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1.
BMC Infect Dis ; 23(1): 800, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968601

RESUMO

PURPOSE: Post-COVID-19-Syndrome (PCS) frequently occurs after an infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the understanding of causative mechanisms is still limited. Aim of this study was to determine the PCS rate among SARS-CoV-2 seropositive blood donors as representatives of supposedly healthy adults, who had experienced an asymptomatic or mild COVID-19 disease course, and to examine whether Epstein-Barr virus (EBV) is reactivated in individuals reporting PCS. METHODS: The PCS rate was determined using questionnaires that included questions about infection and persistent symptoms. Pre-pandemic blood samples and samples collected at regular, pre-defined times after a SARS-CoV-2 infection were analysed for neopterin, a marker for antiviral immune responses, by an enzyme-linked immunosorbent assay (ELISA). Additionally, we determined the rate of SARS-CoV-2 anti-N total antibodies using an electrochemiluminescence immunoassay (ECLIA). Furthermore, quantitative real-time polymerase chain reaction (qPCR) to detect EBV DNA and ECLIA screening for EBV viral capsid-antigen (VCA) IgM, IgG and EBV nuclear antigen 1 (EBNA) IgG were performed. RESULTS: Our data reveal that 18% of all infections result in PCS, with symptoms lasting for up to one year. In individuals reporting PCS, no elevated levels of neopterin were detected, indicating no persisting pro-inflammatory, antiviral immune response. SARS-CoV-2 antibody levels were declining in all participants in comparable manner over time, pointing to a successful virus clearance. In individuals with PCS, no EBV DNA could be detected. Furthermore, no differences in EBV specific antibody levels could be shown in PCS groups compared to non-PCS groups. CONCLUSION: Our data suggest that PCS in per se healthy, immunocompetent adults cannot be ascribed to a reactivation of EBV.


Assuntos
COVID-19 , Infecções por Vírus Epstein-Barr , Adulto , Humanos , Herpesvirus Humano 4 , Infecções por Vírus Epstein-Barr/diagnóstico , SARS-CoV-2/genética , Antígenos Virais , Neopterina , Anticorpos Antivirais , Imunoglobulina M , Imunoglobulina G , DNA
2.
Infection ; 49(6): 1187-1194, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34132990

RESUMO

PURPOSE: Frequently the infection with coronavirus 2 (SARS-CoV-2) can be asymptomatic or provoke only mild symptoms. These cases often remain unnoticed, so it is difficult to estimate the actual numbers of infections. Aim of this study was to determine the seroprevalence of anti-SARS-CoV-2 total antibody in Austrian blood donors. METHODS: 20,228 blood donors aged between 18 and 72 years resident in four Austrian federal states were screened for anti-SARS-CoV-2 total antibody between 5th of June and 4th of December 2020. To evaluate the impact of sex, age, AB0-blood group and donation period on the anti-SARS-CoV-2 seroprevalence, multiple logistic regression was done. RESULTS: Our data reveal an anti-SARS-CoV-2 seroprevalence of 2.5% overall, significantly depending on the time point of blood donation: after the first Austrian lockdown the seroprevalence was lower compared to the following months, when the rate was constantly rising. While younger blood donors showed significantly higher seroprevalence, no differences were found concerning sex or AB0 blood group. CONCLUSION: Broad testing strategies are required to better determine the number of SARS-CoV-2 infections. Screening blood donors as a representative group for the adult population could be a valid tool to determine the number of recorded and unrecorded cases of SARS-CoV-2 infection.


Assuntos
Doadores de Sangue , COVID-19 , Adolescente , Adulto , Idoso , Anticorpos Antivirais , Áustria/epidemiologia , Controle de Doenças Transmissíveis , Humanos , Pessoa de Meia-Idade , SARS-CoV-2 , Estudos Soroepidemiológicos , Adulto Jovem
3.
Transfus Med Hemother ; 48(2): 99-108, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33976610

