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Vanadium (V) is a metal that can enter the environment through natural routes or anthropogenic activity. In the atmosphere, V is present as V oxides, among which vanadium(III) oxide (V2O3) stands out. Cytogenetic studies have shown that V2O3 is genotoxic and cytostatic and induces DNA damage; however, the molecular mechanisms leading to these effects have not been fully explored. Therefore, we treated human peripheral blood lymphocytes in vitro, evaluated the effects of V2O3 on the phases of the cell cycle and the expression of molecules that control the cell cycle and examined DNA damage and the induction of oxidative stress. The results revealed that V2O3 did not affect cell viability at the different concentrations (2, 4, 8 or 16⯵g/mL) or exposure times (24â¯h) used. However, V2O3 affected the percentage of G1- and S-phase cells in the cell cycle, decreased the expression of mRNAs encoding related proteins (cyclin D, cyclin E, CDK2 and CDK4) and increased the expression of γH2AX and the levels of reactive oxygen species. The ability of V2O3 to cause a cell cycle delay in G1-S phase may be associated with a decrease in the mRNA and protein expression of the cyclins/CDKs and with intracellular oxidative stress, which may cause DNA double-strand damage and H2AX phosphorylation.
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BACKGROUND AND OBJECTIVES: cardiovascular changes during pregnancy carry greater risk in heart disease. We analyze cardiovascular, obstetric and perinatal adverse effects associated with congenital and acquired heart disease during pregnancy and postpartum. MATERIALS AND METHODS: Cross-sectional and retrospective study, which included the 2017-2023 registry of pregnant or postpartum patients hospitalised with diagnosis of congenital or acquired heart disease. Adverse events (heart failure, stroke, acute pulmonary edema, maternal death, obstetric haemorrhage, prematurity and perinatal death) were compared with the clinical variables and the implemented treatment. RESULTS: 112 patients with a median age of 28 years (range 15-44) were included. Short circuits predominated 28 (25%). Thirty-six patients (32%) were classified in class IV of the modified WHO scale for maternal cardiovascular risk. Heart failure occurred in 39 (34.8%), acute lung edema 12 (10.7%), stroke 2 (1.8%), maternal death 5 (4.5%), obstetric haemorrhage 4 (3.6%), prematurity 50 (44.5%) and perinatal death 6 (5.4%). Shunts were associated with prematurity (adjusted odds ratio 4; 95% CI: 1.5-10, pâ¯=â¯0.006). Peripartum cardiomyopathy represented higher risk of pulmonary edema (adjusted OR 34; 95% CI: 6-194, pâ¯=â¯0.001) and heart failure (adjusted OR 16; 95% CI: 3-84, pâ¯=â¯0.001). An increased risk of obstetric haemorrhage was observed in patients with prosthetic valves (adjusted OR 30; 95% CI: 1.5-616, pâ¯=â¯0.025) and with the use of acetylsalicylic acid (adjusted OR 14; 95% CI: 1.2-16, pâ¯=â¯0.030). Furthermore, the latter was associated with perinatal death (adjusted OR 9; 95% CI: 1.4-68, pâ¯=â¯0.021). CONCLUSIONS: severe complications were found during pregnancy and postpartum in patients with heart disease, which is why preconception evaluation and close surveillance are vital.
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Cardiopatias , Complicações Cardiovasculares na Gravidez , Transtornos Puerperais , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Adulto , Estudos Transversais , Complicações Cardiovasculares na Gravidez/epidemiologia , Adulto Jovem , Adolescente , Transtornos Puerperais/epidemiologia , Transtornos Puerperais/etiologia , Recém-Nascido , Edema Pulmonar/epidemiologia , Edema Pulmonar/etiologia , Período Pós-PartoRESUMO
Survival of CHD has significantly improved, but children with CHD remain susceptible to neurodevelopmental and psychosocial impairments. Our goal was to investigate the association between socio-demographic factors and psychosocial adaptation for future intervention. A retrospective cross-sectional study of an independent children's hospital's records was conducted. Psychosocial adaptation was measured by the Pediatric Cardiac Quality of Life Inventory Psychosocial Impact score (range 0-50, higher score indicates greater psychosocial adaptation). Bivariate and regression analyses were performed to estimate relationships between Psychosocial Impact score and socio-demographic variables including Child Opportunity Index, family support, financial support, academic support, and extracurricular activities. A total of 159 patients were included. Compared to patients in high opportunity neighbourhoods, patients in low opportunity neighbourhoods had a 9.27 (95% confidence interval [-17.15, -1.40], p = 0.021) point lower Psychosocial Impact score, whereas patients in moderate opportunity neighbourhoods had a 15.30 (95% confidence interval [-25.38, -5.22], p = 0.003) point lower Psychosocial Impact score. Compared to patients with adequate family support, those with limited support had a 6.23 point (95% confidence interval [-11.82, -0.643], p = 0.029) lower Psychosocial Impact score. Patients in moderate opportunity neighbourhoods had a higher Psychosocial Impact score by 11.80 (95% confidence interval [1.68, 21.91], p = 0.022) when they also had adequate family support compared to those with limited family support. Our findings indicate that among children with CHD, psychosocial adaptation is significantly impacted by neighbourhood resources and family support structures. These findings identify possible modifiable and protective factors to improve psychosocial adaptation in this vulnerable population.
