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Biomedical subjects

B D Srinivasan

Publications and source records attributed to B D Srinivasan.

At least 19 recordsLinked to original sources
PubMed1993

Calcific band keratopathy on a keratoprosthesis.

We describe a case of calcific band keratopathy in a patient with a nut-and-bolt keratoprosthesis. To our knowledge, this is the first reported case of this condition involving a prosthesis. The patient had initially suffered lye burns to both eyes. The prosthesis was placed in the right eye; numerous procedures had to be undertaken to maintain it. The patient was also treated surgically and pharmacologically for glaucoma. Seventeen years after initial implantation, white flakes appeared on the prosthesis in the classical band pattern. Pathologic examination revealed them to be calcific. Theories concerning corneal and contact lens calcific deposition are evaluated to assess their applicability to this case. We conclude that multiple factors may be responsible for calcific deposition on the keratoprosthesis and that this may call into question previous explanations of this disorder.

Adult↗
PubMed1989

Inhibitors of the arachidonic acid cascade in the management of ocular inflammation.

At the present time, corticosteroids are still the most effective class of drugs for the treatment of ocular inflammation. However, since their prolonged use may result in severe ocular side effects, it would be therapeutically beneficial to develop nonsteroidal anti-inflammatory drugs that have similar or greater efficacy than steroids, but do not share their ocular side effects. Several currently available non-steroidal drugs have been used clinically as prophylactic or therapeutic agents for the following: 1. Prevention of pupillary constriction during intraocular surgery (cataract extraction). 2. Prevention of postoperative inflammation, i.e., incidence of anterior chamber cellular reaction and aqueous flare (breakdown of blood-aqueous barrier) and IOP rise following cataract surgery, intraocular lens implantation, and argon laser trabeculoplasty. 3. Prevention of contact lens induced corneal neovascularization. 4. Improvement of lens opacity (bendazac). 5. Prevention of cystoid macular edema following intraocular surgery. Treatment over long-term period may be effective; postoperative treatment is ineffective. 6. Prevention of conjunctival hyperemia. Some prophylactic ocular uses such as prevention of surgical miosis or postoperative fluorescein leakage have been reported to be successful. However, it is unclear whether the reported success reflected the pharmacological effects due to inhibition of the AA cascade - and hence, reflects the role of some eicosanoids in surgical miosis or postoperative fluorescein leakage - or reflect the effects of these drugs on unexplored physiological or pharmacological mechanisms. For example, pretreatment with flurbiprofen to prevent surgical miosis was based on the assumption that PGs are potent miotic agents in all mammals, including humans. It remains to be established however, whether the small reduction in the extent of pupillary miosis is due to prevention of PG synthesis by this drug or to the prevention of the synthesis of other AA products, such as prostacyclin and thromboxane or possibly to some entirely different mechanism. Prevention of post-surgical fluorescein leakage by prophylactic pre and/or post surgical treatment with a variety of nonsteroidal anti-inflammatory agents is also assumed to be due to inhibition of intraocular PG synthesis, although the possibility that it is due to prevention of the synthesis of prostacyclin or TxA2 has not been ruled out. Even more important, it has not been demonstrated that prevention of this post operative fluorescein leakage reflects the prevention or inhibition of true CME and associated loss of visual acuity.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex Hormones↗
PubMed1989

Cyclooxygenase and lipoxygenase pathways in anterior uvea and conjunctiva.

