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1.
Bioanalysis ; 14(5): 307-316, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35195039

RESUMO

Aim: HCP002, a phosphate-modified derivative of voriconazole, can improve solubility without using the nephrotoxic solubilizer, sulfobutylether-ß-cyclodextrin. To study pharmacokinetics in humans, LC-MS/MS methods to quantify HCP002 in human plasma and urine were developed and validated. Method: After protein precipitation by acetonitrile containing voriconazole-d3, HCP002 was separated on a ZORBAX SB-Aq column, and LCMS/MS analysis was performed in multi-response monitoring mode. Results: The analytical run time was 3 min. Linearity was observed over the ranges of 0.100-40.0 and 0.400-200 µg/ml in plasma and urine, respectively. Precision and accuracy were within acceptable limits. Sample stability was confirmed. Conclusion: Rapid and reproducible methods quantified HCP002 in urine, and plasma samples were established.


Assuntos
Plasma , Espectrometria de Massas em Tandem , Cromatografia Líquida/métodos , Humanos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
2.
Anal Chem ; 94(24): 8561-8569, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35670335

RESUMO

Liquid chromatography-high-resolution mass spectrometry (LC-HRMS) is the most popular platform for untargeted metabolomics studies, but compound annotation is a challenge. In this work, we developed a new LC-HRMS data-targeted extraction method called MetEx for metabolite annotation. MetEx contains the retention time (tR), MS1, and MS2 information of 30 620 metabolites from freely available spectral databases, including MoNA and KEGG. The tR values of 95.4% of the compounds in our database were calculated by the GNN-RT model. The MS2 spectra of 39.4% compounds were also predicted using CFM-ID. MetEx was initially examined on a mixture of 634 standards, considering chemical coverage and accurate metabolite assignment, and later applied to human plasma (NIST SRM 1950), human urine, HepG2 cells, mouse liver tissue, and mouse feces. MetEx correctly assigned 252 out of 253 standards detected in our instruments. The platform also provided 8.0-44.2% more compounds in the biological samples compared to XCMS, MS-DIAL, and MZmine 2. MetEx is implemented and visualized in R and freely available at http://www.metaboex.cn/MetEx.


Assuntos
Metabolômica , Plasma , Animais , Cromatografia Líquida/métodos , Bases de Dados Factuais , Espectrometria de Massas/métodos , Metabolômica/métodos , Metotrexato , Camundongos
3.
Artigo em Inglês | MEDLINE | ID: mdl-35665644

RESUMO

This work proposes a new method for biomonitoring studies focused on the screening and quantification of xenobiotics in blood-derived samples. The performance of a polydimethylsiloxane/divinylbenzene/polydimethylsiloxane (PDMS/DVB/PDMS) biocompatible extraction phase was investigated for extraction of pesticides and pharmaceuticals from plasma samples via direct immersion solid-phase microextraction (SPME) prior to gas chromatography-mass spectrometry. Under the optimum extraction settings, which included an attentive optimization of the fiber rinsing conditions, the microextraction device was able to endure 100 consecutive extractions from undiluted and diluted plasma with an overall reproducibility up to 28% for all the analytes tested, except chlorpyrifos-methyl. Optimized conditions were used to validate a quantitative method using matrix-matched calibration with isotopically labeled internal standard correction. Accuracy and precision values obtained for analysis of bovine plasma were within 96-132% and 0.05-5.82% respectively. LLOQs for all the analytes were at 1 µg L-1 and LDR ranged within 1-100 µg L-1. The applicability of this method to plasma from different species (human, rat, rabbit) was also investigated. This work represents the first step toward broader use of the biocompatible PDMS/DVB/PDMS extraction phases for analysis of multiclass xenobiotics in plasma and other complex biofluids.


