Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21.828
Filtrar
Mais filtros








Intervalo de ano de publicação
2.
Ann Anat ; 239: 151805, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34265386

RESUMO

BACKGROUND: Users of anatomical donors are at risk of exposure to bloodborne pathogens. This study evaluated screening algorithms for hepatitis B and C virus, human immunodeficiency virus and Treponema pallidum during donor allocation and assessed the impact of postmortem time on hemolysis and how hemolysis affects test results and donor discard rate. METHODS: From 2011 to 2018, demographic data of anatomical donors, time of postmortem blood sampling, presence of sample hemolysis, serological test results (negative; active infection; false reactive screening test; historic infection; inconclusive; technically impracticable) and the actual donor allocation were collected. RESULTS: Donors (n = 537) had a mean age of 77.53 ± 13.67 (24-103) year. Nine (1.68%) had laboratory test results indicative for active infection for hepatitis B (n = 1) and C virus (n = 2), human immunodeficiency virus (n = 5) and T. pallidum (n = 1). Negative screenings ranged from 74.67 to 97.58%, depending on the pathogen. According to the original screening algorithms, 479 (89.20%) donors should have been accepted. In practice, a donor acceptance rate of 91.20% was found. Analysis of potential donor allocation interpretation obstacles resulted in simplification of the in-house laboratory testing algorithms and addition of a nucleic acid test to increase the reliability for identification of active (acute) human immunodeficiency virus infection. Hemolysis was more common when sampling was performed more than 24 h after death (p < 0.001). Hemolytic samples more frequently showed a reactive or indeterminate human immunodeficiency virus test result (p < 0.001). Screening for human immunodeficiency virus and T. pallidum was technically more impracticable when hemolysis was present (p = 0.042 and p = 0.003, respectively). Donors with hemolytic blood samples were more often discarded (46.88%) compared to bodies with non-hemolytic samples (6.32%) (p < 0.001). CONCLUSIONS: Despite the implementation of donor screening algorithms, a significant number of bodies have an inconsistent allocation. New algorithms, to be evaluated in future research, were suggested. Early postmortem blood sampling is key as hemolysis can influence certain test results and donor allocation.


Assuntos
Infecções por HIV , Hepatite C , Sífilis , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Doadores de Sangue , Infecções por HIV/diagnóstico , Vírus da Hepatite B , Hepatite C/diagnóstico , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Estudos Soroepidemiológicos , Sífilis/diagnóstico
3.
Ann Lab Med ; 42(2): 258-267, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635617

RESUMO

Background: With increasing number of migrants in Korea, there is an increasing need for blood products with rare blood antigens. Accordingly, the role of blood donors among migrants has been acknowledged. We investigated migrants' experiences and perceptions of blood donation along with their sociodemographic status and identified the effects on self-reported blood donation status. Methods: A cross-sectional survey using a self-developed, structured questionnaire was conducted on 479 migrants. The questionnaire included items about experiences, knowledge, and perceptions on blood donation and sociodemographic factors of respondents. Results: Most migrants in this study were from Southeast Asia (54.7%) or China (39.9%). Among them, 28.6% (N=137) had donated blood previously, and 2.7% (N=13) had previously donated blood in Korea. All previous blood donors were volunteers, and the two major deterrents of blood donation for non-donors were the fear of pain and lack of knowledge about blood donation. In multivariable logistic regression analysis, the country of birth (odds ratio [OR]=2.65, P<0.001 [China]; OR=4.85, P=0.001 [countries other than China and Southeast Asian countries]) and employment status (OR=2.80, P=0.034) were independently associated with blood donation. Conclusions: This is the first Korean study to analyze migrants' experiences and perceptions of blood donation in relation to their sociodemographic status. Our findings can help establish blood donation policies for migrants, devise campaigns to enhance blood donation awareness, and ultimately create a pool of rare blood resources in a multicultural society.


