an-in-vitro-approach-to-photodynamic-therapy

An <em>In Vitro</em> Approach to Photodynamic Therapy

Photodynamic therapy (PDT) is a medical procedure that involves incubation of an exogenously applied photosensitizer (PS) followed by visible light ...

University of California, Davis

Sacramento VA Medical Center

State University of New York, Downstate Medical Center

The study of free radicals is particularly relevant in the context of human skin carcinogenesis and photoaging because of these oxidants' ability to induce DNA mutations and produce lipid peroxidation byproducts, including 4-hydroxy-2-nonenal (HNE). Therefore, it is important to identify and evaluate agents with the ability to modulate intracellular free radicals and HNE. The purpose of this research is to investigate the ability of antioxidants green tea polyphenols (GTPs) and caffeine, alone and in combination, to modulate the hydrogen peroxide (H2O2)-induced upregulation of reactive oxygen species (ROS) free radicals and HNE in normal human skin fibroblast WS-1 cells in vitro. GTPs and caffeine were selected for evaluation because these compounds have demonstrated antioxidative properties in various skin models. Furthermore, GTPs and caffeine share a close natural botanical association as caffeine is present in green tea, as well. Hydrogen peroxide is a well-known generator of free radicals that is produced during endogenous and UV-induced oxidation processes in human skin and was used to upregulate ROS and HNE in normal human fibroblast WS-1 cells. Using a flow cytometry-based assay, the results demonstrate that at 0.001% concentration, green tea polyphenols alone, and in combination with 0.1 mM caffeine, inhibited the upregulation of H2O2-generated free radicals and HNE in human skin fibroblasts in vitro. Caffeine alone demonstrated limited anti-oxidant properties.

Complementary antioxidant function of caffeine and green tea polyphenols in normal human skin fibroblasts.

Low level light therapy has garnered significant interest within the past decade. The exact molecular mechanisms of how red and near infrared light result in physiologic modulation are not fully understood. Heme moieties and copper within cells are red and near infrared light photoreceptors that induce the mitochondrial respiratory chain component cytochrome C oxidase, resulting in a cascade linked to cytoprotection and cellular metabolism. The copper centers in cytochrome C oxidase have a broad absorption range that peaks around 830 nm. Several in vitro and in vivo animal and human models exist that have demonstrated the benefits of red light and near infrared light for various conditions. Clinical applications for low level light therapy are varied. One study in particular demonstrated improved durable functional outcomes status post-stroke in patients treated with near infrared low level light therapy compared to sham treatment [1]. Despite previous data suggesting the beneficial effect in treating multiple conditions, including stroke, with low level light therapy, limited data exists that measures transmission in a human model.

Transcranial red and near infrared light transmission in a cadaveric model.

HIV facial lipoatrophy (FLA) is characterized by facial volume loss. HIV FLA affects the facial contours of the cheeks, temples, and orbits, and is associated with social stigma. Although new highly active antiretroviral therapy medications are associated with less severe FLA, the prevalence of HIV FLA among treated individuals exceeds 50%. The goal of our systematic review is to examine published clinical studies involving the use of filler agents for aesthetic treatment of HIV FLA and to provide evidence-based recommendations based on published efficacy and safety data. A systematic review of the published literature was performed on July 1, 2015, on filler agents for aesthetic treatment of HIV FLA. Based on published studies, poly-L-lactic acid is the only filler agent with grade of recommendation: B. Other reviewed filler agents received grade of recommendation: C or D. Poly-L-lactic acid may be best for treatment over temples and cheeks, whereas calcium hydroxylapatite, with a Food and Drug Administration indication of subdermal implantation, may be best used deeply over bone for focal enhancement. Additional long-term randomized controlled trials are necessary to elucidate the advantages and disadvantages of fillers that have different biophysical properties, in conjunction with cost-effectiveness analysis, for treatment of HIV FLA. 

A systematic review of filler agents for aesthetic treatment of HIV facial lipoatrophy (FLA).

Actinic keratoses (AKs) are generally accepted as common precursor lesions to invasive squamous cell carcinoma. Photodynamic therapy (PDT) is a common, in-office, field therapy modality used in the treatment of AKs. Clinical and laboratory observations have demonstrated that temperature modulation can affect PDT efficacy.

Temperature-dependent impact of thermal aminolaevulinic acid photodynamic therapy on apoptosis and reactive oxygen species generation in human dermal fibroblasts.

Lack of evidence that bedbugs transmit pathogens to humans.

