scholarly journals Pathology and Pathogenesis of Lassa Fever: Novel Immunohistochemical Findings in Fatal Cases and Clinico-pathologic Correlation

Author(s):  
Wun-Ju Shieh ◽  
Austin Demby ◽  
Tara Jones ◽  
Cynthia S Goldsmith ◽  
Pierre E Rollin ◽  
...  

Abstract Background Lassa fever is a zoonotic, acute viral illness first identified in Nigeria in 1969. An estimate shows that the “at risk” seronegative population (in Sierra Leone, Guinea, and Nigeria) may be as high as 59 million, with an annual incidence of all illnesses of three million, and fatalities up to 67,000, demonstrating the serious impact of the disease on the region and global health. Methods Histopathologic evaluation, immunohistochemical assay, and electron microscopic examination were performed on postmortem tissue samples from 12 confirmed Lassa fever cases. Results Lassa fever virus antigens and viral particles were observed in multiple organ systems and cells, including cells in the mononuclear phagocytic system and other specialized cells where it had not been described previously. Conclusions The immunolocalization of Lassa fever virus antigens in fatal cases provides novel insightful information with clinical and pathogenetic implications. The extensive involvement of the mononuclear phagocytic system, including tissue macrophages and endothelial cells suggests participation of inflammatory mediators from this lineage with the resulting vascular dilatation and increasing permeability. Other findings indicate the pathogenesis of LF is multifactorial and additional studies are needed.

Author(s):  
T. L. Benning ◽  
P. Ingram ◽  
J. D. Shelburne

Two benzofuran derivatives, chlorpromazine and amiodarone, are known to produce inclusion bodies in human tissues. Prolonged high dose chlorpromazine therapy causes hyperpigmentation of the skin with electron-dense inclusion bodies present in dermal histiocytes and endothelial cells ultrastructurally. The nature of the deposits is not known although a drug-melanin complex has been hypothesized. Amiodarone may also cause cutaneous hyperpigmentation and lamellar lysosomal inclusion bodies have been demonstrated within the cells of multiple organ systems. These lamellar bodies are believed to be the product of an amiodarone-induced phospholipid storage disorder. We performed transmission electron microscopy (TEM) and energy dispersive x-ray microanalysis (EDXA) on tissue samples from patients treated with these drugs, attempting to detect the sulfur atom of chlorpromazine and the iodine atom of amiodarone within their respective inclusion bodies.A skin biopsy from a patient with hyperpigmentation due to prolonged chlorpromazine therapy was fixed in 4% glutaraldehyde and processed without osmium tetroxide or en bloc uranyl acetate for Epon embedding.


2016 ◽  
pp. S139-S148 ◽  
Author(s):  
N. TRIBULOVA ◽  
V. KNEZL ◽  
B. SZEIFFOVA BACOVA ◽  
T. EGAN BENOVA ◽  
C. VICZENCZOVA ◽  
...  

We aimed to determine the impact of Ca2+-related disorders induced in intact animal hearts on ultrastructure of the cardiomyocytes prior to occurrence of severe arrhythmias. Three types of acute experiments were performed that are known to be accompanied by disturbances in Ca2+ handling. Langedorff-perfused rat or guinea pig hearts subjected to K+-deficient perfusion to induce ventricular fibrillation (VF), burst atrial pacing to induce atrial fibrillation (AF) and open chest pig heart exposed to intramyocardial noradrenaline infusion to induce ventricular tachycardia (VT). Tissue samples for electron microscopic examination were taken during basal condition, prior and during occurrence of malignant arrhythmias. Cardiomyocyte alterations preceding occurrence of arrhythmias consisted of non-uniform sarcomere shortening, disruption of myofilaments and injury of mitochondria that most likely reflected cytosolic Ca2+ disturbances and Ca2+ overload. These disorders were linked with non-uniform pattern of neighboring cardiomyocytes and dissociation of adhesive junctions suggesting defects in cardiac cell-to-cell coupling. Our findings identified heterogeneously distributed high [Ca2+]i-induced subcellular injury of the cardiomyocytes and their junctions as a common feature prior occurrence of VT, VF or AF. In conclusion, there is a link between Ca2+-related disorders in contractility and coupling of the cardiomyocytes pointing out a novel paradigm implicated in development of severe arrhythmias.


2018 ◽  
Vol 28 (4) ◽  
pp. 1-8
Author(s):  
Solomon Chuwang Chollom ◽  
Daniel Zanyu Egah ◽  
Patricial Lar ◽  
Sophia Osawe ◽  
Alash’le Abimiku

Open Medicine ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. 745-751 ◽  
Author(s):  
Nilufer Kocak ◽  
Candan Ozogul ◽  
Suleyman Kaynak ◽  
Ulker Sonmez ◽  
Mehmet Zengin ◽  
...  

