328 research outputs found

    Bioprosthetic Aortic Valve degeneration: a review from a basic science perspective

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    Introduction: The increase in the prevalence of aortic stenosis due to an aging population has led to an increasing number of surgical aortic valve replacements. Over the past 20 years, there has been a major shift in preference from mechanical to bioprosthetic valves. However, despite efforts, there is still no "ideal" bioprosthesis. It is crucial to understand the structure, biology, and function of native heart valves to design more intelligent, strong, durable, and physiological heart valve tissues. Methods: A comprehensive review of the literature was performed to identify articles reporting the basic mechanisms of bioprosthetic valve dysfunction and the biology of native valve cells. Searches were run in PubMed,MEDLINE (R) (the Medical Literature Analysis and Retrieval System Online), and Google Scholar. Terms for subject heading and keywords search included "biological heart valve dysfunction", "bioprosthesis dysfunction", "bioprosthesis degeneration", and "tissue heart valves". Results: All the relevant findings are summarized in the appropriate subsections. Structural dysfunction is a logical and expected consequence of the chemical, mechanical, and immunological processes that occur during fixation, manufacture, and implantation. Conclusion: Biological prosthesis valve dysfunction is a clinically significant process. It has become a major issue considering the growing rate of bioprosthesis implantation and improved long-term patient survival. Understanding bioprosthetic aortic valve degeneration from a basic science perspective is a key point to improve technologic advances and specifications that lead to a new generation of bioprostheses.info:eu-repo/semantics/publishedVersio

    Expressão da progranulina durante os primeiros estágios de desenvolvimento hepático em ratos Fischer 344

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    Transplants are the only effective therapy for the treatment of advanced liver diseases such as cirrhosis. Given the limited number of organ donors, regenerative medicine has sought for sources of cells and tissues for replacement therapy. Embryonic stem cells are a promising source of material for transplantation because of their exclusive property of being expanded indefinitely in culture, thus, they are a source of replacement tissue. Moreover, they are capable of differentiating into practically all cell types, and may be utilized in replacement therapy in various diseases. The liver bud has bipotent stem cells that have not yet differentiated into hepatocytes or biliary duct cells; however, they have great potential of proliferation and differentiation. Thus, the challenge is to identify methods that promote their differentiation in specific and functional strains. This study aimed to evaluate the role of the progranulin growth factor PGRN during the liver development of rats F344, since this growth factor could be utilized in protocols of differentiation of stem cells of the liver bud in functional hepatocytes. The results showed that PGRN is present during different periods of hepatogenesis in F344 rats, and that this growth factor should be involved in the process of differentiation of hepatoblasts into hepatocytes after activation by HNF4α , however, PGRN seems not to exert a cellular proliferation function during the hepatogenesis. Thus, PGRN can be used in future protocols of liver cell differentiation directed toward cellular therapy in Regenerative Medicine.Os transplantes são a única terapia eficaz para o tratamento de doenças hepáticas avançadas, como a cirrose. Dado o número limitado de doadores de órgãos, a medicina regenerativa tem procurado fontes de células para a terapia de substituição. As células embrionárias são uma fonte promissora de material para o transplante devido à sua propriedade exclusiva de ser expandida indefinidamente em cultura, assim, elas são uma fonte de tecido de substituição. Além disso, são capazes de se diferenciar em praticamente todos os tipos celulares, e podem ser utilizadas na terapia de substituição em várias doenças. O broto hepático tem células-tronco (CT) bipotenciais que ainda não se diferenciam em hepatócitos ou células do ducto biliar, contudo, elas têm um grande potencial de proliferação e de diferenciação. Desse modo, o desafio é identificar métodos que promovam sua diferenciação em linhagens específicas e funcionais. Este estudo teve como objetivo avaliar o papel do fator de crescimento progranulina (PGRN) durante o desenvolvimento hepático em ratos F344, uma vez que a PGRN poderia ser utilizada em protocolos de diferenciação de CT do broto hepático em hepatócitos funcionais. Os resultados mostraram que PGRN está presente durante diferentes períodos da hepatogênese em ratos F344, e que a mesma deve estar envolvida no processo de diferenciação de hepatoblastos em hepatócitos após ativação por HNF4α, no entanto, a PGRN parece não desempenhar uma função de proliferação celular durante a hepatogênese. Assim, a PGRN pode ser usada em futuros protocolos de diferenciação de células hepáticas voltadas para a terapia celular na medicina regenerativa

    Morphological evaluation of fetal membranes and placenta of wild life Mazama gouazoubira deer in the first third of pregnancy

