Ultrastructural alterations caused by immunological reactions after intracardiac injection of allogeneic antibodies against blood group antigens: An experimental study using the in vitro whole-rat embryo culture

Teratology ◽  
1995 ◽  
Vol 52 (2) ◽  
pp. 57-70 ◽  
Author(s):  
D. C. Van Der Zee ◽  
E. De Heer ◽  
J. Piersma ◽  
Chr. Vermeij-Keers
1994 ◽  
Vol 72 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Ian Guest ◽  
Harpal S. Buttar ◽  
Susan Smith ◽  
Daya R. Varma

Ingestion of the anticonvulsant drag valproic acid and of the angiotensin converting enzyme inhibitor captopril during pregnancy has been associated with abnormal fetal outcome in humans. In contrast, the use of the antiinflammatory drug ibuprofen and the antihistamine diphenhydramine has not been documented to be embryotoxic in humans. We evaluated the rat embryo culture system as a predictive model of teratogenesis, using these four drugs as test agents. Valproic acid, ibuprofen, and diphenhydramine were embryotoxic, inducing concentration-dependent decreases in growth and a significant increase in anomalies. Valproic acid caused an increase in neural tube defects, ibuprofen increased the incidence of abnormal maxillary processes, and diphenhydramine increased the number of embryos with distorted body morphology. These abnormalities were induced at concentrations of valproic acid and diphenhydramine that are used clinically, but ibuprofen only induced toxicity at concentrations greatly exceeding the therapeutic range. Captopril was not embryotoxic up to 5 mM, the highest concentration tested. These results suggest that the rat embryo culture system produces both false positive and false negative data on the teratogenic potential of drugs. Although such an in vitro assay may be suitable to determine the mechanism of teratogenesis, it is not a sensitive indicator of potential human teratogens on its own. These data support the view that in vitro systems can only supplement clinical and epidemiological observations in humans, possibly as a method to determine mechanisms of actions of teratogens.Key words: embryo culture, teratogenesis, valproic acid, captopril, ibuprofen, diphenhydramine.


1999 ◽  
Vol 62 (10) ◽  
pp. 1385-1389 ◽  
Author(s):  
Edward J. Kennelly ◽  
Thomas J. Flynn ◽  
Eugene P. Mazzola ◽  
John A. Roach ◽  
Thomas G. McCloud ◽  
...  

1996 ◽  
Vol 24 (2) ◽  
pp. 201-209
Author(s):  
Aldert H. Piersma ◽  
Rudolf Bechter ◽  
Nathalie Krafft ◽  
Beat P. Schmid ◽  
Jeanne Stadler ◽  
...  

The usefulness of the post-implantation rat embryo culture method in screening xenobiotic compounds for developmental toxicity was validated in four laboratories with five pairs of compounds. This approach was chosen to provide information on the interlaboratory reproducibility of the results and to compare the effects of chemical analogues in embryo culture. By testing analogous compounds which are known to have different embryotoxic potencies in vivo, the discriminating power of the embryo culture method for the compound classes under study could be optimally assessed. The classes selected for testing were triazole antifungals, phthalic ester metabolites, substituted pyridines, sulphonamides and methylated xanthines. In summary, it was possible to distinguish between the compounds in three of the pairs, it was not possible to discriminate between the compounds of one pair, and it was possible to discriminate between the compounds of the other pair at two out of the four laboratories. The embryo culture results generally show a good correspondence with the embryotoxic properties of the compounds tested in vivo, although the embryo culture method appeared to be able to discriminate between only some of the pairs of chemical analogues. Some discrepancies may have arisen among the laboratories, because of methodological differences. These results suggest that the post-implantation rat embryo culture method may be a useful tool for screening xenobiotics within classes of compounds known to interfere with embryogenesis during the period of development represented in culture.


