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Scientific articles where FotoSan® has been used

1. In vitro evaluation of the cytotoxicity of FotoSan™ light-activated disinfection on human fibroblasts.
Gambarini G, Plotino G, Grande NM, Nocca G, Lupi A, Giardina B, De Luca M, Testarelli L.
Department of Endodontics, Sapienza University of Rome, Rome, Italy. endo@gianlucaplotino.com

Root canal disinfection needs to be improved because actual techniques are not able to eliminate all microorganisms present in the root canal system. The aim of the present study was to investigate the in vitro cytotoxicity of FotoSan (CMS Dental APS, Copenhagen Denmark), 17% EDTA and 2% chlorhexidine.
Fibroblasts of periodontal ligament from healthy patients were cultured. FotoSan (with and without light activation for 30 sec.), 17% EDTA and 2% chlorexidine were used for the cell viability tests. Untreated cells were used as control. The cellular vitality was evaluated by MTT test. The production of reactive oxygen species (ROS) was measured using an oxidation-sensitive fluorescent probe. Results were statistically analyzed by ANOVA, followed by a multiple comparison of means by Student-Newman-Keuls, and the statistical significance was set at p<0.05.
MTT tests showed that cytotoxic effects of FotoSan (both photocured and uncured) were statistically lower (p<0.05) than that observed using 2% Chlorhexidine, while no significant differences were found in comparison with 17% EDTA. No alterations in ROS production were detectable in any of the tested materials.
Since the toxicity of the FotoSan photosensitizer, both light-activated and not light-activated, is similar to common endodontic irrigants, it can be clinically used with precautions of use similar to those usually recommended for the above-mentioned irrigating solutions.  
2. Evaluation of Photodynamic Therapy Using a Light-emitting Diode Lamp against Enterococcus faecalis in Extracted Human Teeth
Alejandro Rios, DDS, Jianing He, DMD, PhD, Gerald N. Glickman, DDS, MS, MBA, JD, Robert Spears, PhD, Emet D. Schneiderman, PhD, and Allen L. Honeyman, PhD

Introduction: Photodynamic therapy (PDT) with high- power lasers as the light source has been proven to be effective in disinfecting root canals. The aim of this study was to evaluate the antimicrobial effect of PDT using toluidine blue O (TBO) and a low-energy light-emitting diode (LED) lamp after the conventional disinfection protocol of 6% NaOCl.
Methods: Single-rooted extracted teeth were cleaned, shaped, and sealed at the apex before incubation with Enterococcus faecalis for 2 weeks. Roots were randomly assigned to five experimental groups and three control groups. Dentin shavings were collected from the root canals of all groups with a #50/.06 rotary file, colony-forming units were determined, and the bacterial survival rate was calculated for each treatment.
Results: The bacterial survival rate of the NaOCl/TBO/light group (0.1%) was significantly lower (P < .005) than the NaOCl (0.66%) and TBO/light groups (2.9%).
Conclusions: PDT using TBO and a LED lamp has the potential to be used as an adjunctive antimicrobial procedure in conventional endodontic therapy. (J Endod 2011;37:856–859)
3. Endodontic photoactivated disinfection using a conventional light source: an in vitro and ex vivo study
Sebastian Schlafer, DDS, Michael Vaeth, Preben Hørsted-Bindslev, DDS, and Ellen V. G. Frandsen, Dr Odont, Aarhus, Denmark FACULTY OF HEALTH SCIENCES, AARHUS UNIVERSITY

