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At least 19 recordsLinked to original sources
PubMed1989

Effects of heparin and chlorbutol on bacterial colonisation of intravascular cannulae in an in vitro model.

An in vitro model was used to study the effects of heparinised saline, with or without the preservative chlorbutol, on the colonisation of intravascular cannulae. Chlorbutol significantly reduced cannula colonisation by Staphylococcus epidermidis. Flushing colonised cannulae with heparinised saline plus chlorbutol significantly reduced the number of organisms adhering to the inner surface of cannulae, when compared with the use of heparinised saline without preservative. Chlorbutol-preserved heparinised saline may not only maintain cannula patency by the prevention of thrombus formation, but may also reduce the incidence of bacterial colonisation of cannulae in vivo.

Bacterial Infections↗
PubMed1990

Antibacterial activity of lomefloxacin in a pharmacokinetic in vitro model.

An in vitro model simulating two-compartment pharmacokinetics was used to study the antibacterial activity of lomefloxacin after single oral doses of 200 and 400 mg. Lomefloxacin produced reliable bactericidal activity against gram-negative aerobic bacteria and staphylococci. Bacterial strains for which MICs were less than 0.5 microgram/ml were inhibited with both dosing schedules. Doubling the dose from 200 to 400 mg increased the bactericidal activity only against Pseudomonas aeruginosa. Against Enterococcus faecalis lomefloxacin showed no effect. Selection of resistant variants during the simulation of treatment was observed with Staphylococcus aureus and P. aeruginosa.

4-Quinolones↗
PubMed1992

Evaluation of the hepatotoxicological effects of a drug in an in vivo/in vitro model.

Both in vivo and in vitro models have certain disadvantages for the study of the chronic hepatotoxicity of drugs. The aim of this work was to evaluate a new approach based on an in vivo/in vitro model. After chronic in vivo treatment of rats with Vincamine and Vindeburnol (an eburnamenine derivative which exhibits hepatotoxic properties in man) liver cells were isolated, and functional and metabolic disorders (metabolic utilization of fructose and protein biosynthesis) were studied to determine injury. The results showed no modification of blood parameters, but a direct relationship between the dose of Vindeburnol administered in vivo and the metabolic disorders observed in vitro, evidencing the high sensitivity and reliability of this model.

Animals↗
PubMed1992

Comparison of gentamicin dosing regimens using an in-vitro model.

An in-vitro model which simulates in-vivo pharmacokinetics was used to compare the efficacy against Pseudomonas aeruginosa of dosing regimens of gentamicin which achieve different peak/trough concentrations but use the same total dose over 24 h. First exposure to gentamicin produced a rapid bactericidal effect which was proportional to the initial peak concentration. Subsequent doses of gentamicin produced a smaller bactericidal effect. Regrowth occurred with all dosing regimens, even after very high initial concentrations (26 mg/L). The time to reach bacterial counts above starting values was prolonged in relation to peak concentrations. Regrowth was also demonstrated in continuous infusion experiments which maintained very high concentrations (26 mg/L), although an inhibitory effect was evident compared with single dose experiments and the experiments mimicking in-vitro pharmacokinetics. There was little evidence of a post-antibiotic effect. The data supports the use of larger initial and longer interval bolus dosing compared with current recommendations.

Drug Administration Schedule↗
PubMed1989

Modulation of arterial endothelial permeability: studies on an in vitro model.

