Biomedical subjects

J L van Delft

Publications and source records attributed to J L van Delft.

At least 19 recordsLinked to original sources

PubMed1999

Flurbiprofen, S(+), eyedrops: formulation, enantiomeric assay, shelf-life and pharmacology.

Aphakic cystoid macula edema, occurring after cataract extraction is ascribed to trauma-induced production of intra-ocular prostaglandins. Sufficient experimental and clinical evidence supports the use of prostaglandin synthesis inhibitors to countervail this clinical condition. The active S(+)-enantiomer of flurbiprofen, a prostaglandin synthesis inhibitor, has been formulated into a stereoselective, ballast free eyedrop solution in a concentration of 0.015%. Analysis by capillary zone electrophoresis shows shelf-life stability up to four years at room temperature of this enantiomer. The inhibitory effect on the synthesis of prostaglandins as measured on a homogenate bovine iris/ciliary body, remained unaffected during a shelf-life period of three years.

Animals↗

PubMed1996

HLA expression and tumor-infiltrating immune cells in uveal melanoma.

BACKGROUND: In uveal melanoma, both the amount of tumor-infiltrating cells and the level of expression of HLA antigens are quite variable. We hypothesized that low levels of HLA expression lead to a lack of antigen presentation, which might prevent proper immunologic recognition of the tumor. This lack of recognition might subsequently lead to low levels of tumor-infiltrating cells. METHODS: To test this hypothesis, we determined the type and number of tumor-infiltrating cells in tumor sections from 24 uveal melanomas. We applied monoclonal antibodies directed against different types of immune cells and compared the results with the expression of HLA class I and class II antigens on the tumor cells. RESULTS: Infiltrating immune cells were observed in all uveal melanomas (although in small amounts), with a predominance of T lymphocytes. Significant positive correlations were observed between the number of CD3+ cells (T lymphocytes) and monomorphic HLA class I expression, allele-specific HLA-A2 and Bw4 expression, and HLA class II expression. Furthermore, the number of CD4+ cells (T helper cells, monocytes/ macrophages) and of CD11b+ cells (monocytes/macrophages) was significantly correlated with the level of monomorphic HLA class I expression. CONCLUSION: These data support our hypothesis that low levels of HLA expression (and therefore a lack of presentation of tumor-specific antigens) may lead to a low level of tumor infiltrate.

Adult↗

PubMed1995

Endogenous fluorescence of ocular malignant melanomas.

The endogenous fluorescence of human choroid, sclera, and retinal pigment epithelium (RPE) in normal tissue and tissue with uveal melanoma was studied in vitro by a non-invasive and non-destructive fluorescence technique which had previously been applied for the diagnostic evaluation of pigmented lesions of the skin. The fluorescence of the normal choroid is rather dark, the normal sclera exhibits blue fluorescence and the RPE bright yellow fluorescence due to deposits of lipofuscin. In choroidal melanoma, the lipofuscin granulae at the level of the retinal pigment epithelium are cleaved off above the tumour and broken up into small remnants. The fluorescence intensity emitted from the tumour is rather low which agrees with previous findings on skin melanomas. The results may become interesting for diagnostic evaluation of uveal melanomas, uveal naevi, and pigmented conjunctival tumours by endogenous fluorescence.

Choroid Neoplasms↗

PubMed1994

Hamster Greene melanoma in the rabbit eye: immunosuppressive treatment to improve this tumor model.

BACKGROUND: The hamster Greene melanoma (HGM) implanted in the anterior chamber of the rabbit eye has been used to study experimental therapies for human uveal melanoma. However, the occurrence of spontaneous necrosis limits the value of this model for long-term evaluation of experimental treatments. In the present study we tested the hypothesis that an immune response is the cause of this necrosis and that prevention of the immune response can prolong the experimentation time METHODS: HGM was implanted in the anterior chamber of control, presensitized and immunosuppressed rabbits. The effects of sensitization and immunosuppression were assessed by clinical and histological observation RESULTS: Sensitization led to a significant slowing down of tumor growth, but not to a difference in necrosis. Immunosuppressive treatment with cyclosporin A improved the success rate of implantation and decreased the amount of necrosis in the tumor CONCLUSION: The immune response plays a role in the occurrence of necrosis. However, although immunosuppressive treatment with cyclosporin A decreased the amount of necrosis, significant necrosis still occurred, suggesting that other factors like angiogenesis play a part as well and still limit the usefulness of this model in the long-term evaluation of experimental therapies.