Assuntos
Microextração em Fase Sólida , Xenobióticos , Animais , Bovinos , Dimetilpolisiloxanos/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Plasma , Coelhos , Ratos , Reprodutibilidade dos Testes , Microextração em Fase Sólida/métodos
4.
Metabolomics ; 18(6): 38, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35687195

RESUMO

Functional gastrointestinal disorders (FGID) such as functional dyspepsia (FD) and irritable bowel syndrome (IBS) are highly prevalent and debilitating attributed to altered gut function and gut-brain interactions. FGID can be reliably diagnosed based upon the symptom pattern; but in the clinical setting FD or IBS a frequent diagnoses of exclusion after relevant structural causes of symptoms have been ruled out by appropriate testing. Thus far, there is no established biomarker for FGIDs. To address this limitation, we utilised multi-omics and chemometrics integration to characterise the blood plasma biochemistry in patients with IBS, FD, an overlap of FD/IBS, and controls using liquid chromatography-mass spectrometry (LC-MS) techniques.Cholesterol metabolism products Cholest-5,24-dien-3ß-ol, 3-O-ß-D-glucopyranoside, energy pathway metabolites, immunoglobulin-γ2 and immunoglobulin-κ, and carbonic anhydrase-1 proteins were particularly elevated in IBS. Furthermore, arginine and proline metabolisms, thyroid hormone synthesis, ferroptosis and, complementary and coagulation cascades were particularly upregulated in patients with IBS. Cer(d18:1/26:1(17Z)) and PI(14:0/22:1(11Z)) lipids were elevated in FD and FD-IBS but were depleted in IBS. Markers of central carbon metabolism and lipidome profiles allowed better discrimination and model predictability than metaproteome profile in healthy and FGID conditions.Overall, the multi-omics integration allowed the discrimination of healthy controls and FGID patients. It also effectively differentiated the biochemistry of FGID subtypes including FD, IBS and FD-IBS co-occurrence. This study points towards the possibility of multi-omics integration for rapid and high throughput analysis of plasma samples to support clinicians screen and diagnose patients with suspected FGIDs.


Assuntos
Dispepsia , Gastroenteropatias , Síndrome do Intestino Irritável , Arginina , Dispepsia/diagnóstico , Dispepsia/etiologia , Gastroenteropatias/complicações , Gastroenteropatias/diagnóstico , Humanos , Síndrome do Intestino Irritável/diagnóstico , Lipídeos , Metabolômica , Plasma , Prolina
5.
AACN Adv Crit Care ; 33(2): 154-161, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35657762

RESUMO

BACKGROUND: Although evidence supports an increased risk of mortality after major trauma among patients with type O blood, the relationship between patient blood type and clinical outcomes aside from mortality has not been fully elucidated. OBJECTIVE: To examine the relationship between patient blood type and time to hemostasis after trauma and massive transfusion. METHODS: A secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial was performed (N = 544). Blood type was dichotomized into type O versus non-type O. It was hypothesized that patients with non-type O blood would achieve hemostasis more quickly owing to the theoretical presence of increased clotting factors. Bivariate analysis and multiple Cox regression were conducted to test this assumption. RESULTS: No significant difference was found in time to hemostasis between patients with type O blood and those with non-type O blood. However, mechanism of injury, diastolic blood pressure, and international normalized ratio affected the time to hemostasis in these trauma patients. CONCLUSION: This study showed no significant difference in time to hemostasis by blood type.


Assuntos
Hemorragia , Hemostasia , Transfusão de Sangue , Hemorragia/terapia , Humanos , Plasma , Ressuscitação
6.
Molecules ; 27(11)2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35684513

RESUMO

The aim of this work was to develop and validate a sensitive and robust method of liquid chromatography coupled with tandem mass spectrometry to quantitate ST-246 (tecovirimat) in plasma using an internal standard (2-hydroxy-N-{3,5-dioxo-4-azatetracyclo [5.3.2.02.6.08.10]dodec-11-en-4-yl}-5-methylbenzamide). The method was validated in negative multiple reaction monitoring mode following recommendations of the European Medicines Agency for the validation of bioanalytical methods. The calibration curve for the analyte was linear in the 10-2500 ng/mL range with determination coefficient R2 > 0.99. Intra- and inter-day accuracy and precision for three concentrations of quality control were <15%. Testing of long-term stability of ST-246 (tecovirimat) in plasma showed no degradation at -20 °C for at least 3 months. The method was applied to a clinical assay of a new antipoxvirus compound, NIOCH-14. Thus, the proposed method is suitable for therapeutic drug monitoring of ST-246 (tecovirimat) itself and of NIOCH-14 as its metabolic precursor.