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OBJECTIVES: To characterize the splicing machinery (SM) of leukocytes from primary antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome with lupus (APS + SLE) patients, and to assess its clinical involvement. METHODS: Monocytes, lymphocytes and neutrophils from 80 patients (22 APS, 35 SLE and 23 APS + SLE) and 50 HD were purified, and 45 selected SM components were evaluated by qPCR-microfluidic array. Relationship with clinical features and underlying regulatory mechanisms were assessed. RESULTS: APS, SLE and APS + SLE leukocytes displayed significant and specific alterations in SM-components (SMC), associated with clinical features [autoimmune profiles, disease activity, lupus nephritis (LN), and CV-risk markers]. A remarkable relationship among dysregulated SMC in monocytes and the presence of LN in SLE was highlighted, revealing a novel pathological mechanism, which was further explored. Immunohistology analysis of renal biopsies highlighted the pathological role of the myeloid compartment in LN. Transcriptomic analysis of monocytes from SLE-LN(+) vs SLE-LN(-) identified 271 genes differentially expressed, mainly involved in inflammation and IFN-signaling. Levels of IFN-related genes correlated with those of SMC in SLE-LN(+). These results were validated in two external SLE-LN(+) datasets of whole-blood and kidney biopsies. In vitro, SLE-LN(+)-serum promoted a concomitant dysregulation of both, the IFN signature and several SMC, further reversed by JAKinibs treatment. Interestingly, IFNs, key inflammatory cytokines in SLE pathology, also altered SMC. Lastly, the over/down-expression of selected SMC in SLE-monocytes reduced the release of inflammatory cytokines and their adhesion capacity. CONCLUSION: Overall, we have identified, for the first time, a specific alteration of SMC in leukocytes from APS, SLE and APS + SLE patients that would be responsible for the development of distinctive clinical profiles.
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Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Inflamação , CitocinasRESUMO
Cells with subcellular lumens form some of the most miniature tubes in the tubular organs of animals. These are often crucial components of the system, executing functions at remote body locations. Unlike tubes formed by intercellular or autocellular junctions, the cells with junctionless subcellular lumens face unique challenges in modifying the cell shape and plasma membrane organization to incorporate a membrane-bound tube within, often associated with dramatic cellular growth and extensions. Results in the recent years have shown that membrane dynamics, including both the primary delivery and recycling, is crucial in providing the cell with the flexibility to face these challenges. A significant portion of this information has come from two in vivo invertebrate models; the Drosophila tracheal terminal cells and the C. elegans excretory cell. This review focuses on the data obtained from these systems in the recent past about how trafficking pathways influence subcellular tube and branching morphogenesis. Given that such tubes occur in vertebrate vasculature, these insights are relevant to human health, and we contrast our conclusions with the less understood subcellular tubes of angiogenesis.
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Proteínas de Drosophila , Animais , Humanos , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Caenorhabditis elegans/metabolismo , Morfogênese , Drosophila/metabolismoRESUMO
Currently, cancer treatments are highly invasive, and they have been associated with a lot of adverse effects that put patient integrity at risk. Therefore, research of novel molecules and delivery systems capable of achieving a therapeutic effect that modifies inhibits and reduces the proliferative activity in cancer cells and, at the same time, reduce adverse effects associated with conventional therapies is imperative. In this study, we analyzed the biological effect of a novel cinnamic acid derivative, 3,4-dichlorobencil-p-phenoxylcilamide, in polymeric nanoparticles over MCF-7 breast cancer cells. The nanoparticulated system showed an inhibitory influence over cellular metabolism at equal or higher concentrations than 25 µM of 3,4-dichlorobencil-p-phenoxylcilamide, which is associated with PPARγ transcriptional activity, in addition to the decrease in the proliferation antigen Ki-67 basal levels. Those results position this kind of nanoscale system as an alternative on breast cancer treatment and lay the basis for research on the action mechanism associated with its cellular metabolism modulation and relationship with another hallmark on breast cancer cellular models.