RESUMO

INTRODUCTION: Antibody-mediated transfusion-related acute lung injury (TRALI) is caused by antibodies against human leukocyte antigens (HLAs) or human neutrophil antigens (HNAs), and is one of the most serious complications associated with transfusion medicine. Prevention strategies like testing allo-exposed female blood donors have not yet been introduced nationwide in Austria. To assess the need and feasibility of routine leukocyte antibody testing, the prevalence of leukocyte-reactive antibodies in an Austrian female donor population was been determined using classical cell-based methods which were compared with a high-throughput bead-based method. METHODS: Sera from 1,022 female blood donors were screened using a granulocyte aggregation test (GAT) and a white blood cell immunofluorescence test (WIFT) after retesting and specification of positive samples by granulocyte immunofluorescence test (GIFT) and monoclonal antibody-specific immobilization of granulocyte antigens (MAIGA). Potential HLA reactivities were confirmed using the microbeads assay LabScreenTM Mixed. The results in 142 donor sera and 38 well-defined reference sera were investigated by the microbeads assay LabScreenTM Multi and compared with classical cell-based methods. RESULTS: Reactivity with either granulocytes and/or lymphocytes was detected in 79 sera (7.7%), with the majority being HLA-specific. Antibodies against HNA were obtained in 7 samples (0.7%). The aggregating potential of the detected antibodies was observed in 9 cases (0.9%). Most of the leukocyte-reactive antibodies occurred at a donor age of between 35 and 59 years (n = 61). LabScreen Multi showed good agreement (κ = 0.767) for HNA antibody detection by cell-based assays, but double/multiple specificities (100% of 7 anti-HNA-1b sera) as well as false-negative results (40% of 15 HNA-3-specific sera) occurred. DISCUSSION: Leukocyte-reactive antibody screening is advised in Austrian female donors for safe blood transfusion, including single-donor convalescent plasma treatment of COVID-19 that may be implemented soon. For the introduction of LabScreen Multi, the combination with GAT should be considered to ensure correct anti-HNA-3a detection.

4.
J Clin Apher ; 35(1): 50-58, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31755575

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease with unmet therapeutic need in a critical cohort of recalcitrant cases. Immunoadsorption (IA) aims at an immunomodulatory depletion of pathogenic serum mediators and has recently revealed promising clinical results for the treatment of AD. OBJECTIVE: To determine efficacy, sustainability, safety, and clinical impact of IgE selective IA in AD using a single-use IgE immunoadsorber column. METHODS: This open-label pilot study comprised five patients (mean SCORAD 67.9 ± 11.4, range 52.2-81.9; mean serum IgE level 5904 ± 5945 U/mL, range 1000-15 600 IU/mL) who underwent IgE-selective IA. Three patients continued prior therapy with systemic immunosuppressive drugs during IA as an add-on therapeutic approach. All patients received three courses of IA. The first course consisted of three consecutive daily treatments followed by two sequences with two consecutive applications. All courses were performed on a monthly regimen. RESULTS: IA proved efficacy in selectively depleting serum IgE levels in all participants (mean reduction by cycle of 81% ± 12%, range 64%-93%). It further led to a clinically relevant and sustained improvement of AD with a maximum decline in SCORAD and EASI scores by up to 35% and 52%, respectively, compared to baseline. Scores persisted below baseline for at least 12 weeks beyond the last IA. The intervention was also well tolerated with no severe adverse events during a total of 35 procedures. CONCLUSION: Data of this preliminary trial indicates clinical efficacy, feasibility, safety as well as tolerability of IgE-selective IA in AD.


Assuntos
Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/imunologia , Imunoglobulina E/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoglobulina A/imunologia , Técnicas de Imunoadsorção , Imunossupressores/uso terapêutico , Inflamação , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
5.
J Clin Apher ; 32(1): 12-15, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26939709

