Cytotoxic and Immunomodulatory Effects of Hypericin as a Photosensitizer in Photodynamic Therapy Used on Skin Cell Cultures.

Determination of the hypericin-photodynamic (HY-PDT) effect on the secretion of cytokines secreted by the skin cells, may be the basis for using the immunomodulatory effect of photodynamic action in the treatment of inflammatory skin diseases. The study aimed to evaluate the cytotoxic and immunomodulatory effects of hypericin (HY) in photodynamic therapy (PDT) performed in vitro on cultures of selected skin cell lines. The study used two human cell lines, primary dermal fibroblast (HDFa) and primary epidermal keratinocytes (HEKa). The MTT test was used to define the metabolic activity of treated cells. Cell supernatants subjected to sublethal PDT were assessed to determine the interleukins: IL-2, IL-8, IL-10, IL-11, IL-19, IL-22, and metalloproteinase 1 (MMP-1). The results confirm the destructive effect of HY-PDT and the immunomodulatory effects of sublethal doses on the selected skin cells, depending on the concentration of HY and the light doses. No statistically significant differences were noted in IL-2 and IL-10 concentration after HY-PDT for HEKa and HDFa lines. After using HY-PDT, the concentration of IL-8, MMP-1, IL-22, and IL-11 significantly decreased in the HEKa line. Moreover, the concentration of IL-19 and MMP-1 significantly decreased in the HDFa line. The concentration of IL-11 in the HDFa line after using only the HY, without the light, increased but decreased after HY-PDT. Our experiment confirmed that HY-PDT has not only a cytotoxic effect but, used in sublethal doses, also presents immunomodulatory properties. These may be an advantage of HY-PDT when used in the treatment of persistent skin inflammation, connected with the release of pro-inflammatory cytokines resistant to conventional treatment methods.

Potential Aspects of the Use of Cytokines in Atopic Dermatitis.

Atopic dermatitis (AD) is an abnormal inflammatory response in the skin to food, environmental IgE, or non-IgE allergens. This disease belongs to a group of inflammatory diseases that affect both children and adults. In highly developed countries, AD is diagnosed twice as often in children than in adults, which may possibly be connected to increased urbanization. The immune system's pathomechanisms of AD involve humoral mechanisms with IgE, cellular T lymphocytes, dendritic cells occurring in the dermis, Langerhans cells occurring in the epidermis, and other cells infiltrating the site of inflammation (eosinophils, macrophages, mast cells, neutrophils, and basophils). Cytokines are small proteins that affect the interaction and communication between cells. This review characterizes cytokines and potential aspects of the treatment of atopic dermatitis, as well as new strategies that are currently being developed, including targeting cytokines and their receptors.

Current Photodynamic Therapy for Glioma Treatment: An Update.

Research on the development of photodynamic therapy for the treatment of brain tumors has shown promise in the treatment of this highly aggressive form of brain cancer. Analysis of both in vivo studies and clinical studies shows that photodynamic therapy can provide significant benefits, such as an improved median rate of survival. The use of photodynamic therapy is characterized by relatively few side effects, which is a significant advantage compared to conventional treatment methods such as often-used brain tumor surgery, advanced radiotherapy, and classic chemotherapy. Continued research in this area could bring significant advances, influencing future standards of treatment for this difficult and deadly disease.

Photodynamic Therapy of Breast Cancer in Animal Models and Their Potential Use in Clinical Trials-Role of the Photosensitizers: A Review.

In this article, we reviewed the use of photodynamic therapy (PDT) for breast cancer (BC) in animal models. These in vivo models imitate the cancer disease progression, aid diagnosis, as well as create opportunities to assess treatment during the approval process for the new drug. BC ranks first among women's cancers. Nowadays, there are many diagnostic methods and therapy options for BC but the majority of them have severe side effects. This article discusses the advantages and some disadvantages of the use of small and large animals used for BC models. A literature review showed that the majority of studies have used large animal models, and recently there has been more interest in developing BC in small animal models. BC cell lines such as MCF-7, BT-474, MDA-MB-231, and 4T1 are commercially available for two-dimensional and three-dimensional in vitro cell cultures and subcutaneous models. The purpose of this article is to discuss the performance of PDT in animal models and its further clinical implications. PDT is known to be a non-invasive therapy, which uses monochromatic light and energy to excite photosensitizers (PSs) for the generation of reactive oxygen species as the required factors. Herein, we discuss the use of five photosensitizers in BC models such as chlorin e6 (Ce6), methylene blue, indocyanine green, 5-aminolevulinic acid, and meta-tetra(hydroxyphenyl)chlorin. The database PubMed and Scopus were searched for keywords: 'photodynamic therapy', 'breast cancer', 'animal model', 'clinical studies', and 'photosensitizer(s)'. The PDT search results in animal experiments and its effect on a living organism indicate the possibility of its application in clinical trials on women with local and disseminated BC. The availability and accessibility of small and large BC animal models enable the progress and trial of cancer drugs for innovative technologies and new diagnostics and treatments.