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Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Antineoplásicos/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos/química , Feminino , Humanos , Antígeno Ki-67/metabolismo , Células MCF-7 , PPAR gama/metabolismoRESUMO
Plasma membranes fulfil many physiological functions. In polarized cells, different membrane compartments take on specialized roles, each being allocated correct amounts of membrane. The Drosophila tracheal system, an established tubulogenesis model, contains branched terminal cells with subcellular tubes formed by apical plasma membrane invagination. We show that apical endocytosis and late endosome-mediated trafficking are required for membrane allocation to the apical and basal membrane domains. Basal plasma membrane growth stops if endocytosis is blocked, whereas the apical membrane grows excessively. Plasma membrane is initially delivered apically and then continuously endocytosed, together with apical and basal cargo. We describe an organelle carrying markers of late endosomes and multivesicular bodies (MVBs) that is abolished by inhibiting endocytosis and which we suggest acts as transit station for membrane destined to be redistributed both apically and basally. This is based on the observation that disrupting MVB formation prevents growth of both compartments.
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Membrana Celular/metabolismo , Endossomos/metabolismo , Organogênese/fisiologia , Transcitose/fisiologia , Animais , Drosophila melanogasterRESUMO
FUNDAMENTO Y OBJETIVOS: el cáncer de pulmón (CP) es el que provoca mayor mortalidad, especialmente por su frecuente diagnóstico tardío, con menos posibilidades de curación. En el inicio del proceso carcinogénico, previo al diagnóstico clínico, los oligoelementos (metales o metaloides), desempeñan un papel importante al activar o inhibir las reacciones enzimáticas y las metaloproteínas. El objetivo de nuestro estudio es analizar la utilidad de diversos metales como biomarcadores (BM) precoces de CP, obtenidos en muestras de suero, orina, y lavado broncoalveolar (LBA)MATERIAL Y MÉTODOS: hemos analizado las concentraciones totales, incluyendo fracciones de alto y bajo peso molecular, de 11 metales en muestras de suero, orina y LBA de pacientes CP, controles sanos (CS) y pacientes con patología respiratoria no cáncer (NCP) empleando una técnica de análisis basada en un plasma de acoplamiento inductivo-espectrometría de masas (ICP-QQQ-MS). RESULTADOS: obtuvimos una clara discriminación entre los grupos en las tres muestras analizadas. Hemos obtenido metales sobreexpresados o reducidos en el CP que podrían utilizarse como BM. La concentración de vanadio (V) y cromo (Cr) en suero es claramente mayor en pacientes con CP. Hemos demostrado que varios metales (V, Cr y cobre), relacionados con procesos metabólicos alterados en CP como estrés oxidativo y homeostasis, y/o sus relaciones podrían ser buenos BM de CP. CONCLUSIONES: diversos metales, y sus relaciones y correlaciones, en la población estudiada diferencian claramente a los pacientes con cáncer de pulmón de los CS y NCP y parecen ser buenos biomarcadores en el diagnóstico precoz del cáncer de pulmón
BACKGROUND AND OBJECTIVES: Lung cancer (LC) has the highest mortality rate, especially due to its late diagnosis, with a lower chance of recovery. At the start of the carcinogenic process, before a clinical diagnosis, trace elements (metals or metalloids) play an important role by activating or inhibiting enzymatic reactions and metalloproteins. The objective of our study is to analyze the utility of different metals as early biomarkers (BM) for LC which are obtained in serum, urine and bronchoalveolar lavage (BAL) samples. MATERIAL AND METHODS: We analyzed the total concentrations, including fractions of high and low molecular weight, of 11 metals in serum, urine and BAL samples from patients with LC, healthy controls (HC) and patients with non-cancerous respiratory pathology (NCP) using an analysis technique based on inductively coupled plasma mass spectrometry (ICP-QQQ-MS).RESULTS: We obtained a clear discrimination between groups for the three samples analyzed. We obtained overexpressed or reduced metals in LC that could be used as BM. The concentration of vanadium (V) and chromium (Cr) in serum is clearly higher in patients with LC. We have shown that several metals (V, Cr and copper) related to the altered metabolic processes in LC such as oxidative stress and homeostasis and/or their connections could be good BM for LC. CONCLUSIONS: in the population studied, several metals and their connections and correlations were clearly differentiated in the patients with lung cancer compared to the HC and NCP groups and they appear to be good biomarkers for the early diagnosis of lung cancer
