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ABSTRACT: Most humans are infected with herpes simplex virus (HSV) type 1 in early childhood and remain latently infected throughout life. While most individuals have mild or no symptoms, some will develop destructive HSV keratitis. Ocular infection with HSV-1 and its associated sequelae account for the majority of corneal blindness in industrialized nations. Neuronal latency in the peripheral ganglia is established when transcription of the viral genome is repressed (silenced) except for the latency-associated transcripts and microRNAs. The functions of latency-associated transcripts have been investigated since 1987. Roles have been suggested relating to reactivation, establishment of latency, neuronal protection, antiapoptosis, apoptosis, virulence and asymptomatic shedding. Here, we review HSV-1 latent infections, reactivation, recurrent disease and antiviral therapies for the ocular HSV diseases.
Future Microbiology 08/2011; 6(8):877-907. · 3.82 Impact Factor
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ABSTRACT: To determine whether trifluorothymidine (TFT) and ganciclovir (GCV) are synergistic against herpes simplex virus type 1 (HSV-1).
TFT and GCV activity against 12 strains of HSV-1 (including an acyclovir-resistant strain) was measured by plaque-forming unit (PFU) inhibition. Cellular toxicity was assessed with an MTT dye reduction assay. Synergism was determined by calculating fractional inhibitory concentration (FIC indices) based on PFU reduction.
Concentrations of TFT resulting in 50% inhibition of PFUs (IC(50)) of acyclovir-susceptible HSV-1 strains ranged from 3.07 ± 0.36 to 12.52 ± 0.61 μM. GCV IC(50) values ranged from 0.40 ± 0.02 to 1.59 ± 0.14 μM. IC(50) values of TFT and GCV against the acyclovir-resistant strain were 15.40 ± 3.17 and 93.00 ± 9.64 μM, respectively. Concentrations of TFT or GCV resulting in 50% cell cytotoxicity (CC(50)) were 0.99 ± 0.01 and 92.91 ± 8.92 μM, respectively. TFT and GCV combined (10:1) were 10 times more potent against all acyclovir-susceptible HSV-1 strains. For 8 of 12 HSV-1 strains, the IC(50) of TFT and GCV combined was lower than the CC(50) of either drug. For acyclovir-susceptible HSV-1 strains, TFT and GCV combined generated a FIC index of <0.5, suggesting strong synergism between the two drugs. The FIC value for TFT and GCV combined against the acyclovir-resistant HSV-1 strain was 0.84, indicating nonantagonism.
TFT and GCV are synergistic against acyclovir-susceptible HSV-1 at concentrations significantly less toxic than if each antiviral were used as a sole agent.
Investigative ophthalmology & visual science 02/2011; 52(2):830-3. · 3.43 Impact Factor
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ABSTRACT: To assess the effect of high doses of valacyclovir (VCV) on HSV-1 DNA shedding into tears of latently infected rabbits.
Three oral doses of VCV were tested. Corneas were inoculated with HSV-1, and latent infection was allowed to establish. Starting on postinoculation (PI) day 28, tear swabs were collected once daily for 6 consecutive days before treatment. The rabbits were placed in five balanced groups: group 1 had no treatment, group 2 received placebo, group 3 received 7 mg/kg VCV, group 4 received 70 mg/kg, and group 5 received 140 mg/kg. The treatment was administered by oral gavage twice daily, starting on PI day 36 and continuing for 14 days. The ocular swabs were collected beginning on PI day 40 and continuing for 10 days.
The mean copy number of HSV-1 DNA before treatment was 370+/-70, 569+/-273, 368+/-86, 408+/-108, and 396+/-91, and the mean HSV-1 DNA copy number after treatment was 232+/-183, 564+/-186, 518+/-122, 67+/-63, and 13+/-7 in groups 1 to 5, respectively.
There was no observable toxicity in any group. The 70- and 140-mg/kg doses of VCV significantly reduced the HSV-1 DNA copy number, compared with that of the other three groups. A daily dose of 500 mg (approximately 7 mg/kg) VCV in healthy human volunteers did not suppress HSV-1 DNA shedding in tears and saliva. Thus, higher doses of VCV may be necessary to reduce asymptomatic shedding in healthy human subjects.
