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Biomedical subjects

M Araie

Publications and source records attributed to M Araie.

At least 163 records · Page 9Linked to original sources

The loss of fluorescein, fluorescein glucuronide and fluorescein isothiocyanate dextran from the vitreous by the anterior and retinal pathways.

The pathways by which fluorescein (F), fluorescein glucuronide (FG) and fluorescein dextran (FD) leave the vitreous body of the rabbit were examined by measuring the concentration distribution of the injected fluorophores in sections of the frozen eyes. The contours of F, as already known, show that it leaves the vitreous predominantly across the retinal surface. Mathematical analysis of the concentration gradient leads to an average outward permeability coefficient of 1.4 x 10(-3) cm min-1 for the retinal layers. The contours of FG and FD show that they leave predominantly by diffusion into the posterior chamber, encountering only a minor barrier at the anterior hyaloid membrane. The anterior contours indicate that there can be no substantial posteriorly directed fluid flow through the vitreous; if it occurs its velocity across the retinal surface must be less than 2 x 10(-5) cm min-1. The contours of FD near the posterior pole of the retina suggest that such a flow may be taking place. Some time after the systemic administration of F, an analysis of the rate of loss of fluorescence from the vitreous body shows that this corresponds to the movement of FG out through the anterior chamber. Its value bears little relationship to the condition of the blood-vitreal barrier.

Animals↗

Effect of systemic acetazolamide on the fluid movement across the aqueous-vitreous interface.

In an attempt to study the effect of systemic acetazolamide on the fluid flow between the aqueous and vitreous in normal eyes, 50 mg kg(-1) acetazolamide was given intravenously every hour for 3 hr and the time change of the aqueous flow rate was calculated in two groups of rabbits, applying one of the following two different methods to each: the fluorescein method II of Jones and Maurice, a classical fluorometric method, or the more recently developed Johnson-Maurice method which entails intravitreal injection of FITC-dextran and measurements of its concentration in the anterior chamber many days after the injection. The flow rate after acetazolamide calculated by the fluorescein method II of Jones and Maurice in one group of rabbits was reduced to 55 +/- 5% (mean +/- S.E. n = 9) of the control on the average. When calculated by the Johnson-Maurice method in another group of rabbits, the reduction was to 80 +/- 4% (n = 11) of the control rate. The difference between the above figures was significant (P less than 0.005). Furthermore, the effect of acetazolamide calculated by the first procedure was significantly greater than that calculated by the second at 1 and 2.33 hr and at later times after the acetazolamide injection (P less than 0.05-0.01). On the other hand, the outflow pressure was reduced by 53-60% in both groups. The difference between the flow rates after acetazolamide determined by the above two methods was best explained by assuming that the FITC-dextran movement from the vitreous into the aqueous was reduced by about 25% after acetazolamide administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗

Calcium metabolism in acidotic patients induced by carbonic anhydrase inhibitors: responses to citrate.

Calcium metabolism and its response to citrate were examined in 51 patients with glaucoma receiving carbonic anhydrase inhibitors (acetazolamide or methazolamide). Metabolic acidosis, hypocitraturia and increased incidence of nephrolithiasis were induced by both drugs. However, the acidosis was milder with methazolamide administration. Normocalciuria was observed in 29 patients and was shown to be a result of low filtered calcium. Renal hypercalciuria in 16 patients was associated with elevated parathyroid hormone but nephrogenic cyclic adenosine monophosphate remained within normal limits. Citrate in the form of potassium citrate (4.3 mmol.) and sodium citrate (4.0 mmol.) did not correct the metabolic acidosis or hypocitraturia but consistently decreased fasting and 24-hour urinary calcium excretion in patients with renal hypercalciuria. This event did not occur in patients with normocalciuria or absorptive hypercalciuria. These results suggest that a small amount of citrate could reverse renal hypercalciuria without correcting the metabolic acidosis.

Acetazolamide↗

Effects of a cyclic AMP phosphodiesterase inhibitor, 8'-pivaloyloxymethyl ester of griseolic acid, on aqueous humor dynamics in rabbits.

The mechanism by which pivaloyloxymethyl (POM) ester of griseolic acid (GA), a potent cyclic AMP-phosphodiesterase inhibitor, lowers intraocular pressure (IOP) in albino rabbits was studied. The rate of aqueous flow, measured by fluorophotometry, was significantly lower in GA POM ester-treated eyes (2.36 +/- 0.24 microliters/min) than in control eyes (3.02 +/- 0.24 microliters/min). Topically applied GA POM ester did not alter tonographic outflow or uveoscleral outflow. No differences in aqueous humor protein concentrations between GA POM ester-treated and control eyes were observed. It was thought that the GA POM ester lowered the IOP by decreasing the aqueous inflow. Topical application of this compound caused no inflammatory response in the eye or changes in the blood aqueous barrier.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Effects of topical application of UF-021, a novel prostaglandin derivative, on aqueous humor dynamics in normal human eyes.

