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At least 19 recordsLinked to original sources

Comparison of fluconazole pharmacokinetics in serum, aqueous humor, vitreous humor, and cerebrospinal fluid following a single dose and at steady state.

The objective of this study was to characterize the pharmacokinetic parameters and penetration of fluconazole following a single dose in the serum, aqueous humor, vitreous humor and cerebrospinal fluid (CSF) of non pigmented rabbits using serial sampling techniques and to determine if the pharmacokinetic parameters in the eye and CSF are similar. Twenty healthy male rabbits received intravenous fluconazole 20 mg/kg as a single dose or 20 mg/kg every 12 hours for 4 doses. Serum, aqueous humor, vitreous humor and CSF samples were taken 15 minutes after the initial intravenous injection and hourly thereafter for six hours. Fluconazole concentrations were determined by microbiological assay. Pharmacokinetic analyses were performed using a nonlinear least-square regression program. Fluconazole's penetration in all anatomical compartments was > 70% than in the serum. Similar elimination half-lives and time to reach maximum concentrations were noted in all compartments. While mean concentrations in each anatomical compartment were similar in animals receiving a single dose or among those at serum steady state, the mean concentrations achieved in the serum, aqueous and vitreous humors and CSF were between 1.82 and 2.17 times higher at serum steady state than following a single dose. At serum concentrations that are comparable to those in humans, the penetration of fluconazole into the noninflamed aqueous and vitreous humors and CSF were > or = 70%. The CSF and ocular pharmacokinetic parameters closely resembled each other, so that either could be used as a surrogate for the other.

Animals↗

Phosphorylation of small molecular weight polypeptides in the iris-ciliary complex, aqueous humor and vitreous humor.

The polypeptides of vitreous humor, aqueous humor and iris-ciliary complex cells of eyes were phosphorylated with [gamma-32P]ATP without exogenous protein kinase. Phosphorylated polypeptides were analyzed by sodium dodecyl sulfate gel electrophoresis and autoradiography. The phosphorylated polypeptides of rabbit vitreous humor showed many high molecular weight prominent bands, but no detectable phosphoproteins were found in the 12 kDa or lower range. Bovine vitreous humor has predominantly acidic polypeptides and some of them are below 20 kDa. Rabbit and bovine iris-ciliary complex and rabbit aqueous humor showed a prominent common 4 kDa phosphopolypeptide which could also be synthesized by cloned populations of cells from the bovine iris and the rabbit iris-ciliary body. It is possible that the 4 kDa phosphopolypeptide of the aqueous humor is synthesized by the iris-ciliary complex cells.

Adenosine Triphosphate↗

Intracorneal, aqueous humor, and vitreous humor penetration of topical and oral ofloxacin.

OBJECTIVES: To investigate the intracorneal, aqueous, and vitreous penetration of ofloxacin, and to assess the concentration of the drug after topical administration alone and after combined topical and oral administration. METHODS: Twenty consecutive patients undergoing penetrating keratoplasty with vitrectomy for bullous keratopathy received 2 drops of 0.3% ofloxacin every 30 minutes starting 4 hours before surgery. Group A (10 patients) received topical therapy alone. Group B (10 patients) received an additional 3 doses of oral ofloxacin, 400 mg, every 12 hours starting 26 hours before surgery. Aqueous humor, vitreous humor, and corneal specimens were analyzed for ofloxacin levels. RESULTS: For group A, the mean intracorneal ofloxacin level was 4.51 micrograms/mL (range, 0.58-8.77 micrograms/mL; 10 specimens), the mean aqueous humor level was 1.34 micrograms/mL (range, 0.07-4.98 micrograms/mL; 8 specimens), and the mean vitreous humor level was 0.37 micrograms/mL (range, 0.05-0.90 micrograms/mL; 8 specimens). For group B, the mean intracorneal ofloxacin level was 8.59 micrograms/mL (range, 1.18-23.24 micrograms/mL; 10 specimens), the mean aqueous humor level was 2.77 micrograms/mL (range, 0.25-5.80 micrograms/mL; 10 specimens), and the mean vitreous humor level was 2.55 micrograms/mL (range, 0.28-4.97 micrograms/mL; 9 specimens). CONCLUSIONS: Topically applied ofloxacin achieves therapeutic levels in the cornea and aqueous. Mean levels achievable are well above the 90% minimal inhibitory concentration (MIC90) for the majority of bacteria responsible for endophthalmitis and corneal ulceration. The addition of oral ofloxacin to topical therapy increased vitreous penetration 7-fold in this assay trial.