Investigative ophthalmology & visual science 09/2010; 51(9):4703-6. · 3.43 Impact Factor
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ABSTRACT: To test the effect of valacyclovir alone and with aspirin on the asymptomatic shedding of HSV-1 DNA in tears and saliva of healthy individuals. METHOD. The subjects (n = 45) were randomized into three groups without regard to age, sex, or race. Group 1 (n = 14) received the placebo, group 2 (n = 15) received a dose of 500 mg valacyclovir once daily, and group 3 (n = 16) received a dose of 500 mg valacyclovir once daily and 350 mg aspirin twice daily for 30 days. Ocular and oral swabs were collected twice daily for 30 days. DNA was extracted from all swabs and HSV-1 DNA copy numbers were determined. Statistical analysis was performed to compare the DNA copy numbers of the three groups.
There was no significant difference in the HSV-1 DNA copy numbers in the tears or saliva among any of the three treatment groups. The mean copy numbers +/- SE of mean (SEM) of HSV-1 DNA in tears were 340 +/- 35, 1074 +/- 320, and 630 +/- 51 for groups 1, 2, and 3, and in saliva were 238 +/- 35, 963 +/- 462, and 493 +/- 25, respectively, for groups 1, 2, and 3.
No correlation was found between HSV-1 shedding and valacyclovir and valacyclovir with aspirin treatment. The HSV-1 DNA copy number was not reduced by treatment with 500 mg of valacyclovir daily or with a combination of daily valacyclovir (500 mg) plus twice-daily doses of aspirin (350 mg) over 30 days.
Investigative ophthalmology & visual science 08/2009; 50(12):5601-8. · 3.43 Impact Factor
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ABSTRACT: Twelve squirrel monkeys were inoculated in both eyes with the Rodanus strain of herpes simplex virus type 1 (HSV-1) and were examined for the presence of acute epithelial keratitis. All of the eyes developed dendritic keratitis within 72 hours after inoculation. The twelve monkeys plus two additional similarly infected monkeys were also examined for the presence of clinical recurrences of ocular herpes infections and spontaneous shedding of virus in their tears. Two of the eyes developed stromal disease, and 13 of the monkeys had at least one episode of recurrent clinical epithelial disease. Virus was isolated from two of the eyes with recurrent dendrites.
Current Eye Research 07/2009; 6(1):277-279. · 1.28 Impact Factor
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ABSTRACT: This article has been withdrawn at the request of the author(s). The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
International journal of antimicrobial agents 02/2009; · 3.03 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the effect of BAY 57-1293, a helicase-primase inhibitor, on herpes simplex virus type 1 (HSV-1) reactivation in mice and its efficacy on established disease in rabbits.
BALB/c mice latent for McKrae-strain HSV-1 were reactivated via heat stress, treated with BAY 57-1293, and their corneas were swabbed for virus or the trigeminal ganglia (TG) obtained for quantification of viral DNA. New Zealand white rabbits were infected and treated topically or orally in comparison with trifluridine or valacyclovir.
Oral BAY 57-1293 suppressed reactivation in HSV-1-infected mice and reduced the viral load in TG up to four orders of magnitude. In the rabbits, the therapeutic efficacies of topical BAY 57-1293 and trifluridine were similar. Once-daily oral BAY 57-1293 was significantly more effective than valacyclovir and as effective as twice a day topical trifluridine.
BAY 57-1293 may be more effective than valacyclovir, without the cytotoxicity or potential healing retardation seen with trifluridine. Oral BAY 57-1293 may be a substitute for eye drops as an effective treatment for herpetic keratitis and might be useful in treating stromal keratitis and iritis, as well as preventing recurrences of ocular herpes.
Journal of Ocular Pharmacology and Therapeutics 03/2008; 24(1):34-42. · 1.51 Impact Factor
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ABSTRACT: To compare the efficacy of Dermabond with conventional nylon sutures for sealing linear corneal incisions.
A keratome knife was used to create a 4-mm full-thickness linear corneal incision anterior to the limbal arcade in 20 fresh pig eyes. The incision was sealed with Dermabond tissue adhesive or closed with 10-0 nylon sutures. A 27-gauge needle connected via tubing to a bottle containing balanced salt solution (BSS) was inserted into the anterior chamber. Infusion pressure was controlled by varying the height of the column of BSS. The tensile strength of the incisions was measured by increasing the infusion pressure to the point where leakage was noted.
