This chapter reviews the literature applying health behavior theories to indoor tanning. Few studies have tried to fit full versions of health behavior models to indoor tanning. Theoretical models from the family of theories referred to as the reasoned action approach (e.g., theory of planned behavior, behavioral alternative model, prototype willingness model, etc.) have been most commonly used to study indoor tanning. Results indicate that these models fit indoor tanning data moderately to extremely well. Two lesser known models, problem behavior theory and the terror management health model, have also demonstrated a reasonable fit. Two other common models, the health belief model and social cognitive theory, have never been fully tested with indoor tanning. However, key constructs from these models (e.g., perceived susceptibility and threat, modeling) have been used to understand indoor tanning. Empirical research conducted represents a solid start toward developing strong, comprehensive models of indoor tanning that can guide intervention efforts. This initial work needs to be expanded by conducting longitudinal studies and by including a broader age range in studies because the majority of existing work has focused on young adults. Incorporating findings related to tanning dependency, peer group affiliation, media influences and other constructs into these foundational models will also improve our understanding and ability to develop efficacious interventions to reduce engagement in this health risk behavior.

This chapter reviews the literature examining interventions to reduce indoor tanning (IT). The first objective was to highlight programs that show promise for large scale dissemination. The second objective was to promote criteria and standards for future intervention research efforts. The scope of interest for this review includes universal (for everyone in the population), selective (for those in the population who are at a greater risk), and indicated (for those who already are experiencing conditions that identify them as at risk) programs. The evaluation of the interventions resulted in three levels of evidence: (1) most promising, (2) emerging, and (3) mixed. For an intervention to be considered “most promising”, it was required that ten criteria be met through examination of research findings in published reports consistent with Flay and colleagues (Prev Sci 6(3):151–175, 2005). Interventions that were classified as “emerging” met most of the criteria. Finally, interventions classified as “mixed” did not reach threshold on more than two criteria that were deemed critical. The results revealed that there was very limited research on IT interventions that meet all the evaluation criteria. Only one intervention approach met all of the criteria (Appearance Booklet) (Hillhouse and Turrisi, Behav Med 25(4):395–409, 2002; Hillhouse et al., Cancer 113(11):3257–3266, 2008). Although the number of published papers in the IT area has increased dramatically over the past decade, these efforts have yet to translate into rigorously conducted intervention trials. The review points to important issues that need to be addressed in future research on the prevention of IT. Keywords

Malignant cutaneous melanoma is the deadliest form of skin cancer, and a majority of melanoma diagnoses are a result of exposure to ultraviolet (UV) radiation. UV radiation causes DNA damage, which if not repaired correctly via nucleotide excision repair (NER) can result in mutations and melanomagenesis. The melanocortin 1 receptor (MC1R) is a Gs protein coupled receptor located on melanocyte plasma membranes and is involved in protecting the skin from UV induced damage. MC1R signaling results in the activation of two protective pathways: 1) induction of eumelanin synthesis downstream of micropthalmia-associated transcription factor (MITF) and 2) acceleration of NER downstream of ataxia telangiectaseia mutated and Rad3 related (ATR). MC1R signaling, however, also promotes melanocyte proliferation, therefore, the activation of the MC1R pathway must be regulated. The overall hypothesis of this dissertation is that the pathways downstream of MC1R can be manipulated to protect against UV induced damage. Chapter 2 investigates the regulation of the MC1R neutral antagonist human β-defensin 3 (βD3). UV damage did not induce βD3 mRNA expression in ex vivo human skin explants. The induction of βD3 expression instead correlated with inflammatory cytokines including TNF. Chapter 3 investigates the interdependence and cross talk between the two protective pathways downstream of MC1R. We directly tested the effect of MITF on the acceleration of NER and the effect of ATR on the induction of eumelanin synthesis following MC1R activation. MITF was not required for the acceleration of NER as mediated by ATR, however, the induction of transcription of enzymes involved in eumelanin synthesis was dependent upon ATR kinase activity. Finally, Chapter 4 investigates the mechanism by which MC1R promoted proliferation and whether the two UV protective pathways downstream of MC1R could be selectively activated without the risk of melanocyte proliferation. MC1R signaling resulted in activation of the mechanistic target of rapamycin complex 1 (mTORC1), a major regulator of cell growth and proliferation. Inhibition of mTORC1 signaling via rapamycin prevented MC1R induced proliferation in vitro. Rapamycin, however, did not prevent MC1R induced eumelanin synthesis or the acceleration of NER in vitro or in vivo suggesting it is possible to selectively activate the beneficial signaling pathways without the risk of melanocyte proliferation. The results of this dissertation suggest that MC1R signaling could be augmented in individuals to prevent UV induced damage.