Animals↗

PubMed1993

Antagonist of platelet-activating factor prevents prostaglandin E2 induced ocular hypertension in rabbits.

Topical application of 250 micrograms of platelet activating factor (PAF) or 5 micrograms of prostaglandin E2 (PGE2) to the rabbit's eye is followed by a rise in intraocular pressure (IOP). The occurrence of PAF in the anterior chamber is held responsible for this effect, as appears from the observed concentrations of PAF in a ng/ml-range in the aqueous humor and from the inhibition in the rise of IOP by systemic pretreatment of rabbits with the PAF-antagonist BN 52021 (10 mg/kg). Corneal and conjunctival edema, occurring after application of PAF, are not influenced by BN 52021. Thus, these effects may be ascribed to the non-specific membrane pertubant action of the high local concentration of PAF, necessary to achieve effective concentrations of PAF in the anterior chamber.

Animals↗

PubMed1993

Antagonists and inhibitors of lipid mediators in experimental inflammation of the cornea.

In experimental immunogenic keratitis, provoked in rabbits by intracorneal injection of 20 microliters of human serum albumin (HSA), various anti-inflammatory agents were studied in their effects on corneal edema, neovascularisation and leukocyte infiltration. Prophylactic treatment with a corticosteroid completely prevented the occurrence of keratitis. Nonsteroidal anti-inflammatory drugs such as a cyclooxygenase inhibitor partly prevented neovascularisation and corneal edema, a lipoxygenase inhibitor, a leukotriene antagonist or platelet-activating factor (PAF)-antagonist BN 52021 partially prevented mainly leukocyte infiltration. Prophylactic topical treatment with the poly-unsaturated fatty acids eicosapentaenoic acid and columbinic acid or a dietary supplement with fish oil showed less symptoms of keratitis in all respects.

Animals↗

PubMed1993

Production of lipid mediators in experimental keratitis of rabbit eye.

The inhibitors of prostaglandin (PG) or leukotriene (LT) synthesis and antagonists of platelet-activating factor (PAF) or LTs are inhibitory in experimental keratitis and clinical symptoms of keratitis are reproduced by application of these lipid mediators. This suggests that PGE2, LTB4, LTD4, and PAF are involved in experimental immunogenic and toxic keratitis. The objective of the present study is the measurement of the concentrations of lipid mediators in the aqueous humour and their release by the cornea and iris during keratitis. In both inflammatory models the concentrations of PGE2, LTB4, LTD4, and PAF in the aqueous humour were significantly increased as compared to their controls. The release of PGE2, LTB4 and LTD4 from the cornea, and of PGE2, LTB4, and PAF from the iris was significantly increased compared to that from control tissues. The results are consistent with a role for these lipid mediators in the inflammatory models. Combined therapeutic use of synthesis inhibitors or antagonists of these mediators in eye inflammation seems possible and may serve as an alternative to topical corticosteroid therapy.

Animals↗

PubMed1992

The effect of high-intensity focused ultrasound on intraocular pressure in therapy-resistant glaucoma 3-4 months and 1 year after treatment.

The effect of therapeutic ultrasound for the treatment of refractory glaucoma was evaluated in 44 patients by comparing average IOP curves measured before and 3-4 months after treatment. The insonification regime was standardized and the glaucoma medication in each individual patient was unchanged during IOP curve measurements. The average IOP decrease 3-4 months after insonification was 42.2% +/- SD 31.9. In 23 patients who were followed for at least one year the average IOP 3-4 months after treatment was compared with the average IOP 1 year after treatment. In this group average IOP 3-4 months after treatment was 25.3 mmHg +/- SD 16.4 and average IOP 1 year after treatment was 24.1 mmHg +/- SD 15.9. The correlation coefficient between IOP 3-4 months after treatment and IOP 1 year after treatment was 0.79 (P < 0.0001).

Adult↗

PubMed1992

Hamster Greene melanoma implanted in the anterior chamber of a rabbit eye: a reliable tumor model?