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/diagnóstico , Biomarcadores/sangue , Biomarcadores/urina , Diagnóstico Precoce , Oligoelementos/análise , Lavagem Broncoalveolar/métodos , Espectrometria de Massas/métodos , Prognóstico , Curva ROCRESUMO
La asociación entre cáncer y enfermedad tromboembólica (ETV) se encuentra bien establecida. La ETV presenta una elevada morbimortalidad, objetivándose un incremento del riesgo de ETV hasta 4 veces mayor en aquellos pacientes con cáncer respecto a la población general. Sin embargo, existe poca evidencia científica sobre la CVRS (calidad de vida relacionada con la salud) en pacientes oncológicos con ETV, cuando es presumible que esta patología suponga un agravante sobre la percepción del estado de salud de los pacientes oncológicos. Nuestro objetivo es presentar el estudio "QCa Study", el cual pretende evaluar la CVRS de los pacientes oncológicos con ETV aguda sintomática en comparación con pacientes oncológicos sin ETV. "QCa study" es un estudio nacional de cohortes, prospectivo, de casos y controles en pacientes con cáncer activo. Definimos "caso" como aquel paciente oncológico con ETV aguda sintomática, y "control" aquel paciente oncológico sin ETV aguda sintomática. Los criterios de inclusión son: para los casos: presentar cáncer activo al momento de la inclusión. Tener más de 18 años, pacientes diagnosticados de trombosis venosa profunda (TVP) en miembros inferiores aguda sintomática o de embolia de pulmón (EP) confirmado de forma objetiva mediante pruebas de imagen y firma del consentimiento informado. Para los controles; presentar cáncer activo. Tener más de 18 años. Firma del consentimiento informado. Dado los escasos datos publicados respecto a la CVRS en pacientes con ETV, hemos diseñado el estudio Qca, para poder determinar el impacto que genera la ETV en la calidad de vida de los pacientes con cáncer
The association between cancer and venous thromboembolic disease (VTD) is well established. VTD presents a high rate of morbidity and mortality, with patients with cancer showing an increased risk of VTD that is up to 4 times greater than the general population. However, there is little scientific evidence on HRQoL (health-related quality of life) in cancer patients with VTD when this disease is likely to be an aggravating factor in perceived state of health among cancer patients. Our objective is to present the QCa study, which aims to evaluate the HRQoL of cancer patients with acute symptomatic VTD in comparison with cancer patients without VTD. The QCa study is a prospective, case-control national cohort study in patients with active cancer. We define "case" as a cancer patient with acute symptomatic VTD and "control" as a cancer patient without acute symptomatic VTD. Inclusion criteria for cases were: having active cancer at the time of inclusion, being over the age of 18, patients diagnosed with acute symptomatic deep vein thrombosis (DVT) in the lower extremities or pulmonary embolism (EP) that was objectively confirmed through imaging tests, and having signed the informed consent. For the controls: having active cancer, being over the age of 18, and having signed the informed consent. Given the scarce data published with regard to HRQoL in patients with VTD, we designed the QCa study to determine the impact VTD has on the quality of life of patients with cancer
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Humanos , Qualidade de Vida , Tromboembolia Venosa/etiologia , Neoplasias/complicações , Estudos de Casos e Controles , Nível de Saúde , Estudos Prospectivos , Inquéritos e Questionários , AntropometriaRESUMO
AIM: To quantify the expression of angiogenic growth factors (ANG2, VEGFA, TGFß1) and their corresponding receptors (VEGFR1, VGFR2, NRP1 and TGFßR1) in human dental pulps from extracted third molars with complete and incomplete root development. METHODOLOGY: Fifty-six dental pulp samples obtained from freshly extracted human third molars were divided equally into two groups according to their stage of root development; 28 third molars with complete root development and 28 third molars with incomplete root development. All samples were processed and total RNA was extracted, cDNA was then synthetized for each sample and the target genes expression profiles for ANG2, VEGFA, VEGFR1, VEGFR2, NRP1, TGFß1 and TGFßR1 were obtained by RT2-PCR. The data was analysed with a Student's t-test to compare the replicate ∆∆Ct values for each gene. RESULTS: Teeth with incomplete root development were associated with a significantly greater gene expression of TGFßR1 (P = 0.03), whereas in teeth with complete root development the genes that had significantly greater expression were VEGFA (P = 0.04). CONCLUSION: The angiogenic growth factors (ANG2, VEGFA, TGFß1) and their receptors (NRP1, VEGFR1, VEGFR2 and TGFßR1) were expressed in pulps of teeth with complete and incomplete root development measured by RT2-PCR, with TGFBR1 genes being significantly different in teeth with incomplete root development and VEGFA genes in teeth with complete root development.