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    Mazama gouazoubira, o veado-catingueiro, é uma espécie de cervídeo de porte pequeno, que pode ser encontrado na América do Sul, desde o sul do Uruguai até o norte de Mato Grosso, no Brasil. Este estudo teve como objetivo descrever as membranas fetais e a placenta de M. gouazoubira no terço inicial de gestação. As amostras coletadas foram analisadas macroscopicamente e microscopicamente. O exame do útero demonstrou uma gestação univitelina e um embrião com crown-rump de 13mm. Na análise do embrião pode ser observado o olho pigmentado, as saliências auriculares, o mesonefro e e metanefro em desenvolvimento, o fígado e sua proeminência externa, o estômago, os membros torácicos e os brotos dos membros pélvicos. A placenta apresentou-se oligocotiledonária e no útero puderam ser observadas nove carúnculas. O saco gestacional mediu 15cm de comprimento e, como observado no início da gestação dos ruminantes domésticos, os cotilédones não puderam ser identificados macroscopicamente. Uma fraca adesão foi observada entre as carúnculas e a membrana corioalantóica (cotilédones) que formavam os placentônios. A membrana corioalantóica demonstrou um alantóide bem vascularizado composto por uma fina camada de células de núcleos e citoplasmas alongados. Na outra face da membrana, o cório foi composto por células cúbicas, de citoplasmas escassos e núcleos grandes e arredondados, características de células trofoblásticas. Envolvendo o embrião visualizou-se o saco amniótico constituído de duas camadas passíveis de separação mecânica, que apresentaram morfologia similar, sendo formadas por um epitélio pavimentoso avascular. Não foi observado saco vitelino no estágio gestacional do espécime estudado. Conclui-se que a placenta de M. gouazoubira é oligocotiledonária, como observado em outros cervídeos, e que as membranas fetais apresentam semelhanças com a de outros ruminantes, incluindo as características citológicas. Estudos adicionais são necessários para determinar a presença do saco vitelino e quando ocorre sua regressão.Mazama gouazoubira is a small-sized deer, which can be found in South America, from southern Uruguay to the north of Mato Grosso, Brazil. This study aimed to describe the fetal membranes and placenta of M. gouazoubira in the first third of pregnancy. Samples collected were macroscopically and microscopically analyzed. Uterus examination demonstrated univitelinic gestation with an embryo measuring a crown-rump length of 13mm. In the embryo analysis we could identify the pigmented eye, auricular hillocks, mesonephron and early metanephron, liver and its external prominence, stomach, thoracic members and buds of pelvic members. Placenta was oligocotyledonary and nine caruncles were found in the uterus. Gestational sac measured 15cm in length, and, as observed in the early gestation of domestic ruminants, cotyledons could not be identified macroscopically. A weak adhesion was found between caruncles and chorioallantoic membrane (cotyledons) forming the placentomes. The chorioallantoic membrane showed a well-vascularized allantoid composed by a thin layer of cells with stretched nucleus and cytoplasm. On the other side of the membrane, the chorion was composed by cubic cells with scant cytoplasm and large-rounded nuclei, features of trophoblast cells. Involving the embryo we identified a two-layered amniotic sac. Layers could be mechanically separated and had similar morphology, showing a non-vascularized squamous epithelium. There was no yolk sac in the gestational stage of this specimen. We concluded that the placenta of M. gouazoubira is an oligocotyledonary placenta, as observed in others cervids, and that the fetal membranes showed similarities with those from other domestic ruminants, including cytological characteristics. Further studies are required in order to determine the presence of the yolk sac and its regression time

    Effects of 2 or 5 consecutive exercise days on adipocyte area and lipid parameters in Wistar rats

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    <p>Abstract</p> <p>Background</p> <p>Exercise has been prescribed in the treatment and control of dyslipidemias and cholesterolemia, however, lipid responses to different training frequencies in hypercholesterolemic men have been inconsistent. We sought to verify if different frequencies of continuous moderate exercise (2 or 5 days/week, swimming) can, after 8 weeks, promote adaptations in adipocyte area and lipid parameters, as well as body weight and relative weight of tissues in normo and hypercholesterolemic adult male rats.</p> <p>Methods</p> <p>Normal cholesterol chow diet or cholesterol-rich diet (1% cholesterol plus 0.25% cholic acid) were freely given during 8 weeks to the rats divided in 6 experimentals groups: sedentary normal cholesterol chow diet (C); sedentary cholesterol-rich diet (H); 5× per week continuous training normal cholesterol chow diet (TC5) and cholesterol-rich diet (TH5); 2× per week continuos traning normal cholesterol chow diet (TC2) and cholesterol-rich diet (TH2).</p> <p>Results</p> <p>No changes were observed in lipid profile in normal cholesterol chow diet, but both 2 a 5 days/week exercise improved this profile in cholesterol-rich diet. Body weight gain was lower in exercised rats. Decrease in retroperitoneal and epididymal relative weights as well as reductions in adipocyte areas under all diets types were observed only in 5 days/week, while 2 days/week showed improvements mainly in cholesterol-rich diet rats.</p> <p>Conclusion</p> <p>Our results confirm the importance of exercise protocols to control dyslipidemias and obesity in rats. The effects of 5 days/week exercise were more pronounced compared with those of 2 consecutive days/week training.</p

    In Vitro Murine Lymphoma L5178y-R Cells Growth Inhibition By Endophytic Fungi Isolated From Lophocereus Marginatus