Administration, Oral↗

Expression and characterization of SPARC in human lens and in the aqueous and vitreous humors.

SPARC (secreted protein, acidic and rich in cysteine) is a matricellular glycoprotein that regulates morphogenesis, cellular proliferation, and differentiation. SPARC is a critical factor in the development and maintenance of lens transparency in mice. SPARC-null mice develop lenticular opacity at an early age that progresses gradually to mature cataract. Despite the high level of homology between the mouse and human genes, little is known about SPARC in the human lens. We have studied the expression of SPARC protein in human lens and surrounding ocular tissues from normal human donors (60-70 years old). Immunohistochemical and immunoblot analyses were conducted on lens, aqueous humor, vitreous, ciliary epithelium, pigment epithelium, cornea and retina. The epithelia and capsule of the lens contained SPARC, whereas the cortical and nuclear fibers did not. In contrast, the aqueous humor and vitreous, which provide nutrients to the lens and regulate its development and function, contained significant amounts of SPARC. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of extracts of various ocular tissues revealed bands of 43 and 29 kD after disulfide bond reduction that were reactive with anti-SPARC IgG. Despite the presence of protease inhibitors during sample preparation, we observed cleavage of intact SPARC to a 29 kD fragment, a peptide reported in other tissues and attributed to endogenous proteolysis. In addition, bands of molecular mass 150 and 200 kD were present that appeared to be disulfide-bonded complexes of SPARC monomers. Human cornea, ciliary epithelium, pigment epithelium and retina also contained SPARC. The presence of SPARC in the aqueous humor and vitreous, as well as in the lens, indicates a functional importance of SPARC in adult human eye as well as in lens development.

Aged↗

Reduced viability of vascular endothelial cells by high concentration of ascorbic acid in vitreous humor.

Normal mammalian vitreous humor maintains its avascularity after regression of hyaloid vessels. Neovascularization in adults is only detected under pathological conditions which suggests that antiangiogenic factors are present in the vitreous humor. To elucidate the mechanism of vitreal angiogenic inhibition, we investigated the effect of vitreous humor on cultured vascular endothelial cells. When bovine aortic endothelial cells were cultured in the presence of bovine vitreous humor in medium, a decrease in cell viability was observed within 24 h. Ascorbic acid from vitreous humor has been identified as a cell death inducing factor with high performance liquid chromatography (HPLC) and molecular mass analysis. Ascorbic acid reduced endothelial cell viability at concentrations normally present in vitreous humor. This effect was completely inhibited by antioxidants, N-acetylcysteine and catalase. Amongst the ascorbic acid derivatives tested, ascorbic acid 2-phosphate did not induce cell death, suggesting that the production of ascorbyl radical is required for induction of cell death. Furthermore, capillary formation in three-dimensional collagen gel cultures characteristic of vascular endothelial cells were disrupted in the presence of ascorbic acid. Since ascorbic acid is highly concentrated in ocular tissues, especially in vitreous humor, it may function as a neovascularization inhibitor.

Acetylcysteine↗

Penetration of topical and oral ofloxacin into the aqueous and vitreous humor of inflamed rabbit eyes.

PURPOSE: This study aimed to investigate the penetration of topical and oral ofloxacin into aqueous humor and vitreous humor in post-traumatic endophthalmitis model in rabbits. METHODS: A standardized intraocular infection after penetrating injury was made in the right eyes of 16 rabbits. Intraocular infection was induced by intravitreal injection of a suspension of Staphylococcus aureus. The intact left eyes were maintained as controls. The animals were divided randomly into two groups. (1) In the topical group, two drops of ofloxacin 0.3% eyedrops were instilled to both eyes every 30 min for 4 h. (2) In the topical-oral group, two doses of 25 mg/kg of ofloxacin at 12-h intervals were given orally, then the protocol of the first group was applied. Aqueous and vitreous humor samples were taken 30 min after the last drop. Ofloxacin concentrations were measured by using HPLC. RESULTS: Mean aqueous levels of ofloxacin in control eyes were: 3.25 +/- 2.55 microg/ml in topical group. 4.58 +/- 5.39 microg/ml in topical-oral group. Mean aqueous levels in inflamed eyes were: 5.21 +/- 4.55 microg/ml in topical group, 10.34 +/- 8.88 microg/ml in topical-oral group. Mean vitreous levels of ofloxacin in control eyes were: 0.17 +/- 0.07 microg/ml in topical group, 1.30 +/- 1.23 microg/ml in topical-oral group. Mean vitreous levels in inflamed eyes were: 0.35 +/- 0.22 microg/ml in topical group, 3.48 +/- 2.69 microg/ml in topical-oral group. There was no significant difference among the groups (P > 0.05), however. CONCLUSIONS: The result of this study suggests that oral supplementation of ofloxacin to topical instillation increased the ocular levels of ofloxacin in the post-traumatic endophthalmitis model. Mean drug concentrations in aqueous and vitreous humors were above the 90% minimum inhibitory concentrations (MIC90) for most of the common microorganisms causing endophthalmitis in all eyes, except in the vitreous humors of the intact eyes instilled topically.