Entre as estratégias de fotoproteção encontra-se a inibição da formação e/ou o seqüestro de radicais livres e espécies reativas de oxigênio geradas em conseqüência da exposição à radiação UV, mediante aplicação tópica de antioxidantes. No presente trabalho avaliou-se a permeação cutânea e o efeito da aplicação tópica de um extrato de Pothomorphe umbellata nos efeitos da exposição aguda e crônica à radiação ultravioleta, na pele de camundongos sem pêlo. No estudo de permeação cutânea foram testadas três formulações (gel, gel-creme e creme) contendo o princípio ativo do extrato (4-nerolidilcatecol) isolado. Também foram testadas duas formulações (gel, e gel-creme) contendo o extrato hidroalcoólico liofilizado de Pothomorphe umbellata, quanto à permeação do princípio ativo 4-nerolidilcatecol. A formulação gel tanto para o princípio ativo isolado, quanto para o princípio ativo presente no extrato, apresentou o melhor desempenho, sendo o gel o veículo escolhido para preparação da formulação utilizada nos ensaios de exposição crônica e aguda à radiação ultravioleta. Nos estudos de exposição aguda à radiação UVB não foram observadas alterações significativas nos níveis de ácido ascórbico e na atividade enzimática, mas sim uma redução de 40% (p<0,01) na concentração de &#945;-tocoferol na pele do grupo de. camundongos sem pêlo, controle irradiado. No grupo tratado com P. umbellata, o &#945;-tocoferol foi totalmente preservado, quando comparado aos níveis encontrados no grupo controle não irradiado (&#8776;100%, p>0,05). No estudo de exposição crônica dos camundongos sem pêlo à radiação ultravioleta, os grupos irradiados que não receberam tratamento com gel de P. umbellata apresentaram a pele fotoenvelhecida. O grupo irradiado e tratado com o gel de Pothomorphe umbellata não apresentou diferença significativa em relação ao grupo controle não irradiado, o que demostra que o extrato de Pothomorphe umbellata pode ser empregado com sucesso como agente foto protetor tópico no fotoenvelhecimento da pele. / Topical administration of antioxidants provides an efficient way to enrich the endogenous antioxidant system and thus may be a successful strategy for diminishing ultraviolet radiation-mediated oxidative damage in the skin. The Brazilian Flora is rich in medicinal plants with a high potential to provide these antioxidant substances. Crude dried root ethanolic extracts of Pothomorphe umbellata, from the piperaceae family, demonstrated a significant activity in the prevention of in vitro spontaneous brain lipid peroxidation. This activity was attributed to 4-nerolidylcathecol, a compound isolated from the hexane extracts of roots and leaves of P. umbellata. In this work we evaluated the influence of topical application of P. umbellata root extract gel, containing 0,1% of 4-nerolidylcathecol, on the antioxidant network in ultraviolet-induced oxidative damage in hairless mouse skin. In this study we evaluated the influence of three different formulations (gel, gel-emulsion and emulsion) on the percutaneous absorption of 4-nerolidylcathecol, an antioxidant compound isolated from Pothomorphe umbellata root extracts. Also the absorption of the isolated 4-nerolidylcathecol was compared with its absorption when dried Pothomorphe umbellata root ethanolic extract was incorporated in gel and gel-emulsion formulations. The 4-nerolidylcathecolgel formulation presented the higher rate of penetration, leading to higher dry drug levels in the tissue.4-nerolidylcathecol was also absorbed in biological conditions and was stable when exposed to UV-irradiation. The UV-irradiation had no influence on ascorbic acid levels, or on the antioxidant enzymes activities, but topical P. umbellata treatment protected &#945;-tocopherol from depletion after UV-irradiation. After UV-irradiation &#945;-tocopherol concentration decreased significantly (&#8776;40%, p<0.01) in irradiated control groups, while in the P. umbellata treated group, a-tocopherol was totally preserved (&#8776;100%, p>0.05). We also tested the extract activity on animals chronically exposed to UV-radiation. The extract was able to prevent photoaging of the irradiated animals skin. These data demonstrate that P. umbellata may successfully employed as a topical photoprotective agent.

