Development of Animal Models, Presenting Appropriate Analogues to Respective Human Systems

Author(s):  
Iskra V Sainova

The main idea of the current study was directed to developed appropriate experimental animal models, imitating respective systems with the human origin, and giving a possibility when the last is not available, experiments about necessary applications to humans to be performed. So, an additional copy of oncogene Dcn1 in normal mouse embryonic stem cells (mESCs), was inserted, by appropriate recombinant DNA-constructs, based on the AAV DNA-genome. All derived genetically-manipulated cellular types were co-cultivated with early myeloid and lymphoid progenitors, derived from non-transfected mESCs in the presence of GM-CSF (for induction of initial stages of both myeloid and lymphoid differentiation), and subsequently, malignant antigens were added (about further phagocyte and plasmatic cell differentiation, respectively). The derived and selected mESCs, containing an additionally-inserted copy of oncogene Dcn1, which indicated preserved normal/non-malignant characteristics both in vitro and in vivo, presented appropriate experimental normal mouse cellular analog of the cited in the scientific literature human embryonic trophoblasts, immortalized by infection with virus SV40. Additionally, the results obtained showed a possibility about the expression of membrane receptor glycoproteins by non-lymphoid and non-myeloid cellular types inappropriate conditions. Also, the presented study demonstrated the importance of the blood-testes barrier (BTB) for the prevention of malignancy development in the experimental hamster Graffi tumor model. The role of bio-molecules, as well as of intra- and extra-cellular inter-molecular interactions in cascade regulatory mechanisms, inactivation of the differentiation of embryonic and adult stem/progenitor cells in normal types, as well as for suppression of malignant transformation, was suggested. The established analogy of the developed and investigated in the current study experimental animal models gives a possibility for their application about performing of specific experiments when the respective systems with human origin are not available.

2000 ◽  
Vol 44 (10) ◽  
pp. 2848-2852 ◽  
Author(s):  
Nalin Rastogi ◽  
Khye Seng Goh ◽  
Mylene Berchel ◽  
André Bryskier

ABSTRACT The in vitro activities of HMR 3647 (telithromycin) and HMR 3004, two novel semisynthetic ketolides, were investigated and compared with that of the reference macrolide drug, clarithromycin, against 34 strains of slowly growing mycobacteria at pHs 6.8 and 7.4, as determined radiometrically. The MICs at pH 7.4 were about 1 to 2 dilutions lower than those observed at pH 6.8. In terms of the highest to the lowest activity, the three antibiotics could be classified as follows: clarithromycin > HMR 3004 > HMR 3647. Among the species tested, Mycobacterium bovis BCG, M. ulcerans, M. avium, and M. paratuberculosis were moderately susceptible to HMR 3004 and HMR 3647 (MICs at pH 7.4, ≤5.0 and ≤20.0 μg/ml, respectively, versus ≤1.25 μg/ml for clarithromycin), whereas M. tuberculosis, M. africanum, M. bovis, andM. simiae were resistant (MICs, ≥10.0 and ≥40.0 μg/ml, respectively, at pH 7.4). Although not more active than clarithromycin in vitro, the high level of intracellular accumulation of the two ketolides inside phagocytes warrants further screening in experimental animal models.


1988 ◽  
Vol 8 (3) ◽  
pp. 223-232 ◽  
Author(s):  
Jeffrey M. Isner ◽  
Dov Gal ◽  
P. Gabriel Steg ◽  
Stephen T. DeJesus ◽  
Anthony J. Rongione ◽  
...  

2010 ◽  
Vol 7 (1) ◽  
pp. 8 ◽  
Author(s):  
Ilpo Huhtaniemi ◽  
Maria Alevizaki ◽  
◽  

The concept of the direct involvement of gonadotrophins in tumorigenesis has been around for a long time. First, because the gonads are direct targets of gonadotrophin action, their tumours have been proposed to be gonadotrophin-dependent. Second, the recent findings of gonadotrophin receptors in extragonadal tissues has prompted the hypothesis that some extragonadal tumours (e.g. breast, uterus, prostate, pituitary and adrenal) could also be under the direct regulatory action of gonadotrophins. However, although supported by numerousin vitroexperiments and experimental animal models, the clinical evidence for a direct tumorigenic role of gonadotrophins remains weak. The purpose of this brief review is to present a critical evaluation of current information, both clinical and experimental, about the involvement of gonadotrophins in the induction and growth of gonadal and extragonadal tumours.


Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1685
Author(s):  
Pernille Tveden-Nyborg

Severe and long-term vitamin C deficiency can lead to fatal scurvy, which is fortunately considered rare today. However, a moderate state of vitamin C (vitC) deficiency (hypovitaminosis C)—defined as a plasma concentration below 23 μM—is estimated to affect up to 10% of the population in the Western world, albeit clinical hallmarks in addition to scurvy have not been linked to vitC deficiency. The brain maintains a high vitC content and uniquely high levels during deficiency, supporting vitC’s importance in the brain. Actions include both antioxidant and co-factor functions, rendering vitamin C deficiency likely to affect several targets in the brain, and it could be particularly significant during development where a high cellular metabolism and an immature antioxidant system might increase sensitivity. However, investigations of a non-scorbutic state of vitC deficiency and effects on the developing young brain are scarce. This narrative review provides a comprehensive overview of the complex mechanisms that regulate vitC homeostasis in vivo and in the brain in particular. Functions of vitC in the brain and the potential consequences of deficiency during brain development are highlighted, based primarily on findings from experimental animal models. Perspectives for future investigations of vitC are outlined.


2013 ◽  
Vol 13 (3) ◽  
pp. 1660-1670 ◽  
Author(s):  
Jayeeta Sengupta ◽  
Poulami Datta ◽  
Hirak. Kr. Patra ◽  
Anjan Kr. Dasgupta ◽  
Antony Gomes

2010 ◽  
Vol 285 (2) ◽  
pp. 207-214 ◽  
Author(s):  
U. Avcıbaşı ◽  
H. Demiroğlu ◽  
P. Ünak ◽  
F. Z. B. Müftüler ◽  
Ç. A. İçhedef ◽  
...  

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