Effective Biofilm Eradication on Orthopedic Implants with Methylene Blue Based Antimicrobial Photodynamic Therapy In Vitro.

Periprosthetic joint infections (PJI) are difficult to treat due to biofilm formation on implant surfaces, often requiring removal or exchange of prostheses along with long-lasting antibiotic treatment. This in vitro study investigated the effect of methylene blue photodynamic therapy (MB-PDT) on PJI-causing biofilms on different implant materials. MB-PDT (664 nm LED, 15 J/cm2) was tested on different Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Cutibacterium acnes strains in both planktonic form and grown in early and mature biofilms on prosthetic materials (polyethylene, titanium alloys, cobalt-chrome-based alloys, and bone cement). The minimum bactericidal concentration with 100% killing (MBC100%) was determined. Chemical and topographical alterations were investigated on the prosthesis surfaces after MB-PDT. Results showed a MBC100% of 0.5-5 µg/mL for planktonic bacteria and 50-100 µg/mL for bacteria in biofilms-independent of the tested strain, the orthopedic material, or the maturity of the biofilm. Material testing showed no relevant surface modification. MB-PDT effectively eradicated common PJI pathogens on arthroplasty materials without damage to the materials, suggesting that MB-PDT could be used as a novel treatment method, replacing current, more invasive approaches and potentially shortening the antibiotic treatment in PJI. This would improve quality of life and reduce morbidity, mortality, and high health-care costs.

Medicinal plants from the Himalayan region for potential novel antimicrobial and anti-inflammatory skin treatments.

BACKGROUND AND OBJECTIVES: Adequate treatment of wounds remains one of the major medical needs globally, most notably in the regions with poor or limited access to health care. In many local and traditional systems of medicine, plants are often widely used for treating infected wounds. AIM AND OBJECTIVES: The overarching aim of this project was selection of potential species for use in a future treatment by combining with plant resources with aspects of antimicrobial photodynamic therapy (aPDT). Specifically, we focussed on species used locally in the Himalayan region for the treatment of skin disorders and then assessed the existing pharmacological evidence for key species based on the published evidence available. METHODS: Database searches were performed to identify relevant publications describing local and traditional uses of plants in the Himalayan region of Bhutan, PR China, India, Nepal and Pakistan. Using the Global Biodiversity Information Facility (GBIF), species were researched in terms of their distribution including in different climatic regions, focussing on species mostly found in higher climatic zones (based on the Köppen-Geiger climate classification). For species used in three or more countries and restricted to the higher altitudes, data on safety, pharmacology, as it relates to dermatological conditions, and phytochemistry were retrieved. KEY FINDINGS: The study identified a total of 606 species that are used in the treatment of various skin conditions often associated with infections reported in 84 articles. Common weeds like Ageratum conyzoides and Bidens pilosa, widely used and cultivated species like Centealla asiatiaca and Prunus armenica were excluded. This ultimately led to the identification of a core group of five widely used species restricted to the Himalayan region (Cedrus deodara, Nardostachys jatamansi, Pinus wallichiana, Pinus roxburghii and Valeriana jatamansi). CONCLUSIONS: Here we apply a novel approach comprising an assessment of the published information on the use of medicinal plants (i.e. local and traditional knowledge) in the context of their potential to be used in a biomedical form of clinical treatment - aPDT. Then, once sustainable sourcing based on access and benefit-sharing arrangements is in place, these species are investigated for their potential in wound treatment. Ultimately, the goal is to develop a new baseline for primary health care in some of the regions of the world with poor or limited access to health care.

"Tobacco Is the Chief Medicinal Plant in My Work": Therapeutic Uses of Tobacco in Peruvian Amazonian Medicine Exemplified by the Work of a Maestro Tabaquero.

