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1.
J Biol Chem ; 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33288674

RESUMO

Phospholipase D3 (PLD3) and phospholipase D4 (PLD4), the most recently described lysosomal nucleases, are associated with Alzheimer`s disease, spinocerebellar ataxia, and systemic lupus erythematosus. They exhibit 5' exonuclease activity on single-stranded DNA, hydrolyzing it at the acidic pH associated with the lysosome. However, their full cellular function is inadequately understood. To examine these enzymes, we developed a robust and automatable cell-based assay based on fluorophore- and fluorescence-quencher coupled oligonucleotides for the quantitative determination of acidic 5' exonuclease activity. We validated the assay under knockout and PLD-overexpression conditions, and then applied it to characterize PLD3 and PLD4 biochemically. Our experiments revealed PLD3 as the principal acid 5' exonuclease in HeLa cells, where it showed a markedly higher specific activity compared to PLD4. We further used our newly developed assay to determine the substrate specificity and inhibitory profile of PLD3, and found that proteolytic processing of PLD3 is dispensable for its hydrolytic activity. We followed the expression, proteolytic processing, and intracellular distribution of genetic PLD3 variants previously associated with Alzheimer's disease and investigated each variant's effect on the 5' nuclease activity of PLD3, finding that some variants lead to reduced activity, but others not. The development of a PLD3/4-specific biochemical assay will be instrumental in understanding better both nucleases and their incompletely unknown roles in vitro and in vivo.

2.
Antioxidants (Basel) ; 9(12)2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33302572

RESUMO

Oxidative conditions are frequently enhanced by the presence of redox metal ions. In this study, the role of capsaicin (8-methyl-N-vanillyl-6-nonenamide, CAP) in copper-induced oxidative stress was investigated using density functional theory simulations. It was found that CAP has the capability to chelate Cu(II), leading to complexes that are harder to reduce than free Cu(II). CAP fully turns off the Cu(II) reduction by Asc-, and slows down the reduction in this cation by O2•-. Therefore, CAP is proposed as an •OH-inactivating ligand by impeding the reduction in metal ions (OIL-1), hindering the production of •OH via Fenton-like reactions, at physiological pH. CAP is also predicted to be an excellent antioxidant as a scavenger of •OH, yielded through Fenton-like reactions (OIL-2). The reactions between CAP-Cu(II) chelates and •OH were estimated to be diffusion-limited. Thus, these chelates are capable of deactivating this dangerous radical immediately after being formed by Fenton-like reactions.

3.
JBRA Assist Reprod ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33094607

RESUMO

OBJECTIVE: The primary objective was to establish the endometrial predictors of clinical pregnancy in a population of repeated implantation failure with oocyte donation after specific endometrial treatment. The secondary one was to evaluate reproduction outcomes in terms of Implantation rate (IR), Clinical pregnancy (CP), Live birth delivery rate (LBDR) and Prematurity, in relation to normalization or no-normalization of the predictors. METHODS: 66 patients were assigned to the study. We ran a Pipelle endometrial biopsy to investigate the endometrium lymphocyte population by Flow Cytometry and abnormal/normal patterns by histopathology in pre/post-treatment. We employed the binary logistic regression model to identify the predictors for CP. For the secondary objective, we assessed the clinical outcomes in function to the normalization or no normalization in post-treatment. RESULTS: Endometrial histopathology and endometrial NK cell counts resulted in CP predictors (Wald chi2 test (p=0.044 and 0.001)), respectively. We had a higher IR, CP and LBDR when both predictors were normalized in comparison with no normalization (p<0.001). There was a high percentage of prematurity in both normalized vs. non-normalized groups (34.4% (11/32) and 71.43% (5/7), respectively) without significant differences. CONCLUSION: Endometrial histopathology and endometrial NK cell counts showed that they are valid predictors of pregnancy outcome in repeated implantation failure after treatment. In post-treatment, the pregnancy outcomes were significantly higher in the presence of both normalized predictors. Pregnancy rates were zero in the no-normalization of both predictors. There was a high percentage of prematurity in both groups.

