Le FORUM, Vol. 39 No. 3

https://digitalcommons.library.umaine.edu/francoamericain_forum/1046/thumbnail.jp

Electrocardiographic, echocardiographic and heart biomarker parameters in sheep experimentally poisoned by Palicourea marcgravii (Rubiaceae).

ABSTRACT - The present study aimed to identify and describe cardiac alterations in sheep experimentally poisoned with Palicourea marcgravii through analysis of serum cardiac biomarkers (serum troponin I and creatine kinase - CK-MB) and electro and echocardiographic assessments to contribute to a better understanding of the poisoning pathophysiology. P. marcgravii is the main plant within a group of 22 species that cause sudden death in Brazil; its toxic principle is sodium monofluoroacetate. Eight healthy crossbreed male sheep, aged between five and twelve months, weighing 14 to 27kg, were evaluated. The animals received 1g kg-1 of P. marcgravii plants orally. The sheep were evaluated before administering the plant (T0) through electro and echocardiography and blood collection to assess cardiac biomarkers (CK-MB and cTnI). Collections and analyses were repeated every four hours until the animal?s death. During the study, there was the presence of extravasation of serum troponin I carried out in a qualitative test, with positive values at time T4, and the serum CK-MB biomarker had a peak at T4 and slightly decreased at T8. The electro and echocardiographic examinations showed that the cause of death in these animals was due to acute heart failure characterized by arrhythmias, tachycardia/ventricular fibrillation, drop in cardiac output, left ventricular (LV) systolic dysfunction by the progressive decrease in the LV ejection fraction (EF), decrease in LV fractional shortening (FS), and decrease in aortic flow velocity and aortic flow gradient. This study seems to be the first to evaluate cardiac alterations in sheep poisoned by P. marcgravii through cardiac biomarkers and electro and echocardiographic exams. RESUMO - O presente estudo objetivou identificar e descrever as alterações cardíacas de ovinos intoxicados experimentalmente por Palicourea marcgravii através das análises de biomarcadores cardíacos séricos (troponina I sérica e a creatinoquinase - MB) e das avaliações eletro e ecocardiográficas contribuindo para o melhor entendimento da fisiopatologia da intoxicação. Palicourea marcgravii é a principal planta dentro de um grupo de 22 espécies que causam ?morte súbita? no Brasil e seu princípio tóxico é o monofluoracetato de sódio. Foram utilizados oito ovinos saudáveis machos, sem raça definida, com idades entre cinco e doze meses e peso de 14 a 27kg. Os animais receberam 1g/kg de Palicourea marcgravii por via oral. Os ovinos foram avaliados momentos antes da administração da planta (T0) através de eletro e ecocardiograma e coleta de sangue para avaliação dos biomarcadores cardíacos (CK-MB e cTnI). As análises e coletas foram repetidas a cada quatro horas até o óbito do animal. Durante o estudo observou-se extravasamento de troponina I sérica realizada em teste qualitativo, com valores positivos já em T4, assim como o biomarcador CK-MB sérico teve seu pico de aumento em T4 e em T8 houve uma leve redução. Aos exames eletro e ecocardiográfico foi possível determinar que a causa do óbito nestes animais ocorreu devido à insuficiência cardíaca aguda caracterizada por arritmias, taquicardia/fibrilação ventricular, queda no débito cardíaco, disfunção sistólica do ventrículo esquerdo (VE) pela diminuição progressiva da fração de ejeção (EF) do VE, diminuição na fração de encurtamento (FS) do VE, diminuição da velocidade do fluxo aórtico e do gradiente do fluxo aórtico. Este é o primeiro estudo que avalia as alterações cardiológicas de ovinos intoxicados por P. marcgravii através de biomarcadores cardíacos e exames eletro e ecocardiográficos

Mise à jour 2014 des recommandations du GEFPICS pour l’évaluation du statut HER2 dans les cancers du sein en France

