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Biomedical subjects

S M Podos

Publications and source records attributed to S M Podos.

At least 73 records · Page 4Linked to original sources
PubMed1988

A long Krupin-Denver valve implant attached to a 180 degrees scleral explant for glaucoma surgery.

A long glaucoma valve implant attached to an external scleral explant was used during filtration surgery in 72 eyes: 39 eyes with neovascular glaucoma and 33 eyes with other types of secondary glaucomas or with primary glaucoma in which prior filtration surgery had failed. The implant consisted of an open Silastic tube (outside diameter, 0.64 mm), which was placed into the anterior chamber. The external end of the tube contained a pressure-sensitive (opening pressure, 11 mmHg) and unidirectional slit-valve, and was sutured within the groove of a #220 Silastic explant. The 180 degree explant was placed beneath three rectus muscles and then sutured so that the grooved side was against the sclera, with the anterior edge 8 to 12 mm posterior to the limbus. The long glaucoma valve implant resulted in a large, posterior bleb extending over the area of the Silastic explant. The mean preoperative intraocular pressure (IOP) of 43.9 mmHg in the eyes with neovascular glaucoma was reduced to 17.4 mmHg after a mean follow-up of 20.2 months. The mean preoperative IOP of 38.1 mmHg in the eyes after failure of previous filtration surgery was reduced to 17.6 mmHg at a mean follow-up of 21.0 months. Postoperative IOP was less than 21 mmHg in 77% of eyes with neovascular glaucoma (47% required additional medication) and in 82% of eyes with previous failure of filtration surgery (56% required additional medication).

Adolescent↗
PubMed1988

The evaluation of corneal endothelial permeability in PERK study patients.

Sixteen patients enrolled in the PERK study were evaluated by fluorophotometry 24 hours or six months following radial keratotomy. A comparison of eyes operated and not operated upon showed that endothelial permeability was not significantly altered 24 hours and six months after surgery. Aqueous humour flow rates and anterior chamber elimination coefficients were significantly higher 24 hours after surgery in the eyes operated on than in those not operated on. Six months after surgery there was no longer a significant difference in these factors. The increase in aqueous humour flow rates 24 hours after surgery may represent a subclinical breakdown in the blood-aqueous barrier.

Adult↗
PubMed1988

Multiple dosing of prostaglandin F2 alpha or epinephrine on cynomolgus monkey eyes. III. Histopathology.

Prostaglandins (PGs), or their derivatives, are potent ocular hypotensive agents which may prove useful in glaucoma therapy. PGF2 alpha (250 micrograms in 50 microliter saline) or epinephrine 2% solution (50 microliter) was topically applied twice daily for 2 weeks to one eye of six cynomolgus monkeys for each agent. Contralateral control eyes received their respective vehicles. By light microscopy, there was no evidence of inflammation, corneal changes, retinal pathology (including cystoid macular edema), or other adverse effects. Likewise, by electron microscopy of the peripheral cornea, anterior chamber angle, iris base and ciliary body, no differences were noted between treated and control eyes. Therefore, multiple dosing with PGF2 alpha in subhuman primate eyes did not result in notable histopathological changes that would contraindicate a clinical trial in glaucoma patients.

Animals↗
PubMed1988

Nd:YAG laser posterior capsulotomy does not produce elevation of intraocular pressure in cynomolgus monkeys.

The mechanism of the intraocular pressure (IOP) elevation commonly seen in patients following neodymium (Nd):YAG laser posterior capsulotomy is unclear. Substance P, a potent polypeptide that is released into the eye after trigeminal nerve stimulation, may be the cause. In rabbits, topical application of nitrogen mustard causes a rise in IOP which is blocked by capsaicin, a presumed substance P depletor. In the present study, six eyes of three cynomolgus monkeys underwent extracapsular lensectomies. After 2 to 3 months, capsaicin was administered by retrobulbar injection on one side of each animal, and vehicle on the contralateral side. One day later, Nd:YAG laser posterior capsulotomies were performed using 31 mJ (total energy) per eye. Diurnal IOP measurements were made before and after the retrobulbar injections and the capsulotomies. Ten weeks later, laser capsulotomies were repeated using 200 mJ/eye without pretreatment with any potential blockers. None of the six eyes, each undergoing two separate capsulotomies 10 weeks apart, showed a postoperative rise in IOP. These results demonstrate that the cynomolgus monkey is a poor model for studying IOP elevation that often occurs following Nd:YAG laser posterior capsulotomy.