4.
Saudi J Biol Sci ; 27(11): 3113-3124, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33100872

RESUMO

Ethnopharmacological relevance: Verbesina crocata (Cav.) Less. (Arnica or Capitaneja) is an endemic plant from Mexico restricted to the western part of the country. The aerial parts are used in traditional medicine for the treatment of wounds and burns. The objective of this investigation was to carry out a pharmacognostic study of V. crocata and establish markers that allow for the recognition of the characteristics of the plant and validate its traditional use. The study includes anatomical and chemical characteristics of the plant as well as evaluations of its antioxidant capacity and wound healing ability in a murine model. Materials and methods: An anatomical study of V. crocata was performed on the middle part of the leaf and stem. A methanolic extract of this species (VcME) was obtained by methanolic maceration of the aerial parts. Subsequently, a partition of the VcME was made to obtain a hexanic fraction (VcH). The phytochemical preliminary screening and characterization by high-performance liquid chromatography/mass spectrometry (HPLC-ESI/MS) of the VcME and VcH were performed. The antioxidant activity and total phenolic content were quantified. The wound healing capacity of the methanolic extract was determined in CD-1 mice by the healing rate, the tensiometric method, and histological analysis. Results: The anatomical study of V. crocata showed the presence of two types of secretory structures and their position on the leaves. In addition, the characteristics of the middle vein and trichomes are potentially useful for recognition of the species. Chemical compounds detected by HPLC-ESI/MS reveal the presence of sitosterol glycoside and catechin derivatives as principal constituents of V. crocata. The VcME showed low antioxidant capacity and total phenolic. V. crocata had a similar healing effect to Recoveron® in the tensiometric method, but the rate of healing was higher. According to the histological analysis, the treatment of V. crocata promoted the remodelling phase 15 days after the incisional wound. Conclusion: This is the first pharmacognostic study of this species that covers the plant anatomy, chemical content and biological properties related to its traditional use. V. crocata favours wound healing according to physical and histological evaluations. In addition, the characteristics of the middle vein, trichomes and catechin glycosides are potentially useful for the recognition of this species.

5.
J Mol Model ; 26(11): 321, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33113023

RESUMO

The single-electron transfer (SET) reactions from the neutral and mono-anion species of five imidazole alkaloids (lepidines A, B, C, D, and E) against hydroperoxyl radicals have been studied using the density functional theory and the Marcus theory. The deprotonated species of three alkaloids were found to have free radical scavenging activity. The antioxidant activity was studied via single-electron transfer (SET) under physiological conditions. The SET reactions for lepidines B, D, and E were found to have rate constants ranging from 105 to 106 M-1 s-1. Therefore, they are predicted to be able to deactivate hydroperoxyl radicals and therefore the damage caused by them to polyunsaturated fatty acids. It is important to mention that the acid-base equilibrium plays an important role in their free radical scavenging activity. Graphical abstract Lepidines are predicted to be able to deactivate hydroperoxyl radicals and the damage caused by them to polyunsaturated fatty acids.

6.
Pathogens ; 9(10)2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32992452

RESUMO

Skin infections have been associated with Acanthamoeba, nevertheless the events during skin invasion and UV-B light effects on it are unknown. The early morphological events of Acanthamoeba castellanii skin invasion are shown in SKH-1 mice that were chronically UV-B light irradiated. Mice that developed skin lesions (group 1) were topical and intradermally inoculated with A. castellanii trophozoites and sacrificed 48 h or 18 days later. Mice that showed no skin lesions (group 2) were intradermally inoculated and sacrificed 24, 48 or 72 h later. Mice ventral areas were considered controls with and without trophozoites intradermally inoculated. Skin samples were processed by histological and immunohistochemistry techniques. In group 1, trophozoites were immunolocalized in dermal areas, hair cysts, sebaceous glands, and blood vessels, and collagen degradation was observed. One of these mice shown trophozoites in the spleen, liver, and brain. In group 2, few trophozoites nearby collagenolytic activity zones were observed. In control samples, nor histological damage and no trophozoites were observed. Adherence and collagenolytic activity by A. castellanii were corroborated in vitro. We can infer that UV-B light irradiated skin could favor A. castellanii invasiveness causing damage in sites as far away as the brain, confirming the invasive capacity and pathogenic potential of these amphizoic amoebae.

