Role of UVA in the pathogenesis of melanoma and non-melanoma skin cancer. A short review

It is well established, at least in mice, that not only ultraviolet C (UVC) or ultraviolet B (UVB), but also ultraviolet A (UVA) is able to induce squamous cell carcinomas. Results from animal models, epidemiological studies, and clinical observations suggest that UVA might play an important role in the pathogenesis of malignant melanoma as well. In contrast to UVC or UVB, UVA is hardly able to excite the DNA molecule directly and produces only few pyrimidine dimers. Oxidative DNA base damage, generated indirectly through photosensitizers, might be responsible for the mutagenic and carcinogenic properties of UVA. This is supported by differences in mutation spectra induced by UVA and UVB in mammalian cells and tumors. Avoidance of natural and artificial UVA sources is recommended, especially for melanoma-prone individuals.     

Cytotoxicity of occupationally and environmentally relevant mycotoxins

Mycotoxins can cause various toxic effects in humans. Acute and chronic respiratory diseases were reported after inhalation of organic dust containing toxigenic moulds and mycotoxins, respectively. To gain first insights into health effects from airborne exposure to these compounds, five toxigenic airborne moulds of the genera Aspergillus and Penicillium collected at composting plants and eight reference mycotoxins were tested for cytotoxicity in four established cell lines as a surrogate of tissues known or suspected to be targets of toxic effects of mycotoxins. The known mycotoxins sterigmatocystin, fumagillin, verruculogen, penitrem A, and roquefortine C were detected in extracts of the moulds. All five extracts caused serious toxic effects in the cell lines. Sterigmatocystin caused a 80-fold higher toxicity in the A-549 lung cell line compared to Hep-G2 liver cells indicating a specific susceptibility of A-549 to this agent. Since only a minor part of the toxic effects of the extracts in A-549 cells and--to a lesser extent--in the other cell lines could be explained by contents of the identified mycotoxins, the presence of additional mycotoxins or other toxic principles is assumed in the mould extracts. However, the detected mycotoxins in the mould extracts and their distinctive cytotoxicity support the hypothesis that mycotoxins may be involved in the aetiology of lung diseases due to the inhalation of organic dust.     

Efficacy and tolerability of an ulcer compression stocking for therapy of chronic venous ulcer compared with a below-knee compression bandage: results from a prospective, randomized, multicentre trial

OBJECTIVE: To investigate the possibility of improving healing rates in ulcus cruris venosum by using an ulcer compression stocking (U-Stocking) (Venotrain ulcertec) as compared to compression bandages. RESEARCH DESIGN AND SETTING: Prospective, multicentre, open-labelled, randomized, active-controlled study with blinded assessment of the primary endpoint. Sixteen phlebology outpatient clinics in Germany or the Netherlands or German medical practices specialized in phlebology. PATIENTS AND METHODS: 134 patients with venous leg ulcers entered the study. Among others, patients with infected ulcer or obesity were excluded. 121 patients were eligible for primary efficacy analyses. U-Stocking or bandages applied for at least eight hours per day and for up to 12 weeks. The primary endpoint was the healing rate after 12 weeks as assessed by planimetric measures. The secondary outcome variables were time to healing, changes in ulcer size (planimetry), experience of use and patient compliance. MAIN OUTCOME MEASURES: Therapy with the U-Stocking produced a significantly higher rate of complete healing of 47.5% (29/61) versus 31.7% (19/60) with bandages, 1-sided p = 0.0129 [CI: 95% for differences: 4.3% to 28.5%]. Mean time to healing was 46 days in both groups. Time required for application of the U-Stocking was a mean of 5.4 min (SD 5.4) versus 8.5 min (SD 6.5) for bandages, p = 0.0001. Around three patients in each treatment group were affected by serious adverse events. All treatment-related adverse events are known for compression therapy. CONCLUSIONS: The U-Stocking was superior to bandages in compression therapy for venous ulcer. This is of significance to new treatment standards as well as to future studies of longer term therapy (> 12 weeks) for unhealed ulcers or prevention of recurrence.     

Cyto- and genotoxic effects of coordination complexes of platinum,palladium and rhodium in vitro

The growing industrial use of platinum group elements as catalysts, especially in automobile exhaust detoxification (trimetal catalytic converters), is causing increasing occupational and environmental pollution. The cytotoxic and mutagenic properties of industrially used coordination complexes of platinum, palladium and rhodium were investigated using the neutral red cytotoxicity assay on two established cell lines and theSalmonella typhimurium/microsome test system (Ames test). Cytotoxic effects of the platinum complexes, measured as ED₅₀, occurred at test concentrations of 0.2 mM. The analogous palladium salts tested were 3 times less toxic with ED₅₀ being 0.6 mM, while the rhodium salts proved to be 30 times less toxic (ED₅₀=6 mM). Levels of toxicity of the different complexes of a particular metal did not differ significantly from each other, which indicates that the metal itself is responsible for the toxic effects. In the Ames test, the spontaneous mutation rates increased by factors of 3 to 20 when the four tester strains were exposed to the platinum complexes. The analogous rhodium compounds proved to be considerably less mutagenic, and palladium demonstrated no mutagenic potential. As all of the four tester strains contain different mutations, the mutagenic potential of platinum and rhodium complexes appears to be based on a variety of mechanisms that damage DNA. From these in vitro experiments, it can be concluded that water-soluble complex salts of rhodium are less toxic and have a smaller mutagenic potential than the analogous platinum complexes. For palladium there is no evidence of any mutagenic property. From this point of view, the development of a catalytic converter containing predominantly palladium may be a possible means of minimizing potential health risks from this exhaust detoxification technique.     

