Valproic acid induced selective apoptosis of ocular fibrous tunic in mice fetuses.

BACKGROUND: Valproic acid (VPA), a prescribed drug commonly used for various neurological perturbations, has been implicated in teratogenic inflictions on developing fetuses during pregnancy. The purpose of this research was to delineate the gross morphological and histological effects of VPA in the developing eye tunics and lens. METHODS: A time-dependent administration of 500 mg/kg VPA to BALB/c groups of female mice was coordinated during organogenesis (gestational days 7, 8, and 9) and compared to controls that received normal saline. Seized fetuses were checked for macroscopic eye anomalies, histological malformations with Azan trichrome staining, and levels of apoptotic activity with the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. RESULTS: Histochemical analysis showed that VPA-treated groups exhibited collagen deficiency (2.5-50% decrease in aniline blue intensity) and a marked increase in TUNEL-positive cells (p < .05) in corneal stroma and sclera/choroid layers while less was detected in retina and lens, when compared to controls. CONCLUSIONS: Since the evaluation of the inner structures did not manifest major differences, we conclude that VPA teratogenic influence display eclectic toxicity, as seen by increased apoptosis to eye layers with high degree fibrous context, particularly the outer tunics.

The human embryo following biopsy on day 5 versus day 3: viability, ultrastructure and spindle/chromosome configurations.

RESEARCH QUESTION: Are there any differences in viability, spindle abnormalities and mitochondrial and other organelle structures amongst embryos biopsied on day 3 versus day 5 before and after vitrification? DESIGN: A total of 240 day 3 biopsied embryos that developed to blastocysts but were rejected for transfer following preimplantation genetic testing for monogenic/single gene defects (PGT-M) (n = 115) or for aneuploidies (PGT-A) (n = 125) were divided into two groups: (i) 120 blastocysts treated for viability, spindle/chromosome configuration (SCC) analysis and transmission electron microscopy (TEM) analysis (fresh n = 20, n = 20, n = 20 and following vitrification/warming n = 20, n = 20, n = 20); (ii) 120 embryos were re-biopsied at the blastocyst stage and treated for viability, SCC and TEM analysis (fresh n = 20, n = 20, n = 20 and following vitrification/warming n = 20, n = 20, n = 20). Also, 60 vitrified blastocysts biopsied only on day 5 that were rejected for transfer following PGT-M (n = 6) or PGT-A (n = 54) were treated following warming for viability (n = 20), SCC (n = 20) and TEM analysis (n = 20). RESULTS: No differences were observed in SCC and ultrastructure between embryos biopsied on day 5 and day 3 but following vitrification higher numbers of abnormal spindles, distension of mitochondria, multivesicular bodies, lipofuscin droplets, altered cell junctions and occasionally excessive accumulation of glycogen granules were evident. The fresh day 3 biopsied group also had a lower incidence of damaged (propidium iodide-stained) cells compared with the fresh day 3+5 (P = 0.02) and the vitrified day 5 (P = 0.001) biopsied groups. CONCLUSIONS: Biopsies on day 5 and day 3 do not adversely affect embryo viability, SCC or ultrastructure, although following vitrification minimal embryo quality-dependent increases in spindle abnormalities and cell damage are observed.

The role of neuronal apoptosis in Valproic Acid brain-related teratogenesis: a histochemical and immunohistochemical study in BALB/c mice.

OBJECTIVES: The purpose of this study was to examine the teratogenic effects of Valproic Acid (VPA) and to investigate the role of apoptosis in neural tissue development. Although an apoptotic activity due to VPA has been reported, a direct connection of VPA-induced apoptosis with embryonic brain and∕or spine malformations and teratogenesis has not yet been established. MATERIALS AND METHODS: VPA was administered to BALB∕c mice, from the 7th to the 10th gestational days. Macroscopical congenital anomalies were registered under a stereomicroscope and were further histologically studied. Immunohistochemistry was performed with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) staining. RESULTS: Birth defects were described and an increase of the apoptotic activity in the brain was immunohistochemically identified. CONCLUSIONS: Considering the increased and very intense TUNEL expression of the neural cells of treated animals' fetuses, it is suggested that VPA triggers a pathological increase of apoptosis resulting in an imbalance between cell proliferation and cell death, the final result of which is malformation.

The attitudes of medical students in Europe toward the clinical importance of histology.

Many studies have been undertaken to assess the attitudes of medical students to the clinical importance of gross anatomy. However, much less is known about their attitudes toward the clinical importance of histology. Using Thurstone and Chave methods to assess attitudes, over 2,000 early stage medical students across Europe provided responses to a survey that tested the hypothesis that the students have a high regard for histology's clinical relevance. Regardless of the university and country surveyed, and of the teaching methods employed for histology, our findings were not consistent with our hypotheses, students providing a more moderate assessment of histology's importance compared to gross anatomy but more positive than their attitudes toward embryology. Histology should play a significant role in medical education in terms of appreciating not just normal structure and function but also pathology. We conclude that teachers of histology should pay special attention to informing newly-recruited medical students of the significant role played by histology in attaining clinical competence and in underpinning their status as being learned members of a healthcare profession. This work was conducted under the auspices of the Trans-European Pedagogic Research Group (TEPARG). Clin. Anat. 30:635-643, 2017. © 2017 Wiley Periodicals, Inc.