7.
Rev. chil. pediatr ; 91(7): 60-74, set. 2020. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1138696

RESUMO

Resumen: La aparición del SARS-CoV-2 a partir de diciembre de 2019 y su rápida expansión en el mundo alcanzando el estatus de Pandemia, se ha convertido en un gran desafío para los equipos de salud. Aunque la evidencia de la infección en niños aún es escasa comparada a la de los adultos, se ha hecho evidente que a nivel de la población pediátrica, la mayor parte de las veces la infección es asintomática o de curso leve, sin embargo no todos los pacientes tienen esta evolución, lo que ha motivado la discusión en los equipos de Cuidados Criticos Pediátricos respecto a cómo enfrentar estos pacientes con enfermedad grave. Este consenso es fruto del trabajo de la Rama de Cuidados Intensivos Pe diátricos de la Sociedad Chilena de Pediatría, recogiendo la evidencia disponible al momento de la revisión más la opinión de expertos nacionales en Cuidados Intensivos Pediátricos. El propósito de estas recomendaciones, es ofrecer a los equipos que atienden a pacientes críticos pediátricos, una guía para el diagnóstico y tratamiento de pacientes que evolucionen con COVID 19 grave, que puedan ser aplicadas en todas las UPC Pediátricas de nuestro país, haciendo especial énfasis en aquellas medidas que han demostrado mayor efectividad a nivel de estudios diagnósticos, tratamiento y cuidados del personal de salud.


Abstract: The appearance of SARS-CoV-2 from December 2019 and its rapid expansion in the world reaching Pandemic status, has become a great challenge for health teams. Although the evidence of infection in children is still scarce compared to that of adults, it has become evident that at the pediatric po pulation level, most of the time the infection is asymptomatic or mild, but not all the patients have this evolution, which has motivated the discussion in the Pediatric Critical Care teams regarding how to face these patients with a more serious disease. This consensus is the result of the work of the Pediatric Intensive Care Branch of the Chilean Society of Pediatrics, collecting the evidence available at the time of the review plus the opinion of national experts in Pediatric Intensive Care. The purpose of these recommendations is to offer teams that care for critically ill pediatric patients a guide for the diagnosis and treatment of patients who evolve with severe COVID 19, which can be applied in all Pediatric UPCs in our country, with special emphasis in those measures that have shown greater effectiveness at the level of diagnostic studies, treatment and care of health personnel.

8.
Appl Bionics Biomech ; 2020: 2724783, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802156

RESUMO

This paper establishes design criteria for soft exogloves (SEG) to be used as rehabilitation or assistance devices. This research consists in identifying, selecting, and grouping SEG features based on the analysis of 91 systems that have been proposed during the last decade. Thus, function, mobility, and usability criteria are defined and explicitly discussed to highlight SEG design guidelines. Additionally, this study provides a detailed description of each system that was analysed including application, functional task, palm design, actuation type, assistance mode, degrees of freedom (DOF), target fingers, motions, material, weight, force, pressure (only for fluids), control strategy, and assessment. Such characteristics have been reported according to specific design methodologies and operating principles. Technological trends are contemplated in this contribution with emphasis on SEG design opportunity areas. In this review, suggestions, limitations, and implications are also discussed in order to enhance future SEG developments aimed at stroke survivors or people with hand disabilities.

9.
Nutrition ; 78: 110901, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32736300

RESUMO

OBJECTIVE: The aim of this study was to evaluate the association between glycemic control (hemoglobin (Hb) A1c <7%) and the dietary patterns identified in Mexican patients with type 2 diabetes mellitus (T2DM). METHODS: This was a secondary analysis conducted with 4838 patients with T2DM in Mexico. Biochemical blood profiles, socioeconomic level, anthropometric measurements, and dietary data were obtained. Dietary data from a food frequency questionnaire were used to derive dietary patterns. Factor analysis was conducted to ascertain dietary patterns, and multivariate analysis was fitted to assess the relationship between glycemic control and consumption of dietary patterns. RESULTS: Three dietary patterns were identified. After control for potential cofounders (age, sex, duration of T2DM, body mass index, pharmacologic treatment, intensity of physical activity, socioeconomic level, and kcal/kg ideal weight), we found that consuming a Western-style diet (odds ratio [OR], 1.533, 95% confidence interval [CI], 1.253-1.875; P < 0.000), and the sweets and dairy diet (fats and sugars; OR, 1.444; 95% CI, 1.133-1.841; P = 0.003) patterns were associated with HbA1c ≥7%, whereas consuming a healthy dietary patter (OR, 0.800; 95% CI, 0.642-0.998; P = 0.048) was associated with HbA1c <7%. CONCLUSIONS: Consuming a healthy diet was associated with glycemic control; whereas the Western-style or sweets and dairy patterns promoted a lack of metabolic control. These results support the promotion of a healthy pattern in the Mexican population with T2DM.

