Cretaceous to Miocene cooling of Austroalpine units southeast of the Tauern Window (Eastern Alps) constrained by multi-system thermochronometry

The cooling history of the Polinik and Kreuzeck Blocks of the Austroalpine units to the southeast of the Tauern Window are reexamined in the light of new mica Ar/Ar-, zircon fission track and apatite fission track data. Our new data demonstrate that the two blocks experienced a significantly different thermal evolution during Mesozoic-Cenozoic times: The Polinik Block revealed Late Cretaceous Ar/Ar ages (87.2–81.6 Ma), which reflect cooling subsequent to the thermal peak of Eo-Alpine metamorphism. The Kreuzeck Block, in contrast, shows early Permian Ar/Ar ages (295–288 Ma) that reflect post-Variscan extension and cooling. Late Cretaceous zircon fission track ages (67.8 and 67.3 Ma) found in the Kreuzeck Block are interpreted to reflect post-metamorphic exhumational cooling after the Eo-Alpine metamorphism. Miocene apatite fission track ages (21.3–8.7 Ma) and transdimensional inverse thermal history modelling results suggest that the Polinik Block cooled rapidly through the apatite partial annealing zone and exhumed to near surface temperatures in the middle Miocene. The Kreuzeck Block, in contrast, cooled and exhumed to near surface temperatures already in the Oligocene and early Miocene as evidenced by apatite fission track ages (29.1–16.4 Ma) and thermal history modelling results. Based on the temperature difference between the uppermost and lowermost samples from steep elevation profiles, calculated paleo-geothermal gradients are in the range between 47 and 43 °C/km for the late Oligocene and middle Miocene periods. These high values likely resulted from an elevated heat flow associated with magmatism in the area and from the fast exhumation of hot Penninic domains during Oligocene and Miocene times

Human germ cell tumours: expression of γ-glutamyl transpeptidase and sensitivity to cisplatin

Previous studies have shown that the enzyme γ-glutamyl transpeptidase (GGT) is essential for the nephrotoxicity of cisplatin. This study was designed to determine whether GGT activity is necessary for the therapeutic effect of the drug. The relationship between GGT expression and clinical response to platinum-based chemotherapy was examined in 41 human germ cell tumours. Sections of formalin-fixed, paraffin-embedded tumours were immunohistochemically stained with an antibody directed against human GGT. There was no expression of GGT in any of the 17 seminomas or four dysgerminomas; whereas, 12/12 ovarian yolk sac tumours and 4/4 embryonal carcinomas of the testis were GGT-positive. In stage I tumours fewer tumour cells expressed GGT than in later stage tumours. In four germ cell tumours of mixed histology, the seminomatous and dysgerminoma areas were GGT-negative while the areas of the tumour with yolk sac or embryonal histology contained GGT-positive tumour cells. The patients with seminomas or dysgerminomas who were treated with cisplatin-based chemotherapy, all had a complete response despite the absence of GGT expression in these tumours. Fifteen of the 16 patients with yolk sac or embryonal carcinomas received cisplatin-based chemotherapy following surgery. Twelve had a complete response, while three failed to respond to platinum-based therapy. There was no correlation between the level of GGT-expression and response to therapy in this group. Three of the four patients with tumours of mixed histology were treated with cisplatin-based therapy, and had a complete response. Therefore, expression of GGT is not necessary for the therapeutic effect of cisplatin in germ cell tumours. The results from this study suggest that systemic inhibition of GGT would inhibit the nephrotoxic side-effect of cisplatin without interfering with its activity towards germ cell tumours. © 1999 Cancer Research Campaig

Comparing United States and Canadian population exposures from National Biomonitoring Surveys: Bisphenol A intake as a case study

The Centers for Disease Control and Prevention provides biomonitoring data in the United States as part of the National Health and Nutrition Examination Survey (NHANES). Recently, Statistics Canada initiated a similar survey — the Canadian Health Measures Survey (CHMS). Comparison of US and Canadian biomonitoring data can generate hypotheses regarding human exposures from environmental media and consumer products. To ensure that such comparisons are scientifically meaningful, it is essential to first evaluate aspects of the surveys' methods that can impact comparability of data. We examined CHMS and NHANES methodologies, using bisphenol A (BPA) as a case study, to evaluate whether survey differences exist that would hinder our ability to compare chemical concentrations between countries. We explored methods associated with participant selection, urine sampling, and analytical methods. BPA intakes were also estimated to address body weight differences between countries. Differences in survey methods were identified but are unlikely to have substantial impacts on inter-survey comparisons of BPA intakes. BPA intakes for both countries are below health-based guidance values set by the US, Canada and the European Food Safety Authority. We recommend that before comparing biomonitoring data between surveys, a thorough review of methodologic aspects that might impact biomonitoring results be conducted

Bisphenol A and 17β-Estradiol Promote Arrhythmia in the Female Heart via Alteration of Calcium Handling

