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1.
Biol Sport ; 41(3): 97-104, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38952919

RESUMEN

The objective of this paper was to determine the impact of EEG-biofeedback training on the motivation and efficiency of powerlifters during the bench press exercise in relation to the external load and the level of training. The study included 18 trained powerlifters who were divided into the intermediate (IG) and the advanced (AG) groups. EEG-biofeedback training was conducted every three days, lasting 27 minutes each time (5 × 3-minute intervals with recovery periods - lying on a bench - between them 4 × 3 minutes), and ended with a final EEG measurement in the second cycle of research. The repeated measures ANOVA showed intra-group differences due to external loading for the FAI (Frontal Alpha Asymmetry) obtained in the EEG both before and after biofeedback training. In AG group analysis revealed significant differences between 65%1RM and 35%1RM. In the IG group between 35%1RM and 50, 65 and 80%1RM. One of the major variables influencing the efficiency of strength training, including bench press workouts, is the level of training. The more successfully an athlete uses motivation when exercising, the better their training, which translates into greater results and a lower chance of injury.

2.
Transfus Med Hemother ; 48(3): 137-147, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34177417

RESUMEN

BACKGROUND: Convalescent plasma is one of the treatment options for COVID-19 which is currently being investigated in many clinical trials. Understanding of donor and product characteristics is important for optimization of convalescent plasma. METHODS: Patients who had recovered from CO-VID-19 were recruited as donors for COVID-19 convalescent plasma (CCP) for a randomized clinical trial of CCP for treatment of severe COVID-19 (CAPSID Trial). Titers of neutralizing antibodies were measured by a plaque-reduction neutralization test (PRNT). Correlation of antibody titers with host factors and evolution of neutralizing antibody titers over time in repeat donors were analysed. RESULTS: A series of 144 donors (41% females, 59% males; median age 40 years) underwent 319 plasmapheresis procedures providing a median collection volume of 850 mL and a mean number of 2.7 therapeutic units per plasmapheresis. The majority of donors had a mild or moderate course of COVID-19. The titers of neutralizing antibodies varied greatly between CCP donors (from <1:20 to >1:640). Donor factors (gender, age, ABO type, body weight) did not correlate significantly with the titer of neutralizing antibodies. We observed a significant positive correlation of neutralization titers with the number of reported COVID-19 symptoms and with the time from SARS-CoV-2 diagnosis to plasmapheresis. Neutralizing antibody levels were stable or increased over time in 58% of repeat CCP donors. Mean titers of neutralizing antibodies of first donation and last donation of repeat CCP donors did not differ significantly (1:86 at first compared to 1:87 at the last donation). There was a significant correlation of neutralizing antibodies measured by PRNT and anti-SARS-CoV-2 IgG and IgA antibodies which were measured by ELISA. CCP donations with an anti-SARS-CoV-2 IgG antibody content above the 25th percentile were substantially enriched for CCP donations with higher neutralizing antibody levels. CONCLUSION: We demonstrate the feasibility of collection of a large number of CCP products under a harmonized protocol for a randomized clinical trial. Titers of neutralizing antibodies were stable or increased over time in a subgroup of repeat donors. A history of higher number of COVID-19 symptoms and higher levels of anti-SARS-CoV-2 IgG and IgA antibodies in immunoassays can preselect donations with higher neutralizing capacity.

3.
Transfusion ; 58(6): 1516-1526, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29732580

RESUMEN

BACKGROUND: Research with primary human white blood cell (WBC) subpopulations requires high quantity, quality, and functionality of peripheral blood mononuclear cells (PBMCs) as a source to further characterize cellular subpopulations such as T and B lymphocytes, monocytes, or natural killer cells. Apart from buffy coats derived from whole blood, residual blood from preparative hemapheresis kits are used as a source for PBMCs, but knowledge on the yield and functionality of cells from different devices is limited. STUDY DESIGN AND METHODS: We evaluated quantity and quality of PBMCs isolated from apheresis kits of two apheresis devices (AMICUS, Fenwal; and Trima Accel, Terumo BCT), the latter being our standard source for many years. PBMCs derived from Trima or AMICUS were tested for yield and subtype composition by flow cytometry. Functionality was assessed by cytokine induction of CD4+ and CD8+ T cells and by degranulation. Moreover, cytotoxic activity of natural killer cells was quantified by a real-time killing assay. RESULTS: Mean numbers of isolated cells were 5.5 ± 2.4 × 108 for AMICUS, and 10.3 ± 6.4 × 108 for Trima Accel, respectively. The proportion of WBC subtypes corresponded to well-known numbers from whole blood, with minor differences between the two apheresis systems. Likewise, minor differences in cytokine induction were found in stimulated CD4+ or CD8+ T cells. Finally, PBMCs derived from the two systems showed comparable cytotoxic activity. CONCLUSION: PBMC derived from residual blood of the AMICUS and Trima Accel apheresis devices serve as an economic and easily accessible source for functional PBMCs with comparable quantity and quality to PBMCs derived from whole blood.


