Vaccination inhibits the human adenoviral transduction in a mouse keratoconjunctivitis model.

Adenovirus infections are a major cause of epidemic keratoconjunctivitis (EKC), which can lead to corneal subepithelial infiltrates and multifocal corneal opacity. In the current study, we investigated the use of an E1/E3-deleted adenovirus serotype 5 (Ad5) vector as a vaccine administered intramuscularly (IM) or intranasally (IN) against subsequent challenges with a luciferase-expressing Ad5 (Ad5-Luci) vector via eyedrop. We evaluated the adaptive immune response to Ad5 vector vaccination and confirmed a robust polyfunctional CD8 T cell response in splenic cells. Neutralizing Ad5 antibodies were also measured in the sera of vaccinated mice as well as Ad5 antibody in the eye wash solutions. Upon challenge with Ad5-Luci vector 8 weeks post the primary immunization, transduction was significantly reduced by > 70% in the vaccinated mice, which was slightly better in IM- vs. that in IN-vaccinated animals. Resistance to subsequent challenge was observed 10 months post primary IM vaccination, with sustained reduction up to 60% in the Ad5-Luci vector transduction. Passive immunization of naive mice with antisera from IM to vaccinated mice subsequently challenged with the Ad5-Luci vector resulted in approximately 40% loss in transduction efficiency. Furthermore, the mice that received IM immunization with or without CD8 T cell depletion showed > 40% and 70% reductions, respectively, in Ad8 genomic copies after Ad8 topical challenge. We conclude that Ad-vector vaccination successfully induced an adaptive immune response that prevented subsequent Ad transduction in the cornea and conjunctiva-associated tissues in a mouse model of adenovirus keratoconjunctivitis, and that both cellular and humoral immunity play an important role in preventing Ad transduction.

[Microbial contamination of nipradiol with and without benzalkonium chloride].

PURPOSE: To compare microbial contamination of nipradiol both with and without benzalkonium chloride (BAC). SUBJECTS AND METHODS: Twenty primary open angle glaucoma patients treated with nipradiol with BAC were studied. The nipradiol with BAC was switched to nipradiol without BAC. Four weeks after switching, the nipradiol without BAC was once again switched to nipradiol with BAC. The bottle caps, nozzles, filters, and solutions were cultured and examined for contamination. RESULTS: In nipradiol without BAC microorganisms were isolated from caps (30%), nozzles (50%), solutions (0%), and filters (15%), whereas in nipradiol with BAC they were isolated from caps (35%), nozzles (40%), and solutions (25%). The microorganisms in the nipradiol without BAC were coagulase-negative Staphylococci (38.2%) and Propionibacterium acnes (29.4%), and in the nipradiol with BAC they were coagulase-negative Staphylococci (20.5%), Alcaligenes xylosoxidans (12.8%). CONCLUSIONS: In nipradiol without BAC, the bacteria were detected outside the filters, but not in the solution. The rate of microbial contamination of the nipradiol without BAC was similar to that of the nipradiol with BAC. Both the bacteria detected from the nipradiol with and those detected in the solution without BAC consisted only of bacterial flora of the cul-de-sac and skin.

A randomized, double-blind study comparing the safety and efficacy of clopidogrel versus ticlopidine in Japanese patients with noncardioembolic cerebral infarction.

BACKGROUND: Patients treated with ticlopidine require careful hematologic monitoring. Clopidogrel may have greater tolerability. However, no direct comparison of these two drugs has been reported and evidence of improved safety with clopidogrel is not yet established in the Japanese population. A comparison of both agents was therefore conducted in Japanese stroke patients. METHODS: Patients with noncardioembolic cerebral infarction were randomized to clopidogrel 75 mg or ticlopidine 200 mg once daily for 52 weeks. The primary endpoint was safety; the major secondary endpoint was the incidence of vascular events. RESULTS: Clopidogrel was associated with significantly fewer safety events than ticlopidine (7.0 versus 15.1%; p < 0.001) and no significant difference in efficacy between the two treatments was seen [hazard ratio 0.977 (95% confidence interval: 0.488-1.957)]. CONCLUSIONS: In Japanese stroke patients, clopidogrel 75 mg is better tolerated than ticlopidine 200 mg once daily.

