Shining light on multi-drug resistant Candida auris: Ultraviolet-C disinfection, wavelength sensitivity, and prevention of biofilm formation of an emerging yeast pathogen.

Candida auris is an emerging fungal superbug of worldwide interest. It is associated with high mortality rates and exhibits increased resistance to antifungals. Ultraviolet subtype C (UVC) light can be used to disinfect surfaces to mitigate its spread. The objectives of this study were (1) To investigate UVC disinfection performances and wavelength sensitivity of C. auris. (2) To evaluate the UVC dose required for the prevention of biofilm formation on stainless-steel, plastic (polystyrene), and poly-cotton fabric surfaces. C. auris was grown following standard procedures. The study utilized six different UVC LED arrays with wavelengths between 252 and 280 nm. Arrays were set at similar intensities, to obtain doses of 5-40 mJ cm-2 and similar irradiation time. Disinfection performance for each array was determined using log reduction value (LRV) and percentage reduction by comparing the controls against the irradiated treatments. Evaluation of the ability of 267 nm UVC LEDs to prevent C. auris biofilm formation was investigated using stainless-steel, plastic coupons, and poly-cotton fabric. Peak sensitivity to UVC disinfection was between 267 and 270 nm. With 20 mJ cm-2 , the study obtained ≥LRV3. On stainless-steel coupons, 30 mJ cm-2 was sufficient to prevent biofilm formation, while on plastic, this required 10 mJ cm-2 . A dose of 60 mJ cm-2 reduced biofilms on poly-cotton fabric significantly (R2 = 0.9750, p = 0.0002). The study may allow for the design and implementation of disinfection systems.

Differences in the Effects of Broad-Band UVA and Narrow-Band UVB on Epidermal Keratinocytes.

BACKGROUND: The sun is a natural source of UV radiation. It can be divided into three bands, UVA (315-400 nm), UVB (280-315 nm) and UVC (100-280 nm), where the radiation up to 290 nm is very effectively eliminated by the stratospheric ozone. Although UV radiation can have a beneficial effect on our organism and can be used in the treatment of several skin diseases, it must primarily be considered harmful. METHODS: In the presented work, we focused on the study of the longer-wavelength UV components (UVA and UVB) on the human epidermal keratinocyte line HaCaT. As UVA and UVB radiation sources, we used commercially available UVA and UVB tubes from Philips (Philips, Amsterdam, The Netherlands), which are commonly employed in photochemotherapy. We compared their effects on cell viability and proliferation, changes in ROS production, mitochondrial function and the degree of DNA damage. RESULTS: Our results revealed that UVB irradiation, even with significantly lower irradiance, caused greater ROS production, depolarization of mitochondrial membrane potential and greater DNA fragmentation, along with significantly lowering cell viability and proliferative capacity. CONCLUSIONS: These results confirm that UV radiation causes severe damages in skin cells, and they need to be protected from it, or it needs to be applied more cautiously, especially if the component used is UVB.

The Associations Between Light Exposure During Pumping and Holder Pasteurization and the Macronutrient and Vitamin Concentrations in Human Milk.

BACKGROUND: During pumping, storage, and pasteurization human milk is exposed to light, which could affect the concentrations of light-sensitive vitamins. Currently, milk banks do not regulate light exposure. RESEARCH AIM: The aim of this paper was to determine the influence of light exposure during pumping, storage, and pasteurization on (1) macronutrients, (2) select water-soluble vitamins, and (3) select fat-soluble vitamins. METHODS: All 13 participants donated 4 milk samples each. Each sample underwent 1 of 4 treatments: raw and light protected, raw and light exposed, pasteurized and light protected, and pasteurized and light exposed. Samples were analyzed for macronutrients and Vitamins B1, B2, retinol, γ-tocopherol, α-tocopherol, and ß-carotene. RESULTS: ß-carotene concentrations were not influenced by light exposure. Vitamin B1 was significantly (p < 0.05) affected by light-exposure (M = 0.23, SD = 0.01mg/L) compared to light-protected (M = 0.27, SD = 0.01mg/L) samples. Vitamin B2 concentrations were reduced (p < 0.05) by light-exposure in raw (M = 62.1, SD = 0.61µg/L) and pasteurized (M = 73.7, SD = 0.72µg/L) samples compared to light-protected raw samples (M = 99.7, SD = 0.66µg/L). No other tested nutrients were affected by light exposure. CONCLUSIONS: If milk is exposed to excessive amounts of light, Vitamins B1 and B2 concentrations may degrade below the current Adequate Intake recommendations for infants 0-6 months of age, increasing the risk of insufficient vitamin supply to the exclusively human milk-fed infant. Thus, pumped or processed human milk should be protected from light to preserve milk vitamin concentrations.

Printable UV-Light Sensor for Human Eye Protection.

