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1.
J Chem Phys ; 154(3): 034303, 2021 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-33499610

RESUMEN

A realistic double many-body expansion potential energy surface (PES) is developed for the 2A″ state of the carbon-nitrogen-oxygen (CNO) system based on MRCI-F12/cc-pVQZ-F12 ab initio energies. The new PES reproduces the fitted points with chemical accuracy (root mean square deviation up to 0.043 eV) and explicitly incorporates long range energy terms that can accurately describe the electrostatic and dispersion interactions. Thermal rate coefficients were computed for the C(3P) + NO(2Π) reaction for temperatures ranging from 15 K to 10 000 K, and the values are compared to previously reported results. The differences are rationalized, and the major importance of long range forces in predicting the rate coefficients for barrierless reactions is emphasized.

2.
Hum Reprod ; 35(2): 265-274, 2020 02 29.
Artículo en Inglés | MEDLINE | ID: mdl-31990346

RESUMEN

STUDY QUESTION: What are the effects of endocannabinoid anandamide (AEA) in uterine natural killer (unK) cells from miscarriage decidua, regarding their cytokine profile and endometrial stromal cell (ESC) crosstalk? SUMMARY ANSWER: uNK-conditioned media from miscarriage samples present high TNF-α levels which inhibit ESC decidualisation. WHAT IS KNOWN ALREADY: AEA plasma levels are higher in women who have suffered a miscarriage. Moreover, AEA inhibits ESC proliferation and differentiation, although the levels and impact on the uNK cell cytokine profile at the feto-maternal interface remain elusive. STUDY DESIGN, SIZE, DURATION: This laboratory-based study used human primary uNK cells which were isolated from first-trimester decidua (gestational age, 5-12 weeks) derived from 8 women with elective pregnancy termination and 18 women who suffered a miscarriage. PARTICIPANTS/MATERIALS, SETTING, METHODS: The first-trimester placental tissues were assayed for AEA levels by UPLC-MS/MS and respective enzymatic profile by western blot. The uNK cells were isolated and maintained in culture. The expression of angiogenic markers in uNK cells was examined by quantitative PCR (qPCR). The uNK-conditioned medium was analysed for IFN-γ, TNF-α and IL-10 production by enzyme-linked immunosorbent assay, and the impact on ESC differentiation was assessed by measuring decidual markers Prl, Igfbp-1 and Fox01 mRNA expression using qPCR. MAIN RESULTS AND THE ROLE OF CHANCE: AEA levels were higher in miscarriage decidua compared with decidua from elective terminations. The uNK cell-conditioned medium from the miscarriage samples exhibited high TNF-α levels and interfered with the decidualisation of ESCs. Exacerbated inflammation and elevated TNF-α levels at the feto-maternal interface may trigger AEA signalling pathways that, in turn, may impact decidualisation and the angiogenic ability of uNK cells. LARGE-SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Primary uNK cell responses are based on a simple in vitro model. Thus, in complex microenvironments, such as the feto-maternal interface, the mechanisms may not be exactly the same. Also, the inflammatory events of miscarriage that, in this study, have happened prior to processing of the samples may cause different responses to that observed. In addition, the magnitude of the inflammatory response, required to trigger the AEA pathways that impact decidualisation and the uNK angiogenic ability in vivo, is still unclear. WIDER IMPLICATIONS OF THE FINDINGS: The endocannabinoid AEA is a modulator of reproductive competence. AEA not only may contribute to neuroendocrine homeostasis but also can take part in uterine changes occurring during early pregnancy. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by UID/MULTI/04378/2019 with funding from Fundação para a Ciência e a Tecnologia (FCT)/MCTES through national funds and PORTUGAL 2020 Partnership Agreement, NORTE-01-0145-FEDER-000024. S.C. Cunha acknowledges FCT for the IF/01616/2015 contract. There are no conflicts of interest.