INTRODUCTION: Harmful usage of tobacco is a public health problem of global concern and, in many countries, the main risk factor for non-communicable diseases. Yet, in the Peruvian Amazon, the geographical region believed to be tobacco's historical birthplace, this plant is associated with a strikingly different usage and repute: Tobacco (especially Nicotiana rustica L.) in this area is described as a potent medicinal plant, used topically or via ingestion to treat a variety of health conditions. The goal of this transdisciplinary field study was to investigate clinical applications of the tobacco plant as per Amazonian medicine exemplified in the practice of a reputed Maestro Tabaquero, an Amazonian traditional healer whose medical specialization focuses on tobacco-based treatments. METHODS: Using a transdisciplinary clinical approach, we conducted in-depth interviews with the tabaquero applying the systematizing expert interview method, in order to map modes of preparation and administration, indications, contraindications, effects, risks, adverse effects, and systemic aspects of tobacco-based remedies. RESULTS: The informant's descriptions revealed refined knowledge on this plant's therapeutic properties and scope, safety profile, and application techniques. The main indications mentioned included "problems of the mind," of the respiratory system, parasitic illnesses (intestinal/skin), gout, and Amazonian epistemic conditions described as spiritual-energetic in nature. A liquid remedy taken orally was his most commonly used preparation, with acute/sub-acute effects involving a pronounced psychoactive component (altered state of consciousness) and physiological response (emesis, nausea). A skilled tabaquero that knows how to dose, administer, and intervene in case of adverse effects was considered imperative for safe treatment delivery. CONCLUSIONS: To our knowledge, this is the first study employing a transdisciplinary clinical approach to examine therapeutic applications of tobacco by an Amazonian tabaquero. Our findings significantly contribute to the growing research literature on Amazonian medicine and emergent psychedelic-assisted therapies and could, in the long-term, open new treatment avenues in several domains. Forthcoming studies should assess toxicity/safety and clinical outcomes of patients receiving Amazonian tobacco-based treatment.

Who Turns to Amazonian Medicine for Treatment of Substance Use Disorder? Patient Characteristics at the Takiwasi Addiction Treatment Center.

OBJECTIVE: Complementary medicines are an emergent field in the treatment of substance use disorders (SUDs) and include Amazonian medicines, such as ayahuasca. The aim of this multimodal cross-sectional study was to investigate characteristics of people who seek treatment for SUDs at an accredited healthcare facility that applies Amazonian medicines along with conventional psychotherapy. METHOD: We collected clinical and sociodemographic data of consecutive admissions at the Takiwasi Addiction Treatment Center (Tarapoto, Peru) using structured questionnaires, interviews, and letters submitted upon program application describing motivation for treatment. RESULTS: The sample of 50 male participants admitted between 2014 and 2016 was culturally heterogeneous, including patients from Peru (42%), other Latin American countries (34%), and North America/Europe (24%). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria indicated dependencies on cannabis (72%), alcohol (52%), cocaine/base paste (48%), and others; multiple substance use was common (84%). Self-reported depression and anxiety scores showed moderate elevation. Comparison of Addiction Severity Index composite scores to a large U.S. sample suggested somewhat more severe problems in the drug and psychiatric domains. Common motives for selecting the program included interest in Amazonian medicine, the Takiwasi concept of treatment, and unfavorable experiences with past treatments. Being motivated by family, a desire for self-transformation, and spiritual/existential motives were common themes for treatment initiation. CONCLUSIONS: Our results suggest that the Amazonian medicine-based therapy attracts a diverse patient group not limited to regional residents and may be particularly appealing to more impaired SUD patients with a history of unsuccessful treatment. The sample's cultural diversity suggests an existing interest in such therapies among international SUD treatment-seeking patients. These findings are relevant in light of the need for improved SUD therapies and contribute to the emergent research literature on ayahuasca-based treatments.

Short-Term Treatment Effects of a Substance Use Disorder Therapy Involving Traditional Amazonian Medicine.

