Mode of action of amphotericin B on chick embryo fibroblasts and on mouse Ehrlich tumour cells: a cytological and cytochemical analysis

1975 ◽  
Vol 18 (3) ◽  
pp. 441-451
Author(s):  
F. De Paermentier ◽  
R. Bassleer ◽  
A. Lepoint ◽  
C. Desaive ◽  
G. Goessens ◽  
...  

Chick embryo fibroblasts cultivated in vitro and Ehrlich ascites tumor cells (in vivo or in vitro) have been treated with amphotericin B. Cell multiplication is strongly inhibited. Large clear zones appear in the fibroblast nucleoi (phase-contrast and electron-microscope observations). Many treated fibroblasts and tumour cells have a high DNA content (pre-mitotic or polyploid level; measurements by cytophotometry). However, the RNA content (cytophotometry) and the total protein content (cytophotometry and micro-interferometry) are relatively low in the tumour cells. As shown by autoradiography, DNA synthesis is active but RNA synthesis and, in some cases, protein synthesis are inhibited. Due to this unbalanced growth, the cells cannot divide.

2004 ◽  
Vol 92 (1) ◽  
pp. 81-86 ◽  
Author(s):  
I. A. Abd El-Gawad ◽  
E. M. El-Sayed ◽  
S. A. Hafez ◽  
H. M. El-Zeini ◽  
F. A. Saleh

The effect of yoghurt and soya yoghurt containing Bifidobacterium lactis Bb-12 or B. longum Bb-46 on Ehrlich ascites tumour cell proliferation was investigated in vitro and in vivo. Tumour cells were incubated with B. lactis Bb-12 or B. longum Bb-46 cultivated in de Mann Rogosa Sharpe (MRS) broth medium, or with their centrifuged supernatant fractions or sediments, for 2 h at 37°C. Treatment resulted in the inhibition of tumour cell proliferation by 85·42 (sd 0·78) and 85·10 (sd 1·28) % by intact micro-organisms, 77·61 (sd 0·29) and 71·43 (sd 1·75) % by their supernatant fractions, but only 4·00 (sd 0·19) and 9·09 (sd 1·24) % by the two sedimented bacteria, respectively. The incubation of tumour cells with yoghurt and soya yoghurt containing Bb-12 for 2 h resulted in 83·01 (sd 0·11) and 88·23 (sd 0·06) % inhibition, respectively, while it was 83·82 (sd 0·24) and 86·36 (sd 0·06) %, respectively for the same products containing Bb-46. Corresponding values for plain yoghurt and soya milk (without bifidobacteria) were 32·81 (sd 0·14) and 5·55 (sd 0·12) %, respectively. The differences between yoghurt or soya yoghurt containing Bb-12 or Bb-46 and plain yoghurt, soya milk or control treatments were statistically significant (n 3; P>0·05). Female Swiss albino mice were injected intraperitoneally with the same tumour cells. The lifespan of mice fed diets supplemented with yoghurt or soya yoghurt containing Bb-12 or Bb-46 was prolonged by 16, 23, 34 and 39%, respectively compared with that of the positive control group (n 6; P>0·05). The lifespan of groups fed plain yoghurt or soya milk was prolonged by 15 and 8%, respectively. Prolongation of lifespan was positively correlated with faeces bifidobacterial count in the groups fed yoghurt or soya yoghurt containing bifidobacteria (r 0·917; P>0·05).


1974 ◽  
Vol 140 (1) ◽  
pp. 87-94 ◽  
Author(s):  
Randall K. Johnson ◽  
W. Robert Jondorf

(−)-Emetine has little or no effect on O2 consumption of Ehrlich ascites-cell suspensions or on the viability of transplanted Ehrlich ascites-tumour cells exposed to, or incubated with, the drug in vitro before inoculation into new-host mice. (−)-Emetine administered as a single injection to mice bearing Ehrlich ascites-tumour cells slows the growth rate of the tumour. The subcutaneous or intraperitoneal injection of the drug depresses protein and DNA synthesis of the tumour cells in vivo in a reversible manner. Mice bearing ascitic sarcoma 180 or Ehrlich ascites-tumour cells when given a course of treatment with (−)-emetine or (−)-O-methyltubulosine have a substantially lower tumour load than untreated controls and correspondingly longer survival times.