Light-emitting diode based electronic screens emit near-ultraviolet radiation, which causes harm to the human eye after prolonged exposure. Thus, it is of paramount importance to prepare a sensitive and adjustable visible near-ultraviolet sensor for retinal warning. Herein, a series of bipyridine derivatives were synthesized to investigate effects of substituent groups and anions on photochromic properties via both experimental and theoretical studies. The introduction of dual hydrogen bonding urea onto substituted groups significantly accelerated the photochromic rate due to strong intermolecular interactions, which reduces molecular spacing and promotes the electron-transfer effect. Moreover, the photochromic rate was tuned by changing the size of the anion. Larger anions widen the molecular spacing and weaken the electron transfer and eventually lead to a decrease in the photochromic rate. Finally, bipyridine derivatives were printed on a polyethylene terephthalate film or paper as a sensitive, adjustable, and visible sensor to monitor near-ultraviolet radiation emitted by an light-emitting diode screen.

PLGA- corosolic acid implants for potential application in ocular neovascularization diseases

Angiogenesis is the formation of new blood vessels from preexisting vasculature. Uncontrolled angiogenesis is associated with progression of several ocular pathologies, such as diabetic retinopathy and macular degeneration. Thus, the inhibition of this process consists in an interesting therapeutic target. Corosolic acid (CA) is a natural derivative of ursolic acid, found in many medicinal herbs and exhibits numerous biological properties, including the antiangiogenic activity. The present study reports the production of CA-loaded poly d,l-lactidecoglycolide acid (PLGA) devices by melt technique. HPLC-UV method was developed and validated to evaluate the uniformity and the release profile of the developed systems. The devices were also characterized by Fourier transform infrared spectroscopy, thermal analysis, and scanning electron morphology. It was studied the antiangiogenic activity of the CA-polymer system, using an in vivo model, the chorioallantoic membrane assay (CAM). CA was dispersed uniformly in the polymer matrix and no chemical interaction between the components of the formulation was verified. The implants presented a sustained release of the drug, which was confirmed by the morphological study and demonstrated an antiangiogenic activity. Therefore, the developed delivery system is a promising therapeutic tool for the treatment of ocular diseases associated with neovascularization or others related to the angiogenic process.

Is Vitamin D Level at Melanoma Diagnosis Associated With Stage Of Tumor? An Observational Study of Melanoma Patients Living in a High Ultraviolet Radiation Environment.

OBJECTIVES: This study will assess the relationship between vitamin D concentration at melanoma diagnosis and melanoma tumor characteristics, in individuals in a high ultraviolet radiation (UVR) environment. METHODS: We aim to recruit 600 recently diagnosed melanoma patients from Queensland, Australia, a high UVR location with one of the world's highest melanoma incidence rates. Patients are recruited through general practitioner, skin cancer specialist, dermatological and hospital-based practices. As close as possible to diagnosis, participants provide a blood sample for vitamin D analysis and have their sun exposure/sun protection behavior, melanoma risk factors and dietary vitamin D intake assessed by questionnaire and phone interview. Details of tumor pathology, including tumor level, thickness, and ulceration, are abstracted from cancer registry records. Here, we describe the study methods and present preliminary findings from early participants. RESULTS: As of December 2017, we have recruited 128 participants (48% male, mean age 60.2 years, mean Breslow thickness 0.63 mm). CONCLUSIONS: When complete, this study will give insights into the association between vitamin D at diagnosis and melanoma tumor characteristics whilst adjusting for recent sun exposure and sun protection use. This study may impact military sun exposure and nutrition policies as vitamin D may play a role in melanomagenesis.

Inactivation of airborne bacteria using different UV sources: Performance modeling, energy utilization, and endotoxin degradation.

Airborne bacteria-containing bioaerosols have attracted increased research attention on account of their adverse effects on human health. Ultraviolet germicidal irradiation (UVGI) is an effective method to inactivate airborne microorganisms. The present study models and compares the inactivation performance of three UV sources in the UVGI for aerosolized Escherichia coli. Inactivation efficiency of 0.5, 2.2 and 3.1 logarithmic order was obtained at an exposure UV dose of 370 J/m3 under UVA (365 nm), UVC (254 nm) and UVD (185 nm) sources, respectively. A Beer-Lambert law-based model was developed and validated to compare the inactivation performances of the UV sources, and modeling enabled prediction of inactivation efficiency and analysis of the sensitivity of several parameters. Low influent E. coli concentrations and high UV doses resulted in high energy consumption (EC). The change in airborne endotoxin concentration during UV inactivation was analyzed, and UVC and UVA irradiation showed no marked effect on endotoxin degradation. By contrast, both free and bound endotoxins could be removed by UVD treatment, which is attributed to the ozone generated by the UVD source. The results of this study can provide a better understanding of the air disinfection and airborne endotoxin removal processes.

Sun Exposure Public Health Directives.