Chronic illness management today commonly involves alternative medicines. Substance use disorder (SUD), as a chronic psychosomatic illness, might benefit from a similar approach. The accredited Takiwasi Center offers such an SUD treatment program involving Amazonian medicine combined with psychotherapy. The current study assessed this integrative program's short-term therapeutic effects. We measured baseline data from 53 dependence-diagnosed males admitted to treatment (T1) and repeated clinical outcome variables at treatment completion (T2). Paired samples t-tests were used to assess changes between T1 and T2 (n = 36). Nearly all participants (age M= 30.86, SD= 8.17) were dependent on multiple substances, most prominently cannabis, alcohol, and cocaine-related drugs. A significant decrease (T1 to T2) was found for addiction severity outcomes drug use (p < .001), alcohol use (p < .001), psychiatric status (p < .001), and social/familial relationships (p < .001). Emotional distress also diminished significantly (p < .001), as did substance craving (p < .001). Quality of life increased significantly from T1 to T2 (p < .001). Our results provide first indications for significantly improved SUD symptoms after the Amazonian medicine-based treatment. These findings are preliminary given the design, but strongly encourage further investigation of this therapy, which in the long term may open new therapeutic avenues for SUDs.

Conceptions and practices of an integrative treatment for substance use disorders involving Amazonian medicine: traditional healers' perspectives

Objective: The harmful use of psychoactive substances represents one of today's largest public health problems. Yet, in spite of its global relevance, current treatment for substance use disorders (SUDs) is still not entirely successful. The purpose of this study was to investigate alternative treatments and conceptions from traditional Amazonian medicine adapted to SUDs. Methods: We conducted semi-structured interviews with 13 practicing experts at a well-established addiction treatment center in the Peruvian Amazon and performed qualitative content analysis on the collected data. Main categories were deductively defined and corresponding subcategories inductively developed. Results: Our findings revealed characteristic features and consequences, causes and antecedents, and treatment methods of SUDs as the main categories. Overall, concepts of disease etiology bore resemblance with contemporary biopsychosocial models of SUDs. The Amazonian therapeutic means however differed markedly from current Western ones. The main methods involved dietary retreats, healing ceremonies, and purging rituals. The integral application of Amazonian methods, as well as their traditional implementation according to prescribed ritual protocols, were emphasized by the experts as crucial for efficacy and safety of treatment delivery. Conclusion: We suggest further scientific attention to these therapies, including clinical studies, for which our results provide conceptual underpinnings. Findings from this research expand the cross-cultural understanding of SUDs and, in the long run, may enhance its treatment options.

Conceptions and practices of an integrative treatment for substance use disorders involving Amazonian medicine: traditional healers' perspectives.

OBJECTIVE: The harmful use of psychoactive substances represents one of today's largest public health problems. Yet, in spite of its global relevance, current treatment for substance use disorders (SUDs) is still not entirely successful. The purpose of this study was to investigate alternative treatments and conceptions from traditional Amazonian medicine adapted to SUDs. METHODS: We conducted semi-structured interviews with 13 practicing experts at a well-established addiction treatment center in the Peruvian Amazon and performed qualitative content analysis on the collected data. Main categories were deductively defined and corresponding subcategories inductively developed. RESULTS: Our findings revealed characteristic features and consequences, causes and antecedents, and treatment methods of SUDs as the main categories. Overall, concepts of disease etiology bore resemblance with contemporary biopsychosocial models of SUDs. The Amazonian therapeutic means however differed markedly from current Western ones. The main methods involved dietary retreats, healing ceremonies, and purging rituals. The integral application of Amazonian methods, as well as their traditional implementation according to prescribed ritual protocols, were emphasized by the experts as crucial for efficacy and safety of treatment delivery. CONCLUSION: We suggest further scientific attention to these therapies, including clinical studies, for which our results provide conceptual underpinnings. Findings from this research expand the cross-cultural understanding of SUDs and, in the long run, may enhance its treatment options.

Short-term effectiveness of inpatient cancer rehabilitation: A longitudinal controlled cohort study.

