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2.
Cancers (Basel) ; 15(22)2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38001691

RESUMO

Adult acute lymphoblastic leukemia (ALL) is associated with poor outcomes. ALL is initiated by primary aberrations, but secondary genetic lesions are necessary for overt ALL. In this study, we reassessed the value of primary and secondary aberrations in intensively treated ALL patients in relation to mutator enzyme expression. RT-PCR, genomic PCR, and sequencing were applied to evaluate primary aberrations, while qPCR was used to measure the expression of RAG and AID mutator enzymes in 166 adult ALL patients. Secondary copy number alterations (CNA) were studied in 94 cases by MLPA assay. Primary aberrations alone stratified 30% of the patients (27% high-risk, 3% low-risk cases). The remaining 70% intermediate-risk patients included BCR::ABL1pos subgroup and ALL lacking identified genetic markers (NEG ALL). We identified three CNA profiles: high-risk bad-CNA (CNAhigh/IKZF1pos), low-risk good-CNA (all other CNAs), and intermediate-risk CNAneg. Furthermore, based on RAG/AID expression, we report possible mechanisms underlying the CNA profiles associated with poor outcome: AID stratified outcome in CNAneg, which accompanied most likely a particular profile of single nucleotide variations, while RAG in CNApos increased the odds for CNAhigh/IKZF1pos development. Finally, we integrated primary genetic aberrations with CNA to propose a revised risk stratification code, which allowed us to stratify 75% of BCR::ABL1pos and NEG patients.

3.
Healthcare (Basel) ; 10(12)2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36553969

RESUMO

Social media is one of the most common sources of medical information. We aimed to evaluate the information contained on websites, including social media and descriptions of fundraisers, in terms of the reliability of knowledge about SMA and gene therapy with onasemnogen abeparvovec. We used a set of available online links found using the Newspointtool. Initially, 1525 texts were included in the study, and after applying the inclusion and exclusion criteria, 112 texts were qualified for analysis using the DISCERN scale and the set of questions prepared by the authors. We observed that most of the texts had poor (48.65%) and medium (27.03%) reliability in the final reliability assessment. All the texts selected for the study were related to gene therapy, although few contained key information about it. In addition, the authors of the entries used various words and phrases that influenced the readers' perceptions of the text. Of the analyzed sources, 68.8% had an emotional component. Social media is a poor source of information about gene therapy for SMA in Poland. The analyzed texts do not provide a full and complete description of the SMA problem. However, it is important to remember that the Internet is a changing source of information and will hopefully contain more relevant entries in the future.

4.
Nurs Educ Perspect ; 42(4): 246-247, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34152103

RESUMO

ABSTRACT: Over the past decade, the Agency for Healthcare Research and Quality and The Joint Commission have identified that communication problems are a root cause of most serious adverse events and that patients with limited English proficiency are more likely than others to suffer physical harm when such errors occur. It is essential to educate nursing students on the challenges of patients with limited English proficiency and empower them with tools, such as the National Culturally and Linguistically Appropriate Services standards, to minimize this phenomenon in their future nursing practice. We describe an educational intervention designed to accomplish this using Kolb's experiential learning theory as a foundation for implementation.


Assuntos
Aprendizagem Baseada em Problemas , Estudantes de Enfermagem , Humanos
5.
Transfus Apher Sci ; 59(6): 102917, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32948464

RESUMO

There are many reports on factors predicting the outcome of PBSC (peripheral blood stem cell) mobilization, such as the donor's gender, age, weight, white blood cell count, platelets pre apheresis, LDH and iron status. Although there are reports of seasonal variation in the physiology of the human immune system and hematopoiesis there are no data that such differences play a role in the response to G-CSF in healthy hematopoietic stem cell donors. The response to G-CSF could also impact the collection results during different seasons. To assess the possible impact of seasonal variation we performed a retrospective, single-center analysis of mobilization and harvest of PBSC in 330 healthy unrelated donors. We found no significant differences in the number of CD34+ cells in peripheral blood after G-CSF mobilization and in collection results when all donors were analyzed. In the subgroup of male donors the number of CD34+ stem cells after G-CSF mobilization was higher than average in summer and autumn (p = 0.036), however, it did not translate into clinically relevant differences in stem cell harvest. We conclude that although there is possible seasonal variation in the response to G-CSF in male donors there is no impact on PBSC harvest in healthy unrelated donors.