Asunto(s)
Aborto Espontáneo/metabolismo , Cannabinoides/metabolismo , Endocannabinoides/fisiología , Células Asesinas Naturales/metabolismo , Placenta/metabolismo , Receptores de Cannabinoides/fisiología , Células del Estroma/metabolismo , Ácidos Araquidónicos , Agonistas de Receptores de Cannabinoides , Endocannabinoides/genética , Endocannabinoides/metabolismo , Endometrio/metabolismo , Femenino , Humanos , Alcamidas Poliinsaturadas , Portugal , Embarazo , Receptores de Cannabinoides/genética , Receptores de Cannabinoides/metabolismo
3.
Lupus ; 28(4): 475-482, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30755143

RESUMEN

BACKGROUND: Choroidopathy is a rare manifestation of systemic lupus erythematosus (SLE). This entity is associated with active phases of severe SLE and it is frequently accompanied by acute kidney failure, central nervous system involvement and coagulopathy. PURPOSE: To evaluate the choroid thickness of patients with lupus nephritis (LN) without choroidopathy, and to compare this with that of age-matched SLE patients without LN and healthy control subjects. STUDY DESIGN: Cross-sectional case control study. MATERIAL AND METHODS: Fifteen women with LN in remission phase (study group), 15 women with SLE in remission without LN (SLE control group), and 15 healthy women (healthy control group), without ocular diseases or significant refractive error, were recruited. Full ophthalmological examination and a macular optical coherence tomography in enhanced depth imaging mode were performed. The choroid thickness was measured at nine macular points and six lines of mean choroidal thickness were determined. A comparative analysis between the three groups was performed using the one-way ANOVA test and the paired t-test. The choroid thickness of patients under corticotherapy was also compared to that of patients without corticotherapy. Additionally, the correlation between choroid thickness and disease duration was evaluated using the Pearson analysis. RESULTS: The mean macular choroidal thickness was 295.73 ± 67.62 µm in the study group, 233.34 ± 41.01 µm in the SLE control group, and 240.98 ± 37.93 µm in the control group ( p = 0.00006 and p = 0.0003, respectively). Additionally, the choroid thickness was significantly thicker than in the SLE and healthy control groups at the foveal ( p = 0.004 and p < 0.000), nasal ( p < 0.000 and p = 0.001), superior ( p = 0.002 and p < 0.000) and inferior ( p < 0.000 and p = 0.001) mean lines. The choroidal thickness in this group was not associated with the duration of the disease. The subgroup of patients with LN under corticotherapy did not reveal a significantly different choroidal thickness. CONCLUSION: This study suggests a relationship between LN and choroidal changes, which may represent an increased risk for choroidopathy in these patients. Choroid thickening was not related with the duration of the disease. This thickening may be correlated with histopathological changes similar to those occurring in kidney glomeruli.


Asunto(s)
Coroides/patología , Hidroxicloroquina/uso terapéutico , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/patología , Prednisolona/uso terapéutico , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Coroides/diagnóstico por imagen , Estudios Transversales , Femenino , Humanos , Nefritis Lúpica/diagnóstico por imagen , Persona de Mediana Edad , Tomografía de Coherencia Óptica
4.
Epidemiol Infect ; 147: e237, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-31364556

RESUMEN

Different countries, especially Brazil, that have faced recurrent dengue epidemics for decades and chikungunya epidemics since 2014, have had to restructure their health services to combat a triple epidemic of arboviruses - Zika, dengue and Chikungunya - transmitted by the same vector, mainly Aedes aegypti, in 2015-2016. Several efforts have been made to better understand these three arboviruses. Spatial analysis plays an important role in the knowledge of disease dynamics. The knowledge of the patterns of spatial diffusion of these three arboviruses during an epidemic can contribute to the planning of surveillance actions and control of these diseases. This study aimed to identify the spatial diffusion processes of these viruses in the context of the triple epidemic in 2015-2016 in Rio de Janeiro, Brazil. Two study designs were used: cross-sectional and ecological. Sequential Kernel maps, nearest-neighbour ratios calculated cumulatively over time, Moran global autocorrelation correlograms, and local autocorrelation changes over time were used to identify spatial diffusion patterns. The results suggested an expansion diffusion pattern for the three arboviruses during 2015-2016 in Rio de Janeiro. These findings can be considered for more effective control measures and for new studies on the dynamics of these three arboviruses.