De nouvelles recommandations internationales pour l’évaluation du statut HER2 dans les cancers du sein, basées sur plus de dix ans d’expérience et sur les résultats d’études cliniques et de concordance entre les différentes techniques de détection, viennent tout juste de voir le jour. Le présent article a pour objet de faire le point sur ces nouvelles recommandations, à la lumière de la publication récente du groupe de travail de l’American Society of Clinical Oncology (ASCO) et du Collège des pathologistes américains (CAP), adaptées à la pratique de la pathologie en France et revues par le groupe GEFPICS. À l’ère de la médecine personnalisée, la détermination du statut HER2 reste un élément phare dans le panel des biomarqueurs théranostiques des cancers du sein. Si l’interprétation du statut HER2 dans les cancers du sein est aisée dans la majorité des cas, un certain nombre de situations anatomocliniques est d’interprétation plus délicate, telles que la possibilité rare mais réelle de l’hétérogénéité intra-tumorale du statut de HER2, les formes à différenciation micropapillaire ou la ré-évaluation du statut des biomarqueurs lors de la rechute métastatique. Ces nouvelles recommandations abordent ces différentes questions, reprécisent les conditions pré-analytiques optimales et les critères d’interprétation (notamment des cas 2+), afin de réduire au maximum le risque de faux négatifs. Plus que jamais, la mobilisation de la spécialité d’anatomo-cytopathologie autour de la qualité des tests théranostiques témoigne de son implication dans la chaîne des soins en cancérologie., Summary International guidelines on HER2 determination in breast cancer have just been updated by the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP), on the basis of more than ten-year practice, results of clinical trials and concordance studies. The GEFPICS group, composed of expert pathologists in breast cancer, herein presents these recommendations, adapted to the French routine practice. These guidelines highlight the possible diagnosis difficulties with regards to HER2 status determination, such as intra-tumor heterogeneity, special histological subtypes and biomarker re-evaluation during metastatic relapse. Pre-analytical issues and updated scoring criteria (especially for equivocal cases) are detailed, in order to decrease the occurrence of false negative cases. In the era of personalized medicine, pathologists are more than ever involved in the quality of oncotheranostic biomarker evaluation.

Recommandations du GEFPICS concernant la phase pré-analytique pour l’évaluation de HER2 et des récepteurs hormonaux dans le cancer du sein : mise à jour 2014

Les tumeurs fixées et incluses en paraffine sont quotidiennement utilisées pour l’évaluation des biomarqueurs nécessaires au traitement des patientes atteintes d’un cancer du sein invasif. Les nouvelles recommandations internationales sur la phase pré-analytique ont été récemment revues, confirmant l’importance de la prise en charge optimale des prélèvements pour garantir des tests d’immunohistochimie ou d’hybridation in situ de qualité, quel que soit le biomarqueur envisagé. Incluant les procédés de fixation et de préparation des tissus, toutes les procédures pré-analytiques doivent être validées, standardisées et tracées. Elles nécessitent la collaboration et la formation de toutes les personnes impliquées dans le circuit du prélèvement, du préleveur jusqu’au technicien de pathologie et au pathologiste en passant par l’infirmière, ou le coursier. La prise en charge initiale optimale des pièces et une fixation de qualité sont des étapes majeures à maîtriser dans la phase pré-analytique. Cette mise à jour des recommandations du groupe d’étude des facteurs pronostiques immunohistochimiques dans le cancer du sein (GEFPICS) détaille et commente les différentes étapes pré-analytiques. L’observation de ces règles de bonne pratique, l’utilisation rigoureuse de témoins internes et externes et la participation régulière à des programmes d’assurance qualité sont autant de garanties pour une évaluation correcte et pérenne des biomarqueurs oncothéranostiques., Summary Biomarker assessment of breast cancer tumor samples is part of the routine workflow of pathology laboratories. International guidelines have recently been updated, with special regards to the pre-analytical steps that are critical for the quality of immunohistochemical and in situ hybridization procedures, whatever the biomarker analyzed. Fixation and specimen handling protocols must be standardized, validated and carefully tracked. Cooperation and training of the personnel involved in the specimen workflow (e.g. radiologists, surgeons, nurses, technicians and pathologists) are of paramount importance. The GEFPICS’ update of the recommendations herein details and comments the different steps of the pre-analytical process. Application of these guidelines and participation to quality insurance programs are mandatory to ensure the correct evaluation of oncotheranostic biomarkers