Assuntos
Antígenos CD34/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco de Sangue Periférico/metabolismo , Adolescente , Adulto , Doadores de Sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estações do Ano , Adulto Jovem
6.
Transplant Proc ; 52(7): 2186-2192, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32222395

RESUMO

BACKGROUND: Renal impairment (RI) is one of the multiple myeloma (MM)-defining events for initiating therapy. After induction therapy, high-dose chemotherapy followed by autologous peripheral blood stem cell transplant (ASCT) remains the standard of care for transplant-eligible patients with MM. According to the International Myeloma Working Group (IMWG), the organ criterion for kidney damage is defined by a serum creatinine concentration (CrC) > 2 mg/dL or estimated glomerular filtration rate (eGFR) < 40 mL/min. In this long-term study, we evaluated the impact of CrC and eGFR calculated by the Modification of Diet in Renal Disease equation on progression-free and overall survival using a lower threshold than the IMWG criteria. PATIENTS AND METHODS: We studied the longitudinal outcomes as measured by progression-free survival and overall survival in 59 transplant-eligible patients with MM: 38 patients with normal renal function and 21 patients with RI defined as a CrC higher than upper limit of normal (≥ 1.1 mg/dL), eGFR < 60 mL/min, treated with ASCT from 1998 to 2004. RESULTS: The risk of disease progression and death following ASCT increased by 16.5% (P = .005) and 19% (P < .0009) per 1 mg/dL of CrC, respectively. The thresholds for the association of renal insufficiency and negative outcomes were CrC > 1.4 mg/dL and eGFR < 55mL/min. CONCLUSIONS: We observed a negative correlation between minimal renal insufficiency and long-term outcomes. Management of patients with even marginally increased CrC and/or decreased eGFR not fulfilling IMWG RI criteria requires more concentrated effort to reverse even minimal renal insufficiency.


Assuntos
Mieloma Múltiplo/complicações , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Insuficiência Renal/diagnóstico , Insuficiência Renal/etiologia , Adulto , Idoso , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Insuficiência Renal/classificação , Transplante Autólogo
7.
Medicine (Baltimore) ; 98(1): e13956, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30608431

RESUMO

Angiogenesis represents one of the critical mechanisms that facilitates carcinoma development. The study objective was to evaluate whether the microsatellite instability of colorectal carcinoma has impact on the angiogenesis activity in liver metastases.In a cohort of 80 randomly selected patients with stage IV colorectal carcinoma, 30% were recognized as microsatellite unstable (Microsatellite instability high-frequency (MSI-H)). The endothelial progenitor cell fraction (CD309+) was counted within the subpopulation of CD34+CD45+ cell and CD34+CD45- cells by flow cytometer. vascular endothelial growth factor (VEGF) factor levels were quantified in serum samples by enzyme-linked immunosorbent assay (ELISA). A control group consisted of 36 healthy volunteers. The relationship of genomic instability to angiogenesis activity was evaluated by multivariate analysis in comparison to the controls, adopting a P < .05 value as statistically significant.The expression of endothelial progenitor cells (EPCs) and VEGF was significantly higher in MSI-H compared to both microsatellite stability (MSS) patients and healthy controls (P < .008). Multi-parametric analysis showed microsatellite instability (OR=9.12, P < .01), metastases in both lobes (OR = 32.83, P < .001) and simultaneous metastases outside liver (OR = 8.32, P < .01), as independent factors associated with increased angiogenesis as assessed by measures of EPC and VEGF. A higher percentage of EPCs within the white blood cell fraction (total % EPCs / white blood cells (WBC)) and higher serum concentrations of VEGF were present in patients with MSI-H colorectal cancer, and not with MSS cancers (P < .001).MSI-H patients with colorectal cancer metastases are associated with the overexpression of circulating EPCs and VEGF, potentially driving angiogenesis. This should be considered in therapeutic decision-making.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/patologia , Instabilidade de Microssatélites , Neovascularização Patológica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/cirurgia , Células Progenitoras Endoteliais/metabolismo , Feminino , Instabilidade Genômica/genética , Voluntários Saudáveis/estatística & dados numéricos , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Estadiamento de Neoplasias , Neovascularização Patológica/genética , Telemedicina/métodos , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
Artigo em Inglês | MEDLINE | ID: mdl-30200412