The mechanism underlying the intraocular pressure (IOP) lowering effect of a prostaglandin-related compound, isopropyl 20-ethyl-9 alpha,11 alpha-dihydroxy-15-keto-cis-delta 5-prostanoate (UF-021), and its possible adverse effects in long-term use were studied in normal human eyes. A single instillation of 0.12% UF-021 significantly lowered IOP without affecting aqueous flow rate, tonographic C value or episcleral venous pressure. Protein concentration in the anterior chamber and corneal endothelial permeability to fluorescein remained unaffected. It was suggested that UF-021 lowers IOP mainly by increasing uveoscleral outflow. Twice daily application of 0.12% UF-021 for 4 weeks caused no significant changes in aqueous protein concentration, aqueous flow rate or corneal endothelial permeability. Neither single nor long-term use of topical UF-021 induced irritative responses in the outer segment of the eye. The present study suggests that UF-021 has potential as a safe and effective ocular hypotensive drug with a mechanism of action different from other drugs currently available for the treatment of glaucoma.

Administration, Topical↗

[Kinetic study of movement of fluorescein across the isolated rabbit retinal pigment epithelium--choroid].

Using an Ussing-type chamber, the transport of fluorescein (F) across the isolated retinal pigment epithelium (RPE)-choroid of the rabbit was studied. The outward movement (from the vitreous to the choroidal side) of F was significantly greater than the inward movement (from the choroidal to the vitreous side) and was suppressed by the application of 10(-4)M probenecid, 30mM hippurate or 5mM iodipamide to 41%, 45% or 39% of the control, respectively, while the inward movement was not affected by any of these agents. As the F concentration in the chamber increased, the inward movement of F also increased in a linear fashion, but the outward movement showed nonlinearity. The difference between the outward and inward movement of F was thought to represent the net flux of F across the RPE-Choroid and this value showed nonlinearity and saturation as the F concentration increased. The Lineweaver-Burk plot of the reciprocals of the net flux of F concentration gave the apparent Km of 4.5 x 10(-5)M and apparent Vmax of 2.27 nmoles/hr/cm2, which suggested that the F transport system in the rabbit RPE-Choroid had a greater affinity to the substrate but lower transporting capacity as compared with the F transport system in the rabbit iris-ciliary body or the ascorbate transport system in the iris-ciliary body.

Animals↗

[Analysis of transport of fluorescein across the isolated retinal pigment epithelium-choroid using an ussing type chamber].

Retinal pigment epithelium (RPE)-choroid preparations from albino rabbits were sealed in an Ussing type chamber under stabilized conditions for 3 hours. The transepithelial potential was 1.2 +/- 0.08 mV and the transepithelial resistance was 175.2 +/- 9.1 omega.cm2 (mean +/- SE, n = 16). The transport of fluorescein across the isolated rabbit RPE-choroid was studied under short circuit condition and outward (vitreous----choroid) and inward (choroid----vitreous) permeability to fluorescein were determined. The outward permeability was 1.63 +/- 0.20 x 10(-5) cm/sec and inward permeability was 0.44 +/- 0.13 x 10(-5) cm/sec (mean +/- SE, n = 8). The former was 4 times greater than the latter (p less than 0.01). The outward permeability was decreased to 1.02 +/- 0.08 x 10(-5) cm/sec (n = 7), 0.75 +/- 0.11 x 10(-5) cm/sec (n = 5), 0.67 +/- 0.11 x 10(-5) cm/sec (n = 6) by 10(-6) M of ouabain, 10(-5) M of 2,4-dinitrophenol and 10(-4) M of probenecid, respectively. Low temperatures (0.5-1.0 degree C) markedly decreased the outward permeability to 0.05 +/- 0.04 x 10(-5) cm/sec (n = 4, mean +/- SE). These results suggest that active transport plays a role in the outward movement of fluorescein across the rabbit RPE-choroid.

Animals↗

[Diurnal variation of intraocular pressure in low tension glaucoma].

