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3.
J Chromatogr A ; 1651: 462329, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34157477

RESUMO

Efficiently tunable capture of the glycosylated/phosphorylated proteins is critical to meet the need of in-depth glycoproteome and phosphoproteome studies. Reported here is a new bifunctional polymer monolithic column by introducing benzeneboronic acid and phosphonic acid onto monolithic column (denoted as poly (EDMA-co-VPBA-co-VPA) monolith) for tunable and specific enrichment of glycoproteins and phosphoproteins via switching different mobile phases. Based on boronate affinity and immobilized metal affinity, the as-prepared poly (EDMA-co-VPBA-co-VPA) monolith exhibited superior performance in selective separation of small molecules and biomacromolecules containing cis-diol/phosphate groups or not. And the frontal chromatography analysis showed that the binding capacity of the poly (EDMA-co-VPBA-co-VPA) monolith towards horseradish peroxidase (HRP, glycoprotein) or ß-casein (phosphoprotein) is four-fold higher than that of bovine serum albumin (BSA, non-glycosylated/phosphorylated protein). Furthermore, combined with mass spectrometry identification, the successful application in specific enrichment of glycopeptides/phosphopeptides from tryptic digests of HRP/ß-casein and direct capture of low abundant endogenous phosphopeptides from human serum proved great practicability in complex samples. This study provides a novel insight for fabricating the monolithic columns with multifunctionalization to facilitate further post-translational modification (PTM)-proteomics development.


Assuntos
Análise Química do Sangue/instrumentação , Cromatografia/instrumentação , Glicoproteínas/isolamento & purificação , Fosfoproteínas/isolamento & purificação , Polímeros/química , Ácidos Borônicos/química , Caseínas/metabolismo , Glicopeptídeos/isolamento & purificação , Peroxidase do Rábano Silvestre/metabolismo , Humanos , Fosfopeptídeos/química , Ácidos Fosforosos/química , Soroalbumina Bovina/isolamento & purificação
4.
J Chromatogr A ; 1650: 462228, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34090133

RESUMO

Bioactive 11-oxygenated C19 adrenal-derived steroids (11-oxy C19) are potentially relevant in diverse endocrine and metabolic contexts. We report the development and validation of a liquid chromatography electrospray ionization tandem mass spectrometric method (LC-ESI-MS/MS) for the simultaneous quantification of seven 11-oxy C19 using 200 µL of plasma or serum. Sample preparation involved chemical derivatization using hydroxylamine after liquid-liquid extraction to improve specificity and sensitivity. The method allowed the quantitation of total 11-oxy C19 (free + sulfate and glucuronide conjugates) following enzymatic hydrolysis. This included the abundant precursor 11-hydroxyandrostenedione (11OHA4) and the most potent androgenic derivatives 11-keto-testosterone (11KT) and 11-keto-dihydrotestosterone (11KDHT), their abundant metabolites 11-hydroxyandrosterone (11OHAST) and 11-keto-androsterone (11KAST) potentially feeding back into the pool of potent androgens, in addition to 11-keto-androstenedione (11KA4) and 11-hydroxytestosterone (11OHT). Stable isotopes were used as internal standards, and calibrators and quality controls were prepared in the same matrix as the study samples. Performance was validated against the Food and Drug Administration Criteria. The method was sensitive with lower limit of quantification (LLOQ) values of 10 and 20 pg/mL for free and total 11-oxy C19, respectively. The applicability was demonstrated in men and women adult donors that showed sex-differences. All steroids were quantified well above LLOQ, except 11KDHT that remained undetectable suggesting interfering endogenous molecules present in non-derivatized samples in which a peak was observed. By providing accurate and reliable quantitative data, this method will permit to evaluate how profiling of 11-oxy C19 will be most informative as diagnostic, prognostic and/or theranostic tools.


