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1.
J Pharm Biomed Anal ; 222: 115082, 2023 Jan 05.
Article in English | MEDLINE | ID: mdl-36183577

ABSTRACT

The diagnostic methods in an emergency scenario must be simple, fast, and efficient to provide an effectiveness and efficient treatment, thus reducing the consequences of exposure. Considering the sample analysis, the protein precipitation combined with LC-MS/MS has been shown to be a good strategy for the simultaneous determination of compounds of toxicological interest, such as medicines and drugs of abuse. In this study, a rapid and simple multi-analyte method was developed and validated for the quantification of 57 pharmaceuticals and illicit drugs in plasma samples. Sample pre-treatment consists of protein precipitation of 50 µL of the sample with 240 µL of organic solvent mixture (MeOH:ACN, 3:1, v/v), centrifugation, and injection into the LC-MS/MS, with a chromatographic run time of 7 min. The method was validated considering lower limit of quantification (LLOQ), interferences, linearity, precision, accuracy, dilution integrity, carryover, and matrix effect. The LLOQs ranged from 5 to 20 ng/mL and all analytes were linear (r2>0.99) in the tested concentration ranges. The method proved to be precise and accurate, presenting QC concentrations for all analytes within acceptable limits by the guideline used (CV % ≤20 % and bias ± 20 %). The developed method was successfully applied in 470 plasma samples of real cases of poisoning. A total of 80 % of the samples were positive for at least one substance, with acetaminophen (32.1 %), diazepam (25.1 %), and lidocaine (18.9 %) being the most detected. The most prevalent exposure circumstance among the cases was suicide attempt. The most frequent age groups were young adults between 20 and 29 years old and children under 5 years old. The methodology developed proved to be efficient in the simultaneous determination of 57 substances of toxicological interest, contributing to a correct diagnosis and, consequently, to the most appropriate management and treatment of the intoxicated patient. Furthermore, it is possible to observe the most commonly involved toxic agents in the Rio Grande do Sul, southern Brazil, helping to trace a profile of the poisoning patient, important in toxicovigilance actions.


Subject(s)
Illicit Drugs , Humans , Child , Child, Preschool , Young Adult , Adult , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods , Plasma , Brazil , Reproducibility of Results , Limit of Detection
2.
Int J Cancer ; 152(2): 214-226, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36054767

ABSTRACT

The underlying biological mechanisms causing persistent fatigue complaints after colorectal cancer treatment need further investigation. We investigated longitudinal associations of circulating concentrations of 138 metabolites with total fatigue and subdomains of fatigue between 6 weeks and 2 years after colorectal cancer treatment. Among stage I-III colorectal cancer survivors (n = 252), blood samples were obtained at 6 weeks, and 6, 12 and 24 months posttreatment. Total fatigue and fatigue subdomains were measured using a validated questionnaire. Tandem mass spectrometry was applied to measure metabolite concentrations (BIOCRATES AbsoluteIDQp180 kit). Confounder-adjusted longitudinal associations were analyzed using linear mixed models, with false discovery rate (FDR) correction. We assessed interindividual (between-participant differences) and intraindividual longitudinal associations (within-participant changes over time). In the overall longitudinal analysis, statistically significant associations were observed for 12, 32, 17 and three metabolites with total fatigue and the subscales "fatigue severity," "reduced motivation" and "reduced activity," respectively. Specifically, higher concentrations of several amino acids, lysophosphatidylcholines, diacylphosphatidylcholines, acyl-alkylphosphatidylcholines and sphingomyelins were associated with less fatigue, while higher concentrations of acylcarnitines were associated with more fatigue. For "fatigue severity," associations appeared mainly driven by intraindividual associations, while for "reduced motivation" stronger interindividual associations were found. We observed longitudinal associations of several metabolites with total fatigue and fatigue subscales, and that intraindividual changes in metabolites over time were associated with fatigue severity. These findings point toward inflammation and an impaired energy metabolism due to mitochondrial dysfunction as underlying mechanisms. Mechanistic studies are necessary to determine whether these metabolites could be targets for intervention.