Objective: The antimicrobial effect of photoactivated disinfection (PAD) using toluidine blue and an LED lamp was tested on endodontic pathogens in planktonic suspension and after inoculation into extracted teeth. Irradiation time was limited to 30 seconds.
Study design: The effect of PAD on planktonic suspensions of Escherichia coli, Candida albicans, Enterococcus faecalis, Fusobacterium nucleatum, and Streptococcus intermedius was analyzed using Poisson regression. Moreover, cultures of S. intermedius were inoculated into prepared root canals of extracted molars. The effect of PAD performed immediately after inoculation or after overnight bacterial incubation was determined by a 2-sample t test.
Results:Photoactivated disinfection yielded significant reductions (P < .001) in the viable counts of all organisms in planktonic suspension. The PAD treatment of S. intermedius in root canals yielded a mean log10 reduction of 2.60 (P < .001) immediately after inoculation and of 1.38 (P <.001) after overnight incubation.
Conclusion: Photoactivated disinfection using a conventional light source strongly reduces the number of viable endodontic pathogens in planktonic suspension and in root canals. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:634-641).
4. I-Dr. Lean Heong Foo
Effect of photodynamic therapy on matrix metalloproteinases-8 (MMP-8) in periodontitis patients
Lean Heong Foo*, Kai Soo Tan, and Lum Peng Lim, Faculty of Dentistry, National University of Singapore
Introduction: Photodynamic therapy is a minimally invasive therapy which is able to kill bacterial pathogens presents in deep periodontal pockets and reduce gingival inflammation. Matrix Metalloproteinases-8 (MMP-8) is associated with periodontal disease activity as it is the proteinases that cleaves the type I collagen in the connective tissue.
Objectives: To investigate the effectiveness of photodynamic therapy in reducing periodontal parameters and proteinase MMP-8.
Materials and Methods: 45 systemically healthy periodontitis patients seeking periodontal treatment were recruited for this study. Gingival clevicular fluids (GCFs) were collected before treatment, on 3rd and 6th month reviews after periodontal therapy. Scaling and root planing were performed on both test and control quadrants which were randomly assigned. Photodynamic therapy was carried out using commercially available device (Fotosan) with photosensitizer (toluidine blue) for 20 seconds at pockets deeper than 4 mm at test quadrant and was repeated again within one week after scaling and root planing. GCFs collected were analyzed using enzyme-link immunoabsorbent assay (ELISA) to detect MMP-8. Data collected were analyzed with SPSS using Non-parametric tests.
Results: PDT group showed a lower bleeding on probing score at 3 months (P<0.05).*
At 3rd  months and 6th  months both modalities of therapy resulted in significant reduction in probing depths (P< 0.05). This was accompanied by a corresponding reduction in MMP-8 (P<0.05).  For sites with PD improvement >2mm, both PDT and control sites showed significant change in MMP-8 at 3rd month and 6th month.
Conclusion :Periodontal therapy with or without adjunctive PDT are effective in reducing probing depths  and MMP-8 at 3 months and 6 months following treatment. 
Keywords: Photodynamic therapy; Gingival crevicular fluid; Matrix Metalloproteinases-8
*The bleeding on probing is not indicated on the conclusion because the title is about immunology.
5. II-Dr. Jacinta Loo
Effect of Photodynamic Therapy on Subgingival Microflora in
Periodontitis Patients
Jacinta Loo,  Kai Soo Tan, and Lum Peng Lim, Faculty of Dentistry, National University of Singapore
BACKGROUND: The antibacterial effect of photodynamic therapy (PDT) has been shown in several in vitro studies, but human clinical results on the microbiological changes following periodontal therapy have been conflicting.
OBJECTIVES: To validate the effectiveness of adjunctive PDT in the reduction of subgingival periopathogens Porphyromonas gingivalis (P.g) and Aggregatibacter actinomycetemcomitans (A.a) in the treatment of periodontitis.
MATERIALS AND METHODS: 49 patients with chronic periodontitis were included in this single blind, split mouth design study.. Two quadrants were randomly assigned to either receive oral hygiene instructions  and scaling and  root planing alone (control) or with adjunctive PDT (test). At baseline and 3 months after therapy, probing depths (PD) of selected sites were recorded and quantitative analysis of subgingival concentrations of P.g and A.a was performed using a commercially available polymerase chain reaction (PCR) test kit. The results were analysed using non-Parametric tests.
RESULTS: A general trend in the reduction of PD and microbial counts were found following both modalities of periodontal treatment at 3 months.  Using Wilcoxon signed rank test, PD and P.g were significantly reduced in both groups ( P<0.O5). The reduction of A.a in both groups however did not reach statistical significance (P>0.05). At 3 months, when sites that demonstrated improvement in PD of at least 2mm were selected, significant reductions in concentrations of A.a was only found in the PDT group.
CONCLUSIONS: Improvement in Probing depth with a corresponding reduction in P.g concentrations were found following periodontal treatment with or without adjunctive PDT. At sites showing reduction of at least 2mm probing depth, adjunctive PDT may confer additional short term changes on A.a as compared with scaling and root planing alone.
