Photodynamic therapy and adapalene in dermatology: synergistic effects in immortal human keratinocytes

We compared the effects of methyl levulinate (MAL)/photodynamic therapy (PDT) and adapalene, evaluated singly, versus combination therapy on HaCaT keratinocytes. Our aim was to determine whether the additive/synergistic outcomes of combination treatment were such that doses of each component could be reduced without affecting treatment efficacy. The analysis of data from specific PDT/adapalene combinations results indicating effects ranging from additive to clearly synergistic. We first evaluated the effects on cell viability, cell cycle and protein expression profiles of each individual treatment, then we tried to understand the reasons and the mechanisms whereby cells under combined treatment move more efficiently to death. Although we observed therapeutic strengthening by increasing either drug doses or light fluences, reinforcement was particularly marked in combinations in which PDT was predominant. Thus, if PDT is appropriately tuned, the dose of the drug can be reduced without compromising the therapeutic response. As both photodynamic therapy and adapalene have been and are therapeutic approaches to treat different dermatological pathologies such as acne, actinic keratosis etc., our data suggest that the adapalene-PDT combination may have important spin-off in clinical dermatology as a strategy to tackle this nasty condition

Fohotodermatoses and Skin Cancer

Preface Skin cancer is one of the most common types of tumors in Western countries. In the United States only, more than one million people are diagnosed with skin cancer each year. Although the absolute number of skin cancer patients is increasing, the death is inversely decreasing, due to the early detection and treatment. Basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma are three major types of skin cancer. BCC and SCC rarely have metastasis; over 95 percent BCC and SCC patients can be cured. Melanoma only accounts for a small percentage of skin cancer, but it causes 75 percent death of this disease. In this book, we invited a number of experts to present their latest accomplishments on skin cancer research. Although the topics are varied, the authors did great work to help readers better understand skin cancer and learn the knowledge to prevent this disease. There are three sections in this book, starting with etiology. Ultraviolet (UV) light exposure is overwhelmingly believed to be the most frequent cause of skin cancer. In this section, the association between UV and photodermatoses, as well as skin cancer is discussed. Desmosomal cadherins are important molecules in tumor cell adhesion and invasion, and their important roles in BCC are also presented in details. In the diagnosis and treatment section, a few new methodologies are described. As known, the outcome of malignant melanoma greatly depends on the thickness of the tumor at the time of treatment. Accurate determination of melanoma lateral and depth of margins using non-invasive imaging technologies is of importance when making sound decisions for treatment and evaluating a five year survival rate. A novel method named differential scanning calorimetry is capable of predicting metastasis of melanoma patients by monitoring the temperature changes of plasma. Electronic miniature X-ray brachytherapy is introduced as a new technology to treat nonmelanoms skin cancer. Although its potential has not yet been fully realized, chemoprevention, in terms of using chemical agents that naturally occur in foods, or are administered as pharmaceuticals to retard or reverse the process of carcinogenesis and progression of cancer, has been recognized to benefit individuals with precancerous lesions or genetic susceptibilities to cancer. In the prevention section, two chapters summarized the most recognized dietary phytochemicals and their potential application in skin cancer. X Preface This book would not have been possible without the contributions of all authors and the support from the publisher. Especially, I will convey my sincere appreciation to Ms. Tajana Jevtic, who has always been available and supportive of me to accomplish this project. Yaguang Xi, M.D., Ph.D. Assistant Professor of Oncologic Sciences, University of South Alabama, US

Taurisolo®, a novel nutraceutical formulation based on grape pomace polyphenols, as a tool for the management of oxidative stress- and atherosclerosis-related diseases

The present PhD thesis summarises evidence from all the studies performed during the three-year PhD Course in Pharmaceutical Science, at the NutraPharmaLabs of the Department of Pharmacy, University of Naples Federico II, having as mail goal the evaluation of the nutraceutical potential of Taurisolo®, a novel nutraceutical formulation based on grape pomace polyphenolic extract. In particular, the present PhD project has been conducted in cooperation with both industrial (MBMed Company, Turin, Italy) and foreign University (University of Balearic Islands, Palma del Mallorca, Spain) partners. The entire project was planned with a dual view: design and formulate a novel nutraceutical product starting from re-use of agri-food by-products, following all the steps required by the nutraceutical industry, including preventive characterisation of the chemical profile, evaluation of bioaccessibility and bioavailability of bioactive compounds, optimisation of the productive processes and their translation in large-scale, marketing techniques evaluation of the biological activities, following a pharmacological approach including pre-clinical and clinical studies. More specifically, results herein presented refer to all the studies performed in our Labs and in collaboration with other Departments and Research Institutes. They include in vitro studies, animal-based studies and randomised clinical trials conducted on both healthy and pathological subjects. Further studies are still ongoing with the aim to clarify the main putative mechanisms of action for the cardioprotective role played by Taurisolo® or to provide novel insight regarding the observed clinical results. In summary, data so far collected allow concluding that Taurisolo® is a useful and valid polyphenol-based formulation with promising nutraceutical properties in reduction of risk factors related to both development and progression of cardiovascular diseases, in particular atherosclerosis