Subject(s)
Cancer Survivors , Colorectal Neoplasms , Humans , Survivors , Fatigue/etiology , Plasma , Colorectal Neoplasms/complications
3.
Bioanalysis ; 14(5): 307-316, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35195039

ABSTRACT

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.


Subject(s)
Plasma , Tandem Mass Spectrometry , Chromatography, Liquid/methods , Humans , Reproducibility of Results , Tandem Mass Spectrometry/methods
4.
Medicine (Baltimore) ; 101(43): e31322, 2022 Oct 28.
Article in English | MEDLINE | ID: mdl-36316901

ABSTRACT

RATIONALE: Dengue obstructive shock syndrome is a fatal complication commonly observed in the late critical phase of dengue infection and is associated with a high mortality rate. The main pathogenesis involves a dramatic increase in chest pressure, owing to severe plasma leakage and mechanical respiratory support, hampering the heart's ability to pump effectively and impeding adequate blood venous return to the heart chambers. To date, there is a paucity of clinical data about Dengue obstructive shock syndrome reported. PATIENT CONCERNS: The 2 reported patients presented with prolonged and decompensated dengue shock with critical multi-organ failures and mechanical ventilation. The patients' hemodynamics were profoundly affected by high pressure in the thoracic and abdominal cavities resulting from Dengue-induced severe plasma leakage and mechanical ventilation. DIAGNOSES: Clinical presentations, laboratory data, mini-fluid challenge test, and point-of-care (POCUS) were used to make diagnoses and guide management. INTERVENTIONS: Clinical monitoring, judicious fluid (colloids and blood products) administration guided by repeated POCUS to properly assess the adequacy of the intravascular volume, homeostasis adjustments by plasma exchange, and continuous renal replacement therapies. OUTCOMES: The patients had favorable outcomes. LESSONS: Our study highlights the clinical manifestations and management of children with dengue obstructive shock syndrome and underscores the importance of monitoring hemodynamics by consecutive POCUS at the bedside in order to make a timely diagnosis and assess intravascular fluid volume inadequacy accurately as well as closely monitor the fluid management responses.


Subject(s)
Dengue , Respiration, Artificial , Child , Humans , Hemodynamics , Monitoring, Physiologic , Plasma , Dengue/complications , Dengue/diagnosis , Dengue/therapy
5.
Nat Commun ; 13(1): 6547, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36319635

ABSTRACT

Lipids are a structurally diverse class of biomolecules which can undergo a variety of chemical modifications. Among them, lipid (per)oxidation attracts most of the attention due to its significance in the regulation of inflammation, cell proliferation and death programs. Despite their apparent regulatory significance, the molecular repertoire of oxidized lipids remains largely elusive as accurate annotation of lipid modifications is complicated by their low abundance and often unknown, biological context-dependent structural diversity. Here, we provide a workflow based on the combination of bioinformatics and LC-MS/MS technologies to support identification and relative quantification of oxidized complex lipids in a modification type- and position-specific manner. The developed methodology is used to identify epilipidomics signatures of lean and obese individuals with and without type 2 diabetes. The characteristic signature of lipid modifications in lean individuals, dominated by the presence of modified octadecanoid acyl chains in phospho- and neutral lipids, is drastically shifted towards lipid peroxidation-driven accumulation of oxidized eicosanoids, suggesting significant alteration of endocrine signalling by oxidized lipids in metabolic disorders.


Subject(s)
Diabetes Mellitus, Type 2 , Tandem Mass Spectrometry , Humans , Chromatography, Liquid , Tandem Mass Spectrometry/methods , Workflow , Lipids/chemistry , Plasma/chemistry
6.
Georgian Med News ; (328-329): 118-121, 2022.
Article in English | MEDLINE | ID: mdl-36318854

ABSTRACT

The aim of the study is to evaluate the dependence of associations of ST2, and Troponin I level on the nature of the anatomical lesion of the coronary arteries. We examined 200 patients with NSTEMI aged 38 to 80 years, who were urgently hospitalized in the Vinnytsya Regional Clinical Center of Cardiovascular Pathology. All patients underwent laboratory testing of ST2, and Troponin I level in plasma by enzyme-linked immunosorbent assay on the first day of hospitalization before coronary angiography. In the association of relatively high levels of ST2 and relatively high levels of Troponin I, there is a positive correlation between the degree of coronary arteries damage, while in the association of relatively low levels of ST2 and Troponin I, severe stenotic coronary arteries lesions can be ruled out. Determining the associations of ST2 and Troponin I before coronary angiography allows to predict the degree of stenotic lesions of the coronary arteries and to determine the expected intervention strategy in patients with NSTEMI.


