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1.
Soft Matter ; 19(16): 2993-3001, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37016959

RESUMO

Cell migration is a physical process central to life. Among others, it regulates embryogenesis, tissue regeneration, and tumor growth. Therefore, understanding and controlling cell migration represent fundamental challenges in science. Specifically, the ability of cells to follow stiffness gradients, known as durotaxis, is ubiquitous across most cell types. Even so, certain cells follow positive stiffness gradients while others move along negative gradients. How the physical mechanisms involved in cell migration work to enable a wide range of durotactic responses is still poorly understood. Here, we provide a mechanistic rationale for durotaxis by integrating stochastic clutch models for cell adhesion with an active gel theory of cell migration. We show that positive and negative durotaxis found across cell types are explained by asymmetries in the cell adhesion dynamics. We rationalize durotaxis by asymmetric mechanotransduction in the cell adhesion behavior that further polarizes the intracellular retrograde flow and the protruding velocity at the cell membrane. Our theoretical framework confirms previous experimental observations and explains positive and negative durotaxis. Moreover, we show how durotaxis can be engineered to manipulate cell migration, which has important implications in biology, medicine, and bioengineering.


Assuntos
Mecanotransdução Celular , Adesão Celular , Movimento Celular , Membrana Celular
2.
Catheter Cardiovasc Interv ; 87(2): 262-9, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26213338

RESUMO

OBJECTIVE: Functional assessment of coronary artery stenosis is performed by measuring the fractional flow reserve (FFR) under hyperemic conditions (Adenosine). However, the use of adenosine portends limitations. OBJECTIVE: We sought to investigate the relationship and correlation between FFR and the Pd/Pa value obtained just after the intracoronary infusion (acute drop) of nitroglycerin (Pd/Pa-NTG) and if this parameter enhances diagnostic accuracy for FFR prediction compared to the resting baseline Pd/Pa. METHODS: We conducted a multicenter study including prospectively patients presenting intermediate coronary artery stenosis (30-70%) evaluated with pressure wire. Resting baseline Pd/Pa, Pd/Pa-NTG and FFR were measured. RESULTS: 283 patients (335 lesions) were included. Resting baseline Pd/Pa value was 0.72 to 1.0 (0.93 ± 0.04), Pd/Pa-NTG was 0.60 to 1.0 (0.87 ± 0.07) and FFR 0.55 to 1.0 (0.83 ± 0.08). The ROC curves for resting baseline Pd/Pa and for Pd/Pa-NTG, using a FFR ≤ 0.80 showed an AUC of 0.88 (95% CI: 0.84-0.92, P < 0.001) and 0.94 (95% CI: 0.92-0.96, P < 0.001) respectively. The optimal cutoff values of resting baseline Pd/Pa and Pd/Pa-NTG for an FFR > 0.80, were >0.96 and >0.88, respectively. These values were present in a 29.8% (n = 100) and a 47.1% (n = 158), of the total lesions. Scatter plots showed a better correlation and agreement points with Pd/Pa-NTG than resting baseline Pd/Pa. The cutoff value of Pd/Pa-NTG > 0.88 showed an excellent NPV (96.2% for FFR > 0.8 and 100% for FFR > 0.75) and sensitivity (95% for FFR > 0.8 and 100% for FFR > 0.75) which were consistently high across all the subgroups analysis. CONCLUSION: The cutoff value of acute Pd/Pa-NTG > 0.88 has a high NPV meaning adenosine-FFR can be avoided in almost half of lesions.


Assuntos
Adenosina/administração & dosagem , Pressão Arterial , Cateterismo Cardíaco , Estenose Coronária/diagnóstico , Vasos Coronários/fisiopatologia , Reserva Fracionada de Fluxo Miocárdico , Nitroglicerina/administração & dosagem , Vasodilatadores/administração & dosagem , Idoso , Área Sob a Curva , Velocidade do Fluxo Sanguíneo , Angiografia Coronária , Estenose Coronária/fisiopatologia , Vasos Coronários/diagnóstico por imagem , Feminino , Humanos , Hiperemia/fisiopatologia , Infusões Intra-Arteriais , Masculino , Microcirculação , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Espanha , Procedimentos Desnecessários
3.
J Theor Biol ; 379: 16-23, 2015 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-25956359