Assuntos
Doadores de Sangue , Migrantes , Estudos Transversais , Humanos , Percepção , República da Coreia
4.
BMC Med ; 19(1): 303, 2021 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-34794434

RESUMO

BACKGROUND: By August 2021, the COVID-19 pandemic has been less severe in sub-Saharan Africa than elsewhere. In Malawi, there have been three subsequent epidemic waves. We therefore aimed to describe the dynamics of SARS-CoV-2 exposure in Malawi. METHODS: We measured the seroprevalence of anti-SARS-CoV-2 antibodies amongst randomly selected blood transfusion donor sera in Malawi from January 2020 to July 2021 using a cross-sectional study design. In a subset, we also assessed in vitro neutralisation against the original variant (D614G WT) and the Beta variant. RESULTS: A total of 5085 samples were selected from the blood donor database, of which 4075 (80.1%) were aged 20-49 years. Of the total, 1401 were seropositive. After adjustment for assay characteristics and applying population weights, seropositivity reached peaks in October 2020 (18.5%) and May 2021 (64.9%) reflecting the first two epidemic waves. Unlike the first wave, both urban and rural areas had high seropositivity in the second wave, Balaka (rural, 66.2%, April 2021), Blantyre (urban, 75.6%, May 2021), Lilongwe (urban, 78.0%, May 2021), and Mzuzu (urban, 74.6%, April 2021). Blantyre and Mzuzu also show indications of the start of a third pandemic wave with seroprevalence picking up again in July 2021 (Blantyre, 81.7%; Mzuzu, 71.0%). More first wave sera showed in vitro neutralisation activity against the original variant (78% [7/9]) than the beta variant (22% [2/9]), while more second wave sera showed neutralisation activity against the beta variant (75% [12/16]) than the original variant (63% [10/16]). CONCLUSION: The findings confirm extensive SARS-CoV-2 exposure in Malawi over two epidemic waves with likely poor cross-protection to reinfection from the first on the second wave. The dynamics of SARS-CoV-2 exposure will therefore need to be taken into account in the formulation of the COVID-19 vaccination policy in Malawi and across the region. Future studies should use an adequate sample size for the assessment of neutralisation activity across a panel of SARS-CoV-2 variants of concern/interest to estimate community immunity.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Doadores de Sangue , Vacinas contra COVID-19 , Estudos Transversais , Humanos , Pandemias , Estudos Soroepidemiológicos
5.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(11): 1015-1021, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34809741

RESUMO

Objective By investigating the distribution of ABO and Rh blood groups in Shaanxi Province, to discuss the influence of regional division and population migration on blood group distribution. Methods The data of 3 691 624 blood donors from 10 cities in Shaanxi province in the past 20 years was collected. According to the geographical characteristics of Shaanxi province, the data was divided into three regions: Northern Shaanxi, Southern Shaanxi, and Guanzhong, to statistically analyse the distribution of ABO and Rh blood groups across different regions. Heat map software was used to present the ABO blood group on Shaanxi map. The temporal and spatial characteristics of ABO blood group distribution during 2008 and 2018 were analysed and compared. Results ABO blood group distribution of Shaanxi people was O>B>A>AB, with a Rh negative ratio of 0.41%. Based on the ABO blood group distribution map of Shaanxi Province, obvious regional differences were found in ABO blood group distribution. The ABO blood group distribution in Guanzhong, Southern Shaanxi and Northern Shaanxi was B>O>A>AB, O>A>B>AB, and O>B>A>AB respectively, with the lowest proportion of type A being 26.12% in Northern Shaanxi, the lowest proportion of type B being 27.48% in Southern Shaanxi, and the highest proportion of type O being 32.60% and 32.10% in Northern Shaanxi and SouthernShaanxi respectively. Compared with 2008, the distribution of ABO blood groups in the three regions of Shaanxi province changed significantly in 2018. Conclusion The distribution of ABO blood group in Shaanxi province is O>B>A>AB in general. However, there are significant differences in blood group distribution among different regions. It was also found that population migration had an impact on blood group distribution from 1998 to 2018.


Assuntos
Sistema ABO de Grupos Sanguíneos , Doadores de Sangue , Humanos
6.
Medicine (Baltimore) ; 100(41): e27537, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731151

RESUMO

ABSTRACT: The corona virus disease-19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, had health and economic results that profoundly affected communities worldwide. Investigating the seroprevalence of SARS-Cov-2 in blood donors is of a significant clinical and scientific value as it adds to knowledge about local herd immunity levels.To study the prevalence of SARS-Cov-2 infection among blood donors at a tertiary referral hospital in the north of Jordan.This is a prospective study that included all blood donors between September 2020 and March 2021. Donors' IgG antibodies were qualitatively immunoassayed to determine the antibody status against SARS-CoV-2. The Elecsys Anti-SARS-CoV-2 technique was utilized.One thousand samples were tested by total antibody against SARS-CoV-2. The median age was 29 years, 96.7% were males. The seroprevalence was 14.5%, and 80% of the positive participants did not report previous COVID-19 infection. The seroprevalence of COVID-19 antibodies was less among smokers and those with an O blood group and higher among donors with an AB blood group.The prevalence of COVID-19 among healthy young blood donors at a tertiary teaching health facility in the north of Jordan was 14.5%. Smokers and those with an O blood group were less likely to be seropositive, as opposed to donors with an AB blood group.