Background: Inpatient rehabilitation for cancer patients has been demonstrated to improve patients' health related quality of life (HRQoL) effectively. The purpose of this study was to compare changes in general health and HRQoL of cancer patients who were referred to inpatient rehabilitation (IR) with those in two control groups who underwent outpatient management either with advice for inpatient rehabilitation (A+) or without (A-). Methods: In this naturalistic, longitudinal, controlled cohort study, changes in general health and HRQoL were assessed at either discharge of acute hospital or start of rehabilitation (baseline) and at the follow-up 3 weeks later or end of rehabilitation. Outcome variables included general health and HRQoL assessed by the Short Form 36 (SF-36) and the Functional Assessment of Cancer Therapy (FACT), and fatigue (FACT-F), depression and anxiety by the Hospital Anxiety and Depression Scale (HADS). Changes on the scores were compared with bivariate and multivariate analyses using standardized mean differences (SMD). Results: IR patients (n=133) were on average older, reported lower HRQoL and health, and suffered more frequently from carcinoma than patients of the A+ (n=30) and the A- (n=82) groups. In the IR patients, pain, physical functioning, mental health, vitality, and fatigue improved significantly compared to the A+ controls. Compared to the A- group, the bivariate effects were lower but still statistically significant on many scales. Conclusions: IR showed moderate, statistically significant superior effects over outpatient management of cancer patients after acute treatment. Findings indicate that inpatient cancer rehabilitation can be recommended as an effective management after acute treatment. As today, referrals to inpatient rehabilitation for cancer patients are still not based on structured standardized procedures, the implementation of such screening is needed to address patients' needs and to render the potential for rehabilitation more reliable.

Lipid nanoemulsions and liposomes improve photodynamic treatment efficacy and tolerance in CAL-33 tumor bearing nude mice.

BACKGROUND: Photodynamic therapy (PDT) as promising alternative to conventional cancer treatments works by irradiation of a photosensitizer (PS) with light, which creates reactive oxygen species and singlet oxygen (1O2), that damage the tumor. However, a routine use is hindered by the PS's poor water solubility and extended cutaneous photosensitivity of patients after treatment. In our study we sought to overcome these limitations by encapsulation of the PS m-tetrahydroxyphenylchlorin (mTHPC) into a biocompatible nanoemulsion (Lipidots). RESULTS: In CAL-33 tumor bearing nude mice we compared the Lipidots to the existing liposomal mTHPC nanoformulation Foslip and the approved mTHPC formulation Foscan. We established biodistribution profiles via fluorescence measurements in vivo and high performance liquid chromatography (HPLC) analysis. All formulations accumulated in the tumors and we could determine the optimum treatment time point for each substance (8 h for mTHPC, 24 h for Foslip and 72 h for the Lipidots). We used two different light doses (10  and 20 J/cm2) and evaluated immediate PDT effects 48 h after treatment and long term effects 14 days later. We also analyzed tumors by histological analysis and performing reverse transcription real-time PCR with RNA extracts. Concerning tumor destruction Foslip was superior to Lipidots and Foscan while with regard to tolerance and side effects Lipidots were giving the best results. CONCLUSIONS: We could demonstrate in our study that nanoformulations are superior to the free PS mTHPC. The development of a potent nanoformulation is of major importance because the free PS is related to several issues such as poor bioavailability, solubility and increased photosensibility of patients. We could show in this study that Foslip is very potent in destroying the tumors itself. However, because the Lipidots' biocompatibility is outstanding and superior to the liposomes we plan to carry out further investigations and protocol optimization. Both nanoformulations show great potential to revolutionize PDT in the future.

Use of inpatient rehabilitation for cancer patients in Switzerland: who undergoes cancer rehabilitation?