Asunto(s)
Eliminación de Componentes Sanguíneos/instrumentación , Leucocitos Mononucleares/citología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD8-positivos/efectos de los fármacos , Citocinas/farmacología , Citometría de Flujo , Humanos , Células Asesinas Naturales/fisiología , Recuento de Leucocitos
4.
Thromb Haemost ; 123(9): 867-879, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37037212

RESUMEN

To identify recurrent inflammation in hemophilia, we assessed the acute-phase response in the blood of patients with hemophilia A and B. Compared to age- and weight-matched controls, blood levels of interleukin-6 (IL-6), C-reactive protein (CRP), and LPS-binding protein (LBP) were significantly elevated in the entire cohort of hemophilia patients but exhibited a particularly pronounced increase in obese hemophilia patients with a body mass index (BMI) ≥30. Subgroup analysis of the remaining nonobese hemophilia patients (BMI: 18-29.9) revealed a significant spike of IL-6, CRP, and LBP in connection with a de-novo increase of soluble IL-6 receptor α (sIL-6Rα) in patients with bleeding events within the last month. Hemophilia patients who did not experience recent bleeding had IL-6, CRP, and sIL-6Rα blood levels similar to healthy controls. We did not find increased IL-6 or acute-phase reactants in hemophilia patients with arthropathy or infectious disease. The role of IL-6 as a marker of bleeding in hemophilia was confirmed in hemophilia patients with acute bleeding events as well as in transgenic hemophilia mice after needle puncture of the knee, which exhibited an extensive hematoma and a 150-fold increase of IL-6 blood levels within 7 days of the injury compared to needle-punctured control mice. Notably, IL-6 blood levels shrunk to a fourfold elevation in hemophilia mice over controls after 28 days, when the hematoma was replaced by arthrofibrosis. These findings indicate that acute-phase reactants in combination with sIL-6Rα could be sensitive biomarkers for the detection of acute and recent bleeding events in hemophilia.


Asunto(s)
Hemofilia A , Ratones , Animales , Hemofilia A/diagnóstico , Interleucina-6/metabolismo , Reacción de Fase Aguda , Proteína C-Reactiva/metabolismo , Ratones Transgénicos , Hematoma
5.
J Hum Kinet ; 89: 247-258, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38053968

RESUMEN

The aim of the study was to expand the current knowledge on the effects of EEG biofeedback training on the reaction time of judo athletes, as well as to develop an optimal EEG training protocol in terms of the number of sessions and their duration that would significantly improve the reaction time of athletes. The study included 24 male athletes from the national team of the Polish Judo Association. The selected group was randomly divided into two subgroups: experimental and control. The study was conducted in four cycles varying in terms of frequency and duration of neurofeedback (NFB) sessions, both in the control and experimental groups. In the experimental group, each training cycle consisted of 15 sessions, followed by a four-week break. The effects of NFB training on the visual reaction time of judo athletes were evaluated using computerized simple and complex reaction time tests along with selected trials of the Vienna Test System (VTS). Following NFB training according to the theta/beta1 protocol, while maintaining appropriate duration and frequency of individual training sessions, statistically significant improvements in reaction times to visual stimuli of athletes, both in simple and complex tasks, were observed in the experimental group. No such changes were found in the control group. The greatest improvement in reaction times was observed in complex tasks, indicating the high effectiveness of EEG biofeedback training in enhancing this ability.