1. An in vitro model of the arterial endothelial barrier was established in which transfer of trypan blue-labelled albumin across confluent monolayers of pig aortic endothelial cells grown on polycarbonate membranes was measured. 2. A range of inflammatory mediators, i.e. histamine, bradykinin, platelet activating factor and thrombin, had no effect on the transfer of labelled albumin across aortic endothelial monolayers. 3. Calcium ionophore A23187 and the phorbol ester, phorbol myristate acetate (PMA), each induced concentration-dependent increases in transfer of labelled albumin. These increases were associated with changes in cell shape, consistent with endothelial contraction. Ionophore A23187 caused some detachment of cells. 4. The ability of PMA to increase transfer of labelled albumin probably results from activation of protein kinase C since it was not shared by the inactive analogue, 4 alpha-phorbol 12,13-didecanoate. 5. Neither a combination of superoxide dismutase and catalase nor the cyclo-oxygenase inhibitor, flurbiprofen, affected resting or PMA-induced increases in albumin transfer. Oxygen-derived free radicals and prostaglandins appear not to be involved in the response to PMA. 6. Each of three procedures designed to elevate adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels, i.e. dibutyryl cyclic AMP, forskolin and (+/-)-isoprenaline, reduced the ability of PMA to promote increased transfer of labelled albumin but had no effect on resting transfer. The effect of (+/-)-isoprenaline was abolished by the beta-adrenoceptor blocking agent, propranolol. 7. Elevation of cyclic GMP content by use of 8 bromo cyclic GMP or atriopeptin II had no effect on resting or PMA-induced transfer of labelled albumin. 8. Arterial endothelial barrier function can be compromised by agents that promote endothelial contraction. Agents that increase endothelial cyclic AMP levels, and so reduce entry of high molecular weight substances into the arterial wall, may warrant evaluation as potential anti-atherogenic drugs.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

The effect of antibiotics on bacterial colonisation of vascular cannulae in a novel in-vitro model.

An in-vitro model for studying semi-quantitatively the bacterial colonisation of the external and internal surfaces of peripheral intravascular cannulae is described. Using this model, we studied the effect of ciprofloxacin, teicoplanin and fusidic acid on cannula colonisation by Staphylococcus epidermidis. Exposure of colonised cannulae to sub-MICs of ciprofloxacin and fusidic acid reduced bacterial attachment, whereas sub-MIC levels of teicoplanin had little effect. Pre-exposure of S. epidermidis to sub-MICs of ciprofloxacin and fusidic acid also reduced slime production and colonisation. In comparison, pre-exposure of S. epidermidis to teicoplanin 1.0 mg/L did not influence colonisation, whereas at 0.1 mg/L it was reduced. The model allowed investigation of bacterial colonisation of cannulae and offers a screening system for the assessment of potential agents for the prophylaxis and treatment of these infections.

Anti-Bacterial Agents↗
PubMed1986

A simple in vitro model of mechanical injury of confluent cultured endothelial cells to study quantitatively the repair process.

A model of in vitro mechanical injury of confluent human endothelial cells (EC) in culture was developed. Human EC were obtained from umbilical veins and grown to confluence. Application on the EC monolayer of a calibrated disk of cellulose polyacetate paper resulted in removal of the EC, leaving a continuous subendothelial extracellular matrix (ECM) on the culture dish. The regeneration time depended on the original size of the lesion. Regeneration was similar with EC grown on different substrates such as human fibronectin, human subendothelial ECM, bovine collagen type I or surfaces coated with Transglutine, a surgical glue containing adhesive proteins. A human brain extract containing growth factor activity accelerated significantly the repair of the lesion, especially at low serum concentration. This simple in vitro model of mechanical injury allows the quantitative study of the effects of matrices, growth factors and pharmacological agents on the repair process.

Cells, Cultured↗
PubMed1990

In vitro models.

The development of in vitro models is advancing rapidly, with the application of cell culture methods as an alternative to animals in toxicological screening; non-cellular systems are also being used. Any screening test, whether for detecting irritants, carcinogens or teratogens should be well validated against known animal studies. It should, for example, be able to correctly identify a teratogen as well as a non-teratogen. Various types of in vitro systems are utilised. Some validated test systems have been used for several years to detect genotoxins and are acceptable to many regulatory authorities. This is not the case for other in vitro systems, although some for skin irritation and corrosion are acceptable to some authorities. A non-comprehensive range of tests to measure responses in ocular, immune, cardiac, vascular, neurological, sensory, hepatic, testicular and embryological systems are described. Some tests are empirical and others much more closely mimic the animal model they represent. Some of the methods described are much closer to validation than others.