Around-the clock intraocular pressure (IOP) measurement were performed in 104 eyes of 52 low tension glaucoma (LTG) cases. Subjects were all hospitalized and IOP measurements were done every 2 hours from 6:00 AM to 12:00 PM and every 3 hours from 12:00 PM to 6:00 AM. All LTG patients met the following criteria, (1) glaucomatous optic nerve head change and corresponding visual field defect, (2) normal open angle, (3) IOP less than or equal to 21mmHg at any time of IOP measurement, (4) no obvious neurological or rhinological disorders that could affect the optic nerve, (5) no history of hemodynamic crisis or cardiovascular disorders except mild hypertension. Peak IOPs were most frequently observed at 10:00 AM, but about 55% of all observed peaks were in the time period from 6:00 PM to 8:00 AM. Most troughs were observed from 2:00 PM to 10:00 PM. The mean IOP, the diurnal variation and the difference between both eyes in the same person averaged 14.1, 4.9, and 0.6mmHg, respectively. Assuming that the period of rhythm is 24 hours, the results of IOP measurements fitted a cosine curve using the least square method. In 44% of all eyes, significant correlation coefficient (r greater than or equal to 0.6, p less than 0.05) between the measured and the predicted IOPs was noted, and an equation, IOP = 14.3 + 1.7cos 2 pi (t/24-0.4 radian), was obtained. Comparing the present results with former ones, we concluded that the IOP changes in LTG patients were similar to those in normal individuals.

Circadian Rhythm↗

Time course of changes in aqueous protein concentration and flow rate after oral acetazolamide.

The coefficient of plasma protein entry into the aqueous humor, kin, was calculated in the human eyes from the aqueous protein concentration measured with a flare-cell meter and from the aqueous flow rate determined with fluorophotometry. The value of kin averaged 3.47 +/- 0.25 x 10(-5) min-1 (mean +/- SEM) in 12 eyes of six normal young volunteers. The time course of changes in aqueous protein concentration after oral administration of 500 mg acetazolamide was measured with a flare-cell meter in 24 eyes of 12 subjects. Aqueous protein concentration significantly increased from 2-10 hr postadministration with a maximum increase of 41 +/- 7% (mean +/- SEM) at 6 hr postadministration. Assuming that kin is not affected by the drug treatment, we calculated the time change of aqueous flow rate from that of aqueous protein concentration using the value of kin above. The calculated flow rate after the administration of acetazolamide decreased between 1.25 and 8 hr, with a maximum reduction of 40 +/- 11% at 1.75 hr postadministration. These measurements obtained with the flare-cell meter corresponded well to those obtained by fluorophotometry in a separate group of volunteers given the same treatment. It was shown that oral acetazolamide increases aqueous protein concentration, and that the time change of its effect on aqueous flow rate can be monitored by measuring aqueous protein concentration.

Acetazolamide↗

Intraocular irrigating solutions and permeability of the blood-aqueous barrier.

The effects of intraocular irrigating solutions on the blood-aqueous barrier were studied using rabbits injected with fluorescein isothiocyanate-labeled rabbit albumin. Two days after the injection, the anterior chamber was perfused for 121 minutes with one of the following solutions: normal saline, a commercially available citrate-acetate bicarbonate solution, or a glucose glutathione bicarbonate solution; the amount of fluorescein isothiocyanate-labeled rabbit albumin collected in the outflowing perfusate standardized to its plasma concentration was adopted as a blood-aqueous barrier permeability index. Of the three solutions, normal saline showed the highest permeability index and glucose glutathione bicarbonate solution showed the lowest. The effects of oxidized glutathione on the blood-aqueous barrier were also studied, using solutions containing various concentrations of oxidized glutathione. The permeability index for the solution containing 0.3 mmol/L of oxidized glutathione was significantly smaller than that for the solution without oxidized glutathione, suggesting that oxidized glutathione has a beneficial effect on the integrity of the blood-aqueous barrier.

Acetates↗

A new ophthalmic electronic videoendoscope system for intraocular surgery.

A new ophthalmic electronic videoendoscope system has a 20-guage probe for intraocular observation, a standard size for vitreous microsurgical instruments, and both endoscopic and operating microscopic images are displayed on a split-screen monitor system to provide surgeos a simultaneous view of both images. Using this endoscope system at any time during surgery, surgeons can examine the intraocular structure such as the ciliary sulcus, pars plana, or vitreous base and obtain valuable but otherwise unobtainable information for completing the surgery.

Adult↗

Effects of subconjunctival 5-fluorouracil injections on the corneal endothelium and ciliary epithelium.

