Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of timolol, propranolol, epinephrine, and isoproterenol on intraocular pressure (IOP) (measured by tonometry) were compared after topical administration in conscious rabbits. Epinephrine and isoproterenol decreased IOP in normotensive rabbits, whereas propranolol had no effect. Timolol produced only a slight and inconsistent lowering of IOP in normotensive rabbits. All four agents reduced IOP elevated by an oral water load; the adrenergic agonists were substantially more active than the two beta-adrenergic blocking agents. In alpha-chymotrypsin-induced ocular hypertension, epinephrine, isoproterenol, and timolol were essentially equally effective, whereas propranolol exhibited only weak activity. In this latter model, timolol did not lose its effectiveness after multiple instillations (three/day) over an 8-day period. The concentration of timolol in the acqueous humor after topical application of effective hypotensive doses was relatively high as compared to that found in plasma. In addition, topical doses of timolol required to lower IOP were considerably greater than those needed to reduce or block the ocular hypotensive activity of isoproterenol. The mode of action and therapeutic implications of beta-adrenergic blocking agents in glaucoma are discussed.
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PMID:Comparison of the effects of timolol and other adrenergic agents on intraocular pressure in the rabbit. 2 Nov 45

The authors have carried out a statistical study on two large groups of patients operated on for cataract and in whom the enzyme alph-chymotrypsin has been used, and the occurrence of ocular hypertension has been examined. One group, which contained 1,003 operations most of which were under the microscope using a firm closure technique, was compared with another group of 324 cases operated under the same conditions but without using the enzyme. In all cases the intraocular pressure was measured 24-48 hours after the operation. The rise in pressure, the rapidity of its development were studied together with its duration and the concentration of the enzyme. In addition these findings were compared with another group of 2,334 eyes operated on several years previously with standard techniques using a less hermetic wound suture, without a microscope, with alpha-chymotrypsin, but whose tensions were controlled from the third week. The results show conclusively that there is a greater frequency of the occurrence of raised intra-ocular pressure when the enzyme is used (40,3%) than when it is not used (25,3%). This ocular hypertension persists in all cases to the end of three weeks. The time of the appearance of the hypertension, the numbers affected and the duration of the intraocular pressure were not significantly meaningful in the statistical analysis.
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PMID:[Enzymatic ocular hypertension: a statistical study (author's transl)]. 14 59

The injection of alpha-chymotrypsin into the posterior chamber of the eye is known to produce an experimental ocular hypertension of long duration in animals. The present study reports the pathological changes which occur in the eye during the first nine months after the ocular injection of alpha-chymotrypsin in rabbits. Six weeks after treatment most of the eyes showed a buphthalmia and an intraocular pressure elevation which varied greatly from animal to animal. The anterior chamber angle of the treated eyes showed a progressive enlargement. Several days after the enzyme injection a transient increase in thickness of the cornea and Descemet membrane was noted. Cupping of the optic disc, characterized by a total disappearance of the optic nerve head fibers and an excavation beginning at margins of the retina appeared after four months and in most cases were present seven months after the treatment. More or less prominent retinal degeneration was also evidenced three months after enzyme injection. The results indicate alpha-chymotrypsin-induced occular hypertension in the rabbit leads after several months to pathological change in the eye analogous to that observed in human glaucoma.
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PMID:[Experimental alpha-chymotrypsin model of glaucoma in the rabbit: histopathological studies (author's transl)]. 52 8

D-isoproterenol d-bitartrate applied topically lowers intraocular pressure (IOP) in normal albino rabbits and rabbits with alpha-chymotrypsin-induced glaucoma. This effect is independent of any effect on systemic blood pressure or pulse rate. A similar response could not be obtained in monkey or human eyes. Subconjunctival injection of d-isoproterenol d-bitartrate to monkey eyes did not alter IOP.
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PMID:The effect of d-isoproterenol on intraocular pressure of the rabbit, monkey, and man. 81 36