Asunto(s)
Fiebre Chikungunya/epidemiología , Dengue/epidemiología , Transmisión de Enfermedad Infecciosa/estadística & datos numéricos , Mosquitos Vectores/virología , Infección por el Virus Zika/epidemiología , Animales , Brasil/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Estudios Retrospectivos , Población Urbana
5.
J Phys Chem A ; 123(33): 7195-7200, 2019 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-31356075

RESUMEN

The predicted rate constants for C + NO and O + CN collisions in three potential energy surfaces (PESs) for the 2A' state of the CNO molecule are compared using quasiclassical trajectories. Different temperature dependencies are obtained for the C + NO reaction, which are explained in terms of the long-range properties of the PESs. Recommended values and mechanistic details are also reported. For O + CN collisions, a better agreement between the theoretical results is found, except for temperatures below 100 K.

6.
Arch Toxicol ; 93(3): 649-658, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30659320

RESUMEN

Cannabis use has become a hot topic in several countries due to the debate about its legalization for medical purposes. However, data are limited regarding adverse events, safety and potential impact on reproductive health. Cannabis consumption during pregnancy has been associated with gestational disorders such as preterm birth, intrauterine growth restriction, low birth weight and increased risk of miscarriage, though the underlying biochemical mechanisms are still unknown. Given that the endocannabinoid system (ECS) is involved in several reproductive processes, we tested the hypothesis that the negative outcomes may result from the impact on the ECS homeostasis caused by the main psychoactive compound of cannabis, Δ9-tetrahydrocannabinol (THC). We demonstrate that THC (10-40 µM) impairs placental endocannabinoid system by disrupting the endocannabinoid anandamide (AEA) levels and the expression of AEA synthetic and degrading enzymes N-arachidonoylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), respectively. Although, no alterations in cannabinoid receptors CB1 and CB2 expression were observed. Thus, long-term local AEA levels are associated with a shift in the enzymatic profile to re-establish ECS homeostasis. In chronic cannabis users, high AEA levels in placenta may disturb the delicate balance of trophoblast cells turnover leading to alterations in normal placental development and foetal growth.


Asunto(s)
Dronabinol/toxicidad , Endocannabinoides/metabolismo , Homeostasis/efectos de los fármacos , Placenta/efectos de los fármacos , Psicotrópicos/toxicidad , Amidohidrolasas/metabolismo , Ácidos Araquidónicos/metabolismo , Cannabis , Femenino , Humanos , Placenta/fisiología , Alcamidas Poliinsaturadas/metabolismo , Embarazo , Receptor Cannabinoide CB1/metabolismo
7.
J Dairy Sci ; 102(1): 678-683, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30415844

RESUMEN

Staphylococci are the main etiological agents of bovine mastitis. Bacteriocins and nanoparticles have emerged as promising alternatives for the future development of antimicrobial agents. This study evaluated the activity of the bacteriocin nisin and bicelles of the synthetic cationic lipid dioctadecyldimethylammonium bromide, alone and in combination, against multidrug-resistant Staphylococcus spp. strains isolated from bovine mastitis. In summary, cationic nisin/dioctadecyldimethylammonium bromide nanoparticles are shown to be a promising alternative for the control of mastitis caused by multidrug-resistant Staphylococcus spp.