RESUMO

BACKGROUND: Extracorporeal photopheresis (ECP) is an important cell-based therapy for various diseases but is limited to patients eligible for apheresis. We developed an alternative mini buffy coat (BC) preparation method using the Spectra Optia® apheresis system and compared its efficacy of white blood cell (WBC) recovery with the standard mini BC preparation method already established for pediatric patients. METHODS: Whole blood (450 ± 45 mL) samples were collected from 30 randomly selected healthy volunteer blood donors and divided into two groups. In the first group, WBCs were separated with a fully automated separator device (Compomat G4® ). In the second group, BCs were separated with the bone marrow processing program of the Spectra Optia apheresis system. RESULTS: There were no significant differences in total leukocyte counts per product between the two groups. In contrast, lymphocyte counts per product were significantly higher (P < 0.001) in BCs separated from apheresis. CONCLUSION: Our novel technique resulted in similar WBC yields but higher lymphocyte yields than the standard mini BC preparation method. This method can serve as an alternative to WBC collection in conventional ECP for adult patients with apheresis contraindications. J. Clin. Apheresis 32:12-15, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Buffy Coat/citologia , Fotoferese/métodos , Adulto , Remoção de Componentes Sanguíneos/métodos , Remoção de Componentes Sanguíneos/normas , Separação Celular/métodos , Humanos , Contagem de Leucócitos , Leucócitos/citologia , Contagem de Linfócitos , Fotoferese/normas
6.
Transfusion ; 56(10): 2520-2531, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27480171

RESUMO

BACKGROUND: The Rh system is the most complex and polymorphic blood group system in humans with more than 460 alleles known for the RHD gene. The DAU cluster of RHD alleles is characterized by the single-nucleotide change producing the p.Thr379Met amino acid substitution. It is called the DAU-0 allele and has been postulated to be the primordial allele, from which all other alleles of the DAU cluster have eventually evolved. STUDY DESIGN AND METHODS: For two novel DAU alleles, the nucleotide sequences of all 10 exons as well as adjacent intronic regions, including the 5' and 3' untranslated regions (UTR), were determined for the RHD and RHCE genes. A phylogenetic tree for all DAU alleles was established using the neighbor-joining method with Pan troglodytes as root. Standard hemagglutination and flow cytometry tests were performed. RESULTS: We characterized two DAU alleles, DAU-11 and DAU-5.1, closely related to DAU-3 and DAU-5, respectively. A phylogenetic analysis of the 18 known DAU alleles indicated point mutations and interallelic recombination contributing to diversification of the DAU cluster. CONCLUSIONS: The DAU alleles encode a group of RhD protein variants, some forming partial D antigens known to permit anti-D in carriers; all are expected to cause anti-D alloimmunization in recipients of red blood cell transfusions. The DAU alleles evolved through genomic point mutations and recombination. These results suggest that the cluster of DAU alleles represent a clade, which is concordant with our previous postulate that they derived from the primordial DAU-0 allele.


Assuntos
Alelos , Sistema do Grupo Sanguíneo Rh-Hr/genética , Adulto , África , Evolução Molecular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Mutação Puntual , Gravidez , Recombinação Genética
7.
Transfusion ; 55(5): 996-1000, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25413608

RESUMO

BACKGROUND: Phlebotomy represents the standard treatment option for iron overload in hemochromatosis (HC). Recently, red blood cell (RBC) apheresis has increasingly been used to remove iron. In this study we evaluated the depletion program of the newly developed Spectra Optia device. STUDY DESIGN AND METHODS: Adult male patients (n = 11) with HC were RBC depleted with the Spectra Optia device (Terumo BCT). In total, 24 procedures were performed. A volume of 300 to 550 mL of RBCs was withdrawn per single treatment. RESULTS: No significant adverse events were recorded. A median blood volume of 857.3 ± 23.3 mL was processed. The median procedure time was 12.0 ± 0.4 minutes. The mean reduction of Hct value in each procedure was approximately 6% (Hct pre 42.6 ± 0.5% vs. Hct post 36.6 ± 0.6%) and iron removed per procedure was 405.2 ± 23.3 mg. CONCLUSION: The Spectra Optia device proved to be highly efficient in depleting RBCs in HC patients and allows for short procedure time. The Optia device can be safely used in this clinical setting. We recommend its use in case of severe iron overload if rapid iron depletion needs to be achieved and in case of cardiac compromise due to less blood volume removed.