Assuntos
Doadores de Sangue/estatística & dados numéricos , COVID-19/epidemiologia , Adulto , Antígenos de Grupos Sanguíneos/imunologia , Feminino , Humanos , Jordânia/epidemiologia , Masculino , Pandemias , Prevalência , Estudos Prospectivos , SARS-CoV-2
7.
Front Cell Infect Microbiol ; 11: 753970, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722340

RESUMO

Background: Donor-derived human parvovirus B19 (B19V) infections are rarely reported. Thus, its incidence in kidney transplantation is still unknown due to lack of surveillance studies. Similarly, whether the donor needs to be routinely screened for B19V and whether the kidneys from those with B19V DNAemia could be accepted also remain unknown. Methods: This retrospective study aims to evaluate the donor-derived B19V infections occurring in 823 living and 1,225 deceased donor kidney transplantations from January 2016 to December 2020. The serum viral load of living donors and their corresponding recipients was evaluated before and after transplantation. Meanwhile, for the deceased donor kidney transplantation, the serum viral load of recipients was only tested after transplantation; if recipients of a deceased donor subsequently developed B19V infection, the serum viral load of recipients and their corresponding donors before transplantation would then be further traced. Results: A total of 15 living donors were B19V DNAemia positive before the donation, of which B19V DNAemia occurred in three corresponding recipients. In deceased donor kidney transplantation, DNAemia occurred simultaneously in 18 recipients and their corresponding nine donors. A progressive decline in hemoglobin and reticulocyte count could be observed in one living donor recipient and other 11 deceased donor recipients, which were all well controlled by treatment eventually. Conclusion: The incidence of donor-derived B19V infection was 0.4% and 1.5% in living and deceased kidney transplantations, respectively. B19V was seemingly unnecessary to be routinely screened for the donor. Moreover, kidneys of the donors with B19V infection were acceptable.


Assuntos
Eritema Infeccioso , Transplante de Rim , Infecções por Parvoviridae , Doadores de Sangue , DNA Viral , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos
8.
Wiad Lek ; 74(9 cz 1): 2192-2196, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34725299

RESUMO

OBJECTIVE: The aim: To identify the main fears of donation among young people in the city and ways to eliminate these phobias with the help of modern marketing tools. PATIENTS AND METHODS: Materials and methods: It was conducted the questionnaire among Sumy State University students on donation fears. The questionnaire included questions about experience of donation, reason for non donation and age. After that a focus group among students who feared donation was organized. Participants were shown a 360 degree video recorded in the blood center and discussed how to donate blood after watching the video. RESULTS: Results: The main phobias were fear of becoming infected during the procedure (37.7%), fear of the procedure itself due to ignorance and misunderstanding of what to expect (14.0%), and fear of the needle, blood, and the discomfort possibility during the procedure (10.0%); 26.7% indicated that they could not be donors due to poor health, and 11.6% due to personal laziness. It was developed a 360o video, which demonstrates the blood donation process, showing the next steps with the selected blood in facilities. Its continues for 20 minutes. This video was shown in the focus group for ten non-donors with some donation fear. 60% of them reported a change from blood to a positive, which may indicate this tool's effectiveness. CONCLUSION: Conclusions: Due a 360o video some non-donor people can ensure safety, sterility of the process, reduce the fear of donation and further increase the likelihood of becoming regular donors.