RESUMO

Background: The International Classification of Functioning, Disability, and Health (ICF) Core Sets for children and youth with cerebral palsy (CP) offer service providers and stakeholders a specific framework to explore functioning and disability for assessment, treatment, evaluation, and policy purposes in a global context. Objective: Describe global initiatives applying the ICF Core Sets for children and youth with CP, with a focus on contributions to clinical practice and challenges in their implementation. Methods: This is a descriptive cross-sectional study. Ongoing initiatives applying the ICF Core Sets for CP in Russia, Poland, Malawi, and Brazil are included. Results: The main contributions of applying the ICF Core Sets for children and youth with CP include: (1) an objective description of abilities and limitations in everyday activities; (2) a consistent identification of facilitators and barriers influencing functioning; (3) a practical communication tool promoting client-centered care and multidisciplinary teamwork; and, (4) a useful guideline for measurement selection. The main challenges of adopting the ICF Core Sets are related to lack of ICF knowledge requiring intense training and translating results from standardized measures into the ICF qualifiers in a consistent way. Conclusions: Global initiatives include research and clinical applications at the program, service and system levels. The ICF Core Sets for CP are useful tools to guide service provision and build profiles of functioning and disability. Global interprofessional collaboration, capacity training, and informatics (e-records) will maximize their applications and accelerate adoption.


Assuntos
Paralisia Cerebral/classificação , Avaliação da Deficiência , Pessoas com Deficiência/classificação , Atividades Cotidianas , Adolescente , Brasil , Criança , Humanos , Classificação Internacional de Funcionalidade, Incapacidade e Saúde , Malaui , Polônia , Federação Russa
9.
Sci Rep ; 8(1): 10462, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29993003

RESUMO

Pathological levels of oxidative stress (OS) have been implicated in many diseases including diabetes mellitus, neurodegenerative diseases, inflammatory diseases, atherosclerosis, and cancer. Studies of oxidative stress are however complicated by the low concentration of oxidation products. To resolve this problem, we tested a new derivative of aminoadipic semialdehyde (Fmoc-Aea-OH) in the solid-phase synthesis of carbonylated peptides. We prepared a series of peptides with free and acetylated N-terminal amino groups using the Fmoc-Aea-OH reagent. LC-MS, ESI-MS, and MS/MS spectra confirmed the sequences of the modified peptides, although the LC-MS and ESI-MS spectra were dominated by signals corresponding to dehydration products. NMR studies of acetylated products revealed that the dominant product formed in this reaction contains a 1,2,3,4-tetrahydropyridine-2-carboxylic acid residue. Another side reaction in this system was the cleavage of the amide bond between the Aea residue and the amino acid moiety preceding it resulting in the formation of a side product with a six-membered ring at the N-terminus (2,3,4,5-tetrahydropyridine-2-carboxylic acid residue). We found that, depending on the peptide sequence, one of those side products is predominant. Our work suggests new methods for the solid-state synthesis of peptides containing unnatural amino acids.


Assuntos
Adipatos/química , Aldeídos/química , Estresse Oxidativo , Peptídeos/síntese química , Técnicas de Síntese em Fase Sólida/métodos , Sequência de Aminoácidos , Cromatografia Líquida , Ciclização , Oxirredução , Espectrometria de Massas em Tandem
10.
Transfus Apher Sci ; 57(3): 401-405, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29778714