Animals↗
PubMed1990

Ventricular reentry around a fixed barrier. Resetting with advancement in an in vitro model.

We studied an in vitro model of reentrant tachycardia in a ring of ventricular endocardial tissue surrounding the canine mitral and aortic valves to understand how the response of a reentrant tachycardia to premature impulses can provide insight into the underlying tachycardia mechanism, circuit characteristics, and nature of the central barrier. Reproducible regular reentrant tachycardias (cycle length range, 177-450 msec) were induced with programmed stimulation in 19 intact preparations studied at 34-38 degrees C. Tachycardias were sustained and stable until terminated by programmed stimulation in 95% of preparations. Reentry was reliably reinitiated during experiments lasting 2-15 hours. Data supporting reentry as the mechanism of these tachycardias included sequential activation around the ring that spanned the cycle length of the tachycardia, unidirectional block during initiation of the reentrant rhythm, and termination of the tachycardia after interruption of the circuit. Tachycardias in 13 preparations were systematically reset by premature stimuli. During reentry, each of these preparations had full recovery of excitability by the end of their excitable gap as evidenced by a flat portion along their resetting response curve (eight of 13) or by lack of faster conduction velocity during the second poststimulus beat after premature impulses that produced a long return cycle (13 of 13). From analysis of the conduction of premature impulses and their return cycles, we reached several conclusions useful for interpreting resetting response curves when the reentrant circuit is not fully accessible for study. The duration of a flat portion of the resetting response curve indicated the duration of the shortest fully recovered excitable gap in the reentrant circuit. The window of reset of the tachycardia reflected only the local excitable gap at the site of stimulation and did not define the shortest excitable gap within the circuit. The extent of advancement of the tachycardia provided a lower-limit estimate of the shortest excitable gap in the reentrant circuit. Advancement of a tachycardia in time by premature stimuli indicated advancement at each point in the circuit. Finally, for tachycardias advanced by premature impulses, the length of the reentrant path cannot be determined by the recovery of a refractory barrier.

Animals↗
PubMed1990

The effects of contrast dye on bacterial growth: an in vitro model.

We devised an in vitro model to examine the effects of Conray 60 contrast dye on microorganisms commonly found in septic arthritis. Using 42 culture plates in aerobic and anaerobic environments, we found no adverse effect on bacterial growth using 30, 7.5, 3.75, and 1.875% concentrations of Conray 60 contrast dye on cultures of Staphylococcus aureus, Hemophilus influenza, and Streptococcus pneumonia.

Arthritis, Infectious↗
PubMed1990

An in vitro model of ischemia/reperfusion-induced microvascular injury.

The major objective of this study was to develop an in vitro model of ischemia/reperfusion (I/R)-induced microvascular injury. Cultured venular endothelial cells were grown to confluency, labeled with 51Cr, and exposed to different durations of anoxia (0.5, 1, 2, 3, and 4 h). 51Cr release and cell detachment (indexes of cell injury) were determined at different times after reoxygenation (1, 2, 4, 6, 8, and 18 h). Because in vivo studies have implicated neutrophils in I/R injury, in some experiments human neutrophils were added to the endothelial cells upon reoxygenation. Periods of anoxia greater than or equal to 2 h resulted in 70-80% 51Cr release and 80-95% cell detachment upon reoxygenation. Under these conditions (near maximal injury), the addition of neutrophils produced negligible effects. Periods of anoxia less than or equal to 1 h resulted in 30-40% 51Cr release and 50-60% cell detachment. Under these conditions (moderate cell injury), addition of neutrophils enhanced endothelial cell injury. Using a 30-min period of anoxia, we also assessed the effects of superoxide dismutase (SOD; 300 U/ml) and allopurinol (20 microM) on anoxia/reoxygenation (A/R)-induced injury in the presence or absence of neutrophils. In the absence of neutrophils, SOD or allopurinol did not protect against A/R-induced injury. However, in the presence of neutrophils, both SOD and allopurinol attenuated the increases in 51Cr release. The results derived using this in vitro model of I/R injury are largely consistent with published in vivo studies. Thus this in vitro model may provide further insights regarding the mechanisms involved in I/R injury.