Efficacy of rebamipide as adjunctive therapy in the treatment of recurrent oral aphthous ulcers in patients with Behçet's disease: a randomised, double-blind, placebo-controlled study.

BACKGROUND: Behçet's disease (BD) is a recurrent inflammatory disease involving chronic recurrent oral aphthous ulcers (aphthae), uveitis, skin lesions and genital ulcers. We prospectively investigated the efficacy of rebamipide, a gastroprotective drug, against oral aphthous ulcers in BD patients. METHODS: In a multicentre, double-blind, placebo-controlled study, 35 patients with BD, having as the main symptom oral aphthosis, were randomised to receive rebamipide 300 mg/day or placebo for 12 to 24 weeks between August 1994 and December 1996. Oral aphthosis must have occurred within 4 weeks prior to enrolment and must have been visible for at least 7 days during that time. Oral aphthae count and pain scores were recorded daily in a diary by the patients themselves. Monthly aphthae count and pain scores were defined as the sum of aphthae count and pain scores for a month, respectively. Investigators rated the global improvement in aphthae count and pain using a 6-point scale. The rate of change in monthly aphthae count and pain scores in the first 3 and last 3 months of treatment were assessed in patients with more severe symptoms whose aphthae count and pain score were >28 at baseline (trial entry). RESULTS: The rate of moderate or marked improvement in aphthae count and pain was 36% (5 of 14 subjects) in the placebo group and 65% (11 of 17 subjects) in the rebamipide group. During months 2 to 6 of treatment, aphthae count tended to increase and reached a peak at month 4 in the placebo group but decreased in the rebamipide group. Pain score decreased to the same extent in both groups for the first 3 months of treatment; however, in the fourth to sixth months of treatment, the pain score tended to increase in the placebo group but decreased in the rebamipide group. In patients with a monthly aphthae pain score >28 at baseline, pain and count scores decreased throughout the 6 months of rebamipide treatment but increased during the last 3 months of treatment in the placebo group (p < 0.01 for the between-group comparisons). CONCLUSIONS: Rebamipide is well tolerated and improves the aphthae count and pain score in BD patients. It may therefore be useful in the treatment and prevention of frequently recurrent oral aphthous ulcers (not restricted to BD). Administration of rebamipide is not cumbersome, and it does not cause any discomfort, which corticosteroid ointments for example may do; furthermore, there are no specific adverse drug reactions. Rebamipide is therefore recommended as a long-term treatment for recurrent oral aphthous ulcers.

Raised plasma adrenomedullin level in Behçet's disease patients.

Abstract To investigate the role of plasma adrenomedullin (AM) in the pathogenesis of Behçet's disease (BD) patients with inactive ocular complications or ocular attack, 18 consecutive BD patients with ocular complications, including 1 BD patient with ocular attack, another group of 6 BD patients with ocular attack, and 10 normal volunteers were evaluated. All BD patients were regularly followed at ophthalmic outpatient clinics. Levels of both total and mature AM in plasma were measured by immunoradiometric assay. Plasma levels of endothelin-1 (ET-1) were also measured by radioimmunoassay. We also measured the levels of C-reactive protein (CRP) in plasma. Levels of total AM in plasma (mean ± SD, 19.6 ± 6.9 fmol/l) were significantly higher in BD patients than in normal volunteers (14.5 ± 3.6 fmol/l) (P = 0.01). The levels of mature AM were also higher in BD patients (1.6 ± 0.4 fmol/l) than in normal volunteers (0.3 ± 0.6 fmol/l) (P = 0.002). The levels of AM in patients with ocular attack were higher than those in normal volunteers, although there was no significant difference compared to levels of AM in BD patients without ocular attack. AM may play an important role as an antiinflammation factor or may reflect endothelial damage as a marker of disease activity in BD patients.