Asunto(s)
Resistencia a Múltiples Medicamentos , Membrana Dobles de Lípidos/farmacología , Mastitis Bovina/microbiología , Nanopartículas/administración & dosificación , Nisina/farmacología , Staphylococcus/efectos de los fármacos , Animales , Antibacterianos/farmacología , Bacteriocinas/farmacología , Cationes , Bovinos , Femenino , Staphylococcus aureus Resistente a Meticilina , Compuestos de Amonio Cuaternario/farmacología
8.
Neth Heart J ; 27(7-8): 347-353, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30977040

RESUMEN

INTRODUCTION: Exercise-based cardiac rehabilitation (EBCR) is part of the management of patients who have suffered an acute myocardial infarction (AMI). Patients with a reduced ejection fraction (EF) comprise a higher-risk subgroup and are referred less often for these programmes. This study aimed at assessing the impact of the baseline EF on the functional benefits, as assessed by peak oxygen uptake (pVO2) and exercise duration, of an EBCR programme in AMI survivors. METHODS: Observational, retrospective cohort study including all patients admitted to a tertiary centre due to an AMI who completed a phase II EBCR programme after discharge, between November 2012 and April 2017. Functional parameters were assessed by a symptom-limited cardiopulmonary exercise test. RESULTS: A total of 379 patients were included [40.9% with reduced EF (<50%) at discharge]. After the programme, pVO2 and exercise duration increased significantly (p < 0.001). Patients with a reduced EF had a lower pVO2 and completed a shorter duration of exercise at the beginning and end of the programme. This group presented a higher increase in pVO2 (p = 0.001) and exercise duration (p = 0.007). This was maintained after adjusting for age, gender, history of coronary artery disease, number of sessions, Killip classification, arterial hypertension, dyslipidaemia, diabetes mellitus, smoking status and baseline pVO2. CONCLUSION: A phase II EBCR programme was associated with significant improvements in pVO2 and exercise duration among AMI survivors, irrespective of baseline EF classification. Those with a reduced baseline EF derived an even greater improvement, highlighting the importance of EBCR in this subgroup of patients.

9.
J Phys Chem A ; 122(16): 4198-4207, 2018 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-29620887

RESUMEN

We report a new global double many-body expansion potential energy surface for the ground state of the CNO(2A') manifold, calculated by the explicit correlation multireference configuration interaction method. The functional form was accurately fitted to 3701 ab initio points with a root mean squared deviation of 0.99 kcal mol-1. All stationary points reported in previous forms are systematically described and improved, in addition to three new ones and a characterization of an isomerization transition state between the CNO and NCO minima. The novel proposed form gives a realistic description of both short-range and long-range interactions and hence is commended for dynamics studies.

10.
Public Health ; 159: 99-106, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29559184

RESUMEN

OBJECTIVE: To present a predictive model of alcohol abuse among adolescents based on prevalence projections in various population subgroups. STUDY DESIGN: Cross-sectional study. METHODS: The sample consisted of 785 adolescents enrolled in the second year of high school in Rio de Janeiro, Brazil. Alcohol consumption was assessed using the Alcohol Use Disorder Identification Test. Socio-economic, demographic, family, individuals, and school-related variables were examined as potential predictors. The logit model was used to estimate the prevalence projections. Model fitting was examined in relation to the observed data set, and in a subset, that was generated from 200 subsamples of individuals via a bootstrap process using general fit estimators, discrimination, and calibration measures. RESULTS: About 25.5% of the adolescents were classified as positive for alcohol abuse. Being male, being 17-19 years old, not living with mothers, presenting symptoms suggestive of binge eating, having used a strategy of weight reduction in the last 3 months, and, especially, being a victim of family violence were important predictors of abusive consumption of alcohol. While the model's prevalence projection in the absence of these features was 8%, it reaches 68% in the presence of all predictors. CONCLUSIONS: Knowledge of predictive characteristics of alcohol abuse is essential for screening, early detection of positive cases, and establishing interventions to reduce consumption among adolescents.