6. Light-activated disinfection using a light-emitting diode lamp in the red spectrum: clinical and microbiological short-term findings on periodontitis patients in maintenance.
A randomized controlled split-mouth clinical trial 
Lasers Med Sci
DOI 10.1007/s10103-012-1225-x 
C. Mongardini (*) : A. Pilloni Department of Dental Sciences and Maxillo-Facial Surgery, Section of Periodontics, University of Rome “Sapienza”, Via Caserta 6, 00161 Rome, Italy e-mail: claudio.mongardini@uniroma1.it
G. L. Di Tanna Department of Public Health and Infectious Diseases, University of Rome “Sapienza”,
Rome, Italy
Key findings Although further studies are needed, photodynamic therapy, applying a LED light as the light source, is an easy to use antiinfective therapy for the daily practice in the periodontal clinic, without the problems raised by antibiotic treatments and with less initial costs compared to laser lights. 
Abstract Eradication or suppression of pathogens is a major goal in periodontal therapy. Due to the increase in antibiotic resistance, the need of new disinfection therapies is raising. Photodynamic therapy (PDT) has demonstrated anti-infective potential. No data are available on the use of light-emitting diode (LED) lights as the light source in PDT. The aim of this study was to investigate the microbiological and clinical adjunctive outcome of a new photodynamic LED device, compared to scaling and root planing in perio- dontitis patients in maintenance [supportive periodontal therapy (SPT)]. In this masked, split-mouth design study, 30 treated chronic periodontitis subjects (mean age, 46.2 years; 13 males) in SPT were included. Two residual interdental sites with probing pocket depth (PPD) ≥ 5 mm in two opposite quadrants, with positive bleeding on probing (BOP) and comparable periodontal breakdown, were select- ed. PPD, BOP and subgingival microbiological samples for real-time PCR analysis (Carpegen® PerioDiagnostics, Car- pegen GmbH, Münster, Germany) were recorded at baseline and 1 week after treatment. Scaling and root planing was performed under local anesthesia. Randomly one of the sites was selected to receive adjunctive photodynamic therapy by inserting a photosensitizer (toluidine blue O solution) and exposing it to a LED light in the red spectrum (Fotosan®, CMS Dental, Copenhagen, Denmark), according to the manufacturer’s instructions. After 1 week, 73 % of the control sites and 27 % of the test sites were still BOP+. These differences compared to baseline values and in- between groups were statistically significantly different (p < 0.001). Mean PPD decreased from 5.47 mm (±0.68) to 4.73 mm (±0.74, p < 0.001) in control sites and from 5.63 mm (±0.85) to 4.43 mm (±1.25, p < 0.001, test vs control p00.01) in the test group. Microbiologically, higher reductions of relative proportions of red complex bacteria were observed in test sites (68.1 vs. 4.1 %; p 0 0.01). This study showed that adjunctive photodynamic treatment by LED light may enhance short-term clinical and microbio- logical outcome in periodontitis subjects in SPT. 
Key findings Although further studies are needed, photodynamic therapy, applying a LED light as the light source, is an easy to use anti- infective therapy for the daily practice in the periodontal clinic, without the problems raised by antibiotic treatments and with less initial costs compared to laser lights.
7. Effect of photoactivated disinfection with a light-emitting diode on bacterial species and biofilms associated with periodontitis and peri-implantitis 
Photodiagnosis and Photodynamic Therapy (2013) xxx, xxx—xxx
Sigrun Eick DMDa,∗, Giedre Markauskaitea,
Sandor Nietzsche PhDb, Oliver Laugisch DMDa, Giovanni E. Salvi Professora, Anton Sculean Professora
a Department of Periodontology, School of Dental Medicine, University of Bern, Freiburgstrasse 7, CH-3010 Bern, Switzerland
b Center of Electron Microscopy, University Hospital of Jena, Ziegelmühlenweg 1, D-07743 Jena, Germany 
Background: To determine the effect of photoactivated disinfection (PAD) using toluidine blue and a light-emitting diode (LED) in the red spectrum (wave length at 625—635nm) on species associated with periodontitis and peri-implantitis and bacteria within a periodonto- pathic biofilm.
Methods: Sixteen single microbial species including 2 Porphyromonas gingivalis and 2 Aggregati- bacter actinomycetemcomitans and a multispecies mixture consisting of 12 species suspended in saline without and with 25% human serum were exposed to PAD. Moreover, single-species biofilms consisting of 2 P. gingivalis and 2 A. actinomycetemcomitans strains and a multi-species biofilm on 24-well-plates, grown on titanium discs and in artificial periodontal pockets were exposed to PAD with and without pretreatment with 0.25% hydrogen peroxide. Changes in the viability were determined by counting the colony forming units (cfu).
Results: PAD reduced the cfu counts in saline by 1.42log10 after LED application for 30s and by 1.99 log10 after LED application for 60 s compared with negative controls (each p < 0.001). Serum did not inhibit the efficacy of PAD. PAD reduced statistically significantly (p < 0.05) the cfu counts of the P. gingivalis biofilms. The viability of the A. actinomycetemcomitans biofilms and the multi-species biofilms was statistically significantly decreased when PAD was applied after a pretreatment with 0.25% hydrogen peroxide. The biofilm formed in artificial pockets was more sensitive to PAD with and without pretreatment with hydrogen peroxide compared with those formed on titanium discs. 