Assuntos
Androgênios , Análise Química do Sangue , Cromatografia Líquida , Espectrometria de Massas em Tandem , Adulto , Androgênios/sangue , Androstenodiona/análogos & derivados , Androstenodiona/sangue , Análise Química do Sangue/métodos , Feminino , Glucuronídeos , Humanos , Hidroxitestosteronas/sangue , Limite de Detecção , Masculino , Oxigênio/química , Esteroides/sangue , Testosterona/análogos & derivados , Testosterona/sangue
6.
J Clin Neurosci ; 88: 16-21, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33992178

RESUMO

BACKGROUND: There are no established ranges for metabolic values prior to death by neurologic criteria/brain death determination (DNC/BD) and the thresholds required by institutional protocols and accepted by neurointensivists is unknown. METHODS: We designed a survey that addressed 1) the metabolic tests required in institutional guidelines prior to brain death determination, 2) the metabolic tests the respondent reviewed prior to brain death determination, and 3) the metabolic test thresholds for laboratory tests that were perceived to preclude or permit clinical DNC/BD determination. The survey was distributed online to physicians in the Neurocritical Care Society from September to December 2019. Respondents were dichotomized based on the number of brain death evaluations they had performed (≤20 vs. > 20) and responses were compared between groups. RESULTS: The survey was completed by 84 physicians. Nearly half (47.6%) of respondents did not believe their institutions required metabolic testing. The metabolic testing for which institutions most commonly provided a defined threshold were arterial pH (34.5%, 29/84), sodium (28.6%, 24/84), and glucose (15.5%, 13/84). Nearly all (97.6%) respondents routinely reviewed metabolic tests prior to brain death evaluation, the most common of which were: sodium (91.7%, 77/84), arterial pH (83.3%, 70/84), and glucose (79.8%, 67/84). Respondents who had performed > 20 evaluations were less likely to check thyroxine and total bilirubin (3.6%, 2/55 vs. 20.7%, 6/29 (p = 0.011) and 12.7%, 7/55 vs. 31%, 9/29 (p = 0.042), respectively), and had a more liberal upper limit of potassium (6.3 mEq/L vs 6.0 mEq/L, p = 0.045). CONCLUSION: Prior to brain death evaluation, neurocritical care providers commonly review similar metabolic tests and have similar thresholds regarding values that would preclude clinical brain death determination. This finding is independent of experience with brain death determination.


Assuntos
Morte Encefálica/sangue , Morte Encefálica/diagnóstico , Cuidados Críticos/normas , Guias como Assunto , Adulto , Idoso , Análise Química do Sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Médicos , Valores de Referência , Inquéritos e Questionários
7.
N Engl J Med ; 384(22): 2124-2130, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-33835768

RESUMO

We report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (Covid-19). The patients were health care workers who were 32 to 54 years of age. All the patients had high levels of antibodies to platelet factor 4-polyanion complexes; however, they had had no previous exposure to heparin. Because the five cases occurred in a population of more than 130,000 vaccinated persons, we propose that they represent a rare vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia.


Assuntos
Autoanticorpos/sangue , Vacinas contra COVID-19/efeitos adversos , Fator Plaquetário 4/imunologia , Trombocitopenia/etiologia , Trombose/etiologia , Adulto , Doenças Autoimunes/etiologia , Análise Química do Sangue , Ensaio de Imunoadsorção Enzimática , Evolução Fatal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária , Contagem de Plaquetas
8.
N Engl J Med ; 384(22): 2124-2130, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: covidwho-1174740

RESUMO

We report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (Covid-19). The patients were health care workers who were 32 to 54 years of age. All the patients had high levels of antibodies to platelet factor 4-polyanion complexes; however, they had had no previous exposure to heparin. Because the five cases occurred in a population of more than 130,000 vaccinated persons, we propose that they represent a rare vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia.


Assuntos
Autoanticorpos/sangue , Vacinas contra COVID-19/efeitos adversos , Fator Plaquetário 4/imunologia , Trombocitopenia/etiologia , Trombose/etiologia , Adulto , Doenças Autoimunes/etiologia , Análise Química do Sangue , Ensaio de Imunoadsorção Enzimática , Evolução Fatal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária , Contagem de Plaquetas
9.
N Engl J Med ; 384(22): 2092-2101, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: covidwho-1174739

RESUMO

BACKGROUND: Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder. METHODS: We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)-heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4-heparin immunoassay. RESULTS: Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4-heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor-blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4-heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation. CONCLUSIONS: Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.).