Assuntos
Remoção de Componentes Sanguíneos/métodos , Hemocromatose/sangue , Hemocromatose/terapia , Ferro/sangue , Adulto , Humanos , Masculino
8.
Blood Transfus ; 22(2): 150-156, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37458722

RESUMO

BACKGROUND: Extracorporeal photopheresis (ECP) is a well-established but lengthy and burdensome cell-based therapy for various diseases such as cutaneous T-cell lymphoma, graft-versus-host disease and organ rejection after transplantation. The number of mononuclear cells (MNCs) that needs to be collected to obtain a clinical response to ECP is still under debate. The purpose of this retrospective study was to determine the number of lymphocytes, monocytes and neutrophils in mononuclear cell products (MCP) by flow cytometry and the collection efficiency in the offline ECP setting. MATERIALS AND METHODS: We collected data from 10 different patients undergoing 162 ECP procedures using the Spectra Optia device for MNC collection. White blood cell (WBC) count of MCP was determined using a hematology analyzer. MNCs were analyzed for CD45 and CD14 expression by flow cytometry to exactly determine the collected lymphocyte and monocyte fractions. RESULTS: Collected MCP showed high cell yields with 55.3×106/kg MNCs and 41.1×106/kg lymphocytes. MCP were characterized by high MNC (81.3%) and low neutrophils (18.7%) percentage. Mean collection efficiency for WBCs and for MNCs was 23.9% and 62.0%, respectively. The MNC fraction showed a moderate to high correlation between peripheral blood cell count of patients and MCP count. DISCUSSION: This study is one of a few reports showing the monocyte-to-lymphocyte relation in MCP for ECP determined by flow cytometry. In comparison to historical data from inline ECP, the offline ECP processing one total blood volume results in considerably higher cell yields. For this reason, and to reduce the burden on patients, we propose that the offline ECP processing time can be substantially reduced.


Assuntos
Doença Enxerto-Hospedeiro , Fotoferese , Humanos , Fotoferese/métodos , Leucócitos Mononucleares , Estudos Retrospectivos , Linfócitos , Contagem de Leucócitos , Doença Enxerto-Hospedeiro/terapia
9.
Infect Dis (Lond) ; : 1-11, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869944

RESUMO

BACKGROUND: Understanding the dynamics of SARS-CoV-2 reinfections is crucial for public health policy, vaccine development, and long-term disease management. However, data on reinfections in the general population remains scarce. OBJECTIVES: This study aimed to investigate SARS-CoV-2 antibody dynamics among Austrian blood donors, representing healthy adults, over two years following primary infection and to evaluate the reinfection risk. METHODS: 117,895 blood donations were analysed for SARS-CoV-2 total anti-N levels from June 2020 to December 2023. We examined anti-N and anti-S antibody dynamics and in vitro functionality in 230 study participants at five defined times during 24 months, assessing associations with demographics, vaccination status, and reinfection awareness. RESULTS: The seroprevalence of SARS-CoV-2 infection-derived anti-N antibodies increased over time, reaching 90% by February 2023 and remaining at that level since then. According to serological screenings, we found an 88% reinfection rate, which is in contrast to participants' reports indicating a reinfection rate of 59%. Our data further reveal that about 26% of reinfections went completely unnoticed. Antibody dynamics were independent of age, sex, and ABO blood group. Interestingly, individuals with multiple reinfections reported symptoms more frequently during their primary infection. Our results further show that vaccination modestly affected reinfection risk and disease course. CONCLUSION: SARS-CoV-2 reinfections were uncommon until the end of 2021 but became common with the advent of Omicron. This study highlights the underestimation of reinfection rates in healthy adults and underscores the need for continued surveillance, which is an important support for public health policies and intervention strategies.

10.
Proteome Sci ; 10(1): 71, 2012 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-23173604

RESUMO

BACKGROUND: Microarray technology may offer a new opportunity to gain insight into disease-specific global protein expression profiles. The present study was performed to apply a serum antibody microarray to screen for differentially regulated cytokines in Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). RESULTS: Serum samples were obtained from patients with clinical diagnoses of PD (n = 117), MSA (n = 31) and PSP/CBS (n = 38) and 99 controls. Cytokine profiles of sera from patients and controls were analyzed with a semiquantitative human antibody array for 174 cytokines and the expression of 12 cytokines was found to be significantly altered. In a next step, results from the microarray experiment were individually validated by different immunoassays. Immunoassay validation confirmed a significant increase of median PDGF-BB levels in patients with PSP/CBS, MSA and PD and a decrease of median prolactin levels in PD. However, neither PDGF-BB nor prolactin were specific biomarkers to discriminate PSP/CBS, MSA, PD and controls. CONCLUSIONS: In our unbiased cytokine array based screening approach and validation by a different immunoassay only two of 174 cytokines were significantly altered between patients and controls.