There have been many public health recommendations for avoiding UV radiation exposures. This is primarily due to concerns about skin cancer and especially melanoma, the most serious type of skin cancer. However, UV radiation is also known as the primary source of vitamin D and other compounds needed for good health. This brief commentary lists several of the many important recent studies of adverse health effects associated with low sun exposure, including some specific cancers, multiple sclerosis, diabetes, cardiovascular disease, autism, Alzheimer's disease, and age-related macular degeneration. Our conclusion is that non-burning UV exposure is a health benefit and-in moderation-should be recommended as such.

Relative Contributions of UVB and UVA to the Photoconversion of (6-4) Photoproducts into their Dewar Valence Isomers.

Dewar valence isomers are photoisomerization products of pyrimidine (6-4) pyrimidone photoproducts, a major class of UV-induced DNA lesions, which exhibits a maximal absorption around 320 nm. However, Dewar isomers are not produced in significant amounts in cells exposed to biologically relevant doses of UVB. In contrast, they are readily produced when cells are exposed to a combination of UVA and UVB. The present computational work demonstrates that, on the basis of known absorption properties and formation quantum yields, the difference in Dewar formation between the two types of radiation can be explained by the role of normal bases. In the UVB range, at the low level of (6-4) photoproducts present in cells exposed to realistic doses, normal bases are present in overwhelming amounts and absorb the vast majority of the incident photons. In contrast, the absorption of DNA bases is much weaker in the UVA range while that of (6-4) photoproducts is still significant, making photoisomerization possible. This two-photon process makes it difficult to define an action spectrum for the formation of Dewar isomers.

Oxidação de resíduos de triptofano em proteínas: formação de ligação cruzada ditriptofano e implicações patofisiológicas / Oxidation of tryptophan residues in proteins: formation of the ditryptophan cross-link and pathophysiological implications

Apesar de extensa investigação das modificações oxidativas irreversíveis sofridas pelas proteínas in vitro e in vivo, os produtos formados pela oxidação de resíduos de triptofano ainda permanecem apenas parcialmente conhecidos. Recentemente, nosso grupo caracterizou uma ligação cruzada de ditriptofano produzida pela recombinação de radicais hSOD1-triptofanila gerados pelo ataque do radical carbonato produzido durante a atividade peroxidásica da enzima superóxido dismutase humana (hSOD1). Neste trabalho, examinamos se a ligação ditriptofano pode ser formada em outras proteínas, além da hSOD1 e por outros oxidantes, além do radical carbonato. A lisozima da clara do ovo e a beta cristalino bovina foram utilizadas como alvos de oxidação. A lisozima foi utilizada por ser uma enzima pequena (129 aminoácidos) e de estrutura bem conhecida, contendo seis resíduos de Trp. Os resultados mostraram que o radical carbonato, gerado enzimatica ou fotoliticamente, promove a oxidação, dimerização e inativação da lisozima. Os principais produtos de oxidação caracterizados por análise de nano-ESI-Q-TOF-MS/MS foram hidroxi-triptofano e N-formilquinurenina juntamente com um dímero de lisozima (lisozima-Trp28-Trp28-lisozima) e um hetero dímero lisozima-hSOD1 (lisozima-Trp28-Trp32-hSOD1), ambos ligados por uma ligação ditriptofano. Também demonstramos que a irradiação da lisozima com luz UVC leva à formação do dímero lisozima-Trp28-Trp28-lisozima. Em consequência, resolvemos tratar a beta cristalino bovina com radical carbonato gerado fotoliticamente ou com luz UVC, e a proteína também sofreu oxidação, dimerização e agregação. Os principais produtos de oxidação caracterizados por nano-ESI-Q-TOF-MS/MS foram hidroxi-triptofano, N-formilquinurenina, DOPA e um dímero de beta cristalino (ßB2-Trp151-Trp151-ßB2). A irradiação com luz UVC também levou à formação de um dímero intra-cadeia, caracterizado como ßA2-Trp78-Trp81. Quando a beta cristalino foi irradiada com um simulador de luz solar (UVA e UVB) também foi possível observar um dímero, caracterizado como ßA2-Trp150-Trp150-ßA2. A presença de produtos de oxidação de resíduos de Trp, dentre eles a ligação cruzada ditritpofano, também foi avaliada in vivo, utilizando o cristalino de pacientes que foram submetidos a cirurgia para remoção de catarata. Beta, alfa e gama cristalino foram as principais proteínas identificadas nas frações solúvel e insolúvel do cristalino. A principal modificação pós-traducionais identificada foi deamidação. Um alto conteúdo de resíduos de metionina e triptofano oxidados foram identificados nas proteínas presentes na fração insolúvel. Os principais produtos de oxidação de Trp identificados por nano-ESI-Q-TOF-MS/MS foram quinurenina e N-formilquinurenina. A presença de dímeros covalentes no cristalino com catarata foi confirmada por análises de massas. A completa caracterização desses dímeros (ßB1-Trp127-Trp127-ßB1 e ßB1-Trp193-Trp193-ßB1) confirmou que as cadeias polipeptídicas foram ligadas por uma ligação ditriptofano. Em síntese, nossos dados demonstraram que o radical carbonato e a luz UV podem produzir dímeros de ditriptofano em diferentes proteínas. Também, a presença da ligação cruzada de ditriptofano in vivo (catarata humana) foi pela primeira vez detectada