QUESTION UNDER STUDY: Rehabilitation for cancer patients aims to reduce physical disability and mental distress resulting from the disease and its treatment. However, little is known about the use of cancer inpatient rehabilitation in Switzerland in relation to sociodemographic and medical characteristics. The main purpose of this study was to evaluate whether there are differences in sociodemographic and medical characteristics between patients who underwent inpatient rehabilitation (users) and those who did not (nonusers). METHODS: A total of 238 cancer patients from the University Hospital Zurich were included. The sociodemographic and medical characteristics of inpatient rehabilitation users were assessed and compared with those of nonusers. We analysed the differences between inpatient rehabilitation users and nonusers. RESULTS: Of the patients included, 101 (42.4%) used inpatient rehabilitation. They were less likely to be employed (p = 0.029), stayed longer in hospital (p <0.001), and were more likely to have semiprivate or private supplementary health insurance (p = 0.030) than nonusers. There were differences in cancer site (p = 0.001). Patients with tumours of the digestive organs or of the thoracic organs were more likely to use rehabilitation, whereas breast cancer patients were less likely to use it. Stratified analyses showed that male patients with semiprivate or private supplementary health insurance (p = 0.037), lower education (p = 0.039), and lower likelihood of employment (p = 0.051) were more likely to use rehabilitation. Women with an advanced tumour stage used inpatient rehabilitation more often (p = 0.012). CONCLUSIONS: Findings show the influence of duration of hospitalisation, insurance type, cancer site, employment status, and gender on the use of inpatient cancer rehabilitation. The results indicate the need of structured standardised procedures for medical referral to be implemented based on screening.

Veterinary photodynamic therapy: a review.

Whereas in human medicine photodynamic therapy represents a well-known and recognized treatment option for diverse indications, it is still little known and unfortunately not yet established treatment option for pets. Various photosensitizers and light sources have been used and clinical results have been published. The main indication is a frequently occurring skin tumor in cats: in situ carcinoma/squamous cell carcinoma, mainly found in not or only slightly pigmented areas of the head. For early stages of this tumor, promising results have been published, partly using new, selective drugs to decrease light sensitivity after systemic administration and to increase response rates. Other possible indications are urinary tract neoplasia of dogs and equine sarcoids, the latter representing very common tumors in horses where no effective treatment is known so far. This review article summarizes the role of photodynamic therapy in veterinary medicine.

Photodynamic mechanisms induced by a combination of hypericin and a chlorin based-photosensitizer in head and neck squamous cell carcinoma cells.

The aim of this study was to elucidate photodynamic therapy (PDT) effects mediated by hypericin and a liposomal meso-tetrahydroxyphenyl chlorin (mTHPC) derivative, with focus on their 1:1 mixture, on head and neck squamous cell carcinoma cell lines. Absorption, excitation and photobleaching were monitored using fluorescence spectrometry, showing the same spectral patterns for the mixture as measured for single photosensitizers. In the mixture mTHPC showed a prolonged photo-stability. Singlet oxygen yield for light-activated mTHPC was Φ(Δ) = 0.66, for hypericin Φ(Δ) = 0.25 and for the mixture Φ(Δ) = ~0.4. A linear increase of singlet oxygen yield for mTHPC and the mixture was found, whereas hypericin achieved saturation after 35 min. Reactive oxygen species fluorescence was only visible after hypericin and mixture-induced PDT. Cell viability was also more affected with these two treatment options under the selected conditions. Examination of death pathways showed that hypericin-mediated cell death was apoptotic, with mTHPC necrotic and the 1:1 mixture showed features of both. Changes in gene expression after PDT indicated strong up-regulation of selected heat-shock proteins. The application of photosensitizer mixtures with the features of reduced dark toxicity and combined apoptotic and necrotic cell death may be beneficial in clinical PDT. This will be the focus of our future investigations.

Effects of hypericin and a chlorin based photosensitizer alone or in combination in squamous cell carcinoma cells in the dark.