RESUMO

BACKGROUND: Recently, novel protocol utilizing Continuous Mononuclear Cell Collection (cMNC) have been introduced for leukapheresis. We compared the efficacy of cMNC with an older protocol - mononuclear cell collection (MNC) for CD34+ cell collection in unrelated donors with negative stem cell collection predictors. MATERIAL AND METHODS: Retrospective data from a series of 258 consecutive unrelated hematopoietic stem cell donors was included in this single-center study (80 donors collected with cMNC and 178 with MNC). The donors with poor predictors for collection such as low number of circulating CD34+ cells and/or weight disproportion were assigned to the cMNC arm. RESULTS: The cMNC protocol yielded a higher number of CD34 + cells per donor body weight (7.63 × 106/kg vs 6.82 × 106/kg, p = 0.027). One apheresis was sufficient for collection of target cell number in 89% individuals from both groups despite negative predictors in the cMNC group. In donors with CD34 + cell count <100/µL and a body weight disproportion between donor and recipient one apheresis was sufficient in 83% of donors in cMNC group and in 58% in MNC group (p = 0.0345) with collection efficiency CE2% values of 61% for cMNC and 62% for MNC (p = 0.77). CONCLUSION: cMNC protocol is more efficient in donors with low pre-apheresis CD34+ cell count and weight disproportion between donor and recipient. This suggests that the use of cMNC in unrelated donors could possibly further improve the results of HSC collections.


Assuntos
Remoção de Componentes Sanguíneos/métodos , Mobilização de Células-Tronco Hematopoéticas/métodos , Leucócitos Mononucleares/metabolismo , Transplante Homólogo/métodos , Feminino , Humanos , Masculino
11.
Aerobiologia (Bologna) ; 34(1): 111-118, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29497242

RESUMO

We report on the determination of the spore concentration and the species composition of the airborne fungi in selected caves of the Tatra Mountains, Poland. The following caves were surveyed: Mylna, Oblazkowa, Mrozna, Zimna and Naciekowa. The sampling was carried out in July 2015 and in January 2016. The aeromycological analyses were performed with the impact method, using the Air Ideal 3P apparatus and potato dextrose agar (PDA, Biocorp) culture medium. In the course of the July 2015 analysis, 17 species of fungi were isolated and 11 species were isolated in January 2016. In Mylna and Naciekowa caves, the dominant species were Cladosporium cladosporioides and Stachybotrys cylindrospora. In Oblazkowa cave, Rhizoctonia predominated and in Zimna cave-the colonies of the yeast-like fungi, along with S. cylindrospora. In Mrozna cave, Penicillium notatum was the most abundant taxon. In the winter time, in the majority of the caves Penicillium spp. predominated, with the exception of Mrozna and Naciekowa caves where Aspergillus niger was dominant. We propose that aeromycological monitoring be performed regularly in the following caves: Mrozna, Naciekowa and Zimna.

12.
J Clin Apher ; 33(3): 249-258, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28922455

RESUMO

INTRODUCTION: High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) improves the outcome of patients with multiple myeloma (MM). It seems that auto-HSCT is also a feasible therapeutic option in MM dialysis-dependent (MMDD) patients. However, to perform transplantation, a sufficient number of stem cells must be collected. MATERIALS AND METHODS: Given that data on mobilization of auto-HSC efficacy and safety in dialysis-dependent patients are limited, we report data from all Polish Centers belonging to the Polish Myeloma Study Group. Twenty-eight dialysis-dependent MM-patients were enrolled into this retrospective analysis. The study population comprised patients diagnosed between 2004 and 2015 in whom an attempt to collect auto-HSC was made (68%: women, median age: 56). Patients received granulocyte-colony stimulating factor (G-CSF) alone or in combination with chemotherapy and autologous peripheral blood stem cells (auto-PBSCs) were collected by leukapheresis. RESULTS AND CONCLUSIONS: The success rate in terms of obtaining sufficient number of CD34(+) cells/kg for an auto-HSCT (≥2 × 106 cells/kg body weight) during the first mobilization attempt was 92% (26/28 patients), and for 2 auto-HSCTs (≥4 × 106 cells/kg) - was 75% (21/28 patients). After the second mobilization attempt (undertaken in 8 patients), a sufficient number of CD34(+)/kg cells for an auto-HSCT was obtained for all patients and the number of CD34(+)/kg collected cells was sufficient for 2 auto-HSCT in 6 additional patients. Hematologic toxicity and infections were the most frequent complications. Higher doses of cytarabine (>1.6 g/m2 ) and cyclophosphamide (> 2 g/m2 ) should be avoided in MMDD patients due to toxicity. Further studies are needed to establish mobilization regimens, confirm their safety, and dosing in MMDD patients.


Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Antígenos CD34/análise , Feminino , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Polônia , Diálise Renal , Estudos Retrospectivos , Transplante Autólogo
13.
Ann Hematol ; 96(10): 1735-1739, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28801752

RESUMO

The World Marrow Donor Organization recommends original granulocyte-colony stimulating factor (G-CSF) for the mobilization of stem cells in healthy unrelated hematopoietic stem cell donors. We report the comparison of a biosimilar G-CSF (Zarzio) with two original G-CSFs (filgrastim and lenograstim) in mobilization in unrelated donors. We included data of 313 consecutive donors who were mobilized during the period from October 2014 to March 2016 at the Medical University of Warsaw. The primary endpoints of this study were the efficiency of CD34+ cell mobilization to the circulation and results of the first apheresis. The mean daily dose of G-CSF was 9.1 µg/kg for lenograstim, 9.8 µg/kg for biosimilar filgrastim, and 9.3 µg/kg for filgrastim (p < 0.001). The mean CD34+ cell number per microliter in the blood before the first apheresis was 111 for lenograstim, 119 for biosimilar filgrastim, and 124 for filgrastim (p = 0.354); the mean difference was even less significant when comparing CD34+ number per dose of G-CSF per kilogram (p = 0.787). Target doses of CD34+ cells were reached with one apheresis in 87% donors mobilized with lenograstim and in 93% donors mobilized with original and biosimilar filgrastim (p = 0.005). The mobilized apheresis outcomes (mean number of CD34+ cells/kg of donor collected during the first apheresis) was similar with lenograstim, biosimilar filgrastim, and filgrastim: 6.2 × 106, 7.6 × 106, and 7.3 × 106, respectively, p = 0.06. There was no mobilization failure in any of the donors. Biosimilar G-CSF is as effective in the mobilization of hematopoietic stem cells in unrelated donors as original G-CSFs. Small and clinically irrelevant differences seen in the study can be attributed to differences in G-CSF dose and collection-related factors. Active safety surveillance concurrent to clinical use and reporting to donor outcome registry (e.g., EBMT donor outcome registry or WMDA SEAR/SPEAR) might help to evaluate the possible short- and long-term complications of biosimilar G-CSF.


Assuntos
Medicamentos Biossimilares/administração & dosagem , Filgrastim/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Doadores de Tecidos , Adulto , Feminino , Humanos , Lenograstim , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem
14.
J Nurs Educ ; 56(5): 292-294, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28467558

RESUMO

BACKGROUND: Schools of nursing have moved to multiple choice test questions to help prepare students for licensure and practice. However, students can buy test banks to help them "get through" nursing school. Accurate assessment of nursing students' knowledge and judgment comprises access to test banks. METHOD: The purpose of this exploratory study was to gain an understanding about nursing faculty's knowledge concerning test bank security issues, to assess whether publishers were aware of this issue, and vendor's reasons for supplying test banks to students. RESULTS: Overall, the results indicated that the majority of faculty were unaware of student access to test banks, and although most do not use test banks verbatim, general consensus existed that test bank security is a concern. CONCLUSION: Implications include increasing faculty awareness of test bank access by students, supporting educators to develop their own test bank items, and promoting security of all examinations. [J Nurs Educ. 2017;56(5):292-294.].


Assuntos
Bases de Dados como Assunto , Educação em Enfermagem , Avaliação Educacional , Atitude do Pessoal de Saúde , Comércio , Docentes de Enfermagem , Humanos , Internet , Inquéritos e Questionários
15.
J Community Health Nurs ; 33(3): 139-44, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27383777

RESUMO

Health disparities, especially among minorities, persist; obesity is a national concern; and the combined effect can be significant for families and populations. In an effort to address obesity at an early age, the National Association of Hispanic Nurses (NAHN), developed the Muevete USA™ project. Muevete USA™ (from the Spanish verb for "to move") features five lesson plans on healthy lifestyles for children and their families. This article describes Muevete USA™, the partnership with a local school of nursing, the implementation of the program at the local level and the emerging program and student outcomes of a successful partnership.