Despite extensive investigation of irreversible oxidative modifications suffered by proteins in vitro and in vivo, the products formed by oxidation of tryptophan residues remain partially characterized. Our group recently described a ditryptophan cross-link produced by recombination of hSOD1-tryptophanyl radicals generated by attack of the carbonate radical produced during the peroxidase activity of the human superoxide dismutase (hSOD1) enzyme. Here, we examine whether the ditryptophan cross-link can be produced in others proteins besides the hSOD1 and by other oxidants, in addition to the carbonate radical. The egg white lysozyme and bovine beta crystalline were used as targets. Lysozyme was used because it is a small enzyme (129 amino acids) with a well-known structure, containing six Trp residues. The results showed that the carbonate radical, generated enzymatically or photolytically, promotes lysozyme oxidation, inactivation and dimerization. The major oxidation products characterized by nano-ESI-Q-TOF-MS/MS analysis were hydroxy-tryptophan and N-formylkynurenine together with a dimer of lysozyme (lysozyme-Trp28-Trp28-lysozyme) and a hetero dimer hSOD1-lysozyme (lysozyme-Trp28-Trp32-hSOD1), both bound by a ditryptophan cross-link. Also, it was demonstrated that lysozyme irradiation with UVC light leads to the formation of the dimer lysozyme-Trp28-Trp28-lysozyme. In view of these results, we decided to treat beta crystalline bovine with photolytically generated carbonate radical and UVC. Beta crystalline also suffered oxidation, dimerization and aggregation. The major oxidation products characterized were hydroxy-tryptophan, N-formylkynurenine, DOPA and a beta crystalline dimer (ßB2-Trp151-Trp151-ßB2) by nano-ESI-Q-TOF-MS/MS. Irradiation with UVC light also led to the formation of an intra-chain dimer, which was characterized as ßA2-Trp78-Trp81. When beta crystalline was irradiated with a solar simulator (UVA and UVB), it was also possible to observe a dimer which was characterized as ßA2-Trp150-Trp150-ßA2. The presence of oxidized tryptophan products, including the ditryptophan cross-link, was also evaluated in vivo in the lenses of patients submitted to cataract removal. Beta, alpha and gamma crystalline were the main proteins identified in soluble and insoluble fractions of the lenses. The main post translational modification identified was deamidation. A high content of oxidized methionine and tryptophan residues were identified in proteins present in the insoluble fraction. The main tryptophan oxidation products identified by nano-ESI-Q-TOF-MS/MS were kynurenine and N-formylkynurenine. The presence of covalent dimers in the lenses with cataract was demonstrated by mass analysis. Full MS/MS characterization of the dimers ßB1-Trp127-Trp127-ßB1 and ßB1-Trp193-Trp193-ßB1 confirmed that they were linked by a ditryptophan bond. In summary, our data demonstrate that the carbonate radical and UV light can produce ditryptophan dimers in different proteins. Also, the presence of the ditryptophan cross-link was first detected in vivo (human cataract)

Investigation of micronucleus induction in MTH1 knockdown cells exposed to UVA, UVB or UVC.

The longer wave parts of UVR can increase the production of reactive oxygen species (ROS) which can oxidize nucleotides in the DNA or in the nucleotide pool leading to mutations. Oxidized bases in the DNA are repaired mainly by the DNA base excision repair system and incorporation of oxidized nucleotides into newly synthesized DNA can be prevented by the enzyme MTH1. Here we hypothesize that the formation of several oxidized base damages (from pool and DNA) in close proximity, would cause a high number of base excision repair events, leading to DNA double strand breaks (DSB) and therefore giving rise to cytogenetic damage. If this hypothesis is true, cells with low levels of MTH1 will show higher cytogenetic damage after the longer wave parts of UVR. We analyzed micronuclei induction (MN) as an endpoint for cytogenetic damage in the human lymphoblastoid cell line, TK6, with a normal and a reduced level of MTH1 exposed to UVR. The results indicate a higher level of micronuclei at all incubation times after exposure to the longer wave parts of UVR. There is no significant difference between wildtype and MTH1-knockdown TK6 cells, indicating that MTH1 has no protective role in UVR-induced cytogenetic damage. This indicates that DSBs induced by UV arise from damage forms by direct interaction of UV or ROS with the DNA rather than through oxidation of dNTP.

