The Role of Microscopy in Preclinical Safety Assessment

2000 ◽  
Vol 6 (S2) ◽  
pp. 998-999
Author(s):  
Barbara J. Dovey-Hartman

Microscopy plays a vital role in assessing the safety of New Chemical Entities (NCE) in the pre-clinical phase of drug development. Light microscopy (LM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM) are used at the Schering-Plough Research Institute (SPRI) for evaluation of NCE. To support regulatory submissions, NCE are routinely tested in rodents in short-term studies such as one-month toxicity studies, and in longterm studies such as oncogenicity studies that may last 24 months. At the completion of a study, the animals are necropsied and the required tissues collected and stored in fixative. The tissues for LM are processed to slides and stained with Hematoxylin and Eosin (H&E). The information derived from the examination of these tissues by LM becomes an essential part of the pathology report. The LM examination of these tissues usually yields the information needed to either progress a NCE or otherwise deter or halt development.

2018 ◽  
Vol 66 (2) ◽  
pp. 108 ◽  
Author(s):  
Isabella Veríssimo Nader Haddad ◽  
Lygia Dolores Ribeiro de Santiago-Fernandes ◽  
Silvia Rodrigues Machado

Programmed cell death (PCD) is defined as a sequence of genetically regulated events leading to controlled and organised cellular degradation. It plays a vital role in plant development; however, little is known about the role of PCD in reproductive development. Sterility in pistillate flowers of Maytenus obtusifolia Mart. has been shown to be related to cytoplasmic male sterility (CMS) based on reproductive biology and anatomical analysis. The recurrent PCD led us to investigate changes in the tapetum and sporogenic tissue during the establishment of male sterility using light and transmission electron microscopy combined with the use of TUNEL (terminal deoxynucleotidyl transferase mediated dUDP end-labelling) assay. The interruption of pollen development in pistillate flowers is a result of premature PCD in the tapetum and consequently in the sporogenic cells. Autophagy, via macroautophagy, occurs in the sporogenic cells and involves the formation of autophagosomes, through rough endoplasmic reticulum, and of complex macroautophagic structures. In the final stage of PCD, massive autophagy takes place. Male sterility in female individuals is thus reasonably interpreted as sporophytic CMS associated to autophagy.


Author(s):  
Benjamin F. Trump ◽  
Irene K. Berezesky ◽  
Raymond T. Jones

The role of electron microscopy and associated techniques is assured in diagnostic pathology. At the present time, most of the progress has been made on tissues examined by transmission electron microscopy (TEM) and correlated with light microscopy (LM) and by cytochemistry using both plastic and paraffin-embedded materials. As mentioned elsewhere in this symposium, this has revolutionized many fields of pathology including diagnostic, anatomic and clinical pathology. It began with the kidney; however, it has now been extended to most other organ systems and to tumor diagnosis in general. The results of the past few years tend to indicate the future directions and needs of this expanding field. Now, in addition to routine EM, pathologists have access to the many newly developed methods and instruments mentioned below which should aid considerably not only in diagnostic pathology but in investigative pathology as well.


Author(s):  
L. Tang ◽  
G. Thomas ◽  
M. R. Khan ◽  
S. L. Duan

Cr thin films are often used as underlayers for Co alloy magnetic thin films, such as Co1, CoNi2, and CoNiCr3, for high density longitudinal magnetic recording. It is belived that the role of the Cr underlayer is to control the growth and texture of the Co alloy magnetic thin films, and, then, to increase the in plane coercivity of the films. Although many epitaxial relationship between the Cr underlayer and the magnetic films, such as ﹛1010﹜Co/ {110﹜Cr4, ﹛2110﹜Co/ ﹛001﹜Cr5, ﹛0002﹜Co/﹛110﹜Cr6, have been suggested and appear to be related to the Cr thickness, the texture of the Cr underlayer itself is still not understood very well. In this study, the texture of a 2000 Å thick Cr underlayer on Nip/Al substrate for thin films of (Co75Ni25)1-xTix dc-sputtered with - 200 V substrate bias is investigated by electron microscopy.