10.
PLoS One ; 15(7): e0235490, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32628708

RESUMO

Mutations in KRAS, NRAS, and BRAF (RAS/BRAF) genes are the main predictive biomarkers for the response to anti-EGFR monoclonal antibodies (MAbs) targeted therapy in metastatic colorectal cancer (mCRC). This retrospective study aimed to report the mutational status prevalence of these genes, explore their possible associations with clinicopathological features, and build and validate a predictive model. To achieve these objectives, 500 mCRC Mexican patients were screened for clinically relevant mutations in RAS/BRAF genes. Fifty-two percent of these specimens harbored clinically relevant mutations in at least one screened gene. Among these, 86% had a mutation in KRAS, 7% in NRAS, 6% in BRAF, and 2% in both NRAS and BRAF. Only tumor location in the proximal colon exhibited a significant correlation with KRAS and BRAF mutational status (p-value = 0.0414 and 0.0065, respectively). Further t-SNE analyses were made to 191 specimens to reveal patterns among patients with clinical parameters and KRAS mutational status. Then, directed by the results from classical statistical tests and t-SNE analysis, neural network models utilized entity embeddings to learn patterns and build predictive models using a minimal number of trainable parameters. This study could be the first step in the prediction for RAS/BRAF mutational status from tumoral features and could lead the way to a more detailed and more diverse dataset that could benefit from machine learning methods.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Modelos Estatísticos , Taxa de Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Redes Neurais de Computação , Estudos Retrospectivos
11.
Mater Sci Eng C Mater Biol Appl ; 115: 111045, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32600682

RESUMO

Electrospinning is a well-established and widely used method for the production of protein-based fibrous biomaterials. The visualization of the morphology and the characterization of sample features related to the three-dimensional (3D) structure, like the porosity and fibers thickness, is crucial for the design and fabrication of tailor-made and application-optimized materials. Here, we evaluated the benefits of using 3D X-ray imaging in a laboratory setup with a resolution in the sub-micrometer range for the characterization of electrospun gelatin fibrous mats. We used phase-contrast X-ray computed tomography at the nanoscale (nano-CT) for the evaluation of the time-course morphological changes of the mats induced by chemical cross-linking of the gelatin fibers. We present an image processing protocol that enables the segmentation of the fibers and quantification of the mats porosity, the analysis of the shape and size of the pores, and of the fibers thickness and orientation. We compared the results obtained from the processed nano-CT data with those obtained with the conventional methods used for the characterization of electrospun fibrous materials, and we discuss the advantages and limitations of each method when applied to gelatin electrospun samples. Our results reveal that the use of phase-contrast nano-CT provides quick additional and relevant information for the characterization of fibrous mats and, thus, provides beneficial insights for the design and fabrication of novel fibrous materials.