Allopurinol↗
PubMed1988

Neoplastic transformation of osteogenic cells: quantitative morphometric analysis of an in vitro model for osteosarcoma.

Previously we have reported the development of a model in vitro system for the study of osteosarcoma. In this system, when chick periosteal explants are infected with Fujinami sarcoma virus (FSV), osteosarcoma-like tissue is formed. In the present study, a series of histopathologic parameters of neoplastic transformation and osteogenesis were quantitated, at a single cell level, by computer-assisted morphometry. Most significantly, it was found that compared to uninfected (control) cultures, in the FSV-infected (experimental) cultures, the bone to osteoid ratio per unit area was decreased due to a relative decrease in the area of bone and an increase in the area of osteoid. The cellularity of the FSV-infected tissues was significantly increased due to an increase in the number of unlabeled and [3H]thymidine-labeled cells, while the proportion of alkaline phosphatase (AP) positive cells decreased. Double-label immunohistochemistry (with anti-P140gag-fps) and histochemistry for AP activity was performed, to demonstrate production of the oncogene-encoded protein, and osteoblastic differentiation respectively. In an in vitro transformation assay, single cells derived from control, uninfected cultures did not grow, while those derived from FSV-infected cultures formed colonies in semisolid medium. Some of these colonies demonstrated AP staining. Taken together these data show that in this in vitro system (i) neoplastic transformation of osteogenic cells does occur, (ii) changes in osteoid and bone production are related to neoplastic transformation, and (iii) osteosarcoma-like changes can be quantitated at the individual cell level.

Animals↗
PubMed1984

The activity of cefotiam on beta-lactamase-producing bacteria in an in-vitro model.

The activity of cefotiam was tested in an in-vitro model simulating human serum pharmacokinetics. Bacterial strains used for inoculation either produced a penicillinase or a cephalosporinase. The rate of hydrolysis and the MICs of cefotiam were determined in comparison with those of ampicillin and cephalothin. The influence of these beta-lactamases on the killing kinetics and the degradation of cefotiam in the in-vitro model were then measured. Although all beta-lactamases hydrolyzed cefotiam, only the chromosomal cephalosporinases, especially those from Enterobacter and Klebsiella, reduced the elimination of the bacteria by degradation of the drug. A rough correlation between the hydrolytic activity and MIC could be demonstrated for cefotiam but not for ampicillin, while a correlation between killing ability and MIC only existed for strains with cefotiam MICs higher than 16 mg/l.

Ampicillin↗
PubMed1988

Low Ca2+ stripping of differentiating cell layers in human epidermal cultures: an in vitro model of epidermal regeneration.

An in vitro model of the epidermal regeneration process is described. Incubation of multilayered, keratinizing cultures of human epidermal cells in Ca2+-free medium for 72 h results in a complete stripping of all suprabasal layers. When the Ca2+ stripped cultures are refed normal Ca2+ medium a reproducible series of morphologic and cell kinetic changes takes place. It is suggested that these changes represent a general pattern of regeneration after epidermal wounding. After an initial lag phase the regenerative response is principally effected by a recruitment to the proliferating pool of cells with a high rate of DNA synthesis. The cells seem to be programmed to rapid differentiation. Studies with cholera toxin suggest that this adenylate cyclase-stimulating agent is able to induce significant changes in the regenerative process causing a prolonged, but less intense, proliferative response leading to lateral growth rather than to rapid differentiation.