Human exposure to airborne aniline and formation of methemoglobin: a contribution to occupational exposure limits

Aniline is an important starting material in the manufacture of polyurethane-based plastic materials. Aniline-derived methemoglobinemia (Met-Hb) is well described in exposed workers although information on the dose–response association is limited. We used an experimental design to study the association between aniline in air with the formation of Met-Hb in blood and the elimination of aniline in urine. A 6-h exposure of 2 ppm aniline in 19 non-smoking volunteers resulted in a time-dependent increase in Met-Hb in blood and aniline in urine. The maximum Met-Hb level in blood (mean 1.21 ± 0.29 %, range 0.80–2.07 %) and aniline excretion in urine (mean 168.0 ± 51.8 µg/L, range 79.5–418.3 µg/L) were observed at the end of exposure, with both parameters rapidly decreasing after the end of exposure. After 24 h, the mean level of Met-Hb (0.65 ± 0.18 %) returned to the basal level observed prior to the exposure (0.72 ± 0.19 %); whereas, slightly elevated levels of aniline were still present in urine (means 17.0 ± 17.1 vs. 5.7 ± 3.8 µg/L). No differences between males and females as well as between slow and fast acetylators were found. The results obtained after 6-h exposure were also comparable to those observed in four non-smoking volunteers after 8-h exposure. Maximum levels of Met-Hb and aniline in urine were 1.57 % and 305.6 µg/L, respectively. Overall, our results contribute to the risk assessment of aniline and as a result, the protection of workers from aniline-derived adverse health effects at the workplace.     

Exposure assessment of potash miners at elevated CO2 levels

Purpose

In a potash mine in the center of Germany, stationary measurements 40 cm above ground level have revealed occasional increases in the carbon dioxide (CO₂) levels that exceed the 0.5 vol.% German occupational exposure limit (OEL). This study, therefore, aimed to examine the individual exposures of potash miners to CO₂ at their underground workplaces.

Methods

119 miners were equipped with personal CO₂ detectors to log the individual CO₂ exposures during underground work. We decided to use electrochemical monitors due to their compactness and minimal mass. Furthermore, generated CO₂ measurements with precipitated overshooting and false positive CO₂ values were studied using diverse CO₂ test gases and different fumigation times.

Results

The personal detectors showed short-term CO₂ peak exposures at very high concentrations in a limited number of workers. Twenty-two threshold limit value violations were observed according to the present OEL, and the personal CO₂ monitoring allowed categorization into three exposure groups, low (n = 83), moderate (n = 26) and high burdens (n = 10) of CO₂.

Conclusions

The electrochemical sensors used have numerous properties that can potentially influence the assessment of exposures. The current findings suggest that assessing similar exposure scenarios, with respect to elevated and strongly fluctuating CO₂ concentrations, the behavior of electrochemical sensors should be taken into consideration.     

Das Programm für Nationale VersorgungsLeitlinien von BÄK, AWMF und KBV

The Programme for National Disease Management Guidelines (German DM-CPG Programme) aims at the implementation of best practice recommendations for prevention, acute care, rehabilitation and chronic care. The programme, focussing on high priority healthcare topics, has been sponsored since 2003 by the German Medical Association (BAEK), the Association of the Scientific Medical Societies (AWMF), and by the National Association of Statutory Health Insurance Physicians (KBV). It is organised by the German Agency for Quality in Medicine, a founding member of the Guidelines International Network (G-I-N). The main objective of the programme is to establish consensus of the medical professions on evidence-based key recommendations covering all sectors of health care provision and facilitating the coordination of care for the individual patient through time and across disciplines. Within this framework experts from national patient self-help groups have been developing patient guidance based upon the recommendations for healthcare providers. The article describes goals, topics and selected contents of the DM-CPG programme - using asthma as an example.     

Booster immunization with a hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus vaccine and Haemophilus influenzae type b conjugate combination vaccine in the second year of life: safety, immunogenicity and persistence of antibody responses

The immunogenicity and reactogenicity of booster vaccination with GSK Biologicals' hexavalent DTPa-HBV-IPV/Hib vaccine was assessed in toddlers aged 12-18 months previously primed with the same combination (N=341), or with DTPa-IPV/Hib and HBV administered separately (N=102; Trials 217744/059 and 217744/096). Antibody persistence at age 4-6 years was also assessed in children who had received a 4th consecutive dose of DTPa-HBV-IPV/Hib vaccine or separate DTPa-IPV/Hib and HBV vaccines in this study and in another study conducted under similar conditions in Germany. Prior to booster vaccination in the second year of life, antibody concentrations and seroprotection rates were similar irrespective of the primary vaccine used. One month after boosting with DTPa-HBV-IPV/Hib, substantial antibody increases were observed against all vaccine antigens indicative of previous immune priming. Seropositivity and booster response rates against all antigens were 97.4-100%. Reactogenicity following booster vaccination with DTPa-HBV-IPV/Hib was similar regardless of the primary regimen used. Three to four years after administration of the 4th DTPa-HBV-IPV/Hib dose, >90% vaccinees had persistent protective antibody concentrations against diphtheria, hepatitis B, Hib and the three poliovirus types. Anti-tetanus antibody concentrations were > or = 0.1 IU/ml in 76.4% subjects and seropositivity for pertussis antibodies ranged from 34.5% for PT to 98.9% for FHA. In conclusion, the combined hexavalent DTPa-HBV-IPV/Hib vaccine is immunogenic and safe when used for boosting in the second year of life, regardless of the primary vaccine used, and offers sustained protection during early childhood and beyond.