Добірка наукової літератури з теми "Leysin (Switzerland)"

Production of biogas from different organic materials is a most interesting source of renewable energy. The biomethane potential (BMP) of these materials has to be determined to get insight in design parameters for anaerobic digesters. Although several norms and guidelines for BMP tests exist, inter-laboratory tests regularly show high variability of BMPs for the same substrate. A workshop was held in June 2015, in Leysin, Switzerland, with over 40 attendees from 30 laboratories around the world, to agree on common solutions to the conundrum of inconsistent BMP test results. This paper presents the consensus of the intense roundtable discussions and cross-comparison of methodologies used in respective laboratories. Compulsory elements for the validation of BMP results were defined. They include the minimal number of replicates, the request to carry out blank and positive control assays, a criterion for the test duration, details on BMP calculation, and last but not least criteria for rejection of the BMP tests. Finally, recommendations on items that strongly influence the outcome of BMP tests such as inoculum characteristics, substrate preparation, test setup, and data analysis are presented to increase the probability of obtaining validated and reproducible results.

Abstract Context: Steroidogenic factor-1 (SF-1/NR5A1) is a nuclear receptor that regulates adrenal and reproductive development and function. NR5A1 mutations have been detected in 46,XY individuals with disorders of sexual development (DSD) but apparently normal adrenal function and in 46,XX women with normal sexual development yet primary ovarian insufficiency (POI). Objective: A group of 100 46,XY DSD and two POI was studied for NR5A1 mutations and their impact. Design: Clinical, biochemical, histological, genetic, and functional characteristics of the patients with NR5A1 mutations are reported. Setting: Patients were referred from different centers in Spain, Switzerland, and Turkey. Histological and genetic studies were performed in Barcelona, Spain. In vitro studies were performed in Bern, Switzerland. Patients: A total of 65 Spanish and 35 Turkish patients with 46,XY DSD and two Swiss 46,XX patients with POI were investigated. Main Outcome: Ten novel heterozygote NR5A1 mutations were detected and characterized (five missense, one nonsense, three frameshift mutations, and one duplication). Results: The novel NR5A1 mutations were tested in vitro by promoter transactivation assays showing grossly reduced activity for mutations in the DNA binding domain and variably reduced activity for other mutations. Dominant negative effect of the mutations was excluded. We found high variability and thus no apparent genotype-structure-function-phenotype correlation. Histological studies of testes revealed vacuolization of Leydig cells due to fat accumulation. Conclusions: SF-1/NR5A1 mutations are frequently found in 46,XY DSD individuals (9%) and manifest with a broad phenotype. Testes histology is characteristic for fat accumulation and degeneration over time, similar to findings observed in patients with lipoid congenital adrenal hyperplasia (due to StAR mutations). Genotype-structure-function-phenotype correlation remains elusive.