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Polpa Dentária , Dente Serotino , Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização IntercelularRESUMO
The use of nanometric systems to deliver biologically active substances is a successful tool in different fields. In this study, we investigated nanometric systems with antioxidant capacity to modulate events associated with the redox state in human chondrocytes. We used nanoparticles (NPs) prepared with chitosan and glutathione (GSH) and an in vitro model: primary cultures of human chondrocytes were extracted from hyaline cartilage. The cells were exposed to CdCl2 in the presence or absence of NPs. CdCl2 is a widely known oxidizing agent. Fluorescence and confocal microscopy showed the location of the NPs within the cells. The results obtained showed that the NPs did not significantly affect cell viability. We studied the antioxidant capacity of the NPs by estimating the GSH, TBARs, and Cell Rox content and the enzymatic activity of glutathione peroxidase (GPx). In vitro assays showed that GSH levels, GPx activity and reactive oxygen species (Cell Rox) levels were modified with both concentrations of NPs, while lipoperoxidation (TBARs) decreased when cells exposed to CdCl2 were in contact with the NPs. All these results suggest the ability of NPs to modulate the cell redox state in a dose-dependent manner.
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Antioxidantes/farmacologia , Quitosana/química , Glutationa/farmacologia , Nanopartículas , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/administração & dosagem , Cloreto de Cádmio/administração & dosagem , Cloreto de Cádmio/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Relação Dose-Resposta a Droga , Glutationa/administração & dosagem , Humanos , OxirreduçãoRESUMO
Essentials Fibrinogen prothrombin time-derived (FIBPT-d) behavior in anticoagulated patients is under studied. FIBPT-d method overestimates fibrinogen in rivaroxaban and low molecular weight heparin samples. Unfractionated heparin and dabigatran samples showed similar bias to the control group. Rabbit brain and human recombinant thromboplastin behavior was different in rivaroxaban samples. SUMMARY: Background The fibrinogen prothrombin time-derived (FIBPT-d) method with photo-optical coagulometers is easy and economical. However, there are few reports on the behavior of this test on samples from patients anticoagulated with direct oral anticoagulants or low molecular weight heparin (LMWH). Objective To compare fibrinogen results obtained with the Clauss (FIB C) method and the FIBPT-d method with two thromboplastins in anticoagulated patients. Population The study population comprised 295 consecutive anticoagulated patients: 99 treated with vitamin K antagonists (VKAs), 49 treated with unfractionated heparin (UFH), 47 treated with LMWH, 50 treated with rivaroxaban, 50 treated with dabigatran, and 100 normal controls (NCs). Methods Dabigatran samples were analyzed by the use of FIB C with HemosIL Fibrinogen C or 100 NHI thrombin units mL-1 reagents; rabbit brain and human recombinant thromboplastins with HemosIL PTFibrinogen HS plus (HS) and Recombiplastin 2G (RP) were used for FIBPT-d method. Heparin and rivaroxaban levels were assessed with HemosIL Liq antiXa with specific calibrators; dabigatran levels were determined with the HemosIL Direct Thrombin Inhibitor Assay. All assays were performed on the ACL TOP platform in two laboratories. Percentage biases for the FIBPT-d method versus the FIB C method were calculated by the use of Bland-Altman plots. Results Positive biases of the FIBPT-d method versus the FIB C method with both thromboplastins were seen in NC samples (13.7% and 18.9% for HS and RP, respectively), but biases with HS in rivaroxaban and VKA patient samples were higher than that in NC samples, at 31.9% and 34.0%, respectively. LMWH patient samples showed higher bias than NC samples: 26.5% and 29.3.0% with HS and RP, respectively. UFH and dabigatran patient samples showed similar bias as NC samples. Conclusion The FIBPT-d method should not be used in anticoagulated patients, because the FIBPT-d mathematical algorithm has been validated only in normal subjects, so overestimation could occur in these patients.
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Tango1 enables ER-to-Golgi trafficking of large proteins. We show here that loss of Tango1, in addition to disrupting protein secretion and ER/Golgi morphology, causes ER stress and defects in cell shape. We find that the previously observed dependence of smaller cargos on Tango1 is a secondary effect. If large cargos like Dumpy, which we identify as a Tango1 cargo, are removed from the cell, nonbulky proteins reenter the secretory pathway. Removal of blocking cargo also restores cell morphology and attenuates the ER-stress response. Thus, failures in the secretion of nonbulky proteins, ER stress, and defective cell morphology are secondary consequences of bulky cargo retention. By contrast, ER/Golgi defects in Tango1-depleted cells persist in the absence of bulky cargo, showing that they are due to a secretion-independent function of Tango1. Therefore, maintenance of ER/Golgi architecture and bulky cargo transport are the primary functions for Tango1.