Subject(s)
Myocardial Infarction , Non-ST Elevated Myocardial Infarction , Humans , Troponin I , Coronary Vessels/pathology , Non-ST Elevated Myocardial Infarction/pathology , Interleukin-1 Receptor-Like 1 Protein , Plasma , Biomarkers
7.
Hematology ; 27(1): 1217-1222, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36367991

ABSTRACT

OBJECTIVES: This study evaluates the efficacy and safety of plasmapheresis without plasma transfusion tandem with chemotherapy in treating multiple myeloma (MM). METHOD: This retrospective study involves seventy-two patients, newly diagnosed with multiple myeloma, divided into two groups; one with plasmapheresis without plasma transfusion tandem with the chemotherapy group (Trial group), while the second was chemotherapy group (Control group). The levels of Plasma Globulin, ß2-microglobulin, Creatinine, Vascular endothelial growth factor (VEGF), and IL-6 were monitored after plasmapheresis, at initial diagnosis, and after four chemotherapy courses. Overall response rate of groups after four courses of chemotherapy was analyzed, and the adverse events were recorded. RESULTS AND DISCUSSION: The baseline data showed that sixty-seven percent of patients were at the ISS III stage and showed more severe renal insufficiency in the Trial group. The Plasma Globulin, ß2-microglobulin, VEGF and IL-6 levels were significantly different between the two groups during the initial diagnosis. After three times plasmapheresis, Plasma Globulin, ß2-microglobulin, VEGF, and IL-6 were significantly reduced in the plasmapheresis group. The Creatinine levels were also lowered, but the differences were not statistically significant. After four courses of chemotherapy, the levels of VEGF and IL-6 in the two groups were significantly reduced than the initial diagnosis; the differences were statistically considerable. No adverse events were found in the trial group as compared to the control group. CONCLUSION: Plasmapheresis reduces Globulin, ß2-microglobulin, serum VEGF and IL-6 levels in MM, improves renal functions, and releases some patients from dialysis dependence.


Subject(s)
Multiple Myeloma , Humans , Multiple Myeloma/drug therapy , Vascular Endothelial Growth Factor A/therapeutic use , Creatinine , Retrospective Studies , Interleukin-6 , Blood Component Transfusion , Plasma , Plasmapheresis
8.
Magnes Res ; 35(2): 51-61, 2022 04 01.
Article in English | MEDLINE | ID: mdl-36354242

ABSTRACT

Deficiency of serum magnesium is associated with the incidence of migraine attacks. The present study aimed to evaluate plasma and erythrocyte magnesium levels in a group of patients diagnosed with migraine. Human donors were selected from basic health units (migraine, n = 25) and from a collection and transfusion unit (control, n = 25), both located in the city of Sinop, Brazil. Plasma and erythrocyte magnesium were assessed using flame atomic absorption. Plasma magnesium concentration was significantly lower in the migraine group (0.172 ± 0.018) compared to the control group (0.197 ± 0.020 mg/L), and erythrocyte magnesium concentration was also lower in the migraine group (0.393 ± 0.053 mg/L) compared to the control group (0.432 ± 0.056 mg/L). The method for analysis of magnesium in human plasma and erythrocytes by flame atomic absorption was shown to be in accordance with validation guidelines. This study shows that plasma and erythrocyte magnesium levels were significantly lower in volunteers diagnosed with migraine compared to healthy volunteers. Furthermore, erythrocyte magnesium proved to be a better marker than plasma magnesium for patients with migraine.