Assuntos
Pesquisa Participativa Baseada na Comunidade , Estudantes de Enfermagem , Criança , Saúde da Criança , Humanos , Obesidade , Instituições Acadêmicas
16.
J Mol Neurosci ; 56(1): 154-63, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25487315

RESUMO

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Four distinct disease courses are known, although approximately 90% of patients are diagnosed with the relapsing-remitting form (RRMS). The name "multiple sclerosis" pertains to the underlying pathology: the presence of demyelinating plaques in the CNS, in particular in the periventricular region, corpus callosum, cervical spine, and the cerebellum. There are ongoing efforts to discover biomarkers that would allow for an unequivocal diagnosis, assess the activity of inflammatory and neurodegenerative processes, or warn of disease progression. At present, small noncoding RNA particles-microRNA (miRNA, miR) seem to be particularly noteworthy, as they take part in posttranscriptional regulation of expression of various genes. Changes in composition as well as function of miRNA found in body fluids of MS patients are subjects of research, in the hope they prove accurate markers of MS activity. This preliminary study aims to evaluate the expression of selected extracellular microRNA particles (miRNA-let-7a, miRNA-92a, miRNA-684a) in patients experiencing MS relapse and remission, with healthy volunteers serving as a control group and to evaluate the correlation between miRNA expression and selected clinical parameters of those patients. Thirty-seven patients suffering from MS formed two examined groups: 20 patients undergoing relapse and 17 in remission. Thirty healthy volunteers formed the control group. All patients who were subjects to peripheral blood sampling had been hospitalized in the Department of Neurology and Stroke(1). Four milliliters of venous whole blood had been collected into EDTA tubes. The basis for the selection of the three particular miRNA investigated in this study (miRNA-let-7a, miRNA-92a, miRNA-684a) was a preliminary bioinformatic analysis of data compiled from several medical databases, including Ovid MEDLINE®, Embase, Cochrane Database of Systematic Reviews (CDSR), miRWalk, and miRBase. The isolation of extracellular microRNA from plasma was carried out using miRNeasy Mini Kit (Qiagen) reagents. The reverse transcription was carried out with TaqMan® MicroRNA Reverse Transcription Kit (Applied Biosystems), as per manufacturers' instructions. Standard microRNA TaqMan® tests (Applied Biosystems) were used for miRNA quantification. The qPCR were performed on a 7900 HT Fast Real-Time PCR System (Applied Biosystems) and analyzed using Sequence Detection System 2.3 software. In addition, all patients at the Department of Neurology and Stroke undergo a routine complete blood count with differential. The main objective of this study was to evaluate the expression of selected microRNA (has-miR-let-7a, miR-92a, and miR-648a) in the plasma of patients with MS during a relapse as well as in remission and attempt to correlate the acquired data with clinically relevant parameters of the disease. Finding such correlations may potentially lead to the use of miRNA as a biomarker of MS, which could help diagnose the disease and assess its severity and the efficacy of treatment. The difference in the expression of has-miR-let-7a in the remission group and the control group was statistically significant (p = 0.002). Similarly, the expression of miRNA-648a in patients in remission was significantly different from the expression in the control group (p = 0.02). Analysis of the correlation between the expression of miRNA-92a and the severity of the disease as measured by the EDSS scale in patients undergoing relapse showed significant negative linear correlation (r = -0.54, p = 0.01). Higher miR-648a expression correlated with more frequent flare-ups in the joint group of patients in remission and relapse (p = 0.03). This study is one of the few that demonstrate significantly changed expression of selected extracellular miRNA in plasma of MS patients and correlate those findings with clinical parameters. These observations may suggest that some miRNA subsets may be potential biomarkers for MS activity.


Assuntos
MicroRNAs/sangue , Esclerose Múltipla/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino
17.
Ann Transplant ; 19: 444-6, 2014 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-25189633

RESUMO

BACKGROUND: This is a single-center, retrospective study in the field of mobilization of hematopoietic stem cell from unrelated donors. We aimed to investigate whether delaying the last G-CSF dose after the start of apheresis influences its results. MATERIAL AND METHODS: The medical records of 55 unrelated hematopoietic stem cell donors during the period 2010-2013 were analysed. In this series, 40 received donors the last G-CSF injection prior to the leukapheresis procedure, and 15 received the last injection after apheresis was initiated. RESULTS: In the delayed G-CSF application group, more donors had already reached the requested cell number during first apheresis than in the group treated following the standard procedure (73% vs. 35%, respectively; p<0.01). Also, the average total G-CSF dose needed to mobilize the requested cell number was lower (41 µg/kg vs. 48 µg/kg, respectively, p=0.002). CONCLUSIONS: Delayed G-CSF use in donors undergoing stem cell mobilization shows a better efficiency of stem cell mobilization.