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Translocador Nuclear Receptor Aril Hidrocarboneto/fisiologia , Proteínas de Drosophila/fisiologia , Retículo Endoplasmático/fisiologia , Complexo de Golgi/fisiologia , Proteínas de Transporte Vesicular/fisiologia , Animais , Drosophila melanogaster , Estresse do Retículo Endoplasmático/fisiologia , Técnicas de Silenciamento de Genes , Mutagênese , Transporte Proteico/fisiologiaRESUMO
The growth plate is the responsible for longitudinal bone growth. It is a cartilaginous structure formed by chondrocytes that are continuously undergoing a differentiation process that starts with a highly proliferative state, followed by cellular hypertrophy, and finally tissue ossification. Within the growth plate chondrocytes display a characteristic columnar organization that potentiates longitudinal growth. Both chondrocyte organization and hypertrophy are highly regulated processes influenced by biochemical and mechanical stimuli. These processes have been studied mainly using in vivo models, although there are few computational approaches focused on the rate of ossification rather than events at cellular level. Here, we developed a model of cellular behavior integrating biochemical and structural factors in a single column of cells in the growth plate. In our model proliferation and hypertrophy were controlled by biochemical regulatory loop formed between Ihh and PTHrP (modeled as a set of reaction-diffusion equations), while cell growth was controlled by mechanical loading. We also examined the effects of static loading. The model reproduced the proliferation and hypertrophy of chondrocytes in organized columns. This model constitutes a first step towards the development of mechanobiological models that can be used to study biochemical interactions during endochondral ossification.
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Condrócitos/patologia , Simulação por Computador , Lâmina de Crescimento/patologia , Modelos Biológicos , Fenômenos Biomecânicos , Diferenciação Celular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Força Compressiva/efeitos dos fármacos , Proteínas Hedgehog/farmacologia , Hipertrofia , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Resistência à Tração/efeitos dos fármacos , Fatores de Tempo , Suporte de CargaRESUMO
BACKGROUND: Homozygous or double heterozygous factor XIII (FXIII) deficiency is characterized by soft tissue hematomas, intracranial and delayed spontaneous bleeding. Alterations of thromboelastography (TEG) parameters in these patients have been reported. The aim of the study was to show results of TEG, TEG Lysis (Lys 60) induced by subthreshold concentrations of streptokinase (SK), and to compare them to the clot solubility studies results in samples of a 1-year-old girl with homozygous or double heterozygous FXIII deficiency. CASE: A year one girl with a history of bleeding from the umbilical cord. During her first year of life, several hematomas appeared in soft upper limb tissue after punctures for vaccination and a gluteal hematoma. One additional sample of a heterozygous patient and three samples of acquired FXIII deficiency were also evaluated. MATERIALS AND METHODS: Clotting tests, von Willebrand factor (vWF) antigen and activity, plasma FXIII-A subunit (pFXIII-A) were measured by an immunoturbidimetric assay in a photo-optical coagulometer. Solubility tests were performed with Ca(2+)-5 M urea and thrombin-2% acetic acid. Basal and post-FXIII concentrate infusion samples were studied. TEG was performed with CaCl2 or CaCl2 + SK (3.2 U/mL) in a Thromboelastograph. RESULTS: Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, fibrinogen, factor VIIIc, vWF, and platelet aggregation were normal. Antigenic pFXIII-A subunit was < 2%. TEG, evaluated at diagnosis and post FXIII concentrate infusion (pFXIII-A= 37%), presented a normal reaction time (R), 8 min, prolonged k (14 and 11min respectively), a low Maximum-Amplitude (MA) ( 39 and 52 mm respectively), and Clot Lysis (Lys60) slightly increased (23 and 30% respectively). In the sample at diagnosis, clot solubility was abnormal, 50 and 45 min with Ca-Urea and thrombin-acetic acid, respectively, but normal (>16 hours) 1-day post-FXIII infusion. Analysis of FXIII deficient and normal plasma mixtures (< 2-102% of pFXIII-A), showed that Ca-urea solubility was abnormal at pFXIII-A < 9%, thrombin-acetic acid at pFXIII-A<18%, but TEG MA and elasticity at 23% and Lys60 with SK at pFXIII-A< 40%. CONCLUSIONS: TEG parameters MA and elasticity, and Lys 60 in TEG either with Ca(2+) or Ca(2+) and SK are more sensitive to low levels of pFXIII than solubility tests. The increased Lys60 induced by a subthreshold concentration of SK could probably reflect the clot characteristics "in vivo" in many patients with pFXIII levels between 5-40% and could be potentially considered as screening test.
