Uric acid and acute kidney injury in high-risk patients for developing acute kidney injury undergoing cardiac surgery: A prospective multicenter study.

PURPOSE: It is unclear whether preoperative serum uric acid (SUA) elevation may play a role in the development of acute kidney injury (AKI) associated with cardiac surgery (CSA-AKI). We conducted a cohort study to evaluate the influence of preoperative hyperuricemia on AKI in patients at high risk for developing SC-AKI. DESIGN: Multicenter prospective international cohort study. SETTING: Fourteen university hospitals in Spain and the United Kingdom. PARTICIPANTS: We studied 261 consecutive patients at high risk of developing CSA-AKI, according to a Cleveland score ≥ 4 points, from July to December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKIN criteria were used for the definition of AKI. Multivariable logistic regression models and propensity score-matched pairwise analysis were used to determine the adjusted association between preoperative hyperuricemia (≥7 mg/dL) and AKI. Elevated preoperative AUS (≥7 mg/dL) was present in 190 patients (72.8%), whereas CSA-AKI occurred in 145 patients (55.5%). In multivariable logistic regression models, hyperuricemia was not associated with a significantly increased risk of AKI (adjusted Odds Ratio [OR]: 1.58; 95% confidence interval [CI]: 0.81-3; P = .17). In propensity score-matched analysis of 140 patients, the hyperuricemia group experienced similar adjusted odds of AKI (OR 1.05, 95%CI 0.93-1.19, P = .37). CONCLUSIONS: Hyperuricemia was not associated with an increased risk of AKI in this cohort of patients undergoing cardiac surgery at high risk of developing CSA-AKI.

[Translated article] Infrapatellar fat pad resection effect on the osteoarthritis development: Experimental study in sheep.

INTRODUCTION: The fat of the synovial joints can be used to maintain the joint structure. Our objective is to analyse the evolution of joint degeneration in knees with and without adipose pack. MATERIAL AND METHODOLOGY: In six sheep, the anterior cruciate ligament was sectioned in both knees, to cause osteoarthritis. In one group the fat pack was preserved and in another group it was completely removed. We performed a histological and molecular biology study analyzing the expression, in the synovial membrane, subchondral bone, cartilage, fat, meniscus, and synovial fluid, of RUNX2, PTHrP, cathepsin-K, and MCP1. RESULTS: We did not find morphological differences. We found increased expression of RUNX2 in synovial membrane, PTHrP and Cathepsin K in synovial fluid in the group without fat, and increased expression of RUNX2 in the meniscus and MCP1 in synovial fluid in the group with fat. CONCLUSION: Infrapatellar fat participates in the inflammatory process that accompanies osteoarthritis, since Hoffa fat pad resection alters pro-inflammatory markers, while the model with intact fat increases the pro-inflammatory marker MCP1 in synovial fluid.

Infrapatellar Fat Pad resection effect on the osteoarthritis development: Experimental study in sheep. / Efecto de la resección de la grasa del paquete infrapatelar de la rodilla en el desarrollo de la artrosis. Estudio experimental en ovejas.

INTRODUCTION: The fat of the synovial joints can be used to maintain the joint structure. Our objective is to analyze the evolution of joint degeneration in knees with and without adipose pack. MATERIAL AND METHODOLOGY: In six sheep, the anterior cruciate ligament was sectioned in both knees, to cause osteoarthritis. In one group the fat pack was preserved and in another group it was completely removed. We performed a histological and molecular biology study analyzing the expression, in the synovial membrane, subchondral bone, cartilage, fat, meniscus, and synovial fluid, of RUNX2, PTHrP, cathepsin-K, and MCP1. RESULTS: We did not find morphological differences. We found increased expression of RUNX2 in synovial membrane, PTHrP and Cathepsin K in synovial fluid in the group without fat, and increased expression of RUNX2 in the meniscus and MCP1 in synovial fluid in the group with fat. CONCLUSION: Infrapatellar fat participates in the inflammatory process that accompanies osteoarthritis, since Hoffa fat pad resection alters pro-inflammatory markers, while the model with intact fat increases the pro-inflammatory marker MCP1 in synovial fluid.

