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1.
Andrology ; 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37873918

RESUMO

BACKGROUND: The implications of SARS-CoV-2 infection on male fertility remain largely unknown. Besides their well-known pro- and anti-inflammatory actions, prostaglandins and polyamines are present in semen, where they play key roles in sperm quality. OBJECTIVES: To analyze semen parameters, oxidative profile and the seminal fluid prostaglandin and polyamine systems in samples collected from individuals without coronavirus disease 2019 diagnosis and men who recovered from coronavirus disease 2019. MATERIALS AND METHODS: This study compared semen collected from men without positive coronavirus disease 2019 diagnosis with samples obtained from individuals 1-6 months and 7-30 months post SARS-CoV-2 infection. Semen parameters, thiobarbituric acid reactive substances, cyclooxygenase 2 expression by fluorescence immunocytochemistry and immunoblotting, prostaglandin levels by enzyme immunoassay, ornithine decarboxylase activity by a radioactive assay, and polyamine and acetylated polyamine levels by thin-layer chromatography were assessed. RESULTS: In both groups of semen samples from coronavirus disease 2019 recovered men, sperm vitality, total and progressive sperm motility, and putrescine levels were significantly decreased when compared with samples from the uninfected group. In contrast, lipid peroxidation, leukocyte-associated cyclooxygenase 2 expression, and prostaglandin D2 levels were higher in semen from coronavirus disease 2019 recovered men than in samples from uninfected individuals. While sperm concentration and morphology, ornithine decarboxylase activity, and N-acetylputrescine levels were statistically diminished in semen obtained up to 6 months after coronavirus disease 2019 recovery, these parameters remained unchanged when samples were collected 7-30 months after coronavirus disease 2019 recovery. Coronavirus disease 2019 vaccination did not show negative effects on any of the parameters evaluated. DISCUSSION AND CONCLUSION: Our work provides insights into the detrimental impact of coronavirus disease 2019 on several sperm parameters, in some cases, even more than a year after SARS-CoV-2 infection, which would be accompanied by alterations in the seminal fluid prostaglandin and polyamine profiles. Therefore, future treatments targeting the prostaglandin and polyamine pathways in coronavirus disease 2019 recovered men could lead to a successful reinstatement of semen parameters.

2.
Reprod Domest Anim ; 58(10): 1439-1447, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37603017

RESUMO

The identification of different morphometric patterns of spermatozoa serves as a basis for improving our understanding of the diversity in an ejaculate and to relate them to the potential fertility of males. In this study, we aimed to examine the semen subpopulation structure, following dilution in semen of extenders, using a mathematical approach a possible application to fertility analyses. Ten sexually mature Bos taurus bulls were randomly allotted to one of three groups: (1) Tris-citric acid-egg yolk extender (Tris-EY); (2) commercial egg yolk extender OptiXcell® and (3) commercial egg yolk extender Triladyl®. The results showed significant differences (p < .05) between extenders in terms of values for head size and head shape variables of individual sperm, indicating an influence of extender composition. Sperm head width was found to significantly differ (p < .05) according to the extender, decreasing in the following order: OptiXcell® (4.836 ± 0.017 µm), Triladyl® (4.695 ± 0.012 µm) and Tris-EY (4.638 ± 0.010 µm). Principal component analysis allowed us to identify two subpopulations in OptiXcell®, and three subpopulations were each found in Triladyl® and Tris-EY. Overall, we observed significant differences between sperm subpopulations within each extender (p < .05), with differences in sperm head size and shape between bovine species that can be related to functionality and fertility capabilities.