Subject(s)
Magnesium , Migraine Disorders , Humans , Migraine Disorders/diagnosis , Erythrocytes , Plasma , Volunteers
9.
Nutrients ; 14(21)2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36364861

ABSTRACT

Obesity increases the risk of insulin resistance and type 2 diabetes through increased inflammation at cellular and tissue levels. Therefore, study of the molecular elements involved in obesity-related inflammation may contribute to preventing and controlling it. Inorganic polyphosphate is a natural phosphate polymer that has recently been attracting more attention for its role in inflammation and hemostasis processes. Polyphosphates are one of the main constituents of human platelets, which are secreted after platelet activation. Among other roles, they interact with multiple proteins of the coagulation cascade, trigger bradykinin release, and inhibit the complement system. Despite its importance, determinations of polyphosphate levels in blood plasma had been elusive until recently, when we developed a method to detect these levels precisely. Here, we perform cross sectional studies to evaluate plasma polyphosphate in: 25 children, most of them with obesity and overweight, and 20 adults, half of them with severe type 2 diabetes. Our results show that polyphosphate increases, in a significant manner, in children with insulin resistance and in type 2 diabetes patients. As we demonstrated before that polyphosphate decreases in healthy overweight individuals, these results suggest that this polymer could be an inflammation biomarker in the metabolic disease onset before diabetes.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Pediatric Obesity , Child , Humans , Polyphosphates/metabolism , Polyphosphates/pharmacology , Overweight , Cross-Sectional Studies , Pediatric Obesity/complications , Plasma/metabolism , Inflammation/metabolism , Polymers
10.
Zhonghua Yan Ke Za Zhi ; 58(11): 946-947, 2022 Nov 11.
Article in Chinese | MEDLINE | ID: mdl-36348538

ABSTRACT

The patient was a 48-year-old male with a previous history of diabetes mellitus and hypertension. The patient had persistent bleeding after vitrectomy of the left eye, and the patient was examined for abnormal coagulation factor Ⅷ combined with Ⅻ. This case suggests that we need effective control of blood glucose and blood pressure in patients undergoing vitrectomy in clinical work, and adequate examination of coagulation function. Patients with coagulation factor deficiency should be treated with plasma transfusion to supplement coagulation factors before performing the necessary surgical treatment to prevent severe bleeding.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Male , Humans , Middle Aged , Diabetic Retinopathy/therapy , Factor VIII/therapeutic use , Blood Component Transfusion , Plasma , Vitrectomy , Laser Coagulation , Diabetes Mellitus/surgery
11.
PLoS One ; 17(11): e0277476, 2022.
Article in English | MEDLINE | ID: mdl-36374928

ABSTRACT

Histidine is an essential amino acid for broiler chickens and a precursor for the dipeptides carnosine and anserine, but little information is available about its metabolism in modern, fast-growing broilers. We used untargeted metabolomics to investigate the metabolic changes caused by the use of different standardized ileal digestible His:Lys ratios in broiler diets with and without ß-alanine supplementation. A total of 2204 broilers were randomly divided into 96 pens of 23 birds each. The pens were divided into 16 blocks, each containing one pen for all six feeding groups (total of 16 pens per group). These feeding groups were fed three different His:Lys ratios (0.44, 0.54, and 0.64, respectively) without and with a combination of 0.5% ß-alanine supplementation. Five randomly selected chickens of one single randomly selected pen per feeding group were slaughtered on day 35 or 54, blood was collected from the neck vessel, and plasma was used for untargeted metabolomic analysis. Here we show that up to 56.0% of all metabolites analyzed were altered by age, whereas only 1.8% of metabolites were affected by the His:Lys ratio in the diet, and 1.5% by ß-alanine supplementation. Two-factor analysis and metabolic pathway analysis showed no interaction between the His:Lys ratio and ß-alanine supplementation. The effect of the His:Lys ratio in the diet was limited to histidine metabolism with a greater change in formiminoglutamate concentration. Supplementation of ß-alanine showed changes in metabolites of several metabolic pathways; increased concentrations of 3-aminoisobutyrate showed the only direct relationship to ß-alanine metabolism. The supplementation of ß-alanine indicated few effects on histidine metabolism. These results suggest that the supplements used had limited effects or interactions on both His and ß-alanine metabolism. In contrast, the birds' age has the strongest influence on the metabolome.