Asunto(s)
Consumo de Bebidas Alcohólicas/psicología , Alcoholismo/diagnóstico , Alcoholismo/prevención & control , Adolescente , Alcoholismo/epidemiología , Brasil/epidemiología , Estudios Transversales , Diagnóstico Precoz , Femenino , Humanos , Modelos Logísticos , Masculino , Valor Predictivo de las Pruebas , Prevalencia , Adulto Joven
11.
Biochim Biophys Acta ; 1861(3): 205-12, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26698196

RESUMEN

In recent years, endocannabinoids emerged as new players in various reproductive events. Recently, we demonstrated the involvement of 2-arachidonoylglycerol (2-AG) in human cytotrophoblast apoptosis and syncytialization. However, 2-AG impact in hormone production by the syncytiotrophoblast (hST) was never studied. In this work, we demonstrate that 2-AG activates cannabinoid (CB) receptors, exerting an inhibitory action on cyclic AMP/protein kinase A (cAMP/PKA) and mitogen-activated protein kinase (MAPK) p38 pathways, and enhancing ERK 1/2 phosphorylation. Furthermore, 2-AG affects the synthesis of human chorionic gonadotropin (hCG), leptin, aromatase, 3-ß-hydroxysteroid dehydrogenase (3-ß-HSD), and placental protein 13 (PP13). These 2-AG effects are mediated by the activation of CB receptors, in a mechanism that may involve p38, ERK 1/2 and cAMP/PKA pathways, which participate in the regulation of placental proteins expression. To our knowledge, this is the first study that associates the endocannabinoid signalling and endocrine placental function, shedding light on a role for 2-AG in the complex network of molecules that orchestrate the production of placental proteins essential for the gestational success.


Asunto(s)
Ácidos Araquidónicos/farmacología , Agonistas de Receptores de Cannabinoides/farmacología , Endocannabinoides/farmacología , Glicéridos/farmacología , Biosíntesis de Proteínas/efectos de los fármacos , Trofoblastos/efectos de los fármacos , Trofoblastos/metabolismo , 3-Hidroxiesteroide Deshidrogenasas/biosíntesis , Aromatasa/biosíntesis , Células Cultivadas , Gonadotropina Coriónica/biosíntesis , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Galectinas/genética , Galectinas/metabolismo , Humanos , Leptina/biosíntesis , Fosforilación , Embarazo , Proteínas Gestacionales/genética , Proteínas Gestacionales/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
12.
BMC Infect Dis ; 17(1): 571, 2017 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-28810911

RESUMEN

BACKGROUND: The implementation of rapid drug susceptibility testing (DST) is a current global priority for TB control. However, data are scarce on patient-relevant outcomes for presumptive diagnosis of drug-resistant tuberculosis (pDR-TB) evaluated under field conditions in high burden countries. METHODS: Observational study of pDR-TB patients referred by primary and secondary health units. TB reference centers addressing DR-TB in five cities in Brazil. Patients age 18 years and older were eligible if pDR-TB, culture positive results for Mycobacterium tuberculosis and, if no prior DST results from another laboratory were used by a physician to start anti-TB treatment. The outcome measures were median time from triage to initiating appropriate anti-TB treatment, empirical treatment and, the treatment outcomes. RESULTS: Between February,16th, 2011 and February, 15th, 2012, among 175 pDR TB cases, 110 (63.0%) confirmed TB cases with DST results were enrolled. Among study participants, 72 (65.5%) were male and 62 (56.4%) aged 26 to 45 years. At triage, empirical treatment was given to 106 (96.0%) subjects. Among those, 85 were treated with first line drugs and 21 with second line. Median time for DST results was 69.5 [interquartile - IQR: 35.7-111.0] days and, for initiating appropriate anti-TB treatment, the median time was 1.0 (IQR: 0-41.2) days. Among 95 patients that were followed-up during the first 6 month period, 24 (25.3%; IC: 17.5%-34.9%) changed or initiated the treatment after DST results: 16/29 MDRTB, 5/21 DR-TB and 3/45 DS-TB cases. Comparing the treatment outcome to DS-TB cases, MDRTB had higher proportions changing or initiating treatment after DST results (p = 0.01) and favorable outcomes (p = 0.07). CONCLUSIONS: This study shows a high rate of empirical treatment and long delay for DST results. Strategies to speed up the detection and early treatment of drug resistant TB should be prioritized.