The mean height at which leakage was detected was 100.20 +/- 31.19 cm H(2)O (equivalent to a pressure of 73.70 +/- 22.99 mm Hg) for the nylon suture group (n = 10 eyes) and 113.80 +/- 31.20 cm H(2)O (equivalent to a pressure of 83.71 +/- 22.95 mm Hg) for the Dermabond group (n = 10 eyes). The difference was not significant (P = 0.343).
The mean leakage pressures were comparable for the 2 groups. Either method of closure should be able to withstand any postoperative increases in intraocular pressure. Dermabond adhesive may be considered as an alternative to conventional sutures in corneal wound closure.
Cornea 12/2005; 24(8):998-9. · 1.73 Impact Factor
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ABSTRACT: To explore the immune mechanism of Graves ophthalmopathy (GO) by analyzing infiltrating cells in orbital connective tissue (OCT) specimens of patients with active GO using immunohistochemical methods.
Five OCT specimens obtained from patients with active GO and five control specimens obtained from forensic cadavers who died from nonmedical reasons were stained with anti-CD3, CD4, CD8, CD45RO, HLA-Dr, CD25, and TNF-alpha monoclonal antibodies. Positively stained cells were counted and results were interpreted as cell counts/mm2. Four of five GO patients had never been treated with any immunomodulating therapy. Only one had received oral prednisolone prior to tissue sampling, but this treatment had ceased 5 months before surgery.
The retro-orbital tissue specimens obtained from forensic cadavers did not show any significant positive staining for any monoclonal antibody tested. However, the specimens from GO patients showed positively stained means of 36.66 +/- 4.61 HLA-Dr+, 12.8 +/- 3.42 CD8+, 11.8 +/- 1.78 CD4+, 16.6 +/- 1.81 CD3+, 21.2 +/- 3.12 CD45RO+, 10.4 +/- 2.07 TNF-alpha+, 7.2 +/- 1.48 CD25+, 3.2 +/- 1.09 CD4+CD8+, 4.6 +/- 1.67 CD4+CD45RO+, 2.8 +/- 0.83 CD8+CD45RO+, 1.6 +/- 0.89 CD4+CD25+, and 1.8 +/- 1 0.83 CD8+CD25+ cells/mm2.
Our study supports that most of the infiltrating lymphocytic cells in the active stage of GO are T cells, and a significant proportion of them are CD45RO+ cells. Infiltration of OCT by HLA-Dr+, CD25+, and TNF-alpha cells suggests that Th1-type immune reaction with the interference of proinflammatory cytokine(s) (TNF-alpha) may be important in the pathogenesis of disease. Further studies are needed to understand the disease pathogenesis and may provide a scientific basis for future treatment alternatives for the disease (e.g., anti-cytokine treatment).
Current Eye Research 09/2005; 30(8):631-8. · 1.28 Impact Factor
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ABSTRACT: Recurrent herpes virus infection, in which the virus reactivates from the nervous system and causes painful lesions in peripheral tissues, is a significant clinical problem. Our recent studies showing that the amount of cyclooxygenase 2 (COX-2) in the trigeminal ganglia of heat-stressed untreated mice is higher than the amount in heat-stressed mice treated with the COX-2 inhibitor, celecoxib, have indicated that the prostaglandin synthesis pathway--and in particular COX-2--may be an intermediate in the pathway to herpes viral reactivation. To further study this process, we infected the corneas of mice using topical application to a lightly scratched epithelium and waited 30 days for Herpes simplex virus type 1 (HSV-1) latency to be established in the trigeminal ganglia. Prior to the induction of viral reactivation, the mice were treated orally with celecoxib. Treated and untreated mice were induced to undergo reactivation by immersion in 43 degrees C water for 10 min. The shedding of virus at the ocular surface was determined by culturing ocular swabs with indicator cells. The presence of infectious virus in the trigeminal ganglion was evaluated by incubating ganglion homogenates with indicator cells and observing for cytopathic effect. Celecoxib treatment significantly suppressed viral reactivation when given prophylactically by the gastrointestinal route. The numbers of corneas and ganglia containing infectious virus were significantly lower in the celecoxib-treated animals, compared to the placebo-treated mice. These experiments demonstrate that a selective COX-2 inhibitor can suppress hyperthermic stress-induced herpes viral reactivation in the nervous system. It may be possible to use COX-2 inhibitors to prevent viral reactivation in high-risk patients by drug prophylaxis.
Journal of Ocular Pharmacology and Therapeutics 05/2005; 21(2):114-20. · 1.51 Impact Factor
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ABSTRACT: To assess the frequency of shedding of herpes simplex virus type 1 (HSV-1) DNA in tears and saliva of asymptomatic individuals.