RESUMO

Endothelial cells are key units in the regulatory biological process of blood vessels. They represent an interface to transmit variations on the fluid dynamic changes. They are able to adapt its cytoskeleton, by means of microtubules reorientation and F-actin reorganization, due to new mechanical environments. Moreover, they are responsible for initiating a huge cascade of biological processes, such as the release of endothelins (ET-1), in charge of the constriction of the vessel and growth factors such as TGF-ß and PDGF. Although a huge efforts have been made in the experimental characterization and description of these two issues the computational modeling has not gained such an attention. In this work we study the 3D remodeling of endothelial cells based on the main features of blood flow. In particular we study how different oscillatory shear index and the time average wall shear stresses modify the endothelial cell shape. We found our model fitted the experimental works presented before in in vitro studies. We also include our model within a computational fluid dynamics simulation of a carotid artery to evaluate endothelial cell shape index which is a key predictor of atheroma plaque formation. Moreover, our approach can be coupled with models of collagen and smooth muscle cell growth, where remodeling and the associated release of chemical substance are involved.


Assuntos
Células Endoteliais/metabolismo , Modelos Cardiovasculares , Actinas/metabolismo , Animais , Células Endoteliais/citologia , Endotelina-1/metabolismo , Humanos , Microtúbulos/metabolismo , Fator de Crescimento Transformador beta/metabolismo
4.
Hepatogastroenterology ; 60(128): 1839-40, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24719916

RESUMO

The hepatocellular carcinoma (HCC) is the fifth most frequent tumor in the world, and the third cause of death related to cancer. Histological samples obtained from diseased liver likely to have HCC are currently prescribed in selected patients in whose imaging studies and tumor markers are not sufficient for the diagnosis. In recent years, a risk of tumoral seeding along needle tract of FNAC to obtain histological samples has been reported. We present a case of tumor implantation of HCC cells in the needle tract, a year and four months after a percutaneous fine needle aspiration cytology (FNAC).


Assuntos
Biópsia por Agulha Fina/efeitos adversos , Carcinoma Hepatocelular/secundário , Neoplasias Hepáticas/patologia , Inoculação de Neoplasia , Neoplasias de Tecidos Moles/secundário , Idoso , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Reoperação , Neoplasias de Tecidos Moles/cirurgia , Fatores de Tempo , Resultado do Tratamento
5.
Biomaterials ; 301: 122273, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37639974

RESUMO

Local mechanical tissue properties are a critical regulator of cell function in the central nervous system (CNS) during development and disorder. However, we still don't fully understand how the mechanical properties of individual tissue constituents, such as cell nuclei or myelin, determine tissue mechanics. Here we developed a model predicting local tissue mechanics, which induces non-affine deformations of the tissue components. Using the mouse hippocampus and cerebellum as model systems, we show that considering individual tissue components alone, as identified by immunohistochemistry, is not sufficient to reproduce the local mechanical properties of CNS tissue. Our results suggest that brain tissue shows a universal response to applied forces that depends not only on the amount and stiffness of the individual tissue constituents but also on the way how they assemble. Our model may unify current incongruences between the mechanics of soft biological tissues and the underlying constituents and facilitate the design of better biomedical materials and engineered tissues. To this end, we provide a freely-available platform to predict local tissue elasticity upon providing immunohistochemistry images and stiffness values for the constituents of the tissue.


Assuntos
Encéfalo , Animais , Camundongos , Camundongos Endogâmicos C57BL , Materiais Biocompatíveis/química , Modelos Biológicos , Modelos Animais , Viscosidade , Elasticidade
6.
Nucleic Acids Res ; 36(Web Server issue): W523-8, 2008 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-18515346

RESUMO

In the last few years, advances in high-throughput technologies are generating large amounts of biological data that require analysis and interpretation. Nonnegative matrix factorization (NMF) has been established as a very effective method to reveal information about the complex latent relationships in experimental data sets. Using this method as part of the exploratory data analysis, workflow would certainly help in the process of interpreting and understanding the complex biology mechanisms that are underlying experimental data. We have developed bioNMF, a web-based tool that implements the NMF methodology in different analysis contexts to support some of the most important reported applications in biology. This online tool provides a user-friendly interface, combined with a computational efficient parallel implementation of the NMF methods to explore the data in different analysis scenarios. In addition to the online access, bioNMF also provides the same functionality included in the website as a public web services interface, enabling users with more computer expertise to launch jobs into bioNMF server from their own scripts and workflows. bioNMF application is freely available at http://bionmf.dacya.ucm.es.