The effects of 14 successive daily subconjunctival 5-fluorouracil (5-FU) injections on corneal endothelial and ciliary epithelial cells were studied in pigmented rabbits. A total of 100 microliters 5% or 1.25% 5-FU was injected subconjunctivally in one eye and vehicle solution was injected in the other eye. At 12 h or 14 days after the 14th and last injection, both eyes were processed for observation with scanning or transmission electron microscopy. In other groups of rabbits injected with 5% 5-FU, effects on the corneal thickness, corneal endothelial permeability, blood-aqueous barrier permeability, intraocular pressure and aqueous flow rate were also studied. In the fellow eyes and treated eyes examined 14 days after the last injection, no significant morphological changes were seen. In eyes examined 12 h after the last injection, the following findings were obtained. The corneal endothelial cells showed moderate cytoplasmic swelling and mitochondrial swelling and vacuolation. The changes were dose-dependent and most marked in the area near the injection site, whereas they were minimal in the area apposing it. In the ciliary body adjacent to the injection site, disarrangement of the basal infoldings of non-pigmented epithelial cells was seen in eyes injected with 5% 5-FU, whereas no significant change was observed in those injected with 1.25% 5-FU. However, the physiological parameters examined remained unaltered.

Animals↗

The ocular penetration of topical forskolin and its effects on intraocular pressure, aqueous flow rate and cyclic AMP level in the rabbit eye.

The ocular penetration of 14C-forskolin in suspension was studied using albino rabbits. The effects of topical forskolin suspension on cyclic AMP (cAMP) synthesis, aqueous flow and intraocular pressure (IOP) were also studied. It was shown that only 0.03% of the instilled forskolin penetrated the ocular tissue. The calculated kep value for forskolin was 0.2 X 10(-4) cm/hr. The peak concentrations were calculated to be 4 X 10(-7) mole/liter, 4.6 X 10(-7) and 2.7 X 10(-7) mole/1,000 g tissue in aqueous, iris and ciliary body, respectively, after instillation of 1% forskolin suspension. Topical 1% forskolin suspension caused cAMP increase in the aqueous humor 30 minutes after instillation, but cAMP returned to baseline level 60 minutes after instillation. The cAMP level in the ciliary body was not increased by forskolin. Aqueous flow did not change, and the IOP was slightly decreased 45 and 60 minutes after instillation of forskolin suspension. The in vivo least-effective concentration of forskolin in the ciliary epithelium was considered to be about 2.7 X 10(-7) mole/1,000 g tissue. The weak IOP lowering effect of topical forskolin suspension was considered to be due to its poor ocular penetration. However, slight modification of molecular structure might increase ocular penetration. Present results suggest only a slight increase in penetrative potential would be needed to make forskolin effective in antiglaucoma therapy.

Administration, Topical↗

[Changes in intraocular pressure and aqueous humor dynamics of normal human eyes after topical application of bunazosin hydrochloride].

The effects of topically applied bunazosin hydrochloride, a recently developed highly selective alpha 1-adrenergic antagonist, on intraocular pressure, pupillary diameter, aqueous protein concentration, anterior chamber volume, aqueous flow rate and tonographic outflow facility were investigated in eight normal human volunteers. A single application of 0.1% bunazosin hydrochloride caused a significant unilateral reduction in the intraocular pressure from 30 minutes through 4 hours after the application, with a maximum decrease of 2.0 +/- 0.5mmHg (mean +/- SEM) below the contralateral control eyes at 2 hours post-application. Neither pupillary diameter, anterior chamber volume nor outflow facility was affected by the drug application. Both aqueous protein concentration measured with a flare-cell meter and aqueous flow rate determined by fluorophotometry were unaltered. The mechanism of intraocular pressure reduction appears to be an increase in uveoscleral outflow and/or a decrease in episcleral venous pressure.

Adrenergic alpha-Antagonists↗

A new approach to the study of aqueous humor dynamics by measuring the intensity of Tyndall's effect.

A technique is described for studying aqueous humor dynamics by measuring aqueous flare intensity with the laser flare-cell meter. Aqueous flare intensity measured with this instrument was converted into the equivalent human albumin concentration (Ca). A differential equation was given to express the relationship among Ca, aqueous flow rate, plasma protein concentration, anterior chamber volume and the coefficient of entry into the anterior chamber (k(in)) for plasma protein. When k(in) is constant, the time course of changes in aqueous flow rate can be determined from a series of measurements of Ca with the laser flare-cell meter. Using this technique, we assessed the effects of oral acetazolamide on aqueous flow rate. Oral administration of 500 mg acetazolamide decreased aqueous flow rate from 1.25 to 8 hours post-administration, with a maximum reduction of 40% at 1.75 hours post-administration. The validity of this technique was confirmed by comparing the results with those of fluorophotometric measurements. In situations where k(in) is affected by ocular procedures, the time course of changes in k(in) can be monitored by measuring Ca, aqueous flow rate and anterior chamber volume in the same eye. We applied this method to investigate the effects of pilocarpine on the rate of protein entry into the aqueous humor. Single instillation of 1% pilocarpine increased k(in) from 4 to more than 10 hours after the application, with a maximum increase of 37% observed at 9 hours post-application.