12.
Neuro Oncol ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32413139

RESUMO

BACKGROUND: Infant medulloblastoma represents an enormous challenge in neuro-oncology, due to their simultaneous high-risk of recurrence and high risk of severe neurodevelopmental sequelae with craniospinal irradiation. Currently infant medulloblastoma are treated with intensified protocols, either comprising intraventricular methotrexate or autologous transplant, both of which carry significant morbidity and are not feasible in the majority of the world. We sought to evaluate the molecular predictors of outcome in a cohort of infants homogeneously treated with induction chemotherapy, focal radiation and maintenance chemotherapy. METHODS: A retrospective analysis of twenty-nine young children treated with a craniospinal irradiation sparing strategy from Hospital Garrahan in Buenos Aires were profiled using Illumina HumanMethylationEPIC arrays, and correlated with survival. RESULTS: Twenty-nine children (range 0.3 - 4.6 years) were identified, comprising 17 SHH, 10 Group 3/4 and 2 non-medulloblastomas. Progression-free survival (PFS) across the entire cohort was 0.704 (95% CI 0.551-0.899). t-SNE analysis revealed three predominant groups, SHHß, SHHγ and Group3. Survival by subtype was highly prognostic with SHHγ having an excellent 5-year PFS of 100% (95% CI 0.633-1) and SHHß having a PFS of 0.56 (95% CI 0.42-1). Group 3 had a PFS of 0.50 (95% CI 0.25-1). Assessment of neurocognitive outcome was performed in 11 patients, the majority of survivors fell within the low average to mild intellectual disability, with a median IQ of 73.5. CONCLUSIONS: We report a globally feasible and effective strategy avoiding craniospinal radiation in the treatment of infant medulloblastoma, including a robust molecular correlation along with neurocognitive outcomes.

13.
J Clin Endocrinol Metab ; 105(7)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32309857

RESUMO

CONTEXT: Little is known about the association between haptoglobin level and cardiometabolic traits. A previous genome-wide association study identified rs2000999 in the HP gene as the stronger genetic contributor to serum haptoglobin level in European populations. OBJECTIVE AND DESIGN: We investigated the association of HP rs2000999 with serum haptoglobin and childhood and adult obesity in up to 540/697 and 592/691 Mexican cases and controls, respectively. Anthropometric and biochemical data were collected. Serum haptoglobin was measured by an immunoturbidimetry assay. HP rs2000999 was genotyped using the TaqMan technology. Mendelian randomization analysis was performed using the Wald and inverse variance weighting methods. RESULTS: Haptoglobin level was positively associated with childhood and adult obesity. HP rs2000999 G allele was positively associated with haptoglobin level in children and adults. HP rs2000999 G allele was positively associated with childhood but not adult obesity. The association between HP rs2000999 and childhood obesity was removed after adjusting for haptoglobin level. In a Mendelian randomization analysis, haptoglobin level genetically predicted by HP rs2000999 showed a significant causal effect on childhood obesity by the Wald and inverse variance weighting methods. CONCLUSION: Our data provide evidence for the first time for a causal positive association between serum haptoglobin level and childhood obesity in the Mexican population. Our study contributes to the genetic elucidation of childhood obesity and proposes haptoglobin as an important biomarker and treatment target for obesity.

14.
Memory ; 28(4): 516-527, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32148184

RESUMO

Intrusive involuntary memories and images are a cardinal phenomenon in a range of psychological disorders, but not systematically examined in social anxiety. We examined potential biases upon generating involuntary versus voluntary memories and future projections in individuals with high and low levels of social anxiety. Participants recorded involuntary and voluntary autobiographical events, and their associated emotional response in a structured mental time travel diary. High social anxiety was associated with more intense anxiety and embarrassment and greater use of a range of emotion regulation strategies upon generating all types of autobiographical events. Involuntary (versus voluntary) memories and future events were associated with a heightened emotional response independent of social anxiety, and memories were associated with more embarrassment than imagined future events. The effects of high versus low social anxiety and involuntary versus voluntary generation process were independent from each other. The findings have implications for affective and cognitive models of involuntary memories and future projections in emotional disorders.