6.
Lancet Haematol ; 10(11): e913-e921, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37858328

RESUMEN

BACKGROUND: Acquired haemophilia A is caused by neutralising autoantibodies against coagulation factor VIII, leading to severe bleeding. Standard treatment involves immunosuppressive therapy, which is associated with adverse events and mortality in the frail population of patients with acquired haemophilia A. This study investigated whether emicizumab, a factor VIIIa mimetic antibody, protects patients with acquired haemophilia A from bleeding and allows deferral of immunosuppression during the first 12 weeks after diagnosis. METHODS: We report final results of an open-label, single-arm, phase 2 clinical trial. Adult patients with acquired haemophilia A from 16 haemophilia treatment centres in Germany and Austria were eligible if they had not previously received immunosuppression. Patients received emicizumab subcutaneously (6 and 3 mg/kg on days 1 and 2, 1·5 mg/kg weekly until week 12), but no immunosuppression. Follow-up was until week 24. The primary endpoint was the number of clinically relevant bleeds per patient-week until week 12. Emicizumab was considered effective if the mean bleeding rate was significantly below 0·15 bleeds per patient-week, the rate observed in a previous study of patients with acquired haemophilia A treated with bypassing agents and immunosuppression but no emicizumab. The study is registered with clinicaltrials.gov, NCT04188639 and is complete. FINDINGS: Of 49 patients screened from March 25, 2021, to June 10, 2022, 47 were enrolled (23 women, 24 men). Median age was 76 years (IQR 66-80), 46 (98%) of 47 patients were White, median factor VIII activity was 1·4 IU/dL (0·3-5·6), and median inhibitor concentration was 11·4 Bethesda units per mL (3·9-42·7). Mean breakthrough bleeding rate was 0·04 bleeds per patient-week (upper 97·5% CI 0·06). 33 (70%) of 47 patients had no bleeding events, seven patients (15%) had one bleed, six patients (13%) had two bleeds, and one patient (2%) had three bleeds. Adverse events of grade 3 or worse included COVID-19 (n=2), acute kidney injury (n=2), and stroke (n=1). Four of 47 patients died, including two deaths related to bleeding, one from COVID-19, and one from cardiac arrest (none were judged as related to emicizumab). INTERPRETATION: This study suggests that emicizumab prophylaxis prevents bleeding in patients with acquired haemophilia A and that immunosuppressive therapy can be deferred while patients are receiving this treatment. The low number of thromboembolic events, severe infections, and fatalities observed in this study are promising. FUNDING: This study was supported by funding from Hoffman-La Roche.


Asunto(s)
COVID-19 , Hemofilia A , Masculino , Adulto , Humanos , Femenino , Anciano , Hemofilia A/tratamiento farmacológico , Factor VIII/uso terapéutico , Hemorragia/etiología , Hemorragia/prevención & control , Hemorragia/tratamiento farmacológico
7.
Angiogenesis ; 15(1): 115-29, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22203240

RESUMEN

Angiogenesis is important for tumor growth and metastasis. CLT1 (CGLIIQKNEC), a peptide that binds to tumor interstitial spaces in the presence of fibrin-fibronectin, has structural similarity to the anti-angiogenic ß-sheet peptides anastellin and anginex. This similarity is reflected in the ability of CLT1 to form co-aggregates with fibronectin that induce an unfolded protein response and cause autophagic cell death in proliferating endothelial cells. CLT1 cytotoxicity is mediated at least in parts by a novel CLT1 binding protein, Chloride Intracellular Channel 1 (CLIC1), which promotes internalization of CLT1-fibronectin co-aggregates in a mechanism that depends on the LIIQK amino acid sequence of CLT1. LIIQK encompasses amino acid residues relevant for CLT1 binding to CLIC1 and in addition, facilitates the formation of CLT1-fibronectin co-aggregates, which in turn promote translocation of CLIC1 to the endothelial cell surface through ligation of integrin αvß3. Paralleling the in vitro results, we found that CLT1 co-localizes with CLIC1 and fibronectin in angiogenic blood vessels in vivo, and that CLT1 treatment inhibited angiogenesis and tumor growth. Our findings show that CLT1 is a new anti-angiogenic compound, and its mechanism of action is to form co-aggregates with fibronectin, which bind to angiogenic endothelial cells through integrins, become internalized through CLIC1 and elicit a cytotoxic unfolded protein response. The simple structure and high potency of CLT1 make it a potentially useful compound for anti-angiogenic treatments.


Asunto(s)
Canales de Cloruro/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Fibronectinas/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Péptidos Cíclicos/farmacología , Secuencia de Aminoácidos , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Endocitosis/efectos de los fármacos , Fibronectinas/química , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Masculino , Ratones , Ratones Desnudos , Datos de Secuencia Molecular , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Péptidos Cíclicos/química , Péptidos Cíclicos/uso terapéutico , Estructura Cuaternaria de Proteína
8.
J Clin Invest ; 132(24)2022 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-36326824

