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  • 11
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary A spontaneously immortalized human keratinocyte line, HaCaT, was used as an in vitro model to predict the cutaneous irritation of anionic surfactants. For this purpose, a number of sodium salts of N-alkyl sulphates with hydrocarbon chain lengths varying between C8 and C16 were studied for possible cytotoxic effects. The endpoints used to assess toxicity were uptake of the vital dye neutral red (NR) and cell morphology criteria 24 h after dosing. A linear proportionality between keratinocyte number and NR uptake was established. All tested surfactants had cytotoxic effects as demonstrated by a decreased NR uptake, which showed a clear dose–response relationship. Concentrations resulting in 50% inhibition of NR uptake (IC-50) ranged from 0·15 mmol (sodium lauryl sulphate, C12) to 1·23 mmol (sodium octyl sulphate, C8). The in vitro cytotoxicity data were highly reproducible when the test was repeated after several weeks. The cytotoxicity data from these assays were compared with the irritant responses (as evaluated by measurement of erythema and transepidermal water loss) obtained after 24 h application of the same compounds (300 μ1 of 20 mmol aqueous solution) to the volar forearm of human volunteers. There were significant linear correlations between the IC-50 values and both barrier damage (transepidermal water loss) and erythema (as evaluated by skin colour reflectance measurements). For the test substances, however, the sensitivity of the in vitro system was between 10 and 100 times higher than that observed in human skin in vivo. This quantitative difference can largely be ascribed to the effective permeability barrier of normal human skin in vivo, which protects living keratinocytes from the cytotoxic effects of surfactant molecules.The results indicate that normal human keratinocytes in culture are a promising screening method for predicting the irritation potential of anionic surfactants. Confirmation, however, has still to be obtained by appropriate in vivo testing in human volunteers.
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  • 12
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background While great efforts have been made in recent years to develop in vitro methods for assessing skin irritation potential, there are relatively few data that correlate in vitro data with in vivo data. Objectives To expand our previously reported investigations on in vitro vs. in vivo correlation of a series of homologous N-alkyl sulphates of different alkyl chain length to include primary skin irritants of different chemical classes. Methods Anionic surfactants (three different sodium alkyl sulphonates and sodium lauryl sulphate), cationic surfactants (three alkyl trimethyl ammonium bromides), non-ionic surfactants (polyoxyethylene-20-cetyl ether and Tween 20), benzoic acid, dimethyl sulphoxide and phenol were chosen as model irritants. A spontaneously immortalized human keratinocyte line, HaCaT, was used as an in vitro model to predict the cutaneous irritation. The end-point used to assess toxicity was uptake of the vital dye neutral red (NR) 24 h after dosing. The cytotoxicity data from these assays were compared with the irritant responses (as evaluated by measurement of erythema and transepidermal water loss) obtained after 24-h application of the same compounds (100 µL of 20 mmol L−1 aqueous solution) to the volar forearm of human volunteers. Results All tested irritants had cytotoxic effects as demonstrated by a decreased NR uptake, which showed a clear dose–response relationship. Concentrations resulting in 50% inhibition of NR uptake (IC50) ranged from 8 µmol L−1 (hexadecyl trimethyl ammonium bromide) to 328 mmol L−1 (dimethyl sulphoxide). We found a good overall correlation between in vitro cytotoxicity (NR uptake IC50 values) and in vivo irritation potential in humans. Only the high molecular weight compounds Tween 20 and polyoxyethylene-20-cethyl ether were problematic, as their irritation potential was overestimated by the in vitro assay. This non-conformity of these high molecular weight (〉 1000) compounds was expected, and can be largely attributed to the epidermal permeability barrier. The epidermal barrier, which greatly limits the percutaneous penetration of xenobiotics in vivo, does not exist in cell culture models. Conclusions The in vitro cytotoxicity model is a useful screening tool, but data should be interpreted critically and require confirmation by appropriate in vivo studies.