Embryology and Teratology in the Curricula of Healthcare Courses

Significant changes are occurring worldwide in courses for healthcare studies, including medicine and dentistry. Critical evaluation of the place, timing, and content of components that can be collectively grouped as the anatomical sciences has however yet to be adequately undertaken. Surveys of teaching hours for embryology in US and UK medical courses clearly demonstrate that a dramatic decline in the importance of the subject is in progress, in terms of both a decrease in the number of hours allocated within the medical course and in relation to changes in pedagogic methodologies. In this article, we draw attention to the need to provide within medical and dental curricula a universally accepted terminology for embryology and teratology, to develop core syllabuses and, in addition to providing professional training, to follow the practice of university education in taking students to the frontiers of knowledge. We also discuss different ways of teaching and assessing embryology and teratology, preferring to see the employment of practical methodologies, and we highlight problems related to the poor attitudes of students towards the perceived clinical relevance of embryology and teratology

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A core syllabus for the teaching of embryology and teratology to medical students.

Clinical relevance in the teaching of biomedical sciences within health care courses presupposes that there is internationally agreed core material within the curricula. However, with the exception of a syllabus for neuroanatomy and gross anatomy of the head and neck for medical students, core syllabuses within many of the specialized anatomical sciences have yet to be developed. The International Federation of Associations of Anatomists aims to formulate internationally accepted core syllabuses for all anatomical sciences disciplines initially using Delphi Panels that comprise anatomists, scientists, and clinicians who evaluate syllabus content. Here, the suggestions of a Delphi Panel for embryology and teratology are presented prior to their publication on the website of the International Federation of Associations of Anatomists. Hence, to obtain a more definitive syllabus, it is required that anatomical and embryological/teratological societies, as well as individual anatomists, embryologists and clinicians, freely comment upon, elaborate and amend, this draft syllabus. The goal is to set internationally recognized standards and thereby provide guidelines concerning embryological and teratological knowledge when involved with course development. Clin. Anat. 30:159-167, 2017. © 2016 Wiley Periodicals, Inc.

The attitudes of medical students in Europe toward the clinical importance of embryology.

Although there have been many studies reporting the attitudes of medical students to the clinical importance of gross anatomy, little is known about their opinions concerning the clinical importance of embryology. Using Thurstone and Chave methods to assess attitudes, nearly 1,600 medical students across Europe in the early stages of their training provided responses to a survey that tested the hypothesis that they do not regard embryology as highly clinically relevant. Indeed, we further proposed that student attitudes to gross anatomy are much more positive than those toward embryology. Our findings show that our hypotheses hold, regardless of the university and country surveyed and regardless of the teaching methods employed for embryology. Clearly, embryology has a significant part to play in medical education in terms of understanding prenatal life, of appreciating how the organization of the mature human body has developed, and of providing essential information for general medical practice, obstetrics and pediatrics, and teratology. However, while newly recruited medical students understand the importance of gross anatomy in the development of professional competence, understanding the importance of embryology requires teachers, medical educationalists, and devisors of medical curricula to pay special attention to informing students of the significant role played by embryology in attaining clinical competence and achieving the knowledge and understanding of the biomedical sciences that underpins becoming a learned member of a health care profession.

Ultrastructural alterations in the mouse lung caused by real-life ambient PM10 at urban traffic sites.

Current levels of ambient air particulate matter (PM) are associated with mortality and morbidity in urban populations worldwide. Nevertheless, current knowledge does not allow precise quantification or definitive ranking of the health effects of individual PM components and indeed, associations may be the result of multiple components acting on different physiological mechanisms. In this paper, healthy Balb/c mice were exposed to ambient PM10 at a traffic site of a large city (Thessaloniki, northern Greece), in parallel to control mice that were exposed to filtered air. Structural damages were examined in ultrafine sections of lung tissues by Transmission Electronic Microscopy (TEM). Ambient PM10 samples were also collected during the exposure experiment and characterized with respect to chemical composition and oxidative potential. Severe ultrastructural alterations in the lung tissue after a 10-week exposure of mice at PM10 levels often exceeding the daily limit of Directive 2008/50/EC were revealed mainly implying PM-induced oxidative stress. The DTT-based redox activity of PM10 was found within the range of values reported for traffic sites being correlated with traffic-related constituents. Although linkage of the observed lung damage with specific chemical components or sources need further elucidation, the magnitude of biological responses highlight the necessity for national and local strategies for mitigation of particle emissions from combustion sources.