Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of human skin and corneal fibroblasts with prednisolone-21-phosphate did not increase the capacity of these cells to replicate type I herpes simplex virus (HSV). The steroid however was found to (1) inhibit human lymphocytes from mediating antibody-dependent cell-mediated cytotoxicity (ADCC) against HSV-infected fibroblasts and (2) suppress the replication of virus in PHA-stimulated human lymphocytes. The data suggest that the exacerbation observed when patients with dendritic keratitis are inadvertently treated with prednisolone may be due to the steroid suppressing ADCC and not by promoting the growth of virus in the corneal cells.
 ...
PMID:The effect of prednisolone on antibody-dependent cell-mediated cytotoxicity and the growth of type I herpes simplex virus in human cells. 20 20

An experimental model of staphylococcal keratitis in guinea pigs was devised that is suitable for quantitative evaluation of therapy. The growth curve in the cornea of a virulent strain of Staphylococcus aureus was determined. The organism multiplied rapidly, reached a peak in about 12 hours, and began to decline in numbers after three days. Infections were relatively resistant to therapy begun 24 hours after infection was established. Treatment started earlier when fewer bacteria were present was more effective than treatment begun later. Treatment begun at the time of infection, which might be considered prophylaxis, was highly effective. When treatment was begun eight hours after infection, tobramycin sulfate and gentamicin sulfate solutions administered topically in doses of 20 mg/ml were more effective than topical bacitracin, erythromycin, clindamycin phosphate, or a solution containing polymyxin B sulfate, neomycin sulfate, and gramicidin. Bacitracin and erythromycin ointments were ineffective.
 ...
PMID:Staphylococcal keratitis. Experimental model in guinea pigs. 71 6

We studied the inhibitory effects of chicken egg-white ovomacroglobulin (ovoM) on keratitis induced by 56,000-Da protease (56 KP) of Serratia marcescens and by elastase (PE) and alkaline protease (PAP) of Pseudomonas aeruginosa. The effects of ovoM on the serratial and pseudomonal keratitis in rabbits were also elucidated. In one model, four drops of 56 KP, PE, or PAP (1 mg/ml) were applied to wounded corneas of eight eyes. Thereafter, 80 microliters ovoM (10 mg/ml) was dropped into four eyes and 0.01 M phosphate-buffed 0.15 M saline (pH 7.4) into the other eyes as a control. The other in vivo test system involved intrastromal injection of S. marcescens or P. aeruginosa, by which each sample (10(5)-10(7) colony-forming units) mixed with ovoM was injected into one cornea and the other cornea received organisms without ovoM. OvoM completely inhibited the activity of these bacterial proteases in vitro and reduced corneal destruction in experimental keratitis in rabbits. In addition, greatly accelerated wound healing was observed.
 ...
PMID:Inhibitory effects of ovomacroglobulin on bacterial keratitis in rabbits. 186 68

An intrastromal injection of endotoxin lipopolysaccharide (LPS) in one eye of New Zealand albino rabbits induced a prominent keratitis characterized clinically and microscopically by edema and infiltration. Polymorphonuclear leukocytes (PMNs) constituted the primary invading leukocytic element. Collagen synthesis was measured by pulsing the corneas with 3H-proline before inducing inflammation. The invasion of the cornea by leukocytes did not alter the conversion of proline to hydroxyproline significantly in the stroma during the 14-day observation period, signifying that there were only negligible changes in the rate of collagen synthesis. However, the percentage of total stromal protein represented by collagen (ie, collagen/total protein) was only 50% of that in comparable corneas receiving an injection of phosphate-buffered saline. Some animals were rendered leukopenic by intravenous nitrogen mustard before intrastromal LPS injection caused a less severe corneal inflammatory response, characterized microscopically by fewer infiltrating leukocytes. Similarly, in nonleukopenic rabbits, topical therapy with 1% prednisolone acetate markedly reduced the corneal inflammatory response which also was characterized by fewer invading leukocytes. In neither instance was there extreme collagen loss, suggesting that the loss of stromal collagen is related to PMN infiltration.
 ...
PMID:Quantification of stromal destruction in the inflamed cornea. 200 34