Animals↗
PubMed1987

Intraocular pressure effects of multiple doses of drugs applied to glaucomatous monkey eyes.

The effects of multiple dosing with 0.5% timolol maleate, 2% epinephrine hydrochloride, 4% pilocarpine hydrochloride, 1% vanadate, 1% forskolin (nonproprietary name, colforsin), or 0.5% prostaglandin F2 alpha on intraocular pressure (IOP) were each tested on eight cynomolgus monkey eyes in which glaucoma was induced by photocoagulating the trabecular meshwork with the argon laser. The week prior to drug therapy, baseline IOP measurements were carried out at hourly intervals from 9:30 am to 3:30 pm on three days. One to two days later, therapy was initiated. Each drug was applied topically to both eyes of each monkey twice daily for at least four days. The IOP was measured with a calibrated pneumatonometer at the same hourly intervals on treatment days as on the baseline days. The IOP at each time of day on treatment days was compared with the average baseline IOP measured at the corresponding time of day. Topical application of timolol, epinephrine, pilocarpine, vanadate, and prostaglandin F2 alpha significantly reduced IOP without evidence of tolerance or tachyphylaxis during the course of therapy. Forskolin did not significantly decrease IOP after the second day of treatment.

Animals↗
PubMed1987

Electrophysiological evidence that early glaucoma affects foveal vision.

The pattern electroretinogram (PERG) and visual evoked potential (PVEP) were recorded simultaneously using a 1.1 cpd pattern which was counterphase modulated at 1 Hz. The responses of ocular hypertensive (OHT) eyes (with normal visual fields) and eyes with early glaucoma (with early visual field defects and/or early cupping of the optic nervehead) were compared to age-matched normal observers. All patients (26 eyes) and normal observers (14 eyes) had normal transient flash electroretinograms. Delays were seen in mean PERG latency in both OHT and early glaucoma eyes, while mean PERG amplitude was significantly reduced only in the early glaucoma eyes. The PVEP responses were 'unmeasurable' in 11/26 patient eyes because the waveforms were grossly abnormal in shape, making it impossible to identify the N- and P-components. The data were categorized in this manner: a patient response was considered abnormal if latency or amplitude exceeded normal limits (PERG or PVEP) or if the waveform was 'unmeasurable' due to its shape (PVEP only). Of the 26 patient eyes, we found that 8 eyes had normal PERG and PVEP, 11 eyes had abnormal PERG and PVEP, one eye had an abnormal PERG and a normal PVEP, and 6 eyes (3 patients) had a normal PERG and an abnormal PVEP. These data support the proposition that foveal vision (as assessed by the PVEP) may be affected by early glaucomatous damage. The relationship between the PERG and PVEP also was evaluated using a new measurement which we call the 'latency window'. Using this measurement, 15/26 patient eyes were abnormal-9 of these had 'unmeasurable' PVEPs. This measurement could be useful in classifying 'W'-shaped PVEPs as normal or abnormal.

Adult↗
PubMed1987

Effect of topical pergolide on aqueous dynamics in normal and glaucomatous monkeys.