Assuntos
Doadores de Sangue , Medo , Adolescente , Humanos , Marketing , Estudantes , Inquéritos e Questionários
9.
BMC Infect Dis ; 21(1): 1131, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34727874

RESUMO

BACKGROUND: SARS-CoV-2 emerged in China and spread throughout the world due to its rapid transmission. The exposure rate in the healthy population is unknown, mainly in resource-limited countries. Herein, we estimated the seroprevalence of anti-SARS-CoV-2 antibodies and risk factors among blood donors in Luanda, the capital city of Angola. METHODS: This was a retrospective study conducted with 343 blood donors. Chi-square and logistic regression were calculated to predict the independent variable for SARS-CoV-2 infection and deemed significant when p < 0.05. RESULTS: Seroprevalence of anti-SARS-CoV-2 was 4.7%. Positivity rates varied to age groups (3.5-14.3%), gender (0-5%), area of residence (3.1-.6%), educational level (5.1-10.2%), occupation (4.4-7.7%), and the blood donor category (2.0-5.1%). Past and recent infections were detected in 3.2% and 1.5%, respectively. Blood donors under the age of 20 years (OR: 4.58, p = 0.241) and from non-urbanized areas (OR: 1.86, p = 0.293) presented a high risk related to infection. The infection was higher in blood group A and lower in blood group O. The risk of SARS-CoV-2 infection has increased from January 2020 (OR: 0.03, p = 0.001) to August 2020 (OR: 0.57, p = 0.426). CONCLUSIONS: We provide an estimate of the exposure of healthy blood donors in Luanda. Also, we detected anti-SARS-CoV-2 in January 2020, indicating that the SARS-CoV-2 could have been imported during the first month of 2020. Further studies should be performed to assess the exposure rate in different groups from Angola.


Assuntos
Doadores de Sangue , COVID-19 , Adulto , Angola/epidemiologia , Anticorpos Antivirais , Estudos Transversais , Humanos , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Estudos Soroepidemiológicos , Adulto Jovem
10.
Clin Immunol ; 232: 108871, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34619377

RESUMO

Despite the burgeoning field of coronavirus disease-19 (COVID-19) research, the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibodies remains unclear. This study validated two high-throughput immunological methods for use as surrogate live virus neutralisation assays and employed them to examine the half-life of SARS-CoV-2 neutralising antibodies in convalescent plasma donations made by 42 repeat donors between April and September 2020. SARS-CoV-2 neutralising antibody titres decreased over time but typically remained above the methods' diagnostic cut-offs. Using this longitudinal data, the average half-life of SARS-CoV-2 neutralising antibodies was determined to be 20.4 days. SARS-CoV-2 neutralising antibody titres appear to persist in the majority of donors for several months. Whether these titres confer protection against re-infection requires further study and is of particular relevance as COVID-19 vaccines become widely available.


Assuntos
Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/metabolismo , COVID-19/metabolismo , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/uso terapêutico , Doadores de Sangue , COVID-19/imunologia , COVID-19/terapia , Feminino , Meia-Vida , Humanos , Imunização Passiva , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Plasma/imunologia , Plasma/metabolismo , SARS-CoV-2/imunologia , Adulto Jovem
11.
Front Immunol ; 12: 739037, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594341

RESUMO

Background: Transfusion of COVID-19 convalescent plasma (CCP) containing high titers of anti-SARS-CoV-2 antibodies serves as therapy for COVID-19 patients. Transfusions early during disease course was found to be beneficial. Lessons from the SARS-CoV-2 pandemic could inform early responses to future pandemics and may continue to be relevant in lower resource settings. We sought to identify factors correlating to high antibody titers in convalescent plasma donors and understand the magnitude and pharmacokinetic time course of both transfused antibody titers and the endogenous antibody titers in transfused recipients. Methods: Plasma samples were collected up to 174 days after convalescence from 93 CCP donors with mild disease, and from 16 COVID-19 patients before and after transfusion. Using ELISA, anti-SARS-CoV-2 Spike RBD, S1, and N-protein antibodies, as well as capacity of antibodies to block ACE2 from binding to RBD was measured in an in vitro assay. As an estimate for viral load, viral RNA and N-protein plasma levels were assessed in COVID-19 patients. Results: Anti-SARS-CoV-2 antibody levels and RBD-ACE2 blocking capacity were highest within the first 60 days after symptom resolution and markedly decreased after 120 days. Highest antibody titers were found in CCP donors that experienced fever. Effect of transfused CCP was detectable in COVID-19 patients who received high-titer CCP and had not seroconverted at the time of transfusion. Decrease in viral RNA was seen in two of these patients. Conclusion: Our results suggest that high titer CCP should be collected within 60 days after recovery from donors with past fever. The much lower titers conferred by transfused antibodies compared to endogenous production in the patient underscore the importance of providing CCP prior to endogenous seroconversion.