Scientific articles where similar LAD treatment has been used.

1. Endodontic Photodynamic Therapy Ex Vivo
Raymond Ng, DDS, Fiza Singh, DDS, Despina A. Papamanou, DDS, Xiaoqing Song, MD, MS, Chitrang Patel, BS, Colleen Holewa, BS, Niraj Patel, BS, MS, Vanja Klepac-Ceraj, PhD, Carla R. Fontana, DDS, PhD, Ralph Kent, ScD, Tom C. Pagonis, DDS, MS,Philip P. Stashenko, DMD, PhD and Nikolaos S. Soukos, DDS, PhD

Introduction: The objective of this study was to eval- uate the antimicrobial effects of photodynamic therapy (PDT) on infected human teeth ex vivo.
Methods: Fifty-two freshly extracted teeth with pulpal necrosis and associated periradicular radiolucencies were obtained from 34 subjects. Twenty-six teeth with 49 canals received chemomechanical debridement (CMD) with 6% NaOCl, and 26 teeth with 52 canals received CMD plus PDT. For PDT, root canal systems were incubated with methylene blue (MB) at concentration of 50 mg/ mL for 5 minutes, followed by exposure to red light at 665 nm with an energy fluence of 30 J/cm2. The contents of root canals were sampled by flushing the canals at baseline and after CMD alone or CMD+PDT and were serially diluted and cultured on blood agar. Survival fractions were calculated by counting colony-forming units (CFUs). Partial characterization of root canal species at baseline and after CMD alone or CMD+PDT was performed by using DNA probes to a panel of 39 endodontic species in the checkerboard assay.
Results: The Mantel- Haenszel c2 test for treatment effects demonstrated the better performance of CMD+PDT over CMD (P = .026). CMD+PDT significantly reduced the frequency of positive canals relative to CMD alone (P = .0003). After CMD+PDT, 45 of 52 canals (86.5%) had no CFUs as compared with 24 of 49 canals (49%) treated with CMD (canal flush samples). The CFU reductions were similar when teeth or canals were treated as independent entities. Post-treatment detection levels for all species were markedly lower for canals treated by CMD+PDT than they were for those treated by CMD alone. Bacterial species within dentinal tubules were detected in 17 of 22 (77.3%) and 15 of 29 (51.7%) canals in the CMD and CMD+PDT groups, respectively (P = .034).
Conclusions: Data indicate that PDT significantly reduces residual bacteria within the root canal system, and that PDT, if further enhanced by technical improvements, holds substantial promise as an adjunct to CMD. (J Endod 2011;37:217–222)
2. Photodynamic Therapy Associated with Conventional Endodontic Treatment in Patients with Antibiotic-resistant Microflora: A Preliminary Report
Aguinaldo S. Garcez, PhD, Silvia C. Nun ~ez, PhD, Michael R. Hamblim, PhD, Hideo Suzuki, and Martha S. Ribeiro, PhD.

Introduction: This study reports the antimicrobial effect of photodynamic therapy (PDT) combined with endodontic treatment in patients with necrotic pulp in-fected with microflora resistant to a previous antibiotic therapy.
Methods: Thirty anterior teeth from 21 patients with periapical lesions that had been treated with conventional endodontic treatment and antibiotic therapy were selected. Microbiological samples were taken (1) after accessing the root canal, (2) after endodontic therapy, and (3) after PDT. Results: All the patients had at least 1 microorganism resistant to antibiotics. PDT used polyethylenimine chlorin(e6) as a photosensitizer and a diode laser as a light source (P = 40 mW, t = 4minutes, E = 9.6 J). Endodontic therapy alone produced a significant reduction in numbers of microbial species but only 3 teeth were free of bacteria, whereas the combination of endodontic therapy with PDT eliminated all drug-resistant species and all teeth were bacteria-free. Conclusions: The use of PDT added to conventional endodontic treatment leads to a further major reduction of microbial load. PDT is an efficient treatment to kill multi-drug resistant microorganisms. (J Endod 2010;36:1463–1466)
3. Periimplantitis
Lethal photosensitization for decontamination of implant surfaces in the treatment of peri-implantitis
Orhun Dörtbudak, Robert Haas, Thomas Bernhart, Georg Mailath-Pokorny
Clin. Oral Impl. Res. 12, 2001; 104–108
Key words: photosensitization, peri-implantitis, diode laser

Abstract: Peri-implantitis is considered to be a multifactorial process involving bacterial contamination of the implant surface. A previous study demonstrated that a combination of toluidine blue O (100 mg/ml) and irradiation with a diode soft laser with a wavelength of 905 nm results in an elimination of Porphyromonas gingivalis (P. gingivalis), Prevotella intermedia (P. intermedia), and Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) on different implant surfaces (machined, plasma-flamesprayed, etched, hydroxyapatite-coated). The aim of this study was to examine the laser effect in vivo. In 15 patients with IMZ implants who showed clinical and radiographic signs of peri-implantitis, toluidine blue O was applied to the implant surface for 1 min and the surface was then irradiated with a diode soft laser with a wavelength of 690 nm for 60 s. Bacterial samples were taken before and after application of the dye and after lasing. The cultures were evaluated semiquantitatively for A. actinomycetemcomitans, P. gingivalis, and P. intermedia. It was found that the combined treatment reduced the bacterial counts by 2 log steps on average. The application of TBO and laser resulted in a significant reduction (P,0.0001) of the initial values in all 3 groups of bacteria. Complete elimination of bacteria was not achieved.