Assuntos
Análise por Conglomerados , Biologia Computacional , Software , Algoritmos , Perfilação da Expressão Gênica , Internet
7.
Science ; 370(6514)2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33060332

RESUMO

The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. In this study, we found that cells measure the degree of spatial confinement by using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope. This activates signaling to the actomyosin cortex via nuclear envelope stretch-sensitive proteins, up-regulating cell contractility. We established that the tailored contractile response constitutes a nuclear ruler-based signaling pathway involved in migratory cell behaviors. Cells rely on the nuclear ruler to modulate the motive force that enables their passage through restrictive pores in complex three-dimensional environments, a process relevant to cancer cell invasion, immune responses, and embryonic development.


Assuntos
Mecanotransdução Celular , Membrana Nuclear/fisiologia , Actomiosina/metabolismo , Animais , Movimento Celular , Desenvolvimento Embrionário , Células HeLa , Humanos , Camundongos , Cadeias Pesadas de Miosina/metabolismo , Invasividade Neoplásica , Neoplasias/patologia
8.
R Soc Open Sci ; 6(6): 190607, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31312506

RESUMO

The glycocalyx has been identified as a key mechano-sensor of the shear forces exerted by streaming blood onto the vascular endothelial lining. Although the biochemical reaction to the blood flow has been extensively studied, the mechanism of transmission of the haemodynamic shear forces to the endothelial transmembrane anchoring structures and, consequently, to the subcellular elements in the cytoskeleton, is still not fully understood. Here we apply a multiscale approach to elucidate how haemodynamic shear forces are transmitted to the transmembrane anchors of endothelial cells. Wall shear stress time histories, as obtained from image-based computational haemodynamics models of a carotid bifurcation, are used as a load and a continuum model is applied to obtain the mechanical response of the glycocalyx all along the cardiac cycle. The main findings of this in silico study are that: (1) the forces transmitted to the transmembrane anchors are in the range of 1-10 pN, which is in the order of magnitude reported for the different conformational states of transmembrane mechanotranductors; (2) locally, the forces transmitted to the anchors of the glycocalyx structure can be markedly different from the near-wall haemodynamic shear forces both in amplitude and frequency content. The findings of this in silico approach warrant future studies focusing on the actual forces transmitted to the transmembrane mechanotransductors, which might outperform haemodynamic descriptors of disturbed shear as localizing factors of vascular disease.

9.
Eur J Mass Spectrom (Chichester) ; 14(3): 191-200, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18708699

RESUMO

The reliability of ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC- MS/MS) for high throughput screening in anti-doping control has been tested. A method to screen for the presence of diuretics and other doping agents in urine has been optimised and validated. The extraction procedure consisted of an alkaline extraction (pH 9.5) with ethyl acetate and salting-out effect (sodium chloride). The extracts were analysed by UPLC-MS/MS. Analysis of 34 forbidden drugs and metabolites was achieved in a total run time of 5 min, using a C18 column (100 mm x 2.1 mm i.d., 1.7 microm particle size) and a mobile phase containing deionised water and acetonitrile with formic acid, with gradient elution at a flow-rate of 0.6 mL min(-1). Identification of the compounds was performed by multiple reaction monitoring, using electrospray ionisation in positive- or negative-ion mode. Precursor and product ions were studied for each compound and cone voltage and collision energy were optimised. Due to the different chemical structure of the compounds under study, extraction recoveries varied from less than 10% to 100% depending on the analyte. The limits of detection ranged from 50 ng mL(-1) to 200 ng mL(-1), and all the compounds comply with the requirements of quality established by the World Anti-doping Agency. Intra-assay precision was evaluated at two concentrations for each compound and, in most cases, a relative standard deviation of the signal ratio lower than 20% was obtained. The method has demonstrated to be reliable when analysing routine samples and the short analysis time resulting from a simple sample preparation and a rapid instrumental analysis allow a fast turn-around time and makes it of great interest for routine anti-doping control purposes.