INTRODUCTION: The toxic influence of photosensitizers in the dark is poorly investigated. In our study we used the photosensitizers liposomal meso-tetrahydroxyphenyl chlorin derivative (Foslipos(®)) and hypericin as well as their 1:1 combination on two different head and neck squamous cell carcinoma (HNSCC) cell lines (UMB-SCC 745 and UMB-SCC 969). MATERIALS AND METHODS: We examined uptake, efflux and localization of the photosensitizers with confocal microscopy. Fluorescence quantification was measured with a micro-plate spectrometer. Special interest was given to effects on cell proliferation (BrdU proliferation assay), RNA quality (Bioanalyzer measurements) and DNA damage (comet assays) in the dark. RESULTS: Foslipos(®) uptake was linear over time and its efflux was not achieved even after 24 h while uptake of hypericin reached a plateau after 5 h and was almost eliminated after 24 h. Localization of Foslipos(®) was organelle-unspecific. Hypericin was found mainly at membranes and in trans-golgi network. Foslipos(®) treated cells showed cell toxicity for the highest concentration (10 µg/mL). In contrast, hypericin was toxic for all concentrations (10-0.6 µg/mL). The photosensitizer combination was non-toxic for all concentrations (10-0.6 µg/mL). No changes in RNA quality were monitored. Initial DNA damage was found only in hypericin treated UMB-SCC 745, which recovered after 3h. No significant DNA damage was found for UMB-SCC 969. CONCLUSION: Our data shows that the combinatorial application decrease photosensitizer toxicity, which can be advantageous in PDT treatments.

Uptake and fate of surface modified silica nanoparticles in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is currently the eighth leading cause of cancer death worldwide. The often severe side effects, functional impairments and unfavorable cosmetic outcome of conventional therapies for HNSCC have prompted the quest for novel treatment strategies, including the evaluation of nanotechnology to improve e.g. drug delivery and cancer imaging. Although silica nanoparticles hold great promise for biomedical applications, they have not yet been investigated in the context of HNSCC. In the present in-vitro study we thus analyzed the cytotoxicity, uptake and intracellular fate of 200-300 nm core-shell silica nanoparticles encapsulating fluorescent dye tris(bipyridine)ruthenium(II) dichloride with hydroxyl-, aminopropyl- or PEGylated surface modifications (Ru@SiO2-OH, Ru@SiO2-NH2, Ru@SiO2-PEG) in the human HNSCC cell line UMB-SCC 745. RESULTS: We found that at concentrations of 0.125 mg/ml, none of the nanoparticles used had a statistically significant effect on proliferation rates of UMB-SCC 745. Confocal and transmission electron microscopy showed an intracellular appearance of Ru@SiO2-OH and Ru@SiO2-NH2 within 30 min. They were internalized both as single nanoparticles (presumably via clathrin-coated pits) or in clusters and always localized to cytoplasmic membrane-bounded vesicles. Immunocytochemical co-localization studies indicated that only a fraction of these nanoparticles were transferred to early endosomes, while the majority accumulated in large organelles. Ru@SiO2-OH and Ru@SiO2-NH2 nanoparticles had never been observed to traffic to the lysosomal compartment and were rather propagated at cell division. Intracellular persistence of Ru@SiO2-OH and Ru@SiO2-NH2 was thus traceable over 5 cell passages, but did not result in apparent changes in cell morphology and vitality. In contrast to Ru@SiO2-OH and Ru@SiO2-NH2 uptake of Ru@SiO2-PEG was minimal even after 24 h. CONCLUSIONS: Our study is the first to provide evidence that silica-based nanoparticles may serve as useful tools for the development of novel treatment options in HNSCC. Their long intracellular persistence could be of advantage for e.g. chronic therapeutic modalities. However, their complex endocytotic pathways require further investigations.

Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in vitro.

