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Biomedical subjects

A C Ventura

Publications and source records attributed to A C Ventura.

7 recordsLinked to original sources

Generic two-variable model of excitability.

We present a simple model that displays all classes of two-dimensional excitable regimes. One of the variables of the model displays the usual spikes observed in excitable systems. Since the model is written in terms of a "standard" vector field, it is always possible to fit it to experimental data displaying spikes in an algorithmic way. In fact, we use it to fit a series of membrane potential recordings obtained in the medicinal leech and time series generated with the FitzHugh-Nagumo equations and the excitability model of Eguía et al. [Phys. Rev. E 58, 2636 (1998)]. In each case, we determine the excitability class of the corresponding system.

Animals↗

Corneal thickness and endothelial density before and after cataract surgery.

BACKGROUND/AIMS: Deturgescence of the corneal stroma is controlled by the pumping action of the endothelial layer and can be monitored by measurement of central corneal thickness (pachymetry). Loss or damage of endothelial cells leads to an increase in corneal thickness, which may ultimately induce corneal decompensation and loss of vision. Little is known about the effect of moderate reductions in endothelial cell number on the thickness of the corneal stroma. This study aimed to investigate this matter further using patients who had incurred moderate decreases in their endothelial cell counts as a result of cataract surgery. METHODS: Central corneal thickness was measured 1 day before surgery, 1 day after surgery, and again at 3 months or 1 year. Endothelial cell counts were also performed 1 day before surgery and thereafter at 3 months or 1 year after surgery. The relationship between these two parameters was assessed statistically. Precise measurements of central corneal thickness were made by optical low coherence reflectometry. For comparative purposes, this parameter was also determined by ultrasonic pachymetry. Central corneal endothelial cell numerical density was estimated on photomicrographs taken with a specular microscope. RESULTS: All patients had significant postoperative corneal swelling on the day after surgery; preoperative values were restored by 3 and 12 months, even though significant endothelial cell losses had occurred. No correlation existed between central corneal thickness and central corneal endothelial cell numerical density. Measurements estimated by ultrasonic pachymetry were more variable and significantly higher than those determined by optical low coherence reflectometry. CONCLUSION: As long as the numerical density of the corneal endothelial cells does not fall below the physiological threshold, a moderate decrease in this parameter does not compromise the pumping activity of the layer as a whole.

Adult↗

Central corneal thickness measurements in patients with normal tension glaucoma, primary open angle glaucoma, pseudoexfoliation glaucoma, or ocular hypertension.

BACKGROUND/AIMS: Recent studies have revealed patients with ocular hypertension to have thicker than normal central corneas and those with normal tension glaucoma to have thinner than normal ones, as determined by ultrasonic pachymetry. Since corneal thickness measurements and applanation tonometric estimates of intraocular pressure (IOP) correlate positively, monitoring of the former parameter have served as the basis for adjusting readings pertaining to the latter, with the consequence that many patients have had to be reclassified. With a view to validating these pachymetric studies, the central corneal thickness was determined in patients with normal tension glaucoma, primary open angle glaucoma, pseudoexfoliation glaucoma, or ocular hypertension, as well as that of normal subjects, using optical low coherence reflectometry, which is a new and more precise method than ultrasonic pachymetry. METHODS: 34 patients with normal tension glaucoma, 20 with primary open angle glaucoma, 13 with pseudoexfoliation glaucoma, and 12 with ocular hypertension, together with 21 control subjects, were included in this observational, concurrent case-control study. One eye per individual was randomly selected for investigation. IOP was measured by Goldmann applanation tonometry and central corneal thickness by optical low coherence reflectometry. RESULTS: Central corneal thickness was significantly higher (p < or =0.001) in patients with ocular hypertension than in normal individuals or in subjects with either normal tension glaucoma, primary open angle glaucoma, or pseudoexfoliation glaucoma, there being no significant differences between the latter four groups. Patients with ocular hypertension were also significantly younger (p < or =0.003) than those within any of the three glaucomatous groups. CONCLUSION: This study confirms that a significant number of patients with ocular hypertension have normal IOPs after the appropriate adjustments have been made for deviations from normal in their central corneal thickness. The accurate measurement of this latter parameter is important not only for individual patient care, in permitting more precise estimations of IOP, but also for clinical studies, in assuring a more reliable classification of subjects.

Adult↗

Pentoxifylline influences the autocrine function of organ cultured donor corneas and enhances endothelial cell survival.