Low-level red laser therapy alters effects of ultraviolet C radiation on Escherichia coli cells.

Low-level lasers are used at low power densities and doses according to clinical protocols supplied with laser devices or based on professional practice. Although use of these lasers is increasing in many countries, the molecular mechanisms involved in effects of low-level lasers, mainly on DNA, are controversial. In this study, we evaluated the effects of low-level red lasers on survival, filamentation, and morphology of Escherichia colicells that were exposed to ultraviolet C (UVC) radiation. Exponential and stationary wild-type and uvrA-deficientE. coli cells were exposed to a low-level red laser and in sequence to UVC radiation. Bacterial survival was evaluated to determine the laser protection factor (ratio between the number of viable cells after exposure to the red laser and UVC and the number of viable cells after exposure to UVC). Bacterial filaments were counted to obtain the percentage of filamentation. Area-perimeter ratios were calculated for evaluation of cellular morphology. Experiments were carried out in duplicate and the results are reported as the means of three independent assays. Pre-exposure to a red laser protected wild-type and uvrA-deficient E. coli cells against the lethal effect of UVC radiation, and increased the percentage of filamentation and the area-perimeter ratio, depending on UVC fluence and physiological conditions in the cells. Therapeutic, low-level red laser radiation can induce DNA lesions at a sub-lethal level. Consequences to cells and tissues should be considered when clinical protocols based on this laser are carried out.

Low-level red laser therapy alters effects of ultraviolet C radiation on Escherichia coli cells

Low-level lasers are used at low power densities and doses according to clinical protocols supplied with laser devices or based on professional practice. Although use of these lasers is increasing in many countries, the molecular mechanisms involved in effects of low-level lasers, mainly on DNA, are controversial. In this study, we evaluated the effects of low-level red lasers on survival, filamentation, and morphology of Escherichia colicells that were exposed to ultraviolet C (UVC) radiation. Exponential and stationary wild-type and uvrA-deficientE. coli cells were exposed to a low-level red laser and in sequence to UVC radiation. Bacterial survival was evaluated to determine the laser protection factor (ratio between the number of viable cells after exposure to the red laser and UVC and the number of viable cells after exposure to UVC). Bacterial filaments were counted to obtain the percentage of filamentation. Area-perimeter ratios were calculated for evaluation of cellular morphology. Experiments were carried out in duplicate and the results are reported as the means of three independent assays. Pre-exposure to a red laser protected wild-type and uvrA-deficient E. coli cells against the lethal effect of UVC radiation, and increased the percentage of filamentation and the area-perimeter ratio, depending on UVC fluence and physiological conditions in the cells. Therapeutic, low-level red laser radiation can induce DNA lesions at a sub-lethal level. Consequences to cells and tissues should be considered when clinical protocols based on this laser are carried out.

An Experimental Model Design for Photoaging.

UNLABELLED: Autologous adipose-derived stem cells have shown great promise in applications that treat photodamaged skin. Adipose-derived stem cells also have an antiwrinkle effect; consequently, they have become a topic of primary interest. Nude mice have been used extensively in studies of adipose-derived stem cells, human dermal fibroblasts, and other filler injections. However, a nude mouse model of photoaging has not yet been developed. Thus, we attempted to develop a nude mouse model of photoaging in this study. MATERIALS AND METHODS: Fourteen, 5-week-old female BALB/c nude mice were irradiated with ultraviolet-B rays, 6 times a week for 6 weeks. The minimum erythema dose was established before the mice underwent ultraviolet irradiation to minimize the inflammation of the irradiated skin and to determine the initial irradiation dosage. The mean sizes of the wrinkled areas of skin and the mean depths of the wrinkles were compared between the study groups using replica analysis. Skin biopsies were performed on the 6th and 10th weeks of the study. RESULTS: The mean sizes of the wrinkled areas of skin and the mean depths of the wrinkles increased significantly in the ultraviolet-B-irradiated nude mice compared with the nonirradiated mice, and the thicknesses of the epidermis and dermis of the skin from the upper and lower back were significantly greater after ultraviolet-B irradiation up to the 6th week of treatment (P < 0.05). Furthermore, the ultraviolet-B-irradiated group demonstrated reduced collagen fiber levels. CONCLUSIONS: We have successfully developed a nude mouse model for research into photoaging, and these results indicate that the nude mouse is a suitable model for investigating the development of photoaging.