Assuntos
Autoanticorpos/sangue , Vacinas contra COVID-19/efeitos adversos , Fator Plaquetário 4/imunologia , Trombocitopenia/etiologia , Trombose/etiologia , Adulto , Doenças Autoimunes/etiologia , Análise Química do Sangue , Coagulação Intravascular Disseminada/etiologia , Ensaio de Imunoadsorção Enzimática , Evolução Fatal , Feminino , Humanos , Hemorragias Intracranianas/etiologia , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária , Trombocitopenia/imunologia , Trombose/imunologia , Adulto Jovem
10.
Int J Mol Sci ; 22(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: covidwho-1134169

RESUMO

Fibrinolysis is an important process in hemostasis responsible for dissolving the clot during wound healing. Plasmin is a central enzyme in this process via its capacity to cleave fibrin. The kinetics of plasmin generation (PG) and inhibition during fibrinolysis have been poorly understood until the recent development of assays to quantify these metrics. The assessment of plasmin kinetics allows for the identification of fibrinolytic dysfunction and better understanding of the relationships between abnormal fibrin dissolution and disease pathogenesis. Additionally, direct measurement of the inhibition of PG by antifibrinolytic medications, such as tranexamic acid, can be a useful tool to assess the risks and effectiveness of antifibrinolytic therapy in hemorrhagic diseases. This review provides an overview of available PG assays to directly measure the kinetics of plasmin formation and inhibition in human and mouse plasmas and focuses on their applications in defining the role of plasmin in diseases, including angioedema, hemophilia, rare bleeding disorders, COVID-19, or diet-induced obesity. Moreover, this review introduces the PG assay as a promising clinical and research method to monitor antifibrinolytic medications and screen for genetic or acquired fibrinolytic disorders.


Assuntos
Análise Química do Sangue/métodos , Doença , Fibrinolisina/análise , Fibrinolisina/metabolismo , Animais , Antifibrinolíticos/sangue , Fibrina/análise , Fibrina/química , Fibrinolíticos/sangue , Humanos , Plasminogênio/análise , Plasminogênio/química , Plasminogênio/metabolismo
11.
N Engl J Med ; 384(22): 2092-2101, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-33835769

RESUMO

BACKGROUND: Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder. METHODS: We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)-heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4-heparin immunoassay. RESULTS: Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4-heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor-blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4-heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation. CONCLUSIONS: Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.).


Assuntos
Autoanticorpos/sangue , Vacinas contra COVID-19/efeitos adversos , Fator Plaquetário 4/imunologia , Trombocitopenia/etiologia , Trombose/etiologia , Adulto , Doenças Autoimunes/etiologia , Análise Química do Sangue , Coagulação Intravascular Disseminada/etiologia , Ensaio de Imunoadsorção Enzimática , Evolução Fatal , Feminino , Humanos , Hemorragias Intracranianas/etiologia , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária , Trombocitopenia/imunologia , Trombose/imunologia , Adulto Jovem
12.
Nutrients ; 13(4)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33924317

RESUMO

BACKGROUND: Maternal triglycerides are increasingly recognised as important predictors of infant growth and fat mass. The variability of triglyceride patterns during the day and their relationship to dietary intake in women in late pregnancy have not been explored. This prospective cohort study aimed to examine the utility of monitoring capillary triglycerides in women in late pregnancy. METHODS: Twenty-nine women (22 with gestational diabetes (GDM) and 7 without) measured capillary glucose and triglycerides using standard meters at home for four days. On two of those days, they consumed one of two standard isocaloric breakfast meals: a high-fat/low-carbohydrate meal (66% fat) or low fat/high carbohydrate meal (10% fat). Following the standard meals, glucose and triglyceride levels were monitored. RESULTS: Median capillary triglycerides were highly variable between women but did not differ between GDM and normoglycaemic women. There was variability in capillary triglycerides over four days of home monitoring and a difference in incremental area under the curve for capillary triglycerides and glucose between the two standard meals. The high-fat standard meal lowered the incremental area under the curve for capillary glucose (p < 0.0001). Fasting (rho 0.66, p = 0.0002) and postpradial capillary triglycerides measured at home correlated with venous triglyceride levels. CONCLUSIONS: The lack of differences in response to dietary fat intake and the correlation between capillary and venous triglycerides suggest that monitoring of capillary triglycerides before and after meals in pregnancy is unlikely to be useful in the routine clinical practice management of women with gestational diabetes mellitus.