Asunto(s)
Antituberculosos/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis/tratamiento farmacológico , Adulto , Anciano , Brasil , Farmacorresistencia Bacteriana , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/patogenicidad , Resultado del Tratamiento , Tuberculosis/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología
13.
Cell Tissue Res ; 362(2): 441-6, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26202891

RESUMEN

The human syncytiotrophoblast (hST) has a major role in the production of important placental hormones. Several molecules regulate hST endocrine function but the role of endocannabinoids in this process is still unknown. Here, we report that the endocannabinoid anandamide (AEA) decreased cAMP levels, impaired human chorionic gonadotropin secretion, placental alkaline phosphatase activity and decreased aromatase mRNA levels and protein expression, through cannabinoid (CB) receptor activation. AEA also downregulated leptin and placental protein 13 transcription, though via a CB receptor-independent mechanism. All this evidence suggests AEA is a novel modulator of hormone synthesis by the syncytiotrophoblast, supporting the importance of the endocannabinoid signalling in placental function.


Asunto(s)
Ácidos Araquidónicos/metabolismo , Moduladores de Receptores de Cannabinoides/metabolismo , Endocannabinoides/metabolismo , Galectinas/biosíntesis , Alcamidas Poliinsaturadas/metabolismo , Proteínas Gestacionales/biosíntesis , Receptor Cannabinoide CB1/biosíntesis , Trofoblastos/metabolismo , Femenino , Humanos , Placenta/metabolismo , Embarazo , Transducción de Señal/fisiología
14.
Bioprocess Biosyst Eng ; 38(10): 1835-44, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26084256

RESUMEN

The efficiency of linear alkylbenzene sulfonate (LAS) removal from laundry wastewater and the related microbial community was investigated in an anaerobic fluidized bed reactor (AFBR). The AFBR was operated in three stages, in addition to the biomass adaptation stage without LAS (stage I). The stages were differentiated by their supplementary co-substrates: stage II had sucrose plus ethanol, stage III had only ethanol, and stage IV had no co-substrate. The replacement of sucrose plus ethanol with ethanol only for the substrate composition favored the efficiency of LAS removal, which remained high after the co-substrate was removed (stage II: 52 %; stage III: 73 %; stage IV: 77 %). A transition in the microbial community from Comamonadaceae to Rhodocyclaceae in conjunction with the co-substrate variation was observed using ion sequencing analysis. The microbial community that developed in response to an ethanol-only co-substrate improved LAS degradation more than the community that developed in response to a mixture of sucrose and ethanol, suggesting that ethanol is a better option for enriching an LAS-degrading microbial community.


Asunto(s)
Bacterias/metabolismo , Etanol/metabolismo , Consorcios Microbianos/fisiología , Sacarosa/metabolismo , Tensoactivos/metabolismo , Contaminantes Químicos del Agua/metabolismo , Ácidos Alcanesulfónicos/aislamiento & purificación , Ácidos Alcanesulfónicos/metabolismo , Aniones , Bacterias/clasificación , Bacterias/aislamiento & purificación , Biodegradación Ambiental , Reactores Biológicos/microbiología , Especificidad de la Especie , Tensoactivos/aislamiento & purificación , Microbiología del Agua , Contaminantes Químicos del Agua/aislamiento & purificación , Purificación del Agua/métodos
15.
Int Endod J ; 47(10): 909-19, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24354338

RESUMEN

AIM: To test the effects of a mineral trioxide aggregate-based sealer (MTA Fillapex(®)) and MTA (MTA-Ângelus(®)) on viability and on the production of cytokines, reactive oxygen species (ROS) and nitrogen species (NO) by M1 and M2 inflammatory macrophages. METHODOLOGY: M1 (from C57BL/6 mice) and M2 (from BALB/c mice) peritoneal inflammatory macrophages were obtained and cultured in vitro in the presence of original and diluted extracts of MTA and MTA Fillapex (FLPX). The cell viability, ROS release and the release of tumour necrosis factor-a, interleukin (IL)-12, IL-10 and NO in response to stimulation with interferon-γ and Fusobacterium nucleatum or Peptostreptococcus anaerobius were evaluated. The data were analysed using the Mann-Whitney test and Student's t-test. RESULTS: Fillapex was cytotoxic at the highest concentrations (1:1;1:2) and decreased the viability (P < 0.05) of both macrophage types (<20%). MTA did not interfere with cellular viability. FLPX inhibited the release of ROS and decreased NO release in F. nucleatum and P. anaerobius -stimulated M1 and M2 macrophages (≤25 µ mol L(-1)). F. nucleatum-stimulated M2 macrophage cultures released lower levels of TNF-α when FLPX was added (≤1 ng mL(-1)). M2 macrophages released higher (>5 ng mL(-1)) levels of IL-10 than M1 macrophages. Only M1 macrophage cultures produced IL-12p70. CONCLUSIONS: Fillapex impaired effector immune responses during inflammation (M1 macrophages), as well as during healing (M2 macrophages) responses.