AbstractTo analyze the retinal toxicity of bevacizumab at various doses both in vitrectomized and non-vitrectomized rabbit models. Twenty- eight rabbits were included in the study. Twenty- four rabbits were assigned to six groups, with 4 of the rabbits in the control group. The animals in Groups 1, 2 and 3 received bevacizumab at a dose of 0.3 mg, 0.5 mg and 1.5 mg /eye, respectively. The rabbits in Groups 4, 5 and 6 received intravitreal bevacizumab of 0.3 mg, 0.5 mg and 1.5mg/eye, respectively, after gas compression vitrectomy. Two weeks after the procedure, the rabbits were euthanized. Retina tissue samples were then obtained and examined with both light and electron microscopes. In Groups 1, 2 and 3 after bevacizumab injection, toxic degeneration in the photoreceptor and retinal pigment epithelium cells was observed via electron microscopic examination. The findings in Groups 4 and 5 were normal as compared to the control group. In Group 6, toxicity in the bipolar neurons and photoreceptor cells was noticed. Increased toxicity and retinal penetration were noticed in all administered doses of bevacizumab in the presence of vitreous. In addition, ocular toxicity occurred through the injection of the highest dose of bevacizumab after vitrectomy. It is possible that the bevacizumab dose and the, vitreous are as important as the drug half-life in the vitreous.


1988 ◽  
Vol 157 (3) ◽  
pp. 605-605 ◽  
Author(s):  
J. F. Saluzzo ◽  
F. Adam ◽  
J. B. McCormick ◽  
J. P. Digoutte

2021 ◽  
Vol 22 (3) ◽  
pp. 336-343
Author(s):  
J.A. Shenge ◽  
G.N. Odaibo ◽  
D.O. Olaleye

Background: Outbreaks of respiratory disease, febrile illness and rash occurred in two adjoining rural communities of Imo State, Southeastern, Nigeria, at different times between 2006 and 2020. Laboratory investigation was carried out to determine the aetiological agent of the outbreak. Methodology: Oropharyngeal swabs were collected from 6 individuals showing symptoms of disease, within 3-4 days of appearance of rash. Venous blood samples were also collected from a total of 41 symptomatic persons, their contacts and individuals with resolved infections. Swabs were inoculated into Vero, HEp-2c, B95a and MDCK cell lines. Sera were analyzed using enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G and M to rubella and measles viruses, while immunofluorescence assay was used to detect Lassa fever virus immunoglobulins. Descriptive data were analyzed using the Statistical Package for the Social Sciences (SPSS). Results: Four of the 6 (66.7%) swab samples showed viral activity or cytopathic effect characterized by clumping of cells in Vero cells while 2 (33.3%) in Hep-2c characterized by rounding up of cells. Thirty-nine (95.1%) sera were positive for measles IgG while 13 (31.7%) were positive for IgM. Thirty-six (87.8%) sera were positive for rubella IgG but none was positive for IgM. None of the sera was positive for Lassa fever virus IgG and IgM. Conclusion: Measles virus was responsible for the outbreak among previously vaccinated population in the communities, while Rubella and Lassa fever viruses were excluded as the etiological agents of the outbreak. Keywords: Epidemics; IgG and IgM; Cell lines; Vaccination; Measles virus   French title: Épidémie de rougeole dans la population vaccinée du sud-est du Nigéria Contexte: Des flambées de maladies respiratoires, de maladies fébriles et d'éruptions cutanées sont survenues dans deux communautés rurales voisines de l'État d'Imo, dans le sud-est du Nigéria, à des moments différents entre 2006 et 2020. Une enquête en laboratoire a été menée pour déterminer l'agent étiologique de l'épidémie. Méthodologie: Des écouvillons oropharyngés ont été prélevés sur 6 individus présentant des symptômes de maladie, dans les 3 à 4 jours suivant l'apparition de l'éruption cutanée. Des échantillons de sang veineux ont également été prélevés sur un total de 41 personnes symptomatiques, leurs contacts et des personnes souffrant d'infections résolues. Des écouvillons ont été inoculés dans des lignées cellulaires Vero, HEp-2c, B95a et MDCK. Les sérums ont été analysés en utilisant un test immuno-enzymatique (ELISA) pour les immunoglobulines G et M contre les virus de la rubéole et de la rougeole, tandis que le test d'immunofluorescence a été utilisé pour détecter les immunoglobulines du virus de la fièvre de Lassa. Les données descriptives ont été analysées à l'aide du progiciel statistique pour les sciences sociales (SPSS). Résultats: Quatre des 6 échantillons sur écouvillon (66,7%) ont montré une activité virale ou un effet cytopathique caractérisé par l'agglutination des cellules dans les cellules Vero, tandis que 2 (33,3%) dans Hep-2c étaient caractérisés par un arrondissement des cellules. Trente-neuf (95,1%) sérums étaient positifs pour les IgG contre la rougeole tandis que 13 (31,7%) étaient positifs pour les IgM. Trente-six (87,8%) sérums étaient positifs pour les IgG contre la rubéole, mais aucun n'était positif pour les IgM. Aucun des sérums n'était positif pour les IgG et IgM du virus de la fièvre de Lassa. Conclusion: Le virus de la rougeole était responsable de l'épidémie parmi la population précédemment vaccinée dans les communautés, tandis que les virus de la rubéole et de la fièvre de Lassa ont été exclus comme agents étiologiques de l'épidémie. Mots clés: épidémies; IgG et IgM; Lignées cellulaires; Vaccination; Virus de la rougeole


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