Avaliação do efeito fotoprotetor de compostos fenólicos sobre culturas de células da pele irradiadas por UVA e UVB / Photoprotective effect evaluation phenolic compounds on skin cell cultures irradiated with UVA and UVB

A exposição excessiva à radiação Ultravioleta (UV) resulta em manifestações clínicas à pele humana como queimaduras, fotoenvelhecimento e câncer. A radiação UVA, preferencialmente, induz à formação de espécies reativas de oxigênio, enquanto que a radiação UVB é absorvida diretamente pelo DNA. Apesar de mecanismos endógenos auxiliarem na prevenção/reparação dos danos causados pela radiação UV, quando o dano excede a capacidade de reparação celular, diversos efeitos lesivos ocorrem na pele como alterações da matriz dérmica, resposta inflamatória e desidratação do estrato córneo. O uso de compostos fenólicos com atividade antioxidante pode auxiliar na prevenção das consequências patológicas da exposição à radiação UV. O presente trabalho teve como objetivo estudar em cultura de células da pele (HaCaT -queratinócito humano imortalizado e FHPD - fibroblasto humano primário dermal) exposta às radiações UVA e UVB a atividade fotoprotetora de 3 compostos fenólicos, ácido cafeico (AC), clorogênico (ACG) e rosmarínico (AR). Inicialmente, células HaCaT e FHPD cultivadas em monocamada foram expostas às doses crescentes de radiação UVA ou UVB e, após 24 horas, foram analisadas quanto a viabilidade, marcadores de morte celular, mediadores inflamatórios, presença de aquaporina e lesões de DNA. HaCaT quando exposta às radiações UVA e UVB são conduzidas à morte por apoptose, com aumento de Caspases 3 e 9, p53 e redução de PARP. Após a exposição à radiação UVA, HaCaT responde com aumento na liberação de IL-6, TNF-α e COX-2, internalização/redução de AQP3 da membrana, redução na liberação de MMP-2 e 9, aumento na liberação de MMP-1 e na produção de ERO. Quando expostos à radiação UVB, HaCaT aumenta a liberação de IL-6 e COX-2, promove internalização/redução de AQP3 na membrana e redução na liberação de MMP-2 e 9. FHPD são menos sensíveis à exposição a ambas as radiações, mostrando redução de viabilidade com parada de ciclo apenas frente à radiação UVA. Além disto, FHPD exposto a radiação UVA responde com aumento na liberação de IL-6 e danos no DNA do tipo 8-oxo-dG. Dentre os compostos, o ACG apresentou melhor atividade fotoquimioprotetora perante ambas as radiações UVA e UVB, pois foi capaz de reverter em HaCaT a morte celular induzida por ambas as radiações e de reverter a parada de ciclo em FHPD expostos à radiação UVA. HaCaT tratado com ACG e exposto à radiação UVA responde com aumento na expressão de AQP3 e PARP, aumento na expressão gênica de AQP3, redução na expressão gênica de CDKN1A e na liberação de MMP-1, 2 e 9. Após a radiação UVB, o tratamento com ACG aumenta a expressão gênica de AQP3, reduz a expressão gênica de CDKN1A, reduz a produção de COX-2 e aumenta a liberação de MMP-2 e 9. O tratamento com o AR apresentou atividade fotoquimioprotetora frente à radiação UVA, com HaCaT respondendo a radiação com aumento na população de células viáveis, aumento na expressão de AQP3 e PARP e na expressão gênica de AQP3, redução na liberação de MMP-1 e 9 e redução na produção de COX-2. FHPD tratados com AR apresentaram aumento na população em fase G1, na expressão de p21, e redução de danos de DNA tipo 8-oxo-dG. O tratamento de HaCaT com AC foi capaz de reverter a morte celular, aumentar a expressão de p53 e aumentar a liberação de MMP-2 e 9 frente à radiação UVB e de reduzir a produção de ERO, a expressão de p21 e a liberação de MMP-1, 2 e 9 frente à radiação UVA. Para FHPD, o tratamento com AC foi capaz apenas de reduzir a formação de danos de DNA tipo 8-oxo-dG. Os resultados indicam que o modelo proposto foi capaz de discriminar a atividade fotoprotetora dos compostos frente à radiação UVA e UVB. Além disto, foi possível demonstrar que os compostos antioxidantes se comportam de maneira distinta enquanto fotoprotetores no modelo empregado