The effects on corneal wound healing of two topical nonsteroidal anti-inflammatory agents, flurbiprofen sodium (0.03%) and diclofenac sodium (0.1%), and the topical corticosteroid, prednisolone sodium phosphate (1%), were evaluated in masked, controlled rabbit studies. Healing of epithelial scrape wounds was significantly retarded in all three treatment groups for the first 3 days after wounding. There was no difference in the epithelial healing rate between the two nonsteroidal or corticosteroid treatment groups. Clinical grading of epithelial quality, conjunctival hyperemia, keratitis, stromal edema, and corneal haze were similar in all groups. There was a significant early decrease in the iritis score in the diclofenac treatment group. The strength of 2-mm central penetrating corneal trephination wounds and the collagen content of these wounds were similar in all groups. Both the topical nonsteroidal anti-inflammatory agents and the corticosteroid used in the preparations and dosages investigated in this study decreased early epithelialization of scrape wounds but had no apparent effect on corneal stromal healing. No toxic effects of the various drugs were found.
 ...
PMID:Topical nonsteroidal agents and corneal wound healing. 232 60

Topical steroids potentiate Pseudomonas keratitis in the absence of concomitant antibiotic therapy. The effects of other anti-inflammatory agents on microbial keratitis are unknown, but if these agents do not intensify the infection, they may be useful in the initial management of microbial keratitis by limiting ulceration and thus the size of the resultant corneal scar. In rabbit models of untreated Pseudomonas keratitis and pneumococcal keratitis, topical 1% prednisolone phosphate, 0.03% flurbiprofen sodium, and vehicle were applied hourly. In cases of Pseudomonas keratitis, prednisolone worsened the clinical disease, and flurbiprofen further worsened the disease. When combined with effective antibiotic therapy, neither anti-inflammatory agent worsened the disease. In pneumococcal keratitis, neither anti-inflammatory agent worsened the disease. Topical anti-inflammatory agents should be used with caution in cases of microbial keratitis at least until effective antibiotic therapy has been instituted.
 ...
PMID:Topical anti-inflammatory agents in an animal model of microbial keratitis. 236 36

We developed an in vitro model for studying the cytotoxicity of pharmacologic agents on corneal epithelium employing 3H-thymidine incorporation. Primary rabbit corneal epithelial cell cultures were established, and the cells plated prior to each experiment. 3H-thymidine incorporation was measured after the addition of drug or vehicle to these confluent cells, and dose-response curves were generated. Marked inhibition of 3H-thymidine incorporation was reached at chemotherapeutic concentrations achieved clinically for cytosine arabinoside (10(-7) M), methotrexate (10(-3) M), and 5-fluorouracil (10(-6) M). A 10(-4) M concentration of 2-deoxycytidine, a naturally occurring competitive inhibitor of cytosine arabinoside, protected cells up to a concentration of 10(-5) M. We utilized these data to undertake an in vivo prophylaxis study in 13 leukemia patients receiving high-dose iv cytosine arabinoside. Topical deoxycytidine 10(-4) M and 1% prednisolone phosphate, given 12 hours prior to the start of antileukemic therapy, were effective in reducing symptoms and signs of keratitis; both were better than historical placebo-treated eyes. Ophthalmic preservatives were studied in vitro at concentrations used clinically: benzalkonium chloride (BAC) (0.004-0.02%) was the most toxic, thimerosal (TMS) (0.001-0.004%) intermediate, and chlorobutanol (CHB) (0.2-0.5%) the least toxic. Antiviral agents (final concentration) included: trifluridine (TFT) (1.0%), ethyldeoxuridine (EDU) (2.0%), and idoxuridine (IDU) (0.1%). Dose but not time-dependent concentrations of these 3 agents were noted to cause toxicity; however, (E)-5(2-bromovinyl)-2'-deoxyuridine (BVDU) (0.1%) was non-toxic. Similarly, tobramycin and amikacin were significantly less toxic than gentamicin and neomycin in this system. These in vitro cytotoxicity data correlate well with previous in vivo and pre-clinical corneal epithelial toxicity studies. Our model may be useful in the toxicologic study of future topical ophthalmic agents.
 ...
PMID:An in vitro method which assesses corneal epithelial toxicity due to antineoplastic, preservative and antimicrobial agents. 248 34