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    Background: Chemotherapy is one of the main treatments to fight cancer. However, about 90% of failures in this procedure are due to the invasion and metastasis of drug-resistant cancer cells. Therefore, the search for new drugs has become critical in oncology. Endophytic fungi, as important sources of bioactive compounds, represent an alternative for the isolation, characterization, and development of new pharmacological treatments for cancer control. The aim of the present study was to evaluate the cytotoxic activity of liquid culture extracts of endophytic fungi isolated from Lophocereus marginatus against murine lymphoma L5178Y-R cells. Methods: Endophytic fungi obtained from L. marginatus stems were isolated and morphologically characterized. Aqueous, methanolic, and ethyl acetate extracts were obtained from fungal liquid cultures. To evaluate the anticancer activity, we used tumor L5178Y-R cells and control peripheral blood mononuclear cells (PBMCs). Extracts were evaluated at 250 and 25 µg/mL and 250 µg/mL, using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide) colorimetric reduction assay to determine cytotoxicity. Vincristine and 1% DMSO were used as positive and negative controls, respectively. The IC50 value and selectivity index (SI) were determined only for the extracts that presented the highest antitumor activity. These isolates were molecularly identified from sequencing of the spacer region of the ribosomal DNA internal transcript (ITS). A metabolite production curve was performed with selected isolates to determine the time of the highest antitumor activity. Results: Ten endophytic fungi from L. marginatus were isolated and morphologically characterized. Results showed that aqueous extracts presented lower lymphoma cells growth inhibition (\u3c 50%) at the highest concentration evaluated (250 µg/mL), as compared with ethyl acetate and methanolic extracts, which showed up to 93.4% and 94.3% cells growth inhibition, respectively. Ten extracts with \u3e 80% tumor cells growth inhibition were selected and evaluated at 250 µg/mL on PBMCs viability. Extracts showing less than 50% cytotoxicity to PBMCs were selected and IC50 and IS were determined. Strain PME-H005 presented the highest toxicity against L5178Y-R cells and the highest SI with IC50 of 39.7 µg/mL and IS \u3e 6.2, as compared with PBMCs. Four isolates that showed the highest antitumor activity were molecularly identified, corresponding to the species Penicillium citrinum, Aspergillus versicolor, Metarhizium anisopliae, and Cladosporium sp. When performing the metabolite production curve, it was observed that only A. versicolor PME-H005 and M. anisopliae PME-H007 strains retained antitumor activity, where the ethyl acetate extracts showed the highest activity with IC50 values of 23.2 µg/ mL (28 d) for the PME-H005 strain and 2.7 µg/mL (21 d) for PME-H007. Conclusions: A. versicolor PME-H005 and M. anisopliae PME-H007 strains extracts showed significant antitumor activity against L5178Y-R lymphoma cells. Further research is required to characterize bioactive compounds responsible for this activity

    Role of omega-6 fatty acid metabolism in cardiac surgery postoperative bleeding risk

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    Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.Cardiac surgery is frequently associated with significant postoperative bleeding. Platelet-dysfunction is the main cardiopulmonary bypass (CPB)-induced hemostatic defect. Not only the number of platelets decreases, but also the remaining are functionally impaired. Although lipid metabolism is crucial for platelet function, little is known regarding platelet metabolic changes associated with CPB-dysfunction. Our aim is to explore possible contribution of metabolic perturbations for platelet dysfunction after cardiac surgery. Design: Prospective cohort study. Setting: Tertiary academic cardiothoracic-surgery ICU. Patients: Thirty-three patients submitted to elective surgical aortic valve replacement. Interventions: Samples from patients were collected at three time points (preoperative, 6- and 24-hr postoperative). Untargeted metabolic analysis using high-performance liquid chromatography-tandem mass spectrometry was performed to compare patients with significant postoperative bleeding with patients without hemorrhage. Principal component analyses, Wilcoxon matched-pairs signed-rank tests, adjusted to FDR, and pairwise comparison were used to identify pathways of interest. Enrichment and pathway metabolomic complemented the analyses. Measurements and main results: We identified a platelet-related signature based on an overrepresentation of changes in known fatty acid metabolism pathways involved in platelet function. We observed that arachidonic acid (AA) levels and other metabolites from the pathway were reduced at 6 and 24 hours, independently from antiagreggation therapy and platelet count. Concentrations of preoperative AA were inversely correlated with postoperative chest tube blood loss but were not correlated with platelet count in the preoperative, at 6 or at 24 hours. Patients with significant postoperative blood-loss had considerably lower values of AA and higher transfusion rates. Values of postoperative interleukin-6 were strongly correlated with AA variability. Conclusions and relevance: Our observations suggest that an inflammatory-related perturbation of AA metabolism is a signature of cardiac surgery with CPB and that preoperative levels of AA may be more relevant than platelet count to anticipate and prevent postoperative blood loss in patients submitted to cardiac surgery with CPB.info:eu-repo/semantics/publishedVersio
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