Cryopreservation of seeds of Neonotonia wightii Wight and Arn: a strategy for conservation, dormancy breaking and preservation of nutritional status.

BACKGROUND: N. wightii (Leguminosae) is valued as a cover crop and as a potential source of protein in food insecure countries. However, plantlet establishment is limited by physical dormancy. Our previous work has shown that exposure of N. wightii seeds to cryogenic temperatures is able to overcome physical dormancy. OBJECTIVE: The current study is an extension of that work where the field performance and nutritional composition of plants regenerated from N. wightii seeds was investigated. RESULTS: It was evident that plants regenerated from cryopreserved seeds displayed faster growth rates than those from control seeds. In addition, cryopreservation did not alter the nutritional profile of plants produced from cryo-stored seeds. CONCLUSION: Collectively, the results indicate that cryopreservation serves as a suitable strategy for the preservation of seeds of N. wightii with the added benefit of also serving as a dormancy breaking mechanism upon retrieval from cryogenic temperatures. Doi.org/10.54680/fr23510110712.

Exposure of maize seeds to liquid nitrogen modifies the morphology and hormonal response of young plants.

BACKGROUND: Cryopreservation currently represents the most suitable strategy for the long-term conservation of plant germplasm. While much effort has focused on the development of protocols to enable successful cryostorage, there are few, if any reports, that consider the effect of cryogenic temperatures on the phytohormone status of the seed and developing seedlings. OBJECTIVE: To investigate the effect of cryopreservation on external seed coat features as well as levels of indole-3-acetic acid (IAA), abscisic acid (ABA) and 1-aminocyclopropane-1-carboxylic acid (ACC) in maize. MATERIALS AND METHODS: Two groups of seeds at 6% moisture content were compared: one was maintained at 4 degree C (control) while the other was exposed to LN within cryo-vials. RESULTS: Seeds exposed to cryogenic temperatures were characterized by the presence of large cracks in the seed coat compared with control seeds. Cryogenic exposure also resulted in a reduction in biomass and plant height. Results from the phytohormone analysis showed an initial reduction in the levels of IAA, ABA and ACC after 7 days of growth followed by sharp increase in levels relative to the control by 14 days. Whilst the roles of ABA and ethylene (and by extension, its precursor ACC) are well studied as stress response molecules, much less is known about the potentially vital role of auxins in regulating plant growth under conditions of low temperature stress. CONCLUSION: It is postulated that the interaction of all three hormones modulate crosstalk between various stress responses and recovery pathways to ameliorate the damage caused by freezing stress and enable plant survival. Given the dearth of information on phytohormones in cryobiology, more studies are needed to fully elucidate these relationships in the context of freezing stress caused by liquid nitrogen. Doi.org/10.54680/fr23610110612.

Exposure of Calophyllum antillanum seeds to liquid nitrogen delays seedling emergence and decreases leaf anthraquinones.

BACKGROUND: Trees within the Calophyllum genus are multi-use trees that produce valuable wood, phytochemicals with a range of biological activities, and seed oil as a source of biodiesel. As a consequence of climate change, there is a need to develop strategies to preserve valuable plant genetic resources. Cryopreservation represents the most suitable option for the long-term storage of germplasm with minimal space and maintenance requirements. OBJECTIVE: To determine appropriate methods to cryopreserve seeds of Calophyllum antillanum and maintain secondary compound production. MATERIALS AND METHODS: Seeds at a moisture content of 6% were used to evaluate two treatments: seeds immersed in liquid nitrogen and control seeds. Biosynthetic pathway efficiency was assessed post-cryo by determining anthraquinone contents in roots, stems and leaves following 30 and 75 d of seedling growth. RESULTS: The results indicated that exposure to liquid nitrogen delayed germination and seedling emergence for a period of up to 45 d after seed sowing. By 60 d of cultivation, no significant differences in plant growth were observed for cryostored and control seeds. The levels of anthraquinones, which were also measured in seeds and seedlings, were lower in plants regenerated from cryostored seeds following 30 d of growth, but there were no differences in roots and stems by 75 d of growth. Furthermore, the difference in leaf anthraquinone levels for cryopreserved and control seeds at 75 d was much smaller than at 30 d. CONCLUSION: The low initial anthraquinone levels in emerging seedlings correlated with the initial slow growth of cryopreserved seeds.