Fifty subjects without signs of ocular herpetic disease participated. Serum samples from all subjects were tested for HSV IgG antibodies by enzyme-linked immunosorbent assay (ELISA) and for HSV-1 by neutralization assay. HSV-1 DNA copy number and frequency of shedding were determined by real-time polymerase chain reaction (PCR) analysis of tear and saliva samples collected twice daily for 30 consecutive days.
Thirty-seven (74%) of the 50 subjects were positive for HSV IgG by ELISA. The percentages of positive eye and mouth swabs were approximately equivalent: 33.5% (941/2806) and 37.5% (1020/2723), respectively. However, the percentage of samples with high HSV-1 genome copy numbers was greater in saliva than in tears, which may have been a result of the sample volume collected. Shedding frequency in tears was nearly the same in men (347/1003; 34.6%) and women (594/1705; 34.8%); in saliva, men had a higher frequency of shedding (457/1009; 45.3% vs. 563/1703; 33.1%, men versus women). Overall, 49 (98%) of 50 subjects shed HSV-1 DNA at least once during the course of the 30-day study.
The percentage of asymptomatic subjects who intermittently shed HSV-1 DNA in tears or saliva was higher than the percentage of subjects with positive ELISA or neutralization antibodies to HSV. Because most HSV transmission occurs during asymptomatic shedding, further knowledge of the prevalence of HSV-1 DNA in tears and saliva is warranted to control its spread. Shedding is simple to study, and its suppression may be an efficient way to evaluate new antivirals in humans.
Investigative Ophthalmology & Visual Science 02/2005; 46(1):241-7. · 3.60 Impact Factor
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ABSTRACT: To investigate corneal healing and the factor(s) possibly responsible for refractive changes after laser in situ keratomileusis (LASIK).
Twenty eyes of 10 patients who underwent LASIK for myopia were examined clinically and by real-time confocal microscopy for 6 months. Epithelial and posterior stromal thicknesses and the thickness of the keratocyte activation zone were measured, and refractive changes were compared with these values. Keratocyte morphology, flap thickness, and subbasal nerve fiber bundle morphology after LASIK were also investigated.
No significant change was detected over time in epithelial thickness after LASIK treatment; however, the posterior stromal thickness was found to be significantly higher 1 month after surgery. A slight but statistically significant negative correlation was detected between the thickness of the keratocyte activation zone and the spheroequivalent refraction after LASIK. The subbasal nerve fiber bundle's morphology returned to its preoperative appearance 6 months after LASIK, but in the flap stroma the nerve fiber bundle morphology remained abnormal at 6 months after LASIK surgery.
A weak but significant negative correlation between the thickness of the keratocyte activation zone and spheroequivalent refraction was found after LASIK. The different refractive properties of activated keratocytes may be responsible for the myopic shift after LASIK. Further studies are needed to clarify this hypothesis.
Investigative Ophthalmology & Visual Science 06/2004; 45(5):1334-9. · 3.60 Impact Factor
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ABSTRACT: To investigate whether conjunctival inflammation represents a primary event in the pathogenesis of keratoconjunctivitis sicca or whether it is a secondary inflammatory reaction caused by enhanced mechanical irritation as a result of surface dryness and whether anti-inflammatory drops (corticosteroids and nonsteroidal anti-inflammatory) have therapeutic effects and are similar.
Single-masked, randomized, prospective clinical trial.
Thirty-two keratoconjuctivitis patients with or without Sjögren syndrome were included in the study. The patients were randomized to three groups. Group 1 patients received a topical artificial tear substitute (ATS); group 2 received ATS plus nonsteroidal anti-inflammatory drops (NSAID); and group 3 received ATS plus topical corticosteroidal drops. The eye symptom severity scores, Schirmer test values, rose bengal and fluorescein staining scores were evaluated before treatment and 15 and 30 days after start of treatment. Impression cytology specimens were stained using immunohistochemical methods to detect the percentages of human leukocyte antigen II (HLA-DR) positive, Apo 2.7 positive, and periodic acid-Schiff positive cells. Statistical analyses were performed within and between groups. Group 3 patients had significantly lower symptom severity scores, fluorescein and rose bengal staining, and HLA-DR positive cells on days 15 and 30 compared with patients in other groups. They also had a significantly higher number of periodic acid-Schiff positive (goblet) cells in their impression cytology specimens on days 15 and 30 compared with the other patients. On day 30, group 3 patients had significant differences compared with their baseline measurements in terms of above-mentioned parameters. However, we did not detect a significant effect of any treatment schedule on the Shirmer test value and the numbers of Apo 2.7 cells in impression cytology specimens.