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OBJETIVOS: analizar características demográficas, clínicas y pronósticas, en pacientes que requirieron de ventilación mecánica no invasiva (VMNI) durante su ingreso en planta de hospitalización e identificar variables asociadas a mayor mortalidad intrahospitalaria. MATERIAL Y MÉTODOS: estudio observacional prospectivo sobre pacientes hospitalizados que requirieron tratamiento con VMNI por parte del servicio de Neumología. RESULTADOS: se incluyeron 222 pacientes, 55% varones, con edad media de 71,8 +/- 15,7 años. El pH y la PCO2 de inicio de VMNI fue de 7,28 +/- 0,09, 70,6 +/- 19,9 mmHg, respectivamente (media +/- desviación estándar). La puntuación media de la escala de Glasgow fue 13,29 y de la escala de Charlson 3,0. Los diagnósticos presentes al inicio de la VMNI, por orden de frecuencia, fueron: insuficiencia cardíaca congestiva (52%), agudización de EPOC (32%), síndrome obesidad hipoventilación (SOH) (22%), neumonía (13%), neumonía en inmunodeprimido (12%) y toma de sedantes (10%). Los pacientes podían tener uno o más de un diagnóstico. Fallecieron 69 pacientes, siendo la mortalidad intrahospitalaria del 31%. La estancia media hospitalaria fue de 9,16 días. Aquellas variables asociadas a una mayor mortalidad intrahospitalaria fueron (odds ratio ajustada [IC del 95%]) la presencia de SOH (0,20 [0,07 - 0,51]), neumonía (1,99 [1,01 - 4,00]), neumonía en paciente inmunodeprimido (3,90 [1,69 - 8,94] (p = 0,001), neoplasia (2,78 [1,28 - 6,01] y el inicio de VMNI en pacientes con un Glasgow < 11 (2,60 [1,75 - 3,83]). CONCLUSIONES: nuestro trabajo permite evidenciar la utilidad de la VMNI en una planta de hospitalización en pacientes no candidatos a UCI o con orden de no intubación. Al igual que los ensayos clínicos, los estudios en vida real permiten generar hipótesis y planificar áreas de mejora, sobre todo en aquellos pacientes que no son subsidiarios de participar en ensayos clínicos
OBJECTIVES: to analyze prognostic demographic, clinical and patients requiring noninvasive ventilation (NIV) during admission ward and identify variables associated with increased hospital mortality. METHODS: prospective observational study of hospitalized patients requiring treatment with NIV by the Service of Pneumology. RESULTS: 222 patients were included, 55% male, mean age 71.8 +/- 15.7 years. PH, pO2 and pCO2 NIV start was 7,28 +/- 0,09, 70,6 +/- 19,9 mmHg (mean +/- standard deviation). The average score was 13.29 Glasgow scale and the Charlson scale of 3.0. Diagnostics presented to establish NIV, in order of frequency, were: congestive heart failure (52%), exacerbation of COPD (32%), obesity hypoventilation syndrome (OHS) (22%), pneumonia (13%), pneumonia in immunosuppressed (12%) and use of sedatives (10%). Patients could have one or more than one diagnosis. 69 patients died, with hospital mortality of 31%. The mean hospital stay was 9.16 days. Those variables associated with increased hospital mortality were (adjusted odds ratio [95%]) the presence of SOH (0.20 [0.07 to 0.51]), pneumonia (1.99 [1.01 to 4,00]), pneumonia in immunocompromised patients (3.90 [1.69 to 8.94] (p = 0.001), neoplasia (2.78 [1.28 to 6.01] and the start of NIV in patients with a Glasgow score< 11 (2.60 [1.75 to 3.83]). CONCLUSIONS: Our work makes evident the usefulness of NIV in a ward for patients not candidates for ICU or with non-intubation order. As clinical trials, studies in real life can generate hypotheses and planning areas for improvement, especially in patients who are not subsidiary to clinical trials
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Humanos , Respiração Artificial , Insuficiência Respiratória/mortalidade , Síndrome Torácica Aguda/mortalidade , Fatores de Risco , Mortalidade HospitalarRESUMO
INTRODUCCIÓN: nuestro grupo ha comenzado un trabajo para estudiar la relación entre la incidencia de TEP y la contaminación ambiental. Para establecer una relación, es una condición metodológica fundamental contar con todos los casos incidentes en un periodo de tiempo. Por este motivo diseñamos este estudio, para valorar la eficacia de recogida de pacientes consecutivos con TEP. MATERIAL Y MÉTODOS: realizamos un estudio ambispectivo, multicéntrico, de un año de duración. En una primera fase se incluyeron prospectivamente todos los casos que ingresaron con diagnóstico de TEP y posteriormente, de forma retrospectiva, realizamos una revisión de los registros hospitalarios de cada uno de los centros participantes. Así, calculamos la eficacia dividiendo el número de casos incidentes en fase prospectiva por el número total de casos reclutados en ambas fases. RESULTADOS: desde febrero 2012 a febrero 2013 se reclutaron 839 pacientes (440 prospectivamente). El reclutamiento prospectivo presentó una eficacia de detección de TEP del 52,4%, mostrando variabilidad según el centro (29,3 - 100%). Cuando analizamos sólo a los pacientes con TEP agudo sintomático idiopático, la eficacia fue del 59,8 %, con variabilidad según centro (31,7 - 100%). La eficacia de reclutamiento de pacientes con TEP secundario o idiopático fue de 42,1% vs. 59,8%, respectivamente (p < 0,001). CONCLUSIONES: en los estudios prospectivos, el porcentaje de pacientes no diagnosticados no es desdeñable. Los resultados de este estudio nos deben hacer pensar en estrategias adicionales para reclutar pacientes consecutivos de forma correcta, principalmente en aquellos estudios donde la pérdida de pacientes supondría un sesgo a la hora de emitir conclusiones