Assuntos
Análise Química do Sangue/métodos , Capilares , Diabetes Gestacional/diagnóstico , Triglicerídeos/sangue , Adulto , Glicemia/análise , Desjejum , Estudos de Casos e Controles , Diabetes Gestacional/sangue , Diabetes Gestacional/terapia , Gorduras na Dieta , Estudos de Viabilidade , Feminino , Humanos , Período Pós-Prandial , Gravidez , Estudos Prospectivos , Veias
13.
Molecules ; 26(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809301

RESUMO

This study aimed to review and critically appraise the current methodological issues undermining the suitability of the measurement of serum/plasma glutathione, both in the total and reduced form, as a measure of systemic oxidative stress in chronic obstructive pulmonary disease (COPD). Fourteen relevant articles published between 2001 and 2020, in 2003 subjects, 1111 COPD patients, and 892 controls, were reviewed. Nine studies, in 902 COPD patients and 660 controls, measured glutathione (GSH) in the reduced form (rGSH), while the remaining five, in 209 COPD patients and 232 controls, measured total GSH (tGSH). In the control group, tGSH ranged between 5.7 and 7.5 µmol/L, whilst in COPD patients, it ranged between 4.5 and 7.4 µmol/L. The mean tGSH was 6.6 ± 0.9 µmol/L in controls and 5.9 ± 1.4 µmol/L in patients. The concentrations of rGSH in the control group showed a wide range, between 0.47 and 415 µmol/L, and a mean value of 71.9 ± 143.1 µmol/L. Similarly, the concentrations of rGSH in COPD patients ranged between 0.49 and 279 µmol/L, with a mean value of 49.9 ± 95.9 µmol/L. Pooled tGSH concentrations were not significantly different between patients and controls (standard mean difference (SMD) = -1.92, 95% CI -1582 to 0.0219; p = 0.057). Depending on whether the mean concentrations of rGSH in controls were within the accepted normal range of 0.5-5.0 µmol/L, pooled rGSH concentrations showed either a significant (SMD = -3.8, 95% CI -2.266 to -0.709; p < 0.0001) or nonsignificant (SMD = -0.712, 95% CI -0.627 to 0.293; p = 0.48) difference. These results illustrate the existing and largely unaddressed methodological issues in the interpretation of the serum/plasma concentrations of tGSH and rGSH in COPD.


Assuntos
Análise Química do Sangue/métodos , Glutationa/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Análise Química do Sangue/estatística & dados numéricos , Estudos de Casos e Controles , Glutationa/química , Humanos , Oxirredução , Estresse Oxidativo , Plasma/química , Valores de Referência , Pesquisa Médica Translacional
15.
Int J Mol Sci ; 22(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803235

RESUMO

Fibrinolysis is an important process in hemostasis responsible for dissolving the clot during wound healing. Plasmin is a central enzyme in this process via its capacity to cleave fibrin. The kinetics of plasmin generation (PG) and inhibition during fibrinolysis have been poorly understood until the recent development of assays to quantify these metrics. The assessment of plasmin kinetics allows for the identification of fibrinolytic dysfunction and better understanding of the relationships between abnormal fibrin dissolution and disease pathogenesis. Additionally, direct measurement of the inhibition of PG by antifibrinolytic medications, such as tranexamic acid, can be a useful tool to assess the risks and effectiveness of antifibrinolytic therapy in hemorrhagic diseases. This review provides an overview of available PG assays to directly measure the kinetics of plasmin formation and inhibition in human and mouse plasmas and focuses on their applications in defining the role of plasmin in diseases, including angioedema, hemophilia, rare bleeding disorders, COVID-19, or diet-induced obesity. Moreover, this review introduces the PG assay as a promising clinical and research method to monitor antifibrinolytic medications and screen for genetic or acquired fibrinolytic disorders.