Assuntos
Plasma , Espectrometria de Massas em Tandem , Benzamidas , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Humanos , Isoindóis , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
7.
Adv Gerontol ; 35(2): 281-286, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35727935

RESUMO

The aim of the work was to determine the concentration of low-molecular-weight plasma DNA (lmDNA) in patients with COPD and chronic non-obstructive bronchitis (CnonB) of two age groups - 34-59 and 60-80 years. The levels of lmDNA in healthy donors, patients with CnonB, healthy relatives of patients with COPD did not differ, while the concentration of lmDNA in patients with COPD was significantly lower. In COPD patients aged 34-59 years, the level of lmDNA was reduced by more than 7 times, and in COPD patients who survived to 60-80 years, it was 3 times lower compared to the value of this biochemical indicator in healthy donors of the same age. The reduction of lmDNA reflected a reduced systemic apoptotic activity in the body of patients with COPD. A significant difference in the concentration of lmDNA in patients with COPD and CnonB in remission can be used for differential diagnosis of the development of these pathological processes. An increase in the low level of lmDNA in COPD patients during aging may indicate the involvement of epigenetic mechanisms in life extension.


Assuntos
Asma , Bronquite Crônica , Doença Pulmonar Obstrutiva Crônica , DNA/genética , Humanos , Plasma , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/genética
8.
Front Biosci (Schol Ed) ; 14(2): 15, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35730440

RESUMO

Prostate cancer is one of the most common and socially significant cancers among men. The aim of this study was to identify significant changes in the expression of exosomal miRNAs associated with an increase in the level of prostate specific antigen in castration-resistant prostate cancer during therapy and to evaluate them as potential prognostic markers for this category of disease. High-throughput miRNA sequencing was performed on 49 blood plasma samples taken from 11 Russian patients with castration-resistant cancer during therapy. Bioinformatic analysis of the obtained miRNA-seq data was carried out. Additionally, miRNA-seq data from the PRJNA562276 project were analyzed to identify exosomal miRNAs associated with castration-resistant prostate cancer. We found 34 differentially expressed miRNAs associated with the progression of castration-resistant prostate cancer during therapy in Russian patients. It was also shown that hsa-miRNA-148a-3p expression can serve as a potential prognostic marker. We found the exosomal miRNA expression signature associated with castration-resistant prostate cancer progression, in particular on the Russian patient cohort. Many of these miRNAs are well-known players in either oncogenic transformation or tumor suppression. Further experimental studies with extended sampling are required to validate these results.


Assuntos
Exossomos , MicroRNAs , Neoplasias de Próstata Resistentes à Castração , Biologia Computacional , Exossomos/genética , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Plasma/metabolismo , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo
9.
Front Immunol ; 13: 873390, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35734164

RESUMO

Many animals of scientific importance lack species-specific reagents (e.g., monoclonal antibodies) for in-depth studies of immune proteins. Mass spectrometry (MS)-based proteomics has emerged as a useful method for monitoring changes in protein abundance and modifications in non-model species. It can be used to quantify hundreds of candidate immune molecules simultaneously without the generation of new reagents. Here, we used MS-based proteomics to identify and quantify candidate immune proteins in the plasma of the nurse shark (Ginglymostoma cirratum), a cartilaginous fish and representative of the most basal extant vertebrate lineage with an immunoglobulin-based immune system. Mass spectrometry-based LC-MS/MS was performed on the blood plasma of nurse sharks immunized with human serum albumin (n=4) or sham immunized (n=1), and sampled at days 0 (baseline control), 1, 2, 3, 5, 7, 14, 21, 28, 25, 42 and 49. An antigen-specific antibody response was experimentally confirmed post-immunization. To provide a high-quality reference to identify proteins, we assembled and annotated a multi-tissue de novo transcriptome integrating long- and short-read sequence data. This comprised 62,682 contigs containing open reading frames (ORFs) with a length >80 amino acids. Using this transcriptome, we reliably identified 626 plasma proteins which were broadly categorized into coagulation, immune, and metabolic functional groups. To assess the feasibility of performing LC-MS/MS proteomics in nurse shark in the absence of species-specific protein annotations, we compared the results to an alternative strategy, mapping peptides to proteins predicted in the genome assembly of a related species, the whale shark (Rhincodon typus). This approach reliably identified 297 proteins, indicating that useful data on the plasma proteome may be obtained in many instances despite the absence of a species-specific reference protein database. Among the plasma proteins defined against the nurse shark transcriptome, fifteen showed consistent changes in abundance across the immunized shark individuals, indicating a role in the immune response. These included alpha-2-macroglobulin (A2M) and a novel protein yet to be characterized in diverse vertebrate lineages. Overall, this study enhances genetic and protein-level resources for nurse shark research and vastly improves our understanding of the elasmobranch plasma proteome, including its remodelling following immune stimulation.