BACKGROUND: Meso-tetra-hydroxyphenyl-chlorine (mTHPC) is among the most powerful photosensitizers available for photodynamic therapy (PDT). However, the mechanisms leading to cell death are poorly understood. We here focused on changes at DNA and RNA levels after treatment with the liposomal mTHPC derivative Foslipos in vitro. METHODS: After determination of darktoxicity, laser conditions and uptake kinetics, PC-3 prostate carcinoma cells were subjected to PDT with Foslipos, followed by assessment of cell numbers directly (TP0) or 1h (TP1), 2h (TP2), 5h (TP5) and 24h (TP24) after illumination. Nucleic acids had been extracted for evaluation of RNA amounts and integrity as well as for estimation of abasic sites as a measure for DNA damage. Furthermore, expression changes of 84 genes related to oxidative stress were investigated by quantitative polymerase chain reaction. RESULTS: Already at TP0, the number of dead cells was significantly higher after PDT versus controls and at TP24 more than 90% of cells had been destroyed. PDT resulted in a severe damage of both RNA and DNA. Gene expression analyses revealed an impact of PDT on pathways for oxidative and metabolic stress, heat shock, proliferation and carcinogenesis, growth arrest, inflammation, DNA repair and apoptosis signaling. CONCLUSIONS: Mechanisms of Foslipos-mediated PDT comprise a combination of acute and delayed lethal effects in PC-3 cells. The latter may include death processes initiated by nucleic acid damage, activation of stress and growth arrest genes in combination with a reduced capability to adequately cope with oxidative toxicity. Our results will help to better understand molecular photodynamic effects.

The application and challenges of clinical PD-PDT in the head and neck region: a short review.

We review current clinical applications of photodiagnosis (PD) and photodynamic therapy (PDT) in the head and neck field and highlight the actual status, problems, challenges as well as the future of this emerging treatment modality. In recent years literature presented input from many new developments and their applications. This is due to better awareness and developing knowledge about PD-PDT from the clinical staff, both nurses and doctors. But it is also a result of improved drug and hardware development such as lasers, LEDs and related optical devices. Current photo-medical applications in the head and neck region range from diagnostics, treatment of premalignant and malignant lesions, aesthetic and cosmetic applications to the ever expanding anti-microbial applications. Although treatment of premalignant and early malignant lesions of the oropharyngeal cavity have long been the favourite lesions to treat with PDT patients with unsalvageable tumors have also been responding remarkably well to PDT, adding significant quality of life. There is growing interest in anti-microbiological PDT and recent progress has shown that this application is able to significantly reduce the number or even eradicate specific microbial pathogens. During many surgical treatments better control of microbiological activity through PDT may lead to a better outcome. Despite progressive development in this field a few problems remain: prolonged phototoxicity, limited penetration of the photosensitizer and light, inadequate specificity, PDT-related pain as well as the lack of uniformly accepted protocols both for light application as well as photosensitizers. Recent studies have shown that PDT based pain can be separated from other forms of pain, offering hope that a specific management of pain will be possible. If PDT will become fully accepted by patients and doctors we must care about the negative factors such as pain and prolonged phototoxicity.

Hypericin and 5-aminolevulinic acid-induced protoporphyrin IX induce enhanced phototoxicity in human endometrial cancer cells with non-coherent white light.

BACKGROUND: The in vitro experiments described in this study were aimed at exploring a synergistic effect between 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) and hypericin. In a previous study, enhanced phototoxicity was observed in a patient during a clinical study on 5-ALA-based photodynamic tumor localization of breast cancer. This patient ingested a hypericin containing plant extract in parallel to orally applied 5-ALA. METHODS: Human endometrial cancer cells (HEC-1A) were treated with 0.5mM of 5-ALA and 60 nM of hypericin, either separately or combined. Colony formation was assessed after illumination of the cells with both red (635 nm) and white light (400-800 nm) at a dose of 2.5 J/cm(2). Porphyrin metabolites were quantified by HPLC in cells treated with photosensitizers without subsequent illumination. RESULTS: After white light illumination, cells treated with a combination of 5-ALA and hypericin had a significant reduction in colony formation compared with cells treated with 5-ALA only. No significantly enhanced toxicity was found with red light and the 5-ALA plus hypericin combination. In addition, cells treated with both 5-ALA and hypericin tended to produce more PpIX than cells treated with 5-ALA only. CONCLUSIONS: This study demonstrated that treatment of endometrial cancer cells with both 5-ALA and hypericin followed by illumination with white light induced a significantly higher phototoxicity as revealed by colony formation. This setting which generated an in vitro effect similar to the patient's situation, might be applied in the future as an affordable and effective photodynamic therapy (PDT) modality.