An Analysis of the Effects of In Vitro Photodynamic Therapy on Prostate Cancer Tissue by Histopathological Examination and Magnetic Resonance Imaging.

Prostate cancer can significantly shorten the lifetime of a patient, even if he is diagnosed at an early stage. The development of minimally-invasive focal therapies such as photodynamic therapy to reduce the number of neoplastic cells while sparing delicate structures is extremely advantageous for treating prostate cancer. This study investigates the effect of photodynamic therapy performed in prostate tissue samples in vitro, using quantitative magnetic resonance imaging and histopathological analysis. Prostate tissue samples were treated with oxygenated solutions of Rose Bengal (RB) or protoporphyrin IX disodium salt (PpIX), illuminated with visible light, and then analyzed for changes in morphology by microscopy and by measurement of spin-lattice and spin-spin relaxation times at 1.5 Tesla. In the treated prostate tissue samples, histopathological images revealed chromatin condensation and swelling of the stroma, and in some cases, thrombotic necrosis and swelling of the stroma accompanied by pyknotic nuclei occurred. Several samples had protein fragments in the stroma. Magnetic resonance imaging of the treated prostate tissue samples revealed differences in the spin-lattice and spin-spin relaxation times prior to and post photodynamic action.

Immunological differences between atopic dermatitis, psoriasis, and their combination in adult patients.

OBJECTIVES: The simultaneous occurrence of psoriasis (PS) dominated by Th1 lymphocytes and atopic dermatitis (AD) driven by Th2 cells is rare. This study analyzed a group of adult patients with concomitant PS and AD (ADPS) and compared the cytokine profiles of these patients with those of subjects with homogenous PS or AD and healthy controls. MATERIALS AND METHODS: All patients underwent dermatological examinations, including assessment of Scoring Atopic dermatitis (SCORAD) index and Psoriasis Area Severity Index (PASI) scores, TNF-α, IFN-γ, Il-2, Il-4, Il-5, Il-6, Il-8, Il-12, I-17A, Il-18, Il-22, Il-33, and T. There were 39 patients with a diagnosis of ADPS, 45 patients with PS, 47 patients with AD, and 42 healthy controls. RESULTS: Patients with ADPS were mainly men with a proportional distribution of skin lesion areas. Significant differences were observed in the concentration of Il-17A between patients with ADPS and those with AD or PS and controls, which were as follows: 16.1 ± 5.4, 5.8 ± 2.1, 5.0 ± 3.1, and 3.3 ± 1.8 pg/mL, respectively. In conclusion, AD and PS might coexist as a combination disease. The role of T helper 17 cells may be more essential than previously thought.

Photodynamic Therapy-Adjunctive Therapy in the Treatment of Prostate Cancer.

The alarming increase in the number of advanced-stage prostate cancer cases with poor prognosis has led to a search for innovative methods of treatment. In response to the need for implementation of new and innovative methods of cancer tissue therapy, we studied photodynamic action in excised prostate tissue in vitro as a model for photodynamic therapy. To ascertain the effects of photodynamic action in prostate tissue, Rose Bengal (0.01 to 0.05 mM) was used as a photosensitizer in the presence of oxygen and light to generate singlet oxygen in tissues in vitro. Five preset concentrations of Rose Bengal were chosen and injected into prostate tissue samples (60 samples with 12 replications for each RB concentration) that were subsequently exposed to 532 nm light. The effects of irradiation of the Rose Bengal infused tissue samples were determined by histopathological analysis. Histopathological examination of prostate samples subjected to photodynamic action revealed numerous changes in the morphology of the neoplastic cells and the surrounding tissues. We conclude that the morphological changes observed in the prostate cancer tissues were a result of the photogeneration of cytotoxic singlet oxygen. The tissue damage observed post photodynamic action offers an incentive for continued in vitro investigations and future in vivo clinical trials.

The Immunological and Allergen Profiles of Patients with Atopic Dermatitis or Psoriasis.

