Progression of sealed initial bovine enamel lesions under demineralizing conditions in vitro

The use of sealants for the infiltration of proximal enamel lesions could be a promising alternative to the common strategies of remineralization and operative treatment. The aim of the present study was to compare the progression of sealed initial enamel lesions after exposure to a demineralizing solution in vitro. In each of 54 bovine enamel specimens three subsurface lesions were created. Two of the lesions were etched with phosphoric acid and sealed with either a fissure sealant or with various adhesives (1-5) for 15 s or 30 s, respectively, whereas one lesion remained as the untreated control. Subsequently, half of each specimen was covered with nail varnish (baseline) and the other half was reexposed to a demineralizing solution for 14 days (experimental). The specimens were cut perpendicularly to the surface, infiltrated with a low-viscosity fluorescent resin and observed with a confocal laser scanning microscope (CLSM). For lesions sealed with the fissure sealant and adhesives 1-3, the progression of lesion depth (0-31 microm) was significantly decreased (p<0.01; paired t test) compared with the untreated control (57 microm). For the fissure sealant and adhesives 1 and 3 extended penetration times (30 s) resulted in significantly reduced lesion progression compared to 15 s. It can be concluded that filling of the pores in initial enamel lesions with the fissure sealant and adhesives 1-3 can inhibit further demineralization in vitro.     

Inhibition of lesion progression by the penetration of resins in vitro: influence of the application procedure

This study compared the progression of sealed initial enamel lesions penetrated with a fissure sealant (Helioseal, Vivadent) or various adhesives (Heliobond, Excite, Vivadent; Resulcin, Merz; Solobond M, Voco; Prompt L-Pop, 3M-ESPE) after exposure to a demineralizing solution, in vitro. From 27 bovine teeth, 54 enamel specimens were prepared and covered with nail varnish (control), thus obtaining three windows for treatment. After demineralization (pH 5.0; 14 days), two of the windows (A, B) were etched with phosphoric acid (20%; 5 seconds); whereas, the third area served as the control (C). The specimens were divided randomly into six groups (n=9), and the material was applied (90 seconds) either once (A) or twice (B). Light-curing followed each application. Half of the area of each specimen window was then covered with nail varnish, and the samples were again stored in the demineralizing solution (pH 5.0; 14 days). The specimens were cut perpendicular to the surface, and both enamel slabs were studied after infiltration using a fluorescent, low viscous resin (VIRIN) and confocal microscopy (CLSM). Lesion depths were calculated (ImageJ) from the surface to that point in the lesion where the grey values clearly changed to a darker grey. After demineralization, mean lesion depths (SD) (14 days) were measured at 105 (21) microm. The second demineralization led to a mean progression of the lesion depths of 52 (31)%. Adper Prompt L-Pop and Solobond M could not significantly prevent lesion progression after a single application (p > 0.05; t-test); however, the second application of Solobond M significantly decreased lesion progression (p < 0.05; t-test). Helioseal, Heliobond, Resulcin Monobond and Excite showed significantly better inhibition of the demineralization compared to the other materials (p < 0.05; Bonferroni). It can be concluded that the penetration of adhesives into initial lesions inhibited a further demineralization in vitro.     

Evaluation of cavitations in proximal caries lesions at various magnification levels in vitro

Objectives

The aim of this study was to evaluate the cavitation rate of proximal caries using different magnification aids in vitro.

Methods

Radiographs of 285 extracted teeth were taken and the proximal surfaces were graded to the criteria R0 (no radiolucency), R1 (radiolucency confined to the outer half of enamel), R2 (inner half of enamel) and R3 (outer half of dentin). Subsequently, the proximal surfaces were checked for the presence of cavitations with the naked eye (NE), and by using 4.3× magnification eyeglasses (ME), a stereo microscope (SM, 10×), or a scanning electron microscope (SEM, up to 2000× magnification).

Results

In surfaces with R3 caries, cavitations were visible in 56 of 59 cases with the naked eye. When using SEM, all surfaces revealed cavitations (100%). Regarding the surfaces with R2 lesion, 36 of 46 cases showed cavitations (NE); the corresponding values were 39/46 (ME), 41/46 (SM), and 46/46 (SEM); in the latter, in most cases deep defects could be observed. With regard to R1 lesions, 36/60 (NE), 43/60 (ME), 45/60 (SM), and 58/60 (SEM) cases revealed cavitations. A breakdown of radiographically sound surfaces (R0) was present in some 10% of the examined surfaces (24/261, NE; 33/261, SEM).

Conclusions

Cavitations (defined as breakdown of the surface) are present in significantly more cases than previously reported. This might be an explanation why even small radiolucencies tend to progress, albeit slowly. Thus, close follow-ups should strongly be recommended when considering a preventive treatment regimen with small radiolucencies.     