Asunto(s)
Compuestos de Aluminio , Compuestos de Calcio , Citocinas/metabolismo , Macrófagos/metabolismo , Nitrógeno/metabolismo , Óxidos , Selladores de Fosas y Fisuras , Especies Reactivas de Oxígeno/metabolismo , Silicatos , Animales , Combinación de Medicamentos , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL
16.
Int J Comput Vis ; 103(1): 22-59, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23956495

RESUMEN

This paper proposes an original approach for the statistical analysis of longitudinal shape data. The proposed method allows the characterization of typical growth patterns and subject-specific shape changes in repeated time-series observations of several subjects. This can be seen as the extension of usual longitudinal statistics of scalar measurements to high-dimensional shape or image data. The method is based on the estimation of continuous subject-specific growth trajectories and the comparison of such temporal shape changes across subjects. Differences between growth trajectories are decomposed into morphological deformations, which account for shape changes independent of the time, and time warps, which account for different rates of shape changes over time. Given a longitudinal shape data set, we estimate a mean growth scenario representative of the population, and the variations of this scenario both in terms of shape changes and in terms of change in growth speed. Then, intrinsic statistics are derived in the space of spatiotemporal deformations, which characterize the typical variations in shape and in growth speed within the studied population. They can be used to detect systematic developmental delays across subjects. In the context of neuroscience, we apply this method to analyze the differences in the growth of the hippocampus in children diagnosed with autism, developmental delays and in controls. Result suggest that group differences may be better characterized by a different speed of maturation rather than shape differences at a given age. In the context of anthropology, we assess the differences in the typical growth of the endocranium between chimpanzees and bonobos. We take advantage of this study to show the robustness of the method with respect to change of parameters and perturbation of the age estimates.

17.
Clin Transplant ; 26(2): E111-24, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22168269

RESUMEN

Cardiac allograft vasculopathy (CAV) is a significant factor impacting outcomes after heart transplant. We performed a systematic review of risk factors for the development of CAV. A search of electronic databases was performed. The eligibility criteria included cohort and case-control studies with more than 50 adult patients submitted to a heart transplant. The outcome should be CAV diagnosed by angiography and/or intravascular ultrasound (IVUS). Two reviewers performed study selection, data abstraction, and quality assessment. Of 2514 citations, 66 articles were included--46 had 200 participants or less; 61 were single-center; and 44 were retrospective cohorts. The most used definition of CAV using angiography was the detection of any degree of abnormality (21 studies of 58). In studies using IVUS, an intimal thickness ≥0.5 mm was the most used definition (five of eight studies). Quality assessment revealed an inadequate description of patient selection, attrition, and accounting of potential confounders. Donor age, recipient age, recipient gender, etiology of heart failure, ischemic time, human leukocyte antigen matching, cytomegalovirus, lipid profile, and rejection episodes were the most studied factors. Our review indicates that the current evidence is not consistent across different studies. The definite contribution of risk factors for the development of CAV is still to be determined.