It has been demonstrated that normal, uninflamed, anterior uvea and conjunctiva of different species have the capacity to synthesize cyclooxygenase and lipoxygenase products. Cyclooxygenase activity is greater than lipoxygenase activity in both anterior uvea and conjunctival tissues. Other ocular tissues such as cornea, lens, and retina were found to have much lesser capacity than the conjunctiva and anterior uvea to synthesize cyclooxygenase and lipoxygenase products from arachidonic acid. In our preliminary studies, we also observed that human retina have considerably less ability to metabolize AA into cyclooxygenase and lipoxygenase activity. The finding that the anterior uvea of all species studied has a high capacity to synthesize PGs and other cyclooxygenase products maybe of particular physiological significance since several investigators have demonstrated that PGE2 and PGF2 alpha in low doses, lower intraocular pressure in all species studied, including the human eye. Additionally, PGE2 can be shown to have some anti-inflammatory effects. In light of these observations, we must consider that the high endogenous cyclooxygenase activity in normal conjunctiva and anterior uvea may play a role in maintaining normal intraocular pressure and in preventing the development of inflammation in response to normal environmental stimuli. Arachidonic acid is also metabolized into biologically active compounds by cytochrome P450 in corneal endothelium. It is not yet known whether or not other ocular tissues also have the ability to metabolize arachidonic acid via this pathway and whether these compounds, when synthesized from endogenous arachidonic acid stores in vivo have any biological effects on the eye. Studies on omega-3 fatty acid metabolism were done for two main reasons: (1) PGE3 and PGD3 lowered intraocular pressure without causing ocular inflammation in rabbit; and (2) some surveys demonstrated that in Greenland Eskimos whose marine diet is enriched with omega-3 substrate eicosapentaenoic acid, have a lower incidence of open-angle glaucoma as compared to Caucasians, whose diet is rich in arachidonic acid. The ability of anterior uvea to synthesize PGE3 and PGD3 in human, monkey, and rabbit anterior uvea warrants further investigation to determine whether or not these omega-3 PGs play a role in lowering intraocular pressure.

Animals↗
PubMed1987

Eicosapentaenoic acid metabolism in cynomolgus and rhesus conjunctiva and eyelid.

We have demonstrated that cynomolgus and rhesus monkey ocular tissues such as conjunctiva and eyelids have the capacity to synthesize cyclo-oxygenase and lipoxygenase products from arachidonic acid (AA). In the present study, we demonstrate that another fatty acid, eicosapentaenoic acid (C20:5), which is found mainly in marine diets, can be converted by cynomolgus and rhesus monkey conjunctiva and eyelids into cyclo-oxygenase (3-series) and lipoxygenase (5-series) products. EPA-lipoxygenase activity (ranging from 6.5% to 10.4%) was greater than EPA-cyclo-oxygenase activity (ranging from 1.5% to 3.5%) in these tissues. Furthermore, BW755, a cyclo-oxygenase and lipoxygenase inhibitor, inhibited the synthesis of EPA-derived cyclo-oxygenase and lipoxygenase product synthesis, indicating the enzymatic nature of EPA metabolism.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1987

Cyclo-oxygenase and lipoxygenase pathways in cynomolgus and rhesus monkey conjunctiva, anterior uvea and eyelids.

The capacity of cynomolgus and rhesus monkey conjunctiva, anterior uvea and eyelids to synthesize cyclo-oxygenase and lipoxygenase products from arachidonic acid was assessed. Both conjunctiva and eyelid tissues of cynomolgus and rhesus monkeys synthesized detectable amounts of cyclo-oxygenase and lipoxygenase products, indicating the presence of cyclo-oxygenase and 5- and 12-lipoxygenase activities in these tissues. In comparison, cynomolgus anterior uvea synthesized a considerably lesser amount of cyclo-oxygenase products. The cyclo-oxygenase activity was considerably greater than the lipoxygenase activity in cynomolgus and rhesus conjunctiva and eyelids.

Animals↗
PubMed1987

Synthesis of slow-reacting substance-like activity in human anterior uvea.

The present study demonstrates that human anterior uvea synthesizes a 5-lipoxygenase product termed slow-reacting substance (SRS) (a mixture of leukotrienes, C4, D4 and E4) from arachidonic acid (AA). Characterization of SRS was done using the guinea pig ileum (GI) as bioassay tissue. SRS contracted GI and this contraction was antagonized by FPL55712, a leukotriene antagonist. The synthesis of SRS was enzymatic in nature since boiled or BW 755-treated tissues did not synthesize SRS-like activity from AA. Further confirmation that the substance was SRS-like came from the measurement of LTC4-like immunoreactivity.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1986

Eicosapentaenoic acid metabolism in human and rabbit anterior uvea.