RESUMEN

BACKGROUNDResults of many randomized trials on COVID-19 convalescent plasma (CCP) have been reported, but information on long-term outcome after CCP treatment is limited. The objectives of this extended observation of the randomized CAPSID trial are to assess long-term outcome and disease burden in patients initially treated with or without CCP.METHODSOf 105 randomized patients, 50 participated in the extended observation. Quality of life (QoL) was assessed by questionnaires and a structured interview. CCP donors (n = 113) with asymptomatic to moderate COVID-19 were included as a reference group.RESULTSThe median follow-up of patients was 396 days, and the estimated 1-year survival was 78.7% in the CCP group and 60.2% in the control (P = 0.08). The subgroup treated with a higher cumulative amount of neutralizing antibodies showed a better 1-year survival compared with the control group (91.5% versus 60.2%, P = 0.01). Medical events and QoL assessments showed a consistent trend for better results in the CCP group without reaching statistical significance. There was no difference in the increase in neutralizing antibodies after vaccination between the CCP and control groups.CONCLUSIONThe trial demonstrated a trend toward better outcome in the CCP group without reaching statistical significance. A predefined subgroup analysis showed a significantly better outcome (long-term survival, time to discharge from ICU, and time to hospital discharge) among those who received a higher amount of neutralizing antibodies compared with the control group. A substantial long-term disease burden remains after severe COVID-19.Trial registrationEudraCT 2020-001310-38 and ClinicalTrials.gov NCT04433910.FundingBundesministerium für Gesundheit (German Federal Ministry of Health).


Asunto(s)
COVID-19 , Humanos , COVID-19/terapia , COVID-19/etiología , SARS-CoV-2 , Calidad de Vida , Cápside , Estudios de Seguimiento , Inmunización Pasiva/efectos adversos , Anticuerpos Neutralizantes , Anticuerpos Antivirales
9.
J Hum Kinet ; 73: 297-304, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32774560

RESUMEN

Recently, it has been reported that tear osmolarity (Tosm) is correlated with plasma osmolarity and will increase during exertion. We aimed to assess whether inhaling oxygen-enriched air between exercises could significantly change the Tosm value. Thirty men aged 24.9 years were included in the study. A cycloergometer was used to perform the exercise protocol. We recorded the participants' Tosm (mOsm/L), heart rate (HR, beats/minute), oxygen saturation, and blood pressure values. After the first exhaustive exercise (T1), participants inhaled oxygen in the experimental group and a placebo in the control group. After the second exercise (T2), another set of measurements was obtained. The Tosm value before exercise was 297.4 ± 1.21 and 296.53 ± 1.11 mOsm/L (p = 0.61718) and the HR was 72.6 ± 2.59 and 73 ± 2.59 beats/minute (p = 0.39949) in the study and the control group, respectively. At T1, Tosm was 303.67 ± 1.25 and 302.2 ± 1.25 mOsm/L (p = 0.41286) and the HR reached 178.04 ± 2.60 and 176.4 ± 2.60 beats/minute (p = 0.65832), respectively. At T2, Tosm in the study group reached 305.73 ± 0.86 mOsm/L (correlation with the use of oxygen: r = -0.3818), and in the control group, it was 308.4 ± 0.86 mOsm/L (p = 0.0373), while the HR reached 172.20 ± 2.53 beats/minute in the study group and 178.2 ± 2.53 beats/minute in the control group (p = 0.057). It was concluded that inhaling oxygen before and after exercise could increase the rate of recovery after exhaustive exercise.

10.
Int J Occup Med Environ Health ; 33(3): 273-282, 2020 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-32235946

RESUMEN

OBJECTIVES: Vestibular rehabilitation leads to a gradual diminution of the subjective and objective symptoms that accompany the vestibular disorders. The aim of the study was to compare the impact of 2 different types of vestibular rehabilitation on vestibular compensation in patients with chronic unilateral vestibular dysfunction. MATERIAL AND METHODS: The study was conducted on a group of 58 subjects (43 females and 15 males) aged 40-64 years, who presented with chronic unilateral vestibular dysfunction and were hospitalized. The patients were randomly assigned to either of the 2 groups established. The study was conducted in a 6-week period. Group 1 consisted of patients who underwent customized group vestibular rehabilitation in an outpatient setting. The program was performed once a week for 1 h 30 min, under the supervision of a physiotherapist and a physiatrist. Group 2 was instructed to perform Cawthorne-Cooksey exercises and simple balance exercises twice a day for 15 min. RESULTS: An improvement in the outcomes of the Dynamic Gait Index as well as the Berg Balance Scale was statistically significant for group 1. The time for fulfilling the task in the Timed Up and Go Test improved in both groups (p < 0.05). The subjective estimation of the symptoms evaluated with the use of the Dizziness Handicap Inventory and the Visual Analogue Scale revealed a statistically significant improvement in both groups, yet it was higher in group 1. CONCLUSIONS: The compensation achieved after 6 weeks of the customized, supervised outpatient rehabilitation program in group 1 was superior to the results of the home-based unsupervised Cawthorne-Cooksey and balance exercises. Int J Occup Med Environ Health. 2020;33(3):273-82.