Assuntos
Proteoma , Tubarões , Animais , Cromatografia Líquida , Plasma , Proteoma/metabolismo , Tubarões/genética , Espectrometria de Massas em Tandem
10.
Biosensors (Basel) ; 12(6)2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35735559

RESUMO

Interleukin-6 (IL-6) is a biomarker of inflammation, the advanced stage of COVID-19, and several cancers, including ovarian cancer. Two biosensors for the determination of IL-6 in blood plasma by array SPRi have been developed. One of these biosensors consists of the mouse monoclonal anti-IL-6 antibody as the receptor immobilized via the cysteamine linker. The second contains galiellalactone as the receptor, being an inhibitor specific for IL-6, immobilized via octadecanethiol (ODM) as the linker. Both biosensors are specific for IL-6. The biosensor with the antibody as the receptor gives a linear analytical response between 3 (LOQ) and 20 pg mL-1 and has a precision between 8% and 9.8% and recovery between 97% and 107%, depending on the IL-6 concentration. The biosensor with galiellalactone as the receptor gives a linear analytical response between 1.1 (LOQ) and 20 pg mL-1, and has a precision between 3.5% and 9.3% and recovery between 101% and 105%, depending on IL-6 concentration. Both biosensors were validated. Changes in IL-6 concentration in blood plasma before and after resection of ovarian tumor and endometrial cyst, as determined by the two developed biosensors, are given as an example of a real clinical application.


Assuntos
Técnicas Biossensoriais , COVID-19 , Neoplasias Ovarianas , Animais , Feminino , Humanos , Interleucina-6 , Camundongos , Plasma
11.
Sci Rep ; 12(1): 9151, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35650226

RESUMO

Bacterial contamination of blood products is a major problem in transfusion medicine, in terms of both morbidity and mortality. Platelets (PLTs) are stored at room temperature (under constant agitation) for more than 5 days, and bacteria can thus grow significantly from a low level to high titers. However, conventional methods like blood culture and lateral flow assay have disadvantages such as long detection time, low sensitivity, and the need for a large volume of blood components. We used real-time polymerase chain reaction (PCR) assays with antibiotic-conjugated magnetic nanobeads (MNBs) to detect enriched Gram-positive and -negative bacteria. The MNBs were coated with polyethylene glycol (PEG) to prevent aggregation by blood components. Over 80% of all bacteria were captured by the MNBs, and the levels of detection were 101 colony forming unit [CFU]/mL and 102 CFU/mL for Gram-positive and -negative bacteria, respectively. The detection time is < 3 h using only small volumes of blood components. Thus, compared to conventional methods, real-time PCR using MNBs allows for rapid detection with high sensitivity using only a small volume of blood components.


