Estudio immunohistoquímico de tumores de folículos pilosos caninos

El objetivo de este trabajo ha sido analizar los patrones de expresión de varias citoqueratinas e involucrina en tumores del folículo piloso canino con especial interés en los que exhiben menor diferenciación tricofítica. En el estudio se han utilizado 71 tumores foliculares diagnosticados en el Servicio de Diagnóstico de Histología y Anatomía Patológica Comparadas de la UCO. Las muestras, fijadas en formol al 10%, se procesaron de la forma habitual para diagnóstico histopatológico y se utilizó la técnica ABC para el estudio inmunohistoquímico. Los tumores foliculares se clasificaron histopatológicamente según Golsmidht y cols, (1998) como tricoepiteliomas (22), epiteliomas intracutáneos cornificantes (23) y tricoblastomas (5)y pilomatricomas (21)

Immunohistochemistry studies on bovine squamous cell carcinoma morphological characterization of epidermal cell proliferation and differentiation markers and characterization of cytokeratins

Bovine Ocular Squamous Cell Carcinoma (OSCC) is a general designation for a group of primary neoplasias of keratinocytes arising from ocular tissues, especially the lids and particularly the third eye lid. OSCC has been diagnosed all over the world with high prevalence, being the most common bovine tumour and the one causing the most significant economic losses (Hamir & Parry, 1980; Dennis et al., 1985, Heeney & Valli, 1985; Wilcock, 1993). In Portugal, the frequency of these tumours is particularly high in the Azores, where in S. Miguel Island a large number of cattle affected with OSCC is rejected for consumption at slaughter. OSCC is the second most frequent neoplasia after urinary bladder tumours, representing 21% of all cases of rejection due to neoplasia (Pinto et al, 1996). Several reasons have been advanced to explain this situation namely the fact that animals stay in pasture all year around, with a prolonged exposition to day light and benefiting from few shelters. The ingestion of toxic plants present the pasture could also give rise to photosensitazation problems, either primary or due to hepatic toxicity, that could generate predisposing conditions to the development of OSCC

Potential of Donation After Unexpected Circulatory Death Programs Defined by Their Demographic Characteristics

BACKGROUND. Donation after unexpected circulatory death (uDCD) donors are often suggested to increase the number of donor organs. In 2014, a uDCD protocol was implemented in three transplant centers in the Netherlands which unfortunately did not result in additional transplantations. This study was initiated to identify demographic factors influencing the potential success of uDCD programs. METHODS. Dutch resuscitation databases covering various demographic regions were analyzed for potential donors. The databases were compared with the uDCD implementation project and successful uDCD programs in Spain, France, and Russia. RESULTS. The resuscitation databases showed that 61% of all resuscitated patients were transferred to an emergency department. Age selection reduced this uDCD potential to 46% with only patients aged 18–65 years deemed eligible. Of these patients, 27% died in the emergency department. The urban region of Amsterdam showed the largest potential in absolute numbers (52 patients/y). Comparison with the uDCD implementation project showed large similarities in the percentage of potential donors; however, in absolute numbers, it showed a much smaller potential. Calculation of the potential per million persons and the extrapolation of the potential based on the international experience revealed the largest potential in urban regions. CONCLUSIONS. Implementation of a uDCD program should not only be based on the number of potential donors calculated from resuscitation databases. They show promising potential uDCD percentages for large rural regions and small urban regions; however, actual numbers per hospital are low, leading to insufficient exposure rates. It is, therefore, recommendable to limit uDCD programs to large urban regions

Effects of Essential Oils and Polyunsaturated Fatty Acids on Canine Skin Equivalents : Skin Lipid Assessment and Morphological Evaluation

A canine skin equivalent model has been validated for the assessment of a topical formulation effects. Skin equivalents were developed from freshly isolated cutaneous canine fibroblasts and keratinocytes, after enzymatic digestion of skin samples (n = 8) from different breeds. Fibroblasts were embedded into a collagen type I matrix, and keratinocytes were seeded onto its surface at air-liquid interface. Skin equivalents were supplemented with essential oils and polyunsaturated fatty acid formulation or with vehicle. Skin equivalents were histopathologically and ultrastructurally studied, and the three main lipid groups (free fatty acids, cholesterol, and ceramides) were analyzed. Results showed that the culture method developed resulted in significant improvements in cell retrieval and confluence. Treated samples presented a thicker epidermis with increased number of viable cell layers, a denser and compact stratum corneum, and a more continuous basal membrane. Regarding lipid profile, treated skin equivalents showed a significant increase in ceramide content (51.7 ± 1.3) when compared to untreated (41.6 ± 1.4) samples. Ultrastructural study evidenced a compact and well-organized stratum corneum in both treated and control skin equivalents. In conclusion, cell viability and ceramides increase, after lipid supplementation, are especially relevant for the treatment of skin barrier disruptions occurring in canine atopic dermatitis

Non-invasive detection of ischemic vascular damage in a pig model of liver donation after circulatory death