BACKGROUND/AIMS: Scientific interest in pentoxifylline has been reawakened owing to the recognised effects of this drug on immune functions, particularly its influence on cytokine production. In a previous study, the authors demonstrated that spiking of organ culture media with endotoxin elicited a marked enhancement in the release of IL-6 and IL-8 from corneal tissue and that these events coincided with degenerative changes in endothelial cells and a higher incidence of actual loss among this population. Since traces of donor derived endotoxin can be detected in up to 50% of corneal organ cultures, this substance may have a direct influence on graft viability or trigger inflammatory responses in the host. They, therefore, wished to ascertain whether supplementation of media with pentoxifylline improved endothelial cell survival in organ cultured donor corneas. METHODS: 12 fellow pairs of donor corneas were cultured for 20 days, with a change of medium on day 10: One of each pair was incubated in the absence, and the other in the presence, of pentoxifylline (25 microg/ml). Samples of medium were withdrawn at regular intervals during the course of incubation and screened for cytokines IL-6, IL-8, and prostaglandin E2 by ELISA. Endothelial cell morphology and numerical density were assessed on days 0, 10 and 20. RESULTS: Addition of pentoxifylline to organ culture media led to a significant improvement in endothelial cell survival. This drug also elicited a significant increase in the level of IL-6 and marginally suppressed that of IL-8 during the initial 10 day phase of incubation. During the second 10-20 day phase, the level of both IL-6 and IL-8 decreased significantly in the presence of pentoxifylline, the relation between these two cytokines being the inverse of that observed in the absence of the drug. No significant changes in the level of prostaglandin E2 were apparent. CONCLUSION: The addition of pentoxifylline to organ culture media leads, ultimately, to a suppression of IL-6 and IL-8 secretion by corneal tissue. The potentially damaging effects of these cytokines are thereby quelled, as evidenced by the improvement in endothelial cell survival.

Adult↗

Toxicity of pentoxifylline on monolayers of highly proliferative cells of epithelial origin.

Interest in pentoxifylline has been recently reawakened owing to its suppressive effect on cell cytokine production. In this capacity, it may be of value as a routine supplement for culture media containing donor corneas. The purpose of the present study was to evaluate the toxic effects of pentoxifylline on two standardized cell lines of epithelial origin. Vero and Chang cells were incubated with various concentrations of pentoxifylline. Acute toxicity (4 hr) was assessed by monitoring the permeability of cells to propidium iodide; chronic toxicity (7 days) was determined by monitoring the effect of pentoxifylline on esterase activity and cell proliferation. The viability of cells was also assessed by microscopic inspection. Signs of acute toxicity became manifest at a pentoxifylline concentration of 100 mg/l in both Chang and Vero cells. Indications of chronic toxicity were observed at a drug concentration of 10 mg/l in Chang cells but at 1 mg/l in Vero ones. Proliferation was suppressed at pentoxifylline concentrations of 100 mg/l and 10 mg/l in Chang and Vero cells, respectively. Degenerative morphological changes were observed at a drug concentration of 100 mg/l in both cell types. At a concentration of 0.1 mg/l, pentoxifylline elicited no signs of acute or chronic toxicity in either Chang or Vero cells. At this dose, the drug is therefore unlikely to have deleterious effects on cultured donor corneas.

Animals↗

[HLA typing of donor corneas with extended post mortem time].

In case of high-risk patients cornea transplantation should be carried out using HLA-matched donor corneas to minimize the risk of rejection. HLA typing using blood lymphocytes of the donor is impossible because of the long post-mortem times. Alternatively, HLA typing can be performed using retinal pigment epithelium (RPE). Nevertheless, this method is limited by increasing post-mortem times. The aim of the present study was the optimization of culture conditions for RPE cells isolated from donor eyes with long post-mortem times. The HLA type should be evaluated during an acceptable period of organ preservation of the corresponding cornea. In different steps the method for isolation of the cells was optimized and a growth medium for RPE cells was established. Various supplements, including uvea-conditioned medium, were assessed using growth assays. The optimization of culture conditions led to an increase in the estimation of the complete HLA I and HLA II antigens from 36% to 74%. The time needed for the typing-procedure could be reduced from 38 to 17 days (average). At present 30% of the donor tissue with long post-mortem times can be typed in less than 14 days.

Cell Division↗

Detection of endotoxin in media from sterile corneal organ cultures.

Lipopolysaccharides (LPS) are elements of the cell wall of gram-negative bacteria. They are also called endotoxins and are known to stimulate various inflammatory reactions by interaction with cytokines and macrophages. Additionally, they may have a direct effect on other cells. As contamination of sterile organ-culture media with bacterial substances may influence the donor-tissue prognosis, we investigated a series of culture media drawn from organ culture for the presence of endotoxin. A total of 341 samples of sterile organ-culture media from 3 different cornea banks using either organ culture or the refrigerated-storage technique were tested for endotoxin. The assay was performed using the Limulus amebocyte-lysate test. A level of endotoxin above the background threshold was found in 99/341 (29%) culture media. The incidence of endotoxin ranged from 14% up to 50%, depending on the cornea bank and culture system used. Endotoxin detected in sterile corneal organ cultures probably derives from nonreplicating bacterial postmortem donor-tissue contamination. The presence of endotoxin-positive cultures varied between the eye banks but was not related to a given storage method. As endotoxin may directly influence graft viability or trigger inflammatory host responses, these findings may have significance for the clinical results of corneal grafting.

Cornea↗