Assuntos
Bactérias , Contaminação de Medicamentos , Bactérias/genética , Plaquetas/microbiologia , Fenômenos Magnéticos , Plasma
13.
J Chromatogr A ; 1675: 463168, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35667219

RESUMO

A two steps proposal for the purification of immunoglobulin G from human blood plasma is investigated. The first step is precipitation using cold ethanol based on the Cohn method with some modification and the second step is a chromatographic separation by DEAE-Sepharose FF resin as a weak anion exchanger. The presence of interferent in the region3 of chromatographic fractions, which is co-eluted with IgG, restricts the application of the mechanistic chromatography model. Therefore, multivariate cure resolution-alternating least squares (MCR-ALS) as a soft method is employed on measured absorbance data matrix from eluted fractions to recover pure concentration and spectral profiles. Besides, possible solutions for resolved concentration and spectral profiles are investigated. The reaction-dispersive model as a mechanistic hard model for the column is utilized for the evaluation of the ion exchange chromatography. Using a genetic algorithm as a global optimization method, mobile phase modulator (MPM) adsorption model parameters such as ß, kdes,0, and Keq,0, were fitted to the concentration profiles from MCR-ALS as 1.96, 2.87×10-4 m3 mol-1s-1, and 1883, respectively. Furthermore, a new resampling incorporated non-parametric statistics is conducted to assess parameters' uncertainty. Values of 2.00, 1.10×10-3 m3 mol-1s-1, and 549.80 are estimated median, and values of 0.05, 2.5×10-3, and 691.00 are calculated interquartile range (IQR) for ß, kdes,0, and Keq,0, respectively. Finally, results show three and two outliers for ß and kdes,0, respectively.


Assuntos
Anticorpos , Plasma , Cromatografia Líquida de Alta Pressão , Cromatografia por Troca Iônica , Humanos , Análise dos Mínimos Quadrados
14.
BMC Vet Res ; 18(1): 232, 2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35717202

RESUMO

BACKGROUND: Pain in cattle is a major welfare problem, as cattle mask their pain. Subjective and objective parameters to assess pain in cattle have been described. Among the objective parameters to evaluate pain in cattle is substance P (SP). SP is a neurotransmitter, which is involved in the processing of noxious information to the brain; it seems to be a more objective indicator for nociception than cortisol, which has long been used as a biomarker for pain and stress in cattle. The objective of this systematic review was to assess the existing literature about SP during painful procedures, conditions, and diseases in cattle in form of a systematic review. RESULTS: Following the PRISMA statement, 36 out of 236 studies were included in this systematic review. Study design, grouping, age and weight of animals, processing of blood samples for the assessment of SP, and results were heterogenous. The largest number of studies originated from the United States of America and Canada and were published in 2018. A higher number of studies were done on calves (69.4%, n = 25) compared with adult cattle (30.6%, n = 11). Most studies were done to assess SP concentrations after administration of analgesics prior to husbandry procedures in calves. CONCLUSIONS: There is a manageable number of studies assessing SP concentrations during painful procedures, conditions, and diseases in cattle. SP seems to be a suitable biomarker for nociception in cattle, but results of research work are heterogenous, and SP concentrations of calves and adult cattle differ throughout studies. Basic research work is missing and is needed to assess factors others than nociception which might influence the SP concentrations in the blood plasma.


Assuntos
Cornos , Animais , Biomarcadores , Bovinos , Hidrocortisona , Dor/veterinária , Plasma , Substância P
15.
J Immunother Cancer ; 10(6)2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35718373

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the cancer therapy landscape due to long-term benefits in patients with advanced metastatic disease. However, robust predictive biomarkers for response are still lacking and treatment resistance is not fully understood. METHODS: We profiled approximately 800 pre-treatment and on-treatment plasma proteins from 143 ICI-treated patients with non-small cell lung cancer (NSCLC) using ELISA-based arrays. Different clinical parameters were collected from the patients including specific mutations, smoking habits, and body mass index, among others. Machine learning algorithms were used to identify a predictive signature for response. Bioinformatics tools were used for the identification of patient subtypes and analysis of differentially expressed proteins and pathways in each response group. RESULTS: We identified a predictive signature for response to treatment comprizing two proteins (CXCL8 and CXCL10) and two clinical parameters (age and sex). Bioinformatic analysis of the proteomic profiles identified three distinct patient clusters that correlated with multiple parameters such as response, sex and TNM (tumors, nodes, and metastasis) staging. Patients who did not benefit from ICI therapy exhibited significantly higher plasma levels of several proteins on-treatment, and enrichment in neutrophil-related proteins. CONCLUSIONS: Our study reveals potential biomarkers in blood plasma for predicting response to ICI therapy in patients with NSCLC and sheds light on mechanisms underlying therapy resistance.