Entre as estratégias de fotoproteção encontra-se a inibição da formação e/ou o seqüestro de radicais livres e espécies reativas de oxigênio geradas em conseqüência da exposição à radiação UV, mediante aplicação tópica de antioxidantes. No presente trabalho avaliou-se a permeação cutânea e o efeito da aplicação tópica de um extrato de Pothomorphe umbellata nos efeitos da exposição aguda e crônica à radiação ultravioleta, na pele de camundongos sem pêlo. No estudo de permeação cutânea foram testadas três formulações (gel, gel-creme e creme) contendo o princípio ativo do extrato (4-nerolidilcatecol) isolado. Também foram testadas duas formulações (gel, e gel-creme) contendo o extrato hidroalcoólico liofilizado de Pothomorphe umbellata, quanto à permeação do princípio ativo 4-nerolidilcatecol. A formulação gel tanto para o princípio ativo isolado, quanto para o princípio ativo presente no extrato, apresentou o melhor desempenho, sendo o gel o veículo escolhido para preparação da formulação utilizada nos ensaios de exposição crônica e aguda à radiação ultravioleta. Nos estudos de exposição aguda à radiação UVB não foram observadas alterações significativas nos níveis de ácido ascórbico e na atividade enzimática, mas sim uma redução de 40% (p<0,01) na concentração de &#945;-tocoferol na pele do grupo de. camundongos sem pêlo, controle irradiado. No grupo tratado com P. umbellata, o &#945;-tocoferol foi totalmente preservado, quando comparado aos níveis encontrados no grupo controle não irradiado (&#8776;100%, p>0,05). No estudo de exposição crônica dos camundongos sem pêlo à radiação ultravioleta, os grupos irradiados que não receberam tratamento com gel de P. umbellata apresentaram a pele fotoenvelhecida. O grupo irradiado e tratado com o gel de Pothomorphe umbellata não apresentou diferença significativa em relação ao grupo controle não irradiado, o que demostra que o extrato de Pothomorphe umbellata pode ser empregado com sucesso como agente foto protetor tópico no fotoenvelhecimento da pele. / Topical administration of antioxidants provides an efficient way to enrich the endogenous antioxidant system and thus may be a successful strategy for diminishing ultraviolet radiation-mediated oxidative damage in the skin. The Brazilian Flora is rich in medicinal plants with a high potential to provide these antioxidant substances. Crude dried root ethanolic extracts of Pothomorphe umbellata, from the piperaceae family, demonstrated a significant activity in the prevention of in vitro spontaneous brain lipid peroxidation. This activity was attributed to 4-nerolidylcathecol, a compound isolated from the hexane extracts of roots and leaves of P. umbellata. In this work we evaluated the influence of topical application of P. umbellata root extract gel, containing 0,1% of 4-nerolidylcathecol, on the antioxidant network in ultraviolet-induced oxidative damage in hairless mouse skin. In this study we evaluated the influence of three different formulations (gel, gel-emulsion and emulsion) on the percutaneous absorption of 4-nerolidylcathecol, an antioxidant compound isolated from Pothomorphe umbellata root extracts. Also the absorption of the isolated 4-nerolidylcathecol was compared with its absorption when dried Pothomorphe umbellata root ethanolic extract was incorporated in gel and gel-emulsion formulations. The 4-nerolidylcathecolgel formulation presented the higher rate of penetration, leading to higher dry drug levels in the tissue.4-nerolidylcathecol was also absorbed in biological conditions and was stable when exposed to UV-irradiation. The UV-irradiation had no influence on ascorbic acid levels, or on the antioxidant enzymes activities, but topical P. umbellata treatment protected &#945;-tocopherol from depletion after UV-irradiation. After UV-irradiation &#945;-tocopherol concentration decreased significantly (&#8776;40%, p<0.01) in irradiated control groups, while in the P. umbellata treated group, a-tocopherol was totally preserved (&#8776;100%, p>0.05). We also tested the extract activity on animals chronically exposed to UV-radiation. The extract was able to prevent photoaging of the irradiated animals skin. These data demonstrate that P. umbellata may successfully employed as a topical photoprotective agent.