Topical corticosteroids had a clearly beneficial effect both on the subjective and objective clinical parameters of moderate-to-severe dry eye patients. These effects were associated with the reduction of inflammation markers of conjunctival epithelial cells.
American Journal of Ophthalmology 11/2003; 136(4):593-602. · 4.22 Impact Factor
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ABSTRACT: To determine the effect of roscovitine, a potent antiviral in tissue culture administered intramuscularly to rabbits or by eye drops to mice for the treatment of herpetic keratitis this study was commenced.New Zealand white rabbits infected with McKrae strain herpesvirus (HSV-1) were treated twice a day with 10mg Roscovitine or vehicle from day 3 to 7, or 1% trifluridine eye drops five times a day. Severity of keratitis was graded daily by a masked observer. ICR strain mice were randomized into 14 groups. Both corneas of the mice were scarified with a 25-gauge needle, and were inoculated with the KOS strain of HSV-1. Roscovitine was dissolved in Cremophor((R)) and tissue culture medium. Group 1A, 1B, 2A, and 2B mice were treated eight times daily with either 800 micro M Roscovitine or its vehicle. Trifluridine treated animals (groups 3A and 3B) received topical treatment five times daily. In groups 1A-3B, the treatment was begun two days prior to or two days after viral inoculation. Mice were examined on days 2, 3, 5, and 9 after infection. In rabbits, the severity of keratitis in animals treated with intramuscular roscovitine was not significantly different from that in vehicle-treated animals except on day 7 (p=0.0460). In mice, there was no significant difference between roscovitine and vehicle treatment at any time point studied. However, the trifluridine treated mice had significantly lower scores compared to the roscovitine or vehicle-treated mice. Although roscovitine dramatically suppresses viral replication in tissue culture studies, in vivo this drug failed to alter the course of HSV keratitis in rabbits or mice. Considering high cost of roscovitine and the poor efficacy in these experiments, we feel that roscovitine is not feasible antiviral agent for today.
Experimental Eye Research 07/2003; 76(6):679-83. · 3.26 Impact Factor
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ABSTRACT: Background. In this study, we determined the binding characteristics of F(ab′)2 alloantibody fragments to corneal antigens and assessed the capacity of these antibody fragments to protect corneal allografts from immune attack.
Methods. Goat anti-rabbit alloantibodies were pepsin-digested and labeled with 125I, and the time course of association and dissociation of the F(ab′)2 fragments was determined. Corneal allografts were incubated in unlabeled F(ab′)2 fragments and transplanted into allogeneic recipients, and the graft survival times were recorded.
Results. Binding of radiolabeled F(ab′)2 fragments to rabbit cornea cells reached a maximum at 12 hr. At 32°C (rabbit corneal temperature), the radiolabel eluted rapidly from the cornea, reaching baseline at 72 hr. At 4°C (corneal graft storage temperature), significant amounts remained associated with the cornea at 96 hr. Mean survival time for grafts incubated in F(ab′)2 anti-rabbit fragments was significantly greater than that of grafts incubated in nonimmune F(ab′)2 fragments. Three of the corneal allografts incubated in goat F(ab′)2 anti-rabbit fragments survived for 100 days, whereas the longest surviving control allograft incubated in goat F(ab′)2 nonimmune fragments was rejected on day 24. Preincubation of corneas in unlabeled, immune F(ab′)2 fragments followed by incubation in radiolabeled, immune F(ab′)2 fragments suggested that antigen masking was not a factor in the prolongation of graft survival.
Conclusion. Based on the binding and release kinetics and the graft survival times, it appears that the protective effect of immune F(ab′)2 fragments extends well beyond the binding interval of the antibody fragments to corneal cell membranes.