Assuntos
Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antineoplásicos Imunológicos/efeitos adversos , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/patologia , Plasma , Proteômica
16.
BMC Cardiovasc Disord ; 22(1): 248, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35655131

RESUMO

BACKGROUND: Cellular and animal studies have shown that endoplasmic reticulum protein B (Nogo-B) is associated with hypertension, but that association has not been fully studied in humans. Therefore, the expression levels of Nogo-B were investigated in hypertensive patients. METHODS: The plasma Nogo-B levels of 74 patients with hypertension and 67 non-hypertensive patients were measured by enzyme-linked immunosorbent assay. RESULTS: The plasma Nogo-B levels in the hypertensive group [523.43(411.41-746.79)] were higher than in the non-hypertensive group [380.29(281.57-462.13)] (P < 0.01). Pearson's correlation analysis indicated that systolic blood pressure and diastolic blood pressure were linearly and positively correlated with plasma Nogo-B levels. Multivariable logistic regression analysis was performed based on sex, age, BMI, smoking history, drinking history, and levels of TC, TG, LDL, and HDL. The results indicated that the plasma Nogo-B levels were independently associated with hypertension (OR = 1.007, 95%CI: 1.004-1.010, P < 0.01). CONCLUSIONS: The present study suggests that hypertensive participants exhibited higher plasma Nogo-B levels than those without hypertension. Plasma Nogo-B levels are independently associated with hypertension.


Assuntos
Hipertensão , Animais , China/epidemiologia , Humanos , Hipertensão/diagnóstico , Plasma , Fumar
17.
Chem Res Toxicol ; 35(6): 1070-1079, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35622957

RESUMO

Chlorine is a widely available industrial chemical and involved in a substantial number of cases of poisoning. It has also been used as a chemical warfare agent in military conflicts. To enable forensic verification, the persistent biomarkers 3-chlorotyrosine and 3,5-dichlorotyrosine in biomedical samples could be detected. An important shortfall of these biomarkers, however, is the relatively high incidence of elevated levels of chlorinated tyrosine residues in individuals with inflammatory diseases who have not been exposed to chlorine. Therefore, more reliable biomarkers are necessary to distinguish between endogenous formation and exogeneous exposure. The present study aims to develop a novel diagnostic tool for identifying site-specific chlorinated peptides as a more unambiguous indicator of exogeneous chlorine exposure. Human blood plasma was exposed in vitro to various chlorine concentrations, and the plasma proteins were subsequently digested by pronase, trypsin, or pepsin. After sample preparation, the digests were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) and liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). In line with other studies, low levels of 3-chlorotyrosine and 3,5-dichlorotyrosine were found in blank plasma samples in this study. Therefore, 50 site-specific biomarkers were identified, which could be used as more unambiguous biomarkers for chlorine exposure. Chlorination of the peptides TY*ETTLEK, Y*KPGQTVK, Y*QQKPGQAPR, HY*EGSTVPEK, and Y*LY*EIAR could already be detected at moderate in vitro chlorine exposure levels. In addition, the latter two peptides were found to have dichlorinated fragments. Especially, Y*LY*EIAR, with a distinct chlorination pattern in the MS spectra, could potentially be used to differentiate exogeneous exposure from endogenous causes as other studies reported that this part of human serum albumin is nitrated rather than chlorinated under physiological conditions. In conclusion, trypsin digestion combined with high-resolution MS analysis of chlorinated peptides could constitute a valuable technique for the forensic verification of exposure to chlorine.