Asunto(s)
Terapia por Ejercicio/métodos , Equilibrio Postural/fisiología , Enfermedades Vestibulares/rehabilitación , Adulto , Mareo/rehabilitación , Femenino , Marcha , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
11.
J Cell Biol ; 163(4): 871-8, 2003 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-14638862

RESUMEN

A tumor-homing peptide, F3, selectively binds to endothelial cells in tumor blood vessels and to tumor cells. Here, we show that the cell surface molecule recognized by F3 is nucleolin. Nucleolin specifically bound to an F3 peptide affinity matrix from extracts of cultured breast carcinoma cells. Antibodies and cell surface biotin labeling revealed nucleolin at the surface of actively growing cells, and these cells bound and internalized fluorescein-conjugated F3 peptide, transporting it into the nucleus. In contrast, nucleolin was exclusively nuclear in serum-starved cells, and F3 did not bind to these cells. The binding and subsequent internalization of F3 were blocked by an antinucleolin antibody. Like the F3 peptide, intravenously injected antinucleolin antibodies selectively accumulated in tumor vessels and in angiogenic vessels of implanted "matrigel" plugs. These results show that cell surface nucleolin is a specific marker of angiogenic endothelial cells within the vasculature. It may be a useful target molecule for diagnostic tests and drug delivery applications.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/metabolismo , Membrana Celular/metabolismo , Endotelio Vascular/metabolismo , Neovascularización Patológica/metabolismo , Fosfoproteínas/metabolismo , Proteínas de Unión al ARN/metabolismo , Transporte Activo de Núcleo Celular/efectos de los fármacos , Transporte Activo de Núcleo Celular/fisiología , Anticuerpos/farmacología , Anticuerpos/uso terapéutico , Antígenos de Superficie/metabolismo , Biomarcadores de Tumor/antagonistas & inhibidores , Vasos Sanguíneos/citología , Vasos Sanguíneos/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Medio de Cultivo Libre de Suero/farmacología , Endocitosis/efectos de los fármacos , Endocitosis/fisiología , Endotelio Vascular/citología , Epítopos/metabolismo , Heparitina Sulfato/metabolismo , Humanos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/fisiopatología , Fosfoproteínas/antagonistas & inhibidores , Proteínas de Unión al ARN/antagonistas & inhibidores , Nucleolina
12.
J Hum Kinet ; 67: 143-151, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31523313

RESUMEN

Physical exertion leads to the rise in tear osmolarity. However, previous studies have been conducted mostly on males and did not consider sex differences and the possible alteration in blinking during physical exercise. Sixteen women and 18 men aged 25.09 ± 1.70 were divided into equal groups with eyes open and shut. Participants performed 8-min medium-intensity exercise and 5-min intense exercise on a cycloergometer. Tear osmolarity (in mOsm/L) was evaluated before ( T0), after medium-intensity (T1) and intense exercise (T2). The blinking rate was assessed in a group with eyes open. Tear brake up time was measured in T0 and T1. With tear osmolarity measuring 305.72 ± 1.22 and 313.56 ± 1.90 for men and women, respectively, we observed significant differences in T1. In T2, tear osmolarity in men was 303.3 ± 1.28 vs. 310.87 ± 1.36 in women. The blinking rate decreased from 14.24 ± 2.54/min in T0 to 9.41 ± 2.83/min in T1. There was a statistically significant change in tear osmolarity in both groups, that is, in the group with eyes shut from 300.53 ± 1.37 in T0 to 308.06 ± 1.55 in T1 to 304.88 ± 1.54 in T2. In the group with eyes open, tear osmolarity increased from 300.29 ± 1.37 in T0 to 310.76 ± 1.55 in T1 and then dropped to 308.88 ± 1.54 in T2. Tear brake up time measured in T0 was 14.7 ± 1.43 vs. 13.53 ±1.48 in the open eyes condition. Due to physical exercise, short-term changes in tear osmolarity are partially caused by altered blinking. Sex differences in tear osmolarity in response to exertion may confirm the relationship between total body water and tear osmolarity.