Background and objectives: Atopic dermatitis (AD) and psoriasis (PS) are systemic inflammatory diseases with complex and distinct immune mechanisms. That the same factors may aggravate both diseases cannot be ruled out. The aim of this study was to assess the potential differences between a sensitization to inhaled allergens and the immunological profiles of patients diagnosed with AD and PS in comparison with healthy controls. Materials and methods: A total of 139 patients with AD, 115 with PS, and 142 controls were included in the prospective study. Patients were eligible if they were diagnosed with mild to severe AD or PS and between 18 and 65 years of age. In all the participants, the serum concentrations of specific IgE (sIgE) for common inhaled allergens were measured. In all the subjects, the cytokine serum blood profiles for TNF-α, IFN-γ, Il-2, Il-4, Il-5, Il-6, Il-8, Il-12, Il-17, Il-18, Il-22, and Il-24 were measured via an ELISA. Results: The patients with AD had positive sIgE results more frequently than the patients with PS and the controls (113 vs. 36 vs. 21, respectively). A sensitization to mites was dominant in the patients with AD (p < 0.05), and a sensitization to Aspergillus was dominant in the patients with PS (p < 0.05). The patients with multiple allergies to inhaled allergens had a lower risk of developing PS (OR = 0.65; 95% CI: 0.43−0.86) but a greater risk of severe AD (OR = 3.77; 95% CI: 3.25−3.96). The mean concentrations of the most tested cytokines were comparable in the patients with AD and PS. However, high serum concentrations of Il-4, Il-5, and Il-6 were only dominant in the AD group. There were no relationships between the increased serum concentrations of individual cytokines and allergies to the individually examined allergens. Conclusion: Inhalation-dependent IgE sensitizations were prevalent in the AD patients but were also possible in the PS patients; they were often without clinical manifestations in the latter group. The investigated cytokine profiles indicated their high convergence in the studied patients and confirmed the active inflammatory nature of AD and PS.

Colonoscopy: Preparation and Potential Complications.

Colonoscopy is a fairly common test that serves both diagnostic and therapeutic purposes. It has been considered the gold standard in colorectal cancer screening for several years. Due to the nature of the examination, various types of complications may occur. The purpose of this analysis is to describe the various complications related to the period of preparation for colonoscopy among hospitalized patients, including life-threatening ones, in order to know how to avoid complications while preparing for a colonoscopy. We analyzed the nursing and medical reports of 9962 patients who were prepared for colonoscopy between 2005 and 2016. The frequency of various side effects associated with intensive bowel cleansing prior to colonoscopy was assessed. In justified cases, additional medical data were collected from patients, their families or from other doctors providing advice to patients after complications. Out of 9962 patients prepared for colonoscopy, 180 procedures were discontinued due to complications and side effects, and in these cases no colonoscopy was performed. The most common complications were: vomiting; epistaxis; loss of consciousness with head injury; abdominal pain; acute diarrhea; symptoms of choking; heart rhythm disturbances; dyspnea; fractures of limbs and hands; acute coronary syndrome; hypotension; hypertension; cerebral ischemia; severe blood glucose fluctuations; increased muscle contraction and allergic reactions. In addition to the documentation of our own research, several works of other research groups were also analyzed. Currently, the literature does not provide data on the frequency and type of complications in the preparation period for colonoscopy. The advantage of our work is the awareness of the possibility of serious complications and postulating the necessary identification of threats. Individualization of the recommended procedures and increased supervision of patients undergoing bowel cleansing procedure, we hope, will reduce the occurrence of complications and side effects.

The role of photodynamic therapy in breast cancer - A review of in vitro research.

Breast cancer is the most common cancer affecting women and the incidence of occurrence is increasing. Currently, there are many methods of detecting and treating breast cancer. Some treatments have a number of side effects. Photodynamic therapy (PDT) is a minimally invasive method of treatment which uses monochromatic light of low to medium energy to excite previously applied photosensitizers (PS) for ROS production. The purpose of this article is to present a general overview of the use of PDT in in vitro studies of various cancer cell lines. A literature search for articles corresponding to the topic of this review was performed using the PubMed and Scopus databases using the following keywords: 'photodynamic therapy', 'breast cancer', and 'photosensitizer(s).' Much of the reviewed literature is based on evaluations of the cytotoxic potential of various PSs, particularly against the MCF-7 cell line, and enhancement of PDT potential with nanotechnology. Research on photodynamic effects in vitro may be helpful in the pre-clinical search for optimal methods for in vivo clinical treatment.