delta 8-Tetrahydrocannabinol (delta 8-THC), a known antiglaucoma lipophilic drug, was incorporated in a submicron emulsion for ocular administration. The mean droplet size of the emulsion was 130 +/- 41 nm, and no droplet was larger than 400 nm. No change in pH, particle size distribution or zeta potential was noted after sterilization by steam autoclaving or long-term storage over 9 months. An intense and long-lasting intraocular pressure (IOP)-depressant effect was observed after ocular application (50 microliters) of the THC emulsion, 0.4% (w/w), to rabbits with ocular hypertension (chymotrypsin model). Lesser effects were observed in normotensive rabbits. No irritation effect of either the emulsion vehicle or THC emulsion on the rabbit eyes was detected. These results underline the promising properties of submicron emulsions as vehicles for lipophilic ophthalmic drugs. The mechanism by which the emulsion induced the marked delta 8-THC antiglaucoma effect remains unclear. However, the possible involvement of delta 8-THC systemic absorption in the hypotensive effect induced by the emulsion cannot be excluded and will be the subject of further investigation.
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PMID:A submicron emulsion as ocular vehicle for delta-8-tetrahydrocannabinol: effect on intraocular pressure in rabbits. 132 79

There are many unanswered questions about chronic glaucoma which cannot be investigated in the available animal models. The present experiments were designed to develop a rabbit model of chronic intraocular hypertension with characteristics similar to human chronic glaucoma by ligating vortex veins or by making single or multiple intraocular injections of 0.5% or 1% alpha-chymotrypsin, 20% chondroitin sulphate, 2% hydroxypropyl methylcellulose, 2% sodium carboxymethylcellulose or 1% or 2% methylcellulose. Evaluation was based on the clinical findings, intraocular pressure and the retrograde axoplasmic transport function of the optic nerve using a horseradish peroxidase histochemical technique. Most methods either failed to produce moderate chronic intraocular hypertension or were associated with other complications. However, a reliable and relatively long period (eight weeks) of intraocular hypertension was developed by a series of four intra-anterior chamber injections of 1% or 2% methylcellulose. This model has been proved suitable for the study of structural and functional damage to the retina and optic nerve caused by chronic glaucoma.
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PMID:Development of experimental chronic intraocular hypertension in the rabbit. 144 75

ANF binding sites were analysed in the ciliary processes of rabbits with unilateral experimental glaucoma which had been induced by injecting alpha-chymotrypsin into the posterior chamber of the right eyes. The intraocular pressure (IOP) of glaucomatous eyes was significantly greater (28.4 +/- 4 mmHg) than that of normotensive control eyes (13.1 +/- 1.4 mmHg, mean +/- S.E.M., n = 23, P less than 0.05). ANF concentrations in aqueous humour and the ciliary processes were significantly higher in glaucomatous eyes (91 +/- 2 pg ml-1 and 30.4 +/- 4.2 pg g-1 wet weight) than in normal eyes (3.1 +/- 2.2 pg ml-1 and 10.2 +/- 2.7 pg g-1 wet weight, respectively, n = 6, P less than 0.01). The number of ANF-binding sites (Bmax) in the ciliary processes of glaucomatous rabbit eyes was significantly decreased in comparison to the controls (24 +/- 4 vs. 13 +/- 3 fmol mg-1 protein, n = 10, P less than 0.05). These data suggest that ANF receptors in the ciliary processes are down-regulated and that ANF may play an important role in the pathophysiology of experimental glaucoma.
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PMID:Experimental glaucoma significantly decreases atrial natriuretic factor (ANF) receptors in the ciliary processes of the rabbit eye. 166 Apr 4

Effects of topically applied bunazosin, an alpha 1-adrenoceptor blocker, on intraocular pressure (IOP) and pupillary diameter were investigated in normotensive rabbits and cats, in addition to experimentally hypertensive rabbits. Bunazosin (0.005% to 0.1%) applied to both eyes significantly lowered IOP in a concentration-dependent manner in normotensive rabbits and cats. The unilateral application of 0.1% bunazosin significantly lowered the IOP in the treated eye, whereas it caused no significant change in the contralateral eye, suggesting that the effect of bunazosin is due mainly to a direct and local action and is not systemic. Bunazosin was also effective in experimentally hypertensive models induced both by water-loading and by alpha-chymotrypsin in rabbits. There was a significant correlation between the IOP decrease caused by bunazosin and the IOP value before the application, indicating that the IOP-lowering action of bunazosin is dependent on the height of the original IOP level. Bunazosin had no influence on pupillary diameter even when 0.5% was applied to rabbits. Topically applied bunazosin may be useful as a new antiglaucoma agent.
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PMID:[Ocular hypotensive effects of topically applied bunazosin, an alpha 1-adrenoceptor blocker, in rabbits and cats]. 168 8

