Arsenic (As) was isolated for the first time as a chemical element by Jabir-Ibn-Haiyanb in the year 776, and its name comes etymologically from the Greek arsenicon (masculine). It is gray in color and of a shining metallic appearance, has little metallic properties, is distributed widely in the universe and its toxicity depends on the different chemical forms and states of oxidation that it has:-3, 0, +3 and +5. The historical evolution of the toxicology is intimately united to the use of this nonmetal. At present, arsenical substances are used in industry, agriculture, cattle ranching, and medicine. For that reason, the sources of exposure of man to this metal are diverse; out standing are labor, food and medicaments. In this work a revision is made of the etiology, preventive measures, analysis, diagnosis and treatment of the poisoning by As.
A gas chromatographic method of use in determining the following organochlorine pesticides in cow milk has been adapted and validated: alpha-hexachlorocyclohexane (alpha-HCH), beta-HCH, lindane, delta-HCH, hexachlorobenzene, aldrin, heptachlor, heptachlor epoxide, mirex, 2,4-dichlorodiphenyltrichloroethane (2,4-DDT), 4,4-DDT, 2,4-dichlorodiphenyldichloroethane (2,4-DDD), 4,4-DDD, 2,4-dichlorodiphenylethane (2,4-DDE) and 4,4-DDE. The method studied consists of three steps: the extraction of fat by centrifugation, mixing with anhydrous sodium sulfate, and transfer to a glass column and elution with hexane; purification of the extract via concentrated sulfuric acid treatment; and determination of the organochlorine pesticides by gas chromatography equipped with an electron capture detector. The analytical parameters determined to estimate the quality of the method yielded the following results: correlation coefficients (r) of the calibration curves were greater than 0.996, the variation coefficients of the response factors were less than 4.90%--with the exception of aldrin (5.53%) and lindane (5.75%)--the relative standard deviation of the slope (Sm rel) being < or =1.52%. Zero was included in the confidence limits of the independent term range. The method repeatability and reproducibility values were < or =4.73% and < or =5.79%, respectively. The recovery values of the pesticides analyzed were in the range of 81.92% (alpha-HCH) to 105.49% (4,4-DDT), except in the case of aldrin and heptachlor epoxide, which yielded recovery values of under 40%. The quantification limits of the method were < or =1 ng/g, with the exception of mirex (5 ng/g).
Background Deregulated expression of MYC is a driver of colorectal carcinogenesis, suggesting that decreasing MYC expression may have significant therapeutic value. CIP2A is an oncogenic factor that regulates MYC expression. CIP2A is overexpressed in colorectal cancer (CRC), and its expression levels are an independent marker for long-term outcome of CRC. Previous studies suggested that CIP2A controls MYC protein expression on a post-transcriptional level. Methods To determine the mechanism by which CIP2A regulates MYC in CRC, we dissected MYC translation and stability dependent on CIP2A in CRC cell lines. Results Knockdown of CIP2A reduced MYC protein levels without influencing MYC stability in CRC cell lines. Interfering with proteasomal degradation of MYC by usage of FBXW7-deficient cells or treatment with the proteasome inhibitor MG132 did not rescue the effect of CIP2A depletion on MYC protein levels. Whereas CIP2A knockdown had marginal influence on global protein synthesis, we could demonstrate that, by using different reporter constructs and cells expressing MYC mRNA with or without flanking UTR, CIP2A regulates MYC translation. This interaction is mainly conducted by the MYC 5′UTR. Conclusions Thus, instead of targeting MYC protein stability as reported for other tissue types before, CIP2A specifically regulates MYC mRNA translation in CRC but has only slight effects on global mRNA translation. In conclusion, we propose as novel mechanism that CIP2A regulates MYC on a translational level rather than affecting MYC protein stability in CRC.
Opioids have historically been the pharmacological choice in the treatment of moderate to severe pain of oncological and chronic origin but they have also become a growing and controversial tool in the treatment of non-oncological pain that requires a risk/ benefit evaluation. The present study focuses on the opioid tapentadol, the newest opioid considered highly effective in treating cancer and non-cancer pain. According to the WHO Collaborating Center for Drugs Statistics Methodology, the stated Tapendatol Defined Daily Dose (DDD) for oral administration is 400 mg but the prescribed doses range from 100 mg/day in patients without previous opioid treatments up to a maximum of 600 mg/ day. However, the DDD is a unit of measurement that does not have to reflect the prescribed daily dose (PDD) because therapeutic doses usually differ from DDDs by taking into account individual patient considerations and pharmacokinetic conditions.
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