3.
BMC Public Health ; 23(1): 1507, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37559052

RESUMO

BACKGROUND: Evidence on all-cause mortality attributable to joint sitting time and physical inactivity is lacking. In this study, we estimated the proportion and number of deaths attributable to sitting time and physical inactivity in Chilean adults. METHODS: A sample of 5834 adults aged 20-96 years from a 2016-2017 Chilean National Health Survey was included to describe the prevalence of 16 joint categories of sitting time and physical activity. Relative risks for the joint association of sitting time and physical inactivity were obtained from a meta-analysis of individual participant data. We retrieved the number of deaths in adults ≥ 20 years in 2019 from the Chilean Ministry of Health. RESULTS: Participants with high sitting time (> 8 h/day) and low physical activity (< 2.5 MET-hour/week) were more likely to be women, 20-64 years, non-indigenous ethnicity, lived in the urban areas, had middle education level and monthly household income, and had public health insurance. Reducing sitting time and increasing physical activity to a theoretical minimum risk exposure level could prevent up to 11,470 deaths or 10.4% of all deaths. Increasing physical activity to >35.5 MET-hour/week and maintaining sitting time could prevent approximately 10,477 deaths or 9.5% of all deaths. Reducing sitting time to < 4 h/day and maintaining physical activity would not reduce the number of deaths (-3.4% or 38 deaths). CONCLUSION: Reducing sitting time may be ancillary for preventing mortality. Therefore, increasing physical activity should be the primary focus of interventions and policies in Chile.


Assuntos
Exercício Físico , Comportamento Sedentário , Adulto , Feminino , Humanos , Masculino , Chile/epidemiologia , Inquéritos Epidemiológicos , Fatores de Tempo , Adulto Jovem , Pessoa de Meia-Idade
4.
Animals (Basel) ; 13(10)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37238052

RESUMO

Artificial insemination in the swine industry, as in other species, demands adequate semen handling and accurate evaluation for the preparation of seminal doses. Sperm concentration and motility estimates are part of the semen evaluation process and are considered important for maximizing the yield of doses for insemination. In this study, methods were examined for their accuracy in the estimation of boar sperm concentration and motility. Assessments of sperm concentration were carried out using iSperm®, ISAS® v1, Open CASA v2, and the Accuread® photometer. Analyses of sperm motility were performed with iSperm®, ISAS® v1, and Open CASA v2 systems. In this study, boar semen samples were collected from 10 healthy males from two genetic lines. There were no relevant differences between sire lines when sperm concentration was assessed. A Bayesian analysis was applied to the four methods used to assess sperm concentration to examine whether there are relevant differences between them. Results suggested differences in the four methods, with a probability of relevance (PR) of 0.86-1.00. The iSperm® method revealed higher concentration values within the highest posterior density region at 95% confidence interval (HPD95%) = 167.0, 224.2 M/mL, whereas Open CASA v2 showed the lowest values, with HPD95% = 99.3, 155.9 M/mL. The iSperm® demonstrated higher reliability in measuring sperm concentration compared to other methods or devices within the given range of confidence. ANOVAs revealed relevant differences in the three methods of motility estimation. Overall, differences in boar sperm concentration and motility estimates were found using various methods, but further studies are needed for better characterization of these differences.

5.
Animals (Basel) ; 14(1)2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38200863

RESUMO

The objective of the present study was to determine the effects that the reproductive season has on the motility, kinematics, morphology, and sperm morphometry of Brahman bulls evaluated with a commercial CASA system. The experiment was carried out at the Costa Rica Institute of Technology from March to August 2021. A total of eight Brahman bulls were used. A total of 28 ejaculates were collected in the pre-mating period (PMP), during it (DMP), and after it (AMP) using an electroejaculator. The sperm concentration was measured with the Accuread photometer. The motility was measured using a Spermtrack® counting chamber. The analyses were performed with the CASA-Mot ISAS®v1 system. The morphology was analyzed using a microscope with a negative phase contrast objective. Morphometry was evaluated with the CASA-Morph. The sperm concentration did not present differences between the PMP and AMP; however, it was significantly higher than DMP (p > 0.05). Regarding the progressiveness variables, linearity on forward progression (LIN), straightness (STR), and wobble (WOB) were higher (p < 0.05) DMP. A kinematic principal component analysis grouped all the variables into three factors and an effect on the reproductive period was found (p < 0.05) in the parameters of the head and middle part of the sperm, such as width and perimeter, which were greater in the PMP. The length of the sperm head in the PMP and DMP did not show differences; however, both were larger (p < 0.05) than AMP. The insertion distance of the middle piece of the sperm was significantly greater than DMP. Finally, the PMP contained cells with a larger insertion angle (p < 0.05) than AMP. These findings are important to understand the implications of reproductive status on sperm quality and to consider them in andrological evaluations.

