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1.
J Proteomics ; 210: 103529, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31605789

RESUMO

In blood banks, platelets are stored until 7 days after a pathogen reduction technology (PRT) treatment, Mirasol® (vitamin B2 plus UVB light) in the present case. The storage time under these conditions may have an impact on platelets and their releasate leading to potential adverse reactions following transfusion to patients. The aim of this study was to analyze the proteome of extracellular vesicles generated by platelets at different storage days (2 and 7) to gain deeper information on the platelet concentrates state at those moments. EVs were isolated by a centrifugation-based approach and characterized by dynamic light scattering and transmission electron microscopy. Proteomic analysis was by LC-MS/MS and quantification by SWATH. In this way, 151 proteins were found up-regulated at day 7 of storage. This group includes CCL5 and Platelet Factor 4, chemokines with power to attract neutrophils and monocytes, which could generate transfusion adverse reactions. In addition, other glycoproteins and platelet activation markers were also found elevated at day 7. Proteins related to glycolysis and lactate production were found altered with high fold changes, showing a deregulation of platelet metabolism at day 7. The obtained results provide novel information about possible effects of platelet-derived EVs on transfusion adverse reactions. SIGNIFICANCE: We performed the first proteomic analysis of extracellular vesicles derived from platelets upon storage at different time points on blood bank conditions after Mirasol® treatment. We identified a high number of proteins related to platelet activation and platelet storage lesion that could have a role in possible transfusion adverse reactions.

2.
Infectio ; 23(supl.1): 73-91, dic. 2019. tab, graf
Artigo em Espanhol | LILACS-Express | ID: biblio-984511

RESUMO

Resumen: Los pacientes con infección por VIH tienen una mayor incidencia de eventos cardiovasculares en comparación con la población general; los factores que contribuyen al incremento del riesgo de eventos cardiovasculares son la prevalencia de factores de riesgo cardiovascular tradicionales (FRCV), la infección por VIH que condiciona tanto un proceso de inflamación crónica como alteración de la función endotelial y la exposición a los antirretrovirales. Los factores que deben ser objeto de intervención son los FRCV tradicionales, en especial la alta tasa de fumadores entre este grupo de pacientes, la tamización y tratamiento de HTA, el síndrome metabólico y el acceso temprano a la terapia antirretroviral con medicamentos con mayor perfil de seguridad . Esta guía pretende proveer información y recomendaciones en el ámbito nacional acerca de la relación entre la infección por VIH/SIDA (Síndrome de Inmunodeficiencia Adquirida), uso de antirretrovirales y riesgo cardiovascular.


Abstract: Patients with VIH infection have greater risk for cardiovascular diseases compared to general population. Risk factors that increase the frequency of cardiovascular events are: presence of cardiovascular traditional risk factors, chronic inflammation by HIV that impairs endothelial function and the exposure to antiretrovirals. The factors that should be the target for intervention are the traditional know cardiovascular factors such, especially high rate of smokers, screening and treatment for hypertension, metabolic syndrome and early access to HAART. The present guidelines provides information about the use of antiretrovirals in patients with HIV and its relation with cardiovascular risk.

3.
J Thromb Haemost ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31680418

RESUMO

BACKGROUND: Accurate protein quantification is a vital prerequisite for generating meaningful predictions when using systems biology approaches, a method that is increasingly being used to unravel the complexities of sub cellular interactions and as part of the drug discovery process. Quantitative proteomics, flow cytometry and western blotting have been extensively used to define human platelet protein copy numbers, yet for mouse platelets, a model widely used for platelet research, evidence is largely limited to a single proteomic dataset in which the total amount of proteins were generally comparatively higher than those found in human platelets. OBJECTIVES: To investigate the functional implications of discrepancies between levels of mouse and human proteins in the GPVI signalling pathway using a systems pharmacology model of GPVI METHODS: The protein copy number of mouse platelet receptors was determined using flow cytometry. The Virtual Platelet, a mathematical model of Glycoprotein VI (GPVI) signalling, was used to determine the consequences of protein copy number differences observed between human and mouse platelets. RESULTS AND CONCLUSION: Despite the small size of mouse platelets compared to human platelets they possessed a greater density of surface receptors alongside a higher concentration of intracellular signalling proteins. Surprisingly the predicted temporal profile of Syk activity was similar in both species with predictions supported experimentally. Super resolution microscopy demonstrates that the spatial distribution of Syk is similar between species, suggesting that the spatial distribution of receptors and signalling molecules in activated platelets, rather than their copy number, is important for signalling pathway regulation.