Assuntos
Estimulantes do Sistema Nervoso Central/urina , Diuréticos/urina , Dopagem Esportivo , Espectrometria de Massas por Ionização por Electrospray/métodos , Detecção do Abuso de Substâncias/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray/instrumentação
10.
Sci Rep ; 8(1): 9436, 2018 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-29930304

RESUMO

This study is a comparison of the efficiency of three technologies used for Y chromosome capture and the next-generation sequencing (NGS) technologies applied for determining its whole sequence. Our main findings disclose that streptavidin-biotin magnetic particle-based capture methodology offers better and a deeper sequence coverage for Y chromosome capture, compared to chromosome sorting and microdissection procedures. Moreover, this methodology is less time consuming and the most selective for capturing only Y chromosomal material, in contrast with other methodologies that result in considerable background material from other, non-targeted chromosomes. NGS results compared between two platforms, NextSeq 500 and SOLID 5500xl, produce the same coverage results. This is the first study to explore a methodological comparison of Y chromosome capture and genetic analysis. Our results indicate an improved strategy for Y chromosome research with applications in several scientific fields where this chromosome plays an important role, such as forensics, medical sciences, molecular anthropology and cancer sciences.


Assuntos
Cromossomos Humanos Y/genética , Citometria de Fluxo/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Microdissecção e Captura a Laser/métodos , Análise de Sequência de DNA/métodos , Células Cultivadas , Cromossomos Humanos Y/química , Humanos , Masculino
11.
Ann Biomed Eng ; 45(4): 1039-1047, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27913950

RESUMO

Fingertips wrinkle due to long exposure to water. The biological reason for this morphological change is unclear and still not fully understood. There are two main hypotheses for the underlying mechanism of fingertip wrinkling: the 'shrink' model (in which the wrinkling is driven by the contraction of the lower layers of skin, associated with the shrinking of the underlying vasculature), and the 'swell' model (in which the wrinkling is driven by the swelling of the upper layers of the skin, associated with osmosis). In reality, contraction of the lower layers of the skin and swelling of the upper layers will happen simultaneously. However, the relative importance of these two mechanisms to drive fingertip wrinkling also remains unclear. Simulating the swelling in the upper layers of skin alone, which is associated with neurological disorders, we found that wrinkles appeared above an increase of volume of [Formula: see text] Therefore, the upper layers can not exceed this swelling level in order to not contradict in vivo observations in patients with such neurological disorders. Simulating the contraction of the lower layers of the skin alone, we found that the volume have to decrease a [Formula: see text] to observe wrinkles. Furthermore, we found that the combined effect of both mechanisms leads to pronounced wrinkles even at low levels of swelling and contraction when individually they do not. This latter results indicates that the collaborative effect of both hypothesis are needed to induce wrinkles in the fingertips. Our results demonstrate how models from continuum mechanics can be successfully applied to testing hypotheses for the mechanisms that underly fingertip wrinkling, and how these effects can be quantified.


Assuntos
Dedos , Modelos Biológicos , Envelhecimento da Pele , Pele/metabolismo , Pele/fisiopatologia , Humanos , Osmose , Pele/patologia
12.
Redox Biol ; 12: 274-284, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28282615

RESUMO

MLN64 is a late endosomal cholesterol-binding membrane protein that has been implicated in cholesterol transport from endosomal membranes to the plasma membrane and/or mitochondria, in toxin-induced resistance, and in mitochondrial dysfunction. Down-regulation of MLN64 in Niemann-Pick C1 deficient cells decreased mitochondrial cholesterol content, suggesting that MLN64 functions independently of NPC1. However, the role of MLN64 in the maintenance of endosomal cholesterol flow and intracellular cholesterol homeostasis remains unclear. We have previously described that hepatic MLN64 overexpression increases liver cholesterol content and induces liver damage. Here, we studied the function of MLN64 in normal and NPC1-deficient cells and we evaluated whether MLN64 overexpressing cells exhibit alterations in mitochondrial function. We used recombinant-adenovirus-mediated MLN64 gene transfer to overexpress MLN64 in mouse liver and hepatic cells; and RNA interference to down-regulate MLN64 in NPC1-deficient cells. In MLN64-overexpressing cells, we found increased mitochondrial cholesterol content and decreased glutathione (GSH) levels and ATPase activity. Furthermore, we found decreased mitochondrial membrane potential and mitochondrial fragmentation and increased mitochondrial superoxide levels in MLN64-overexpressing cells and in NPC1-deficient cells. Consequently, MLN64 expression was increased in NPC1-deficient cells and reduction of its expression restore mitochondrial membrane potential and mitochondrial superoxide levels. Our findings suggest that MLN64 overexpression induces an increase in mitochondrial cholesterol content and consequently a decrease in mitochondrial GSH content leading to mitochondrial dysfunction. In addition, we demonstrate that MLN64 expression is increased in NPC cells and plays a key role in cholesterol transport into the mitochondria.