Antiviral Activity of a Selective Ribonucleotide Reductase Inhibitor against Acyclovir-Resistant Herpes Simplex Virus Type 1 In Vivo

The present study reports the activity of BILD 1633 SE against acyclovir (ACV)-resistant herpes simplex virus (HSV) infections in athymic nude (nu/nu) mice. BILD 1633 SE is a novel peptidomimetic inhibitor of HSV ribonucleotide reductase (RR). In vitro, it is more potent than ACV against several strains of wild-type as well as ACV-resistant HSV mutants. Its in vivo activity was tested against cutaneous viral infections in athymic nude mice infected with the ACV-resistant isolates HSV type 1 (HSV-1) dlsptk and PAA^r5, which contain mutations in the viral thymidine kinase gene and the polymerase gene, respectively. Following cutaneous infection of athymic nude mice, both HSV-1 dlsptk and PAA^r5 induced significant, reproducible, and persistent cutaneous lesions that lasted for more than 2 weeks. A 10-day treatment regimen with ACV given topically four times a day as a 5% cream or orally at up to 5 mg/ml in drinking water was partially effective against HSV-1 PAA^r5 infection with a reduction of the area under the concentration-time curve (AUC) of 34 to 48%. The effects of ACV against HSV-1 dlsptk infection were not significant when it was administered topically and were only marginal when it was given in drinking water. Treatment under identical conditions with 5% topical BILD 1633 SE significantly reduced the cutaneous lesions caused by both HSV-1 dlsptk and PAA^r5 infections. The effect of BILD 1633 SE against HSV-1 PAA^r5 infections was more prominent and was inoculum and dose dependent, with AUC reductions of 96 and 67% against infections with 10⁶ and 10⁷ PFU per inoculation site, respectively. BILD 1633 SE also significantly decreased the lesions caused by HSV-1 dlsptk infection (28 to 51% AUC reduction). Combination therapy with topical BILD 1633 SE (5%) and ACV in drinking water (5 mg/ml) produced an antiviral effect against HSV-1 dlsptk and PAA^r5 infections that was more than the sum of the effects of both drugs. This is the first report that a selective HSV RR subunit association inhibitor can be effective against ACV-resistant HSV infections in vivo.     

Ranibizumab for the treatment of neovascular age-related macular degeneration: a review

BACKGROUND: Choroidal neovascular (wet) age-related macular degeneration (ARMD) is becoming more prevalent worldwide as life expectancy continues to increase. Ranibizumab for intravitreal injection is an inhibitor of human vascular endothelial growth factor A approved by the US Food and Drug Administration for the treatment of ARMD in June 2006. The actions of ranibizumab result in reduced cell proliferation, reduced formation of new blood vessels, and minimization of vascular leakage. OBJECTIVE: This paper reviews the pharmacologic and pharmacokinetic properties, clinical efficacy, and safety profile of ranibizumab, and pharmacoeconomic considerations associated with its use. METHODS: MEDLINE (1966-December 2006) and International Pharmaceutical Abstracts (1970-December 2007) were searched for original research studies (Phase I, II, III, and IIIb), abstracts, and review articles concerning ranibizumab. The search terms were choroidal neovascularization, macular degeneration, Lucentis, ranibizumab, retinal degeneration, and vascular endothelial growth factor. Preference was given to Phase IlfllI studies. Selected information from the manufacturer of ranibizumab was also included. RESULTS: The efficacy of ranibizumab has been studied in 3 large clinical trials having the same primary efficacy end point, the proportion of patients losing <15 letters from baseline at 12 months (Early Treatment of Diabetic Retinopathy Study chart). A multicenter, Phase III, randomized, double-blind, sham-controlled, 24-month clinical trial evaluated ranibizumab 0.3 and 0.5 mg in 716 patients with minimally classic or occult choroidal neovascularization (CNV) associated with ARMD. The results for the primary efficacy end point were 94.5% and 94.6% in the ranibizumab 0.3- and 0.5-mg groups, respectively, compared with 62.2% in the sham-injection group (P < 0.001, both ranibizumab groups vs sham injection); at 24 months, the corresponding proportions were 92.0%, 90.0%, and 52.9% (P < 0.001, both ranibizumab groups vs sham injection). A 2-year, Phase I/II, single-masked (masked patient and visual acuity examiner, unmasked investigator), multicenter trial evaluated the tolerability and efficacy of the combination of ranibizumab 0.5 mg and verteporfin photodynamic therapy (PDT) compared with verteporfin PDT alone in 162 patients with predominantly classic CNV. For the primary efficacy end point, the results were 90.5% for ranibizumab + PDT and 67.9% for PDT alone (P < 0.001). Receipt of ranibizumab + PDT was also associated with improved visual acuity, with 23.8% of patients gaining >15 letters from baseline, compared with 5.4% of those who received PDT alone (P = 0.003). Finally, an international Phase III, double-blind, active-controlled study compared ranibizumab 0.3 and 0.5 mg with verteporfin PDT in 423 patients with predominantly classic lesions associated with CNV secondary to ARMD. For the primary efficacy end point, the results were 35.7% for ranibizumab 0.3 mg, 40.3% for ranibizumab 0.5 mg, and 5.6% for verteporfin PDT (P < 0.001). Serious adverse ocular events, which occurred in association with < 0.1% of intravitreal injections in these trials, included retinal detachment and endophthalmitis. Less serious adverse ocular reactions occurring in < 2% of patients included intraocular inflammation and increased intraocular pressure. CONCLUSION: The findings of these 3 large clinical trials suggest that ranibizumab was effective and well tolerated in patient.