The effects of pergolide mesylate, an ergoline derivative, were studied on intraocular pressure (IOP), outflow facility, aqueous humor flow, and pupil size in monkeys. Unilateral topical administration of two 20-microliters drops of 0.1% pergolide significantly lowered IOP in the treated- and contralateral eye in both normal- and glaucomatous monkeys. In 12 normal monkeys, the baseline IOP of 18.3 +/- 0.4 mmHg [mean +/- S.E.(M.)] was maximally reduced to 14.4 +/- 0.7 mmHg in the treated eye (P less than 0.001) and 14.6 +/- 0.6 mmHg in the contralateral eye (P less than 0.001) at 2 hr after drug administration. In 10 monkeys made bilaterally glaucomatous by argon laser treatment of the trabecular meshwork, the baseline IOP of 33.9 +/- 3.0 mmHg [mean +/- S.E.(M.)] in the treated eyes and 31.7 +/- 3.3 mmHg in the untreated eyes maximally decreased to 23.9 +/- 2.2 mmHg (P less than 0.05) and 26.2 +/- 3.3 mmHg (P less than 0.005), respectively, at 5 hr. No significant change (P greater than 0.7) in outflow facility occurred in either eye of 11 normal monkeys 2 hr after unilateral 0.1% pergolide treatment. In six normal monkeys, the baseline aqueous humor flow of 1.58 +/- 0.20 microliter min-1 in treated eyes and 1.44 +/- 0.18 microliter min-1 in untreated eyes was reduced to 0.92 +/- 0.08 microliter min-1 (P less than 0.02) and 1.09 +/- 0.11 microliter min-1 (P greater than 0.10), respectively, from 0.5- to 3.5 hr after drug administration. A mydriatic response was observed in both eyes after unilateral treatment from 1- to 2 hr in eight normal monkeys. By the third day of treatment, bilateral twice a day 0.1% pergolide drops in eight glaucomatous monkey eyes no longer significantly (P greater than 0.05) decreased IOP.

Administration, Topical↗
PubMed1987

Analysis of protein kinase activities in rabbit ciliary processes: identification and characterization using exogenous substrates.

Protein-kinase activities in rabbit ciliary process tissue were characterized and quantitated using histone, casein, and myosin light chain as substrates. At least four different protein-kinase activities were separated and identified in the supernatant (soluble) and in the particulate fraction using DEAE-cellulose ion-exchange chromatography. Typical activities of the protein kinases in ciliary processes dissected from one eye were as follows: in the supernatant fraction; protein kinase C, 185.0 pmol min-1; cyclic AMP-dependent protein kinase type II, 34.0 pmol min-1; casein kinase type II, 85.1 pmol min-1; protein kinase M, 9.8 pmol min-1: in the particulate fraction; protein kinase C, 55.1 pmol min-1; cyclic AMP-dependent protein kinase type II, 12.5 pmol min-1; casein kinase type II, 13.4 pmol min-1, and protein kinase M, 5.5 pmol min-1. No cyclic GMP-dependent and no calmodulin-dependent protein-kinase activities were detectable using histone, casein or myosin light chain as substrates. The apparent molecular weight of protein kinase C as estimated by exclusion chromatography on a column of Sephadex G-200 was about 90,000. Inhibitory and stimulatory effects of recently synthesized isoquinolinesulfonamide derivatives (H-7 and H-8), heparin, and polylysine were studied in ciliary process protein kinases. H-7 and H-8 were potent inhibitors of cyclic AMP-dependent protein kinase, protein kinase C and protein kinase M, (IC50 less than 10 microM) but had no inhibitory effects on casein kinase. Heparin at 4 micrograms ml-1 inhibited casein kinase activity almost completely without affecting cyclic AMP-dependent or protein kinase C activities. Poly D- or L-lysine were both found to activate (approximately double) casein kinase activity at 40 micrograms ml-1, but did not significantly activate cyclic AMP-dependent protein kinase or protein kinase C. These results provide basic information on the protein kinase enzymes in the ciliary process and show that protein kinase C is the major kinase in this tissue. This suggests a possible role of the Ca2+ and protein kinase C system in transport functions of ciliary processes and in the regulatory mechanism of aqueous-humor formation additional to the already established importance of the cyclic AMP-dependent protein-kinase enzyme.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1987

Vasoactive intestinal peptide and intraocular pressure: adenylate cyclase activation and binding sites for vasoactive intestinal peptide in membranes of ocular ciliary processes.