Assuntos
Análise Química do Sangue/métodos , Doença , Fibrinolisina/análise , Fibrinolisina/metabolismo , Animais , Antifibrinolíticos/sangue , Fibrina/análise , Fibrina/química , Fibrinolíticos/sangue , Humanos , Plasminogênio/análise , Plasminogênio/química , Plasminogênio/metabolismo
16.
Aust Vet J ; 99(6): 249-254, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33751570

RESUMO

BACKGROUND: Reference intervals for haematology and serum biochemistry parameters were developed for free-ranging Lumholtz's tree-kangaroo (Dendrolagus lumholtzi) using 35 samples from 12 female and 15 male free-ranging animals. Captive tree-kangaroos (n = 12) were also sampled for comparison. Differences were found between free-ranging and captive animals in white blood cell and neutrophil counts, and levels of aspartate aminotransferase, alkaline phosphatase, bilirubin, creatine kinase, phosphate, triglycerides and lipase. These differences may be attributed to diet, activity, capture methods or age group. Reference intervals generated may be used for both free-ranging and captive Lumholtz's tree-kangaroos. This study provides a valuable tool for the assessment of health in rescued and captive tree-kangaroos and will aid in investigations into population health and disease in free-ranging Lumholtz's tree-kangaroos. OBJECTIVE: To develop reference intervals (RIs) for haematology and serum biochemistry parameters in Lumholtz's tree-kangaroos. METHODS: Haematological and serum biochemical RIs were determined using 35 samples from 27 clinically healthy Lumholtz's tree-kangaroos from the Atherton Tablelands region of Queensland examined between 2014 and 2019. Haematology and serum biochemistry parameters were measured from 16 samples from 12 captive animals for comparison. RESULTS: Reference intervals based on 35 samples from free-ranging animals showed higher mean and standard deviation values for white blood cell and neutrophil counts, and levels of aspartate aminotransferase, alkaline phosphatase, bilirubin, creatine kinase, phosphate, triglycerides and lipase than results for 16 samples from captive animals. Captive individuals showed higher mean values than free-ranging individuals for albumin, protein, creatinine as well as Hb, MCV, MCH and MCHC. CONCLUSION: The haematological and serum biochemistry RIs developed for Lumholtz's tree-kangaroos in this study will provide a valuable tool during clinical examination and investigations into disease and population health by veterinarians and researchers. The differences in parameters between free-ranging and captive animals are consistent with differences in diet, age cohort, activity or capture methods. Reference intervals generated from free-ranging animals should also be valid for captive Lumholtz's tree-kangaroos.


Assuntos
Macropodidae , Árvores , Animais , Análise Química do Sangue/veterinária , Creatinina , Feminino , Queensland , Valores de Referência
17.
J Drugs Dermatol ; 20(3): 320-325, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33683085

RESUMO

BACKGROUND AND OBJECTIVES: There are currently no evidence-based recommendations to guide lab monitoring in the first 90 days of methotrexate treatment. The purpose of this study was to determine whether certain monitoring practices or baseline patient characteristics were associated with increased risk of developing clinically meaningful lab abnormalities during the course of methotrexate treatment. PATIENTS AND METHODS: This retrospective cohort study analyzed 243 dermatologically managed patients taking methotrexate at the University of Virginia Health System. Odds ratios were used to analyze the risk of these patients developing lab abnormalities that result in a change in clinical management, referred to as clinically relevant events. Chi-square analysis was used to determine the optimal timing of methotrexate lab monitoring. RESULTS: A diagnosis of congestive heart failure (P=0.03), chronic kidney disease (P=0.03), and an initial low platelet count (P=0.008) increased the odds of developing a clinically relevant event at some point during methotrexate therapy. In the first 15 days following methotrexate initiation, only 1/114 (0.9%) lab draws resulted in discontinuation of the medicine, 1/114 (0.9%) resulted in maintenance of a stable dose, and 2/114 (1.8%) resulted in repeat laboratory testing. CONCLUSION: In the absence of concerning baseline patient characteristics, dermatologists may consider postponing initial lab monitoring until 15 days post methotrexate initiation.J Drugs Dermatol. 2021;20(3):320-325. doi:10.36849/JDD.5790.