Cryopreservation of seeds of the highly valued tropical timber species Swietenia mahagoni.

BACKGROUND: Swietenia mahagoni wood is one of the most valuable in world trade and, as a result, natural populations have been decimated due to unsustainable harvesting. The decline in natural population levels is being exacerbated by climate change. In order to ensure the preservation of valuable genotypes, there is an urgent need to develop strategies to conserve the genetic diversity present within this species. At present, cryopreservation is the most viable option for the long-term storage of plant germplasm, particularly for long-lived species which are challenging to maintain in the field. OBJECTIVE: To cryopreserve intact seeds of S. mahagoni, with the dual goal of retaining the biosynthetic capacity of plants, which is critical since this species is highly valued for medicinal purposes. MATERIALS AND METHODS: Seeds at a moisture content of 6% were immersed in liquid nitrogen (LN) before warming and recovery. Plantlet establishment and growth were assessed over a period of 70 days and anthraquinone synthesis was determined in roots, stems and leaves. RESULTS: The results showed an initial lag in the germination rate of cryopreserved seeds compared with control seeds; however, this difference disappeared over time. The lag in seedling emergence observed in cryostored seeds was also evident in the plant characteristics measured following 30 days of culture when all plant parameters measured were significantly higher in plants produced from control than cryostored seeds. However, after 70 days of growth, these differences were no longer apparent. Anthraquinone levels were also initially lower (at 30 days) in plants regenerated from cryopreserved seeds than those from control seeds, however, this difference was substantially reduced by 70 days thereby indicating the ability of these plants to accumulate secondary metabolites, albeit at a reduced rate, during the early stages of development. CONCLUSION: In S. mahagoni, the delay in anthraquinone production in plants regenerated from cryostored seeds during the early stages of development may have occurred as a consequence of the preferential allocation of resources towards the initiation of recovery processes in response to the stresses imposed by cryopreservation. Once the stresses were overcome and plant growth resumed, resources could be directed to secondary processes such as anthraquinone synthesis. doi.org/10.54680/fr22610110412.

Características y resultados de pacientes COVID-19 tratados con ventilación mecánica invasiva en Hospital San Juan de Dios. Marzo-junio 2020 / Features and evolution of patients with COVID-19 who required mechanical ventilation

BACKGROUND: The overall mortality of patients with COVID-19 admitted to intensive care units is approximately 40%. Aim: To describe the characteristics of a cohort of patients with COVID-19 who required invasive mechanical ventilation due to severe hypoxemic acute respiratory failure at a general hospital in Santiago, Chile. MATERIAL AND METHODS: Review of medical records and follow up for 28 days of patients with COVID-19 confirmed by polymerase chain reaction who required invasive mechanical ventilation and who were admitted to the intensive care unit from March 24 to June 7, 2020. RESULTS: Data from 152 patients aged 58 (interquartile range (IQR) 47-65 years (66% men) was analyzed. As of July 5, 36 (24%) had died, 75 (49%) were discharged, 10 (7%) were still on invasive mechanical ventilation, 11 (7%) remained with tracheostomy but without invasive mechanical ventilation, and 20 (13%) were hospitalized in a basic unit. The median time on invasive mechanical ventilation among extubated patients was 14 days (IQR 10-21) and 121 (80%) were in the prone position. Patients who died were older, had a higher frequency of diabetes mellitus and a higher driving pressure at 7 days than those discharged alive from the intensive care unit. Conclusions: In this study mortality was lower than that reported in the first international studies, probably due to the selection of younger patients and greater knowledge of the disease.

[Features and evolution of patients with COVID-19 who required mechanical ventilation]. / Características y resultados de pacientes COVID-19 tratados con ventilación mecánica invasiva en Hospital San Juan de Dios. Marzo-junio 2020.