6.
Antibiotics (Basel) ; 11(10)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36289954

RESUMO

Multiple toothbrush designs have been developed to enhance dental biofilm removal and decrease bacterial contamination and retention over time. Therefore, the aim of this clinical study was to compare the efficacy of a prototype of a new double-sided thermoplastic polyurethane-based toothbrush with that of a conventional nylon-bristle toothbrush. A crossover study was conducted in systemically healthy volunteers (n = 24) for two one-week periods plus one washout week. As outcome variables, plaque and gingival indices, total bacterial contamination of the toothbrushes by quantitative polymerase chain reaction (qPCR), and patient-reported outcomes were measured. Clinical and microbiological variables were analysed using a general linear model and Friedman and Wilcoxon signed-rank tests. No statistically significant differences between toothbrushes were detected neither for full-mouth PlI (p > 0.05) nor for GI (p > 0.05). Similarly, no statistically significant differences were detected for bacterial contamination after 40 seconds or 1 week of use, with results expressed either in CFU/mL or in CFU/mm2 (p > 0.05). In conclusion, the tested prototype toothbrush was as effective and safe as the control toothbrush, and the participating subjects did not experience any adverse effects from its use and rated its efficiency and effectiveness in cleaning their teeth as satisfactory.

7.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166295, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34718118

RESUMO

Several organs, such as the heart, breasts, intestine, testes, and ovaries, have been reported to be target tissues of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To date, no studies have demonstrated SARS-CoV-2 infection in the female reproductive system. In the present study, we investigated the effects of SARS-CoV-2 infection on ovarian function by comparing follicular fluid (FF) from control and recovered coronavirus disease 2019 (COVID-19) patients and by evaluating the influence of these FF on human endothelial and non-luteinized granulosa cell cultures. Our results showed that most FFs (91.3%) from screened post COVID-19 patients were positive for IgG antibodies against SARS-CoV-2. Additionally, patients with higher levels of IgG against SARS-CoV-2 had lower numbers of retrieved oocytes. While VEGF and IL-1ß were significantly lower in post COVID-19 FF, IL-10 did not differ from that in control FF. Moreover, in COV434 cells stimulated with FF from post COVID-19 patients, steroidogenic acute regulatory protein (StAR), estrogen-receptor ß (Erß), and vascular endothelial growth factor (VEGF) expression were significantly decreased, whereas estrogen-receptor α (ERα) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) did not change. In endothelial cells stimulated with post COVID-19 FF, we observed a decrease in cell migration without changes in protein expression of certain angiogenic factors. Both cell types showed a significantly higher γH2AX expression when exposed to post COVID-19 FF. In conclusion, our results describe for the first time that the SARS-CoV-2 infection adversely affects the follicular microenvironment, thus dysregulating ovarian function.


Assuntos
COVID-19/metabolismo , COVID-19/virologia , Interações Hospedeiro-Patógeno , Ovário/metabolismo , Técnicas de Reprodução Assistida , SARS-CoV-2 , Adulto , Anticorpos Antivirais/imunologia , Biomarcadores , COVID-19/imunologia , Células Cultivadas , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Fertilidade , Líquido Folicular/metabolismo , Células da Granulosa/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunoglobulina G/imunologia , Oócitos/metabolismo , Adulto Jovem
8.
Rev. bras. cineantropom. desempenho hum ; 24: e87232, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1376505