The global population of bed bugs (Cimex lectularius and Cimex hemipterus, family Cimicidae) has undergone a significant resurgence since the late 1990s. This is likely due to an increase in global travel, trade, and the number of insecticide-resistant bed bugs. The global bed bug population is estimated to be increasing by 100-500 % annually. The worldwide spread of bed bugs is concerning, because they are a significant socioeconomic burden and a major concern to public health. According to the United States Environmental Protection Agency, bed bugs are "a pest of significant health importance." Additionally, 68 % of U.S. pest professionals reported that bed bugs are the most challenging pest to treat. Upwards of 45 disease pathogens have been reported in bed bugs. Recent studies report that bed bugs may be competent vectors for pathogens, such as Bartonella quintana and Trypanosoma cruzi. However, public health reports have thus far failed to produce evidence that major infectious disease outbreaks have been associated with bed bugs. Since many disease pathogens have previously been reported in bed bugs and the worldwide bed bug population is now drastically increasing, it stands to reason to wonder if bed bugs might transmit human pathogens. This review includes a literature search on recently published clinical and laboratory studies (1990-2016) investigating bed bugs as potential vectors of infectious disease, and reports the significant findings and limitations of the reviewed studies. To date, no published study has demonstrated a causal relationship between bed bugs and infectious disease transmission in humans. Also, we present and propose to expand on previous hypotheses as to why bed bugs do not transmit human pathogens. Bed bugs may contain "neutralizing factors" that attenuate pathogen virulence and, thereby, decrease the ability of bed bugs to transmit infectious disease. 

Bed bugs and possible transmission of human pathogens: a systematic review.

Skin fibrosis is involved in a variety of pathologic conditions ranging from scar formation secondary to surgery or trauma to immune-mediated processes. Skin fibrosis is a significant international health problem with an estimated incidence of greater than 100 million people affected per year worldwide with few effective treatment options available. Preliminary in vitro data generated by our research group suggests that red light can function as a stand-alone treatment for skin fibrosis. To our knowledge, no prior clinical trials have been performed to determine the safety of high-fluence (dose) light-emitting diode-red light (LED-RL) phototherapy. The goal of this study is to evaluate the safety of LED-RL fluences from 160 J/cm(2) up to 640 J/cm(2) in healthy subjects.

A single-blind, dose escalation, phase I study of high-fluence light-emitting diode-red light (LED-RL) on human skin: study protocol for a randomized controlled trial.

Invasive cutaneous melanoma is a growing health concern. Although surgical excision can effectively treat in situ tumors, use for metastatic melanoma is limited. Laser and light-based therapies may be a valuable palliative treatment option for patients with stage III and stage IV cutaneous metastatic melanoma. Our goal is to review the published literature and provide evidence-based recommendations on laser and light-based palliative therapies for metastatic melanoma. A search of the databases Pubmed, EMBASE, Web of Science, and CINAHL was performed on March 10, 2016. Key search terms were related to melanoma, laser, and light-based modalities. Our search initially identified 13,923 articles and 27 original articles met inclusion criteria for our review. Grade of recommendation: C for non-fractionated carbon dioxide laser, Grade of recommendation: D for fractionated carbon dioxide laser, ruby laser, neodymium laser, near-infrared diode laser, and photodynamic therapy. Non-fractionated carbon dioxide laser had the best palliative efficacy of the reviewed laser and light-based therapies, while other treatment modalities may have potential as adjunctive therapy to standard of care.

Article	Year
Complementary antioxidant function of caffeine and green tea polyphenols in normal human skin fibroblasts. Journal of drugs in dermatology : JDD\| PubMed ID: 21720657	2011
Transcranial red and near infrared light transmission in a cadaveric model. PloS one\| PubMed ID: 23077622	2012
A systematic review of filler agents for aesthetic treatment of HIV facial lipoatrophy (FLA). Journal of the American Academy of Dermatology\| PubMed ID: 26481056	2015
Temperature-dependent impact of thermal aminolaevulinic acid photodynamic therapy on apoptosis and reactive oxygen species generation in human dermal fibroblasts. The British journal of dermatology\| PubMed ID: 26931503	2016
Lack of evidence that bedbugs transmit pathogens to humans. Journal of the American Academy of Dermatology\| PubMed ID: 27185431	2016
Bed bugs and possible transmission of human pathogens: a systematic review. Archives of dermatological research\| PubMed ID: 27295087	2016
A single-blind, dose escalation, phase I study of high-fluence light-emitting diode-red light (LED-RL) on human skin: study protocol for a randomized controlled trial. Trials\| PubMed ID: 27484782	2016
Laser and light-based therapy for cutaneous and soft-tissue metastases of malignant melanoma: a systematic review. Archives of dermatological research\| PubMed ID: 28314913	2017

Jared Jagdeo

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