Anatomical exposure patterns of skin to sunlight: relative contributions of direct, diffuse and reflected ultraviolet radiation

Summary Background  The dose-response between ultraviolet (UV) exposure patterns and skin cancer occurrence is not fully understood. Sun-protection messages often focus on acute exposure, implicitly assuming that direct UV radiation is the key contributor to the overall UV exposure. However, little is known about the relative contribution of the direct, diffuse and reflected radiation components. Objective  To investigate solar UV exposure patterns at different body sites with respect to the relative contribution of the direct, diffuse and reflected radiation. Methods  A three-dimensional numerical model was used to assess exposure doses for various body parts and exposure scenarios of a standing individual (static and dynamic postures). The model was fed with erythemally weighted ground irradiance data for the year 2009 in Payerne, Switzerland. A year-round daily exposure (08:00-17:00 h) without protection was assumed. Results  For most anatomical sites, mean daily doses were high (typically 6·2-14·6 standard erythemal doses) and exceeded the recommended exposure values. Direct exposure was important during specific periods (e.g. midday during summer), but contributed moderately to the annual dose, ranging from 15% to 24% for vertical and horizontal body parts, respectively. Diffuse irradiation explained about 80% of the cumulative annual exposure dose. Acute diffuse exposures were also observed during cloudy summer days. Conclusions  The importance of diffuse UV radiation should not be underestimated when advocating preventive measures. Messages focused on avoiding acute direct exposures may be of limited efficiency to prevent skin cancers associated with chronic exposure.

Estimating the contribution of occupational solar ultraviolet exposure to skin cancer

BACKGROUND: Exposure to solar ultraviolet (UV) light is the main causative factor for skin cancer. Outdoor workers are at particular risk because they spend long working hours outside, may have little shade available and be bound to take their lunch at their workplace. Despite epidemiological evidence of a doubling in risk of squamous cell carcinoma in outdoor workers, the recognition of skin cancer as an occupational disease remains scarce. OBJECTIVE: To assess occupational solar UV doses and its contribution to skin cancer risk. METHODS: A numerical model (SimUVEx) was used to assess occupational and lunch break exposures, characterize exposure patterns and anatomical distribution. Risk of squamous cell carcinoma (SCC) was estimated from an existing epidemiological model. RESULTS: Horizontal body locations received 2.0-2.5 times more UV than vertical locations. Dose associated to lunch outdoor every day was similar to outdoor work one day per week but only half of a seasonal worker. Outdoor workers are associated with an increased risk of SCC but also of frequent acute episodes. CONCLUSION: Occupational solar exposure contributes largely to the overall lifetime UV dose, resulting in an excess risk of SCC. The magnitude of the estimated excess in risk supports the recognition of SCC as an occupational disease.

High-performance liquid chromatography of the renal blood flow marker p-aminohippuric acid (PAH) and its metabolite N-acetyl PAH improves PAH clearance measurements.

PAH (N-(4-aminobenzoyl)glycin) clearance measurements have been used for 50 years in clinical research for the determination of renal plasma flow. The quantitation of PAH in plasma or urine is generally performed by colorimetric method after diazotation reaction but the measurements must be corrected for the unspecific residual response observed in blank plasma. We have developed a HPLC method to specifically determine PAH and its metabolite NAc-PAH using a gradient elution ion-pair reversed-phase chromatography with UV detection at 273 and 265 nm, respectively. The separations were performed at room temperature on a ChromCart (125 mmx4 mm I.D.) Nucleosil 100-5 microm C18AB cartridge column, using a gradient elution of MeOH-buffer pH 3.9 1:99-->15:85 over 15 min. The pH 3.9 buffered aqueous solution consisted in a mixture of 375 ml sodium citrate-citric acid solution (21.01 g citric acid and 8.0 g NaOH per liter), added up with 2.7 ml H3PO4 85%, 1.0 g of sodium heptanesulfonate and completed ad 1000 ml with ultrapure water. The N-acetyltransferase activity does not seem to notably affect PAH clearances, although NAc-PAH represents 10.2+/-2.7% of PAH excreted unchanged in 12 healthy subjects. The performance of the HPLC and the colorimetric method have been compared using urine and plasma samples collected from healthy volunteers. Good correlations (r=0.94 and 0.97, for plasma and urine, respectively) are found between the results obtained with both techniques. However, the colorimetric method gives higher concentrations of PAH in urine and lower concentrations in plasma than those determined by HPLC. Hence, both renal (ClR) and systemic (Cls) clearances are systematically higher (35.1 and 17.8%, respectively) with the colorimetric method. The fraction of PAH excreted by the kidney ClR/ClS calculated from HPLC data (n=143) is, as expected, always <1 (mean=0.73+/-0.11), whereas the colorimetric method gives a mean extraction ratio of 0.87+/-0.13 implying some unphysiological values (>1). In conclusion, HPLC not only enables the simultaneous quantitation of PAH and NAc-PAH, but may also provide more accurate and precise PAH clearance measurements.