Assuntos
Cloro , Espectrometria de Massas em Tandem , Biomarcadores , Cloro/química , Cromatografia Líquida , Humanos , Plasma/metabolismo , Tripsina/metabolismo , Tirosina/química
18.
J Int Soc Sports Nutr ; 19(1): 110-125, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35599919

RESUMO

Background: Physical exercise affects zinc (Zn) homeostasis. This study aimed to analyze the influence of physical training on extracellular (serum, plasma, and urine) and intracellular (erythrocytes and platelets) concentrations of Zn. Methods: Forty young men, divided into a training group (TG; n = 20; 18.15 ± 0.27 years; 68.59 ± 4.18 kg; 1.76 ± 0.04 m) and a control group (CG; n = 20; 19.25 ± 0.39 years; 73.45 ± 9.04 kg; 1.79 ± 0.06 m), participated in this study. The TG was formed by semiprofessional soccer players from a youth category with a regular training plan of 10 h/week. The CG was formed by healthy men who did not practice physical exercise and had not followed any specific training plan. Plasma, serum, urine, erythrocyte, and platelet samples of Zn were obtained and analyzed by inductively coupled plasma mass spectrometry. Results: The TG showed elevated plasma Zn concentrations (p < 0.01) despite similar intakes. However, TG showed reduced absolute (p < 0.01) and relative (p < 0.05) Zn concentrations in erythrocytes. Conclusions: Athletes who underwent regular physical training showed elevated plasma and reduced erythrocyte Zn concentrations despite similar intakes to the CG.


Assuntos
Exercício Físico , Zinco , Adolescente , Atletas , Eritrócitos/química , Humanos , Masculino , Plasma
19.
Front Public Health ; 10: 778037, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35602161

RESUMO

COVID-19 is highly contagious and is caused by severe acute respiratory syndrome coronavirus 2. It spreads by means of respiratory droplets and close contact with infected persons. With the progression of disease, numerous complications develop, particularly among persons with chronic illnesses. Pathological investigations indicate that it affects multiple organs and can induce acute respiratory distress syndrome. Prevention is vital and self-isolation is the best means of containing this virus. Good community health practices like maintaining sufficient distance from other people, wearing protective face masks and regular hand washing should be adopted. Convalescent plasma transfusion and the administration of the antiviral Remdesivir have been found to be effective. Vaccines offer lifesaving protecting against COVID-19 which has killed millions and our best bet for staying safe. Screening, suppression/containment as well as mitigation are the strategies implemented for controlling COVID-19 pandemic. Vaccination is essential to end the COVID-19 pandemic and everyone should have an access to them. The current COVID-19 pandemic brought the global economy to a standstill and has exacted an enormous human and financial toll.


Assuntos
COVID-19 , Transfusão de Componentes Sanguíneos , COVID-19/terapia , Humanos , Imunização Passiva , Pandemias , Plasma
20.
Biochim Biophys Acta Mol Basis Dis ; 1868(9): 166445, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35577177

RESUMO

Early identification of diabetic cardiomyopathy (DCM) can help clinicians develop targeted treatment plans and forensic pathologists make accurate postmortem diagnoses. In the present study, diabetes-induced metabolic abnormalities in the myocardium and biofluids (plasma, urine, and saliva) of db/db mice of various ages (7, 12, and 21 weeks) were investigated by attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy. The results indicated that the diabetic and control groups had significantly different changes in the function groups of lipids, phosphate macromolecules (mostly nucleic acids), protein compositions and conformations, and carbohydrates (primarily glucose) in the myocardium and biofluids. The prediction model for quantifying DCM severity was developed on db/db mice's myocardial spectra using a genetic algorithm (GA)-partial least squares (PLS) regression method. Following that, the linear correlations between the predicted values for DCM severity and spectra for db/db biofluids were evaluated using the GA-PLS regression algorithm. The results showed there were good linear correlations between the predicted values for DCM severity and spectra for plasma (R2 = 0.929), saliva (R2 = 0.967), urine (R2 = 0.954), and combination of plasma and saliva (R2 = 0.980). This study provides a novel perspective on detecting diabetes-related biofluid and cardiac metabolic abnormalities and demonstrates the potential of biofluid infrared spectro-diagnostic models for non/mini-invasive assessment of DCM.


Assuntos
Diabetes Mellitus , Plasma , Animais , Análise dos Mínimos Quadrados , Camundongos , Miocárdio , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
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