Subject(s)
Chickens , Histidine , Animals , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , beta-Alanine/pharmacology , beta-Alanine/metabolism , Chickens/metabolism , Diet/veterinary , Dietary Supplements/analysis , Histidine/metabolism , Metabolome , Plasma/metabolism
12.
Int J Mol Sci ; 23(21)2022 Oct 26.
Article in English | MEDLINE | ID: mdl-36361759

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death that typically presents at an advanced stage. No reliable markers for early detection presently exist. The prominent tumor stroma represents a source of circulating biomarkers for use together with cancer cell-derived biomarkers for earlier PDAC diagnosis. CA19-9 and CEA (cancer cell-derived biomarkers), together with endostatin and collagen IV (stroma-derived) were examined alone, or together, by multivariable modelling, using pre-diagnostic plasma samples (n = 259 samples) from the Northern Sweden Health and Disease Study biobank. Serial samples were available for a subgroup of future patients. Marker efficacy for future PDAC case prediction (n = 154 future cases) was examined by both cross-sectional (ROC analysis) and longitudinal analyses. CA19-9 performed well at, and within, six months to diagnosis and multivariable modelling was not superior to CA19-9 alone in cross-sectional analysis. Within six months to diagnosis, CA19-9 (AUC = 0.92) outperformed the multivariable model (AUC = 0.81) at a cross-sectional level. At diagnosis, CA19-9 (AUC = 0.995) and the model (AUC = 0.977) performed similarly. Longitudinal analysis revealed increases in CA19-9 up to two years to diagnosis which indicates a window of opportunity for early detection of PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , CA-19-9 Antigen , Cross-Sectional Studies , Early Detection of Cancer , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/pathology , Biomarkers, Tumor , Plasma
13.
Thromb Res ; 220: 100-106, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36334396

ABSTRACT

INTRODUCTION: COVID-19 disease, which has recently become an important cause of mortality and morbidity all over the world, is remarkably associated with thrombotic complications. Although many factors are responsible for these increased thrombotic complications in COVID-19 disease, its relationship with a marker that increases the risk of thrombosis such as Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) has not yet been clarified. This is the first study to examine the potential diagnostic and prognostic value of SCUBE1 levels in patients with COVID-19. In this study, we aimed to clarify the relationship between the increased risk of thrombosis and SCUBE1 in the course of COVID-19 disease. MATERIALS AND METHODS: 553 patients with COVID-19 and 553 healthy controls were compared in terms of SCUBE1 levels. Additionally, patients with COVID-19 were divided into two groups according to their SCUBE1 levels and compared in terms of severity of disease, thrombotic complications and in-hospital mortality. RESULTS: SCUBE1 levels were significantly higher in patients with COVID-19 compared to the control group (p < 0.001). Plasma SCUBE1 levels were significantly higher in patients with severe disease and thrombotic complications, those with mild to moderate disease, and those without thrombotic complications (p < 0.001, for both). In addition, SCUBE1 was found to be an independent predictor of in-hospital mortality (p < 0.001). CONCLUSIONS: SCUBE1 may be one of the major determinants of thrombotic complications, which is an increased cause of mortality and morbidity in COVID-19 patients so inhibition of this peptide may be among the therapeutic targets in patients with COVID-19.


Subject(s)
COVID-19 , Thrombosis , Humans , Hospital Mortality , COVID-19/complications , Thrombosis/etiology , Plasma , Severity of Illness Index , Calcium-Binding Proteins
14.
Klin Lab Diagn ; 67(11): 633-639, 2022 Nov 14.
Article in English | MEDLINE | ID: mdl-36398771

