Primary and secondary prevention of skin cancer in mountain guides: attitude and motivation for or against participation.

BACKGROUND: Outdoor professionals such as mountain guides are at a substantial risk of developing non-melanoma skin cancer (NMSC) due to solar ultraviolet radiation (UVR) exposure. Despite major recent primary prevention efforts, studies on secondary skin cancer prevention efforts are limited and corresponding data on outdoor workers scarce. OBJECTIVE: To assess the sun protective behaviour and individual motivations for or against skin cancer screening examinations in the German mountain guide population to aid in the development of effective awareness and prevention strategies. METHODS: A cross-sectional study among all registered mountain guides in Germany was conducted using a 35-item online questionnaire on primary and secondary prevention of NMSC as well as perceived barriers for prevention. RESULTS: A total of 145 mountain guides participated in the study in January 2017. Of these, 86.2% reported using sunscreen often or always, 62.1% with a sun protection factor (SPF) of 30-50% and 60.7% had undergone dermatological examination by a medical professional. The most common reasons for using secondary prevention efforts were hope of an early diagnosis (77.3%), fear of skin cancer (73.9%) and the intention to be aware of one's own health (70.5%). The main reasons for not doing so were absence of conspicuous skin conditions (63.2%) and feeling healthy (59.6%). CONCLUSION: Awareness of prevention strategies recommended by the scientific community is low among affected occupationally high-risk mountain guide populations. Understanding the specific needs of this high-risk group is essential for the development of sustainable awareness and prevention strategies.

Performance of urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and N-acetyl-ß-D-glucosaminidase to predict chronic kidney disease progression and adverse outcomes.

Urinary biomarkers can predict the progression of chronic kidney disease (CKD). In this study, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl-ß-D-glucosaminidase (NAG) were correlated with the stages of CKD, and the association of these biomarkers with CKD progression and adverse outcomes was determined. A total of 250 patients, including 111 on hemodialysis, were studied. Urinary KIM-1, NGAL, and NAG were measured at baseline. Patients not on dialysis at baseline who progressed to a worse CKD stage were compared with those who did not progress. The association of each biomarker and selected covariates with progression to more advanced stages of CKD, end-stage kidney disease, or death was evaluated by Poisson regression. NGAL was moderately correlated (rs=0.467, P<0.001) with the five stages of CKD; KIM-1 and NAG were also correlated, but weakly. Sixty-four patients (46%) progressed to a more advanced stage of CKD. Compared to non-progressors, those patients exhibited a trend to higher levels of KIM-1 (P=0.064) and NGAL (P=0.065). In patients not on dialysis at baseline, NGAL was independently associated with progression of CKD, ESKD, or death (RR=1.022 for 300 ng/mL intervals; CI=1.007-1.037, P=0.004). In patients on dialysis, for each 300-ng/mL increase in urinary NGAL, there was a 1.3% increase in the risk of death (P=0.039). In conclusion, urinary NGAL was associated with adverse renal outcomes and increased risk of death in this cohort. If baseline urinary KIM-1 and NGAL predict progression to worse stages of CKD is something yet to be explored.

Dialysis water treated by reverse osmosis decreases the levels of C-reactive protein in uremic patients.

Atherosclerosis is a major complication of chronic renal failure. Microinflammation is involved in atherogenesis and is associated with uremia and dialysis. The role of dialysate water contamination in inducing inflammation has been debated. Our aim was to study inflammatory markers in patients on chronic dialysis, before and 3 to 6 months after switching the water purification system from deionization to reverse osmosis. Patients had demographic, clinical and nutritional information collected and blood drawn for determination of albumin, ferritin, C-reactive protein (CRP), interleukin-6, and tumor necrosis factor-alpha in both situations. Acceptable levels of water purity were less than 200 colony-forming units of bacteria and less than 1 ng/ml of endotoxin. Sixteen patients died. They had higher median CRP (26.6 vs 11.2 mg/dl, P = 0.007) and lower median albumin levels (3.1 vs 3.9 g/l, P < 0.05) compared to the 31 survivors. Eight patients were excluded because of obvious inflammatory conditions. From the 23 remaining patients (mean age +/- SD: 51.3 +/- 13.9 years), 18 had a decrease in CRP after the water treatment system was changed. Overall, median CRP was lower with reverse osmosis than with deionization (13.2 vs 4.5 mg/l, P = 0.022, N = 23). There was no difference in albumin, cytokines, subjective global evaluation, or clinical and biochemical parameters. In conclusion, uremic patients presented a clinically significant reduction in CRP levels when dialysate water purification system switched from deionization to reverse osmosis. It is possible that better water treatments induce less inflammation and eventually less atherosclerosis in hemodialysis patients.