OMEGA-3 fatty acids contribute to plaque stability differentially affecting the release of matrix metalloproteinases and tissue inhibitors of metalloproteinases by human monocytes/macrophages in culture

Objectives. High intakes of omega-3 fatty acids has been associated with protection from plaque rupture. The secretion of metalloproteinases (MMPs) by macrophages is believed to play a key role in matrix degradation underlying plaque instability. Conversely, tissue inhibitors of metalloproteinases (TIMPs) would contribute to plaque stability. We therefore studied the effects of omega-3 fatty acids on the release and activity of MMPs and TIMPs in cultured human monocytoid cells. Methods. Human U937 monocytoid cells were differentiated into macrophages by exposure for 24 h to 30 ng/mL phorbol myristate acetate (PMA) and 10 ng/mL tumor necrosis factor(TNF)-α. Both monocytes and macrophages were treated for 48 h with the DHA (22:6 n-3) or EPA (22:6 n-3) (25-100 μmol/L) before stimulation for 24 h with 10 ng/ml TNFα. Cell supernatates were used to test the release of gelatinase A (MMP-2), gelatinase-B (MMP-9), collagenase-1 (MMP-1), TIMP-1 and TIMP-2, by ELISAs, and total gelatinase and anti-gelatinase activities by zymography and retro-zymography techniques, respectively. Results. The long term exposure to 50 μmol/L EPA and DHA, but not to arachidonic acid (20:4 n-6), significantly reduced MMP-9 protein release without affecting the release of MMP-1, MMP-2 and TIMP-1. Conversely, TIMP-2 protein release was significantly increased by EPA and DHA (Table). Zymography for MMP-9 and retro-zymography for TIMP-1 and -2 reproduced the same results. Conclusions. The long term exposure to omega-3 fatty acids significantly reduces MMP-9 release without affecting the release of MMP-1 and -2. This effect, associated with the increase of TIMP-2 protein production and activity, may contribute to explaining the plaque-stabilizing effect by omega-3 fatty acid observed in humans

Role of nutrition and adherence to the mediterranean diet in the multidisciplinary approach of hidradenitis suppurativa: Evaluation of nutritional status and its association with severity of disease

Hidradenitis suppurativa (HS) is a chronic, inflammatory and debilitating skin disorder. The exacerbating factors of HS include nutrition and adiposity. We aimed to investigate the relationships between body composition and the adherence to the Mediterranean diet (MD) with the severity of HS in a sample of naive-treatment patients with HS. In this case⁻controlled, cross-sectional study, we enrolled 41 HS patients and 41 control subjects. Body composition was evaluated by a bioelectrical impedance analysis (BIA) phase-sensitive system. PREvención con DIeta MEDiterránea (PREDIMED) and the 7-day food records were used to evaluate the degree of adherence to the MD and dietary pattern, respectively. The clinical severity was assessed by using the Sartorius HS score. HS patients had a worse body composition, in particular lower phase angle (PhA) (p < 0.001), and a lower adherence to the MD than controls, in spite of no differences in energy intake between the two groups. The receiver operator characteristic (ROC) analysis showing a value of PhA of ≤ 5.7 and a PREDIMED score of ≤ 5.0 identified HS patients with the highest clinical severity of the disease. After adjusting for sex, age, body mass index (BMI), and total energy intake, the HS Sartorius score maintained negative correlations with PhA (p < 0.001), PREDIMED score, and n-3 polyunsaturated fatty acids (p = 0.005). The results of the multivariate analysis showed PhA and PREDIMED score were the major determinants of HS Sartorius score, explaining 82.0% and 30.4% of its variability, respectively (p < 0.001). Novel associations were demonstrated between PhA and the degree of adherence to the MD with the HS severity. PhA and PREDIMED score might represent possible markers of severity of HS in a clinical setting

Aggiornamenti epidemiologici sull’echinococcosi animale in Italia

Cystic Echinococcosis (CE) is one of the most widespread parasitoses in the Mediterranean Region (MR). This is due to various factors, the most important being the close association between man, sheep and dogs in areas where open farming is practised. Although this disease has been known for several years and many studies have been carried out, nowadays in Italy there are no complete epidemiological data on its diffusion and distribution. The available data show that CE is mainly diffused in those districts where the sheep-dog cycle can be perpetuated, such as central and southern Italy, and the islands. Furthermore, no data are available on biomolecular characterisation of the strains of Echinococcus granulosus in Italy, apart form those in Sardinia, where the G1 (sheep-dog) and G7 (pig-dog) strains were recently isolated. One of the reasons why CE is a problem with no easy solution is undoubtedly the difficulty of making a certain diagnosis in the dog, the principal definitive host of E. granulosus

S100B Protein Stimulates Proliferation and Angiogenic Mediators Release through RAGE/pAkt/mTOR Pathway in Human Colon Adenocarcinoma Caco-2 Cells

