scholarly journals Enhancement of Transformed Foci and Induction of Prostaglandins in Balb/c 3T3 Cells by Palytoxin: In Vitro Model Reproduces Carcinogenic Responses in Animal Models Regarding the Inhibitory Effect of Indomethacin and Reversal of Indomethacin's Effect by Exogenous Prostaglandins

2005 ◽  
Vol 89 (1) ◽  
pp. 154-163 ◽  
Author(s):  
Daishiro Miura ◽  
Mitsuru Kobayashi ◽  
Satoko Kakiuchi ◽  
Yoshinori Kasahara ◽  
Shiro Kondo
2001 ◽  
Vol 45 (3) ◽  
pp. 673-678 ◽  
Author(s):  
Michael E. Klepser ◽  
Erika J. Ernst ◽  
C. Rosemarie Petzold ◽  
Paul Rhomberg ◽  
Gary V. Doern

ABSTRACT Several new quinolones that exhibit enhanced in vitro activity against Streptococcus pneumoniae have been developed. Using a dynamic in vitro model, we generated time-kill data for ciprofloxacin, clinafloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin against three isolates of quinolone-susceptible S. pneumoniae. Three pharmacokinetic profiles were simulated for each of the study agents (0.1, 1, and 10 times the area under the concentration-time curve [AUC]). Target 24-h AUCs were based upon human pharmacokinetic data resulting from the maximal daily doses of each agent. Ciprofloxacin was the least active agent against all three isolates. With regimens that simulated the human 24-h AUC, ciprofloxacin resulted in an initial, modest decline in the numbers of CFU per milliliter; however, by 48 h the numbers of CFU per milliliter returned to or exceeded the starting inoculum. At the AUC, levofloxacin resulted in variable bacteriostatic and bactericidal activities against the isolates. The remaining agents yielded bactericidal (99.9% reduction) activity by 48 h with regimens that simulated the AUC. At 0.1 time the AUC ciprofloxacin and levofloxacin produced no inhibitory effect, grepafloxacin exhibited bacteriostatic activity, trovafloxacin had mixed static and cidal activities, and clinafloxacin and moxifloxacin caused significant reductions in the numbers of CFU per milliliter by 48 h. All six agents produced cidal activity at 10 times the AUC. In this dynamic in vitro model of infection, the quinolones demonstrated various degrees of activity against S. pneumoniae. The rank order of activity, with respect to bactericidal effect, was ciprofloxacin (least active) ≪ levofloxacin < grepafloxacin, trovafloxacin < clinafloxacin and moxifloxacin (most active). The rank order of the agents with respect to the selection of resistance was ciprofloxacin (most likely) > grepafloxacin, moxifloxacin, and trovafloxacin > levofloxacin > clinafloxacin.


2021 ◽  
Vol 8 (2) ◽  
pp. 18
Author(s):  
Beatrice Belgio ◽  
Federica Boschetti ◽  
Sara Mantero

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly worldwide. So far, the etiology and the progression of AMD are not well known. Animal models have been developed to study the mechanisms involved in AMD; however, according to the “Three Rs” principle, alternative methods have been investigated. Here we present a strategy to develop a “Three Rs” compliant retinal three-dimensional (3D) in vitro model, including a Bruch’s membrane model and retina pigment epithelium (RPE) layer. First, tensile testing was performed on porcine retina to set a reference for the in vitro model. The results of tensile testing showed a short linear region followed by a plastic region with peaks. Then, Bruch’s membrane (BrM) was fabricated via electrospinning by using Bombyx mori silk fibroin (BMSF) and polycaprolactone (PCL). The BrM properties and ARPE-19 cell responses to BrM substrates were investigated. The BrM model displayed a thickness of 44 µm, with a high porosity and an average fiber diameter of 1217 ± 101 nm. ARPE-19 cells adhered and spread on the BMSF/PCL electrospun membranes. In conclusion, we are developing a novel 3D in vitro retinal model towards the replacement of animal models in AMD studies.


2002 ◽  
Vol 46 (11) ◽  
pp. 3574-3579 ◽  
Author(s):  
Charles R. Bonapace ◽  
Lawrence V. Friedrich ◽  
John A. Bosso ◽  
Roger L. White

ABSTRACT Animal infection models have historically been used to study pharmacodynamic relationships. Similar results could theoretically be produced by using an in vitro pharmacodynamic model as an alternative to animal models. We compared the antibiotic effects of ticarcillin administered in various doses and dosing regimens against Pseudomonas aeruginosa ATCC 27853 under conditions analogous to those previously employed in a neutropenic-mouse thigh infection model (B. Vogelman et al., J. Infect. Dis. 158:831-847, 1988). Ticarcillin dosages of either 96, 192, or 384 mg/day were administered at 1-, 2-, 3-, 4-, 8-, 12-, or 24-h intervals into a two-compartment model in order to duplicate the concentration-time profiles of the animal model. Colony counts were enumerated at 0 and 24 h. Linear regression and sigmoidal maximum-effect (Emax) model fitting were used to assess the relationship between the percentage of time that the concentration remained above the MIC (%T>MIC) or above four times the MIC (%T>4×MIC) and the change in the log10 CFU per milliliter (Δlog10 CFU/ml) in the central and peripheral compartments. Statistical analysis of the Δlog10 CFU/ml values was performed for matched regimens of the in vitro and animal models based on the %T>MICs. The slopes of the regression equations of %T>MICs relative to Δlog10 CFU/ml values were similar for the in vitro and animal models, but the y intercept was greater with the in vitro model. The Δlog10 CFU/ml values of the 0- to 24-h colony counts at equivalent %T>MICs in the two models were not statistically different (P = 0.087). Overall, the peripheral compartment of the in vitro model was a better predictor of effect than the central compartment. This study, which compares pharmacodynamic principles between an in vitro and an animal model, demonstrated similar relationships between %T>MICs and effects.