Photodynamic therapy of feline cutaneous squamous cell carcinoma using a newly developed liposomal photosensitizer: preliminary results concerning drug safety and efficacy.

BACKGROUND: Squamous cell carcinomas are common skin tumors in cats. We investigated photodynamic therapy (PDT) using a new liposomal photosensitizer as a minimally invasive, effective treatment that can be easily performed while achieving good cosmetic results. AIM: The goal of this study was to assess and describe possible toxicities using a liposomal formulation of the photosensitizer meta-(Tetrahydroxyphenyl)Chlorin (m-THPC) and investigate if favorable pharmacokinetics translate into favorable tumor response and control. ANIMALS: Eighteen client-owned cats with 20 spontaneous cutaneous squamous cell carcinomas were included in the study. METHODS: PDT was performed using a new, liposomal formulation of the photosensitizer. Toxicity, tumor response, and tumor control were evaluated retrospectively. RESULTS: No general adverse effects were observed in cats treated with the new liposomal formulation. Mild local toxicity such as erythema and edema were seen in 15% of the patients. All cats responded to therapy, with a complete response rate of 100%. The overall 1-year control rate was 75%. The tumor recurrence rate was 20% with a median time to recurrence of 172.25 +/-87.1) days. CONCLUSIONS AND CLINICAL IMPORTANCE: A new liposomal photosensitizer was successfully used for squamous cell carcinoma in cats and was well tolerated. There were no systemic adverse effects observed with the liposomal formulation. The favorable pharmacokinetics of the liposomal drug resulted in a favorable tumor response.

Novel flexible light diffuser and irradiation properties for photodynamic therapy.

Many current light diffusers for photodynamic therapy are inflexible, and the applied light dose is difficult to adjust during treatment, especially on complex body surfaces. A thin and flexible luminous textile is developed using plastic optical fibers as a light distributor. The textile diffuser is evaluated for flexibility, irradiance, brightness distribution, and temperature rise with a 652-nm laser set to 100 mW. The bending force of the textile diffuser resembles a defined optical film. On the textile surface, an average output power of 3.6+/-0.6 mWcm(2) is measured, corresponding to a transmission rate of 40+/-3.8% on an area of 11 cm(2). Aluminum backing enhances the irradiance to the face (treatment side). The measured brightness distribution seems to lie within a range similar to other photodynamic therapy (PDT) devices. A power setting of 100 mW increases the temperature of the textile diffuser surface of up to 27 degrees C, and 1 W raises the temperature above 40 degrees C. Results confirm that the flexible textile diffuser supplies suitable radiation for low fluence rate photodynamic therapy on an area of several cm(2).

Changes in vascularity and blood volume as a result of photodynamic therapy can be assessed with power Doppler ultrasonography.

BACKGROUND AND OBJECTIVES: One principal mechanism of photodynamic therapy (PDT) in tumors is destruction of tumor-associated vasculature. In the present study, the vascular effects of PDT in tumors were investigated with power Doppler ultrasonography. MATERIALS AND METHODS: Seven cutaneous squamous cell carcinomas in cats were treated. Tumors were examined via power Doppler ultrasonography before, 5 minutes, 1 hour, and 24 hours after PDT. Images were digitized for computer-aided assessment of vascularity and blood volume. RESULTS: Mean baseline tumor vascularity and blood volume were moderate. During PDT, a significant decrease in vascularity and blood volume was noted. Lowest values were found 24 hours after PDT. CONCLUSIONS: Power Doppler ultrasonography represents a non-invasive modality to successfully monitor the vascular effects and thus, treatment efficacy, of PDT.