Chronic inflammation and angiogenesis are associated with colonic carcinogenesis. Enteric glia-derived S100B protein has been proposed as an "ideal bridge", linking colonic inflammation and cancer, given its dual ability to up-regulate nuclear factor-kappaB (NF-κB) transcription via receptor for advanced glycation end products (RAGE) signaling and to sequestrate wild type pro-apoptotic wild type (wt)p53. However, its pro-angiogenic effects on cancer cells are still uninvestigated. To this aim, we evaluated the effect of exogenous S100B (0.05-5 µM) protein alone or in the presence of S100B blocking monoclonal antibody (mAb) (1:105-1:104v/v diluted) on (1) cultured Caco-2 cells proliferation, migration and invasiveness in vitro, respectively by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT)-formazan, wound healing and matrigel invasion assays and (2) its effect on the release of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF) by ELISA and immunofluorescence analyses. The effect of S100B alone or in the presence of S100BmAb was then investigated on RAGE/pAkt/mammalian target of rapamycin (mTOR) signaling pathway by immunoblot analysis. Our results showed that S100B markedly increases proliferation and invasiveness of Caco-2 cells, through the release of pro-angiogenic VEGF and NO paralleled to a significant decrease of wtp53 expression mediated by RAGE-p38 mitogen-activated protein kinase (MAPK)/pAkt-mTOR and hypoxia-inducible factor 1-alpha (HIF1α) pathways. Such effects were counteracted by S100BmAb, indicating that S100B targeting is a potential approach to inhibit colon carcinoma proliferation and angiogenesis

Quality assessment of medical record as a tool for clinical risk management: a three year experience of a teaching hospital Policlinico Umberto I, Rome

Introduction: The medical record was defined by the Italian Ministry of Health in 1992 as "the information tool designed to record all relevant demographic and clinical information on a patient during a single hospitalization episode". Retrospective analysis of medical records is a tool for selecting direct and indirect indicators of critical issues (organizational, management and technical). The project’s aim being the promotion of an evaluation and self-evaluation process of medical records as a Clinical Risk Management tool to improve the quality of care within hospitals. Methods: The Authors have retrospectively analysed, using a validated grid, 1,184 medical records of patients admitted to the Teaching Hospital “Umberto I” in Rome during a three-year period (2013-2015). Statistical analysis was performed using SPSS for Windows © 19:00. All duly filled out criteria (92) were examined. “Strengths” and "Weaknesses" were identified through data analysis and Best and Bad Practice were identified based on established criteria. Conclusion: The data analysis showed marked improvements (statistically significant) in the quality of evaluated clinical documentation and indirectly upon behaviour. However, when examining some sub-criteria, critical issues emerge; these could be subject to future further corrective action

Multiplex PCR to detect bacteriophages from natural whey cultures of buffalo milk and characterisation of two phages active against Lactococcus lactis, фApr-1 and фApr-2

This work investigated bacteriophage induced starter failures in artisanal buffalo Mozzarella production plants in Southern Italy. Two hundred and ten samples of whey starter cultures were screened for bacteriophage infection. Multiplex polymerase chain reaction (PCR) revealed phage infection in 28.56% of samples, all showing acidification problems during cheese making. Based on DNA sequences, bacteriophages for Lactococcus lactis (L. lactis), Lactobacillus delbruekii (L. delbruekii) and Streptococcus thermophilus (S. thermophilus) were detected. Two phages active against L.  lactis, фApr-1 and фApr-2, were isolated and characterised. The genomes, approximately 31.4 kb and 31 kb for фApr-1 and фApr-2 respectively, consisted of double-stranded linear DNA with pac-type system. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed one major structural protein of approximately 32.5 kDa and several minor proteins. This is the first report of phage isolation in buffalo milk and of the use of multiplex PCR to screen and study the diversity of phages against Lactic Acid Bacteria (LAB) strains in artisanal Water Buffalo Mozzarella starters

Could Hop-derived Bitter Compounds Improve Glucose Homeostasis by Stimulating the Secretion of GLP-1?

Hops (Humulus lupulus L.) is by far the greatest contributors to the bitter property of beer. Over the past years, a large body of evidence demonstrated the presence of taste receptors in different locations of the oral cavity. In addition to the taste buds of the tongue, cells expressing these receptors have been identified in olfactory bulbs, respiratory and gastrointestinal tract. In the gut, the attention was mainly directed to sweet Taste Receptor (T1R) and bitter Taste Receptor (T2R) receptors. In particular, T2R has shown to modulate secretion of different gut hormones, mainly Glucagon-like Peptide 1 (GLP-1), which are involved in the regulation of glucose homeostasis and the control of gut motility, thereby increasing the sense of satiety. Scientific interest in the activity of bitter taste receptors emerges because of their wide distribution in the human species and the large range of natural substances that interact with them. Beer, whose alcohol content is lower than in other common alcoholic beverages, contains a considerable amount of bitter compounds and current scientific evidence shows a direct effect of beer compounds on glucose homeostasis. The purpose of this paper is to review the available literature data in order to substantiate the novel hypothesis of a possible direct effect of hop-derived bitter compounds on secretion of GLP-1, through the activation of T2R, with consequent improvement of glucose homeostasis