There is wide-spread human exposure to bisphenol A (BPA), a ubiquitous estrogenic endocrine disruptor that has been implicated as having potentially harmful effects on human heart health. Higher urine BPA concentrations have been shown to be associated with cardiovascular diseases in humans. However, neither the nature nor the mechanism(s) of BPA action on the heart are understood. leak suppressed estrogen-induced triggered activities. The rapid response of female myocytes to estrogens was abolished in an estrogen receptor (ER) β knockout mouse model. leak. Our study provides the first experimental evidence suggesting that exposure to estrogenic endocrine disrupting chemicals and the unique sensitivity of female hearts to estrogens may play a role in arrhythmogenesis in the female heart

Cardiotoxicity of Freon among refrigeration services workers: comparative cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Freon includes a number of gaseous, colorless chlorofluorocarbons. Although freon is generally considered to be a fluorocarbon of relatively low toxicity; significantly detrimental effects may occur upon over exposure. The purpose of the present study is to investigate whether occupational exposure to fluorocarbons can induce arterial hypertension, myocardial ischemia, cardiac arrhythmias, elevated levels of plasma lipids and renal dysfunction.</p> <p>Methods</p> <p>This comparative cross-sectional study was conducted at the cardiology clinic of the Suez Canal Authority Hospital (Egypt). The study included 23 apparently healthy male workers at the refrigeration services workshop who were exposed to fluorocarbons (FC 12 and FC 22) and 23 likewise apparently healthy male workers (unexposed), the control group. All the participants were interviewed using a pre-composed questionnaire and were subjected to a clinical examination and relevant laboratory investigations.</p> <p>Results</p> <p>There were no significant statistical differences between the groups studied regarding symptoms suggesting arterial hypertension and renal affection, although a significantly higher percentage of the studied refrigeration services workers had symptoms of arrhythmias. None of the workers had symptoms suggesting coronary artery disease. Clinical examination revealed that the refrigeration services workers had a significantly higher mean pulse rate compared to the controls, though no significant statistical differences were found in arterial blood pressure measurements between the two study groups. Exercise stress testing of the workers studied revealed normal heart reaction to the increased need for oxygen, while sinus tachycardia was detected in all the participants. The results of Holter monitoring revealed significant differences within subject and group regarding the number of abnormal beats detected throughout the day of monitoring (p < 0.001). There were no significant differences detected in the average heart rate during the monitoring period within subject or group. Most laboratory investigations revealed absence of significant statistical differences for lipid profile markers, serum electrolyte levels and glomerular lesion markers between the groups except for cholesterol and urinary β2-microglobulin (tubular lesion markers) levels which were significantly elevated in freon exposed workers.</p> <p>Conclusions</p> <p>Unprotected occupational exposure to chlorofluorocarbons can induce cardiotoxicity in the form of cardiac arrhythmias. The role of chlorofluorocarbons in inducing arterial hypertension and coronary artery diseases is unclear, although significantly elevated serum cholesterol and urinary β2-microglobulin levels raise a concern.</p

Critical evaluation of key evidence on the human health hazards of exposure to bisphenol A

Despite the fact that more than 5000 safety-related studies have been published on bisphenol A (BPA), there seems to be no resolution of the apparently deadlocked controversy as to whether exposure of the general population to BPA causes adverse effects due to its estrogenicity. Therefore, the Advisory Committee of the German Society of Toxicology reviewed the background and cutting-edge topics of this BPA controversy. The current tolerable daily intake value (TDI) of 0.05 mg/kg body weight [bw]/day, derived by the European Food Safety Authority (EFSA), is mainly based on body weight changes in two- and three-generation studies in mice and rats. Recently, these studies and the derivation of the TDI have been criticized. After having carefully considered all arguments, the Committee had to conclude that the criticism was scientifically not justified; moreover, recently published additional data further support the reliability of the two-and three-generation studies demonstrating a lack of estrogen-dependent effects at and below doses on which the current TDI is based. A frequently discussed topic is whether doses below 5 mg/ kg bw/day may cause adverse health effects in laboratory animals. Meanwhile, it has become clear that positive results from some explorative studies have not been confirmed in subsequent studies with higher numbers of animals or a priori defined hypotheses. Particularly relevant are some recent studies with negative outcomes that addressed effects of BPA on the brain, behavior, and the prostate in rodents for extrapolation to the human situation. The Committee came to the conclusion that rodent data can well be used as a basis for human risk evaluation. Currently published conjectures that rats are insensitive to estrogens compared to humans can be refuted. Data from toxicokinetics studies show that the half-life of BPA in adult human subjects is less than 2 hours and BPA is completely recovered in urine as BPA-conjugates. Tissue deconjugation of BPA-glucuronide and -sulfate may occur. Because of the extremely low quantities, it is only of minor relevance for BPA toxicity. Biomonitoring studies have been used to estimate human BPA exposure and show that the daily intake of BPA is far below the TDI for the general population. Further topics addressed in this article include reasons why some studies on BPA are not reproducible; the relevance of oral versus non-oral exposure routes; the degree to which newborns are at higher systemic BPA exposure; increased BPA exposure by infusions in intensive care units; mechanisms of action other than estrogen receptor activation; and the current regulatory status in Europe, as well as in the USA, Canada, Japan, New Zealand, and Australia. Overall, the Committee concluded that the current TDI for BPA is adequately justified and that the available evidence indicates that BPA exposure represents no noteworthy risk to the health of the human population, including newborns and babies