Calcium↗
PubMed1991

The effect of angle and flow rate upon hemodynamics in distal vascular graft anastomoses: an in vitro model study.

A steady flow, in vitro model of distal arterial bypass graft junctions was used to examine the effects of junction angle and flow rate on the local velocity field. Three test sections were fabricated from Plexiglas tubing having anastomotic junction angles of either 30, 45, or 60 deg. Flow visualization revealed velocity profiles skewed toward the outer wall with a flow split around a clear stagnation point along the outer wall. Laser Doppler anemometry [LDA] measurements confirmed a distinct stagnation point at the outer wall and both reverse and forward shear were detected immediately upstream and downstream, respectively, of this site. Axial velocities and shear rates along the outer wall were higher than along the inner wall and occurred in the junction angle order: 45, 60, and 30 deg. This study clearly identified changes in wall shear which varied with the anastomotic angle and flow rate.

Anastomosis, Surgical↗
PubMed1975

Induction of F1 hybrid antiparent cytotoxic effector cells: an in vitro model for hemopoietic histoincompatibility.

An in vitro system has been developed in which F1 spleen cells can generate cytotoxic activity directed specifically against parental cells. The antigenic differences detected are controlled by the H-2D-Hh-1 region of the murine major histocompatibility complex. The parent-F1 combinations demonstrating F1 antiparent activity in vitro are the same as those demonstrating F1 rejection of parental hemopoietic grafts in vivo. Hence, the F1 antiparent cytotoxicity test serves as an in vitro model for the recognition and effector phases of hybrid resistance to parental hemopoietic grafts and may be of value in clinical transplantation.

Age Factors↗
PubMed1984

Suppression of HSV-1 infection in trigeminal ganglion cells. An in vitro model of latency.

The goal of this experiment was to develop an in vitro model of HSV-1 infection and to characterize the virologic parameters associated with such an infection. An in vitro model of HSV-1 infection would offer a defined, efficient, and easily controlled system for studying the mechanisms associated with HSV-1 latency and reactivation. Results indicate that: (1) in the presence of 100 micrograms/ml acyclovir, acute infection is suppressed within 3 days; (2) during suppression, infectious virus was recovered only from whole cell trigeminal ganglion explants (no virus recovery from supernate or homogenized samples); immunofluorescent staining was evident with antiserum to VP175, but not with antiserum to HSV-1 and intranuclear inclusions, but no intact virions were observed in neurons by electron microscopy; (3) 72 hr after desuppression of HSV infected trigeminal ganglion cells infectious HSV-1 was recovered from supernate, homogenized, and whole cell cultures. Immunofluorescent staining was observed with antisera to VP175 and HSV-1; intranuclear inclusions as well as intact virus particles were noted in neurons via electron microscopy.

Acyclovir↗
PubMed1990

Antibacterial activity of cefpodoxime proxetil in a pharmacokinetic in-vitro model.

The antibacterial activity of cefpodoxime proxetil was studied in an in-vitro model simulating doses of 100, 200 and 400 mg. Strains of Klebsiella spp. Proteus mirabilis, Escherichia coli, Streptococcus pyogenes, and Haemophilus influenzae were effectively reduced by a dose of 200 mg. While for Esch. coli no dose-activity relationship was observed--the maximal effect was achieved with a simulated dose of 100 mg--Staphylococcus aureus could be reduced effectively only by a simulated dose of 400 mg. The lower doses showed stepwise lower activities. Apart from broad spectrum beta-lactamases like SHV 2 or TEM 5 the presence of plasmid coded beta-lactamases in Esch. coli and H. influenzae did not affect the antibacterial activity of cefpodoxime proxetil. The results show that cefpodoxime was more active against Gram-negative bacteria than amoxycillin, and comparable activity to intramuscular cefotiam in the in-vitro model.

Amoxicillin↗