Assuntos
Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Colesterol/metabolismo , Fígado/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mitocôndrias/fisiologia , Doenças de Niemann-Pick/metabolismo , Animais , Células CHO , Cricetulus , Dependovirus/genética , Vetores Genéticos/administração & dosagem , Glutationa/metabolismo , Células Hep G2 , Humanos , Fígado/citologia , Potencial da Membrana Mitocondrial , Camundongos , Mitocôndrias/metabolismo , Doenças de Niemann-Pick/genética , Doenças de Niemann-Pick/fisiopatologia , Superóxidos/metabolismo
13.
Comput Methods Biomech Biomed Engin ; 19(10): 1107-15, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26583449

RESUMO

Myocardial infarction, commonly known as heart attack, is caused by reduced blood supply and damages the heart muscle because of a lack of oxygen. Myocardial infarction initiates a cascade of biochemical and mechanical events. In the early stages, cardiomyocytes death, wall thinning, collagen degradation, and ventricular dilation are the immediate consequences of myocardial infarction. In the later stages, collagenous scar formation in the infarcted zone and hypertrophy of the non-infarcted zone are auto-regulatory mechanisms to partly correct for these events. Here we propose a computational model for the short-term adaptation after myocardial infarction using the continuum theory of multiplicative growth. Our model captures the effects of cell death initiating wall thinning, and collagen degradation initiating ventricular dilation. Our simulations agree well with clinical observations in early myocardial infarction. They represent a first step toward simulating the progression of myocardial infarction with the ultimate goal to predict the propensity toward heart failure as a function of infarct intensity, location, and size.


Assuntos
Simulação por Computador , Modelos Cardiovasculares , Infarto do Miocárdio/patologia , Morte Celular , Colágeno/metabolismo , Ventrículos do Coração/patologia , Humanos , Miocárdio/patologia , Miócitos Cardíacos/patologia
14.
Acta Biomater ; 33: 183-93, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26827780

RESUMO

BACKGROUND: Mechanical characteristics of vascular tissue may play a role in different arterial pathologies, which, amongst others, requires robust constitutive descriptions to capture the vessel wall's anisotropic and non-linear properties.Specifically, the complex 3D network of collagen and its interaction with other structural elements has a dominating effect of arterial properties at higher stress levels.The aim of this study is to collect quantitative collagen organization as well as mechanical properties to facilitate structural constitutive models for the porcine carotid artery.This helps the understanding of the mechanics of swine carotid arteries, being a standard in clinical hypothesis testing, in endovascular preclinical trials for example. METHOD: Porcine common carotid arteries (n=10) were harvested and used to (i) characterize the collagen fiber organization with polarized light microscopy, and (ii) the biaxial mechanical properties by inflation testing.The collagen organization was quantified by the Bingham orientation density function (ODF), which in turn was integrated in a structural constitutive model of the vessel wall.A one-layered and thick-walled model was used to estimate mechanical constitutive parameters by least-square fitting the recorded in vitro inflation test results.Finally, uniaxial data published elsewhere were used to validate the mean collagen organization described by the Bingham ODF. RESULTS: Thick collagen fibers, i.e.the most mechanically relevant structure, in the common carotid artery are dispersed around the circumferential direction.In addition, almost all samples showed two distinct families of collagen fibers at different elevation, but not azimuthal, angles.Collagen fiber organization could be accurately represented by the Bingham ODF (κ1,2,3=[13.5,0.0,25.2] and κ1,2,3=[14.7,0.0,26.6]; average error of about 5%), and their integration into a structural constitutive model captured the inflation characteristics of individual carotid artery samples.Specifically, only four mechanical parameters were required to reasonably (average error from 14% to 38%) cover the experimental data over a wide range of axial and circumferential stretches.However, it was critical to account for fibrilar links between thick collagen fibers.Finally, the mean Bingham ODF provide also good approximation to uniaxial experimental data. CONCLUSIONS: The applied structural constitutive model, based on individually measured collagen orientation densities, was able to capture the biaxial properties of the common carotid artery. Since the model required coupling amongst thick collagen fibers, the collagen fiber orientations measured from polarized light microscopy, alone, seem to be insufficient structural information. Alternatively, a larger dispersion of collagen fiber orientations, that is likely to arise from analyzing larger wall sections, could have had a similar effect, i.e. could have avoided coupling amongst thick collagen fibers. STATEMENT OF SIGNIFICANCE: The applied structural constitutive model, based on individually measured collagen orientation densities, was able to capture the biaxial and uniaxial properties of the common carotid artery. Since the model required coupling amongst thick collagen fibers, an effective orientation density that accounts for cross-links between the main collagen fibers has been porposed. The model provides a good approximation to the experimental data.