Administration, Topical↗

Detection of human immunodeficiency virus antigen in vitreous humor.

The vitreous humor from 11 patients with acquired immunodeficiency syndrome was obtained at postmortem examination and tested for human immunodeficiency virus antigen and antibody by using the Abbott enzyme-linked immunosorbent assay procedures. Five patients had detectable antigen, supporting the recent observation that the virus may directly infect the retina.

Acquired Immunodeficiency Syndrome↗

Postmortem endocrine levels in the vitreous humor.

The vitreous humor and sera from 51 autopsy cases were assayed for progesterone, estradiol, thyroxine, triiodothyronine, TSH, FSH, LH and prolactin. The results indicate that the blood retinal barrier has unique properties of its own. All hormones were measurable in the sera. Progesterone, estradiol, T3 and T4 were not detected despite their lipid solubility and their small molecular size while the larger glycoprotein hormones were easily measureable.

Blood-Retinal Barrier↗

High-performance liquid chromatography with column switching for the determination of cocaine and benzoylecgonine concentrations in vitreous humor.

A sample concentration technique was adapted for the determination of cocaine and benzoylecgonine (BE) concentrations in vitreous humor. Vitreous humor (0.5 mL) was diluted 1:1 with water and applied through a filter onto a 3-cm preconcentration column. Following a simple wash step, the analytes were flushed directly onto a reversed-phase analytical high-performance liquid chromatography (HPLC) system. Absolute recoveries were high (above 90%) and the chromatograms were free from interference. Analysis for the drug and its breakdown product was performed using ultraviolet (UV) visible photodiode array detection, which allowed confirmation of peak identity. Recognizable UV spectra could be measured with as little as 20 ng on column. Comparison of the drug levels in 27 blood and vitreous humor samples showed that, while there was only a low correlation between the blood and vitreous concentrations (R = 0.70), vitreous cocaine and BE determinations were good indicators of antemortem cocaine use. In almost all cases, the vitreous BE concentrations were higher than the cocaine concentrations. The technique was easy to perform and the vitreous samples were especially compatible with this low-labor analytical procedure.

Chromatography, High Pressure Liquid↗

Vitreous humor magnesium in alcoholics.

Postmortem vitreous humor magnesium concentrations were determined in 27 alcoholics and in 27 nonalcoholics who died of various causes. No significant differences in magnesium values were present between these two groups. The concentrations in those dying with alcohol withdrawal syndrome or in those with postmortem findings limited to hepatic fatty change did not differ significantly from those in the nonalcoholic group or from those of the alcoholics dying of other causes. There was no correlation between vitreous humor magnesium concentrations and postmortem interval in any group. We conclude that vitreous humor magnesium determination is not helpful in the postmortem evaluation of suspected alcohol-related deaths or in determining postmortem interval.

Adolescent↗

Particle interaction in solutions derived from ox vitreous humor.

Solutions made by homogenization of vitreous humor exhibit anomalous viscosity at low shear rates due to interaction between hyaluronic acid and a hydroxyproline-containing material similar to collagen. The latter can be removed by filtration or centrifugation to give a solution whose viscosity is due to hyaluronic acid. On concentration the viscosity of the latter remains independent of shear rate and it is concluded that hyaluronic acid in the vitreous humor is not greatly asymmetric. There is no evidence that the soluble protein of vitreous humor contributes to the viscosity. Hyaluronic acid in vitreous humor is not in chemical combination with protein. The interaction between the hyaluronic acid and the collagen-like material is ascribed to weak, coulombic forces.

Body Fluids↗