11.
Viruses ; 14(3)2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35337044

RESUMO

The developmental course of antibodies produced after a SARS-CoV-2 infection has been insufficiently investigated so far. Therefore, the aim of this study was to investigate the dynamics of SARS-CoV-2 antibody levels against the viral nucleocapsid- and spike-protein among Austrian blood donors as a representative group of a supposedly healthy population within the first year after a SARS-CoV-2 infection. The impact of age, sex, vaccination status, AB0-blood group and awareness about the infection was evaluated. Our study shows that the level of anti-N antibodies is declining, while anti-S antibody levels remain stable. Antibodies detected were functional in vitro. Age, sex and blood group do not influence antibody dynamics. However, blood group AB shows significantly lower antibody levels and in vitro functionality compared to other blood groups. Our data reveal that one out of five individuals was not aware of a previous SARS-CoV-2 infection and that the disease course neither affects the level of antibody production nor the in vitro functionality. We also found that 14% of participants show persisting COVID-19-related symptoms for up to nine months. Our results provide valuable insights into the dynamics of the immune response after a SARS-CoV-2 infection in a representative cohort of adult blood donors in Central Europe.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Anticorpos Antivirais , Doadores de Sangue , Humanos , Testes Imunológicos
12.
Diagnostics (Basel) ; 12(11)2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36359411

RESUMO

Convalescent plasma (CP) has been in use for the treatment of numerous infectious diseases for more than a century, recently also for coronavirus disease 2019 (COVID-19). A major challenge for this treatment is identifying suitable donors with sufficient levels of functional antibodies and to determine the optimal time span for CP donation. In this retrospective study, we analyzed 189 CP donations of 66 donors regarding anti-SARS-CoV-2 anti-S IgG antibody levels. We found a significant correlation between the semi-quantitative SARS-CoV-2 IgG ratio values and in vitro antibody functionality. A time-to-event analysis allowed us to predict the optimal time span of COVID-19 CP donor suitability. We found that high IgG ratio values, which significantly correlate with high in vitro antibody functionality, were suitable for CP donation for a median of 134 days after the first CP donation. Donors with lower IgG ratios were suitable for a median of 53 days. Our data support plasma collection centers to determine optimal points in time for CP donation by means of widely used semi-quantitative laboratory IgG ratio values.

13.
Crit Care Med ; 37(6): 1886-92, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19384223

RESUMO

OBJECTIVE: To analyze the influence of red blood cell (RBC) transfusions on mortality and outcome of patients with spontaneous subarachnoid hemorrhage (SAH) and to determine predictors of unfavorable neurologic long-term outcome in this patient population. DESIGN: Cohort study with post-intensive care unit (ICU) prospective evaluation of functional long-term outcome. SETTING: Ten-bed neuro-ICU in a tertiary care university hospital. PATIENTS: A consecutive cohort of 292 patients with spontaneous SAH admitted to a neuro-ICU during a 70-month period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 292 consecutive patients with SAH were enrolled in the study. At admission, mean hemoglobin was 13.3 g/dL (+/-sd 1.8 g/dL), comparable in all Hunt and Hess groups (p = 0.61 by analysis of variance). Seventy-nine patients received at least one unit of RBC transfusion in the study period. In-ICU mortality was 20.5% (n = 60). Binary logistic regression analysis comparing survivors with nonsurvivors found only higher Hunt and Hess grades (i.e., Hunt and Hess 3-5) to be significantly (p < 0.01) associated with mortality in the neuro-ICU, whereas transfusion, sex, and even age had no significant influence. Functional long-term outcome was assessed after a mean of 3.3 years (sd +/-1.7 years) by evaluating modified Rankin Scale (mRS) and Glasgow Outcome Scale (GOS). More than 41% of all patients have almost fully recovered (i.e., mRS 0-1; GOS 4-5). Factors associated with unfavorable long-term outcome (i.e., GOS 1-3 and mRS 2-6) were age (odds ratio 1.06; 95% confidence interval 1.03-1.09; p < 0.01), Hunt and Hess Grade (odds ratio 11.43; 95% confidence interval 4.1-31.9; p < 0.01) but not transfusion (p = 0.46). CONCLUSION: Transfusion of RBCs was not associated with in-neuro-ICU mortality or unfavorable long-term outcome. Of all patients with SAH, >41% have almost fully recovered with favorable neurologic long-term outcome.