Acetazolamide↗

Effect of calcium ion concentration on the permeability of the corneal endothelium.

The effect of free Ca2+ ion concentration on the integrity of the barrier function of the corneal endothelium was studied using the endothelial permeability to carboxyfluorescein (Pac) as a quantitative index according to the method of Araie. Paired rabbit corneas were isolated and mounted in a chamber. To serve as a control, one eye of each pair was perfused with a glucose-glutathione-bicarbonate solution at a Ca2+ concentration of 1.1 mEq, the other with a solution at various Ca2+ concentrations ranging from 0.23-1.1 mEq. The Pac ratio of a solution with a Ca2+ concentration of 0.38 mEq or higher to the control solution was close to unity, and the Pac ratio of a solution with a Ca2+ concentration of 0.33 mEq or lower to the control solution was significantly greater than unity. In a separate experiment, it was found that only slight swelling was seen when a solution with a Ca2+ concentration of 0.23 mEq or higher was used; significant swelling was seen with a solution of a Ca2+ concentration of 0.17 mEq or lower. The lowest free Ca2+ concentration needed for maintaining the barrier function of the corneal endothelium, 0.38 mEq, was found to be higher than that needed for maintaining the corneal thickness, 0.23 mEq.

Animals↗

[The influence of the intraocular pressure on the visual field of low tension glaucoma].

To study the effect of the intraocular pressure (IOP) on the visual field (VF) damage in low tension glaucoma (LTG), we compared the IOP and the VF damage in both eyes of 46 LTG patients. As an index of the VF damage, we used the mean deviation (MD) value calculated by the Humphry (30-2) STATPAC program, and for the IOP data, the mean of 24 hour IOP measurements (diurnal IOP) and the mean of the IOPs measured at each visit to our outpatient clinics (follow-up IOP). In 13 cases, the diurnal and the follow-up IOPs were 0.3 mmHg higher or more in the more damaged eye than those in the less damaged eye, and in 7 cases they were 0.3 mmHg higher or more in the less damaged eye than those in the more damaged eye. Between these two groups, no significant difference was seen in the value of MD, but the diurnal IOP and the follow-up IOP was significantly higher in the former than in the latter group. By discrimination analysis, the two groups were distinguished at the diurnal IOP of 14.1 mmHg (hit rate 77.6%) and the follow-up IOP of 15.0 mmHg (74.2%). An analysis using the whole 46 LTG cases yielded the following results: when the diurnal or follow-up IOP of the more damaged eye was higher than the above determined level, the IOP in the more damaged eye was significantly higher than that in the contralateral less damaged eye.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Effect of postoperative subconjunctival 5-fluorouracil injections on the surgical outcome of trabeculectomy in the Japanese.

A controlled study was carried out to evaluate the effect of postoperative subconjunctival 5-fluorouracil (5-FU) injections on the surgical outcomes of trabeculectomy in the Japanese (a total of 196 eyes in 157 patients). The eyes that had undergone trabeculectomy with postoperative 5-FU (5-FU group) included 36 eyes with primary open-angle glaucoma (POAG) and 17 with secondary glaucoma (SG) undergoing their first or second trabeculectomy. There were also 34 eyes with refractory glaucoma. The eyes that had had trabeculectomy without postoperative 5-FU (control group) included 46 POAG and 31 SG eyes undergoing their first or second trabeculectomy and 24 refractory glaucoma eyes. The surgical techniques and postoperative care were virtually identical between the two groups, except that the control group did not receive 5-FU. The results were analyzed by means of a life table method and a postoperative intraocular pressure (IOP) level equal to or less than 20 mmHg was adopted as the criterion for successful IOP control. In the 5-FU group, the success probability (%) at the 3-year follow-up was 93.9 +/- 4.2 (SE) for POAG eyes, 93.8 +/- 6.1 for SG eyes, and 86.7 +/- 5.6 for refractory glaucoma eyes. In the control group, it was 55.0 +/- 7.9, 37.2 +/- 13.5, and 16.1 +/- 7.4, respectively. The difference in success probability between the 5-FU and control groups was highly significant (P less than 0.001 or 0.01). In the POAG and SG eyes, the mean postoperative IOP was significantly lower in the 5-FU group than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