15.
J Environ Manage ; 261: 110255, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32148317

RESUMO

Vegetation Filters (VFs) can be a sustainable solution to treat wastewater and to recover resources such as nutrients, water and biomass from small municipalities and isolated dwellings. However, under certain conditions, the leakage of nutrients, especially of nitrate, can represent a limitation. The addition of two sustainable soil amendments, woodchips and biochar, has been tested as a strategy to improve nutrient attenuation in VFs increasing sorption sites and microbial activity. To this end, unsaturated infiltration and batch experiments have been carried out at laboratory scale. The systems for infiltration experiments contain natural soil, natural soil amended with woodchips and natural soil amended with biochar. To determine the sorption capacity of NH4+, batch tests were performed using an amendment/SWW ratio of 1:20 and an NH4+ initial concentration ranging from 30 to 600 mg L-1. Results from the infiltration experiments show a high attenuation (~95%) of total phosphorous (TP) independently of the amendments. Different behaviour is observed for total nitrogen (TN). The removal of this species is obtained only in the soil amended with woodchips (>85%) whereas the natural soil alone and the soil with biochar have no impact on TN attenuation. In these two porous media, all the NH4+ input concentration is transformed to NO3- that infiltrates without further reactions. According to batch experiment results, the potential role of biochar in the nutrient attenuation is limited to sorption processes (Kd (NH4+) = 21.37-193.18 L kg-1). Woodchips act primarily as a labile source of carbon promoting biodegradation, being more effective for nutrient attenuation than the sorption capacity of biochar.


Assuntos
Poluentes do Solo , Águas Residuárias , Carvão Vegetal , Nitrogênio , Fósforo , Solo
16.
Pediatr Pulmonol ; 55(3): 780-787, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31977167

RESUMO

BACKGROUND: Pediatric home ventilation (HV) has increased worldwide. A Home Ventilation Program (HVP) was started in the Pulmonary Department of the "Hospital de Pediatría Prof. Dr. J. P. Garrahan," Argentina, in 2007. This is the largest Argentine national pediatric tertiary care referral center. Limited studies on pediatric HV from Latin American countries have been published. OBJECTIVE: This study describes and analyzes the cohort of children admitted to the HVP during an 11 years period. METHODS: Longitudinal study. POPULATION: all patients (pts) admitted to the HVP between 2007 and 2018. We analyzed demographic and clinical variables, sleep study results, ventilation setting, and start manner collected in a prospective data base. RESULTS: A total of 244 pts were admitted. Median age at ventilation start was 9.41 (3.47-14.08) years, 84% of pts had health insurance. The most frequent underlying diseases were neuromuscular disease (43%) and genetic syndromes (23%). Home-hospital distance was 100-500 km in 16% of cases and greater than 500 km in 34%. Seventy percent of pts had sleep studies before ventilation initiation. Ventilation was started in our general pediatric ward in 83.6%. Noninvasive ventilation was used in 86.1%. The actual number of pts still on follow up is 133 of 244 (54.5%), 16.8% dropped out, 16.4% were transitioned to adult care, 5.32% resolved their sleep-disordered breathing, and 5.32% died. CONCLUSIONS: The HVP admitted pts from all the country. Ventilation was started on the basis of clinical and objective sleep measures. This long-term experience underlines the feasibility of a HVP in an emergent country.


Assuntos
Serviços de Assistência Domiciliar , Respiração Artificial , Adolescente , Argentina , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Doenças Genéticas Inatas/terapia , Humanos , Estudos Longitudinais , Masculino , Doenças Neuromusculares/terapia
17.
JBRA Assist Reprod ; 24(2): 118-127, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31589391

RESUMO

OBJECTIVE: Our primary objective was to evaluate the endometrial changes before and after the transfer of endometrial mesenchymal stem cells (enMSCs) in a population of thinned endometrium women, with absence or hypo-responsiveness to estrogen and repeated implantation failure (RIF). The secondary objective was to evaluate the clinical outcomes of the intervention in terms of clinical pregnancy (CP), early abortions, ongoing pregnancy and live birth delivery rate (LBDR) per in vitro fertilization (IVF) cycle. METHODS: A longitudinal and experimental study. The intervention was defined as "subendometrial inoculation of enMSCs," and the post-intervention changes were evaluated by the following variables: endometrial thickness (Eth), endometrial flow cytometry (enFC), endometrial histopathology (enHP) and endometrial immunohistochemistry (enIHQ). The variables were analyzed after the intervention (Post-treatment) regarding previous values (Pretreatment). RESULTS: Eth values before and after treatment with enMSCs were 5.24±1.24 mm vs. 9.93±0.77 (p=0.000), respectively. Endometrial Flow Cytometry showed significant differences in favor of Normalized variables in the post-treatment assessment, associated with the pretreatment, LT/Li, LB/Li, NK/Li, CD8/CD3+ and CD4/CD8 (p≤0.015), respectively. Only two variables Li/PC and CD4/CD3 had NS (p=0.167 and 0.118). A similar analysis was performed on enHP with an HP increase post-treatment (p=0.007). The CP rate was 79.31% (23/29), a live birth delivery rate per embryo transfer was 45.45% (10/22) and ongoing pregnancy 7/29 (24.14%). CONCLUSION: Subendometrial enMSCs inoculation produces a significant increase in endometrial thickness; normalize the enHP, enIHQ and enFC. As a result, IVF after treatment with enMSCs yields a higher rate of CP and LBDR.