Development of an epidermal growth factor derivative with EGFR blocking activity.

The members of the epidermal growth factor (EGF)/ErbB family are prime targets for cancer therapy. However, the therapeutic efficiency of the existing anti-ErbB agents is limited. Thus, identifying new molecules that inactivate the ErbB receptors through novel strategies is an important goal on cancer research. In this study we have developed a shorter form of human EGF (EGFt) with a truncated C-terminal as a novel EGFR inhibitor. EGFt was designed based on the superimposition of the three-dimensional structures of EGF and the Potato Carboxypeptidase Inhibitor (PCI), an EGFR blocker previously described by our group. The peptide was produced in E. coli with a high yield of the correctly folded peptide. EGFt showed specificity and high affinity for EGFR but induced poor EGFR homodimerization and phosphorylation. Interestingly, EGFt promoted EGFR internalization and translocation to the cell nucleus although it did not stimulate the cell growth. In addition, EGFt competed with EGFR native ligands, inhibiting the proliferation of cancer cells. These data indicate that EGFt may be a potential EGFR blocker for cancer therapy. In addition, the lack of EGFR-mediated growth-stimulatory activity makes EGFt an excellent delivery agent to target toxins to tumours over-expressing EGFR.

Carotenoid-based colours reflect the stress response in the common lizard.

Under chronic stress, carotenoid-based colouration has often been shown to fade. However, the ecological and physiological mechanisms that govern colouration still remain largely unknown. Colour changes may be directly induced by the stressor (for example through reduced carotenoid intake) or due to the activation of the physiological stress response (PSR, e.g. due to increased blood corticosterone concentrations). Here, we tested whether blood corticosterone concentration affected carotenoid-based colouration, and whether a trade-off between colouration and PSR existed. Using the common lizard (Lacerta vivipara), we correlatively and experimentally showed that elevated blood corticosterone levels are associated with increased redness of the lizard's belly. In this study, the effects of corticosterone did not depend on carotenoid ingestion, indicating the absence of a trade-off between colouration and PSR for carotenoids. While carotenoid ingestion increased blood carotenoid concentration, colouration was not modified. This suggests that carotenoid-based colouration of common lizards is not severely limited by dietary carotenoid intake. Together with earlier studies, these findings suggest that the common lizard's carotenoid-based colouration may be a composite trait, consisting of fixed (e.g. genetic) and environmentally elements, the latter reflecting the lizard's PSR.

The Vitamin A Derivative All-Trans Retinoic Acid Repairs Amyloid-β-Induced Double-Strand Breaks in Neural Cells and in the Murine Neocortex.

The amyloid-β peptide or Aβ is the key player in the amyloid-cascade hypothesis of Alzheimer's disease. Aβ appears to trigger cell death but also production of double-strand breaks (DSBs) in aging and Alzheimer's disease. All-trans retinoic acid (RA), a derivative of vitamin A, was already known for its neuroprotective effects against the amyloid cascade. It diminishes, for instance, the production of Aβ peptides and their oligomerisation. In the present work we investigated the possible implication of RA receptor (RAR) in repair of Aβ-induced DSBs. We demonstrated that RA, as well as RAR agonist Am80, but not AGN 193109 antagonist, repair Aβ-induced DSBs in SH-SY5Y cells and an astrocytic cell line as well as in the murine cortical tissue of young and aged mice. The nonhomologous end joining pathway and the Ataxia Telangiectasia Mutated kinase were shown to be involved in RA-mediated DSBs repair in the SH-SY5Y cells. Our data suggest that RA, besides increasing cell viability in the cortex of young and even of aged mice, might also result in targeted DNA repair of genes important for cell or synaptic maintenance. This phenomenon would remain functional up to a point when Aβ increase and RA decrease probably lead to a pathological state.

The Proteolytic Activation of (H3N2) Influenza A Virus Hemagglutinin Is Facilitated by Different Type II Transmembrane Serine Proteases.