Asunto(s)
Enfermedad Coronaria/etiología , Trasplante de Corazón/efectos adversos , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Humanos , Factores de Riesgo
18.
J Reprod Immunol ; 149: 103468, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35007917

RESUMEN

During pregnancy, the maternal immune system is challenged to tolerate a semi-allogenic fetus. A shift toward a tolerogenic profile is essential to ensure a healthy fetal and placental development. One of the most important mechanisms involved in the maternal immune tolerance towards the fetal antigens is expressed in the activity of the regulatory T (Treg) and Th17 cells. The behavior and equilibrium of these two T lymphocyte populations were rarely studied in normal healthy pregnancies through the beginning of gestation to the postpartum period. We conducted a prospective longitudinal observational study where peripheral blood lymphocyte subsets were analyzed in each trimester of pregnancy and postpartum period in a group of healthy pregnant women. Our study observed a consistent reduction in peripheric Treg cell count through all pregnancy while the Th17 cell count remained stable. The Th17/Treg ratio increases significantly throughout pregnancy to the postpartum period. These changes could be justified by the migration of the immunotolerant Treg cells to the maternal decidua and lead to the establishment of a systemic pro-inflammatory profile by the end of pregnancy. This data could explain why systemic syndromes like preeclampsia develop in susceptible women during the second half of pregnancy or why many autoimmune disorders flourish in the first weeks postpartum.


Asunto(s)
Placenta/inmunología , Embarazo/inmunología , Mujeres Embarazadas , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Adulto , Femenino , Voluntarios Sanos , Humanos , Tolerancia Inmunológica , Inmunidad Celular , Estudios Prospectivos , Adulto Joven
19.
IEEE Trans Image Process ; 31: 2598-2607, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35316178

RESUMEN

Advanced shape analysis studies such as regression and classification need to be performed on curved manifolds, where often, there is a lack of standard statistical formulations. To overcome these limitations, we introduce a novel machine-learning method on the shape space of curves that avoids direct inference on infinite-dimensional spaces and instead performs Bayesian inference with spherical Gaussian processes decomposition. As an application, we study the shape of the cochlear spiral-shaped cavity within the petrous part of the temporal bone. This problem is particularly challenging due to the relationship between shape and gender, especially in children. Experimental results for both synthetic and real data show improved performance compared to state-of-the-art methods.


Asunto(s)
Aprendizaje Automático , Teorema de Bayes , Niño , Humanos , Distribución Normal
20.
Sci Rep ; 12(1): 15096, 2022 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-36064728

RESUMEN

Scalp melanoma (SM) has a worse prognosis than melanoma in other locations likely because of late diagnosis due to hair coverage, difficulties in interpreting dermoscopy findings, and its unique molecular profile. We aimed to describe the clinical, histopathological, molecular, and dermoscopic patterns of SM and its relation to androgenetic alopecia/elastosis at the tumor site. Through a retrospective cross-sectional study, we identified all SM diagnosed at the A.C.Camargo Cancer Center between 2008 and 2018. In all, 48 SM were analyzed: 45.8% of which exhibited moderate/severe androgenetic alopecia and 54.1% exhibited elastosis. Androgenetic alopecia/elastosis at the site of the SM was associated with older age (p < 0.001), chronic sun damage (p < 0.001), lentigo maligna subtype (p = 0.029), and photodamaged dermoscopic pattern (p < 0.001). Additionally, 41 cases were evaluated with a 14-gene panel: 53.7% displayed mutations and 46.3% were wild-type. BRAF mutations were most common (77%), with BRAF V600K being more frequent (50%) than BRAF V600E (31.2%). The NF1 gene was evaluated in 40 samples, of which 20% exhibited mutations. SM presents differently in areas covered by hair compared to in areas with androgenetic alopecia. Patients without alopecia may have higher Breslow thickness due to late diagnosis because of hair concealment. The high frequency of detrimental mutations can also explain the poor prognosis of SM.


Asunto(s)
Alopecia , Melanoma , Proteínas Proto-Oncogénicas B-raf , Cuero Cabelludo , Alopecia/genética , Alopecia/patología , Estudios Transversales , Dermoscopía , Humanos , Melanoma/genética , Melanoma/patología , Proteínas Proto-Oncogénicas B-raf/genética , Estudios Retrospectivos , Cuero Cabelludo/patología
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