18.
Bioorg Chem ; 91: 103091, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31319298

RESUMO

Sensitizing activities exerted by 3,4-dihydro-7-hydroxycadalene (1), rac-3,7-dihydroxy-3(4H)-isocadalen-4-one (4) and (1R,4R)-4H-1,2,3,4-tetrahydro-1-hydroxycadalen-15-oic acid (9), the major cadinanes isolated from Heterotheca inuloides, towards multidrug-resistant MES-SA/MX2 and parental MES-SA epithelial human uterine sarcoma cell lines were evaluated. We also evaluated the in silico interactions (expressed as ΔGbinding in kcal/mol) of cadinanes 1, 4 and 9 in an in vitro assay, and also tested several structurally related natural compounds with the multidrug resistance protein (MDR1, P-glycoprotein), human multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP) structures as pharmacological targets using AutoDock and AutoDock Vina. Compound 1 potentiated the cytotoxicity of doxorubicin and mitoxantrone drugs in resistant MES-SA/MX2 cells, compared to cells treated with each drug alone. Compound 1 could reverse the resistance to doxorubicin 12.44 fold at a concentration of 5 µM. It also re-sensitized cells to mitoxantrone 3.94 fold. Hence, compound 1 may be considered as a potential chemosensitizing agent to overcome multidrug resistance in cancer. The docking analysis suggested that there are interactions between cadinanes from H. inuloides and MDR1, MRP1, and BCRP proteins mainly through π-π interactions and hydrogen bonds.


Assuntos
Transportadores de Cassetes de Ligação de ATP/química , Antineoplásicos Fitogênicos/farmacologia , Asteraceae/química , Produtos Biológicos/farmacologia , Sesquiterpenos Policíclicos/farmacologia , Transportadores de Cassetes de Ligação de ATP/genética , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/isolamento & purificação , Relação Estrutura-Atividade
19.
J Endocr Soc ; 3(5): 937-942, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31020057

RESUMO

We present the case of multiple sclerosing pneumocytomas (SPs) associated with ACTH-secreting carcinoid tumorlets responsible for an ectopic Cushing syndrome (ECS). SP is a rare benign tumor originating from pulmonary epithelial cells. An 18-year-old male presented with shortness of breath and right-sided chest pain after exercise. Chest radiograph indicated right pneumothorax and bilateral lung nodules. CT imaging showed innumerable bilateral hypodense pulmonary nodules and a wedge resection gave the definitive diagnosis of SP with associated carcinoid tumorlets. Two years later, he presented with severe back pain in context of thoracic vertebral compression fracture. He had central fat accumulation, violaceous striae, proximal muscle weakness, hypertension, and diabetes. MRI of the pituitary gland showed a 7-mm adenoma. Inferior petrosal sinus sampling with no central-to-periphery gradient suggested an ectopic origin of ACTH, which was confirmed by ACTH expression in a subset of tumorlet cells in the lung lesions. The patient was started on ketoconazole and subsequently underwent a bilateral adrenalectomy. During follow-up, CT scans showed no growth of the lesions, except for the most recent CT scan, in which an increase in the size of the largest nodule was described. Ten years after the diagnosis, the patient remains asymptomatic of his pulmonary lesions. This article provides a case of ECS in the setting of multiple SP with associated carcinoid tumorlets.