Eicosapentaenoic acid (EPA) metabolism into 3 series cyclooxygenase and 5 series lipoxygenase products was assessed in human and rabbit anterior uvea. Both tissues synthesized 3 series cyclooxygenase products such as delta17 6-keto-PGF1 (PGI3 metabolite), PGE3 alpha, PGE3, PGD3 and TxB3 (a stable product of TxA3) and lipoxygenase products 12-hydroxyeicosapentaenoic acid (HEPE), 5-HEPE and 5,12-diHEPE from 14C-EPA. EPA-derived cyclooxygenase product synthesis was considerably greater than the formation of lipoxygenase products from EPA in both tissues.

Alprostadil↗
PubMed1986

Diclofenac and enolicam as ocular anti-inflammatory drugs in rabbit corneal wound model.

The anti-inflammatory effects of two nonsteroidal agents, enolicam and diclofenac, were assessed in rabbit corneal wound model. Topically applied diclofenac (50 microliter volume) at 0.01%, 0.1% and 0.5% concentrations inhibited the polymorphonuclear leukocyte (PMN) release into tear fluid following partial (6 mm central area) corneal deepithelialization in rabbits. Similarly, enolicam also inhibited this PMN response following corneal injury. Topical diclofenac was found to be more potent than topical enolicam in inhibiting the inflammatory PMN response following partial corneal injury. Both drugs did not affect the rate of reepithelialization following complete (limbal to limbal) corneal deepithelialization.

Administration, Topical↗
PubMed1986

Differential protein synthesis in steroid-treated ocular surface epithelium.

Topical prednisolone and cortexolone, a known glucocorticoid receptor antagonist, differentially affected the synthesis of proteins in normal corneal epithelium and migrating conjunctival epithelium after complete corneal deepithelialization, as measured by 35S-methionine incorporation and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel) electrophoresis. Application of either prednisolone or cortexolone to corneal epithelium resulted in similar protein synthesis patterns, each showing two new protein bands of about 15K and 32K. Cortexolone, but not prednisolone, initiated the appearance of several protein bands of different molecular weights in the migrating conjunctival epithelium, while treatment with prednisolone plus cortexolone resulted in a pattern of protein bands which resembled the saline-treated control. Crude extracts of prednisolone-treated migrating epithelium also enhanced the inhibition of phospholipase A2 activity, and this prednisolone-induced inhibition was reversed by cortexolone.

17-Hydroxycorticosteroids↗
PubMed1985

Comparative in vivo inhibitory effects of nonsteroidal anti-inflammatory agents on prostaglandin synthesis in rabbit ocular tissues.

We have compared the effects of nonsteroidal anti-inflammatory agents (NSAIDs) indomethacin, flurbiprofen, and aspirin administered either intraperitoneally (IP) or topically on rabbit conjunctival and anterior uveal prostaglandin (PG) synthesis. Doses of IP flurbiprofen and aspirin at or above 50 mg/kg almost completely inhibited PG synthesis in the conjunctiva and anterior uvea. Indomethacin at doses up to 100 mg/kg only partially inhibited PG synthesis in rabbit anterior uvea. Although IP flurbiprofen and aspirin were better than IP indomethacin in inhibiting PG synthesis in anterior uvea, 0.5% topical aspirin almost completely inhibited PG synthesis in the conjunctiva and anterior uvea, but 0.5% flurbiprofen and 0.5% indomethacin did not. A lower topical dose (0.01%) of aspirin prevented the production of PGs in the anterior uvea.

Administration, Topical↗
PubMed1985

Anti-inflammatory effects of ketoprofen in rabbit corneal epithelial wound model.