The hamster Greene melanoma (HGM), implanted into the anterior chamber (AC) of a rabbit eye, has previously been used as a model for testing experimental therapies against human uveal melanomas. Even without therapy, the tumor showed necrosis and hemorrhages 8-10 days after inoculation. These changes could interfere with the interpretation of the results of experimental therapies. In 8 rabbits, a piece of HGM was implanted subcutaneously, and after 4 weeks, HGM was also implanted in the AC of the eye. In these eyes, tumor growth in the AC slowed down, and more necrosis and hemorrhages were found clinically and histologically as compared to 8 rabbits without previous subcutaneous implantation of HGM. In spite of the long use of this tumor and frequent transfer, the tumor cells did not lose their antigenic potential.

Animals↗

PubMed1991

Prostaglandin E2 in the vitreous body of the normal rabbit eye and after ocular trauma.

Rabbit eyes were enucleated and frozen in liquid nitrogen. The vitreous was removed and analyzed for prostaglandin E2 (PGE2). The mean level (+/- SEM) of PGE2 in the anterior as well as in the posterior vitreous was 0.09 +/- 0.016 ng/ml (n = 12 rabbits). Animals pretreated with indomethacin 15 min before death, in order to prevent the formation of prostaglandin during enucleation, showed in both the anterior and posterior vitreous mean PGE2 levels of 0.04 +/- 0.008 ng/ml (n = 12) which were significantly lower. Ocular trauma such as paracentesis of the anterior chamber, indentation of the sclera or laser photocoagulation in the fundus 1 h before death of the animals did not increase the concentration of PGE2 in the vitreous humor. There is no evidence either for local release of PGE2 from tissues in the fundus of the eye or for diffusion of PGE2 from the anterior chamber into the vitreous humor.

Animals↗

PubMed1991

Topical administration of leukotriene antagonists in immunogenic keratitis.

Antagonists of leukotriene D4 (LTD4), 3-[7-(2-n-propyl-3-hydroxy-4-acetyl- phenoxy)-propoxy-2-methyl-3,4-dihydro-4-8-n-propyl-2H-1-benzopyran- 2-yl]-propionic acid (SC-39070) and 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy- propoxy]-4-methyl- 2-oxo-2H-1-benzopyran-3-acetic acid (FPL-60319) were locally administered to eyes of rabbits with immunogenic keratitis. The period of circular leukocyte infiltration (Wessely's ring) in the cornea was markedly decreased. Edema and neovascularization of the cornea were not influenced.

Administration, Topical↗

PubMed1991

Morphologic effects of bacteriochlorin a and light in vivo on intraocular melanoma.

To study the development of tissue and cell damage, the early morphologic changes induced by photodynamic therapy (PDT) with the new photosensitizer bacteriochlorin a (BCA) were investigated in Greene hamster melanoma implanted in the anterior eye chamber of white rabbits up to 24 hr after BCA-PDT, using light and electron microscopy. Immediately after BCA-PDT, intracellular spaces were enlarged, and blood vessels were clotted with swollen erythrocytes. By electron microscopy, it was found that some mitochondria had fused inner and outer membranes, and the cristae mitochondriales were affected. With time, the severity of the tissue and cell damage increased, leading to almost complete tumor necrosis after 24 hr. The direct mitochondrial damage and the vascular damage induced by BCA-PDT probably both contribute to tumor necrosis.

Animals↗

PubMed1990

Ocular and systemic disposition of the dopamine agonist N-0437 in monkeys after ocular administration.

The ocular and systemic disposition of the new dopamine agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) was investigated in conscious monkeys after ocular administration of 0.56 mg N-0437. HCl (corresponding to 0.50 mg free base), containing 200 microCi [3H]N-0437, into the right eye. After killing the animal, the eyes were removed and several eye tissues were dissected and assessed for their content of radioactivity. In the treated eye, the iris contained by far the highest concentration of radioactivity, while in the untreated eye the lower conjunctiva, the iris the ciliary body and the choroid possessed the highest levels of radioactivity. In all dissected eye tissues, a substantially higher concentration of radioactivity was established for the treated eye compared to the untreated eye, except for the vitreous in which for both eyes about an equal concentration was measured. This result suggests the presence of a systemic transport, which was confirmed by the occurrence of bradycardia, starting immediately after ocular application of the drug and lasting for about 1.5 hr. As the total amount of radioactivity in both eyes 7 hr after ocular dosing is very low (0.3-0.5% of the dose), one can conclude that N-0437 is almost completely taken up into the general circulation. The radioactive measurements of bile and urine samples collected up to 7 hr after administration revealed that the elimination of N-0437 and its metabolites is very fast, with the urinary excretion (35% of the dose) slightly higher than to the biliary one (31% of the dose).