Assuntos
Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Leucaférese/métodos , Adulto , Contagem de Células , Esquema de Medicação , Feminino , Humanos , Injeções , Lenograstim , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Estudos Retrospectivos , Doadores não Relacionados , Adulto Jovem
18.
J Innate Immun ; 6(4): 417-25, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24355864

RESUMO

Neutrophils and complement are key members of innate immunity. The alternative pathway (AP) of complement consists of C3, factor B, factor D and properdin, which amplifies AP activation. AP has been implicated in many neutrophil-mediated diseases, such as anti-neutrophil cytoplasmic antibody-associated vasculitis. The exact mechanism by which the AP and neutrophils interact remains largely unstudied. We investigated the ability of the AP to interact with neutrophil components which can be exposed and released upon activation. Our studies focused on neutrophil enzymes, including myeloperoxidase (MPO), proteinase 3 (PR3), azurocidin, elastase, lysozyme and cathepsin G. All enzymes except for azurocidin were able to bind properdin. However, only MPO could induce C3 activation. MPO mediated AP complement activation in the presence of MgEGTA compared to the EDTA control. This activation resulted in C3 deposition and required properdin to occur. Furthermore, we could show that MPO binds properdin directly, which then serves as a focus for AP activation. In summary, properdin can directly interact with neutrophil components. MPO demonstrates the ability to activate the AP which is dependent on properdin. Finally, MPO is capable of inducing properdin-initiated C3 and C5b-9 deposition in vitro.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Via Alternativa do Complemento , Neutrófilos/imunologia , Peroxidase/metabolismo , Properdina/metabolismo , Peptídeos Catiônicos Antimicrobianos/metabolismo , Proteínas Sanguíneas/metabolismo , Proteínas de Transporte/metabolismo , Catepsina G/metabolismo , Complemento C3/metabolismo , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Humanos , Imunidade Inata , Muramidase/metabolismo , Mieloblastina/metabolismo , Elastase Pancreática/metabolismo , Ligação Proteica
19.
Methods Mol Biol ; 1100: 161-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24218258

RESUMO

Properdin is a member of the alternative pathway of complement. It is unique in that it is the only known positive regulator of the complement system. Properdin can stabilize and promote complement activation, but in addition is also capable of initiating the alternative pathway, making it a unique protein. This chapter focuses on the methods required for purifying human properdin and testing its functionality.


Assuntos
Properdina/isolamento & purificação , Properdina/metabolismo , Cromatografia de Afinidade , Cromatografia por Troca Iônica , Complemento C3b/metabolismo , Via Alternativa do Complemento , Humanos , Ligação Proteica
20.
Acta Haematol ; 130(3): 169-71, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23735747

RESUMO

The addition of rituximab to standard chemotherapy has improved the results of the treatment of B cell non-Hodgkin's lymphomas. Under specific circumstances, it can be administered locally, as an alternative to systemic administration. We administered rituximab intrapericardially in an attempt to control pericardial effusion. We report the case of an 85-year-old woman, diagnosed with marginal zone lymphoma, who developed heart failure due to lymphomatous infiltration of the pericardium. We discuss in detail the possibility of intrapericardial treatment of such patients. The patient received rituximab intrapericardially at a dose of 100 mg in addition to systemic rituximab, cyclophosphamide, vincristine and prednisone immunochemotherapy. The treatment proved to be safe and effective. The patient has remained in good health for more than 3 years at the time of writing. Intrapericardial administration of rituximab may be a valuable therapeutic option for patients with lymphoma that involves the pericardium and heart.


Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Cardíacas/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Derrame Pericárdico/tratamento farmacológico , Idoso de 80 Anos ou mais , Ciclofosfamida/administração & dosagem , Feminino , Neoplasias Cardíacas/patologia , Humanos , Linfoma de Zona Marginal Tipo Células B/patologia , Invasividade Neoplásica , Derrame Pericárdico/patologia , Prednisona/administração & dosagem , Indução de Remissão , Rituximab , Vincristina/administração & dosagem
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