Our summary:
Significant reduction of P. gingivalis, P. intermedia, and A. actinomycetemcomitans with 15 patients with peri-implantitis
4. Lethal photosensitization and guided bone regeneration in treatment of peri-implantitis: an experimental study in dogs
Jamil Awad Shibli, Marilia Compagnoni Martins, Fernando Salimon Ribeiro, Valdir Gouveia Garcia, FranciscoHumbertoNociti Jr, Elcio Marcantonio Jr
Clin. Oral Impl. Res. 17, 2006 / 273–281
Key words: guided bone regeneration, histology, peri-implantitis, photodynamic therapy/ photosensitizers, reosseointegration

Abstract: The purpose of this study was to evaluate the effect of lethal photosensitization and guided bone regeneration (GBR) on the treatment of ligature-induced peri-implantitis in different implant surfaces. The treatment outcome was evaluated by clinical and histometric methods. A total of 40 dental implants with four different surface coatings (10 commercially pure titanium surface (cpTi); 10 titanium plasma-sprayed (TPS); 10 acid-etched surface; 10 surface-oxide sandblasted) were inserted into five mongrel dogs. After 3
months, the animals with ligature-induced peri-implantitis were subjected to surgical treatment using a split-mouth design. The controls were treated by debridment and GBR, while the test side received an additional therapy with photosensitization, using a GaAlAs
diode laser, with a wavelength of 830nm and a power output of 50mW for 80 s (4 J/cm2), and sensitized toluidine blue O (100 mg/ml). The animals were sacrificed 5 months after therapy. The control sites presented an earlier exposition of the membranes on all coating
surfaces, while the test group presented a higher bone height gain. Re-osseointegration ranged between 41.9% for the cpTi surface and 31.19% for the TPS surface in the test sites; however differences were not achieved between the surfaces. The lethal photosensitization
associated with GBR allowed for better re-osseointegration at the area adjacent to the periimplant defect regardless of the implant surface.

Our summary:
PAD together with guided bone regeneration (GBR) allowed for better re-osseointegration (higher bone height gain) than GBR alone  
5. Periodontitis
In Vivo Killing of Porphyromonas gingivalis by Toluidine Blue-Mediated Photosensitization in an Animal Model

N. Kömerik,1,2 H. Nakanishi,2,3 A. J. MacRobert,2 B. Henderson,4
P. Speight,5 and M. Wilson1*
Department of Microbiology,1 Cellular Microbiology Research Group,4 and Department of Oral Pathology,5
Eastman Dental Institute for Oral Health Care Sciences, and Department of Surgery, National Medical
Laser Centre,2 University College London, London, United Kingdom, and Department of Oral
and Maxillofacial Surgery, University of Tokushima, Tokushima, Japan3


Porphyromonas gingivalis is one of the major causative organisms of periodontitis and has been shown to be susceptible to toluidine blue-mediated photosensitization in vitro. The aims of the present study were to determine whether this technique could be used to kill the organism in the oral cavities of rats and whether this would result in a reduction in the alveolar bone loss characteristic of periodontitis. The maxillary molars of rats were inoculated with P. gingivalis and exposed to up to 48 J of 630-nm laser light in the presence of toluidine blue. The number of surviving bacteria was then determined, and the periodontal structures were examined for evidence of any damage. When toluidine blue was used together with laser light there was a significant reduction in the number of viable P. gingivalis organisms. No viable bacteria could be detected when 1 mg of toluidine blue per ml was used in conjunction with all light doses used. On histological examination, no adverse effect of photosensitization on the adjacent tissues was observed. In a further group of animals, after time was allowed for the disease to develop in controls, the rats were killed and the level of maxillary molar alveolar bone was assessed. The bone loss in the animals treated with light and toluidine blue was found to be significantly less than that in the control groups. The results of this study show that toluidine blue-mediated lethal photosensitization of P. gingivalis is possible in vivo and that this results in decreased bone loss. These findings suggest that photodynamic therapy may be useful as an alternative approach for the antimicrobial treatment of periodontitis.