ABSTRACT

The aim of the study is to develop a method for early diagnosis of intrauterine infection (IUI). A study of markers of inflammation in the venous blood of 60 pregnant women was conducted. The study was followed by a retrospective assessment of the outcomes of pregnancies and childbirth. Of these, 33 patients with a gestation period of more than 37 weeks (full-term pregnancy) and, accordingly, 27 patients from whom the blood sample was taken at a period of less than 37 weeks - patients with the threat of premature birth (PB). PB is the main factor contributing to the development of IUI. 27 patients were diagnosed with premature rupture of the membranes (PROM). Of these, 15 are with the threat of PB. 8 of them had a diagnosed IUI. In all cases of diagnosed PROM, including those with IUI, the concentration of nitrite and nontiolate nitroso compounds (NO2-+RNO) in the mother's blood plasma was 2.3±1.2 µM, while normally it does not exceed 0.1 µM (p<0.001). Regardless of the duration of pregnancy. The use of antibiotics in the case of PROM contributed to the normalization of the concentration (NO2-+RNO). Therefore, increasing of this indicator is result of bacterial infection. Indications of other markers of inflammation: the number of leukocytes in venous blood and in a smear of vaginal contents, the level of C-RB did not significantly change in both PROM and IUI (p>0.1). Since the concentration index (NO2-+RNO) increased in almost all cases of PREM, unlike all other clinical and biochemical indicators used in modern medicine, there is an obvious sense of its use for the current monitoring of the health of pregnant women. But it is still impossible to say unequivocally about the possibility of monitoring the fetal health by concentration (NO2-+RNO) in the mother's blood.


Subject(s)
Communicable Diseases , Fetal Membranes, Premature Rupture , Pregnancy Complications , Premature Birth , Pregnancy , Humans , Female , Nitrites , Fetal Membranes, Premature Rupture/diagnosis , Nitroso Compounds , Retrospective Studies , Nitrogen Dioxide , Plasma , Inflammation
15.
Nat Med ; 28(11): 2321-2332, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36357675

ABSTRACT

Garrod's concept of 'chemical individuality' has contributed to comprehension of the molecular origins of human diseases. Untargeted high-throughput metabolomic technologies provide an in-depth snapshot of human metabolism at scale. We studied the genetic architecture of the human plasma metabolome using 913 metabolites assayed in 19,994 individuals and identified 2,599 variant-metabolite associations (P < 1.25 × 10-11) within 330 genomic regions, with rare variants (minor allele frequency ≤ 1%) explaining 9.4% of associations. Jointly modeling metabolites in each region, we identified 423 regional, co-regulated, variant-metabolite clusters called genetically influenced metabotypes. We assigned causal genes for 62.4% of these genetically influenced metabotypes, providing new insights into fundamental metabolite physiology and clinical relevance, including metabolite-guided discovery of potential adverse drug effects (DPYD and SRD5A2). We show strong enrichment of inborn errors of metabolism-causing genes, with examples of metabolite associations and clinical phenotypes of non-pathogenic variant carriers matching characteristics of the inborn errors of metabolism. Systematic, phenotypic follow-up of metabolite-specific genetic scores revealed multiple potential etiological relationships.


Subject(s)
Metabolism, Inborn Errors , Metabolome , Humans , Metabolome/genetics , Metabolomics , Plasma/metabolism , Phenotype , Metabolism, Inborn Errors/genetics , Membrane Proteins/metabolism , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism
16.
Sci Rep ; 12(1): 19977, 2022 Nov 20.
Article in English | MEDLINE | ID: mdl-36404352

ABSTRACT

Metabolomic analysis of blood plasma samples from COVID-19 patients is a promising approach allowing for the evaluation of disease progression. We performed the metabolomic analysis of plasma samples of 30 COVID-19 patients and the 19 controls using the high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometric detection (LC-MS/MS). In our analysis, we identified 103 metabolites enriched in KEGG metabolic pathways such as amino acid metabolism and the biosynthesis of aminoacyl-tRNAs, which differed significantly between the COVID-19 patients and the controls. Using ANDSystem software, we performed the reconstruction of gene networks describing the potential genetic regulation of metabolic pathways perturbed in COVID-19 patients by SARS-CoV-2 proteins. The nonstructural proteins of SARS-CoV-2 (orf8 and nsp5) and structural protein E were involved in the greater number of regulatory pathways. The reconstructed gene networks suggest the hypotheses on the molecular mechanisms of virus-host interactions in COVID-19 pathology and provide a basis for the further experimental and computer studies of the regulation of metabolic pathways by SARS-CoV-2 proteins. Our metabolomic analysis suggests the need for nonstructural protein-based vaccines and the control strategy to reduce the disease progression of COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Gene Regulatory Networks , Chromatography, Liquid , Tandem Mass Spectrometry , Plasma , Viral Proteins/genetics , Disease Progression
17.
BMC Vet Res ; 18(1): 400, 2022 Nov 12.
Article in English | MEDLINE | ID: mdl-36371198