Background and Aims: Liver graft quality is evaluated by visual inspection prior to transplantation, a process highly dependent on the surgeon's experience. We present an objective, noninvasive, quantitative way of assessing liver quality in real time using Raman spectroscopy, a laser-based tool for analyzing biomolecular composition. Approach and Results: A porcine model of donation after circulatory death (DCD) with normothermic regional perfusion (NRP) allowed assessment of liver quality premortem, during warm ischemia (WI) and post-NRP. Ten percent of circulating blood volume was removed in half of experiments to simulate blood recovery for DCD heart removal. Left median lobe biopsies were obtained before circulatory arrest, after 45 minutes of WI, and after 2 hours of NRP and analyzed using spontaneous Raman spectroscopy, stimulated Raman spectroscopy (SRS), and staining. Measurements were also taken in situ from the porcine liver using a handheld Raman spectrometer at these time points from left median and right lateral lobes. Raman microspectroscopy detected congestion during WI by measurement of the intrinsic Raman signal of hemoglobin in red blood cells (RBCs), eliminating the need for exogenous labels. Critically, this microvascular damage was not observed during WI when 10% of circulating blood was removed before cardiac arrest. Two hours of NRP effectively cleared RBCs from congested livers. Intact RBCs were visualized rapidly at high resolution using SRS. Optical properties of ischemic livers were significantly different from preischemic and post-NRP livers as measured using a handheld Raman spectrometer. Conclusions: Raman spectroscopy is an effective tool for detecting microvascular damage which could assist the decision to use marginal livers for transplantation. Reducing the volume of circulating blood before circulatory arrest in DCD may help reduce microvascular damage

Splicing factor SF3B1 is overexpressed and implicated in the aggressiveness and survival of hepatocellular carcinoma

Splicing alterations represent an actionable cancer hallmark. Splicing factor 3B subunit 1 (SF3B1) is a crucial splicing factor that can be targeted pharmacologically (e.g. pladienolide-B). Here, we show that SF3B1 is overexpressed (RNA/protein) in hepatocellular carcinoma (HCC) in two retrospective (n = 154 and n = 172 samples) and in five in silico cohorts (n > 900 samples, including TCGA) and that its expression is associated with tumor aggressiveness, oncogenic splicing variants expression (KLF6-SV1, BCL-XL) and decreased overall survival. In vitro, SF3B1 silencing reduced cell viability, proliferation and migration and its pharmacological blockade with pladienolide-B inhibited proliferation, migration, and formation of tumorspheres and colonies in liver cancer cell lines (HepG2, Hep3B, SNU-387), whereas its effects on normal-like hepatocyte-derived THLE-2 proliferation were negligible. Pladienolide-B also reduced the in vivo growth and the expression of tumor-markers in Hep3B-induced xenograft tumors. Moreover, SF3B1 silencing and/or blockade markedly modulated the activation of key signaling pathways (PDK1, GSK3b, ERK, JNK, AMPK) and the expression of cancer-associated genes (CDK4, CD24) and oncogenic SVs (KLF6-SV1). Therefore, the genetic and/or pharmacological inhibition of SF3B1 may represent a promising novel therapeutic strategy worth to be explored through randomized controlled trials.Las alteraciones en el splicing son un rasgo distintivo del cáncer. La subunidad 1 del factor de splicing 3B (SF3B1) es un factor de splicing crucial que puede ser objeto de tratamiento farmacológico (por ejemplo, pladienolide-B). En este estudio demostramos que SF3B1 está sobreexpresado (ARN/proteína) en el carcinoma hepatocelular (CHC) en dos cohortes retrospectivas (n = 154 y n = 172 muestras) y en cinco cohortes in silico (n > 900 muestras, incluyendo TCGA) y que su expresión está asociada con la agresividad tumoral, la expresión de variantes de splicing oncogénicas (KLF6-SV1, BCL-XL) y la disminución de la supervivencia global. In vitro, el silenciamiento de SF3B1 redujo la viabilidad, proliferación y migración celular, y su bloqueo farmacológico con pladienolide-B inhibió la proliferación, migración y formación de esferas tumorales y colonias en líneas celulares de cáncer de hígado (HepG2, Hep3B, SNU-387), mientras que sus efectos sobre la proliferación de THLE-2 derivadas de hepatocitos de tipo normal fueron insignificantes. Pladienolide-B también redujo el crecimiento in vivo y la expresión de marcadores tumorales en tumores xenoinjertados inducidos por Hep3B. Además, el silenciamiento y/o bloqueo de SF3B1 moduló notablemente la activación de vías de señalización clave (PDK1, GSK3b, ERK, JNK, AMPK) y la expresión de genes asociados al cáncer (CDK4, CD24) y de SV oncogénicos (KLF6-SV1)

Correction to:Expanding controlled donation after the circulatory determination of death: statement from an international collaborative (Intensive Care Medicine, (2021), 47, 3, (265-281), 10.1007/s00134-020-06341-7)

The article “Expanding controlled donation after the circulatory determination of death: statement from an international collaborative”, written by Domínguez-Gil, B., Ascher, N., Capron, A.M. et al. was originally published electronically on the publisher’s internet portal on 21 February 2021 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on 25 March 2021 to © The Author(s) 2021 and the article is forthwith distributed under a Creative Commons Attribution this article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/. The original article has been corrected