To determine if acyclovir sodium prevents postoperative herpes simplex virus type 1 (HSV-1) recurrences, 21 rabbits harboring latent HSV-1 underwent uniocular autograft penetrating keratoplasty. All operated-on eyes were treated with topical and subconjunctival dexamethasone sodium phosphate. Ten of the 21 rabbits also received oral acyclovir (intravenous acyclovir was given at the time of surgery). Postoperatively, 9 (82%) of 11 operated-on eyes in rabbits not treated with acyclovir had positive HSV-1 ocular cultures. In acyclovir-treated rabbits, however, none of the 10 operated-on eyes had positive ocular cultures. In addition, 9 (82%) of 11 of the operated-on eyes had geographic ulcers develop in the non-acyclovir-treated rabbits, compared with 1 (10%) of 10 in the acyclovir-treated rabbits. Finally, stromal keratitis appeared in 5 (56%) of 9 of the operated-on eyes in non-acyclovir-treated rabbits and 1 (12%) of 8 of the operated-on eyes in acyclovir-treated rabbits. The results of this study indicate that acyclovir significantly lowered the incidence of HSV-1 ocular shedding, geographic ulceration, and stromal keratitis in a rabbit autograft penetrating keratoplasty model.
 ...
PMID:Oral acyclovir reduces the incidence of recurrent herpes simplex keratitis in rabbits after penetrating keratoplasty. 254 52

Topical diclofenac sodium is a non-steroidal anti-inflammatory drug that is being developed for use in the control of postoperative and medical inflammation. A comparison was made of 0.1% diclofenac with 1% prednisolone sodium phosphate, 0.03% flurbiprofen, and a vehicle placebo in rabbit eyes with acute herpetic keratitis in a double-masked study. Maximum corneal epithelial involvement was observed in each group on day 6 postinoculation, and in eyes subsequently treated with prednisolone, the corneal epithelial involvement appeared to be more severe and to resolve more slowly. Conjunctivitis and corneal clouding peaked on days 6 to 7 for all treatment groups and remained most severe in the placebo-treated eyes, followed closely by those treated with prednisolone. The duration of virus shedding was the same for placebo-, flurbiprofen-, and diclofenac-treated groups (50% or more were virus negative by day 10 or 11). Only prednisolone-treated eyes had an extended period of virus shedding, and the rabbit mortality rate in this group was slightly higher. It thus appears that topical diclofenac does not exacerbate acute herpes keratitis; diclofenac-treated eyes displayed less or at least no more severe disease than did the eyes treated with the other anti-inflammatory agents tested, and shedding of virus into tears was not prolonged.
 ...
PMID:Assessment of diclofenac on herpes keratitis in rabbit eyes. 255 66

The present study examined the antiherpetic effect of 2'-nor-cGMP, a new cyclic phosphate derivative of 2'NDG, in vitro and in the mouse keratitis model. The 50% inhibitory dose (ID50) was determined with HSV-1 RE strain in Vero cell monolayers for 2'-nor-cGMP (6.9 mcg./ml), 2'NDG (.06 mcg/ml), and trifluridine (F3T) (.72 mcg/ml). Balb C mice underwent bilateral ocular inoculation with HSV-1 RE strain, and then were treated with different therapeutic regimens. The antiviral efficacy of each drug was evaluated by ocular virus titers, clinical grading of epithelial keratitis, and histological evaluation of stromal keratitis. 2'-nor-cGMP was the most effective drug (P = .0001) in reducing ocular viral titers. Both 2'-nor-cGMP and 2'NDG were significantly more effective (P = .0001) than F3T in reducing epithelial keratitis, and as effective as F3T in reducing stromal keratitis.
 ...
PMID:2'-nor-cGMP, a new cyclic derivative of 2'NDG, inhibits HSV-1 replication in vitro and in the mouse keratitis model. 303 Jun 46


1 2 3 4 Next >>