ABSTRACT

The purpose of this study was to perform a histological and biochemical evaluation of the influence of plasma rich in growth factors (PRGF) on muscle regeneration process after a surgically induced grade II muscle laceration. A randomized, single blind, controlled experimental research was conducted including twenty-one adult healthy sheep, randomly divided in three groups (n = 7). A grade II surgical section was performed in the biceps femoris muscle of both hindlimbs. After two days (basal time), intralesional infiltration of autologous PRGF or Saline solution was randomly administered in both hindlimbs. Treatment was repeated once a week. Animal groups were euthanized at 1 (T1), 2 (T2) or 4 (T4) weeks. Histological assessment showed that PRGF intralesional injection induced a significant decrease of inflammatory cells density, significant higher centrally nucleated fibers percentage and significantly smaller fibrotic areas compared to Saline-treated muscles at T1, T2 and T4. Also, lower vascular density, with lower capillaries cross-sectional area, in PRGF group compared to Saline was observed. Biochemical analysis revealed a significant higher expression level of MYOD1, MYF5 and MYOG genes in PRGF groups at T1 compared to Saline treated muscles. At ultrastructural level, PRGF groups presented scarce edema and loss of connective tissue structure, as well as higher mitochondrial density adequately associated to the sarcomere unit in contrast to the Saline group. In conclusion, histological, biochemical, and ultrastructural results showed that PRGF treatment improved muscle regeneration process leading to more mature histological aspect in newly formed muscle tissue after a surgically induced grade II muscle injury.


Subject(s)
Euthanasia, Animal , Platelet-Rich Plasma , Sheep , Animals , Single-Blind Method , Intercellular Signaling Peptides and Proteins/therapeutic use , Plasma , Muscles
18.
J Extracell Vesicles ; 11(11): e12281, 2022 11.
Article in English | MEDLINE | ID: mdl-36404468

ABSTRACT

Extracellular vesicles (EVs) have found diverse applications in clinical theranostics. However, the current techniques to isolate plasma EVs suffer from burdensome procedures and limited yield. Herein, we report a rapid and efficient EV isolation platform, namely, EV-FISHER, constructed from the metal-organic framework featuring cleavable lipid probes (PO4 3- -spacer-DNA-cholesterol, PSDC). The EV-FISHER baits EVs from plasma by cholesterol and separates them with an ordinary centrifuge. The captured EVs could be released and collected upon subsequent cleavage of PSDC by deoxyribonuclease I. We conclude that EV-FISHER dramatically outperforms the ultracentrifugation (UC) in terms of time (∼40 min vs. 240 min), isolation efficiency (74.2% vs. 18.1%), and isolation requirement (12,800 g vs. 135,000 g). In addition to the stable performance in plasma, EV-FISHER also exhibited excellent compatibility with downstream single-EV flow cytometry, enabling the identification of glypican-1 (GPC-1) EVs for early diagnosis, clinical stages differentiation, and therapeutic efficacy evaluation in breast cancer cohorts. This work portrays an efficient strategy to isolate EVs from complicated biological fluids with promising potential to facilitate EVs-based theranostics.


Subject(s)
Extracellular Vesicles , Ultracentrifugation/methods , Plasma , Flow Cytometry
19.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 40(9): 507-516, Nov. 2022. ilus, tab
Article in English | IBECS | ID: ibc-211212

ABSTRACT

Patients lacking humoral response have been suggested to develop a less severe COVID-19, but there are some reports with a prolonged, relapsing or deadly course. From April 2020, there is growing evidence on the benefits of COVID-19 convalescent plasma (CCP) for patients with humoral immunodeficiency. Most of them had a congenital primary immunodeficiency or were on treatment with anti CD20 antibodies. We report on three patients treated in our hospital and review thirty-one more cases described in the literature. All patients but three resolved clinical picture with CCP. A dose from 200 to 800ml was enough in most cases. Antibody levels after transfusion were negative or low, suggesting consumption of them in SARS-CoV-2 neutralization. These patients have a protracted clinical course shortened after CCP. CCP could be helpful for patients with humoral immunodeficiency. It avoid relapses and chronification. CCP should be transfused as early as possible in patients with COVID-19 and humoral immunodeficiency.(AU)