The Neurogenesis Actuator and NR2B/NMDA Receptor Antagonist Ro25-6981 Consistently Improves Spatial Memory Retraining Via Brain Region-Specific Gene Expression

NR2B-containing NMDA (NR2B/NMDA) receptors are important in controlling neurogenesis and are involved in generating spatial memory. Ro25-6981 is a selective antagonist at these receptors and actuates neurogenesis and spatial memory. Inter-structural neuroanatomical profiles of gene expression regulating adult neurogenesis and neuroapoptosis require examination in the context of memory retrieval and reversal learning. The aim was to investigate spatial memory retrieval and reversal learning in relation to gene expression-linked neurogenetic processes following blockade of NR2B/NMDA receptors by Ro25-6981. Rats were trained in Morris water maze (MWM) platform location for 5 days. Ro25-6981 was administered (protocol days 6–7) followed by retraining (days 15–18 or 29–32). Platform location was tested (on days 19 or 33) then post-mortem brain tissue sampling (on days 20 or 34). The expression of three genes known to regulate cell proliferation (S100a6), differentiation (Ascl1), and apoptosis (Casp-3) were concomitantly evaluated in the hippocampus, prefrontal cortex, and cerebellum in relation to the MWM performance protocol. Following initial training, Ro25-6981 enhanced visuospatial memory retrieval performance during further retraining (protocol days 29–32) but did not influence visuospatial reversal learning (day 33). Hippocampal Ascl1 and Casp-3 expressions were correspondingly increased and decreased while cerebellar S100a6 and Casp-3 activities were decreased and increased respectively 27 days after Ro25-6981 treatment. Chronological analysis indicated a possible involvement of new mature neurons in the reconfiguration of memory processes. This was attended by behavioral/gene correlations which revealed direct links between spatial memory retrieval enhancement and modified gene activity induced by NR2B/NMDA receptor blockade and upregulation

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future

BACKGROUND: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. MATERIALS AND METHODS: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. RESULTS: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. CONCLUSIONS: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe

Deficiency in trefoil factor 1 (TFF1) increases tumorigenicity of human breast cancer cells and mammary tumor development in TFF1-knockout mice

Although trefoil factor 1 (TFF1; previously named pS2) is abnormally expressed in about 50% of human breast tumors, its physiopathological role in this disease has been poorly studied. Moreover, controversial data have been reported. TFF1 function in the mammary gland therefore needs to be clarified. In this study, using retroviral vectors, we performed TFF1 gain- or loss-of-function experiments in four human mammary epithelial cell lines: normal immortalized TFF1-negative MCF10A, malignant TFF1-negative MDA-MB-231 and malignant TFF1-positive MCF7 and ZR75.1. The expression of TFF1 stimulated the migration and invasion in the four cell lines. Forced TFF1 expression in MCF10A, MDA-MB-231 and MCF7 cells did not modify anchorage-dependent or -independent cell proliferation. By contrast, TFF1 knockdown in MCF7 enhanced soft-agar colony formation. This increased oncogenic potential of MCF7 cells in the absence of TFF1 was confirmed in vivo in nude mice. Moreover, chemically induced tumorigenesis in TFF1-deficient (TFF1-KO) mice led to higher tumor incidence in the mammary gland and larger tumor size compared with wild-type mice. Similarly, tumor development was increased in the TFF1-KO ovary and lung. Collectively, our results clearly show that TFF1 does not exhibit oncogenic properties, but rather reduces tumor development. This beneficial function of TFF1 is in agreement with many clinical studies reporting a better outcome for patients with TFF1-positive breast primary tumors