4.
J Mol Neurosci ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31768942

RESUMO

Alzheimer's disease (AD) is one of the most complicated neurodegenerative diseases, and several hypotheses have been associated with its development and progression, such as those involving glucose hypometabolism, the cholinergic system, calcium imbalance, inflammation, oxidative imbalance, microtubule instability, and the amyloid cascade, several of which are related to oxidative stress (free radical generation), which contributes to neuronal death. Therefore, several efforts have been made to establish a sporadic AD model that takes into account these hypotheses. One model that replicates the increase in amyloid beta (Aß) and oxidative stress in vivo is the scopolamine model. In the present work, the chronic administration (6 weeks) of scopolamine was used to analyze the neuroprotective effects of apocynin and galantamine. The results showed that scopolamine induced cognitive impairment, which was evaluated 24 h after the final dose was administered. In addition, after scopolamine administration, the Aß and superoxide anion levels were increased, and NADPH oxidase 2 (NOX2), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa B (NFkB) genes were overexpressed. These effects were not observed when either apocynin or galantamine was administered during the last 3 weeks of scopolamine treatment, and although the results from both molecules were related to lower Aß production and, consequently, lower superoxide anion production, they were likely realized through different pathways. That is, both apocynin and galantamine diminished NADPH oxidase expression, but their effects on transcription factor expression differed. Moreover, experiments in silico showed that galantamine did not interact with the active site of beta secretase, whereas diapocynin, an apocynin metabolite, interacted with the beta-site APP-cleaving enzyme (BACE1) at the catalytic site.

5.
Mol Divers ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664610

RESUMO

11-Beta hydroxysteroid dehydrogenase type 1 (11ß-HSD1) regulates cortisol levels mainly in adipose, hepatic and brain tissues. There is a relationship between the high activity of this enzyme and the development of obesity and metabolic disorders. The inhibition of 11ß-HSD1 has been shown to attenuate the development of type 2 diabetes mellitus, insulin resistance, metabolic syndrome and other diseases mediated by excessive cortisol production. In this work, fifteen benzothiazole derivatives substituted with electron-withdrawing and electron-donating groups were designed to explore their affinity for 11ß-HSD1 using in silico methods. The results show that (E)-5-((benzo[d]thiazol-2-ylimino)(methylthio)methylamino)-2-hydroxybenzoic acid (C1) has good physicochemical properties and favorable interactions with 11ß-HSD1 through hydrogen bonding and hydrophobic interactions in the catalytic site formed by Y183, S170 and Y177. Furthermore, C1 was synthesized and evaluated in vitro and ex vivo using clobenzorex (CLX) as a reference drug in obese Zucker rats. The in vitro results showed that C1 was a better inhibitor of human 11ß-HSD1 than CLX. The ex vivo assay results demonstrated that C1 was capable of reducing 11ß-HSD1 overexpression in mesenteric adipose tissue. Therefore, C1 was able to decrease the activity and expression of 11ß-HSD1 better than CLX.

6.
Phys Chem Chem Phys ; 21(41): 23136-23142, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31612174

RESUMO

The synthesis of two-dimensional transition metal carbides (MXenes) with a predefined number of atomic layers offers a possible way to tune these nanomaterials chemical activity. MXenes have been theoretically predicted to be able to store CO2 even at high temperatures and low CO2 partial pressures, a prediction which has been experimentally confirmed afterwards. In the present work, the influence of the number of atomic layers on CO2 adsorption is systematically investigated by means of density functional theory based calculations, using suitable periodic models representing the (0001) surface of a series of these materials with formula Mn+1Cn (M = Ti, Zr, Hf, V, Nb, Ta, Mo, W) and n = 1-3. The interaction of CO2 with the MXene surfaces is always favorable with the adsorption energy decreasing as the transition metal electronic configuration goes from d2 through d3 to d4, in agreement with previous work for n = 1. The influence of the thickness is found to be rather small, yet noticeable, although somewhat erratic. Nevertheless, the adsorption energy seems to converge to a defined clear limit for sufficiently thick MXenes. Interestingly, this value is close to that corresponding to the (111) surface of bulk Transition Metal Carbides (TMCs). The close structural similarity between the MXene (0001) and TMC (111) surfaces strongly suggests that the former provide a practical way to approach this otherwise unstable surface. The possibility to tune the CO2 interaction based on the MXene thickness is further investigated by means of kinetic phase diagrams. These provide additional evidence that carbide MXene surfaces are promising materials for CO2 capture even at low CO2 partial pressures, and that the MXene thickness can be used to fine tune this appealing behavior.