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  • 13
    ISSN: 1432-1335
    Keywords: Colon ; Rectum ; Adenocarcinoma ; Glutathione ; GSH S-transferase ; GSH peroxidase-γ-Glutamyltranspeptidase ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A high content of total glutathione and high activities of both GSH S-aryltransferase (CDNB) and GSH peroxidase were found in different segments of the human intestinal mucosa comparable to findings in human gastric mucosa. Intraindividual comparisons of tumorous and nontumorous tissue specimens in patients with adenocarcinomas of the colon and rectum revealed no marked differences in their glutathione content and enzyme activities except in the sigma, where we found significantly lower GSH concentrations and higher GSH S-aryltransferase activities in the carcinomatous tissue. γ-Glutamyl-transpeptidase activity, a marker of neoplastic cell growth in experimental hepatocarcinogenesis, did not differ between tumorous and nontumorous tissue areas. The presence and high activity of the GSH-dependent enzyme system in different segments of the human intestinal mucosa may reflect its role in the defense against toxic and putative carcinogenic xenobiotics entering the body via the gastrointestinal tract.
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  • 14
    ISSN: 1530-0358
    Keywords: Colorectal ; Cancer ; Selenium ; Glutathione peroxidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: It is still controversial whether a low selenium level and a reduced activity of the selenium-dependent enzyme, glutathione peroxidase, in blood are associated with an increased risk and poor prognosis of cancer in humans. This study evaluates whether colorectal cancer patients have lower serum selenium and glutathione peroxidase levels than a gender-matched and age-matched control group and whether there is a correlation to clinical data and prognosis. METHODS: In a retrospective study, serum selenium and glutathione peroxidase activity of 106 patients with colorectal cancer were determined. Clinical data were provided by our long-term follow-up program for colorectal cancer patients. RESULTS: Patients with a selenium level 〈70 µg/l had a significantly lower mean survival time and a lower cumulative cancer-related survival rate than patients with a selenium level 〉70 µg/l (P=0.0009). When considering the different tumor stages, a decline of the mean selenium level in the T4 carcinoma group was found in the analysis of variance (P〈0.05). The lowest selenium level was found for patients with advanced tumor disease and in a preoperative situation,i.e., high tumor burden. In comparison with the control group, the cancer group showed a significant reduction of serum glutathione peroxidase activity (P〈0.01) but no significant difference in selenium level. CONCLUSIONS: These results support the hypothesis of an association between low selenium level and advanced tumor disease. From our data, it cannot be decided whether this phenomenon is more likely to be a consequence or a causative factor for development and course of the disease.
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  • 15
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 16
    ISSN: 1432-1440
    Keywords: Glutathione ; GSH-peroxidase ; GSH S-aryltransferase ; Human gastric mucosa ; Gastric carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The γ-glutamyl-transferase activity, the total glutathione content, the GSH-peroxidase activity, and the GSH S-transferase activity using an aryl substrate were estimated in the S9 fraction of gastric biopsy specimens taken from patients with normal stomach morphology (n=24), acute gastritis (n=15), chronic-atrophic gastritis (n=10), gastric ulcer (n=9), and carcinoma of the stomach (n=12). The total glutathione content of normal gastric mucosal specimens was significantly higher than that of human liver biopsy specimens, whereas the GSH-peroxidase and the GSH S-aryltransferase activities were much lower than those found in the liver. Specimens of gastric ulcer had significantly lower enzyme activities of GSH-peroxidase and GSH-aryltransferase, whereas gastric cancer tissue had significantly lower concentrations of total glutathione. The intraindividual comparison of tumorous and non-tumorous tissue showed a consistent decrease of total glutathione as well as of GSH-aryltransferase activity in carcinomatous tissue.