Se ha sugerido que los pacientes carentes de respuesta inmune humoral desarrollan una forma menos severa de COVID-19, pero existen algunos casos de curso prolongado, recurrente o incluso mortal. Desde abril de 2020 existen evidencias de los beneficios del plasma de convalecientes de COVID-19 (PCC) en los pacientes con inmunodeficiencia humoral. La mayoría tienen una inmunodeficiencia congénita primaria o están recibiendo tratamiento con anticuerpos anti-CD20. Describimos tres pacientes con inmunodeficiencia humoral y COVID-19 tratados con PCC en nuestro centro y revisamos los 31 casos más descritos en la literatura. Todos resolvieron el cuadro clínico con PCC, salvo tres. Una dosis de 200-800 mL fue suficiente en la mayoría de los casos. Los niveles de anticuerpos tras la transfusión fueron negativos o bajos, sugiriendo el consumo de los mismos en la neutralización del SARS-CoV-2. Estos pacientes tienen un curso clínico prolongado que se acorta tras la administración del PCC. El PCC podría ser de utilidad en los pacientes con inmunodeficiencia humoral. Evita las recaídas y la cronificación de la COVID-19. El PCC debería transfundirse lo antes posible en los pacientes con COVID-19 e inmunodeficiencia humoral.(AU)


Subject(s)
Humans , Coronavirus Infections/epidemiology , Betacoronavirus , SARS Virus , Plasma , Therapeutics , Rituximab , Immunotherapy , Immunity, Humoral , Microbiology , Communicable Diseases
20.
J Chromatogr A ; 1683: 463535, 2022 Nov 08.
Article in English | MEDLINE | ID: mdl-36208486

ABSTRACT

Efforts to rapidly and easily supply purified human serum albumin (HSA) in remote areas during a pandemic are challenging. Here, we developed an HSA-imprinted microsphere (HSAIM) as a matrix to purify HSA from blood plasma on a small scale. HSAIMs were generated by encapsulating silica-3-(2-imidazoline-1-yl) propyltriethoxysilane-Cu2+-HSA (SiO2-IMEO-Cu2+-HSA) into agarose gel, and the stereospecific template for HSA was obtained by eluting the agarose gel. The physicochemical properties and performance of HSAIM were evaluated, and HSAIMs were applied to purify HSA from human blood plasma. Spherical HSAIMs had an average diameter of 51.2 ± 6.1 µm. HSAIMs had a maximum adsorption of 8.77 × 10-2 µmol HSA g-1 with an imprinting factor of 2.83, and the selectivity factors of BSA, thrombin and IgG were 0.96, 0.59 and 0.26, respectively. HSAIMs had a dynamic binding capacity (DBC10%) of 5.94 × 10-2 µmol HSA g-1 and could be reused up to 10 cycles with an ultimate recovery of 55.92%. HSA adsorption kinetics of HSAIM fitted to a pseudo-second-order mechanism, and HSA binding characteristics fit with a Sips isotherm model. For practical purposes, an initial blood plasma sample containing 24.9 ± 2.5 mg protein was pretreated with ethanol yielding 14.5 ± 4.6 mg protein, and further purification with HSAIM yielded 3.6 ± 1.1 mg protein. Starting with a blood plasma sample containing 149 type proteins, a single protein identified as HSA was obtained after final purification step with the HSAIM column, indicating that HSAIMs stereospecifically bound HSA. Hence, HSAIM was promising for blood plasma purification on a small scale.


Subject(s)
Microspheres , Serum Albumin, Human , Serum Albumin , Humans , Ethanol , Immunoglobulin G , Plasma , Sepharose/chemistry , Serum Albumin/chemistry , Serum Albumin, Human/chemistry , Silicon Dioxide , Thrombin , Chromatography, Affinity/methods
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