RESUMO

abstract Flexibility is related to specific tissue properties of the body, which aim to determine the maximum range of motion of the joints without injury. This study aimed to identify and summarize the evidence on prevalence of adequate levels of flexibility in Brazilian children and adolescents (6 to 19 years old). We performed a systematic search of studies published from 2009 to 2019 in six databases (MEDLINE/PubMed; Scopus; SportDiscus; LILACS; Web of Science; SCIELO). Fourteen studies that compiled data from 11,666 participants in seven different Brazilian states were included. All studies conducted sit and reach tests to assess flexibility. Among all the children and adolescents in the analyzed studies, 58.9% of the total (62.0% of boys and 50.9% of girls) had adequate flexibility. We conclude that more than half of Brazilian children and adolescents have adequate flexibility for health.


resumo A flexibilidade está relacionada com propriedades específicas teciduais que permitem a amplitude máxima de movimento articular sem a presença de lesão. O presente estudo teve como objetivo identificar e sintetizar as evidências sobre a prevalência de níveis adequados de flexibilidade em crianças e adolescentes brasileiros (6 a 19 anos). Foi realizada uma busca sistematizada de estudos publicados de 2009 a 2019 em seis bases de dados (MEDLINE/PubMed; Scopus; SportDiscus; LILACS; Web of Science; SCIELO). Foram incluídos 14 estudos que compilaram dados de 11.666 participantes em sete estados brasileiros diferentes. Todos os estudos realizaram teste de sentar e alcançar para avaliar a flexibilidade. Dentre todas as crianças e adolescentes dos estudos analisados, 58,9% do total (62,0% dos meninos e 50,9% das meninas) apresentaram flexibilidade adequada. Concluímos que mais da metade das crianças e adolescentes brasileiros possuem flexibilidade adequada para a saúde.

9.
Mol Hum Reprod ; 26(8): 585-600, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32467982

RESUMO

Although advances in the prediction and management of ovarian hyperstimulation syndrome (OHSS) have been introduced, complete prevention is not yet possible. Previously, we and other authors have shown that vascular endothelial growth factor, angiopoietins (ANGPTs) and sphingosine-1-phosphate are involved in OHSS etiology. In addition, we have demonstrated that ovarian protein levels of platelet-derived growth factor (PDGF) ligands -B and -D decrease in an OHSS rat model, whilst PDGFR-ß and ANGPT2 remain unchanged. In the present work, we investigated the role of PDGF-B in OHSS by evaluating ligand protein levels in follicular fluid (FF) from women at risk of developing OHSS and by using an immature rat model of OHSS. We demonstrated that PDGF-B and PDGF-D are lower in FF from women at risk of developing OHSS compared to control patients (P < 0.05). In the OHSS rat model, PDGF-B (0.5 µg/ovary) administration decreased ovarian weight (P < 0.05), reduced serum progesterone (P < 0.05) and lowered the percentage of cysts (P < 0.05), compared to untreated OHSS rats, but had no effect on the proportion of follicles or corpora lutea (CL). PDGF-B treatment also restored the expression of steroidogenic acute regulatory protein (P < 0.05) and P450 cholesterol side-chain cleavage enzyme (P < 0.01) to control levels. In addition, PDGF-B increased the peri-endothelial cell area in CL and cystic structures, and reduced vascular permeability compared to untreated OHSS ovaries. Lastly, PDGF-B increased the levels of junction proteins claudin-5 (P < 0.05), occludin (P < 0.05) and ß-catenin (P < 0.05), while boosting the extracellular deposition of collagen IV surrounding the ovarian vasculature (PP < 0.01), compared to OHSS alone. In conclusion, our findings indicate that PDGF-B could be another crucial mediator in the onset and development of OHSS, which may lead to the development of novel prediction markers and therapeutic strategies.