2021 ◽  
Vol 17 (1) ◽  
pp. e1009237
Author(s):  
Yusheng Guo ◽  
Rosario Adriana Candelero-Rueda ◽  
Linda Jean Saif ◽  
Anastasia Nickolaevna Vlasova

Rotaviruses (RVs) are a leading cause of acute viral gastroenteritis in young children and livestock worldwide. Growing evidence suggests that host cellular glycans, such as histo-blood group antigens (HBGAs) and sialic acids (SA), are recognized by the RV surface protein VP4. However, a mechanistic understanding of these interactions and their effects on RV infection and pathogenesis is lacking. Here, we established a porcine crypt-derived 3D intestinal enteroids (PIEs) culture system which contains all intestinal epithelial cells identified in vivo and represents a unique physiologically functional model to study RV-glycan interactions in vitro. PIEs expressing different HBGAs (A+, H+, and A+/H+) were established and isolation, propagation, differentiation and RV infection conditions were optimized. Differentiated PIEs were infected with human RV (HRV) G1P[8] Wa, porcine RV (PRV) G9P[13], PRV Gottfried G4P[6] or PRV OSU G5P[7] virulent and attenuated strains and virus replication was measured by qRT-PCR. Our results indicated that virulent HRV G1P[8] Wa replicated to the highest titers in A+ PIEs, while a distinct trend was observed for PRV G9P[13] or G5P[7] with highest titers in H+ PIEs. Attenuated Wa and Gottfried strains replicated poorly in PIEs while the replication of attenuated G9P[13] and OSU strains in PIEs was relatively efficient. However, the replication of all 4 attenuate strains was less affected by the PIE HBGA phenotypes. HBGA synthesis inhibitor 2-F-Peracetyl-Fucose (2F) treatment demonstrated that HBGAs are essential for G1P[8] Wa replication; however, they may only serve as a cofactor for PRVs G9P[13] and OSU G5P[7]. Interestingly, contrasting outcomes were observed following sialidase treatment which significantly enhanced G9P[13] replication, but inhibited the growth of G5P[7]. These observations suggest that some additional receptors recognized by G9P[13] become unmasked after removal of terminal SA. Overall, our results confirm that differential HBGAs-RV and SA-RV interactions determine replication efficacy of virulent group A RVs in PIEs. Consequently, targeting individual glycans for development of therapeutics may not yield uniform results for various RV strains.


1989 ◽  
Vol 3 (3) ◽  
pp. 221-226 ◽  
Author(s):  
E.J.H. Mulder ◽  
L.J. Brader ◽  
A. Verhoef ◽  
A.H. Piersma ◽  
G.H.A. Visser ◽  
...  

Open Biology ◽  
2014 ◽  
Vol 4 (1) ◽  
pp. 130202 ◽  
Author(s):  
Jafar Mahdavi ◽  
Necmettin Pirinccioglu ◽  
Neil J. Oldfield ◽  
Elisabet Carlsohn ◽  
Jeroen Stoof ◽  
...  

Campylobacter jejuni is an important cause of human foodborne gastroenteritis; strategies to prevent infection are hampered by a poor understanding of the complex interactions between host and pathogen. Previous work showed that C. jejuni could bind human histo-blood group antigens (BgAgs) in vitro and that BgAgs could inhibit the binding of C. jejuni to human intestinal mucosa ex vivo. Here, the major flagella subunit protein (FlaA) and the major outer membrane protein (MOMP) were identified as BgAg-binding adhesins in C. jejuni NCTC11168 . Significantly, the MOMP was shown to be O- glycosylated at Thr 268 ; previously only flagellin proteins were known to be O- glycosylated in C. jejuni . Substitution of MOMP Thr 268 led to significantly reduced binding to BgAgs. The O- glycan moiety was characterized as Gal(β1–3)-GalNAc(β1–4)-GalNAc(β1–4)-GalNAcα1-Thr 268 ; modelling suggested that O- glycosylation has a notable effect on the conformation of MOMP and this modulates BgAg-binding capacity. Glycosylation of MOMP at Thr 268 promoted cell-to-cell binding, biofilm formation and adhesion to Caco-2 cells, and was required for the optimal colonization of chickens by C. jejuni , confirming the significance of this O- glycosylation in pathogenesis.


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