Vasoactive intestinal peptide (VIP)-responsive adenylate cyclase and VIP binding sites were investigated in membranes prepared from ciliary processes dissected from albino rabbit eyes. High-affinity binding sites for VIP (Kd, 0.95 nM; 607 fmol/mg of protein), in addition to beta adrenergic sites labeled by dihydroalprenolol (Kd, 0.48 nM; 123 fmol/mg of protein), were present. Activation of adenylate cyclase by VIP had a Ka of 65 nM, and the maximal response was 3.3-fold greater than that for I-isoproterenol (Ka, 102 nM). A peptide fragment of VIP (sequence 10-28) was inactive in all assays and did not inhibit VIP-stimulated adenylate cyclase at 10 microM. Responses to VIP and isoproterenol in combination were additive at lower doses but less than additive at maximal doses. Responses to VIP in combination with a low dose of forskolin (0.1 microM) were potentiated at all dose levels, whether assays were done in presence of MgCl2 or MnCl2. VIP- and forskolin-activated adenylate cyclase was associated with the nonpigmented epithelial cell fraction and not with pigmented epithelial cells separated on Percoll density gradients after dissociation of cells from processes by collagenase digestion. Intravitreous injection of 10 nmol of VIP into the rabbit eye caused a maximal reduction in intraocular pressure at 40 to 50 hr lasting beyond 72 hr. VIP-responsive and beta adrenergic-responsive adenylate cyclase are present on the same cell type (nonpigmented epithelial cells) and appear to share components of the adenylate cyclase system in the same membrane. VIP may participate in the physiologic regulation of aqueous humor secretion at the level of the epithelial cell membrane.

Adenylyl Cyclases↗
PubMed1987

Effects of inorganic ions on rabbit ciliary process adenylate cyclase.

The interaction of several inorganic ions (Mn2+, Ca2+, VO3-, and F-) with adenylate cyclase in the albino rabbit ciliary process particulate fraction was studied. Effects of these substances were determined on three activity states of the enzyme (basal, Gs-protein stimulated activity via isoproterenol activation of beta-adrenergic receptors, forskolin-activated catalytic unit) in the presence of 3 mM Mg2+, 1 mM EDTA and 0.2 mM EGTA. A different pattern of effects was found for each of the four ions. Addition of Mn2+ (2 mM) increased all three responses; basal by up to ten-fold, isoproterenol and forskolin by four to five-fold. Added Ca2+ (1 mM) increased basal by two to three-fold, but inhibited isoproterenol and forskolin responses by 25-50%. Added vanadate (1-10 mM) increased basal by two to four-fold, had no effect on the isoproterenol response, but doubled the forskolin response at 3 mM. Added F- (10 mM) increased basal by 30-40-fold, decreased the isoproterenol response and potentiated the forskolin response. The response to F- which directly activates G-proteins was much greater than that of non-hydrolysable GTP analogs, which also directly activate G-proteins. The results suggest that more than one type of adenylate cyclase and/or several modes of regulation of adenylate cyclase with different ionic requirements may be present in ciliary process membranes.

Adenylyl Cyclases↗
PubMed1987

Multiple dosing of prostaglandin F2 alpha or epinephrine on cynomolgus monkey eyes. I. Aqueous humor dynamics.

After obtaining baseline intraocular pressure (IOP) measurements for 1 week, prostaglandin (PG) F2 alpha (250 micrograms in 50 microliters saline) or epinephrine 2% solution (50 microliters) was topically applied twice daily for 2 weeks to one eye of six cynomolgus monkeys for each agent tested. Contralateral control eyes received their respective vehicles. PGF2 alpha significantly reduced IOP beginning 2 to 3 hr after the first dose, persisting thereafter. A significant (P less than 0.05) hypotensive effect remained for at least 10 hr after the first dose and at least 14 hr after the sixth dose. At 4 hr after the seventh dose, the mean reduction was 10.2 +/- 3.5 (+/- SD) mmHg below baseline (P less than 0.0025). At this time, there was also a significant (P less than 0.01) mean reduction of IOP in the contralateral vehicle-treated eyes of 6.0 +/- 3.3 (+/- SD) mmHg below baseline, which did not appear to be secondary to diurnal fluctuations, repeated tonometry, experimental manipulation, or inadvertent drug transfer. Epinephrine significantly (P less than 0.05) reduced IOP beginning 3 hr after the first dose, but this reduction was minimal and not consistent. Neither PGF2 alpha nor epinephrine altered aqueous flow as measured by fluorophotometry 2 to 6 hr after the fifth dose. Outflow facility could not be assessed by indentation tonography because IOP was often too low at the time of measurement. Whereas PGF2 alpha did not alter pupil size, epinephrine caused significant pupillary dilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Multiple dosing of prostaglandin F2 alpha or epinephrine on cynomolgus monkey eyes. II. Slit-lamp biomicroscopy, aqueous humor analysis, and fluorescein angiography.