Assuntos
Transfusão de Eritrócitos , Hemorragia Subaracnóidea/mortalidade , Hemorragia Subaracnóidea/terapia , Estudos de Coortes , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
14.
Wien Klin Wochenschr ; 129(3-4): 141-144, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27878613

RESUMO

BACKGROUND: Hereditary hemorrhagic telangiectasia is an inherited autosomal dominant disease presenting with recurrent bleeding episodes and iron deficiency anemia due to vascular malformations. Hereditary hemorrhagic telangiectasia is associated with an increased risk of stroke, gastrointestinal bleeding and pulmonary hypertension and life expectancy is significantly reduced. Excess vascular endothelial growth factor (VEGF) plays a key role in the pathophysiology of the disease. CASE PRESENTATION: Here we report about a male patient with hereditary hemorrhagic telangiectasia presenting with pulmonary and central nervous system involvement experiencing repetitive nosebleeds, necessitating frequent local cauterization and transfusion of more than 100 units of packed red blood cells. After initiation of temporary therapy with the anti-VEGF antibody bevacizumab at a dosage of 1 mg/kg body weight every 2 weeks, the nose bleeding episodes and the epistaxis severity score significantly decreased and long-lasting transfusion independence was achieved. Reinitiation of low-dose bevacizumab after relapse again proved effective without any documented therapy-related adverse events. In comparison to other reported anti-VEGF antibody protocols in hereditary hemorrhagic telangiectasia, our treatment approach proved to be cost-efficient. CONCLUSION: Intermittent low-dose therapy with bevacizumab represents an effective and cost-efficient treatment option for transfusion-dependent patients with hereditary hemorrhagic telangiectasia.


Assuntos
Bevacizumab/administração & dosagem , Epistaxe/prevenção & controle , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Epistaxe/diagnóstico , Epistaxe/etiologia , Humanos , Telangiectasia Hemorrágica Hereditária/complicações , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
15.
Mol Metab ; 6(1): 38-47, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28123936

RESUMO

OBJECTIVE: Elevated serum ferritin has been linked to type 2 diabetes (T2D) and adverse health outcomes in subjects with the Metabolic Syndrome (MetS). As the mechanisms underlying the negative impact of excess iron have so far remained elusive, we aimed to identify potential links between iron homeostasis and metabolic pathways. METHODS: In a cross-sectional study, data were obtained from 163 patients, allocated to one of three groups: (1) lean, healthy controls (n = 53), (2) MetS without hyperferritinemia (n = 54) and (3) MetS with hyperferritinemia (n = 56). An additional phlebotomy study included 29 patients with biopsy-proven iron overload before and after iron removal. A detailed clinical and biochemical characterization was obtained and metabolomic profiling was performed via a targeted metabolomics approach. RESULTS: Subjects with MetS and elevated ferritin had higher fasting glucose (p < 0.001), HbA1c (p = 0.035) and 1 h glucose in oral glucose tolerance test (p = 0.002) compared to MetS subjects without iron overload, whereas other clinical and biochemical features of the MetS were not different. The metabolomic study revealed significant differences between MetS with high and low ferritin in the serum concentrations of sarcosine, citrulline and particularly long-chain phosphatidylcholines. Methionine, glutamate, and long-chain phosphatidylcholines were significantly different before and after phlebotomy (p < 0.05 for all metabolites). CONCLUSIONS: Our data suggest that high serum ferritin concentrations are linked to impaired glucose homeostasis in subjects with the MetS. Iron excess is associated to distinct changes in the serum concentrations of phosphatidylcholine subsets. A pathway involving sarcosine and citrulline also may be involved in iron-induced impairment of glucose metabolism.