Excessive exposure to Ultraviolet radiation (UV) results in clinical manifestations in human skin such as burns, photo-aging and cancer. UVA radiation preferentially induces formation of reactive oxygen species, while UVB radiation is absorbed directly by the DNA. Although endogenous mechanisms are able to prevent/repair cellular damages caused by UV radiation, excess cellular damage retains cells repair capacity and also results on diverse harmful effects on skin, such as, changes in the dermal matrix, inflammatory response and dehydration of the stratum corneum. The use of phenolic compounds with antioxidant activity may help preventing pathological conditions caused by UV radiation. This work aimed to study the photoprotective activity of three phenolic compounds, caffeic (CA), chlorogenic (CGA) and rosmarinic acid (RA) in human skin cells (HaCaT - immortalized human keratinocytes and HDSF - human dermal skin fibroblast) exposed to UVA and UVB radiation. Initially, HDSF and HaCaT cells were exposed to increasing doses of UVA and UVB radiation. After 24 hours of exposure, we evaluated cell viability, cell death, inflammatory mediators, aquaporin and DNA damage. Exposure to UVA and UVB radiation in HaCaT cells results on apoptotic cell death, with an increase of caspases 3 and 9, p53 and reduction of PARP. HaCaT cells when exposed to UVA radiation resulted on increased levels of IL-6, TNF-α and COX-2, internalization of the membrane AQP3, reduction of MMP-2 and MMP-9 release, increase of MMP-1 and ROS production. After UVB radiation, HaCaT cells resulted on an increase of IL-6 and COX-2 production, it also promoted internalization of membrane AQP3 and reduced release of MMP-2 and 9. HDSF were less sensitive to both radiations. Moreover, HDSF resulted in cell viability decrease and cell cycle arrest only after UVA radiation. Furthermore, HDSF when exposed to UVA radiation resulted on an increase of IL-6 production and in DNA damage (8-oxo-dG). Among the studied compounds, CGA presented better photochemiprotective activity towards UVA and UVB radiation. Also, this compound was able to reverse cell death in HaCaT after exposure to both radiations and inhibited cell cycle arrest in HDSF after UVA radiation exposure. HaCaT cells treated with CGA and exposed to UVA radiation resulted on an increase in AQP3 and PARP expression, increased in AQP3 gene expression, reduction in CDKN1A gene expression and reduction in MMP-1, 2 and 9 release. After UVB radiation, GCA treatment increases AQP3 gene expression, reduces CDKN1A gene expression, reduces COX-2 production and increase MMP-2 and 9 releases. The AR treatment showed photochemiprotective activity towards the effects of UVA radiation, with HaCaT responding with an increase on cells viability, increased in PARP and AQP3 expression and in AQP3 gene expression, decreased MMP-1 and 9 releases and reduced COX-2c production. HDSF when treated with AR showed an increase in G1 phase population, in p21 expression and reduced DNA damage-type 8-oxo-dG. HaCaT cells treated with AC reversed cell death, increased p53 expression and increased MMP-2 and 9 releases after UVB radiation and reduced ROS production, p21 expression and MMP -1, 2, 9 release after UVA radiation. HDSF treated with AC was only able to reduce the formation of 8-oxodG DNA damage. These results indicated that the proposed model was able to discriminate the photochemiprotective activity of the studied compounds against the UVA and UVB radiation. In addition, it was demonstrated that the each studied antioxidant have different photoprotective mode of action

Incidencia del cáncer de piel no melanoma en un cupo del Centro de Salud de Zaramaga / Incidence of non-melanoma skin cancer in a population of the Zaramaga Health Centre

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Ultraviolet-C irradiation to titanium implants increases peri-implant bone formation without impeding mineralization in a rabbit femur model.

OBJECTIVES: Volume and bone quality of peri-implant supporting bone, in particular, at implant neck region, as well as bone-implant contact ratio, is important for long-term stability of implants. Ultraviolet-C (UVC) irradiation is known to enhance the osseointegration capability of titanium implants. However, the histological determination was performed only on a rat model, but not pre-clinical animal model such as a rabbit model. The purpose of this study was to determine the effects of UVC irradiation on titanium implants on the volume and mineral density of peri-implant supporting bone formation in a rabbit femur model. MATERIALS AND METHODS: Acid-etched pure titanium screw implants with or without 3 mW/cm2 UVC irradiation for 48 h were placed in rabbit femur diaphyses. Peri-implant bone tissue formation was analyzed at 3 and 8 weeks post-operatively by histology and micro-CT-based bone morphometry after calibration with hydroxyl apatite phantoms. RESULTS: UVC pre-irradiated implants accumulated a higher density of cells and thicker and longer bone tissue attachments that continued into the inner basic lamellae of the surface of existing cortical bone at 3 and 8 weeks than the implants without irradiation. Although the bone mineral density around both implants was equivalent to that of the existing cortical bone, bone volume was greater with UVC pre-irradiation in two-thirds or more of the apical region throughout the observation period. CONCLUSIONS: These results indicate that UVC treatment increased the volume of cortical-like bone tissue in the coronal region of titanium implants without deterioration of bone mineral density.

School students' knowledge and understanding of the Global Solar Ultraviolet Index.