Assuntos
Artérias Carótidas/fisiologia , Colágeno/química , Modelos Cardiovasculares , Animais , Artérias Carótidas/anatomia & histologia , Feminino , Modelos Biológicos , Estresse Mecânico , Sus scrofa , Resistência à Tração
15.
Semergen ; 42(3): 152-7, 2016 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-25910605

RESUMO

OBJECTIVE: To assess therapeutic inertia (TI) in the management of type 2 diabetic patients (DM2), as regards glycemic and lipid control. MATERIALS AND METHODS: Two groups of patients were studied. Group 1: All the patients were older than 14 years, diagnosed with DM2 up to 28th February 2013, and their last determination of HbA1c was ≥ 8.5%. Group 2: All patients, under 60 years old, diagnosed with DM2 between the 1st January 2011 and the 31st December 2012, with no chronic complications and their last determination of HbA1c was ≥ 6.5%. RESULTS: Group 1: 253 patients were included (13% of DM2 diagnosed). TI was 43% for DM2, 83% for LDL cholesterol, and 80% for triglycerides. TI was lower (P=.037) in patients with HbA1c ≥ 10%. There was no difference in TI as regards the management of lipid profile depending on the HbA1c levels. Group 2: All DM2 patients (n=53) who met inclusion criteria were assessed (2.7% of DM2 diagnosed). Percentage of visits of those patients that had TI: 55% for DM2, 63% for LDL cholesterol and 64% for triglycerides. A more intense therapy was observed in patients with HbA1c>7.5% in 3 of the 5 visits made. CONCLUSIONS: TI in both groups was high and there is a lack of recording the reasons for this. It is important to improve the attitude of the professionals who care for the diabetic population.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Lipídeos/sangue , Padrões de Prática Médica/normas , Atenção Primária à Saúde/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude do Pessoal de Saúde , Glicemia/metabolismo , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade
16.
Artigo em Inglês | MEDLINE | ID: mdl-25643608

RESUMO

It is well known that biological tissues adapt their properties because of different mechanical and chemical stimuli. The goal of this work is to study the collagen turnover in the arterial tissue of hypertensive patients through a coupled computational mechano-chemical model. Although it has been widely studied experimentally, computational models dealing with the mechano-chemical approach are not. The present approach can be extended easily to study other aspects of bone remodeling or collagen degradation in heart diseases. The model can be divided into three different stages. First, we study the smooth muscle cell synthesis of different biological substances due to over-stretching during hypertension. Next, we study the mass-transport of these substances along the arterial wall. The last step is to compute the turnover of collagen based on the amount of these substances in the arterial wall which interact with each other to modify the turnover rate of collagen. We simulate this process in a finite element model of a real human carotid artery. The final results show the well-known stiffening of the arterial wall due to the increase in the collagen content.