BACKGROUND: The overall mortality of patients with COVID-19 admitted to intensive care units is approximately 40%. AIM: To describe the characteristics of a cohort of patients with COVID-19 who required invasive mechanical ventilation due to severe hypoxemic acute respiratory failure at a general hospital in Santiago, Chile. MATERIAL AND METHODS: Review of medical records and follow up for 28 days of patients with COVID-19 confirmed by polymerase chain reaction who required invasive mechanical ventilation and who were admitted to the intensive care unit from March 24 to June 7, 2020. RESULTS: Data from 152 patients aged 58 (interquartile range (IQR) 47-65 years (66% men) was analyzed. As of July 5, 36 (24%) had died, 75 (49%) were discharged, 10 (7%) were still on invasive mechanical ventilation, 11 (7%) remained with tracheostomy but without invasive mechanical ventilation, and 20 (13%) were hospitalized in a basic unit. The median time on invasive mechanical ventilation among extubated patients was 14 days (IQR 10-21) and 121 (80%) were in the prone position. Patients who died were older, had a higher frequency of diabetes mellitus and a higher driving pressure at 7 days than those discharged alive from the intensive care unit. CONCLUSIONS: In this study mortality was lower than that reported in the first international studies, probably due to the selection of younger patients and greater knowledge of the disease.

Citoquinas proinflamatorias en la grasa articular y subcutánea del muslo en pacientes artrósicos / Pro-inflammatory cytokines in the knee fat pad and subcutaneous fat of the thigh in osteoarthritic patients

Resumen: Objetivo: Analizar el nivel de citoquinas proinflamatorias en la grasa articular del paquete adiposo en pacientes con gonartrosis, en relación con la grasa subcutánea del muslo. Material y métodos: Efectuamos un estudio de grasa del paquete adiposo articular de la rodilla afectada de artrosis y de la grasa subcutánea del muslo del mismo lado, a la mayor distancia de la articulación en seis pacientes con gonartrosis grave, con una edad media de 68 años (rango: 55-81 años). De las muestras de grasa se obtuvieron las células mesenquimales progenitoras. Los sobrenadantes de células mesenquimales obtenidas se utilizaron para analizar factores inflamatorios (IL-1b, IL6, IL8, IL9, IL1ra, IL12, IL13, IL15) y angiogénicos (VEGF, PDGF bb), así como citoquinas inmunomoduladoras (IP-10 e INF-γ) y se compararon las medias de dos muestras. Resultados: El análisis cuantitativo reveló una disminución significativa (p < 0.05) de IL-1b, IL6, IL8, IL9, IL1ra, IL12, IL13 y un aumento de IL15 en la grasa de Hoffa frente al tejido adiposo subcutáneo. Del mismo modo, el análisis de factores angiógenicos como VEGF y PDGF bb, al igual que los factores IP-10 e INF-γ presentaron una disminución significativa en la grasa de Hoffa (p < 0.05) frente al tejido adiposo subcutáneo. Discusión: Las células mesenquimales del paquete adiposo articular de la rodilla artrósica grave muestran una disminución significativa de citoquinas inflamatorias, aun en el estado crónico, y una disminución significativa de factores angiogénicos y citoquinas inmunomoduladoras (IP10 e INF).

Abstract: Objective: To analyze the level of pro-inflammatory cytokines in osteoarthritis knee joint fat pad in relation to the subcutaneous fat of the thigh. Material and methods: We performed a study of fat of the knee joint adipose affected of osteoarthritis and subcutaneous fat of the thigh of the same side to the greater distance of the joint in six patients with severe gonarthrosis, with a mean age of 68 years (range: 55-81 years). From the fat samples the progenitor mesenchymal cells were obtained. The supernatants of mesenchymal cells obtained to analyze inflammatory factors (IL-1b, IL6, IL9, IL1ra, IL12, IL13, IL15) and angiogenic (VEGF, PDGF bb) and immunomodulatory cytokines (IP-10 and INF-γ) means of two samples. Results: Quantitative analysis revealed a significant (p < 0.05) decrease in IL-1b, IL6, IL8, IL9, IL1ra, IL12, IL13 and increase of IL15 in Hoffa fat pad versus subcutaneous adipose tissue. Likewise, the analysis of angiogenic factors such as VEGF and PDGF, as well as factors IP-10 and INF-γ presented a significant decrease (p < 0.05) in Hoffa fat pad versus subcutaneous adipose tissue. Discussion: Mesenchymal cells from the adipose tissue of the severe osteoarthritic knee show a significant decrease in inflammatory cytokines even in the chronic state and a significant decrease in angiogenic factors and immunomodulatory cytokines (IP10 and INF).