Assuntos
Glucose/metabolismo , Ferro/metabolismo , Adulto , Glicemia/metabolismo , Citrulina/sangue , Citrulina/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Ferritinas/análise , Ferritinas/sangue , Ferritinas/metabolismo , Teste de Tolerância a Glucose , Homeostase , Humanos , Resistência à Insulina/fisiologia , Ferro/sangue , Masculino , Síndrome Metabólica/metabolismo , Metabolômica/métodos , Pessoa de Meia-Idade , Obesidade/sangue , Sarcosina/sangue , Sarcosina/metabolismo
16.
Cancer ; 117(10): 2163-9, 2011 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-21523729

RESUMO

BACKGROUND: Early stage chronic lymphocytic leukemia is characterized by a highly variable course of disease. Because it is believed that regulatory T cells (T(regs) ) are potent suppressors of antitumor immunity, the authors hypothesized that increased T(regs) may favor disease progression. METHODS: T(reg) levels (cluster of differentiation 3 [CD3]-positive, [CD4]-positive, CD25-positive, and CD127-negative) in peripheral blood from 102 patients were analyzed by flow cytometry. Statistical analysis was used to evaluate correlations with clinical data. RESULTS: The relative T(reg) numbers in CD4-positive T cells were significantly greater in patients with chronic lymphocytic leukemia compared with the numbers in a control group of 170 healthy individuals (P = .001). Patients were divided into 2 groups using a median T(reg) value of 9.7% (the percentage of CD4-positive T cells). Patients with higher T(reg) levels had a significantly shorter time to initial treatment (median, 5.9 years) compared with patients who had lower T(reg) levels (median, 11.7 years; log-rank P = .019). Furthermore, T(reg) levels (the percentage of CD4-positive T cells) had significant prognostic power to predict the time to initial treatment in univariate analysis (P = .023) and in multivariate Cox regression analysis that included the variables Rai stage, immunoglobulin heavy-chain variable region gene mutational status, chromosomal aberrations, and CD38 expression (P = .028). CONCLUSIONS: Higher T(reg) levels had significant and independent prognostic power for predicting the time to initial treatment in patients with low to intermediate stage chronic lymphocytic leukemia.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Leucemia Linfocítica Crônica de Células B/sangue , Linfócitos T Reguladores/imunologia , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Contagem de Linfócitos , Prognóstico , Risco , Fatores de Tempo
17.
Transfusion ; 47(7): 1125-33, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17581146

RESUMO

BACKGROUND: This study compared the efficacy of bacterial detection with inactivation for reducing the risk associated with transfusion of platelet (PLT) components contaminated with low levels of bacteria. STUDY DESIGN AND METHODS: Twenty-one double-dose PLTs were spiked with seven species of bacteria at three levels (0.003-0.03, 0.03-0.3, 0.3-3 colony-forming units [CFUs]/mL). After split, each PLT unit contained 1 to 10, 10 to 100, and 100 to 1000 CFUs. One unit was photochemically treated (PCT; 150 micromol/L amotosalen and 3 J/cm(2) ultraviolet A). The other unit was untreated. All units were stored and sampled on Days 1, 2, and 5 of storage for aerobic and anaerobic culture in the BacT/ALERT system (bioMérieux). PLTs were classified as sterile when no bacterial growth was detected after 120 hours of culture. RESULTS: In all PCT PLTs, no bacteria were detected throughout 5 days of storage regardless of species, level of contamination, and sampling time. In untreated PLTs, Staphylococcus aureus was consistently detected by culturing. Growth of 1 to 10 CFUs per unit Staphylococcus epidermidis, 1 to 100 CFUs per unit of Klebsiella pneumoniae, and 1 to 1000 CFUs per unit Propionibacterium acnes was delayed and only detectable after 5, 2, and 5 days of storage, respectively. Low levels of Streptococcus agalactiae (1-10 CFUs/unit), Escherichia coli (1-100 CFUs/unit), and Clostridium perfringens (1-100 CFUs/unit) were not detected during 5 days of storage, although bacterial outgrowth was detected at higher levels of contamination. CONCLUSIONS: For the seven bacterial species examined, contaminated PLTs may be released for transfusion on test-negative-to-date status. In contrast, bacterial inactivation by PCT could reduce the risk associated with transfusion of PLTs contaminated with low levels of these bacteria.


Assuntos
Bactérias/isolamento & purificação , Técnicas Bacteriológicas/métodos , Viabilidade Microbiana , Transfusão de Plaquetas/efeitos adversos , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/transmissão , Técnicas Bacteriológicas/normas , Humanos , Métodos
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