Author(s):  
C. Ewins ◽  
J.R. Fryer

The preparation of thin films of organic molecules is currently receiving much attention because of the need to produce good quality thin films for molecular electronics. We have produced thin films of the polycyclic aromatic, perylene C10H12 by evaporation under high vacuum onto a potassium chloride (KCl) substrate. The role of substrate temperature in determining the morphology and crystallography of the films was then investigated by transmission electron microscopy (TEM).The substrate studied was the (001) face of a freshly cleaved crystal of KCl. The temperature of the KCl was controlled by an electric heater or a cold finger. The KCl was heated to 200°C under a vacuum of 10-6 torr and allowed to cool to the desired temperature. The perylene was then evaporated over a period of one minute from a molybdenum boat at a distance of 10cm from the KCl. The perylene thin film was then backed with an amorphous layer of carbon and floated onto copper microscope grids.


Author(s):  
Alan N. Hodgson

The hermaphrodite duct of pulmonate snails connects the ovotestis to the fertilization pouch. The duct is typically divided into three zones; aproximal duct which leaves the ovotestis, the middle duct (seminal vesicle) and the distal ovotestis duct. The seminal vesicle forms the major portion of the duct and is thought to store sperm prior to copulation. In addition the duct may also play a role in sperm maturation and degredation. Although the structure of the seminal vesicle has been described for a number of snails at the light microscope level there appear to be only two descriptions of the ultrastructure of this tissue. Clearly if the role of the hermaphrodite duct in the reproductive biology of pulmonatesis to be understood, knowledge of its fine structure is required.Hermaphrodite ducts, both containing and lacking sperm, of species of the terrestrial pulmonate genera Sphincterochila, Levantina, and Helix and the marine pulmonate genus Siphonaria were prepared for transmission electron microscopy by standard techniques.


Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 554
Author(s):  
Natália Salomão ◽  
Michelle Brendolin ◽  
Kíssila Rabelo ◽  
Mayumi Wakimoto ◽  
Ana Maria de Filippis ◽  
...  

Intrauterine transmission of the Chikungunya virus (CHIKV) during early pregnancy has rarely been reported, although vertical transmission has been observed in newborns. Here, we report four cases of spontaneous abortion in women who became infected with CHIKV between the 11th and 17th weeks of pregnancy. Laboratorial confirmation of the infection was conducted by RT-PCR on a urine sample for one case, and the other three were by detection of IgM anti-CHIKV antibodies. Hematoxylin and eosin (H&E) staining and an electron microscopy assay allowed us to find histopathological, such as inflammatory infiltrate in the decidua and chorionic villi, as well as areas of calcification, edema and the deposition of fibrinoid material, and ultrastructural changes, such as mitochondria with fewer cristae and ruptured membranes, endoplasmic reticulum with dilated cisterns, dispersed chromatin in the nuclei and the presence of an apoptotic body in case 1. In addition, by immunohistochemistry (IHC), we found a positivity for the anti-CHIKV antibody in cells of the endometrial glands, decidual cells, syncytiotrophoblasts, cytotrophoblasts, Hofbauer cells and decidual macrophages. Electron microscopy also helped in identifying virus-like particles in the aborted material with a diameter of 40–50 nm, which was consistent with the size of CHIKV particles in the literature. Our findings in this study suggest early maternal fetal transmission, adding more evidence on the role of CHIKV in fetal death.


2011 ◽  
Vol 678 ◽  
pp. 75-84 ◽  
Author(s):  
Marcello Cabibbo

Magnesium alloys containing rare earth elements are known to have high specific strength and corrosion resistance. The addition of SiC ceramic particles makes the metal matrix composite stronger with better wear and creep resistance and a still good machinability. The role of the reinforcement particles to the enhanced strength can be quantitatively evaluated using transmission electron microscopy (TEM). This paper presents a quantitative strengthening evaluation in a SiC Mg-RE composite alloy. The different contributions were determined by TEM inspections. The microstructure strengthening mechanism was studied after room temperature compression specimens. The way of combining the different contributions and the comparison to the measured yield stress, is also discussed and justified.