Assuntos
Síndrome de Hiperestimulação Ovariana/tratamento farmacológico , Síndrome de Hiperestimulação Ovariana/metabolismo , Proteínas Proto-Oncogênicas c-sis/farmacologia , Proteínas Proto-Oncogênicas c-sis/uso terapêutico , Adulto , Animais , Western Blotting , Feminino , Humanos , Imuno-Histoquímica , Ratos Sprague-Dawley
10.
Mol Cell Endocrinol ; 499: 110591, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31546019

RESUMO

Metformin (MET) is the most widely prescribed hypoglycemic drug in type 2 diabetes and Polycystic Ovary Syndrome. Besides its effects on glucose metabolism, MET exerts beneficial effects on these patients' fertility. However, the exact mechanisms of action of MET on female fertility are still unclear. In this work, we analyzed a possible direct effect of MET on ovarian cells. We found expression of the organic cation transporters OCT1, OCT2 and OCT3, responsible for MET uptake into the cells, in rat granulosa cells and human cumulus cells. Furthermore, MET increased pAMPK and decreased VEGF levels both in vivo and in rat granulosa cells in culture. These last effects were reversed when OCTs were inhibited. Our results suggest that MET acts directly on ovarian cells regulating cell metabolism and VEGF expression. Our findings are relevant to optimize PCOS fertility treatment and to explore ovarian MET actions in other female pathologies.


Assuntos
Adenilato Quinase/metabolismo , Células do Cúmulo/citologia , Metformina/administração & dosagem , Fatores de Transcrição de Octâmero/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Animais , Proliferação de Células/efeitos dos fármacos , Células do Cúmulo/efeitos dos fármacos , Células do Cúmulo/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Metformina/farmacologia , Modelos Animais , Fosforilação/efeitos dos fármacos , Ratos
11.
Soft Matter ; 12(21): 4821-37, 2016 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-27127809

RESUMO

Coarse-graining (CG) of complex molecules is a method to reach time scales that would be impossible to access through brute force molecular simulations. In this paper, we formulate a coarse-grained model for complex molecules using first principles caculations that ensures energy conservation. Each molecule is described in a coarse way by a thermal blob characterized by the position and momentum of the center of mass of the molecule, together with its internal energy as an additional degree of freedom. This level of description gives rise to an entropy-based framework instead of the usual one based on the configurational free energy (i.e. potential of mean force). The resulting dynamic equations, which account for an appropriate description of heat transfer at the coarse-grained level, have the structure of the dissipative particle dynamics with energy conservation (DPDE) model but with a clear microscopic underpinning. Under suitable approximations, we provide explicit microscopic expressions for each component (entropy, mean force, friction and conductivity coefficients) appearing in the coarse-grained model. These quantities can be computed directly using MD simulations. The proposed non-isothermal coarse-grained model is thermodynamically consistent and opens up a first principles CG strategy for the study of energy transport issues that are not accessible using current isothermal models.

12.
Reprod Fertil Dev ; 28(6): 690-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25485810

RESUMO

Ovarian hyperstimulation syndrome (OHSS) is a complication of ovarian stimulation with gonadotrophins following human chorionic gonadotrophin (hCG) administration. The relationship between hCG and OHSS is partly mediated via the production of angiogenic factors, such as vascular endothelial growth factor A (VEGFA) and angiopoietins (ANGPTs). Here, we investigated the effect of ANGPT1 inhibition on ovarian angiogenesis in follicular fluid (FF) from women at risk of OHSS, using the chorioallantoic membrane (CAM) of quail embryos as an experimental model. We also analysed cytoskeletal changes and endothelial junction protein expression induced by this FF in the presence or absence of an ANGPT1-neutralising antibody in endothelial cell cultures. The presence of this antibody restored the number of vascular branch points and integrin αvß3 levels in the CAMs to control values. ANGPT1 inhibition in FF from OHSS patients also restored the levels of claudin-5, vascular endothelial cadherin and phosphorylated ß-catenin and partially reversed actin redistribution in endothelial cells. Our findings suggest that ANGPT1 increases pathophysiological angiogenesis in patients at risk of OHSS by acting on tight and adherens junction proteins. Elucidating the mechanisms by which ANGPT1 regulates vascular development and cell-cell junctions in OHSS will contribute to identifying new therapeutic targets for the treatment of human diseases with aberrant vascular leakage.