7.
Nutr. hosp ; 36(4): 898-904, jul.-ago. 2019. tab, graf
Artigo em Espanhol | LILACS-Express | ID: ibc-ET2-2842

RESUMO

Introducción: las estrictas restricciones dietéticas que imponemos en la enfermedad renal crónica avanzada (ERCA) tienen un impacto negativo en la calidad de vida. Objetivo: determinar si estas restricciones están justificadas y si un programa de educación nutricional mejoraría los parámetros de calidad de vida relacionada con la salud (CVRS). Material y métodos: realizamos un ensayo clínico de intervención educativa, unicéntrico, randomizado y controlado en los pacientes de la consulta ERCA de Albacete. Se incluyeron 75 pacientes, 35 en el grupo control y 40 en el de intervención. Se realizó la valoración nutricional mediante valoración global subjetiva (VGS) e índice de masa corporal (IMC). Para medir la CVRS se empleó el cuestionario de salud SF-36. En el grupo intervención se realizó la intervención nutricional individual, colectiva y por recuerdo telefónico, adaptando a cada paciente el consejo dietético y ajustando las restricciones de forma personalizada. Resultados: la malnutrición medida por VGS fue del 20% en el grupo control y del 29,3% en el grupo intervención, donde mejoró aunque no fue significativo. El IMC mostró sobrepeso con una media de 28,83 (DE: 5,4) y 26,96 kg/m2 (DE: 4,09) respectivamente, sin cambios a lo largo del estudio. La intervención nutricional supuso una mejoría en las puntuaciones de todas las subescalas excepto en el dolor corporal. Además, los componentes físico y mental también mejoraron sus puntuaciones en el grupo intervención y empeoraron significativamente (p < 0,001) en el control. Conclusiones: la calidad de vida se puede mejorar en los pacientes con ERCA aplicando un programa de educación nutricional


Introduction: the strict dietary recommendations we impose on patients with advanced chronic kidney disease (ACKD) have negative impact on quality of life. Objective: determine whether such restrictions are justified and if an educational program can improve health-related quality of life (HRQL) parameters. Methods: we carried out an educational intervention, single center, randomized, controlled clinical trial on ACKD outpatients in Albacete. Seventy-five patients were included, 35 in the control group and 40 in the intervention group. Nutritional assessment was based on the Subjetive Global Assessment (SGA) and body mass index (BMI). We used the SF-36 health questionnaire to measure HRQL. In the intervention group we carried out individual, collective and telephone nutritional interventions, adapting diet advice and restrictions in a personalized way. Results: malnutrition measured by Subjective Global Assessment (SGA) in the control group was 20%; meanwhile, in the intervention group it was 29.3% and it improved at the end of the study, but not significantly. BMI showed overweight with a mean of 28.83 kg/m² (DE: 5.4) and 26.96 kg/m² (DE: 4.09), respectively, and did not change throughout the study. The nutritional intervention improved the score in all the subscales except for body pain score. Besides, mental and physical components also improved their scores in the intervention group and worsened them in the control group (p < 0.001). Conclusions: quality of life can be improved in ACKD patients applying an educational nutrition program

8.
Int J Nurs Knowl ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31379131

RESUMO

PURPOSE: To establish technical values for nursing diagnoses in primary healthcare with which to weight the delivery of care based on criteria of complexity and relevance. METHODS: A three-phase cross-sectional descriptive study: (1) establishing and weighting of the assessment criteria of technical values, (2) scoring of the assessment criteria per diagnosis, and (3) assigning technical values. FINDINGS: Diagnoses were ordered on the scoring scale obtained and a technical value of 1 to 4 was assigned according to their quartile. CONCLUSIONS: Having a technical value for each nursing diagnosis helps to measure the diversity and complexity of care. IMPLICATIONS FOR NURSING PRACTICE: Technical values may contribute to improving nursing management indicators, as they incorporate a quantitative view into the assessment process.