2007 ◽  
Vol 353-358 ◽  
pp. 2163-2166
Author(s):  
Ming Yang ◽  
Guo Qing Zhou ◽  
Jiang Guo Zhao ◽  
Zhan Jun Li

Nanocubes, monodispersed nanocrystals and nanospheres of Au have been prepared by a simple reaction between HAuCl4·4H2O, NaOH and NH2OH·HCl in the presence of gelatin. The role of gelatin and the affection of pH in producing the nanoparticles of Au were discussed. The products were characterized by X-ray powder diffraction, transmission electron microscopy, and UV-visible absorption spectroscopy. The sizes of the monodispersed nanocrystals of Au were estimated by Debye-Scherrer formula according to XRD spectrum.


1998 ◽  
Vol 523 ◽  
Author(s):  
D. S. Su ◽  
A. T. Tham ◽  
P. Schubert-Bischoff ◽  
I. Hähnert ◽  
W. Neumann ◽  
...  

AbstractIn this paper, the ordering of ternary semiconductor compounds is briefly reviewed by means of a coordination polyhedron model. Long-range ordering of chalcopyrite and CuAu-type structures can be represented as an array of repeating A2B2 tetrahedra. A CuAu-type ordered phase in a chalcopyrite AIBIIICVI2 compound is surrounded by an A3B+ AB3 boundary, whereas a CuPt-type ordered phase in a zinc-blende (A, B)IIICV compound is surrounded mainly by A2B2 type tetrahedra and thus restricted in size. Following the description of the ordered structure model, the detection of the asymmetry in ordering directions in (A, B)IIICV compounds is discussed. Some examples that employ transmission electron microscopy are presented.


2010 ◽  
Vol 134 (3) ◽  
pp. 462-480 ◽  
Author(s):  
Victor L. Roggli ◽  
Allen R. Gibbs ◽  
Richard Attanoos ◽  
Andrew Churg ◽  
Helmut Popper ◽  
...  

Abstract Asbestosis is defined as diffuse pulmonary fibrosis caused by the inhalation of excessive amounts of asbestos fibers. Pathologically, both pulmonary fibrosis of a particular pattern and evidence of excess asbestos in the lungs must be present. Clinically, the disease usually progresses slowly, with a typical latent period of more than 20 years from first exposure to onset of symptoms. Differential Diagnosis: Idiopathic Pulmonary Fibrosis The pulmonary fibrosis of asbestosis is interstitial and has a basal subpleural distribution, similar to that seen in idiopathic pulmonary fibrosis, which is the principal differential diagnosis. However, there are differences between the 2 diseases apart from the presence or absence of asbestos. First, the interstitial fibrosis of asbestosis is accompanied by very little inflammation, which, although not marked, is better developed in idiopathic pulmonary fibrosis. Second, in keeping with the slow tempo of the disease, the fibroblastic foci that characterize idiopathic pulmonary fibrosis are infrequent in asbestosis. Third, asbestosis is almost always accompanied by mild fibrosis of the visceral pleura, a feature that is rare in idiopathic pulmonary fibrosis. Differential Diagnosis: Respiratory Bronchiolitis Asbestosis is believed to start in the region of the respiratory bronchiole and gradually extends outward to involve more and more of the lung acinus, until the separate foci of fibrosis link, resulting in the characteristically diffuse pattern of the disease. These early stages of the disease are diagnostically problematic because similar centriacinar fibrosis is often seen in cigarette smokers and is characteristic of mixed-dust pneumoconiosis. Fibrosis limited to the walls of the bronchioles does not represent asbestosis. Role of Asbestos Bodies Histologic evidence of asbestos inhalation is provided by the identification of asbestos bodies either lying freely in the air spaces or embedded in the interstitial fibrosis. Asbestos bodies are distinguished from other ferruginous bodies by their thin, transparent core. Two or more asbestos bodies per square centimeter of a 5-μm-thick lung section, in combination with interstitial fibrosis of the appropriate pattern, are indicative of asbestosis. Fewer asbestos bodies do not necessarily exclude a diagnosis of asbestosis, but evidence of excess asbestos would then require quantitative studies performed on lung digests. Role of Fiber Analysis Quantification of asbestos load may be performed on lung digests or bronchoalveolar lavage material, employing either light microscopy, scanning electron microscopy, or transmission electron microscopy. Whichever technique is employed, the results are only dependable if the laboratory is well practiced in the method chosen, frequently performs such analyses, and the results are compared with those obtained by the same laboratory applying the same technique to a control population.


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