20.
An. pediatr. (2003. Ed. impr.) ; 90(4): 232-236, abr. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-186614

RESUMO

Introducción: Diversos autores cuestionan la realización sistemática de una ecografía renal en los lactantes con una primera infección del tracto urinario (ITU), dada la alta sensibilidad de las ecografías prenatales para la detección de malformaciones mayores y la baja prevalencia de hallazgos clínicamente significativos. Los objetivos de este trabajo son valorar el rendimiento diagnóstico de la ecografía renal realizada después de la primera ITU en pacientes menores de 2 años y analizar posibles factores de riesgo (FR) de presentar una ecografía renal alterada. Pacientes y métodos: Estudio retrospectivo. Se incluyen los pacientes menores de 2 años diagnosticados de ITU en Urgencias entre julio de 2013 y diciembre de 2014. Se excluyen aquellos con enfermedad nefrourológica, ITU previas y sin ecografía renal prenatal o postinfección. Se considera ecografía renal alterada la presencia de dilatación de las vías urinarias y/o anomalías estructurales. Los posibles FR evaluados son: sexo masculino, edad inferior a 3 meses, fiebre y microorganismo distinto a Escherichia coli. Se realiza estudio univariante y por regresión logística multivariante. Resultados: Se incluyen 306 pacientes. Presentan ecografía renal alterada 35 (11,4%; IC 95% 8,3-15,5): 24 (68,6%) dilatación de las vías urinarias y 11 (31%) alteraciones estructurales. De las ecografías alteradas, el 68,6% corresponden a varones, el 51,4% a una edad inferior a 3 meses, el 74,3% a ITU febriles y el 31,4% por microorganismo distinto a E. coli, respecto al 45% (p = 0,009), el 31,7% (p = 0,021), el 78,2% (p = 0,597) y el 10% (p = 0,001) de las ecografías normales. En el análisis multivariante se mantienen como FR la edad inferior a 3 meses (OR 2,1; IC 95% 1,0-4,3; p = 0,05) y un microorganismo distinto a E. coli (OR 3,8; IC 95% 1,7-8,7; p = 0,002). Conclusiones: El rendimiento de la ecografía renal después de la primera ITU es bajo. Se debería individualizar su indicación según la presencia de FR: edad inferior a 3 meses y microorganismo distinto a E. coli


Introduction: Several authors question the performance of systematic renal ultrasound after first urinary tract infection (UTI) in young children, given the high sensitivity of prenatal ultrasounds to detect major malformations and the low prevalence of clinical relevant findings. The aims of this study are to evaluate the yield of renal ultrasound performed after the first UTI in patients aged less than 2 years and to analyse potential risk factors (RF) of altered renal ultrasound. Patients and methods: Retrospective study, including patients aged less than 2 years diagnosed with UTI in the Emergency Department between July 2013 and December 2014. Patients with an underlying nephro-urological pathology, previous UTIs and those without prenatal or post-infection renal ultrasound were excluded. Altered renal ultrasound was defined as the presence of dilated urinary tract or structural abnormalities. Potential RF analysed were: male, age less than 3 months, presence of fever and microorganism other than Escherichia coli. Univariate and multivariate logistic regression were performed. Results: A total of 306 patients were included. Altered renal ultrasound was found in 35 cases (11.4%; 95% CI 8.3-15.5): 24 (68.6%) urinary tract dilation, and 11 (31%) structural abnormalities. Among the cases with altered ultrasound, 68.6% were male, 51.4% were younger than 3 months, 74.3% were febrile, and 31.4% were caused by microorganisms other than E. coli, compared to 45% (P = .009), 31.7% (P = .021), 78.2% (P = .597) and 10% (P = .001) of cases with normal ultrasound. In the multivariate analysis, age less than 3 months (OR 2.1; 95% CI 1.0-4.3, P = .05) and microorganism other than E. coli (OR 3.8; 95% CI 1.7-8.7, P = .002) remained as RF. Conclusions: The yield of renal ultrasound after the first UTI is low. Its indication should be individualised according to the presence of RF: age less than 3 months and microorganism other than E. coli


Assuntos
Humanos , Masculino , Recém-Nascido , Lactente , Infecções Urinárias/diagnóstico por imagem , Fatores de Risco , Ultrassonografia/métodos , Estudos Retrospectivos , Medicina de Emergência Pediátrica , Fatores Etários , Febre/epidemiologia , Febre/etiologia , Fatores Sexuais , Infecções Urinárias/microbiologia
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