9.
J Chem Theory Comput ; 15(9): 5024-5030, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31369257

RESUMO

The electronic properties of realistic (TiO2)n nanoparticles (NPs) with cuboctahedral and bipyramidal morphologies are investigated within the many-body perturbation theory (MBPT) G0W0 approximation using PBE and hybrid PBEx (12.5% Fock contribution) functionals as starting points. The use of a Gaussian and plane waves (GPW) scheme reduces the usual O4 computational time required in this type of calculation close to O3 and thus allows considering explicitly NPs with n up to 165. The analysis of the Kohn-Sham energy orbitals and quasiparticle (QP) energies shows that the optical energy gap (Ogap), the electronic energy gap (Egap), and the exciton binding energy (ΔEex) values decrease with increasing TiO2 NP size, in agreement with previous work. However, while bipyramidal NPs appear to reach the scalable regime already for n = 84, cuboctahedral NPs reach this regime only above n = 151. Relevant correlations are found and reported that will allow one to predict these electronic properties at the G0W0 level in even much larger NPs where these calculations are unaffordable. The present work provides a feasible and practical way to approach the electronic properties of rather large TiO2 NPs and thus constitutes a further step in the study of realistic nanoparticles of semiconducting oxides.

10.
Biotechnol Bioeng ; 116(11): 2906-2918, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31317526

RESUMO

Concentration gradients that occur in large industrial-scale bioreactors due to mass transfer limitations have significant effects on process efficiency. Hence, it is desirable to investigate the response of strains to such heterogeneities to reduce the risk of failure during process scale-up. Although there are various scale-down techniques to study these effects, scale-down strategies are rarely applied in the early developmental phases of a bioprocess, as they have not yet been implemented on small-scale parallel cultivation devices. In this study, we combine mechanistic growth models with a parallel mini-bioreactor system to create a high-throughput platform for studying the response of Escherichia coli strains to concentration gradients. As a scaled-down approach, a model-based glucose pulse feeding scheme is applied and compared with a continuous feed profile to study the influence of glucose and dissolved oxygen gradients on both cell physiology and incorporation of noncanonical amino acids into recombinant proinsulin. The results show a significant increase in the incorporation of the noncanonical amino acid norvaline in the soluble intracellular extract and in the recombinant product in cultures with glucose/oxygen oscillations. Interestingly, the amount of norvaline depends on the pulse frequency and is negligible with continuous feeding, confirming observations from large-scale cultivations. Most importantly, the results also show that a larger number of the model parameters are significantly affected by the scale-down scheme, compared with the reference cultivations. In this example, it was possible to describe the effects of oscillations in a single parallel experiment. The platform offers the opportunity to combine strain screening with scale-down studies to select the most robust strains for bioprocess scale-up.

11.
Salud Publica Mex ; 61(4): 524-531, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31322845

RESUMO

OBJECTIVE: To analyze the possible effect of certification models and healthcare organizations' (HOs) participation incentives in the General Health Council certification process in the 1999-2017 period. MATERIALS AND METHODS: Official printed and online documents about HOs' certification were collected. Information from instances related to the process was requested through transparency mechanisms. Health organizations' participation in political-administrative periods between 1997-2017 was analyzed. RESULTS: The annual average participation in the certification process during the 1999-2000 period was 259.5 HOs; during the 2013-2016 period, the average was 72.5. Public units' participation in this process has been decreasing. In 2017, certified HO were <1%. CONCLUSIONS: No positive effects of adjustments to the certification model or the incentives applied were identified. Conversely, there is decreasing participation in the different political-administrative periods. The National HO Certification System and its possible effect on clinical quality must be thoroughly evaluated.

12.
Nutr Hosp ; 36(4): 898-904, 2019 Aug 26.
Artigo em Espanhol | MEDLINE | ID: mdl-31291738

RESUMO

Introduction: Introduction: the strict dietary recommendations we impose on patients with advanced chronic kidney disease (ACKD) have negative impact on quality of life. Objective: determine whether such restrictions are justified and if an educational program can improve health-related quality of life (HRQL) parameters. Methods: we carried out an educational intervention, single center, randomized, controlled clinical trial on ACKD outpatients in Albacete. Seventy-five patients were included, 35 in the control group and 40 in the intervention group. Nutritional assessment was based on the Subjetive Global Assessment (SGA) and body mass index (BMI). We used the SF-36 health questionnaire to measure HRQL. In the intervention group we carried out individual, collective and telephone nutritional interventions, adapting diet advice and restrictions in a personalized way. Results: malnutrition measured by Subjective Global Assessment (SGA) in the control group was 20%; meanwhile, in the intervention group it was 29.3% and it improved at the end of the study, but not significantly. BMI showed overweight with a mean of 28.83 kg/m² (DE: 5.4) and 26.96 kg/m² (DE: 4.09), respectively, and did not change throughout the study. The nutritional intervention improved the score in all the subscales except for body pain score. Besides, mental and physical components also improved their scores in the intervention group and worsened them in the control group (p < 0.001). Conclusions: quality of life can be improved in ACKD patients applying an educational nutrition program.