Author(s):  
Hamidou Têeda Ganamé ◽  
Yssouf Karanga ◽  
Ousmane Ilboudo ◽  
Wende-Konté Hazael Conania Nikiema ◽  
Richard Wamtinga Sawadogo ◽  
...  

In this work, the anti-diabetic activity of three extracts of Acacia macrostachya was investigated by following the inhibitory effect of these extracts on -glucosidase using the in vitro model. The antiradical activity of these extracts was also determined. Methanol extracts of root and stem barks showed a very significant inhibitory effect against the enzyme activity of -glucosidase with IC50 2.487 ± 0.441 µg/mL and 1.650 ± 0.229 µg/mL respectively. For antiradical activity, the same extracts presented the highest scavenging of the radical DPPH● with IC50 values of 9.307 ± 0.262 µg/mL and 5.242 ± 0.068 µg/mL respectively. With the cationic radical ABTS●+, IC50 varied from 45.049 ± 0.730 µg/mL for methanolic root barks extract to 14.136 ± 0.161 µg/mL for methanolic extract from stem barks. Thus, the methanol extracts of the root and stem barks of Acacia macrostachya possess compounds with very interesting anti-diabetic and antiradical properties and could justify its traditional use.


2021 ◽  
Vol 4 (s1) ◽  
Author(s):  
Stefania Blasa ◽  
Valentina Pastori ◽  
Alessia D’Aloia ◽  
Marzia M. Lecchi

We induced differentiation in F-11 cells to verify if they could show similarities with sensory neurons, in order to develop an alternative to animal models for research studies in the biomedical field.


2020 ◽  
Vol 11 (4) ◽  
pp. 391-401
Author(s):  
T. Vernay ◽  
I. Cannie ◽  
F. Gaboriau ◽  
S. David-Le Gall ◽  
Z. Tamanai-Shacoori ◽  
...  

Salmonella Heidelberg is one of the most common serovar causing foodborne illnesses. To limit the development of digestive bacterial infection, food supplements containing probiotic bacteria can be proposed. Commensal non-toxigenic Bacteroides fragilis has recently been suggested as a next-generation probiotic candidate. By using an original triple co-culture model including Caco-2 cells (representing human enterocytes), HT29-MTX (representing mucus-secreting goblet cells), and M cells differentiated from Caco-2 by addition of Raji B lymphocytes, bacterial translocation was evaluated. The data showed that S. Heidelberg could translocate in the triple co-culture model with high efficiency, whereas for B. fragilis a weak translocation was obtained. When cells were exposed to both bacteria, S. Heidelberg translocation was inhibited. The cell-free supernatant of B. fragilis also inhibited S. Heidelberg translocation without impacting epithelial barrier integrity. This supernatant did not affect the growth of S. Heidelberg. The non-toxigenic B. fragilis confers health benefits to the host by reducting bacterial translocation. These results suggested that the multicellular model provides an efficient in vitro model to evaluate the translocation of pathogens and to screen for probiotics that have a potential inhibitory effect on this translocation.


1976 ◽  
Vol 4 (6) ◽  
pp. 375-381 ◽  
Author(s):  
R D Mackenzie ◽  
E M Gleason ◽  
G L Schatzman ◽  
M J Cawein

Since no practical animal model is available for the evaluation of compounds in vivo, we have developed an in vitro model for determining the effect of compounds on the rate of sickling of erythrocytes in whole blood taken from patients with sickle cell anaemia. RMI 6792 (a phenethanol-diamine derivative), procaine, and L-glutamine were tested in this in vitro system. RMI 6792 was tested at various concentrations in whole blood. The data indicate that RMI 6792 decreased the rate of sickling at and above 60 μg/ml. Procaine slightly decreased sickling rate at 100 μg/ml. L-glutamine at 555 μg/ml had no inhibitory effect. RMI 6792 and procaine had no effect on the oxygen dissociation curve. RMI 6792 affected the calcium flux of the erythrocytes and the calcium concentration in the erythrocytes.


Author(s):  
Hoda Keshmiri Neghab ◽  
Mohammad Hasan Soheilifar ◽  
Gholamreza Esmaeeli Djavid

Abstract. Wound healing consists of a series of highly orderly overlapping processes characterized by hemostasis, inflammation, proliferation, and remodeling. Prolongation or interruption in each phase can lead to delayed wound healing or a non-healing chronic wound. Vitamin A is a crucial nutrient that is most beneficial for the health of the skin. The present study was undertaken to determine the effect of vitamin A on regeneration, angiogenesis, and inflammation characteristics in an in vitro model system during wound healing. For this purpose, mouse skin normal fibroblast (L929), human umbilical vein endothelial cell (HUVEC), and monocyte/macrophage-like cell line (RAW 264.7) were considered to evaluate proliferation, angiogenesis, and anti-inflammatory responses, respectively. Vitamin A (0.1–5 μM) increased cellular proliferation of L929 and HUVEC (p < 0.05). Similarly, it stimulated angiogenesis by promoting endothelial cell migration up to approximately 4 fold and interestingly tube formation up to 8.5 fold (p < 0.01). Furthermore, vitamin A treatment was shown to decrease the level of nitric oxide production in a dose-dependent effect (p < 0.05), exhibiting the anti-inflammatory property of vitamin A in accelerating wound healing. These results may reveal the therapeutic potential of vitamin A in diabetic wound healing by stimulating regeneration, angiogenesis, and anti-inflammation responses.


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