Our summary:
Rats inoculated with P. gingivalis and treated with LAD:
1. No surviving bacteria in the group treated
2. On histological examination no negative effects
3. Significant less bone resorption after 90 days
in the treated group compared to control group
6. Efficacy of Photodynamic Therapy on Inflammatory Signs and Two Selected Periodontopathogenic Species in a Beagle Dog Model
Bernd W. Sigusch,* Anne Pfitzner,* Volker Albrecht,† and Eike Glockmann*
Correspondence: Dr. Bernd W. Sigusch, Friedrich-Schiller-
Universität Jena, Zentrum für Zahn-, Mund- und Kieferheilkunde,
Poliklinik für Konservierende Zahnheilkunde.
J Periodontol 2005;76:1100-1105

Background: Current research aims to find alternatives to conventional methods for suppressing periodontopathogenic bacteria. Photodynamic therapy (PDT) could be a suitable treatment procedure of periodontal infections.

Methods: In the present study, the PDT method was tested with two photosensitizers, chlorine e6 and BLC1010, in an experiment on beagle dogs. The animals were infected with Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) in all subgingival areas. After infection, we observed clinical signs of gingival inflammation, including an increase of redness and bleeding on probing. Microbiological monitoring before and after treatment was performed using polymerase chain reaction (PCR). PDT was conducted with a diode laser with a wavelength of 662 nm using a power of 0.5 W and the photosensitizers.
Results: The PDT procedure carried out with either of the photosensitizers caused a significant reduction in the clinical inflammation signs of redness and BOP, compared to the controls (laser only and no treatment). Furthermore, PDT with chlorine e6 caused a significant reduction in P. gingivalis-infected sites, whereas there was a lack in suppression after PDT with BLC1010. F. nucleatum could hardly be reduced with chlorine e6, and only to a certain extent with BLC 1010 and laser only. In the control groups, the Pg-infected test sites did not change.
Conclusions: This study demonstrated that the photodynamic therapy using photosensitizer and a 662 nm laser light source is distinctly advantageous in reducing the periodontal signs of redness and bleeding on probing. The procedure also appears to significantly suppress P. gingivalis.

Animal studies; bacterial infections/therapy; periodontal; diseases/therapy; photochemotherapy.
Our summary:
Significant reduction of periodontical signs of redness and bleeding on probing after infection with Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn)
7. Microbiological evaluation of photo-activated disinfection in endodontics (An in vivo study)
S. J. Bonsor,1 R. Nichol,2 T. M. S. Reid3 and G. J. Pearson4
1*General Dental Practitioner, The Dental Practice, 21 Rubislaw Terrace, Aberdeen;
2Senior Chief Biomedical Scientist, 3Consultant Microbiologist, Department of Medical
Microbiology, Grampian University Hospitals Trust, Aberdeen; 4Professor, Department of
Biomaterials in Relation to Dentistry, Barts and London School of Medicine and Dentistry,
Queen Mary University of London

Objective To determine the microbiological effect of photoactivateddisinfection (PAD) as an adjunct to normal root canal disinfection in vivo.

Design A randomised trial carried out in general dental practice.
Subjects and methods Patients presenting with symptoms ofirreversible pulpitis or periradicular periodontitis requiring endodontictherapy were selected at random. A microbiological sample of the canal was taken on accessing the canal, after conventional endodontic therapy,and finally after the PAD process (photosensitiser and light) had been carried out on the prepared canal. All three samples from each canal were plated within 30 minutes of sampling and cultured anaerobically for five days. Growth of viable bacteria was recorded for each sample to
determine bacterial load.
Results Thirty of the 32 canals were included in the results. Cultures from the remaining two did not reach the laboratory within the target time during which viability was sustained. Of the remaining 30, 10 canals were negative to culture. These were either one of the canals in multi rooted teeth where the others were infected or where a pre-treatment with a poly-antibiotic paste had been applied to hyperaemic vital tissue. Sixteen of the remainder were negative to culture after conventional endodontic therapy. Three of the four which had remained infected cultured negative after the PAD process. In the one canal where culturable bacteria were still present, a review of the light delivery system showed a fracture in the fibre reducing the effective light output by 90%.
Conclusions The PAD system offers a means of destroying bacteria remaining after using conventional irrigants in endodontic therapy.

Our summary:
20 root canals out of 30 were infected, 3 root canals were infected after conventional endodontic therapy, but showed no infectious cultures after PAD treatment.
8. Advanced Noninvasive Light-activate Disinfection: Assessment of Cytotoxicity on Fibroblast Versus Antimicrobial Activity Against Enterococcus faecalis
Saji George, BSc, MSc, and Anil Kishen, BDS, MDS, PhD
From the Department of Restorative Dentistry, National University of Singapore, Singapore, Republic of Singapore.
JOE — Volume 33, Number 5, May 2007

Recent interest in light-activated disinfection demands insight on the selectivity towards bacterial cells compared with mammalian cells. This study was aimed to evaluate the cytotoxicity and selectivity of an advanced noninvasive light-activated disinfection (ANILAD) developed in our laboratory. The extent of cytotoxic effect of methylene blue activated by visible light of wavelength 664 nm was tested and compared with sodium hypochlorite (NaOCl) under in vitro and ex vivo conditions on fibroblast L929 cells. Simultaneous evaluation of cytotoxicity and antibacterial effect was also conducted to study the specificity of lightactivated therapy (LAT) toward prokaryotic cells (Enterococcus faecalis). The cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2- yl)-2, 5-diphenyltetrazolium bromide assay and trypan blue viability test, whereas colony-forming units were determined to evaluate bacterial viability.

