Drug induced liver injury (DILI) is a potentially serious adverse reaction in a few susceptible individuals under therapy by various drugs. Health care professionals facing DILI are confronted with a wealth of drug-unrelated liver diseases with high incidence and prevalence rates, which can confound the DILI diagnosis. Searching for alternative causes is a key element of RUCAM (Roussel Uclaf Causality Assessment Method) to assess rigorously causality in suspected DILI cases. Diagnostic biomarkers as blood tests would be a great help to clinicians, regulators, and pharmaceutical industry would be more comfortable if, in addition to RUCAM, causality of DILI can be confirmed. High specificity and sensitivity are required for any diagnostic biomarker. Although some risk factors are available to evaluate liver safety of drugs in patients, no valid diagnostic or prognostic biomarker exists currently for idiosyncratic DILI when a liver injury occurred. Identifying a biomarker in idiosyncratic DILI requires detailed knowledge of cellular and biochemical disturbances leading to apoptosis or cell necrosis and causing leakage of specific products in blood. As idiosyncratic DILI is typically a human disease and hardly reproducible in animals, pathogenetic events and resulting possible biomarkers remain largely undisclosed. Potential new diagnostic biomarkers should be evaluated in patients with DILI and RUCAM-based established causality. In conclusion, causality assessment in cases of suspected idiosyncratic DILI is still best achieved using RUCAM since specific biomarkers as diagnostic blood tests that could enhance RUCAM results are not yet available.

Environmental tobacco smoke (ETS)-associated particulate matter (PM) has to be seen as an independent health hazard and needs to be discussed separately from the already well-known toxic and carcinogenic compounds contained in cigarette smoke. We believe that brand-specific amounts of PM are of public interest and should be investigated. An automatic environmental tobacco smoke emitter was developed and placed into a glass-chamber to generate cigarette smoke as reliably as possible. Cigarettes were smoked automatically according to a standardized protocol. Mean concentrations (Cmean) and area under the curve (AUC) of PM2.5 released by the brands P&S, Virginia (without filter) and the 3R4F standard research cigarette of the University of Kentucky, USA, were measured and compared with each other. Cmean PM2.5 of 3R4F reference was 1,725 μg/m3, for P&S: 1,982 μg/m3 and for Virginia without filter: 1,525 μg/m3. AUC PM2.5 for 3R4F reference was: 527,644 μg/m3×sec, for P&S: 606,171 μg/m3×sec, and for Virginia without filter: 464,788 μg/m3×sec. Our modified ToPIQ-II study protocol shows significant brand-specific differences in the amounts of PM2.5 released by cigarettes into the environment, when compared to 3R4F reference cigarettes. We believe that information about PM-release of all relevant brands in relation to reference cigarettes should be published. In the light of PM as an independent risk factor for morbidity and mortality, this may serve as a basis for further epidemiologic investigations.

Liver injuries caused by the use of exogenous compounds such as drugs, herbs, and alcohol are commonly well diagnosed using laboratory tests, toxin analyses, or eventually reactive intermediates generated during metabolic degradation of the respective chemical in the liver and subject to covalent binding by target proteins. Conditions are somewhat different for idiosyncratic drug induced liver injury (DILI), for which metabolic intermediates as diagnostic aids are rarely available. Although the diagnosis of idiosyncratic DILI can well be established using the validated, liver specific, structured, and quantitative RUCAM (Roussel Uclaf Causality Assessment Method), there is an ongoing search for new diagnostic biomarkers that could assist in and also confirm RUCAM-based DILI diagnoses. With respect to idiosyncratic DILI and following previous regulatory letters of recommendations, selected biomarkers reached the clinical focus, including microRNA-122, microRNA-192, cytokeratin analogues, glutamate dehydrogenase, total HMGB-1 (High Mobility Group Box), and hyperacetylated HMGB-1 proteins. However, the new parameters total HMGB-1, and even more so the acetylated HMGB-1, came under critical scientific fire after misconduct at one of the collaborating partner centers, leading the EMA to recommend no longer the exploratory hyperacetylated HMGB1 isoform biomarkers in clinical studies. The overall promising nature of the recommended biomarkers was considered by EMA as highly dependent on the outstanding results of the now incriminated biomarker hyperacetylated HMGB-1. The EMA therefore correctly decided to officially retract its Letter of Support affecting all biomarkers listed above. New biomarkers are now under heavy scrutiny that will require re-evaluations prior to newly adapted recommendations. With Integrin beta 3 (ITGB3), however, a new diagnostic biomarker may emerge, possibly being drug specific but tested in only 16 patients; due to substantial remaining uncertainties, final recommendations would be premature. In conclusion, most of the currently recommended new biomarkers have lost regulatory support due to scientific misconduct, requiring now innovative approaches and re-evaluation before they can be assimilated into clinical practice.

Green tea (GT) and green tea extracts (GTE) have been postulated to decrease cancer incidence. In vitro results indicate a possible effect; however, epidemiological data do not support cancer chemoprevention. We have performed a PubMED literature search for green tea consumption and the correlation to the common tumor types lung, colorectal, breast, prostate, esophageal and gastric cancer, with cohorts from both Western and Asian countries. We additionally included selected mechanistical studies for a possible mode of action. The comparability between studies was limited due to major differences in study outlines; a meta analysis was thus not possible and studies were evaluated individually. Only for breast cancer could a possible small protective effect be seen in Asian and Western cohorts, whereas for esophagus and stomach cancer, green tea increased the cancer incidence, possibly due to heat stress. No effect was found for colonic/colorectal and prostatic cancer in any country, for lung cancer Chinese studies found a protective effect, but not studies from outside China. Epidemiological studies thus do not support a cancer protective effect. GT as an indicator of as yet undefined parameters in lifestyle, environment and/or ethnicity may explain some of the observed differences between China and other countries.

Chronic particulate matter (PM) exposure is correlated to various health effects, even at low amounts. WHO has defined PM concentration limits as daily and annual mean values which were made legally binding in the European Union. While many studies have focused on PM concentrations in special environments, little is known about the average PM- exposure for both employees and passengers in the German public transportation system. Particulate matter (PM10, PM2.5, PM1) – concentrations were monitored for 30 minutes at 15 different areas in Frankfurt am Main with major public traffic. Maximum and mean concentrations and, as a surrogate for the inhaled dosage, the Area Under the Curve (AUC) for 15 minutes of exposure were calculated. The WHO limits for PM10 and PM2.5 were exceeded at nearly all times and areas. Highest maximum concentrations were found at underground stations, subterranean railway stations and subterranean shopping arcades with much lower values obtained at surface points. In one measurement at a surface test point smokers who neglected the non-smoking policy could be identified as a major cause for a at least temporary strong increase of PM-load as seen in high maximum values and normal averages. Subterranean areas have high particulate matter contamination exceeding WHO limits. Improvement may be achieved by increased ventilation. Subterranean shops and kiosks, being workplaces with long term exposure, should be equipped with external air supply. The non- smoking policy of the “Deutsche Bahn” for public spaces should be enforced.