No description available.

<p>Studies concerning social consequences, gastrointestinal and urinary tract symptoms were conducted in a population-based cohort comprising patients with long-standing type 1 diabetes and matched control persons. Three different questionnaires were sent by mail to diabetic patients and control persons. After a mean duration of 28.7±2.6 years, compared to the controls the diabetic patients showed an almost 10 times higher mortality, a lower employment rate and greater need for welfare benefits. These differences were mainly due to diabetic late complications. Education, housing conditions, life-style, civil state, alcohol and smoking habits were similar in the two groups. The prevalence of gastrointestinal symptoms was significantly higher in the diabetic patients than in the controls, and this was found to be attributable to the female diabetic patients. Female diabetic patients had been treated with antibiotics for urinary tract infections more often than controls, they experienced more social problems than controls in daily life because of urinary tract problems and used clamps to prevent wetting more often than did controls. </p><p>Body composition and bone mineral density were evaluated in parts of the cohort with long-standing type 1 diabetes and control persons in another population-based cohort comprising diabetic females aged 16-19 years with type 1 diabetes since childhood and matched controls. Besides a tendency to reduced abdominal fat mass in diabetic males, no difference was observed in fat mass, muscle mass or bone mineral density between the patients with long-standing type 1 diabetes and controls. Significant correlations were found between insulin dosage and whole body fat mass in diabetic females and between serum cholesterol levels and abdominal fat mass in diabetic males. The female adolescents had a higher body mass index than the controls, and their overweight was shown to consist almost entirely of an increased fat mass. The distribution of fat, expressed as abdominal-to-leg ratio, correlated significantly to HbA1c and daily dosage of insulin. Bone mineral density did not differ between the groups. IGF I was significantly lower both in patients with long-standing type 1 diabetes and in the adolescent diabetic females compared with their matched controls.</p>

<p>Neuroendocrine tumors (NET´s) are often characterized by overproduction of peptide hormones. In spite of pronounced clinical symptoms, the tumor lesions can be small and difficult to detect. The general aim of this thesis was to investigate, in vitro and in vivo, some of the potential monoamine pathways present in NET´s, using radiolabeled tracers for positron emission tomography (PET), with the intention to explore the value of PET-imaging in the management of NET´s.</p><p>We used the 11C-labeled serotonin precursor 5-hydroxy tryptophan (HTP) as the tracer for imaging of NET´s. More than 95% of the subjects displayed a high tracer uptake on PET and tumor detection rate with PET was higher in >50% of the patients compared both to computed tomography (CT) and somatostatin receptor scintigraphy (SRS). The primary tumor was imaged by PET in 84% (16/19), compared to 47% and 42% for SRS and CT, respectively. Tumor visibility was better with PET due to a higher tumor-to-background ratio and a better spatial resolution. There was a strong correlation (r = .907) between changes in urinary-5-hydroxy indole acetic acid and changes in transport rate of 11C-5-HTP during treatment, indicating the use of PET in treatment monitoring of NET´s. </p><p>Pretreatment with carbidopa decreased the urinary radioactivity concentration four-fold and significantly (p<0.001) increased the tumor tracer uptake. This greatly improved image interpretation and tumor lesion detection.</p><p>A screening for expression of monoamine pathways in NET´s revealed a high in vitro binding of the monoamineoxidase-A ligand harmine to tumor sections. PET examinations with 11C-harmine could visualize tumors in all patients, including non-functioning endocrine pancreatic tumors (EPT´s).</p><p>Finally, the in vitro turnover and in vivo distribution of the amino acids glutamate, glutamine and aspartate was investigated. Limited uptake in vivo indicates the lack of utility for these substances as PET-tracers for imaging and characterization of NET´s. </p>