Data from both in vitro and ex vivo experiments showed that cytotoxicity was significantly less in LAT compared with NaOCl (p _ 0.001). E faecalis cells were killed at a faster rate than fibroblasts. An irradiation dose producing 97.7% bacterial killing showed only 30% fibroblast dysfunction. This study indicated that ANILAD produced an insignificant effect on mammalian cells. (J Endod 2007;33:599–602).

Our summary:
Significantly less cytotoxicity of LAD compared to Sodiumhypochlorite
9. Treatment of oral candidiasis with methylene blue–mediated photodynamic therapy in an immunodeficient murine model
M. C. Teichert, BA,a J. W. Jones, MD,b M. N. Usacheva, PhD, DSc,c and M. A. Biel, MD, PhD,d
aMicrobiologist, Advanced Photodynamic Technologies, Inc, Minneapolis, Minn.
bStaff Pathologist, Department of Pathology, Abbott Northwestern
Hospital, Minneapolis, Minn.
cPhotochemist, Advanced Photodynamic Technologies, Inc,
Minneapolis, Minn.
dPresident and Staff, Ear, Nose & Throat Specialty Care of Minnesota,
PA, St Paul, Minn.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002; 93: 155-60

Objective. The purpose of this study was to evaluate the efficacy of using methylene blue (MB)–mediated photodynamic therapy to treat oral candidiasis in an immunosuppressed murine model, mimicking what is found in human patients.

Study design. Seventy-five experimental mice with severe combined immunodeficiency disease were inoculated orally with Candida albicans by swab 3 times a week for a 4-week period. On treatment day, mice were cultured for baseline fungal growth and received a topical oral cavity administration of 0.05 mL MB solution at one of the following concentrations: 250, 275, 300, 350, 400, 450, or 500 µg/mL. After 10 minutes the mice were recultured and underwent light activation with 664 nm of diode laser light with a cylindrical diffuser. After photodynamic therapy the mice were cultured again for colonyforming units per milliliter and then killed, their tissue harvested for histopathology.

Results and conclusions. The results indicate an MB dose-dependent effect. Concentrations from 250 to 400 µg/mL reduced fungal growth but did not eliminate Candida albicans. MB concentrations of 450 and 500 µg/mL totally eradicated Candida albicans from the oral cavity, resulting in reductions from 2.5 log10 and 2.74 log10 to 0, respectively. These results suggest that MB-mediated photodynamic therapy can potentially be used to treat oral candidiasis in immunodeficient patients.

Our summary:
PAD can potentially be used to treat oral candidiasis in immunodeficient patients.

Review Articles on LAD

Photodynamic therapy: a new antimicrobial approach to infectious disease?
Michael R. Hamblin and Tayyaba Hasan
a Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Boston,
MA 02114, USA. E-mail: hamblin@helix.mgh.harvard.edu
b Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA

Photochem. Photobiol. Sci., 2004, 2, 436-450

Photodynamic therapy (PDT) employs a non-toxic dye, termed a photosensitizer (PS), and low intensity visible light which, in the presence of oxygen, combine to produce cytotoxic species. PDT has the advantage of dual selectivity, in that the PS can be targeted to its destination cell or tissue and, in addition, the illumination can be spatially directed to the lesion. PDT has previously been used to kill pathogenic microorganisms in vitro, but its use to treat infections in animal models or patients has not, as yet, been much developed. It is known that Gram-(_) bacteria are resistant to PDT with many commonly used PS that will readily lead to phototoxicity in Gram-(_) species, and that PS bearing a cationic charge or the use of agents that increase the permeability of the outer membrane will increase the efficacy of killing Gram-(_) organisms. All the available evidence suggests that multi-antibiotic resistant strains are as easily killed by PDT as naïve strains, and that bacteria will not readily develop resistance to PDT. Treatment of localized infections with PDT requires selectivity of the PS for microbes over host cells, delivery of the PS into the infected area and the ability to effectively illuminate the lesion. Recently, there have been reports of PDT used to treat infections in selected animal models and some clinical trials: mainly for viral lesions, but also for acne, gastric infection by Helicobacter pylori and brain abcesses. Possible future clinical applications include infections in wounds and burns, rapidly spreading and intractable soft-tissue infections and abscesses, infections in body cavities such as the mouth, ear, nasal sinus, bladder and stomach, and surface infections of the cornea and skin.
Photodynamic Therapy of Microbial Infections: State of the Art and Perspectives
Giulio Jori
Department of Biology, University of Padova, Via Ugo Bassi 58B, 35121 Padova, Italy; jori@bio.unipd.it
Journal of Environmental Pathology, Toxicology, and Oncology, 25(1–2)505–519 (2006)