[Pro-inflammatory cytokines in the knee fat pad and subcutaneous fat of the thigh in osteoarthritic patients]. / Citoquinas proinflamatorias en la grasa articular y subcutánea del muslo en pacientes artrósicos.

OBJECTIVE: To analyze the level of pro-inflammatory cytokines in osteoarthritis knee joint fat pad in relation to the subcutaneous fat of the thigh. MATERIAL AND METHODS: We performed a study of fat of the knee joint adipose affected of osteoarthritis and subcutaneous fat of the thigh of the same side to the greater distance of the joint in six patients with severe gonarthrosis, with a mean age of 68 years (range: 55-81 years). From the fat samples the progenitor mesenchymal cells were obtained. The supernatants of mesenchymal cells obtained to analyze inflammatory factors (IL-1b, IL6, IL9, IL1ra, IL12, IL13, IL15) and angiogenic (VEGF, PDGF bb) and immunomodulatory cytokines (IP-10 and INF-) means of two samples. RESULTS: Quantitative analysis revealed a significant (p 0.05) decrease in IL-1b, IL6, IL8, IL9, IL1ra, IL12, IL13 and increase of IL15 in Hoffa fat pad versus subcutaneous adipose tissue. Likewise, the analysis of angiogenic factors such as VEGF and PDGF, as well as factors IP-10 and INF- presented a significant decrease (p 0.05) in Hoffa fat pad versus subcutaneous adipose tissue. DISCUSSION: Mesenchymal cells from the adipose tissue of the severe osteoarthritic knee show a significant decrease in inflammatory cytokines even in the chronic state and a significant decrease in angiogenic factors and immunomodulatory cytokines (IP10 and INF).

OBJETIVO: Analizar el nivel de citoquinas proinflamatorias en la grasa articular del paquete adiposo en pacientes con gonartrosis, en relación con la grasa subcutánea del muslo. MATERIAL Y MÉTODOS: Efectuamos un estudio de grasa del paquete adiposo articular de la rodilla afectada de artrosis y de la grasa subcutánea del muslo del mismo lado, a la mayor distancia de la articulación en seis pacientes con gonartrosis grave, con una edad media de 68 años (rango: 55-81 años). De las muestras de grasa se obtuvieron las células mesenquimales progenitoras. Los sobrenadantes de células mesenquimales obtenidas se utilizaron para analizar factores inflamatorios (IL-1b, IL6, IL8, IL9, IL1ra, IL12, IL13, IL15) y angiogénicos (VEGF, PDGF bb), así como citoquinas inmunomoduladoras (IP-10 e INF-) y se compararon las medias de dos muestras. RESULTADOS: El análisis cuantitativo reveló una disminución significativa (p 0.05) de IL-1b, IL6, IL8, IL9, IL1ra, IL12, IL13 y un aumento de IL15 en la grasa de Hoffa frente al tejido adiposo subcutáneo. Del mismo modo, el análisis de factores angiógenicos como VEGF y PDGF bb, al igual que los factores IP-10 e INF- presentaron una disminución significativa en la grasa de Hoffa (p 0.05) frente al tejido adiposo subcutáneo. DISCUSIÓN: Las células mesenquimales del paquete adiposo articular de la rodilla artrósica grave muestran una disminución significativa de citoquinas inflamatorias, aun en el estado crónico, y una disminución significativa de factores angiogénicos y citoquinas inmunomoduladoras (IP10 e INF).