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  • 17
    ISSN: 1436-6215
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary For 6–7 months, rats received as sole liquid regular coffee or caffeine solution in two different concentrations. Daily caffeine intake ranged between 35 and 60 mg/kg. Controls received decaffeinated coffee or water. Body weight, food, and liquid consumption were controlled continuously during the experiments. At the end of the observation period, the following parameters were checked: red and white blood count, urinalysis, serum concentrations of glucose, free and esterified fatty acids, cholesterol, GOT and GPT, weights of various organs, total fat and triglyceride content of the livers; in addition, livers, hearts, and kidneys were examined histologically. The rats which had been given regular or decaffeinated coffee or caffeine solution consumed the same amounts of food as the water-drinking controls; in spite of this, at the end of our experiments, body weights of the coffee drinking rats were by 6–7 % lower than those of the controls. Caffeine solution exerted no influence on body weight. Further examinations revealed no toxic effect of coffee or caffeine, and particulary no signs of damage or adipose degeneration of the liver. There was no lipolytic action of coffee or caffeine in these chronic studies. Serum glucose concentrations of the coffee or caffeine consuming rats were slightly lower at the end of experiments than those of the water drinking controls.
    Notes: Zusammenfassung Ratten erhielten über 6–7 Monate als einziges Getränk coffeinhaltigen Kaffee oder Coffeinlösung in zwei verschiedenen Konzentrationen. Die tägliche Coffeinaufnahme lag zwischen 35 und 60 mg/kg. Kontrolltiere konsumierten coffeinfreien Kaffee oder Wasser. Gewicht, Futter- und Flüssigkeitsverbrauch wurden während des gesamten Versuchszeitraumes fortlaufend kontrolliert. Bei Versuchsende wurden folgende Untersuchungen vorgenommen: Blutbild, Harnstatus, Serumkonzentrationen an Glukose, freien und veresterten Fettsäuren, Cholesterin, GOT und GPT, Organgewichte, Gesamtfett- und Triglyceridkonzentrationen der Lebern; Leber, Herz und Nieren wurden außerdem histologisch untersucht. Die mit Kaffee (coffeinhaltig und coffeinfrei) bzw. Coffein versorgten Ratten hatten den gleichen Futterverbrauch wie die wassertrinkenden Kontrolltiere; dennoch war die Gewichtszunahme der mit coffeinhaltigem und die der mit coffeinfreiem Kaffee getränkten Tiere etwas geringer, so daß ihr Körpergewicht bei Versuchsende um 6–7 % niedriger war als das der wassertrinkenden Kontrolltiere. Die weiteren Untersuchungen gaben keinen Anhalt für eine toxische Wirkung des Kaffees bzw. Coffeins. Insbesondere fand sich kein Hinweis auf eine Schädigung oder Verfettung der Leber. Eine lipolytische Wirkung des Kaffees bzw. des Coffeins war in diesen chronischen Versuchen nicht nachzuweisen. Die Serumglukosekonzentrationen der mit Kaffee bzw. Coffeinlösung versorgten Tiere lagen bei Versuchende etwas niedriger als die der mit Wasser getränkten Kontrollen.
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  • 18
    ISSN: 1436-6215
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary Caffeine given in a dose of 400 mg one hour before 1 g/kg ethanol did not influence the course of blood alcohol levels in male volunteers. Furthermore, caffeine did not improve psychomotoric skills impaired by ethanol. Two cups of coffee ingested 30 min. after ethanol (0.5 g/kg) caused a statistically significant increase of blood ethanol levels one hour afterwards (from 0.49 to 0.61‰). This may be due to an accelerated absorption of ethanol caused by the ingestion of warm fluid.
    Notes: Zusammenfassung Coffein ist auch bei sehr hoher Dosierung (400 mg) nicht in der Lage, die Pharmakokinetik des Äthylalkohols beim Menschen zu verändern. Auch die zentralen Ausfallserscheinungen nach Alkohol sind durch Coffein nicht zu kompensieren. Die Tasse Kaffee nach Alkoholgenuß kann somit eine alkoholbedingte Einschränkung der Verkehrstüchtigkeit nicht wiederherstellen, sondern im Gegenteil durch Erzeugung eines falschen Sicherheitsgefühles unter Umständen sogar schaden. Darüber hinaus kann die Flüssigkeitsaufnahme, die mit dem Kaffeegenuß verbunden ist, die Alkoholresorption beschleunigen und hierdurch Zu einer vorübergehenden Anhebung der Blutalkoholspiegel führen.
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