Ocular anti-inflammatory effects of ketoprofen were assessed and compared with indomethacin in the rabbit corneal epithelial wound model. Intraperitoneally (5 mg kg-1 and 50 mg kg-1) and topically (0.01%) administered ketoprofen and topical indomethacin (0.5%) prevented the release of polymorphonuclear leukocytes (PMNs) into the tear fluid of rabbits following partial de-epithelialization. However, 0.001% ketoprofen applied topically potentiated the PMN response. Topical ketoprofen at all doses tested equally inhibited prostaglandin (PG) synthesis in both conjunctiva and iris-ciliary body. In contrast, indomethacin was more effective in inhibiting PG synthesis in conjunctiva than in the iris-ciliary body. In addition, anti-inflammatory doses of ketoprofen did not interfere with wound healing after complete corneal de-epithelialization in rabbits.

Animals↗
PubMed1985

Prostaglandins E3 and D3 lower intraocular pressure.

The effects of the prostaglandin (PG)-3 series products PGE3 and PGD3 on the intraocular pressure of rabbits were studied. PGE3 at 0.001 and 0.01 mg/eye and PGD3 at 0.01 and 0.05 mg/eye doses were applied topically (in 50-microliters volume) to the normal rabbit eye. Both PGE3 and PGD3 significantly lowered intraocular pressure at all doses tested and the IOP lowering response lasted at least 240 min. Topical PGE3 at 0.01 mg/eye caused mild conjunctival hyperemia which lasted up to 180 min. PGD3, on the other hand, did not induce conjunctival hyperemia. In addition, following application of these PGs, there was no miosis or other sign of intraocular inflammation detectable by slit-lamp examination.

Alprostadil↗
PubMed1984

The synthesis of cyclooxygenase products in ocular tissues of various species.

In the present study we compared the synthesis of various cyclooxygenase products in albino rabbit, dog (puppy and adult), cat, cow and human ocular tissues from 14C-arachidonic acid (AA). Albino rabbit conjunctiva synthesized a substantial amount (47%) of cyclooxygenase products, while cat and dog (puppy as well as adult) conjunctival tissues synthesized lesser but significant amounts of cyclooxygenase products from 14C-AA. Cyclooxygenase activity in the anterior uvea of different species tested was in the following order of potency: cat greater than albino rabbit greater than dog greater than human greater than cow. Furthermore, human and cow anterior uvea synthesized significantly lesser amount of cyclooxygenase products from 14C-AA than amounts from an intermediate substrate, 14C-PGH2. Interestingly, cow anterior uvea synthesized PGF2 alpha and 6-keto-PGF1 alpha (a stable metabolite of PGI2) while human anterior uvea synthesized all cyclooxygenase products from 14-C-PGH2.

Animals↗
PubMed1984

Human anterior uvea synthesizes lipoxygenase products from arachidonic acid.

Arachidonic acid is metabolized into biologically active prostaglandins, thromboxanes, and lipoxygenase products, leukotrienes. In the present study, the ability of human anterior uvea to synthesize lipoxygenase products from 14C-radiolabelled arachidonic acid is assessed. Following cyclooxygenase inhibition by indomethacin, human anterior uvea, similar to rabbit conjunctiva and anterior uvea, synthesizes chemotactic products 12-hydroxyeicosatetraenoic acid (HETE) and 5,12-DiHETE, indicating the presence of both 5- and 12-lipoxygenase enzyme activities.

Arachidonic Acids↗
PubMed1983

Noninvasive observations on eyes of cats after long-term maintenance of reduced intraocular pressure by topical application of prostaglandin E2.

Daily or twice daily prostaglandin E2 (PGE2) application to cat eyes was shown to maintain a reduced intraocular pressure (IOP) for several months without causing substantial flare or cellular response. We report now on detailed ophthalmic examinations performed on these cats after 5-9 months of such treatment (ie, after 150 to 250 unilateral PGE2 applications; 100 micrograms/treatment per eye). A comparison of the treated and contralateral control eyes revealed no differences in the axial length of ocular compartments, in the biomicroscopic appearance of the lens, vitreous, retina, or optic nerve head, in the rate of light-induced pupillary constriction or in the wave form of the electroretinogram. The cell density of the corneal endothelium was not decreased, but the endothelial surface did contain a few small "dark spots." A slight iridial heterochromia was generally apparent. In three of the cats PGE2 application had a sialagogic effect that became a conditioned reflex. Cats tended to keep their lids closed after each treatment; lid closure was more prolonged in the PGE2-treated eye than in the contralateral eye that received the same volume (50 microliters) of vehicle solution. It is concluded that daily treatment with PGE2, in doses sufficient to cause a maintained reduction in IOP, does have some side effects. However, none of these side effects are of sufficient importance to exclude the use of eicosanoids as potential anti-glaucoma agents.