Assuntos
COVID-19/terapia , Convalescença , SARS-CoV-2/imunologia , Soroconversão , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antígenos Virais/sangue , Doadores de Sangue , COVID-19/sangue , COVID-19/imunologia , Feminino , Humanos , Imunização Passiva , Cinética , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , RNA Viral/sangue
12.
Viruses ; 13(10)2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34696480

RESUMO

BACKGROUND: COVID-19 convalescent plasma (CCP) has been considered internationally as a treatment option for COVID-19. CCP refers to plasma collected from donors who have recovered from and made antibodies to SARS-CoV-2. To date, convalescent plasma has not been collected in South Africa. As other investigational therapies and vaccination were not widely accessible, there was an urgent need to implement a CCP manufacture programme to service South Africans. METHODS: The South African National Blood Service and the Western Cape Blood Service implemented a CCP programme that included CCP collection, processing, testing and storage. CCP units were tested for SARS-CoV-2 Spike ELISA and neutralising antibodies and routine blood transfusion parameters. CCP units from previously pregnant females were tested for anti-HLA and anti-HNA antibodies. RESULTS: A total of 987 CCP units were collected from 243 donors, with a median of three donations per donor. Half of the CCP units had neutralising antibody titres of >1:160. One CCP unit was positive on the TPHA serology. All CCP units tested for anti-HLA antibodies were positive. CONCLUSION: Within three months of the first COVID-19 diagnosis in South Africa, a fully operational CCP programme was set up across South Africa. The infrastructure and skills implemented will likely benefit South Africans in this and future pandemics.


Assuntos
Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , COVID-19/terapia , SARS-CoV-2/imunologia , Adulto , Idoso , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Remoção de Componentes Sanguíneos/métodos , Doadores de Sangue , Feminino , Humanos , Imunização Passiva/métodos , Masculino , Pessoa de Meia-Idade , África do Sul , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto Jovem
13.
Artigo em Inglês | MEDLINE | ID: mdl-34639841

RESUMO

Vasovagal reaction (VVR) compromises donor safety and reduces the subsequent return rates. Performing applied muscle tension (AMT) during phlebotomy may reduce the incidence of VVR. However, the effectiveness of performing AMT after phlebotomy to reduce delayed VVR remains unclear. With ethics approval, 12 young, first-time donors (YFTD) were recruited to study the effects on stroke volume (SV), cardiac output (CO) and systemic vascular resistance (SVR) while performing AMT from needle insertion to end of recovery. Measurements from 12 matched control YFTD were used for comparison. Pre-donation anxiety and VVR severity were assessed. Compared to controls, donors who performed AMT had higher SV (Control: 57 mL vs. AMT: 69 mL, p = 0.045), higher CO (Control: 3.7 L·min-1 vs. AMT: 5.2 L·min-1, p = 0.006) and lower SVR (Control: 1962 dyn·s·cm-5 vs. AMT: 1569 dyn·s·cm-5, p = 0.032) during mid-phlebotomy. During recovery, the AMT group retained higher SV, higher CO and lower SVR than the control, but not reaching statistical significance. Practicing AMT during recovery resulted in sustained haemodynamic improvements beyond the donation period, despite the reduction in delayed VVR was insignificant compared to the control group. A larger sample size is needed to validate the effectiveness of performing AMT after donation to mitigate delayed VVR.


Assuntos
Flebotomia , Síncope Vasovagal , Doadores de Sangue , Humanos , Tono Muscular , Projetos Piloto , Síncope Vasovagal/prevenção & controle
14.
Curr Issues Mol Biol ; 43(3): 1212-1225, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34698067

RESUMO

The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. However, the factors predisposing individuals to severe disease remain poorly understood. Here, we show that levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells, are elevated in SARS-CoV-2-infected Caco-2 cells, Calu-3 cells, and air-liquid interface cultures of primary human bronchial epithelial cells. Moreover, SARS-CoV-2 infection increases SIRPalpha levels, the binding partner of CD47, on primary human monocytes. Systematic literature searches further indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions that may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, age-related and virus-induced CD47 expression is a candidate mechanism potentially contributing to severe COVID-19, as well as a therapeutic target, which may be addressed by antibodies and small molecules. Further research will be needed to investigate the potential involvement of CD47 and SIRPalpha in COVID-19 pathology. Our data should encourage other research groups to consider the potential relevance of the CD47/ SIRPalpha axis in their COVID-19 research.