Animals↗

PubMed1990

d-Ibuprofen in ocular inflammation induced by paracentesis of the rabbit eye.

The anti-inflammatory compound d-ibuprofen has been investigated for anti-inflammatory and cyclooxygenase inhibitory activity in ocular inflammation induced by paracentesis of eyes of living rabbits. d-Ibuprofen is the dextro-rotary isomer of ibuprofen, a potent non-steroidal anti-inflammatory agent. Eyes pretreated topically with d-ibuprofen 0.8% showed a significant inhibition of aqueous protein (73.0%) and prostaglandin E2 (96.4%) increase after paracentesis as compared to paracentesized untreated fellow eyes and control eyes. In aqueous humor no significant correlation between the increase in prostaglandin E2 and protein could be established after paracentesis. These results indicate that d-ibuprofen could be a useful ocular anti-inflammatory agent as cyclooxygenase inhibitor.

Animals↗

PubMed1990

Tumor destruction by intermediate level hyperthermia.

The tumoricidal effect of hyperthermia was studied in Greene's amelanotic hamster melanoma transplanted into the anterior chamber of rabbit eyes. To achieve optimal depth penetration, hyperthermia was induced with near infrared light of 820-870 nm, during 15 minutes, at a beam diameter of 2.5-6.0 mm resulting in an intermediate level hyperthermia of 45-60 degrees C. At 45 degrees C no tumor destruction occurred, at 50 degrees C the effect varied from no destruction to total thickness tumor destruction. At 55-60 degrees C total tumor destruction with additional lens damage occurred. In comparison photocoagulation with white light revealed only necrosis up to half the tumor thickness.

Animals↗

PubMed1990

Bacteriochlorin a, a new photosensitizer in photodynamic therapy. In vivo results.

The photosensitizing properties of bacteriochlorin a (BCA), a nontoxic derivative of bacteriochlorophyll a, were investigated in vivo. BCA has an absorption band at a wavelength at which tissue penetration is optimal (760 nm), and it shows preferential tumor retention in Greene melanoma implanted in the anterior chamber of rabbit eyes. A dose of 20 mg/kg BCA was administered IV at 4-7 mm tumor diameter; 24 hr later the tumor was irradiated with near-infrared light (30 min, 760 nm, 150-280 J/cm2). On the day after the irradiation it appeared that tumor growth had stopped: fluorescein angiography showed nonperfusion of the tumor. Histopathology after enucleation showed subtotal tumor necrosis with occasionally small clusters of viable cells around a blood vessel and at the tumor periphery. Neither BCA nor light alone had any effect on the eye or melanoma.

Animals↗

PubMed1989

Effect of beta-irradiation by a 106 ruthenium plaque on the rabbit eye choroid.

Fourteen Chinchilla gray rabbit eyes were treated with a ruthenium plaque, receiving 200, 400, or 800 Gy, to assess the effect of beta-irradiation on the normal rabbit choroid. Radiation effects were evaluated using fundus photography, fluorescein angiography, fluorophotometry, and histology. Fluorophotometry showed a fluorescein leakage into the vitreous 1 day after irradiation. Leakage values returned to normal within 1 month after irradiation. Fluorescein angiography showed nonperfusion of the choroid after beta-irradiation; the time between irradiation and the onset of nonperfusion was found to be dose dependent. Five months after 200 Gy irradiation, choroidal atrophy had developed but some vessels still stained with fluorescein; 400 Gy irradiation induced subtotal choroidal nonperfusion within 3 months and 800 Gy within 1 week.

Animals↗

PubMed1989

The effect of therapeutic ultrasound on the average of multiple intraocular pressures throughout the day in therapy-resistant glaucoma.

The effect of therapeutic ultrasound was evaluated in 17 patients with therapy-resistant glaucoma by comparing average intraocular pressure (IOP) curves measured before and 3-4 months after insonification. The insonification regimen was standardized; the medication was identical during both pressure curve measurements. The average IOP decrease was 44% +/- 24 SD (range, 73% decrease to 6% increase). In 82% of the patients the IOP decrease was more than 34%. There was no correlation between the percentage of IOP decrease and the average IOP before insonification (correlation coefficient, 0.21; P = 0.41).

Adult↗