Assuntos
Artérias Carótidas/metabolismo , Colágeno/metabolismo , Simulação por Computador , Hipertensão/metabolismo , Modelos Cardiovasculares , Artérias Carótidas/patologia , Fibroblastos/metabolismo , Análise de Elementos Finitos , Humanos , Hipertensão/patologia , Metaloproteinase 1 da Matriz/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Crescimento Transformador beta/metabolismo
17.
Free Radic Biol Med ; 30(4): 354-62, 2001 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-11182290

RESUMO

The effect of two naturally occurring thiols, such as cysteine and homocysteine, has been examined for their ability to induce deoxyribose degradation and DNA damage. Copper(II) ions have been added to incubation mixtures and oxygen consumption measurements have been performed in order to correlate the observed damaging effects with the rate of metal catalyzed thiol oxidation. Ascorbic acid plus copper has been used as a positive control of deoxyribose and DNA oxidation due to reactive oxygen species. Cysteine or homocysteine in the presence of copper ions induce the degradation of deoxyribose and the yield of 8-hydroxy-2'-deoxyguanosine (8-OHdG), although important differences are observed between the two thiols tested, homocysteine being less reactive than cysteine. DNA cleavage is induced by cysteine in the presence of copper(II) ions but not by homocysteine. Catalase and thiourea, but not superoxide dismutase (SOD), were shown to inhibit the damaging effects of cysteine on deoxyribose or DNA suggesting that H(2)O(2) and *OH radicals are responsible for the observed induced damage. The results indicate that there are differences between the damaging effects of the two thiols tested towards deoxyribose and DNA damage. The pathophysiological importance will be discussed.


Assuntos
Cisteína/farmacologia , Dano ao DNA/efeitos dos fármacos , Desoxiguanosina/análogos & derivados , Desoxirribose/metabolismo , Homocisteína/farmacologia , 8-Hidroxi-2'-Desoxiguanosina , Animais , Ácido Ascórbico/farmacologia , Catalase/química , Bovinos , Cobre/metabolismo , Desoxiguanosina/metabolismo , Eletroforese em Gel de Ágar , Oxirredução , Consumo de Oxigênio , Espécies Reativas de Oxigênio , Espectrofotometria , Superóxido Dismutase/química , Tioureia/química , Timo/química
18.
Euro Surveill ; 9(3): 27-30, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15075484

RESUMO

This work describes and analyses an outbreak of epidemic keratoconjunctivitis which occurred in 2001 and 2002 in a nursing home for the elderly in Leganes (an area of Madrid). This is the first such published case in Spain with these characteristics and this serotype identification. Sociodemographic characteristics, epidemic curve and attack rates are described. Comparisons of the data were carried out using a chi2 test for qualitative variable and t-test for quantitative. Factors associated with the illness are explored by means of contingency tables and logistic regression models. One hundred and two cases were detected, with an attack rate of 36.4% for residents, and 12.9% for workers, not considering spatial or professional differences. The epidemic curve showed an interpersonal transmission pattern. Multivariate analysis identified the following risk factors in the residents: able to wander freely through the building, urinary incontinence and use of shared bathroom. In 34.6% of the conjunctival samples, adenovirus serotype 8 was detected with identical genomic sequence. Establishment of hygienic sanitary guidance adapted for the cleaning of such establishments and contact with residents as well as early diagnosis and good coordination of human and material resources are key factors in the prevention and control of these outbreaks in closed communities.


Assuntos
Infecções por Adenovirus Humanos/epidemiologia , Surtos de Doenças , Ceratoconjuntivite/epidemiologia , Infecções por Adenovirus Humanos/transmissão , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/genética , Adenovírus Humanos/isolamento & purificação , Adulto , Idoso de 80 Anos ou mais , DNA Viral/análise , Feminino , Instituição de Longa Permanência para Idosos , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional , Transmissão de Doença Infecciosa do Profissional para o Paciente , Ceratoconjuntivite/virologia , Modelos Logísticos , Masculino , Análise Multivariada , Casas de Saúde , Espanha
19.
Am J Vet Res ; 60(9): 1111-6, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10490081