13.
Arch Physiol Biochem ; : 1-7, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291139

RESUMO

Aim: The purpose of this work was to identify and measure catecholamines, their metabolites, and the gene expression of catecholamine receptors in osteosarcoma tissue. Materials and methods: The levels of 3,4-dihydroxyphenylacetic acid, norepinephrine, serotonin, and 5-hydroxyindoleacetic acid in cancer tissue and in adjacent and non-oncological bone tissue were analysed by high-performance liquid chromatography, and the gene expression of catecholamine receptors and of dopamine ß-hydroxylase, monoaminoxidase, ki67, and Runx2 in the osteosarcoma tissue, tissue adjacent to the tumour, non-oncological bone, and human brain tissue was analysed by RT-PCR. Results: We found significantly higher levels of 3,4-dihydroxyphenylacetic acid and norepinephrine in the cancer sample than in adjacent and non-oncological bone. We found that ß-adrenergic receptors and dopaminergic receptors, dopamine ß-hydroxylase, ki67, Runx2, and serotonergic receptor gene expression were significantly higher in tumour tissue than in adjacent and non-oncological bone. Conclusion: Catecholamines and their receptors could be potential molecular markers for osteosarcoma progression.

14.
Planta ; 250(4): 1177-1189, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31190117

RESUMO

MAIN CONCLUSION: A MAPK module, of which MPK6 kinase is an important component, is involved in the coordination of the responses to Pi and Fe in the primary root meristem of Arabidopsis thaliana. Phosphate (Pi) deficiency induces determinate primary root growth in Arabidopsis through cessation of cell division in the meristem, which is linked to an increased iron (Fe) accumulation. Here, we show that Mitogen-Activated Protein Kinase6 (MPK6) has a role in Arabidopsis primary root growth under low Pi stress. MPK6 activity is induced in roots in response to low Pi, and such induction is enhanced by Fe supplementation, suggesting an MPK6 role in coordinating Pi/Fe balance in mediating root growth. The differentiation of the root meristem induced by low Pi levels correlates with altered expression of auxin-inducible genes and auxin transporter levels via MPK6. Our results indicate a critical role of the MPK6 kinase in coordinating meristem cell activity to Pi and Fe availability for proper primary root growth.

15.
J Chem Phys ; 150(21): 214305, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31176334

RESUMO

Computational modeling has proven to be extremely useful for understanding how the morphology, size, and structure of TiO2 nanoparticles (NPs) affect their electronic properties and their usage in targeted applications (e.g., photocatalysis). Density functional theory (DFT) based calculations of NPs (on the order of hundreds to thousands of atoms) are, however, computationally highly demanding. Herein, we show that interatomic potentials (IPs) can provide a highly computationally efficient means to prepare NP structures which are sufficiently accurate to significantly reduce the computational cost of subsequent DFT calculations. We first compare the direct DFT optimization of faceted NPs directly cut from the anatase bulk crystal with the same calculation where the NP is preoptimized using four different IPs. We then establish the subsequent computational time saving for the respective complete DFT optimizations. We show that IP-based preoptimizing can greatly speed up DFT convergence, with speed-ups of 3×-10× for single point DFT energy evaluations. Moreover, as IP preoptimized NP structures can be closer to those of DFT energy minima, further speed-ups of 2× for DFT structure optimizations can be achieved. Finally, taking NPs derived from anatase spherical cuts, we show that IP-based molecular dynamics annealing gives rise to significant structural reconstruction with an associated high energetic stabilization, as confirmed by DFT calculations. Although similar results can be achieved using DFT tight binding methods, IP-based methods are 3-4 orders of magnitude faster and thus provide a particularly highly computationally efficient route to the preparation and design of large and diverse NP sets.