Prostaglandin (PG) F2 alpha (250 micrograms in 50 microliters saline) or epinephrine 2% solution (50 microliters) was topically applied twice daily for 2 weeks to one eye of six cynomolgus monkeys for each agent. Contralateral control eyes received their respective vehicles. A trace aqueous humor flare response occurred in some PGF2 alpha-treated eyes, which reached significance (P less than 0.05) only when observed 4 hr after the first or seventh dose. No significant anterior chamber cellular response was observed in treated as compared to control eyes. Slit-lamp biomicroscopic evaluation of the cornea, iris, and lens showed no differences in treated as compared to control eyes throughout the study. Aqueous humor samples were obtained from all eyes 4 hr after the ninth consecutive dose. Soluble protein concentration was significantly (P less than 0.01) greater in the PGF2 alpha-treated eyes (1.22 +/- 0.30 mg/ml) as compared to control (0.56 +/- 0.17 mg/ml) or to epinephrine-treated eyes (0.59 +/- 0.18 mg/ml). Microscopic examination of sediments obtained after centrifugation of the aqueous humor revealed no cells in experimental or control samples. Both PGF2 alpha and PGE2 levels were significantly (P less than 0.025) greater in PGF2 alpha-treated eyes, and showed a trend towards being greater in epinephrine-treated compared to control eyes. Neither cystoid macular edema nor other retinal abnormalities were evident by fluorescein angiography in any eyes during the second week of treatment. Multiple dosing of PGF2 alpha in monkey eyes does not appear to produce clinically significant adverse effects in either the anterior or posterior segment which would contraindicate its use in a multiple-dose clinical trial in glaucoma patients.

Animals↗
PubMed1987

Electrical parameters of the isolated monkey ciliary epithelium and effects of pharmacological agents.

The electrical properties of the isolated monkey ciliary epithelium (CE) were determined in an Ussing-type chamber. In a Hepes, HCO3- buffered solution, transepithelial potential difference (PD), short-circuit current (SCC) and electrical resistance (Rt) were -2.5 mV (aqueous-side negative), 8.5 microA and 246 omega, respectively. Epinephrine (0.01 mM) increased the SCC and PD across the isolated monkey CE when added to the aqueous-side bathing solution but was without effect when added to the blood-side bathing solution. Forskolin (0.01 mM) increased the SCC and PD when added to the bathing solution on either side. A disulfonic stilbene, DIDS (0.1 mM), reduced the SCC and PD when added to the aqueous-side bathing solution but was without effect when added to the blood-side bathing solution. Ouabain (0.1 mM) added to the aqueous-side produced a transient stimulation followed by a gradual inhibition of the SCC and PD. On the blood-side, ouabain directly inhibited the SCC and PD towards zero. Although the general electrical properties were similar to those of the isolated rabbit iris-ciliary epithelium, there were differences in the effects of these pharmacological agents on the electrical properties.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1987

Phorbol ester: effect on intraocular pressure, adenylate cyclase, and protein kinase in the rabbit eye.