Assuntos
Antígenos de Diferenciação/metabolismo , Antígeno CD47/metabolismo , COVID-19/epidemiologia , COVID-19/metabolismo , Pandemias , Receptores Imunológicos/metabolismo , SARS-CoV-2/metabolismo , Índice de Gravidade de Doença , Transdução de Sinais/imunologia , Doadores de Sangue , Western Blotting/métodos , Brônquios/citologia , COVID-19/patologia , COVID-19/virologia , Células CACO-2 , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Voluntários Saudáveis , Humanos , Monócitos/metabolismo , Monócitos/virologia , Reação em Cadeia da Polimerase/métodos , RNA Viral/genética , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação
15.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638936

RESUMO

Nicotinamide adenine dinucleotide (NAD+) and its reduced form (NADH) are coenzymes employed in hundreds of metabolic reactions. NAD+ also serves as a substrate for enzymes such as sirtuins, poly(ADP-ribose) polymerases (PARPs) and ADP-ribosyl cyclases. Given the pivotal role of NAD(H) in health and disease, studying NAD+ metabolism has become essential to monitor genetic- and/or drug-induced perturbations related to metabolic status and diseases (such as ageing, cancer or obesity), and its possible therapies. Here, we present a strategy based on liquid chromatography-tandem mass spectrometry (LC-MS/MS), for the analysis of the NAD+ metabolome in biological samples. In this method, hydrophilic interaction chromatography (HILIC) was used to separate a total of 18 metabolites belonging to pathways leading to NAD+ biosynthesis, including precursors, intermediates and catabolites. As redox cofactors are known for their instability, a sample preparation procedure was developed to handle a variety of biological matrices: cell models, rodent tissues and biofluids, as well as human biofluids (urine, plasma, serum, whole blood). For clinical applications, quantitative LC-MS/MS for a subset of metabolites was demonstrated for the analysis of the human whole blood of nine volunteers. Using this developed workflow, our methodology allows studying NAD+ biology from mechanistic to clinical applications.


Assuntos
Metaboloma , NAD/biossíntese , Plasma/metabolismo , Soro/metabolismo , Espectrometria de Massas em Tandem/métodos , Urina/fisiologia , Animais , Doadores de Sangue , Cromatografia Líquida/métodos , Células Hep G2 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Metabolômica/métodos , Camundongos , Camundongos Endogâmicos C57BL , Monitorização Fisiológica/métodos , Oxirredução , Projetos Piloto , Plasma/química , Soro/química , Urina/química
16.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638950

RESUMO

Mucosal-associated invariant T (MAIT) cells represent a distinct T cell population restricted by the MHC-class-I-related molecule, MR1, which recognizes microbial-derived vitamin B2 (riboflavin) metabolites. Their abundance in humans, together with their ability to promptly produce distinct cytokines including interferon γ (IFNγ) and tumor necrosis factor α (TNFα), are consistent with regulatory functions in innate as well as adaptive immunity. Here, we tested whether the alarmin interleukin 33 (IL-33), which is secreted following inflammation or cell damage, could activate human MAIT cells. We found that MAIT cells stimulated with IL-33 produced high levels of IFNγ, TNFα and Granzyme B (GrzB). The action of IL-33 required IL-12 but was independent of T cell receptor (TCR) cross-linking. MAIT cells expressed the IL-33 receptor ST2 (suppression of tumorigenicity 2) and upregulated Tbet (T-box expressed in T cells) in response to IL-12 or IL-33. Electronically sorted MAIT cells also upregulated the expression of CCL3 (Chemokine C-C motif ligand 3), CD40L (CD40 Ligand), CSF-1 (Colony Stimulating Factor 1), LTA (Lymphotoxin-alpha) and IL-2RA (IL-2 receptor alpha chain) mRNAs in response to IL-33 plus IL-12. In conclusion, IL-33 combined with IL-12 can directly target MAIT cells to induce their activation and cytokine production. This novel mechanism of IL-33 activation provides insight into the mode of action by which human MAIT cells can promote inflammatory responses in a TCR-independent manner.