Correlation between physical examination and intraoperative findings in shoulder disease treated by arthroscopy. Statistical analysis of 150 patients. / Correlación entre la exploración física y los hallazgos intraoperatorios de patología de hombro tratada mediante artroscopia. Análisis estadístico de 150 pacientes.

INTRODUCTION: Only a few clinical exploratory manoeuvres are truly discriminatory and useful in shoulder disease. The aim of this study is to correlate the physical examination results of the shoulder with the true diagnosis found by arthroscopy. METHODS: A retrospective case series of 150 patients with the most common surgical conditions of the shoulder. Data were collected on the suspicion of each pathology, the physical examination of the patient, and the actual discovery of the disease during arthroscopic surgery. RESULTS: The Bankart examination manoeuvres of the lesion show the best results, with a 92.1% positive prediction value (PPV), a 99.1% negative predictive value (NPV), followed by the impingement syndrome, with a PPV of 94.4%, and total cuff rupture with a PPV of 92.3%.Exploration of the superior labrum anterior to posterior (SLAP) lesion had an NPV of 99.1%. CONCLUSION: Physical examination is sufficient to diagnose or rule out Bankart. A positive physical examination provides the complete rupture of the rotator cuff, and requires further studies. The patients suspected of subacromial syndrome only need an NMR if the physical tests are negative. The conclusions drawn from this work can have a significant impact on both cost savings (by reducing forward tests), and saving time in certain cases in which, after appropriate physical examination, surgery may be indicated without losing time in intermediate steps.

Asociación entre calidad de vida y cantidad de sueño en adultos mayores de la Región Metropolitana y Región de Valparaíso, Chile / Association of quality of life perception with sleeping patterns in Chilean older people

Background: An adequate sleeping pattern recovers physical and mental wellbeing and improves mood. Aim: To determine the association between quality of life and quantity of sleep in older people living in Santiago and Viña del Mar, Chile. Material and Methods: The Spanish versions of the Health Promoting Lifestyles survey and the Pittsburgh Sleep Quality Index were answered by 975 non-disabled participants aged 70.7 ± 7.4 years (61% females). Results: Older adults who slept < 7.0 or > 8.5 hours (h) per night were at higher risk of having lower quality of life scores for all sub-domains, compared with those that slept 7.0 to 8.5 h per night. Conclusions: A normal sleep pattern in older adults is associated with a better quality of life perception.

Classical antiferromagnetism in kinetically frustrated electronic models.

We study, by means of the density matrix renormalization group, the infinite U Hubbard model--with one hole doped away from half filling--in triangular and square lattices with frustrated hoppings, which invalidate Nagaoka's theorem. We find that these kinetically frustrated models have antiferromagnetic ground states with classical local magnetization in the thermodynamic limit. We identify the mechanism of this kinetic antiferromagnetism with the release of the kinetic energy frustration, as the hole moves in the established antiferromagnetic background. This release can occur in two different ways: by a nontrivial spin Berry phase acquired by the hole, or by the effective vanishing of the hopping amplitude along the frustrating loops.

Azelaic acid in the treatment of acne in adult females: case reports.

Acne, one of the most common skin problems in dermatological practice, is a condition that affects not only adolescents but also adults. While approximately 80% of cases occurring in adulthood are persistent from teenage years, around 20% are described as 'late-onset' disease, appearing for the first time in adulthood. The disease can be triggered by hormonal changes (including a change from one contraceptive to another), or it can be induced by certain nonhormonal medications, emotional stress, and various underlying diseases such as polycystic ovary syndrome. In many cases acne becomes a chronic skin condition with undulating activity, including improvement and relapse phases, and is often experienced as a major psychological burden. It is, therefore, even more important to provide an effective as well as a safe and tolerable treatment. The spectrum of topical acne treatments has expanded substantially in recent years and various topical medications are available, ranging from azelaic acid, antibiotics, retinoids and benzoyl peroxide to several fixed combinations of these active compounds. The following case collection illustrates how 15% azelaic acid gel, as a well-established monotherapy, can be successfully employed to treat mild-to-moderate forms of adult female acne.

[Association of quality of life perception with sleeping patterns in Chilean older people]. / Asociación entre calidad de vida y cantidad de sueño en adultos mayores de la Región Metropolitana y Región de Valparaíso, Chile.