Dialysis water treated by reverse osmosis decreases the levels of C-reactive protein in uremic patients

Atherosclerosis is a major complication of chronic renal failure. Microinflammation is involved in atherogenesis and is associated with uremia and dialysis. The role of dialysate water contamination in inducing inflammation has been debated. Our aim was to study inflammatory markers in patients on chronic dialysis, before and 3 to 6 months after switching the water purification system from deionization to reverse osmosis. Patients had demographic, clinical and nutritional information collected and blood drawn for determination of albumin, ferritin, C-reactive protein (CRP), interleukin-6, and tumor necrosis factor-alpha in both situations. Acceptable levels of water purity were less than 200 colony-forming units of bacteria and less than 1 ng/ml of endotoxin. Sixteen patients died. They had higher median CRP (26.6 vs 11.2 mg/dl, P = 0.007) and lower median albumin levels (3.1 vs 3.9 g/l, P < 0.05) compared to the 31 survivors. Eight patients were excluded because of obvious inflammatory conditions. From the 23 remaining patients (mean age ± SD: 51.3 ± 13.9 years), 18 had a decrease in CRP after the water treatment system was changed. Overall, median CRP was lower with reverse osmosis than with deionization (13.2 vs 4.5 mg/l, P = 0.022, N = 23). There was no difference in albumin, cytokines, subjective global evaluation, or clinical and biochemical parameters. In conclusion, uremic patients presented a clinically significant reduction in CRP levels when dialysate water purification system switched from deionization to reverse osmosis. It is possible that better water treatments induce less inflammation and eventually less atherosclerosis in hemodialysis patients.

Photoaffinity labeling of protoporphyrinogen oxidase, the molecular target of diphenylether-type herbicides.

Diphenylether-type herbicides are extremely potent inhibitors of protoporphyrinogen oxidase, a membrane-bound enzyme involved in the heme and chlorophyll biosynthesis pathways. Tritiated acifluorfen and a diazoketone derivative of tritiated acifluorfen were specifically bound to a single class of high-affinity binding sites on yeast mitochondrial membranes with apparent dissociation constants of 7 nM and 12.5 nM, respectively. The maximum density of specific binding sites, determined by Scatchard analysis, was 3 pmol.mg-1 protein. Protoporphyrinogen oxidase specific activity was estimated to be 2500 nmol protoporphyrinogen oxidized h-1.mol-1 enzyme. The diazoketone derivative of tritiated acifluorfen was used to specifically photolabel yeast protoporphyrinogen oxidase. The specifically labeled polypeptide in wild-type mitochondrial membranes had an apparent molecular mass of 55 kDa, identical to the molecular mass of the purified enzyme. This photolabeled polypeptide was not detected in a protoporphyrinogen-oxidase-deficient yeast strain, but the membranes contained an equivalent amount of inactive immunoreactive protoporphyrinogen oxidase protein.

Purification and properties of protoporphyrinogen oxidase from the yeast Saccharomyces cerevisiae. Mitochondrial location and evidence for a precursor form of the protein.

Protoporphyrinogen oxidase, the molecular target of diphenylether-type herbicides, was purified to homogeneity from yeast mitochondrial membranes and found to be a 55-kDa polypeptide with a pI of 8.5 and a specific activity of 40,000 nmol of protoporphyrin/h/mg of protein at 30 degrees C. The Michaelis constant (Km) for protoporphyrinogen IX was 0.1 microM. Due to the high affinity of the enzyme toward oxygen, the Km for oxygen could only be approximated to 0.5-1.5 microM. The purified enzyme contained a flavin as cofactor. Studies with rabbit antibodies to yeast protoporphyrinogen oxidase showed that the enzyme is synthesized as a high molecular weight precursor (58 kDa) that is rapidly converted in vivo to the mature (55 kDa) membrane-bound form. Protoporphyrinogen oxidase activity was found only in purified yeast mitochondrial inner membrane (not in the outer membrane). Acifluorfen-methyl, a potent diphenylether-type herbicide, competitively inhibited the purified enzyme (Ki = 10 nM). The mixed inhibition by acifluorfen-methyl previously reported for the membrane-bound protoporphyrinogen oxidase (Camadro, J.M., Matringe, M., Scalla, R., and Labbe, P. (1991) Biochem. J. 277, 17-21) was shown to be related to partial proteolysis of the enzyme.

Reactions of nucleic acid bases with alpha-acetylenic esters. Synthesis and enzymatic evaluation of chemically modified nucleotides.

Analogues of adenine nucleotides, containing an additional chloromethyl-pyrimidone ring fused to the purine base, were obtained by treatment of AMP, ADP and ATP with an alpha-acetylenic ester, methyl 4-chlorobut-2-ynoate. These compounds were tested for their ability to substitute for the natural substrates or cofactors of several enzymes. With the ADP analogue, pyruvate kinase showed a significant increase of the Km value and a moderate decrease of V, while the reverse was observed when hexokinase was tested with modified ATP. Adenylate kinase was active with the ATP analogue but not with the AMP derivative. Myosin accepted the ATP analogue as a substrate, but was irreversibly modified. Among the dehydrogenases tested, only glucose-6-phosphate dehydrogenase was inhibited by the nucleotide analogue. The structure--activity relationship of these nucleotide derivatives, which represent the largest dimensional deviation known from natural nucleotides, is discussed in comparison with some earlier described dimensional probes of enzyme-nucleotide binding sites.

Human platelet actin. Evidence of beta and gamma forms and similarity of properties with sarcomeric actin.

Human blood platelet actin was purified using 30% sucrose to extract actomyosin and potassium iodide to dissociate actomyosin and to depolymerize actin. Pure actin thus obtained resembles skeletic muscle actin in its polymerization properties, CD spectra and ability to activate myosin myosin Mg2+-ATPase. Isoelectric focusing gel analysis shows that human blood platelet actin exists in beta and gamma forms. The ratio of beta to gamma forms is of 5 in purified actin, in whole cell extract and in all the fractions studied.