1987 ◽  
Vol 244 (1) ◽  
pp. 239-242 ◽  
Author(s):  
M W Pierce ◽  
K Coombs ◽  
M Young ◽  
J Avruch

Insulin and insulin-related growth factor 1 (IGF-1) increase by 1.5-1.6-fold the rate of [3H]leucine incorporation into protein in primary monolayer cultures of chick-embryo fibroblasts (CEF); half-maximal hormone concentrations are 10 and 0.25 nM respectively. To investigate the mechanism of this effect, a rapid method is used to prepare a lysate from CEF which is active in protein synthesis. Lysate derived from cells treated for 30-150 min with insulin synthesized protein at 1.8-3.0-fold greater rate than did controls; the increased rate persisted for 20 min in vitro. Pactamycin (0.5 microM), an inhibitor of peptide-chain initiation, inhibited protein synthesis by 50% in lysates derived from insulin-treated and control cells. Thus insulin and IGF-1 cause an increase in the protein-synthesis rate in vivo, which persists in cell-free protein-synthesizing lysates of CEF.


2015 ◽  
Vol 59 (5) ◽  
pp. 2479-2487 ◽  
Author(s):  
Keerti Jain ◽  
Ashwni Kumar Verma ◽  
Prabhat Ranjan Mishra ◽  
Narendra Kumar Jain

ABSTRACTThe present study aimed to develop an optimized dendrimeric delivery system for amphotericin B (AmB). Fifth-generation (5.0G) poly(propylene imine) (PPI) dendrimers were synthesized, conjugated with mannose, and characterized by use of various analytical techniques, including Fourier transform infrared spectroscopy (FTIR),1H nuclear magnetic resonance (1H-NMR) spectroscopic analysis, and atomic force microscopy (AFM). Mannose-conjugated 5.0G PPI (MPPI) dendrimers were loaded with AmB and evaluated for drug loading efficiency,in vitrodrug release profile, stability, hemolytic toxicity to human erythrocytes, cytotoxicity to and cell uptake by J774A.1 macrophage cells, antiparasitic activity against intracellularLeishmania donovaniamastigotes,in vivopharmacokinetic and biodistribution profiles, drug localization index, toxicity, and antileishmanial activity. AFM showed the nanometric size of the MPPI dendrimers, with a nearly globular architecture. The conjugate showed a good entrapment efficiency for AmB, along with pH-sensitive drug release. Highly significant reductions in toxicity toward human erythrocytes and macrophage cells, without compromising the antiparasitic activity of AmB, were observed. The dendrimeric formulation of AmB showed a significant enhancement of the parasiticidal activity of AmB toward intramacrophagicL. donovaniamastigotes. In thein vitrocell uptake studies, the formulation showed selectivity toward macrophages, with significant intracellular uptake. Further pharmacokinetic and organ distribution studies elucidated the controlled delivery behavior of the formulation. The drug localization index was found to increase significantly in macrophage-rich organs.In vivostudies showed a biocompatible behavior of MPPIA, with negligible toxicity even at higher doses, and promising antileishmanial activity. From the results, we concluded that surface-engineered dendrimers may serve as optimized delivery vehicles for AmB with enhanced activity and low or negligible toxicity.


1996 ◽  
Vol 38 (3) ◽  
pp. 485-497 ◽  
Author(s):  
Eryvaldo Sόcrates Tabosa Do Egito ◽  
Martine Appel ◽  
Hatem Fessi ◽  
Gillian Barrett ◽  
Francis Puisieux ◽  
...  

Development ◽  
1969 ◽  
Vol 21 (3) ◽  
pp. 517-537
Author(s):  
Ewert Linder

The appearance of new antigens in the embryo during differentiation has been investigated by a number of authors. Among the proteins studied were myosin (Holtzer, 1961; Ebert, 1962), Jens crystallin (Ten Cate & Van Doorenmaalen, 1950), chick embryo haemoglobin (Wilt, 1962), and keratin during feather formation in chick embryo (Ben-Or & Bell, 1965). The development of liver proteins in the chick embryo was studied by D'Amelio, Mutolo & Piazza (1963). Okada & Sato (1963) and Okada (1965) studied the appearance of a ‘kidney-specific’ antigen in the developing mesonephros. Lahti & Saxen (1966) demonstrated the appearance of mouse kidney-specific tubule antigens during development both in vivo and in vitro. ‘Kidney-specific’ antigens are found in the metanephric proximal secreting tubules of various mammals (Hill & Cruickshank, 1953; Weiler, 1956; Groupe & Kaplan, 1967; Nairn, Ghose & Maxwell, 1967), including man (Nairn, Ghose, Fothergill & McEntegart, 1962), and in the mesonephric tubules of birds.


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