the responsibility of the therapeutic drug monitoring service. This permits optimal dosages by providing the correct weighting factor of assay results in the development of population and individual pharmacokinetic models.


Assuntos
Cromatografia Líquida/métodos , Monitoramento de Medicamentos/métodos , Modelos Biológicos , Medicina de Precisão/métodos , Espectrometria de Massas em Tandem/métodos , Carbamazepina/química , Confiabilidade dos Dados , Fluconazol/química , Humanos , Lamotrigina/química , Análise dos Mínimos Quadrados , Levetiracetam/química , Limite de Detecção , Concentração Osmolar , Soro/química , Software
17.
Am J Ophthalmol ; 213: 260-266, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32006480

RESUMO

PURPOSE: To analyze the biological stability of autologous serum eyedrops after lyophilization. DESIGN: Prospective, comparative experimental study. METHODS: This was a comparative study with serum obtained from 12 healthy volunteers. The concentrations of different epitheliotropic factors (eg, transforming growth factor-ß [TGF-ß1], epidermal growth factor [EGF], platelet-derived growth factor AB [PDGF-AB], and albumin) were measured in fresh and lyophilized serum. The samples were studied after serum preparation (fresh serum) and immediately after saline solution reconstitution of lyophilized serum (0), 15, and 30 days later. The biological effects of both serum samples were also compared on conjunctival and corneal cell cultures. The pH, osmolarity, and serum density were also determined. RESULTS: No significant differences were found in the concentration of growth factors between fresh serum and re-dissolved serum samples after lyophilization. The concentration of growth factors remained stable during 1 month at 4°C in re-dissolved lyophilized form with saline solution. No differences were found related to osmolarity, pH, and density between fresh and lyophilized serum. In addition, no differences were found on the conjunctival and corneal cells proliferation and differentiation in cells cultures between either serum preparation. CONCLUSIONS: The properties of autologous serum remain after lyophilization. The lyophilized serum can be easily stored without temperature restrictions and easily reconstituted for preparation of eyedrops for standard clinical use.


Assuntos
Fator de Crescimento Epidérmico/análise , Soluções Oftálmicas/química , Fator de Crescimento Derivado de Plaquetas/análise , Albumina Sérica Humana/análise , Soro/química , Fator de Crescimento Transformador beta1/análise , Adulto , Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Epitélio Anterior/efeitos dos fármacos , Liofilização , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio , Microscopia de Contraste de Fase , Pessoa de Meia-Idade , Concentração Osmolar , Estudos Prospectivos
18.
Poult Sci ; 99(2): 702-707, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32036974

RESUMO

Improving the digestive efficiency of birds is becoming increasingly important with the diversification of feedstuffs used in poultry diets. Compared with time-consuming chemical analyses that were previously used to measure digestive efficiency, near-infrared spectroscopy has been a great advance as it was fast and thus allowed measurements to be taken from a large number of animals, as required for genetic studies. However, it still implies to rear the birds in cages to collect feces, which is questionable in terms of welfare. The purpose of this study was thus to establish whether the serum color could be used as a biomarker of digestive efficiency that would be easy and fast to measure on floor-reared animals. We first compared the serum color of 2 lines of chickens divergently selected for high or low digestive efficiency when fed with a wheat-based diet. Digestive efficiency was assessed by nitrogen-corrected apparent metabolizable energy. Color was assessed by the absorbance of the serum between 300 and 572 nm. Color differed between the 2 lines between 430 and 572 nm, which corresponds to the absorption zone of carotenoids such as lutein and zeaxanthin. In a second step, we estimated the heritability of serum color measurements and their genetic correlations with digestive efficiency. Taking these parameters into account, in our experimental conditions the best trait among those tested that can be used as a biomarker of digestive efficiency is serum absorbance at 492 nm, with a heritability estimate of 0.31 ± 0.09 and a genetic correlation with digestive efficiency of 0.84 ± 0.28.


Assuntos
Criação de Animais Domésticos/métodos , Galinhas/fisiologia , Digestão , Soro/química , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Biomarcadores/sangue , Galinhas/genética , Cor , Dieta/veterinária , Feminino , Hereditariedade , Masculino , Fenótipo , Seleção Genética
19.
Dis Markers ; 2020: 6501272, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32051697

RESUMO

Background: No epidemiological study has investigated the effect of anion gap (AG) on the prognosis of critically ill patients with acute kidney injury (AKI). Therefore, we aimed to determine the association between serum AG and all-cause mortality in these patients. Methods: From MIMIC III, we extracted demographics, vital signs, laboratory tests, comorbidities, and scoring systems from the first 24 h after patient ICU admission. A generalized additive model was used to identify a nonlinear association between anion gap and 30-day all-cause mortality. We also used the Cox proportional hazards models to measure the association between AG levels and 30-day, 90-day, and 365-day mortality in patients with AKI. Results: A total of 11,573 eligible subjects were extracted from the MIMIC-III. The relationship between AG levels and 30-day all-cause mortality in patients with AKI was nonlinear, with a U-shaped curve. In multivariate analysis, after adjusting for potential confounders, higher AG was a significant predictor of 30-day, 90-day, and 365-day all-cause mortality compared with lower AG (HR, 95% CI: 1.54, 1.33-1.75; 1.55, 1.38-1.73; 1.46, 1.31-1.60). Conclusions: The relationship between AG levels and 30-day all-cause mortality described a U-shaped curve. High-AG levels were associated with increased risk 30-day, 90-day, and 365-day all-cause mortality in critically ill patients with AKI.


Assuntos
Lesão Renal Aguda/mortalidade , Soro/química , Equilíbrio Ácido-Base , Lesão Renal Aguda/sangue , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Estado Terminal , Bases de Dados Factuais , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais
20.
Soft Matter ; 16(9): 2301-2310, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32052004

RESUMO

The behaviour of drug/gene carriers in the blood stream under shear is still a puzzle. In this work, using the complexes formed by 21 bp DNA and poly(ethylene glycol)-b-poly(l-lysine) (PEG-PLL) of varying PEG lengths, we studied the dynamic behaviour of the complexes in the presence of fetal bovine serum (FBS) and under flow at different shear rates, a condition mimicking the internal physical environment of blood vessels. The PEG5k-PLL/DNA complex possesses a dense DNA/PLL core and a loose PEG5k protecting layer. The PEGylated DNA complexes exhibit multiple responses to external shear in the presence of FBS. The loose PEG5k layer is firstly disturbed at a shear rate below 30 s-1. The exposure of the charged core to the environment results in a secondary aggregation of the complex with FBS. The size of the aggregate is limited to a certain range as the shear rate increases to 50 s-1. The dense DNA/PLL core starts to withstand the shear force as the shear rate reaches 500 s-1. The reorganization of the core to accommodate more serum molecules leads to tertiary aggregation of the complexes. If PEG cannot form a valid layer around the complex, as in PEG2k-PLL/DNA, the complex forms an aggregate even without shear, and the first shear dependent region is missing. If the PEG layer is too stable around the complex, as in PEG10k-PLL/DNA, no tertiary aggregation occurs. The mechanism of shear on the behaviour of delivery particles in serum helps to design gene carriers with high efficacy.


Assuntos
DNA/química , Técnicas de Transferência de Genes/instrumentação , Polietilenoglicóis/química , Polilisina/química , Animais , Bovinos , DNA/genética , Soro/química
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