Administration, Topical↗
PubMed1982

Corneal reepithelialization and anti-inflammatory agents.

These studies have demonstrated that nonsteroidal anti-inflammatory agents (cyclooxygenase and lipoxygenase inhibitors) can inhibit PMN arrival in the tear fluid following corneal injury but do not inhibit the reepithelialization either by corneal epithelial cells or by conjunctival epithelial cells. Therefore, they can be used safely in ocular inflammatory conditions even when corneal epithelial defects are present. Corticosteroids, on the other hand, inhibit reepithelialization by conjunctival epithelial cells and not by corneal epithelial cells in the doses tested. This inhibition does not occur with pretreatment prior to injury, suggesting that corticosteroids can be used clinically in conditions that have intact corneal epithelium without fear of slowing down wound healing should epithelial defects occur when not on steroid therapy. Furthermore, the steroid inhibition is temporary since there is a breakthrough in steroid inhibition with time, and occurs only if the steroids have been used shortly after deepithelialization. The steroid inhibition can be reversed by specific steroid antagonist, indicating that the steroid effect is mediated through specific receptors. An exciting and new hypothesis proposes that corticosteroids induce the formation of an inhibitory protein that inhibits the phospholipase enzyme to cause a block in arachidonic acid release from cell membranes. This mechanism of action may also be prevalent in the steroid effect on corneal reepithelialization, and experiments are under way to isolate this inhibitory protein from steroid-treated conjunctival epithelium. This isolation and pharmacologic characterization of this inhibitory protein is of obvious advantage to the field of ophthalmic therapeutics since this protein may have the anti-inflammatory potential of the steroids without their steroid sideeffects.

Adrenal Cortex Hormones↗
PubMed1982

The effect of intravitreal and topical prostaglandins on intraocular inflammation.

We investigated the effects of prostaglandins (PG) E2, PGD2, PGI2, and its metabolites 6-keto-PGE1 and 6-keto-PGF1 alpha, and U46619 (stable analogue of the PG endoperoxide, PGH2) administered either intravitreally or topically on intraocular pressure (IOP), pupil diameter, aqueous protein, and the entry of polymorphonuclear cells (PMNs) in the aqueous. PGE2, 6-keto-PGE1, U46619, and PGI2 increased IOP after either intravitreal or topical administration in a dose-dependent manner, 6-keto-PGE1 was the most potent in increasing IOP. U46619 and PGI2 increased IOP when administered intravitreally; however, these agents also increased IOP of the contralateral control eye. High doses of 6-keto-PGE1 and PGI2 but not 6-keto-PGF1 alpha or PGE2 increased the IOP of both experimental and contralateral eyes, suggesting that this effect may be due to the entry of these agents into the systemic or intraorbital circulation or to stimulation of neuronal pathways. Intravitreal administration of 6-keto-PGE1, PGE2, and PGI2 increased protein of the aqueous, with 6-keto-PGE1 significantly more potent than other PGs. Topically applied PGE2 and 6-keto-PGE1 also increased protein content of the aqueous at doses that elevated IOP. However, topical 6-keto-PGE1 alpha at doses that increased IOP did not increase protein content of the aqueous. In contrast, PGD2 increased the IOP in both eyes; however, it significantly increased aqueous protein content of the experimental eye, indicating that increase in protein content of the aqueous and increase in IOP are not necessarily associated. None of the PGs tested in this study had any effect on pupil diameter or PMN entry into the aqueous. Therefore the classic signs of intraocular inflammation, i.e., increase in IOP, increase in protein content of the aqueous, miosis, and PMN entry into aqueous, are not necessarily associated and sequential, and PGs do not induce all signs of inflammation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