Protein kinase C was identified as a major protein kinase enzyme activity in rabbit ciliary processes. Phorbol myristate acetate (4 beta-PMA) in the presence of Ca2+ activated protein kinase C but did not directly affect the cyclic AMP-dependent protein kinase enzyme isolated from ciliary processes. To elucidate possible roles of protein kinase C, PMA was injected intravitreally into rabbit eyes. Fifty pmoles of PMA produced approximately a 40% decrease of the intraocular pressure relative to the control eye lasting for more than 72 hr. A reduction of intraocular pressure was still elicited by this dose of PMA in animals pretreated with systemic indomethacin given to suppress a possible inflammatory response. The biologically inactive analogue, 4 alpha-phorbol didecanoate (100 pmoles/eye) had no significant effect on intraocular pressure. In vivo and in vitro treatment with PMA had no significant effect on adenylate cyclase in ciliary process membranes assayed in vitro. However, protein kinase C isolated from rat brain, when added together with cofactors to membranes in vitro, augmented adenylate cyclase activation by isoproterenol, vasoactive intestinal peptide and aluminum fluoride. A slight increase in the basal activity and in the forskolin response was not statistically significant. The effect of protein kinase C to increase responsiveness of ciliary process adenylate cyclase was totally dependent on the presence of Ca2+ and was augmented by addition of PMA. These findings indicate modulation of adenylate cyclase activity by protein kinase C acting at the level of the G-proteins and suggest a possible role for this enzyme in water and electrolyte transport in the ciliary processes.

Adenylyl Cyclases↗
PubMed1986

Betaxolol in patients with glaucoma and asthma.

We evaluated the use of topically administered betaxolol, a cardioselective beta-adrenergic blocking agent, in 11 patients (eight women and three men, 40 to 81 years old) who had asthma and severe glaucoma with increased intraocular pressure despite maximally tolerated medical therapy. In each of these patients, timolol was either contraindicated or had previously led to development of pulmonary symptoms or complications. Before betaxolol, mean forced expiratory volumes in one second were 66% in the men and 80% in the women of reported normal values in age- and height-matched groups. Betaxolol was then topically administered twice daily. All patients continued to administer betaxolol without exacerbation of pulmonary symptoms and without deterioration in measured pulmonary function tests. Betaxolol further reduced intraocular pressure by a mean of 18% (4 mm Hg) when added to the patients' otherwise maximal regimen.

Administration, Topical↗
PubMed1986

Lipid peroxidation in cataract of the human.

Lipid peroxidation was investigated as one of the possible mechanisms of cataractogenesis in the human. Malondialdehyde (MDA), a major breakdown product of lipid peroxides, was significantly higher in cataractous lenses as compared to that in normal lenses. 2-Thiobarbituric acid-reactive material, isolated from cortical cataracts and purified by Sephadex G-10 column chromatography, was identified as MDA. In cataractous lenses the enzymic defenses against reactive species of O2 were impaired as evidenced by the significant decrease in activities of superoxide dismutase, catalase and glutathione peroxidase. Hydrogen peroxide in aqueous humor and vitreous humor of human eyes associated with cataract was increased 2-3 fold. It is possible that carbonyl groups of MDA could interact with primary amino groups of proteins and phospholipids of lenticular plasmalemmae by a cross-linking reaction forming Schiff-base conjugates and these mechanisms might be involved in the pathogenesis of cataract.

Adolescent↗
PubMed1986

The effect of refractive error on pattern electroretinograms in primates.

The effect of optical blur on the steady-state (6, 8, 10 Hz) counterphase pattern electroretinogram (PERG) was measured in three normal cynomolgus monkeys. Blur was induced using lenses of -8.00 to +12.00 diopters, and monocular PERGs were recorded at a viewing distance of 0.32 meters. A substantial decrease in PERG amplitude occurred with a 0.51 cpd grating when +4.00 diopters of blur or greater were used. PERG amplitude to a 1.25 cpd grating decreased with lenses greater than +2.00 diopters. Minus lenses caused a steep decline in PERG amplitude of both spatial frequency gratings. These results indicate that refractive state has a significant effect upon the PERG and should be carefully considered in electrophysiologic testing of the primate visual system.

Accommodation, Ocular↗