BACKGROUND: An adequate sleeping pattern recovers physical and mental wellbeing and improves mood. AIM: To determine the association between quality of life and quantity of sleep in older people living in Santiago and Viña del Mar, Chile. MATERIAL AND METHODS: The Spanish versions of the Health Promoting Lifestyles survey and the Pittsburgh Sleep Quality Index were answered by 975 non-disabled participants aged 70.7 ± 7.4 years (61% females). RESULTS: Older adults who slept < 7.0 or > 8.5 hours (h) per night were at higher risk of having lower quality of life scores for all sub-domains, compared with those that slept 7.0 to 8.5 h per night. CONCLUSIONS: A normal sleep pattern in older adults is associated with a better quality of life perception.

Identification of circulating miRNAs profiles that distinguish malignant pleural mesothelioma from lung adenocarcinoma.

Accurate diagnosis of malignant pleura mesothelioma (MPM) is challenging. Differential diagnosis of MPM versus lung adenocarcinoma (AD) is particularly difficult, yet clinically important since the two neoplasias call for different treatment approaches. Circulating miRNA-profiling to identify miRNAs that can be used to distinguish MPM from AD has not been reported. We conducted a wide screening study of miRNA profiles in serum pools of MPM patients (N = 11), AD patients (N = 36), and healthy subjects (N = 45) to identify non-invasive biomarkers for differential diagnosis of MPM and AD, using deep sequencing. Sequencing detected up to 300 known miRNAs and up to 25 novel miRNAs species in the serum samples. Among known miRNAs, 7 were upregulated in MPM and 12 were upregulated in AD compared to healthy controls. Of these, eight were distinctive for AD and three were unique for MPM. Direct comparison of the miRNA profiles for MPM and AD revealed differences in miRNA levels that could be useful for differential diagnosis. No differentially expressed novel miRNAs were found. Further bioinformatics analysis indicated that three upregulated miRNAs in MPM are associated with the p38 pathway. There are unique alterations in serum miRNAs in MPM and AD compared to healthy controls, as well as differences between MPM and AD profiles. Differing miRNA levels between MPM and AD may be useful for differential diagnosis. A potential association to p38 pathway of three upregulated miRNAs in MPM was revealed.

Comparative assessment of PDE 4 and 7 inhibitors as therapeutic agents in experimental autoimmune encephalomyelitis.

BACKGROUND AND PURPOSE: PDE4 inhibition suppresses experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, side effects hinder PDE4 inhibitors clinical use. PDE7 inhibition might constitute an alternative therapeutic strategy, but few data about the anti-inflammatory potential of PDE7 inhibitors are currently available. We have used the EAE model to perform a comparative evaluation of PDE4 and PDE7 inhibition as strategies for MS treatment. EXPERIMENTAL APPROACH: Two PDE7 inhibitors, the sulfonamide derivative BRL50481 and the recently described quinazoline compound TC3.6, were assayed to modulate EAE in SJL mice, in comparison with the well-known PDE4 inhibitor Rolipram. We evaluated clinical signs, presence of inflammatory infiltrates in CNS and anti-inflammatory markers. We also analysed the effect of these inhibitors on the inflammatory profile of spleen cells in vitro. KEY RESULTS: TC3.6 prevented EAE with efficacy similar to Rolipram, while BRL50481 had no effect on the disease. Differences between both PDE7 inhibitors are discussed. Data from Rolipram and TC3.6 showed that PDE4 and PDE7 inhibition work through both common and distinct pathways. Rolipram administration caused an increase in IL-10 and IL-27 expression which was not found after TC3.6 treatment. On the other hand, both inhibitors reduced IL-17 levels, prevented infiltration in CNS and increased the expression of the T regulator cell marker Foxp3. CONCLUSIONS AND IMPLICATIONS: These results provide new information about the effects of Rolipram on EAE, underline PDE7 inhibition as a new therapeutic target for inflammatory diseases and show the value of TC3.6 to prevent EAE, with possible consequences for new therapeutic tools in MS.