UNLABELLED: Cleavage of influenza virus hemagglutinin (HA) by host cell proteases is necessary for viral activation and infectivity. In humans and mice, members of the type II transmembrane protease family (TTSP), e.g., TMPRSS2, TMPRSS4, and TMPRSS11d (HAT), have been shown to cleave influenza virus HA for viral activation and infectivityin vitro Recently, we reported that inactivation of a single HA-activating protease gene,Tmprss2, in knockout mice inhibits the spread of H1N1 influenza viruses. However, after infection ofTmprss2knockout mice with an H3N2 influenza virus, only a slight increase in survival was observed, and mice still lost body weight. In this study, we investigated an additional trypsin-like protease, TMPRSS4. Both TMPRSS2 and TMPRSS4 are expressed in the same cell types of the mouse lung. Deletion ofTmprss4alone in knockout mice does not protect them from body weight loss and death upon infection with H3N2 influenza virus. In contrast,Tmprss2(-/-)Tmprss4(-/-)double-knockout mice showed a remarkably reduced virus spread and lung pathology, in addition to reduced body weight loss and mortality. Thus, our results identified TMPRSS4 as a second host cell protease that, in addition to TMPRSS2, is able to activate the HA of H3N2 influenza virusin vivo IMPORTANCE: Influenza epidemics and recurring pandemics are responsible for significant global morbidity and mortality. Due to high variability of the virus genome, resistance to available antiviral drugs is frequently observed, and new targets for treatment of influenza are needed. Host cell factors essential for processing of the virus hemagglutinin represent very suitable drug targets because the virus is dependent on these host factors for replication. We reported previously thatTmprss2-deficient mice are protected against H1N1 virus infections, but only marginal protection against H3N2 virus infections was observed. Here we show that deletion of two host protease genes,Tmprss2andTmprss4, strongly reduced viral spread as well as lung pathology and resulted in increased survival after H3N2 virus infection. Thus, TMPRSS4 represents another host cell factor that is involved in cleavage activation of H3N2 influenza virusesin vivo.

Synthesis of a tetrahydroimidazo-[2',1':2,3]thiazolo[5,4-c]pyridine derivative with Met inhibitory activity

A straightforward synthesis of the Met antagonist JLK1360 involving an alkylationcyclocondensation process using aminothiazole 1 and nitrophenacyl bromide 2, reduction of the nitro group, and coupling of the resulting tetracyclic aniline 5 with an appropriate N-acyl alanine derivative, is reported.

Synthesis of a tetrahydroimidazo-[2',1':2,3]thiazolo[5,4-c]pyridine derivative with Met inhibitory activity

A straightforward synthesis of the Met antagonist JLK1360 involving an alkylationcyclocondensation process using aminothiazole 1 and nitrophenacyl bromide 2, reduction of the nitro group, and coupling of the resulting tetracyclic aniline 5 with an appropriate N-acyl alanine derivative, is reported.

Análise multicomponente simultânea por espectrofotometria de absorção molecular UV-VIS

This review presents the evolution of simultaneous multicomponent analysis by absorption spectrophotometry in the ultraviolet and visual regions in terms of some qualitative and quantitative analysis techniques, otimization methods, as well as applications and modern trends.

Perfil cromatográfico de duas espécies de Plumbaginaceae: Plumbago scandens L. E Plumbago auriculata Lam

The genus Plumbago belongs to the family Plumbaginaceae, order Plumbaginales. Comparative chemical profile of P. scandens (native) and P. auriculata (cultivated) was obtained by normal and reversed-phase high performance liquid chromatography with photodiode array detector. Comparison of the ultraviolet espectra and the retention times for the compounds allowed to find similar metabolic patterns in roots, stems and leaves. Four flavonoids, one phenolic acid or derivative and the naphtoquinone plumbagin were comparatively identified to standards.

High performance liquid chromatography method for quantification of the N-phenylpiperazine derivative LASSBio-579 in rat plasma

A rapid HPLC analytical method was developed and validated for the determination of the N-phenylpiperazine derivative LASSBio-579in plasma rat. Analyses were performed using a C18 column and elution with 20 mM sodium dihydrogen phosphate monohydrate - methanol. The analyte was monitored using a photodiode array detector (257 nm). Calibration curves in spiked plasma were linear over the concentration range of 0.3-8 mg/mL with determination coefficient > 0.99. The lower limit of quantification was 0.3 mg/mL. The applicability of the HPLC method for pharmacokinetic studies was tested using plasma samples obtained after administration of LASSBio-579 to Wistar rats, showing the specificity of the method.