Assuntos
Dermatologia/normas , Monitoramento de Medicamentos/normas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Metotrexato/efeitos adversos , Dermatopatias/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Química do Sangue/normas , Análise Química do Sangue/estatística & dados numéricos , Criança , Pré-Escolar , Dermatologia/estatística & dados numéricos , Monitoramento de Medicamentos/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Testes de Função Hepática/normas , Testes de Função Hepática/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Dermatopatias/sangue , Dermatopatias/imunologia , Fatores de Tempo , Adulto Jovem
18.
Front Immunol ; 12: 614000, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717096

RESUMO

The aim of the study was to determine how a high-fat diet supplemented with various forms of chromium affects hematological and immune parameters of the blood of rats. The rats received a standard diet or a high-fat diet supplemented with chromium at 0.3 mg/kg body weight (BW) in the form of chromium(III) picolinate, chromium(III)-methionine or nano-sized chromium. Selected hematological parameters were determined in the blood of the rats, including total white blood cell (WBC) count, leukogram, red blood cell (RBC) count, hemoglobin level (HGB), hematocrit (HCT), platelet count (PLT) and platelet percentage (PCT), as well as immune parameters: levels of immunoglobulins A and E (IgA and IgE), interleukin-6 (IL-6), interleukin-2 (IL-2), and tumor necrosis factor α (TNF-α); activity of ceruloplasmin (Cp); and levels of caspase 3 and 8 (Casp3 and Casp8). Feeding rats a high-fat diet increased blood markers of induction of inflammation, ie pro-inflammatory cytokines IL-6 and TNF-α, and also significantly increased IgE. The diet had no effect on the blood count, except for an increase in the number of neutrophils. The chromium compounds tested, particularly Cr-Met and Cr-NPs, stimulated the immune system of the rats, as indicated by increased concentrations of IgA, IgE, IL-2, IL-6, TNF-α, and Cp. Given the increase in inflammatory mediators induced by chromium, it should not be used to mitigate the effects of a high-fat diet. Moreover, chromium picolinate and chromium nanoparticles were shown to increase the content of caspase 3 and 8 in the blood of rats, which indicates a pro-apoptotic effect. The effects of the use of chromium nanoparticles include reductions in the WBC count and in the thrombocyte count (leuko- and thrombopenia). Taking account these data the use of chromium as dietary supplement should be reconsidered.


Assuntos
Biomarcadores/sangue , Fenômenos Fisiológicos Sanguíneos/efeitos dos fármacos , Compostos de Cromo/farmacologia , Citocinas/sangue , Dieta Hiperlipídica , Mediadores da Inflamação/sangue , Animais , Análise Química do Sangue , Testes Hematológicos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Ratos
19.
Arch Microbiol ; 203(5): 2365-2371, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33660021

RESUMO

Micro-RNA (miRNA) is a short stretch of nucleotides that can regulate many genes associated with the various stages of the hepatitis C virus (HCV) life cycle and disease progression. This study evaluates the expression profiling of miRNA-196a in naïve HCV-infected, and Sofosbuvir plus Daclatasvir-treated patients. MiRNA-196a can inhibit HCV replication by silencing the HCV NS5A protein or downregulating the human BACH-I mRNA. The expression level of miRNA-196a was determined by quantitative reverse transcription PCR (RT-qPCR) using the whole RNA extracted from the recruited participant's serum. Results showed a 0.83-fold decrease in the miRNA-196a level in naïve HCV-infected than controls. On the contrary, an increase in the expression level by 0.06-fold was observed in Sofosbuvir plus Daclatasvir-treated patients. A negative but significant correlation was recorded between the HCV-RNA load and miRNA-196a expression level in the naïve-infected patients. Serum miRNA-196a ROC curve analysis revealed an area under the curve of 0.8278 (95% CI 0.7033-0.9524, p < 0.0001) with 82.05% sensitivity and 76.19% specificity in discriminating the healthy controls from the HCV-infected samples. In conclusion, our study explored the comparative expression levels of miRNA-196a in HCV-infected and Sofosbuvir plus Daclatasvir patients. Further studies are needed to examine the possible role of miR-196a as a therapeutic agent for treating HCV-infected patients.


Assuntos
Antivirais/uso terapêutico , Carbamatos/uso terapêutico , Hepatite C/tratamento farmacológico , Imidazóis/uso terapêutico , MicroRNAs/genética , Pirrolidinas/uso terapêutico , Sofosbuvir/uso terapêutico , Valina/análogos & derivados , Adulto , Biomarcadores/sangue , Análise Química do Sangue , Quimioterapia Combinada , Feminino , Hepacivirus , Hepatite C/genética , Interações entre Hospedeiro e Microrganismos , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Valina/uso terapêutico , Carga Viral
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