<p>In sera remitted for anti-nuclear antibody (ANA) analysis, the supplement of a sensitive anti-SSA/Ro ELISA to the conventional ANA screening by immunofluorescence (IF) revealed that one fourth of the individuals with IF-ANA negative, but SSA/Ro ELISA positive sera, had systemic lupus erythematosus (SLE) or cutaneous LE. Consequently, adding a sensitive anti-SSA/Ro ELISA to the ANA screening is valuable for the serological detection of ANA negative SLE/LE patients.</p><p>SLE patients often have measurable interferon-alpha (IFN-α) levels in serum, and IFN-α treatment of patients with non-autoimmune diseases can induce SLE. Thus, the type I IFN system seems to be important in SLE and was therefore investigated. Initially, a decreased IFN-α producing capacity, due to a 70-fold reduction in the number of circulating natural IFN-α producing cells (NIPC), was noted in peripheral blood mononuclear cells (PBMC) from SLE patients. SLE-sera contained an endogenous IFN-α inducing factor (SLE-IIF), consisting of IgG and DNA in the form of small immune complexes (300-1000 kD). The SLE-IIF selectively activated NIPC and was more common in sera from patients with active disease compared to individuals with inactive disease. IFN-α producing cells could be detected by immunohistochemistry in both lesional and unaffected skin from SLE patients, and IFN-α gene transcription could be verified by in situ hybridisation in some of the skin biopsies. A reduced number of NIPC, detected by expression of the blood dendritic cell antigen (BDCA)-2, was noted among SLE-PBMC. The IFN-α production triggered by SLE-IIF in SLE-PBMC was inhibited by monoclonal antibodies (mAbs) to BDCA-2 and markedly decreased by anti-BDCA-4 mAbs. </p><p>The observations in the present thesis may explain the ongoing IFN-α production in SLE patients, indicate an important role for the activated type I IFN system in the pathogenesis, and suggest that direct targeting of SLE-NIPC may constitute a new therapeutic principle in SLE.</p>

<p>In patients with diabetes mellitus (DM), acute myocardial infarction (AMI) is a major cause of death. We have studied two populations with respect to the relationship between DM or related glucometabolic disturbances and AMI.</p><p>In the first population, the prevalence of DM and the importance of the glycaemic state for the long-term prognosis in non-diabetic patients were investigated in patients with AMI admitted to the Coronary Care Unite at Västerås Central Hospital.</p><p>In the second population, the prevalence of impaired glucose tolerance (IGT), DM and other metabolic abnormalities was investigated in patients with AMI and without known DM admitted to the Coronary Care Units at Västerås and Karolinska Hospital, Stockholm.</p><p>21% of the patients with AMI had previously known DM and 4% had newly detected DM if diagnosis is based upon fasting blood glucose (F-BG). The glycemic state, measured as HbA1c, at a 5.5 years follow-up was a risk factor for re-infarction and/or death in non-diabetic patients after AMI.</p><p>If an oral glucose tolerance test (OGTT) is performed, 40-45% of all patients with AMI have DM and in addition about 30% have IGT. Both an OGTT and a single post-challenge blood glucose value after 60 minutes performed at hospital discharge, were independent predictors of IGT or DM at follow-up. Insulin resistance, measured by homeostatic model assessment (HOMA-IR), decreased during hospital stay, with no further decrease from hospital discharge to follow-up.</p><p>In summary, the studies in this dissertation have revealed an unexpectedly high prevalence of abnormal glucose tolerance in patients with AMI. The glycaemic state, reflected by HbA1c, in non-diabetic patients after AMI has an impact on the long-term prognosis. Consequently, in all patients with AMI, HbA1c and casual blood glucose should be measured at admission and, at least, F-BG at hospital discharge.</p>