Assuntos
Junções Aderentes/metabolismo , Angiopoietina-1/metabolismo , Endotélio Vascular/metabolismo , Neovascularização Patológica/etiologia , Folículo Ovariano/metabolismo , Síndrome de Hiperestimulação Ovariana/fisiopatologia , Junções Íntimas/metabolismo , Junções Aderentes/efeitos dos fármacos , Junções Aderentes/patologia , Adulto , Angiopoietina-1/antagonistas & inibidores , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/farmacologia , Argentina/epidemiologia , Bioensaio , Biomarcadores/metabolismo , Linhagem Celular , Células Cultivadas , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/efeitos dos fármacos , Membrana Corioalantoide/metabolismo , Coturnix , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Feminino , Líquido Folicular/citologia , Líquido Folicular/metabolismo , Humanos , Folículo Ovariano/irrigação sanguínea , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/patologia , Síndrome de Hiperestimulação Ovariana/epidemiologia , Síndrome de Hiperestimulação Ovariana/metabolismo , Síndrome de Hiperestimulação Ovariana/patologia , Risco , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/patologia
13.
Mol Reprod Dev ; 81(8): 748-56, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24889290

RESUMO

Polycystic ovary syndrome (PCOS) is the most common endocrinological pathology among women of reproductive age, and is characterized by abnormalities in ovarian angiogenesis, among other features. Consistent with this association, follicular fluid (FF) concentration and ovarian expression of vascular endothelial growth factor (VEGF) are increased in PCOS patients. In this study, we examined the protein levels of platelet-derived growth factor (PDGF) BB and DD (PDGFBB and PDGFDD), angiopoietin 1 and 2 (ANGPT1 and ANGPT2), and their soluble receptor sTIE2 in FF from PCOS and control patients undergoing assisted reproductive techniques. We also analyzed the effect of FF from PCOS and control patients on tight and adherens junction protein expression in an endothelial cell line. PDGFBB and PDGFDD were significantly lower whereas ANGPT1 concentration was significantly higher in FF from PCOS patients than from control patients. No changes were found in the concentration of ANGPT2 or sTIE2. Expression of claudin-5 was significantly increased in endothelial cells incubated for 24 hr in the presence of FF from PCOS versus from control patients, while vascular-endothelial cadherin, ß-catenin, and zonula occludens 1 expression were unchanged. The changes observed in the levels of PDGF isoforms and ANGPT1 may prevent VEGF-induced vascular permeability in the PCOS ovary by regulating endothelial-cell-junction protein levels. Restoring the levels of angiogenic factors may provide new insights into PCOS treatment and the prevention of ovarian hyperstimulation syndrome in affected women.


Assuntos
Angiopoietina-1/metabolismo , Angiopoietina-2/metabolismo , Líquido Folicular/metabolismo , Ovário/metabolismo , Síndrome do Ovário Policístico/metabolismo , Proteínas Proto-Oncogênicas c-sis/metabolismo , Junções Aderentes/metabolismo , Adulto , Becaplermina , Western Blotting , Claudina-5/metabolismo , Células Endoteliais/metabolismo , Estradiol/metabolismo , Feminino , Humanos , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Progesterona/metabolismo , Radioimunoensaio , Técnicas de Reprodução Assistida , Junções Íntimas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
14.
Biol Reprod ; 89(1): 9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23699387

RESUMO

Ovarian granulosa cell tumors (GCTs) represent 3%-5% of all ovarian malignancies. Treatments have limited proven efficacy and biologically targeted treatment is lacking. The aim of this study was to investigate the role of Notch signaling in the proliferation, steroidogenesis, apoptosis, and phosphatidylinositol 3-kinase (PI3K)/AKT pathway in a FOXL2-mutated granulosa tumor cell line (KGN) representative of the adult form of GCTs. When Notch signaling is initiated, the receptors expose a cleavage site in the extracellular domain to the metalloproteinase TACE and, following this cleavage, Notch undergoes another cleavage mediated by the presenilin-gamma-secretase complex. To achieve our goal, DAPT, an inhibitor of the gamma-secretase complex, was used to investigate the role of the Notch system in parameters associated with cell growth and death, using a human granulosa cell tumor line (KGN) as an experimental model. We observed that JAGGED1, DLL4, NOTCH1, and NOTCH4 were highly expressed in KGN cells as compared to granulosa-lutein cells obtained from assisted reproductive techniques patients. The proliferation and viability of KGN cells, as well as progesterone and estradiol production, decreased in the presence of 20 µM DAPT. Apoptotic parameters like PARP and caspase 8 cleavages, BAX, and BCLXs increased in KGN cells cultured with DAPT, whereas others such as BCL2, BCLXl, FAS, and FAS ligand did not change. AKT phosphorylation decreased and PTEN protein increased when Notch signaling was inhibited in KGN cells. We conclude that the Notch system acts as a survival pathway in KGN cells, and might be interacting with the PI3K/AKT pathway.


Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fatores de Transcrição Forkhead/genética , Tumor de Células da Granulosa/metabolismo , Neoplasias Ovarianas/metabolismo , Receptores Notch/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Secretases da Proteína Precursora do Amiloide/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Tumoral , Dipeptídeos , Feminino , Proteína Forkhead Box L2 , Hormônios Esteroides Gonadais/biossíntese , Tumor de Células da Granulosa/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteína Jagged-1 , Proteínas de Membrana/metabolismo , Mutação , Neoplasias Ovarianas/genética , Receptores Notch/antagonistas & inibidores , Proteínas Serrate-Jagged
15.
Mol Cell Endocrinol ; 365(2): 223-30, 2013 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-23123737

RESUMO

Ovarian hyperstimulation syndrome (OHSS) is a disorder associated with ovarian stimulation. OHSS features are ovarian enlargement with fluid shifting to the third space. Disturbances in the vasculature are considered the main changes that lead to OHSS. Our aim was to analyze the levels of angiopoietins 1 and 2 (ANGPT1 and 2) and their soluble and membrane receptors (s/mTie-2) in follicular fluid (FF) and in granulosa-lutein cells culture (GLCs) from women at risk of developing OHSS. We also evaluated the effect of ANGPT1 on endothelial cell migration. In ovaries from an OHSS rat model, we analyzed the protein concentration of ANGPTs, their mTie-2 receptor, and platelet-derived growth factor PDGF-B, -D and PDGFR-ß. ANGPT1 levels were increased in both FF and GLCs from women at risk of OHSS. Incubation of these FF with an ANGPT1 neutralizing antibody decreased endothelial cell migration. In the ovaries of OHSS rat model, mTie-2 protein levels increased and PDGF-B and -D decreased. In summary, these results suggest that ANGPT1 could be another mediator in the development of OHSS.


Assuntos
Angiopoietina-1/metabolismo , Angiopoietina-2/metabolismo , Líquido Folicular/metabolismo , Síndrome de Hiperestimulação Ovariana/metabolismo , Receptor TIE-2/metabolismo , Adulto , Angiopoietina-1/antagonistas & inibidores , Animais , Anticorpos/farmacologia , Estudos de Casos e Controles , Movimento Celular , Células Cultivadas , Feminino , Humanos , Células Lúteas/metabolismo , Ovário/metabolismo , Ovário/patologia , Proteínas Proto-Oncogênicas c-sis/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo
16.
Phys Chem Chem Phys ; 13(22): 10538-45, 2011 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-21442096

RESUMO

We present a general method to obtain parametrised models for the drift and diffusion terms of the Fokker-Planck equation of a coarse-grained description of molecular systems. The method is based on the minimisation of the relative entropy defined in terms of the two-time joint probability and thus captures the full dynamics of the coarse-grained description. In addition, we show an alternative Bayesian argument that starts from the path probability of a diffusion process which allows one to obtain the best parametrised model that fits an actual observed path of the coarse-grained variables. Both approaches lead to exactly the same optimisation function giving strong support to the methodology. We provide an heuristic argument that explains how both approaches are connected.