INTRODUCTION: we are studying the relationship between the incidence of pulmonary embolism (PE) and air pollution, and all symptomatic PE were needed over a period of time to establish a relationship. For this reason we designed this study, to assess the efficacy of collection consecutive patients with PE. METHODS: ambispective, multicenter study, from February 2012 to February 2013. In the first phase, we included prospectively all cases admitted at the hospital with PE diagnosis, and in the second phase, we reviewed retrospectively, hospital records from each participating center. So, we calculate the efficacy by dividing the number of incident cases in prospective phase by the total number of cases recruited in both phases. RESULTS: during one year, 839 patients were recruited (440 prospectively). The prospective recruitment presented a PE efficacy detection of 52.4%, showing variability according to the center between 29.3 to 100%. When we analyzed only patients with idiopathic symptomatic PE, efficacy was 59.8%, with variability according to the center between 31.7 to 100%. The recruitment efficacy of patients with secondary or idiopathic PE was 42.1% vs. 59.8%, respectively (p < 0.001). CONCLUSIONS: A wide percentage of patients can pass up from prospectives studies. The results of this study try to make us think, that we need more strategies to get a good recruit of consecutive patients, especially in those studies where is essential collect all patients
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Humanos , Tromboembolia Venosa/complicações , Prognóstico , Risco Ajustado/estatística & dados numéricos , Estudos Prospectivos , Erros de Diagnóstico/estatística & dados numéricos , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: Prothrombin time (PT) and activated partial thromboplastin time (APTT) sensitivity for detecting isolated factor deficiencies varies with different reagents and coagulometers. The Clinical and Laboratory Standards Institute (CLSI) H47A2 guideline proposed a method to calculate these sensitivities, but some inconsistency has been reported. This study aimed to calculate factor sensitivities using CLSI guideline and to compare them with those obtained from single factor-deficient patients' data. METHODS: Different mixtures of normal pooled and deficient plasmas were prepared (<1IU/dL to 100 IU/dL) according to the CLSI H47A2 guideline. PT with rabbit brain (RB) and human recombinant (HR) thromboplastins, APTT and factors' activities were measured in an ACL TOP coagulometer. Sensitivities (maximum factor concentration that produces PT or APTT values out of the reference range) were calculated from mixtures and from patients with single-factor deficiencies: 17 factor FV, 36 FVII, 19 FX, 39 FVIII, 15 FIX 15 FXI and 24 FXII. RESULTS: PT sensitivity with RB was as follows: FV 38 and 59, FVII 35 and 58, FX 56 and 64 IU/dL; PT sensitivity with HR was as follows: FV 39 and 45, FVII 51 and 50, FX 33 and 61 IU/dL; and APTT sensitivity was as follows: FV 39 and 45, FX 32 and 38, FVIII 47 and 60, FIX 35 and 44, FXI 33 and 43, FXII 37 and 46 IU/dL, respectively. CONCLUSIONS: Reagent-coagulometer combination has adequate sensitivities to factor deficiencies according to guideline recommendations (>30 IU/dL). These should not be considered as actual sensitivities because those obtained by analysing patients' plasmas with single-factor deficiencies were higher for most factors and could induce misinterpretation of the basic coagulation test results.
Assuntos
Coagulação Sanguínea , Transtornos de Proteínas de Coagulação/sangue , Transtornos de Proteínas de Coagulação/diagnóstico , Tempo de Tromboplastina Parcial/normas , Tempo de Protrombina/normas , Fatores de Coagulação Sanguínea , Humanos , Guias de Prática Clínica como Assunto , Valores de Referência , Sensibilidade e EspecificidadeRESUMO
Se reporta el caso de una mujer de 37 años de edad sin antecedentes relevantes, que consulta por cuadro febril ictérico asociado con alteración hepática importante con patrón necroinflamatorio, se documenta hepatitis viral B y presenta una evolución tórpida rápida hasta la muerte. De esta forma, se exponen los posibles factores que influyen en la progresión hacia la insuficiencia hepática fulminante (IHF) descritos en la literatura.
We report the case of a 37 year old woman who came to the hospital because of jaundice and a fever. Her symptoms were associated with significant liver impairment and a necroinflammatory pattern due to viral hepatitis B although she had no relevant medical history. Her symptoms developed rapidly until death. We present the factors that may have influenced her progression to fulminant liver failure as described in the literature.