13.
Thromb Haemost ; 119(2): 234-245, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30650445

RESUMEN

Macrophages make important contributions to inflammation and wound healing. We show here that macrophage polarization is deregulated in haemophilia in response to macrophage colony-stimulating factor (M-CSF) and partially in response to granulocyte-macrophage colony-stimulating factor (GM-CSF). As a result, haemophilia macrophages exhibit a specific impairment of M-CSF-mediated functions involved in wound healing such as clot invasion and phagocytosis. Haemophilia monocytes express reduced amounts of the receptors for M-CSF and GM-CSF, which correlates with a failure to express tumour necrosis factor α (TNFα) and CD163 in M-CSF-treated haemophilia macrophages and reduced expression of TNFα and CD206 after treatment with GM-CSF. Protein expression in response to M-CSF was regained with respect to CD163 and CD206 after embedding haemophilia monocytes in clotted plasma suggesting that a functioning coagulation system has positive effects on macrophage M2 polarization. Mimicking the functional deficits of haemophilia macrophages in normal macrophages was possible by adding leptin, which we found to be elevated in the blood of haemophilia patients, to a monocyte cell line. The increase of leptin occurred in conjunction with C-reactive protein in a body mass index-controlled cohort suggesting that haemophilia patients harbour chronic low-grade inflammation. Together, our data indicate that impaired clotting in haemophilia patients leads to increased inflammation and a deregulation in macrophage differentiation, which may explain the commonly observed deficits in wound healing and tissue regeneration.


Asunto(s)
Coagulación Sanguínea , Hemofilia A/sangre , Macrófagos/citología , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Circulación Sanguínea , Diferenciación Celular , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Eritrocitos/citología , Fibrina/metabolismo , Citometría de Flujo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Hemofilia A/tratamiento farmacológico , Humanos , Lectinas Tipo C/metabolismo , Leucocitos Mononucleares/citología , Factor Estimulante de Colonias de Macrófagos/uso terapéutico , Masculino , Receptor de Manosa , Lectinas de Unión a Manosa/metabolismo , Microscopía Fluorescente , Monocitos/citología , Fagocitosis , Receptores de Superficie Celular/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Adulto Joven
15.
Biomed Res Int ; 2018: 2610637, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30417010

RESUMEN

The aim of this study was to evaluate a novel composite material for tracheal reconstruction in an ovine model. A polymer containing various forms of carbon fibers (roving, woven, and nonwoven fabric) impregnated with polysulfone (PSU) was used to create cylindrical tracheal implants, 3 cm in length and 2.5 cm in diameter. Each implant, reinforced with five rings made of PSU-impregnated carbon-fiber roving, had three external layers made of carbon-fiber woven fabric and the inner layer formed of carbon-fiber nonwoven fabric. The inner surface of five implants was additionally coated with polyurethane (PU), to promote migration of respiratory epithelium. The implants were used to repair tracheal defects (involving four tracheal rings) in 10 sheep (9-12 months of age; 40-50 kg body weight). Macroscopic and microscopic characteristics of the implants and tracheal anastomoses were examined 4 and 24 weeks after implantation. At the end of the follow-up period, outer surfaces of the implants were covered with the tissue which to various degree resembled histological structure of normal tracheal wall. In turn, inner surfaces of the prostheses were covered only with vascularized connective tissue. Inner polyurethane coating did not improve the outcomes of tracheal reconstruction and promoted excessive granulation, which contributed to moderate to severe stenosis at the tracheal anastomoses. The hereby presented preliminary findings constitute a valuable source of data for future research on a tracheal implant being optimally adjusted for medical needs.


Asunto(s)
Materiales Biocompatibles/química , Ovinos/cirugía , Tráquea/cirugía , Animales , Biomimética/métodos , Poliuretanos/química , Prótesis e Implantes , Procedimientos de Cirugía Plástica/métodos , Mucosa Respiratoria/cirugía
16.
J Mol Biol ; 356(4): 876-85, 2006 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-16403516

RESUMEN

Anginex is a synthetic beta-sheet peptide with anti-angiogenic and anti-tumor activity. When added to cultured endothelial cells at concentrations ranging from 2.5 microM to 25 microM, anginex induced cell death, which was reflected by a strong increase of subdiploid cells and fragments, loss of cellular ATP, and LDH release. Cytotoxicity remained the same whether cells were treated with anginex at 4 degrees C or at 37 degrees C. At low temperatures, fluorescein-conjugated anginex accumulated on the endothelial surface, but did not reach into the cytoplasm, indicating that the cell membrane is the primary target for the peptide. Within minutes of treatment, anginex caused endothelial cells to take up propidium iodide and undergo depolarization, both parameters characteristic for permeabilization of the cell membrane. This process was amplified when cells were activated with hydrogen peroxide. Red blood cell membranes were essentially unaffected by anginex. Anginex bound lipid bilayers with high affinity and with a clear preference for anionic over zwitterionic phospholipids. Structural studies by circular dichroism and solid-state nuclear magnetic resonance showed that anginex forms a beta-sheet and adopts a unique and highly ordered conformation upon binding to lipid membranes. This is consistent with lipid micellization or the formation of pore-forming beta-barrels. The data suggest that the cytotoxicity of anginex stems from its ability to target and disrupt the endothelial cell membrane, providing a possible explanation for the angiostatic activity of the peptide.


Asunto(s)
Membrana Celular/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Proteínas/metabolismo , Proteínas/farmacología , Muerte Celular , Membrana Celular/metabolismo , Permeabilidad de la Membrana Celular/efectos de los fármacos , Células Cultivadas , Células Endoteliales/citología , Células Endoteliales/metabolismo , Endotelio Vascular/citología , Humanos , Membrana Dobles de Lípidos/química , Liposomas , Péptidos , Conformación Proteica , Proteínas/química
17.
Endocrinology ; 158(12): 4189-4205, 2017 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-29029019

RESUMEN

Mutations in the p53 tumor suppressor are frequent in patients with castration-resistant prostate cancer but less so in patients with localized disease, and patients who have Li-Fraumeni with germline p53 mutations do not have an increased incidence of prostate cancer, suggesting that additional molecular and/or genetic changes are required for p53 to promote prostate carcinogenesis. ELL-associated factor 2 (EAF2) is a tumor suppressor that is frequently downregulated in advanced prostate cancer. Previous studies have suggested that p53 binds to EAF2, providing a potential mechanism for their functional interactions. In this study, we tested whether p53 and EAF2 could functionally interact in prostate cancer cells and whether concurrent inactivation of p53 and EAF2 could promote prostate carcinogenesis in a murine knockout model. Endogenous p53 coprecipitated with EAF2 in prostate cancer cells, and deletion mutagenesis indicated that this interaction was mediated through the C terminus of EAF2 and the DNA binding domain of p53. Concurrent knockdown of p53 and EAF2 induced an increase in proliferation and migration in cultured prostate cancer cells, and conventional p53 and EAF2 knockout mice developed prostate cancer. In human prostate cancer specimens, concurrent p53 nuclear staining and EAF2 downregulation was associated with high Gleason score. These findings suggest that EAF2 and p53 functionally interact in prostate tumor suppression and that simultaneous inactivation of EAF2 and p53 can drive prostate carcinogenesis.


Asunto(s)
Transformación Celular Neoplásica/genética , Proteínas Nucleares/genética , Próstata/metabolismo , Neoplasias de la Próstata/genética , Transactivadores/genética , Proteína p53 Supresora de Tumor/genética , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Transformación Celular Neoplásica/metabolismo , Células HEK293 , Humanos , Inmunohistoquímica , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Clasificación del Tumor , Proteínas Nucleares/metabolismo , Próstata/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Unión Proteica , Interferencia de ARN , Transactivadores/metabolismo , Proteína p53 Supresora de Tumor/metabolismo
18.
Otolaryngol Pol ; 60(3): 325-30, 2006.
Artículo en Polaco | MEDLINE | ID: mdl-16989443

RESUMEN

INTRODUCTION: The early detection and right monitoring of the laryngeal cancer make a better chance of recovery. Therefore factors that might be showing the presence of neoplastic process are constantly being looked for. The detection of correlation between incidence of cancer and immunity system disorders makes us look for and try to answer an important question: are there any factors that might be cancer markers in immunity system? Cytokines are molecules that regulate the process of differentiation and proliferation. They are also the mediators of immunological and inflammatory reactions. Interleukina-10 (IL-10) is a cytokine that has various important functions stimulating immunity processes. IL-10 is a factor stimulating killer cells/cytoxic lymphocytes/ and is able to kill cancer cells growth spontaneously. It has been detected that some cancer cells can produce some IL-10, too. The aim of the study was to evaluate the serum level concentration of IL-10 in the laryngeal cancer patients before any medical treatment and its denotation after surgery or radiotherapy. MATERIAL AND METHODS: A group of 43 male patients with laryngeal cancer was considered for the purpose of this study. 22 patients were treated by surgery and 21 by radiotherapy. In all the cases the serum concentration of IL-10 before the treatment, in the first and 30th days after therapy was evaluated. The results were compared with the group of 20 healthy volunteers. RESULTS: The mean value of IL-10 concentration in laryngeal cancer patients treated by surgery was 14.0 pg/ml before treatment, 12.8 pg/ml in the 1 day and 14.4 pg/ml 30 days after the therapy. IL-10 concentrations in patients treated by radiotherapy were respectively: 15.4, 14.4 and 15.9 pg/ml. The mean value of IL-10 in the control group was 4.9 pg/ml. The serum concentrations of IL-10 in the laryngeal cancer patients were significantly higher than in the control group. These IL-10 concentrations didn't change significantly after the surgery or radiotherapy. CONCLUSION: The serum concentration of IL-10 in the laryngeal cancer patients is significantly higher than in the healthy control group. The changes of serum concentrations after the surgery or radiotherapy of laryngeal cancer patients are not significant and characteristic.


Asunto(s)
Biomarcadores de Tumor/sangre , Interleucina-10/sangre , Neoplasias Laríngeas/inmunología , Neoplasias Laríngeas/terapia , Adulto , Humanos , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Resultado del Tratamiento
19.
Otolaryngol Pol ; 60(3): 331-6, 2006.
Artículo en Polaco | MEDLINE | ID: mdl-16989444

RESUMEN

INTRODUCTION: Cytokines are molecules that regulate the process of differentiation and proliferation. They are also the mediators of immunological and inflammatory reactions. One of the cytokines that participates in immunological processes is interleukine-2 (IL-2), whose participation in neoplastic processes has been proved in many researches. It's anticancer effect is an indirect one and is connected with stimulating processes of immunologically competent cells, which are cytotoxic for cancer cells. IL-2 is produced by T-helper lymphocytes (THL), and on the basis of feedback it stimulates those lymphocytes to new cells and other cytokines, which stimulate next immunity cells or kill the cancer cells, production. The aim of the study was to evaluate the serum level concentration of IL-2 in the laryngeal cancer patients before any medical treatment and its denotation after the surgical procedure. MATERIAL AND METHODS: A group of 22 male patients with laryngeal cancer was considered for the purpose of this study. All of them were treated by surgery. In all the cases the serum concentration of IL-2 before the treatment, in the first and 30th day after therapy was evaluated. The results were compared with the group of 20 healthy volunteers. RESULTS: The mean value of IL-2 concentration in laryngeal cancer patients treated by surgery was 23.4 pg/ml before treatment, increased to 37.8 pg/ml in the 1 day and to 54.3 pg/ml 30 days after the therapy. The serum concentrations of IL-2 in the laryngeal cancer patients were lower than in the control group before the surgical treatment. These IL-2 concentrations increased significantly after the surgery and 1 month after the treatment were higher than in the healthy population. CONCLUSION: The serum concentration of IL-2 in the laryngeal cancer patients treated by surgery is lower than in the healthy control group. IL-2 increased significantly after the surgery to higher levels than in the control healthy group.


Asunto(s)
Biomarcadores de Tumor/sangre , Interleucina-2/sangre , Neoplasias Laríngeas/inmunología , Neoplasias Laríngeas/cirugía , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Resultado del Tratamiento
20.
J Hum Kinet ; 54: 43-53, 2016 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-28031756

RESUMEN

The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphic variant is a candidate to explain the individual differences in trainability and response to exercise training. Therefore, the aim of the study was to verify whether the A1298C polymorphism influenced the aerobic and anaerobic performance as well as body and mass composition in young Polish women following low-high impact aerobic exercise training. Two hundred and one women aged 21 ± 1 years (range 19-24) were included in the study. All of them completed a 12-week exercise training program and were measured for selected somatic features, aerobic capacity and cardiorespiratory fitness indices as well as peak anaerobic power and anaerobic capacity, before and after the intervention. A mixed 2 x 2 ANOVA for 20 dependent variables grouped in three categories was conducted. No significant interaction of the genotype with training for body mass and body composition variables was observed. Although, there were three significant genotype x training interactions for maximal oxygen uptake variables, regardless of body mass i.e.: for VO2max (p < 0.05), HRmax (p < 0.0001) and HRAT/HRmax (p < 0.0001). Significantly greater improvement in VO2max was gained by the CC+AC group compared to the AA genotype group. The present results support the hypothesis that individual differences in trainability are at least in part determined by the genetic component and MTHFR A1298C seems to be one of the many polymorphisms involved.

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