Assuntos
Simulação de Dinâmica Molecular , Teorema de Bayes , Difusão , Entropia
17.
J Chem Phys ; 131(16): 164106, 2009 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-19894926

RESUMO

The Green-Kubo formula for discrete hydrodynamic variables involves information about not only the fluid transport coefficients but also about discrete versions of the differential operators that govern the evolution of the discrete variables. This gives an intimate connection between discretization procedures in fluid dynamics and coarse-graining procedures used to obtain hydrodynamic behavior of molecular fluids. We observed that a natural definition of discrete hydrodynamic variables in terms of Voronoi cells leads to a Green-Kubo formula which is divergent, rendering the full coarse-graining strategy useless. In order to understand this subtle issue, in the present paper we consider the coarse graining of noninteracting Brownian particles. The discrete hydrodynamic variable for this problem is the number of particles within Voronoi cells. Thanks to the simplicity of the model we spot the origin of the singular behavior of the correlation functions. We offer an alternative definition, based on the concept of a Delaunay cell that behaves properly, suggesting the use of the Delaunay construction for the coarse graining of molecular fluids at the discrete hydrodynamic level.

18.
J Chem Phys ; 131(24): 244117, 2009 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-20059064

RESUMO

By using the standard theory of coarse graining based on Zwanzig's projection operator, we derive the dynamic equations for discrete hydrodynamic variables. These hydrodynamic variables are defined in terms of the Delaunay triangulation. The resulting microscopically derived equations can be understood, a posteriori, as a discretization on an arbitrary irregular grid of the Navier-Stokes equations. The microscopic derivation provides a set of discrete equations that exactly conserves mass, momentum, and energy and the dissipative part of the dynamics produces strict entropy increase. In addition, the microscopic derivation provides a practical implementation of thermal fluctuations in a way that the fluctuation-dissipation theorem is satisfied exactly. This paper points toward a close connection between coarse-graining procedures from microscopic dynamics and discretization schemes for partial differential equations.

19.
Carta med. A.I.S. Boliv ; 17(1): 17-19, 2002. graf
Artigo em Espanhol | LILACS | ID: lil-329775

RESUMO

Se presenta un paciente de 37 años de edad con antecedentes de trabajar por m'as de diez años como operario en las minas de carbón del Cerrejón Guajira. Clínicamente presente disneas y sincopes de esfuerzo, con dolor retroestema, ritmo de galope ocasional e ingurgitación yugular, compatibles con cor-pulmonar crónico. La radiografía de tórax presenta una opacidad conglomerada, mayor de un cintímetro de diámetro ubicada en los lóbulos medios del pulmón, además calcificaciones en forma de cascara de huevo en los gaglios linfáticos biliares y mediastinicos. La espirometría; muestra disminución de la capacidad vital (VC) y del volúmen espiratorio forzado (FEV), gasometría que demuestra disminución al esfuerzo y el reposos de las presiones parciales de O; y CO; respiectivamente. En la biopsia del pulmón se encontró conglomerados fibroticos con pérdida de la arquitectura pulmonar y granulomas necrobioticos con gran inflmación periférica y máculas de carbón alrededor de los bronquiolos. Además se encontró anticuerpos antinucleares positivos en el suero del paciente. El caso se concluyó como una "Silicoantracosis" profesional y corresponde a un grupo de 53 personas compatibles con neumoconiosis, diagnosticadas en 1995 por un estudio previo (Veles H. et. al 1995) de las cuales han fallecido 5 personas. En este mismo estudio se encontraron adem'as otras afecciones profesionales: 50 casos con daño músculo - esqueléticos. 66 casos con trastornos de la visión. 18 con hipoacusia, asi como altos niveles de panículas de carbón supendidas en el aire (más de 400 mg), violentando las normas de la legislación Colombiana para la salud ocupacional (MTSS, 1989). Por estas razones el grupo de investigadores de Universidad Popular del Cesar propone realizar un programa de vigilancia y control para prevenir la aparición de casos nuevos, controlar y rehabilitar los casos existentes y dar cumplimiento a las medidas de protección para el trabajo recomendadas por la Organización Internacional del Trabajo (OIT, 1985)


Assuntos
Humanos , Masculino , Adulto , Biópsia , Pulmão/microbiologia , Tuberculose Pulmonar
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