1. L-662,583 was a potent inhibitor in vitro of purified, human erythrocyte carbonic anhydrase II, possessing an IC50 of 0.7 nM. The IC50 values for MK-927, acetazolamide and methazolamide were 13.0 nM, 10.8 nM and 21.2 nM, respectively. 2. A 1 h pretreatment with one 50 microliters drop of a 0.1% solution of L-662,583 blocked carbonic anhydrase activity in a homogenate of the iris + ciliary body of albino rabbits by 63%. Similar treatment with 0.1% suspensions of acetazolamide and methazolamide elicited inhibitions of 30% and 20%, respectively. This ex vivo model indirectly assesses the ability of an agent to enter the rabbit eye. 3. Concentrations of L-662,583 in the cornea, aqueous humour and iris + ciliary body of albino rabbits were determined by h.p.l.c. at predetermined times after the instillation (one drop of 50 microliters) of a 2% solution of L-662,583. Peak levels for cornea (47.4 micrograms g-1), aqueous humour (4.51 micrograms ml-1) and iris + ciliary body (9.61 micrograms g-1) occurred at 0.5, 2 and 1 h after instillation, respectively. 4. The experimentally elevated intraocular pressure of the right eye of rabbits, induced by prior intraocular injection of alpha-chymotrypsin, was maximally decreased by 4.5 mmHg, 6.2 mmHg and 9.8 mmHg after the instillation (one drop of 50 microliters) of 0.01%, 0.1% and 0.5% solutions of L-662,583, respectively. All three concentrations lowered intraocular pressure at all time points from 1 h up to and including 5 h, the last recorded time point. The unilateral instillation of L-662,583 (0.5%) into the contralateral, left eye failed to lower the elevated intraocular pressure of the untreated, right eye. This finding indicates that the site of action of topically applied L-662,583 in this paradigm is local. The ocular normotensive, albino rabbit was much less susceptible than the ocular hypertensive rabbit to the intraocular pressure lowering effect of topically applied L-662,583, with a 2% solution maximally decreasing intraocular pressure by 2.3 mmHg. 5. Unilateral ocular hypertension was elicited in the right eye of sedated, cynomolgus monkeys by argon laser-induced photocoagulation of the trabecular meshwork. The instillation (one drop of 50 microL) of L-662, 583 (2%) significantly lowered the elevated intraocular pressure of the right eye at all time points from 1 h up to and including 5 h. The maximum decline was 8.3 mmHg at 3 h and this represented a reduction of 23% from the corresponding baseline value of 36.8 mmHg. The intraocular pressure of the hypertensive, right eye was maximally decreased by 4.1 mmHg and 4.8 mmHg after the instillation of 0.5% and 1% solutions of L-662,583, respectively. Like the rabbit, the normotensive eye of cynomolgus monkeys was more resistant than the hypertensive eye to the ocular hypotensive action of L-662, 583, as indicated by the inability of 0.5% and 1% solutions of the agent to lower intraocular pressure. L-662,583 (2%) maximally reduced the intraocular pressure of normotensive monkey eyes by 2.4 mmHg at 2 h. 6. L-662,583 is structurally different from MK-927, a carbonic anhydrase inhibitor that lowers the intraocular pressure of glaucoma patients following the instillation of a 2% solution. These preclinical observations indicate that L-662,583, like MK-927, is a water-soluble carbonic anhydrase inhibitor which, on topical administration, lowers intraocular pressure by virtue of an action confined to within the eye.
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PMID:L-662,583 is a topically effective ocular hypotensive carbonic anhydrase inhibitor in experimental animals. 211 13

Atrial natriuretic factor (ANF) concentration in the aqueous humor (AH) was studied in rabbits with experimental glaucoma induced by injecting alpha-chymotrypsin into the posterior chamber. In normal rabbit eyes, the ANF concentration in AH was 3.1 +/- 1.2 pg/ml (mean +/- SEM; n = 12), ranging from 0 to 5.8 pg/ml, whereas it was significantly higher in AH from glaucomatous rabbit eyes, being 81.0 +/- 9.8 pg/ml (n = 12). These findings were correlated with intraocular pressure (IOP), which was 13.0 +/- 2.4 mmHg (n = 12) in normal rabbit eyes and significantly greater in glaucomatous eyes: 24.4 +/- 3.0 mmHg (n = 12). Our data indicate that enhanced ANF release in AH during experimental glaucoma may play an important physiological role in modulating IOP.
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PMID:Immunoreactive atrial natriuretic factor in aqueous humor: its concentration is increased with high intraocular pressure in rabbit eyes. 214 92


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