17.
J Reconstr Microsurg ; 35(7): 541-548, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31067581

RESUMO

BACKGROUND: In microsurgical reconstruction, vascular obstruction occurs in approximately 20% of patients. Close monitoring is central to their care. Clinical/Doppler detection of vascular obstruction could be enhanced by thermography. METHODS: A diagnostic test design included consecutive cases of hospitalized patients, ≥18 years old, who underwent surgery with free flaps. Two researchers separately evaluated patients with clinical/Doppler methods and thermographic camera hourly for 24 hours, every 2 hours for the next 24 hours, and then every 3 hours until discharge. The gold standard was visualization of thrombus or vascular obstruction during surgical reintervention. Sensitivity, specificity, positive/negative predictive value (PPV/NPV), and a delta temperature receiver operating characteristic (ROC) curve were calculated. RESULTS: A total of 2,364 tests were performed with a thermographic camera in 40 patients (31 females, 9 males) aged 50.12 ± 9.7 years. There were 28 deep inferior epigastric perforator, 5 anterolateral thigh, 3 radial, 2 scapular, 1 fibular, and 1 anteromedial thigh flaps included. Six (15%) had postoperative vascular obstruction (5 venous and 1 arterial). One flap developed partial necrosis and one total necrosis (overall survival 97.5%). ROC curve (area 0.97) showed the best results at ≥ 1.8°C of difference to the surrounding skin. Considering two consecutive positive evaluations, the sensitivity was 93%, specificity 96%, PPV 57%, and NPV 99%. The thermal imaging camera allows to identify the obstruction between 2 and 12 hours before the clinical method. CONCLUSION: Utilizing a thermographic camera can reduce detection time of vascular obstruction by several hours in microvascular free flaps that include the cutaneous island. This method proves useful for early diagnosis of postoperative vascular obstruction.

18.
Hum Pathol ; 89: 90-98, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054899

RESUMO

Discrimination between low- and high-grade endometrial carcinomas (ECs) is clinically relevant but can be challenging for pathologists, with moderate interobserver agreement. Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) is an oncofoetal protein that is associated with nonendometrioid endometrial carcinomas but has been limited studied in endometrioid carcinomas. The aim of this study is to investigate the diagnostic and prognostic value of IMP3 in the discrimination between low- and high-grade ECs and its added value to L1CAM. IMP3 and L1CAM expression was assessed in tumors from 378 patients treated for EC at 1 of 9 participating European Network for Individualised Treatment of Endometrial Cancer centers. IMP3 was expressed in 24.6% of the tumors. In general, IMP3 was more homogeneously expressed than L1CAM. IMP3 expression was significantly associated with advanced stage, nonendometrioid histology, grade 3 tumors, deep myometrial invasion, lymphovascular space invasion, distant recurrences, overall mortality, and disease-related mortality. Simultaneous absence of IMP3 and L1CAM expression showed the highest accuracy for identifying low-grade carcinomas (area under the curve 0.766), whereas simultaneous expression of IMP3 and L1CAM was strongly associated with high-grade carcinomas (odds ratio 19.7; 95% confidence interval 9.2-42.2). Even within endometrioid carcinomas, this combination remained superior to IMP3 and L1CAM alone (odds ratio 8.6; 95% confidence interval 3.4-21.9). In conclusion, IMP3 has good diagnostic value and together with L1CAM represents the optimal combination of diagnostic markers for discrimination between low- and high-grade ECs compared to IMP3 and L1CAM alone. Because of the homogenous expression of IMP3, this marker might be valuable in preoperative biopsies when compared to the more patchy L1CAM expression.

20.
Dermatol Ther ; 32(3): e12892, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30958613

RESUMO

Hailey-Hailey disease (HHD) or chronic benign familial pemphigus is an autosomal dominant genodermatosis with complete penetrance characterized by painful vesicles, erosions, and macerated intertriginous skin. We present a 66-year-old woman with a personal 35-year history of pruritic recurrent vesicles and erosions in both axillae and inguinal folds. HHD was confirmed by cutaneous biopsy. Past treatments had failed, including topical corticosteroids, antibiotics and oral doxycycline, minocycline, dapsone, and acitretin. Phototherapy and intralesional injection of toxin botulinum A was performed in the axillae. The patient was started on naltrexone 6.25 mg nightly. Six weeks later, complete clearing was observed. At typical doses, naltrexone blocks µ and δ opiod receptors, thereby blocking the union of ß-endorphins at those sites. Paradoxically, at low doses, the partial binding to those receptors leads to a homeostatic increase of opioid receptors and an upregulation of endogenous opioids. Low-dose naltrexone (LDN) may also exert an anti-inflammatory action through its antagonist effect on toll-like receptor 4 found on macrophages. We consider that LDN is an effective and safe alternative for the HHD, representing an important progress in the management of this disease with limited therapeutic options.

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