Photodynamic therapy (PDT) is coming of age as an efficient alternative treatment for microbial infections, a problem which is presently aggravated by the increasingly widespread diffusion of antibiotic-resistant microbial strains. In particular, the use of red light-absorbing photosensitizers as photodynamic antimicrobial agents is characterized by various favorable features, including: (a) the broad spectrum of antimicrobial action of selected phenothiazines, porphyrins, and phthalocyanines, which promote the photosensitized inactivation of Gram(+) and Gram(-) bacteria, fungi, mycoplasma, and parasites by using one phototherapeutic protocol and mild irradiation conditions; (b) porphyrins/phthalocyanines display no appreciable toxicity in the dark at photochemically active doses; (c) microbial cell death is primarily a consequence of membrane photodamage through a typically multitarget process, which minimizes the risk of both the onset of mutagenic processes and the selection of photoresistant cells; (d) such photosensitizers act with essentially identical efficiency against both wild and antibiotic-resistant strains, whereas
no selection of photoresistant microbial pathogens has been observed; (e) a combination between antibiotic-based and photodynamic therapy is possible. A typical example of phthalocyanine-sensitized photoinactivation of methicillin-resistant Staphylococcus aureus (MRSA) is provided. At present, antimicrobial PDT appears to be especially convenient for the treatment of localized infections, such as oral candidosis, periodontitis or chronic wounds.

KEY WORDS: photodynamic therapy, microbial infections, porphyrins, phthalocyanines, photosensitization, activated oxygen, antibiotic resistance, bacteria, fungi
Photodynamic Therapy in Dentistry
K. Konopka1* and T. Goslinski2
1Department of Microbiology, University of the Pacific, Arthur A., Dugoni School of Dentistry, San Francisco, CA, USA; and
2Department of Chemical Technology of Drugs, University of Medical Sciences, Poznan, Poland;
*corresponding author: kkonopka@pacific.edu

J Dent Res 86(8): 694-707, 2007

Photodynamic therapy (PDT), also known as photoradiation therapy, phototherapy, or photochemo therapy,
involves the use of a photoactive dye (photosensitizer) that is activated by exposure to light of a specific wavelength in the presence of oxygen. The transfer of energy from the activated photosensitizer to available oxygen results in the formation of toxic oxygen species, such as singlet oxygen and free radicals. These very reactive chemical species can damage proteins, lipids, nucleic acids, and other cellular components. Applications of PDT in dentistry are growing rapidly: the treatment of oral cancer, bacterial and fungal infection therapies, and the photodynamic diagnosis (PDD) of the malignant transformation of oral lesions. PDT has shown potential in the treatment of oral leukoplakia, oral lichen planus, and head and neck cancer. Photodynamic antimicrobial chemotherapy (PACT) has been efficacious in the treatment of bacterial, fungal, parasitic, and viral infections. The absence of genotoxic and mutagenic effects of PDT is an important factor for long-term safety during treatment. PDT also represents a novel therapeutic approach in the management of oral biofilms. Disruption of plaque structure has important consequences for homeostasis within the biofilm. Studies are now leading toward selective photosensitizers, since killing the entire flora leaves patients open to opportunistic infections.
Dentists deal with oral infections on a regular basis. The oral cavity is especially suitable for PACT, because it is relatively accessible to illumination.
Anti-microbial photodynamic therapy: useful in the future?
Tim Maisch
Lasers Med Sci (2007) 22: 83–91

Previous chapters in this volume have focused on fundamental principles and clinical applications of PDT. This chapter will attempt to outline emerging areas of research to identify some new applications that may become useful in the future in clinical practise. The worldwide rise in antibiotic resistance has driven research to the development of novel anti-microbial strategies. Cutaneous diseases caused by MRSA are ideally suited to treatment by anti-microbial photodynamic therapy for eradicating localized infections and for modulating wound healing due to the ability to deliver photosensitizer and light with topical application. The use of photosensitizer and light as an anti-microbial agent against periodontal microbial biofilms should also represent an attractive method of eliminating oral bacteria. Suitable light sources, laser light and non-coherent light will be briefly covered. This chapter will focus on some aspects of anti-microbial photodynamic therapy that appear to be promising for dermatological indications and inactivation of pathogenic bacteria within the oral cavity.

Keywords: Anti-microbial photodynamic therapy. Oral bacteria. MRSA. Photosensitizer. Porphyrin-photosensitization