RESUMO

OBJECTIVE: To compare pharmacokinetic variables of enrofloxacin (ENR) after IV administration in mice, rats, rabbits, sheep, and cows and to perform allometric analysis of ENR. ANIMALS: 47 mice, 5 rats, 5 rabbits, 5 sheep, and 5 cows. PROCEDURE: Serially obtained plasma samples were assayed for ENR concentration, using high-performance liquid chromatography. In vitro plasma protein binding was determined by ultrafiltration. Plasma ENR concentration versus time curves were fitted by use of nonlinear least-squared regression analysis. Pharmacokinetic variables were correlated further with body weight. RESULTS: In all species studied, the best fit was obtained for a two-compartment open model; ENR half-life ranged from 89 minutes in mice to 169 minutes in cows. Volume of distribution was large in all species studied, with values ranging from 10.5 L/kg in mice to 1.5 L/kg in sheep. Body clearance ranged from 68.1 ml/min/kg for mice to 4.6 ml/min/kg for sheep. Unbound ENR was found to be (mean +/- SD) 58+/-2, 50+/-6, 50+/-2, 31+/-2, and 40+/-3% in plasma of mice, rats, rabbits, sheep, and cows, respectively. The only pharmacokinetic variables that could be correlated with body weight were elimination half-life, clearance, and volume of distribution. Allometric exponents denoting proportionality of half-life, body clearance, and volume of distribution with body weight were 0.06, 0.82, and 0.90, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: An allometric approach could provide a suitable method for determining a scale for ENR pharmacokinetics among various mammalian species. This would faciliatate the administration of appropriate doses of ENR to all animals.


Assuntos
Anti-Infecciosos/farmacocinética , Antineoplásicos/farmacocinética , Bovinos/metabolismo , Fluoroquinolonas , Camundongos/metabolismo , Quinolonas/farmacocinética , Coelhos/metabolismo , Ratos/metabolismo , Ovinos/metabolismo , Animais , Anti-Infecciosos/sangue , Antineoplásicos/sangue , Área Sob a Curva , Peso Corporal , Cromatografia Líquida de Alta Pressão/veterinária , Enrofloxacina , Meia-Vida , Injeções Intravenosas/veterinária , Análise dos Mínimos Quadrados , Quinolonas/sangue , Análise de Regressão , Ultrafiltração
20.
Med Clin (Barc) ; 116(1): 1-5, 2001 Jan 13.
Artigo em Espanhol | MEDLINE | ID: mdl-11181252

RESUMO

BACKGROUND: The treatment of osteoporotic hip fracture requires the intervention of different medical specialties. The purpose of this study was to know the clinical profile of patients with an acute hip fracture referred for assessment and management to a geriatric assessment team (GAT) and the influence of this kind of geriatric care in their hospital outcome. PATIENTS AND METHOD: All patients 65 year-old or older admitted in a teaching hospital for a hip fracture in a 12 month period were included. The clinical, functional, cognitive and social status were assessed at admission and at discharge in both groups: the patients managed by the GAT and the patients that were not. The patients' characteristics of both groups were compared, and a multivariant analysis was applied to search the variables independently associated wit a better clinical course. RESULTS: On admission, the GAT patients (n = 202) were significantly (p < 0.05) older (84.4 vs 81.7 years), had more previous functional impairment (Barthel index 72 vs 79), more previous diseases (5.4 vs 3.3) and medications (3.2 vs 1.9), presented more frequency of cognitive impairment (52 vs 41%), of high surgical risk (54 vs 26%) and more need of social assistance at home (57 vs 38%) than non-referred patients (n = 200). At discharge, GAT patients had better functional status (Barthel index 38.5 vs 34), had been surgically treated (92 vs 84%), had received physiotherapy (83.7 vs 66.5%) and walked more (56.1% vs 33.8%) than others. In the multivariant analysis, the GAT intervention shows like an independent variable associated to higher frequency of surgical treatment (OR 4.21; CI, 2.80-6.34), to recovery of walking ability (OR, 8.26; CI, 5.23-13.04) and to receive more medical diagnosis (OR, 79.69; CI: 55.48-114.45). The GAT intervention was not associated to a longer hospital stay. CONCLUSIONS: The patients with hip fracture in acute phase required for management by a GAT are more complex than those who were not consulted. In these patients GAT intervention improve their clinical outcome and the efficiency of hospital admission.


Assuntos
Idoso Fragilizado , Enfermagem Geriátrica , Fraturas do Quadril/terapia , Avaliação de Processos e Resultados em Cuidados de Saúde , Idoso , Feminino , Hospitalização , Humanos , Masculino , Análise Multivariada , Espanha
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