BACKGROUND: The Global Solar Ultraviolet Index (UVI) is a health communication tool used to inform the public about the health risks of excess solar UV radiation and encourage appropriate sun-protection behaviour. Knowledge and understanding of the UVI has been evaluated among adult populations but not among school students. OBJECTIVES: To draw on previously unpublished data from two school-based studies, one in New Zealand (NZ) and the other in South Africa (SA), to investigate and compare students' knowledge of the UVI and, where possible, report their understanding of UVI. METHODS: Cross-sectional samples of schoolchildren in two countries answered questions on whether they had seen or heard of the UVI and questions aimed at probing their understanding of this measure. RESULTS: Self-report questionnaires were completed by 1 177 students, comprising 472 NZ (264 year 8 (Y8), 214 year 4 (Y4) students) and 705 SA grade 7 primary-school students aged 8-13 years. More than half of the NZ Y8 students answered that they had previously heard about or seen the UVI, whereas significantly more SA students and NZ Y4 students replied that they had neither seen nor heard about the UVI. Among the NZ students who had seen or heard of the UVI, understanding of the tool was fairly good. CONCLUSION: The observed lack of awareness among many students in both countries provides an opportunity to introduce an innovative and age-appropriate UVI communication method that combines level of risk with behavioural responses to UVI categories and focus on personal relevance to the UVI message.

Participação da via Notch em lesões labiais fotoinduzidas / Participation of the Notch pathway in photoinduced lip lesions

A intensa exposição ao Sol sujeita o lábio, principalmente o inferior, aos danos provocados pela absorção de radiação ultravioleta (UV). O carcinoma epidermoide é a neoplasia maligna que se desenvolve nos lábios após exposição crônica prolongada aos raios UV e acredita-se que todos os casos sejam precedidos pela desordem potencialmente maligna denominada queilite actínica. Ambas as lesões são causados pelos efeitos nocivos da radiação UV agindo diretamente sobre o DNA, por meio do fenômeno da fotocarcinogênese. Nesse processo, a radiação provoca mutações que são capazes de causar a iniciação, progressão e a promoção de neoplasias. No entanto, é também importante considerar que outros eventos moleculares, além das mutações, estão envolvidos na iniciação e progressão do câncer. Alterações moleculares com ganho ou perda de função de componentes da via de sinalização Notch estão envolvidas em diferentes tipos de cânceres hematológicos e sólidos. Entretanto, a participação da sinalização Notch em câncer de lábio ainda é desconhecida.

Assim, o objetivo desse trabalho foi investigar se a via Notch está relacionada às lesões de queilite actínica e de carcinoma epidermoide de lábio e sua participação na fotocarcinogênese bucal. Para isso, foram utilizados 45 casos de queilite actínica, 15 casos de carcinoma epidermoide de lábio e 05 casos de lábio com aspecto de normalidade, nos quais foi analisada a expressão de Notch1 e Jagged1 por meio da técnica de imuno-histoquímica. Os resultados demonstraram que houve perda da expressão de Notch1 em 40% dos carcinomas epidermoides de lábio, sugerindo que a expressão reduzida de Notch1 pode converter os queratinócitos a um estado ativado e imaturo. Observou-se ainda, diferença nos padrões de marcação de Nocth1 e Jagged1 nas células epiteliais sugerindo que o sinal da via Notch seja transmitido a partir de uma célula apical para uma célula basal devido a localização das células que expressam o receptor e das que expressam o ligante. Concluiu-se, assim, que os resultados imuno-histoquímicos não apontam a uma regulação diferencial da expressão da proteína Notch1 e Jagged1 em lesões UV induzidas.

The intense exposure to the sun subject the lips, particularly the lower, the damage caused by the absorption of ultraviolet (UV) radiation. The squamous cell carcinoma is a malignant tumor that develops on the lips after prolonged chronic exposure to UV rays and it is believed that all cases are preceded by potentially malignant disorder called actinic cheilitis. Both lesions are caused by the harmful effects of UV radiation acting directly on the DNA, through the phenomenon of photocarcinogenesis. In this process, the radiation causes mutations that are capable of causing the initiation, progression and promotion of cancer. However, it is also important to consider that other molecular events, apart from the mutations are involved in the initiation and progression of cancer. Molecular abnormalities with gain or loss of Notch pathway components function are involved in several types of hematological and solid cancer. However,

the participation of Notch signaling in lip cancer is still unknown. The objective of this study was to investigate whether the Notch pathway is related to injuries actinic cheilitis and squamous cell carcinoma of the lip and participation in oral photocarcinogenesis. For this, were used 45 cases of actinic cheilitis, 15 cases of squamous cell carcinoma of the lip and lip 05 cases with normal aspect in which we analyzed the expression of Notch1 and Jagged1 by immunohistochemistry. The results showed loss of Notch1 expression in 40% of squamous cell carcinomas of the lip, suggesting that reduced expression of Notch1 can convert to an activated keratinocytes and immature state. There was also a difference in labeling patterns of Notch 1 and Jagged1 epithelial cells suggesting that the Notch pathway signal is transmitted from an apical cell to a basal cell due to localization of cells expressing the receptor and expressing the ligand. In summary, the immunohistochemical results do not show a differential regulation of Notch 1 and Jagged1 expression in UV induced lesions.