Assuntos
Interferon gama/biossíntese , Interleucina-33/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Células T Invariantes Associadas à Mucosa/efeitos dos fármacos , Células T Invariantes Associadas à Mucosa/imunologia , Transdução de Sinais/efeitos dos fármacos , Células Th1/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Adulto , Doadores de Sangue , Células Cultivadas , Granzimas/biossíntese , Voluntários Saudáveis , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-12/biossíntese , Interleucina-12/farmacologia , Interleucina-33/biossíntese , Receptores de Antígenos de Linfócitos T/imunologia , Transdução de Sinais/imunologia , Proteínas com Domínio T/metabolismo
17.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638952

RESUMO

The growing application of materials containing TiO2 particles has led to an increased risk of human exposure, while a gap in knowledge about the possible adverse effects of TiO2 still exists. In this work, TiO2 particles of rutile, anatase, and their commercial mixture were exposed to various environments, including simulated gastric fluids and human blood plasma (both representing in vivo conditions), and media used in in vitro experiments. Simulated body fluids of different compositions, ionic strengths, and pH were used, and the impact of the absence or presence of chosen enzymes was investigated. The physicochemical properties and agglomeration of TiO2 in these media were determined. The time dependent agglomeration of TiO2 related to the type of TiO2, and mainly to the type and composition of the environment that was observed. The presence of enzymes either prevented or promoted TiO2 agglomeration. TiO2 was also observed to exhibit concentration-dependent cytotoxicity. This knowledge about TiO2 behavior in all the abovementioned environments is critical when TiO2 safety is considered, especially with respect to the significant impact of the presence of proteins and size-related cytotoxicity.


Assuntos
Nanopartículas Metálicas/química , Plasma/metabolismo , Titânio/química , Titânio/metabolismo , Animais , Doadores de Sangue , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cristalização , Meios de Cultura/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas Metálicas/efeitos adversos , Camundongos , Concentração Osmolar , Tamanho da Partícula , Saliva/metabolismo , Propriedades de Superfície , Titânio/efeitos adversos , Água/metabolismo
18.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638997

RESUMO

One of the mechanisms by which PI3 kinase can regulate platelet function is through phosphorylation of downstream substrates, including glycogen synthase kinase-3 (GSK3)α and GSK3ß. Platelet activation results in the phosphorylation of an N-terminal serine residue in GSK3α (Ser21) and GSK3ß (Ser9), which competitively inhibits substrate phosphorylation. However, the role of phosphorylation of these paralogs is still largely unknown. Here, we employed GSK3α/ß phosphorylation-resistant mouse models to explore the role of this inhibitory phosphorylation in regulating platelet activation. Expression of phosphorylation-resistant GSK3α/ß reduced thrombin-mediated platelet aggregation, integrin αIIbß3 activation, and α-granule secretion, whereas platelet responses to the GPVI agonist collagen-related peptide (CRP-XL) were significantly enhanced. GSK3 single knock-in lines revealed that this divergence is due to differential roles of GSK3α and GSK3ß phosphorylation in regulating platelet function. Expression of phosphorylation-resistant GSK3α resulted in enhanced GPVI-mediated platelet activation, whereas expression of phosphorylation-resistant GSK3ß resulted in a reduction in PAR-mediated platelet activation and impaired in vitro thrombus formation under flow. Interestingly, the latter was normalised in double GSK3α/ß KI mice, indicating that GSK3α KI can compensate for the impairment in thrombosis caused by GSK3ß KI. In conclusion, our data indicate that GSK3α and GSK3ß have differential roles in regulating platelet function.


Assuntos
Plaquetas/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Ativação Plaquetária/genética , Agregação Plaquetária/genética , Transdução de Sinais/genética , Trombose/metabolismo , Animais , Doadores de Sangue , Células Cultivadas , Modelos Animais de Doenças , Técnicas de Introdução de Genes , Quinase 3 da Glicogênio Sintase/genética , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Integrinas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Trombina/metabolismo , Trombose/genética
20.
Clin Lab Med ; 41(4): 563-577, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34689965

RESUMO

The maintenance of an adequate and safe blood supply begins with choosing the right donor at the right time. The evolution of donor screening has been shaped by experience, donor satisfaction, and the ever-challenging emergence of relevant infectious diseases. Screening donors has been standardized over the past 6 decades to protect donor and recipient safety. In this review, we outline, define, and simplify the requirements to assess and defer donors with a focus on recent and ongoing changes to provide up to date information on donor qualification and current challenges in maintaining the blood supply.


Assuntos
Doadores de Sangue , Seleção do Doador , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA