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Cell-based therapeutic strategies have been proposed as an alternative for brain and blood vessels repair after stroke, but their clinical application is hampered by potential adverse effects. We therefore tested the hypothesis that secretome of these cells might be used instead to still focus on cell-based therapeutic strategies. We therefore characterized the composition and the effect of the secretome of brain microvascular endothelial cells (BMECs) on primary in vitro human models of angiogenesis and vascular barrier. Two different secretome batches produced in high scale (scHSP) were analysed by mass spectrometry. Human primary CD34+-derived endothelial cells (CD34+-ECs) were used as well as in vitro models of EC monolayer (CMECs) and blood-brain barrier (BBB). Cells were also exposed to oxygen-glucose deprivation (OGD) conditions and treated with scHSP during reoxygenation. Protein yield and composition of scHSP batches showed good reproducibility. scHSP increased CD34+-EC proliferation, tubulogenesis, and migration. Proteomic analysis of scHSP revealed the presence of growth factors and proteins modulating cell metabolism and inflammatory pathways. scHSP improved the integrity of CMECs, and upregulated the expression of junctional proteins. Such effects were mediated through the activation of the interferon pathway and downregulation of Wnt signalling. Furthermore, OGD altered the permeability of both CMECs and BBB, while scHSP prevented the OGD-induced vascular leakage in both models. These effects were mediated through upregulation of junctional proteins and regulation of MAPK/VEGFR2. Finally, our results highlight the possibility of using secretome from BMECs as a therapeutic alternative to promote brain angiogenesis and to protect from ischemia-induced vascular leakage.
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Barrera Hematoencefálica , Células Endoteliales , Proteómica , Humanos , Células Endoteliales/metabolismo , Barrera Hematoencefálica/metabolismo , Proteómica/métodos , Secretoma/metabolismo , Permeabilidad Capilar , Encéfalo/metabolismo , Encéfalo/irrigación sanguínea , Encéfalo/patología , Hipoxia de la Célula , Proteoma/metabolismo , Células Cultivadas , Microvasos/metabolismo , Microvasos/citologíaRESUMEN
INTRODUCTION: Sphingolipids regulate proinsulin folding, insulin secretion and control beta cells apoptosis. Recent evidence has demonstrated that, among other factors, reduced amounts of sulfatide may be relevant in the development of type 1 diabetes (T1D). Thus, fenofibrate, which activates sulfatide biosynthesis, may prolong remission in subjects with T1D. The aim of the study is to evaluate clinical efficacy of fenofibrate on the maintenance of residual beta-cell function in children with newly diagnosed T1D. METHODS AND ANALYSIS: A total of 102 children aged 10-17 years with newly diagnosed T1D will be enrolled in a double-blind, two-centre randomised, non-commercial, placebo-controlled trial. Subjects who will meet all inclusion criteria will be randomly assigned to receive fenofibrate at a dose of 160 mg or an identically appearing placebo, orally, once daily, for 12 months. The primary endpoint will be the area under the curve of the C-peptide level during 2-hour responses to a mixed-meal tolerance test (MMTT). Secondary endpoints include fasting and maximum C-peptide concentration in the MMTT, parameters of diabetes control and glucose fluctuations, daily insulin requirement, inflammation markers, genetic analysis, safety and tolerance of the fenofibrate ETHICS AND DISSEMINATION: The study protocol was approved by the Bioethics Committee. The results of this study will be submitted to a peer-reviewed diabetic journal. Abstracts will be submitted to international and national conferences. TRIAL REGISTRATION NUMBER: EnduraCT 2020-003916-28.
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Diabetes Mellitus Tipo 1 , Fenofibrato , Niño , Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Fenofibrato/uso terapéutico , Péptido C , Sulfoglicoesfingolípidos/uso terapéutico , Insulina/uso terapéutico , Método Doble Ciego , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background: Primary central nervous system lymphoma (PCNSL) is a rare, aggressive form of non-Hodgkin lymphoma contained in the brain and the spinal cord as well as the meninges, cranial nerves, eyes, and cerebrospinal fluid (CSF). Due to its variable presentation and lack of associated B-symptoms, it is quite challenging to diagnose PCNSL, if there is not a high level of suspicion. Methods: This is a retrospective case series examining 13 human immunodeficiency virus- (HIV-) negative patients with PCNSL and DLBCL type, with a median age of 75 years old. Results: The most common presenting symptom was altered mental status. The frontal lobes, basal ganglia, cerebellum, and corpus callosum were most affected. Prior to brain biopsy, 4/13 patients were on steroids, which did not affect biopsy results and the average time to diagnosis was 1 month. 9/13 patients who did not receive steroids had an average time to diagnosis of less than 1 month. Conclusion: Although steroid administration did not appear to diminish the yield of the biopsy, it is a best practice to withhold steroids prior to biopsy to decrease the time to diagnose PCNSL.
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Purpose: Pseudotumor is a rare complication after arthroplasty, most often of the hip joint, in response to metal particles present in the implant. There are merely sporadic reports of pseudotumor in patients with bone sarcoma after sparing surgery with endoprosthesis implant. The aim of this study is to present the characteristic imaging features of pseudotumor. Case report: We present a case of a 21-year-old male patient in whom a scheduled follow-up ultrasound revealed a painless lesion suspected of local recurrence at the border of the endoprosthesis and the bone stump 3.5 years after the end of treatment for osteosarcoma of the femur. Histopathology of the biopsy specimen revealed that the lesion was a pseudotumor. Conclusions: Although pseudotumor is sporadic in patients treated with endoprosthesis for bone sarcoma, their prolonged survival could bear the risk of such a complication. Imaging studies, in particular ultrasound, may be helpful in differentiating from local recurrence of sarcoma, however, the histopathology of the specimen obtained by open biopsy at a reference center is crucial for the final diagnosis.
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BACKGROUND: Cell-based therapeutic strategies have been proposed as an alternative for brain repair after stroke, but their clinical application has been hampered by potential adverse effects in the long term. The present study was designed to test the effect of the secretome of endothelial progenitor cells (EPCs) from stroke patients (scCM) on in vitro human models of angiogenesis and vascular barrier. METHODS: Two different scCM batches were analysed by mass spectrometry and a proteome profiler. Human primary CD34+-derived endothelial cells (CD34+-ECs) were used for designing angiogenesis studies (proliferation, migration, and tubulogenesis) or in vitro models of EC monolayer (confluent monolayer ECs-CMECs) and blood-brain barrier (BBB; brain-like ECs-BLECs). Cells were treated with scCM (5 µg/mL) or protein-free endothelial basal medium (scEBM-control). CMECs or BLECs were exposed (6 h) to oxygen-glucose deprivation (OGD) conditions (1% oxygen and glucose-free medium) or normoxia (control-5% oxygen, 1 g/L of glucose) and treated with scCM or scEBM during reoxygenation (24 h). RESULTS: The analysis of different scCM batches showed a good reproducibility in terms of protein yield and composition. scCM increased CD34+-EC proliferation, tubulogenesis, and migration compared to the control (scEBM). The proteomic analysis of scCM revealed the presence of growth factors and molecules modulating cell metabolism and inflammatory pathways. Further, scCM decreased the permeability of CMECs and upregulated the expression of the junctional proteins such as occludin, VE-cadherin, and ZO-1. Such effects were possibly mediated through the activation of the interferon pathway and a moderate downregulation of Wnt signalling. Furthermore, OGD increased the permeability of both CMECs and BLECs, while scCM prevented the OGD-induced vascular leakage in both models. These effects were possibly mediated through the upregulation of junctional proteins and the regulation of MAPK/VEGFR2 activity. CONCLUSION: Our results suggest that scCM promotes angiogenesis and the maturation of newly formed vessels while restoring the BBB function in ischemic conditions. In conclusion, our results highlight the possibility of using EPC-secretome as a therapeutic alternative to promote brain angiogenesis and protect from ischemia-induced vascular leakage.
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Células Progenitoras Endoteliales , Accidente Cerebrovascular , Barrera Hematoencefálica , Humanos , Hipoxia , Proteómica , Reproducibilidad de los ResultadosRESUMEN
INTRODUCTION: On March 11, 2020 the WHO announced a coronavirus disease 2019 (COVID-19) pandemic. Lockdown restrictions, compromised access to medical care and fear of potential exposure to SARS-CoV-2 have forced patients with non-COVID-19 illnesses such as type 1 diabetes (T1D) to stay home. Thisâ¯situation can lead to delay in T1D diagnosis and insulin treatmentâ¯resultingâ¯in rapid progression to diabetic ketoacidosis (DKA) and therefore increased risk of complications and death.â¯â¯. AIM: The aim of this study was to evaluate the frequency and severity of DKA at the onset of T1D in children diagnosed in our department during COVID-19 pandemic lockdown from March 2020 till May 2020 in comparison to corresponding period of the previous year.â¯. MATERIAL AND METHODS: We collected data ofâ¯children with newly diagnosed T1D. DKA was defined according to ISPAD guidelines.â¯. RESULTS: The study cohort comprised 34 childrenâ¯in groupâ¯2020â¯and 52 in groupâ¯2019 with an average age 9.90 ±4.9 vs. 9.59±4.7 years with mean HbA1c 12.9 ±2.4â¯vs.â¯11.5 ±2.2%,â¯respectively. The incidence of DKA was higher by 12% inâ¯groupâ¯2020 vs.â¯2019 (52.94% vs 40.38%; p = 0.276).⯠Regarding the DKA severity (2020 vs. 2019)â¯32.35% vs. 11.54% wereâ¯severe (p = 0.026), 17.65 vs. 13% were moderate (p = 0.759), and 2.94 vs. 15.38%â¯wereâ¯mild (p = 0.081).â¯None of the analyzed patients were COVID-19 positive. CONCLUSIONS: During the COVID-19 pandemic lockdown changes in society and health care system, the DKA rate has increased by 12 percentage points with more severe cases noted in children with newly diagnosedâ¯T1D. Regular education of the whole society about the symptoms of diabetes could contribute to faster diagnosis of T1D and reduction of DKA prevalence.â¯.
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COVID-19/psicología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Cetoacidosis Diabética/diagnóstico , Cetoacidosis Diabética/etiología , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Cuarentena/estadística & datos numéricos , Adolescente , COVID-19/epidemiología , Niño , Preescolar , Estudios de Cohortes , Diabetes Mellitus Tipo 1/epidemiología , Cetoacidosis Diabética/epidemiología , Femenino , Humanos , Incidencia , Masculino , Pandemias/estadística & datos numéricos , Polonia/epidemiología , Prevalencia , Cuarentena/tendencias , Factores de Riesgo , SARS-CoV-2RESUMEN
The heterodimer of the ecdysone receptor (EcR) and ultraspiracle (Usp), members of the nuclear receptors superfamily, is considered as the functional receptor for ecdysteroids initiating molting and metamorphosis in insects. Here we report the 1.95 A structure of the complex formed by the DNA-binding domains (DBDs) the EcR and the Usp, bound to the natural pseudopalindromic response element. Comparison of the structure with that obtained previously, using an idealized response element, shows how the EcRDBD, which has been previously reported to possess extraordinary flexibility, accommodates DNA-induced structural changes. Part of the C-terminal extension (CTE) of the EcRDBD folds into an alpha-helix whose location in the minor groove does not match any of the locations previously observed for nuclear receptors. Mutational analyses suggest that the alpha-helix is a component of EcR-box, a novel element indispensable for DNA-binding and located within the nuclear receptor CTE. This element seems to be a general feature of all known EcRs.
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Proteínas de Unión al ADN/química , Modelos Moleculares , Receptores de Esteroides/química , Elementos de Respuesta , Factores de Transcripción/química , Sustitución de Aminoácidos , Animales , Sitios de Unión , Cristalografía por Rayos X , ADN/química , Proteínas de Unión al ADN/genética , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Proteínas de Choque Térmico/genética , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Receptores de Esteroides/genética , Factores de Transcripción/genéticaRESUMEN
The formation of tolmetin/N-acetyl-l-tyrosine ethyl ester (ATEE) complex has been reported by means of both theoretical and experimental studies, including quantum mechanical calculations as well as UV-vis absorption, fluorescence and time-resolved spectroscopy measurements. It has been found that the fluorescence of ATEE is quenched due to the formation of a non-fluorescent complex between ATEE and tolmetin in the ground state. The geometrical parameters of ATEE/tolmetin complex have been determined with the use of the DFT method applying the B3LYP correlation-exchange functional and 6-31G(d) basis set. The results of experiments indicated the static ATEE quenching by tolmetin. Additionally, the experimental and theoretically predicted Gibbs free energy of complexation has been calculated.
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Antiinflamatorios no Esteroideos/química , Tolmetina/química , Tirosina/análogos & derivados , Inhibidores de la Ciclooxigenasa/química , Estructura Molecular , Análisis Espectral , Tirosina/químicaRESUMEN
Ecdysteroids coordinate development, reproduction and other essential biological processes in insects and other arthropods through the receptor which is a heterodimer of two members of the nuclear receptors superfamily, the ecdysteroid receptor (EcR) and the Ultraspiracle (Usp). Although the transcriptionally active EcR/Usp heterocomplex is believed to be the only functional form of the receptor, there are data indicating that EcR may be involved in the mediation of the non-genomic effects outside of the nucleus. Since the nucleocytoplasmic shuttling could be a key element determining participation of the single nuclear receptor molecule both in the genomic and non-genomic functions we have analyzed nuclear import and export properties of the EcR and Usp from Drosophila melanogaster. We show for the first time that both receptors exhibit differential distribution of the nuclear localization and nuclear export signals (NLSs and NESs). In particular, the Usp which exhibits exclusively nuclear localization in all cell types analyzed, contains apparently only NLS activity within the DNA-binding domain. In contrast, the three known EcR isoforms (A, B1 and B2) are mosaics of elements which can potentially mediate their nucleocytoplasmic shuttling. We have found two active NESs in ligand binding domain and NLS activity within the DNA-binding domain of all isoforms. Simultaneously we demonstrate that B1 and A isoforms possess an additional NLS activity localized in AB regions. We speculate that this characteristic, along with the previously reported structural pliability of the EcR molecule, allows the single receptor to evoke many different genomic as well as non-genomic ecdysteroid-dependent responses.
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Transporte Activo de Núcleo Celular , Núcleo Celular/metabolismo , Proteínas de Unión al ADN/metabolismo , Receptores de Esteroides/metabolismo , Factores de Transcripción/metabolismo , Secuencia de Aminoácidos , Animales , Células CHO , Células COS , Chlorocebus aethiops , Cricetinae , Cricetulus , Proteínas de Unión al ADN/genética , Proteínas de Drosophila , Drosophila melanogaster , Células HeLa , Humanos , Proteínas Luminiscentes/metabolismo , Modelos Moleculares , Datos de Secuencia Molecular , Señales de Exportación Nuclear/genética , Señales de Exportación Nuclear/fisiología , Señales de Localización Nuclear/metabolismo , Receptores de Esteroides/genética , Proteínas Recombinantes de Fusión/metabolismo , Homología de Secuencia de Aminoácido , Fracciones Subcelulares , Factores de Transcripción/genéticaRESUMEN
Breast cancer (BCa) is the most common cancer affecting women worldwide. Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in ~20-25% of invasive ductal breast carcinomas and is associated with the more aggressive phenotype. Herceptin, a humanized antibody against HER2, is a standard therapy in HER2-overexpressing cases. Approximately one-third of patients relapse despite treatment. Therefore numerous studies have investigated the molecular mechanisms associated with Herceptin resistance. An interaction between HER2 signalling and steroid hormone receptor signalling pathways has been previously investigated, but the effect of this relationship on Herceptin resistance has never been studied. The present study analysed an impact of the steroid hormone, progesterone (PG), on Herceptin-dependent cell growth inhibition. Results indicated that Herceptin-inhibited proliferation of breast cancer cell lines overexpressing HER2 (BT474 and MCF/HER2) in 3D culture is abolished by PG. Furthermore, results demonstrated that PG led to the activation of HER2/HER3-mediated signalling. Moreover, PG treatment induced a shift of Herceptin-dependent cell cycle arrest in G1 phase towards S and G2 phases with concomitant upregulation of cyclin-dependent kinase 2 (CDK2) and downregulation of CDK inhibitor p27Kip1. These results demonstrate for the first time PG involvement in the failure of Herceptin treatment in vitro. The present observations suggest that cross-talk between PG- and HRG/HER2-initiated signalling pathways may lead to the acquisition of resistance to Herceptin in patients with BCa.
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Fhit, the product of tumor suppressor fragile histidine triad (FHIT) gene, exhibits antitumor activity of still largely unknown cellular background. However, it is believed that Fhit-Ap(3)A or Fhit-AMP complex might act as a second class messenger in cellular signal transduction pathway involved in cell proliferation and apoptosis. We demonstrate here for the first time that the photosensitizer, protoporphyrin IX (which is a natural precursor of heme) binds to Fhit protein and its mutants in the active site in vitro. Furthermore, PpIX inhibits the enzymatic activity of Fhit. Simultaneously, PpIX shows lower binding capacity to mutant Fhit-H96N of highly reduced hydrolase activity. In cell-based assay PpIX induced HeLa cell death in Fhit and Fhit-H96N-dependent manner which was measured by means of MTT assay. Moreover, HeLa cells stably expressing Fhit or mutant Fhit-H96N were more susceptible to protoporphyrin IX-mediated photodynamic therapy (2J/cm(2)) than parental cells.
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Ácido Anhídrido Hidrolasas/metabolismo , Proteínas de Neoplasias/metabolismo , Fotoquimioterapia , Protoporfirinas/metabolismo , Ácido Anhídrido Hidrolasas/antagonistas & inhibidores , Ácido Anhídrido Hidrolasas/genética , Ácido Anhídrido Hidrolasas/fisiología , Supervivencia Celular , Células HeLa , Humanos , Mutación , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiología , Fármacos Fotosensibilizantes , Unión Proteica/genética , Protoporfirinas/fisiología , Sistemas de Mensajero SecundarioRESUMEN
Photodynamic therapy (PDT) combining treatment with a light-excited compound and laser light induction, via cellular ROS generation, kills cancer cells by damaging organelles and impairing metabolic pathways. As the exact mechanisms underlying cancer cell death due to PDT treatment remain controversial, the influence of photosensitizer itself, protoporphyrin IX (PpIX) on cancer cells was investigated. The concentration-dependent viability of HeLa cells was estimated after PpIX-treatment. Microscopic analyses revealed that treated cells exhibited apoptosis-like morphology: blebbing, chromatin condensation, nuclear fragmentation, asymmetry of cellular membrane. These results shed a new light on cancer cell death due to PDT because they showed that PpIX can induce apoptosis without light excitation.
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Apoptosis/efectos de los fármacos , Protoporfirinas/farmacología , Apoptosis/genética , Apoptosis/efectos de la radiación , Permeabilidad de la Membrana Celular/efectos de los fármacos , Permeabilidad de la Membrana Celular/efectos de la radiación , Núcleo Celular/efectos de los fármacos , Núcleo Celular/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Supervivencia Celular/efectos de la radiación , Cromatina/efectos de los fármacos , Cromatina/efectos de la radiación , Ensayo Cometa/métodos , Fragmentación del ADN/efectos de los fármacos , Fragmentación del ADN/efectos de la radiación , Relación Dosis-Respuesta a Droga , Células HeLa , Humanos , Peróxido de Hidrógeno/farmacología , Microscopía Fluorescente , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Factores de TiempoRESUMEN
Background. The ELKa system is composed of computer software, with a database of nutrients, and a dedicated USB kitchen scale. It was designed to automatize the everyday calculations of food exchanges and prandial insulin doses. Aim. To investigate the influence of the ELKa on metabolic control in children with type 1 diabetes mellitus (T1DM). Methods. A randomized, parallel, open-label clinical trial involved 106 patients aged <18 years with T1DM, HbA1C ≤ 10%, undergoing intensive insulin therapy, allocated to the intervention group, who used the ELKa (n = 53), or the control group (n = 53), who used conventional calculation methods. Results. After the 26-week follow-up, the intention-to-treat analysis showed no differences to all endpoints. In per protocol analysis, 22/53 (41.5%) patients reporting ELKa usage for >50% of meals achieved lower HbA1C levels (P = 0.002), lower basal insulin amounts (P = 0.049), and lower intrasubject standard deviation of blood glucose levels (P = 0.023) in comparison with the control. Moreover, in the intervention group, significant reduction of HbA1C level, by 0.55% point (P = 0.002), was noted. No intergroup differences were found in the hypoglycemic episodes, BMI-SDS, bolus insulin dosage, and total daily insulin dosage. Conclusions. The ELKa system improves metabolic control in children with T1DM under regular usage. The trial is registered at ClinicalTrials.gov, number NCT02194517.
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Glucemia/análisis , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hemoglobina Glucada/análisis , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Adolescente , Niño , Preescolar , Diabetes Mellitus Tipo 1/sangre , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Resultado del TratamientoRESUMEN
Ecdysteroids coordinate molting and metamorphosis in insects via a heterodimer of two nuclear receptors, the ecdysone receptor (EcR) and the ultraspiracle (Usp) protein. Here we show how the DNA-recognition alpha-helix and the T box region of the EcR DNA-binding domain (EcRDBD) contribute to the specific interaction with the natural response element and to the stabilization of the EcRDBD molecule. The data indicate a remarkable mutational tolerance with respect to the DNA-binding function of the EcRDBD. This is particularly manifested in the heterocomplexes formed between the EcRDBD mutants and the wild-type Usp DNA-binding domain (UspDBD). Circular dichroism (CD) spectra and protein unfolding experiments indicate that, in contrast to the UspDBD, the EcRDBD is characterized by a lower alpha-helix content and a lower stability. As such, the EcRDBD appears to be an intrinsically unstructured protein-like molecule with a high degree of intramolecular plasticity. Because recently published crystal structures indicate that the ligand binding domain of the EcR is also characterized by the extreme adaptability, we suggest that plasticity of the EcR domains may be a key factor that allows a single EcR molecule to mediate diverse biological effects.
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Receptores de Esteroides/química , Receptores de Esteroides/metabolismo , Elementos de Respuesta/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Animales , Análisis Mutacional de ADN , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Drosophila , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Ensayo de Cambio de Movilidad Electroforética , Péptidos y Proteínas de Señalización Intracelular , Datos de Secuencia Molecular , Muda/genética , Mutación/genética , Regiones Promotoras Genéticas/genética , Proteínas Serina-Treonina Quinasas/genética , Estructura Secundaria de Proteína/genética , Estructura Terciaria de Proteína/genética , Receptores de Esteroides/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Simple methods for detection and isolation of protein-porphyrin complexes were elaborated in our laboratory. They are based on the separation of protein-porphyrin complexes in native polyacrylamide gel and measurement of their fluorescence, with the use of two detection systems: the commercially available Gel Doc(TM) 2000 system, and a system specially designed for the purpose of these investigations, concerning protein-porphyrin interactions. The fluorescent complexes can be electro-transferred from the gel onto PVDF membrane, eluted and analyzed in order to identify the protein interacting with porphyrins.
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Porfirinas/análisis , Proteínas/análisis , Electroforesis en Gel de Poliacrilamida , Polivinilos , Porfirinas/metabolismo , Unión Proteica/fisiología , Proteínas/metabolismoRESUMEN
Exercise-induced intravascular haemolysis and "sport anemia" are widely reported in human sports medicine. It has been recognized also in horses, however, the clinical importance and the onset of this condition seem different than in human. In this study we investigated the episodes of intravascular haemolysis, indicated by the increase in plasma haemoglobin and the decrease in serum haptoglobin levels, after routine training sessions in race horses. Heart rate and changes in haematological parameters confirmed, that the exertion was relatively high. Intravascular haemolysis did not appear in stallions but was detected in mares after two training sessions. It has been determined that serum haptoglobin levels were higher in mares than in stallions before and after all training sessions. It is postulated that intravascular haemolysis induced by training is of limited clinical importance because it occurred only in mares which are better adapted due to higher haptoglobin level at rest, and it had no cumulative effect. Therefore gender differences should be taken into consideration in experiments with athletic horses.
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Anemia/veterinaria , Hemólisis/fisiología , Enfermedades de los Caballos/sangre , Condicionamiento Físico Animal/efectos adversos , Caracteres Sexuales , Anemia/etiología , Animales , Femenino , Caballos , MasculinoRESUMEN
The aim of the paper is the recognition and evaluation of demand for medical information among patients suffering from breast cancer. The research was conducted among 120 women with diagnosed breast cancer in the Oncological Surgery Clinic of the Independent Public Research Hospital Nº 1 in Lublin, the Oncological Clinic of the Independent Public Research Hospital Nº 1 in Lublin and the Rehabilitation Centre with the Rehabilitation Clinic at the Lublin Oncology Centre. The research included women from the Club of Women after Mastectomy Amazons, the Club Amazons at the Complex of Specialist Clinics in Ostrowiec Swietokrzyski and the Club Amazons in Radom. Research showed that the demand for medical information among women with diagnosed breast cancer is very high. Respondents want to know all the information concerning the diagnosis, treatment and prognosis (93 percent). They also expect that the doctor will give them medical information concerning further consequences of cancer and its influence on future health and life (78 percent). Most of the respondents expect to receive information concerning medicaments which should be taken (77 percent) and the essence of the conducted treatment (93 percent). The research analysis showed that women with diagnosed breast cancer expect that the doctor will give them reliable and real medical information. Patients want the doctor to present them the probable course of the cancer (85 percent) and all the possible side effects connected with it (89 percent).
El objetivo de este trabajo es el reconocimiento y la evaluación de la demanda de información médica en pacientes con cáncer de mama. Se realizó la investigación con 120 mujeres diagnosticadas con cáncer de mama en la Clínica de Cirugía Oncológica y la Clínica Oncológica del Hospital de Investigación Público Independiente Nº 1 en Lublin, y el Centro de Rehabilitación con la Clínica de Rehabilitación del Centro Oncológico de Lublin. La investigación incluyó mujeres del Club Amazons de Mujeres que han sufrido Mastectomía, el Club Amazons del Complejo de Clínicas Especializadas en Ostrowiec Swietokrzyski y el Club Amazons en Radom. La investigación mostró que la demanda de información médica de mujeres con diagnóstico de cáncer de mama es muy alta. Aquellas que respondieron quieren saber todo acerca del diagnóstico, tratamiento y pronóstico (93 por ciento). También esperan que el médico les dé información médica respecto de posteriores consecuencias del cáncer y su influencia en su salud futura y su vida (78 por ciento). La mayoría de las que respondieron esperan recibir información sobre medicamentos que deberían tomar (77 por ciento) y lo esencial sobre el tratamiento realizado (93 por ciento). El análisis de la investigación muestra que las mujeres diagnosticadas con cáncer de mama esperan que el médico les dé información médica confiable y verdadera, les presente el curso probable del cáncer (85 por ciento) y todos los posibles efectos secundarios conectados (89 por ciento).
O objetivo deste artigo é o reconhecimento e a avaliação da demanda por informação médica entre pacientes que sofrem de câncer de mama. A investigação foi conduzida entre 120 mulheres diagnosticadas com câncer de mama na Oncological Surgery Clinic of the Independent Public Research Hospital Nº 1 de Lublin, a Oncological Clinic of the Independent Public Research Hospital Nº 1 de Lublin e a Rehabilitation Centre with the Rehabilitation Clinic do Lublin Oncology Centre. A pesquisa incluiu mulheres do Club of Women after Mastectomy Amazons, o Club Amazons do Complex of Specialist Clinic sem Ostrowiec Swietokrzyskie o Club Amazonsem Radom. Pesquisa revelou que a demanda por informação médica entre mulheres com diagnóstico de câncer mamário é muito alta. As respondentes queriam saber todas as informações concernentes ao diagnóstico, tratamento e prognóstico (93 por cento). Elas também esperavam que o médico pudesse dar-lhes informação sobre consequências tardias do câncer e a influência sobre a sua saúde e vida futuras (78 por cento). A maioria dos respondentes tinham a expectativa de receber informação sobre medicamentos que deveriam tomar(77 por cento) e a essência do tratamento realizado(93 por cento). A análise da pesquisa demonstrou que as mulheres com diagnóstico de câncer de mama esperavam que o médico pudesse fornecer-lhes informação confiável e honesta. Pacientes queriam que o médico lhes apresentasse o provável curso do câncer (85 por cento) e todos os possíveis efeitos relacionados a ele (89 por cento).
Asunto(s)
Humanos , Adulto , Femenino , Persona de Mediana Edad , Anciano de 80 o más Años , Neoplasias de la Mama , Acceso de los Pacientes a los Registros , Relaciones Médico-Paciente , Revelación de la Verdad , Acceso a la Información , Comunicación , Derechos del Paciente , Encuestas y CuestionariosRESUMEN
Ecdysteroids control molting and metamorphosis in insects via a heterodimeric complex of two nuclear receptors, the ecdysone receptor (EcR) and ultraspiracle protein (Usp). We used fluorescence resonance energy transfer (FRET) to study the topology of the natural pseudopalindromic element from the hsp27 gene (hsp27pal) in complex with the DNA-binding domains of Usp and EcR (UspDBD and EcRDBD, respectively). Steady-state data revealed shortening of the end-to-end distance of the hsp27pal-derived probe. For the 70.8 +/- 0.6 A distance obtained for the UspDBD-complexed DNA a bend of about 23.1 +/- 2.9 degrees was measured. Nearly the same value (23.0 +/- 3.4 degrees) was obtained for the DNA complexed with the UspDBD/EcRDBD heterodimer. The respective bend angles estimated using fluorescence decay measurements were 19.0 +/- 2.1 degrees and 20.9 +/- 3.6 degrees . Thus, the FRET data suggest for the first time that the UspDBD defines the architecture of the UspDBD/EcRDBD heterocomplex due to the significant deformation of the hsp27pal. This suggestion has been further reinforced using gel retardation experiments, which, in conjunction with high-resolution DNase I footprinting, indicate that the main contribution to the observed bend is given by the UspDBD itself, while binding of the EcRDBD molecule brings on a slight additional change of the preformed structure.