Cisplatin is a cytostatic used in the treatment of testicular, ovarian, cervix and bladder cancers, squamous cell carcinoma of a head and a neck, small cell and non-small cell lung cancer. For medical staff, it is available in ampoules of 10 or 50 mg with a concentrate for solution for infusion (1 mg cisplatin/ml). Occupational exposure to cisplatin may occur during production and drug use in hospital wards. Exposure during production is a minor problem because it concerns a relatively narrow group of employees of pharmaceutical companies, that are subjected to requirements of good manufacturing practice and restrictive exposure control. A much larger group of workers exposed to cisplatin are health professionals (nurses, doctors, pharmacists, cleaning service, laundry workers) who care for and have contact with treated patients. The source of exposure for medical and auxiliary personnel may be preparation and administration of drug and excretions and secretions of patients. The main routes of occupational exposure during cisplatin production processes are respiratory and skin. In hospitals, skin is the main route of exposure, although inhalation exposure cannot be excluded, mainly on cisplatin aerosols. The highest concentrations of cisplatin in the occupational environment air were < 5.3 ng/m3, while on different surfaces of pharmacy and hospital rooms, surgical equipment and gloves, concentrations did not exceed 110 ng/cm2. There are no quantitative data on the absorption of cisplatin through the skin or through the respiratory tract in humans, but it is known that the compound can absorb these routes, as demonstrated by studies conducted among pharmacists and medical personnel with significantly higher concentrations of platinum (Pt) in urine compared to the control group. There is little information on the health effects of occupational exposure to cisplatin. Only cases of occupational allergy manifesting by urticaria have been described. The data available in the literature refer mainly to adverse reactions in patients treated with cisplatin. The most commonly reported adverse effects of cisplatin are renal, haematological, hearing, gastrointestinal and neuropathic disorders. In about one third of patients, after the administration of a single dose of cisplatin (50 mg/m2), the toxic effects of the compound were observed on kidneys, bone marrow and hearing. The nephrotoxic, ototoxic and neurotoxic effects of cisplatin can be long-term and permanent. In animal toxicity studies with cisplatin, the compound was administered intraperitoneally or intravenously. Cisplatin affects mainly kidneys of animals, causing biochemical changes (including an increase creatinine and urea nitrogen levels in serum), and histopathological abnormalities, necrosis in the proximal renal tubules. Moreover, there were changes in liver enzymes activities, numerous inflammation and liver necrosis, and disorders in secretory cell distribution, intestinal barrier enzymes activities, and histopathological changes in the small intestine, which disturbed digestive processes and led to appetite disturbances in animals. Cisplatin is also ototoxic, leading to hearing loss in rodents. Changes in the blood parameters and disorders in the hematopoietic system have also been observed. Leukopenia, decreased number of neutrophils, lymphocytes and platelets, and bone marrow suppression occurred in exposed animals. In neurobehavioral tests in animals, cisplatin caused a decrease in physical activity. Cisplatin was mutagenic in tests on bacteria and on mammalian cells, including human lymphocytes. It evoked an increase in the frequency of sister chromatid exchanges and chromosomal aberrations. There were positive comet and micronucleus test results. One of the reported side effects of cisplatin therapy is its carcinogenic effect. The literature describes cases of acute non-lymphoblastic leukemia in patients treated with cisplatin only and carboplatin 6 years after chemotherapy. In the available literature, there are no data on the incidence of cancer of workers professionally exposed only to cisplatin. The existing reports concern simultaneous exposure to various cytostatics. Cisplatin has been shown to be carcinogenic to mice and rats after intraperitoneal administration. In mice exposed to cisplatin an increased number and incidence of lung adenomas were observed. After exposure of animals to cisplatin intraperitoneally, and additionally to epidermal croton oil, skin papillomas were noticed. In the exposed rats, cisplatin induced leukemia. The cisplatin was classified by IARC experts as probably carcinogenic to humans (Group 2A). In DECOS, it was considered as genotoxic carcinogen, NTP also classifies it as a potentially carcinogenic substance for humans. Although cisplatin has not been officially classified in the EU and there is lack of its harmonized classification, most manufacturers classify this compound as a carcinogen 1B category. There is no data available in the literature on clinical cases and results of epidemiological studies on the effect of cisplatin on the fetus and reproduction due to occupational exposure to this compound. Based on the described cases of pregnant patients treated with cisplatin, this compound is known to cross the placenta and into breast milk. Serious malformations were observed in 20% of children of patients treated with cisplatin in the first trimester of pregnancy and 1% of children in patients treated in the second and/or third trimester of pregnancy. In men, chronic administration of cisplatin induced reversible azoospermia and Leydig cell dysfunction. Of the 61 women with ovarian cancer undergoing conservative surgery and cisplatin chemotherapy at reproductive age, 47% gave birth to children after treatment, and 87% of those trying to get pregnant, became pregnant. In laboratory animal studies, cisplatin was highly embryotoxic. Teratogenic changes were less frequently observed. Cisplatin also affected ovarian activity. Based on the cisplatin toxicity data available in humans and animals, it is not possible to determine the dose-response relationship. The analysis of the classification of drugs used by ASHP, NIOSH, IACP and IPCS shows that the cisplatin should have a permissible occupational exposure value within 0.001–0.01 mg/m3. Considering the quantitative carcinogenicity assessment of cisplatin performed by DECOS experts and the acceptable level of occupational risk set by the Interdepartmental Commission on MAC (10-3–10-4) for carcinogens, acceptable concentrations of cisplatin in the work environment should be within 0.005 mg/m3–0.0005 mg/m3. In most countries (in the USA, Belgium, Switzerland and Hungary), the occupational exposure limits for this compound were set at 0.002 mg/m3. The maximum admissible concentration (MAC) value for cisplatin was proposed at 0.002 mg/m3. It was proposed to label the substance as “Carc. 1B” – carcinogenic substance of category 1B, “Ft” – toxic to the fetus and “skin”, because absorption through the skin may be as important as inhalation. There are no substantive basis to establish the value of the short--term (STEL) and permissible concentrations in biological material (DSB) for cisplatin.

Abstract Inter-laboratory reproducibility of biomethane potential (BMP) is dismal, with differences in BMP values for the same sample exceeding a factor of two in some cases. A large group of BMP researchers directly addressed this problem during a workshop held in Leysin, Switzerland, in June 2015. The workshop resulted in a new set of guidelines for BMP tests published in 2016, which is the subject of the present commentary. The work has continued with two international inter-laboratory studies and one additional workshop held in Freising, Germany, in 2018. The dataset generated by the two inter-laboratory studies were used to refine the validation criteria for BMP tests. Based on these new results an update to the original guidelines is proposed here.