Transplantation 02/1999; 67(4):594-599. · 4.00 Impact Factor
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ABSTRACT: 9-(4-Hydroxybutyl)-N2-phenylguanine (HBPG) is a new viral thymidine kinase inhibitor that we tested for the ability to prevent recurrences of herpetic keratitis. Eighteen squirrel monkeys (Saimiri scuireus) were infected in both corneas with the Rodanus strain of herpes simplex virus type 1 (HSV-1). All corneas showed typical dendritic keratitis 3 days after infection, followed by spontaneous healing. On day 21, the monkeys were randomized into two coded groups and ocular examinations were begun. One group received intraperitoneal (i.p.) injections of HBPG, 150 mg/kg, in a corn oil suspension every 8 h, and the other group received i.p. injections of the corn oil vehicle only. On day 22, recurrences were induced by reducing the temperature of the room in the late afternoon so that a low of 18°C was achieved during the night. After the morning treatment, room temperature was raised to the normal ambient temperature (24–27°C), and treatment was discontinued. Treatment was reinstituted on day 27, the room temperature was lowered again on day 28, and treatment was again discontinued as before. Third and fourth cycles of treatment and cold stress were begun on days 34 and 69. Ocular examinations were continued until day 73, at which point the code was broken. We found that the HBPG treatment significantly reduced the number of corneas with recurrences during the treatment periods, compared with recurrences in untreated, cold-stressed animals (P=0.01).
Antiviral Research 01/1997; · 4.30 Impact Factor
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ABSTRACT: We have demonstrated that, in herpetic stromal disease, the clinical manifestation of the disease depends on the presence of herpes virus (HSV) antigens in the stromal layer. In the work reported here, we have shown that the three major groups of HSV glycoproteins were secreted by F, Shealy, E-43, and RE strains, and that glycoprotein C was the major constituent of the secreted proteins. The amount of each glycoprotein secreted varied with the virus strain and the cell line used (VERO, HEp-2, SIRC or RK-13). The stromal disease-producing viruses (RE and Shealy) secreted larger amounts of glycoproteins than the epithelial disease-producing viruses (F and E-43). Our data indicated that there was a correlation between the appearance of stromal or epithelial disease and the amount of glycoproteins secreted. In addition, the manifestations of virus-induced stromal disease were reproduced by the injection of these secreted glycoproteins into the rabbit cornea. We think that the presence of these glycoproteins in the stromal layer at the time of virus growth in the epithelium is an important factor in the induction of herpetic stromal disease.
Experimental Eye Research.
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ABSTRACT: To investigate the effect of acetylsalicylic acid on ocular shedding of herpes simplex virus type 1 (HSV-1).
Mice that were latent for the McKrae strain of HSV-1 were treated with acetylsalicylic acid, a nonspecific inhibitor of cyclooxygenases, either prophylactically or at the time of heat stress-induced viral reactivation. The effect of the drug on viral shedding in the tear film, infectious virus in the cornea and trigeminal ganglion, and viral DNA in the cornea and trigeminal ganglion was determined.
Acetylsalicylic acid inhibited heat stress-induced shedding of virus in the tears and reduced the numbers of corneal and trigeminal ganglion homogenates containing virus. Intraperitoneal therapeutic and oral prophylactic plus therapeutic treatments were similar in their ability to inhibit reactivation.
The results indicate that a cyclooxygenase inhibitor such as acetylsalicylic acid can reduce recurrent viral infection in mice. These findings may implicate prostaglandins as agents in the viral reactivation process and suggest that therapy to suppress viral reactivation using nontoxic inhibitors of prostaglandin synthesis may be effective in humans.
Current Eye Research 29(2-3):119-25. · 1.28 Impact Factor
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ABSTRACT: Early antiviral drugs, such as idoxuridine and vidarabine, are less effective than newer drugs, such as trifluorothymidine and acyclovir. However, trifluorothymidine is less subject to the development of drug-resistant strains and can be administered topically as a clear drop, which increases patient compliance. Acyclovir has low toxicity and is selective for virus-infected cells because it must be phosphorylated by the viral thymidine kinase to become active. However, drug-resistant strains are produced relatively easily in vitro and may also develop in man with long-term use. To date, no antiviral drug alone has been shown to be effective in the treatment of stromal disease, and no antiviral drug is able to eradicate virus latent in the ganglia and thereby prevent recurrent herpetic infections.Combinations of antiviral drugs and antiviral drugs and interferon are being tested for enhanced efficacy in the treatment of ocular herpetic disease, and for prophylactic effects. The development of recombinant interferons has reduced cost and increased availability, but the effects of the ‘manufactured’ interferon are not identical to those of natural human leukocyte interferon in all experimental situations.
Antiviral Research. 4(6):333-338.
