原料药γ辐照灭活细菌内毒素初探

本文用６个剂量的＾６０Ｃｏ－γ射线辐照含有大肠杆菌内毒素的甘露醇、葡萄糖、甲硝唑原料药,并用家兔法和鲎试剂法检验细菌内毒素的活性变化。结果表明,γ辐照能有效地消除原料药中细菌内毒素的生理活性。     

The induction of chromosomal damage and cell killing in mouse spermatogonial stem cells following combined treatments with hydroxyurea, 3-aminobenzamide and X-rays

To analyze in more detail the relation between the sensitivity of spermatogonial stem cells to killing and the induction of genetic damage, mature male mice received combined treatments with hydroxyurea (HU), 3-aminobenzamide (3-AB) and X-rays. Stem cell killing was determined using the repopulation index method and translocations were studied via spermatocyte analysis. HU was administered at 16 or at 48 h before further treatment in order to create stem cell populations with different sensitivities in whic the translocation induction and stem cell killing could be studied and compared. The sensitivities for cell death and genetic damage appeared to be strongly correlated: at 16 h after HU significantly higher values were found than at 48 h or in controls without HU pretreatment.By using 3-AB in the treatment schedules we were able to investigate whether the sensitization of stem cells towards cell death and genetic damage is the outcome of a radiation- or drug-induced G₁ delay. The effect of 3-AB was most pronounced at 16 h after HU. This confirms that at this interval a large fraction of stem cells is in G₁. Our data therefore indicate that all treatments that induce an enrichment of G₁ cells also result in a sensitization of stem cells to cell killing or the induction of mutagenic damage.     

alpha-Fluoro beta alanine in urine of workers occupationally exposed to 5 fluorouracil in a 5 fluorouracil producing factory

Because of possible harmful health effects increased attention is being paid to the occupational exposure to cytostatic drugs of workers in hospitals and industry. In this study a biomarker for exposure to 5-fluorouracil (5FU) based on GC-MSMS was applied to study the occupational exposure of four workers in a pharmaceutical factory producing 5FU. The four workers all excreted-fluoro--alanine (FBAL), a metabolite of 5FU, via the urine (range excretion rates: 0-88 9 g per 8h). This is in accordance with the presence of 5FU and/or its precursor ethoxyfluorouracil (EFU) in stationary and personal air wipe samples taken from the the workplace.     

Recent advances in malaria drug discovery

This digest covers some of the most relevant progress in malaria drug discovery published between 2010 and 2012. There is an urgent need to develop new antimalarial drugs. Such drugs can target the blood stage of the disease to alleviate the symptoms, the liver stage to prevent relapses, and the transmission stage to protect other humans. The pipeline for the blood stage is becoming robust, but this should not be a source of complacency, as the current therapies set a high standard. Drug discovery efforts directed towards the liver and transmission stages are in their infancy but are receiving increasing attention as targeting these stages could be instrumental in eradicating malaria.     

Synthesis and evaluation of 1,3,5-triazine derivatives as sunscreens useful to prevent skin cancer

The incidence of skin cancers such as non-melanoma skin cancer and malignant melanoma has increased in the last few years mainly because of chronic exposure to ultraviolet (UV) radiation. Sunscreens protect the skin against harmful UV radiations; however, some limitations of these products justify the discovery of new UV filters. Novel 1,3,5-triazine derivatives (12a-h) obtained by the optimization of prototype resveratrol were synthesized and characterized. All compounds exhibited sun protection factor (SPF) and UVA protection factor (UVAPF) in the range of 3–17 and 3–13, respectively. These values were superior to resveratrol and the UV filter ethylhexyl triazone (EHT) currently available on the market. In addition, all compounds demonstrated in vitro antioxidant activity and thermal stability with the decomposition at temperatures above 236 °C. In conclusion, the novel 1,3,5-triazine derivatives have emerged as new UV filters with antioxidant effect useful to prevent skin cancer.     

Quantitative analysis of biomarkers,drugs and toxins in biological samples by immunoaffinity chromatography coupled to mass spectrometry or tandem mass spectrometry: A focused review of recent applications

Immunoaffinity chromatography (IAC), mass spectrometry and especially tandem mass spectrometry (MS/MS) represent the most efficient and reliable analytical techniques for specific isolation, unequivocal identification and accurate quantification of numerous natural and synthetic substances in biological samples. This review article focuses on the combined use of these outstanding methodologies in basic and clinical research and in life sciences for the quantitative analysis of low- and high-molecular mass biomarkers, drugs and toxins in urine, plasma or serum samples, in tissue and other biologicals systems published in the last decade. The analytes discussed in some detail include the biomarkers of oxidative stress 15(S)-8-iso-prostaglandin F_2α {15(S)-8-iso-PGF_2α} and 3-nitrotyrosine, the major urinary metabolite of the lipid mediators cysteinyl leukotrienes, i.e., the leukotriene E₄ (LTE₄), melatonin, and the major collagen type II neoepitope peptide in human urine.     

Carbonyl Traps as Potential Protective Agents against Methimazole‑Induced Liver Injury

Liver injury is a deleterious adverse effect associated with methimazole administration, and reactive intermediates are suspected to be involved in this complication. Glyoxal is an expected reactive intermediate produced during methimazole metabolism. Current investigation was undertaken to evaluate the role of carnosine, metformin, and N‐acetyl cysteine as putative glyoxal (carbonyl) traps, against methimazole‐induced hepatotoxicity. Methimazole (100 mg/kg, intraperitoneally) was administered to intact and/or glutathione (GSH)?depleted mice and the role of glyoxal trapping agents was investigated. Methimazole caused liver injury as revealed by an increase in serum alanine aminotransferase and aspartate aminotransferase. Moreover, lipid peroxidation and protein carbonylation occurred significantly in methimazole?treated animals’ liver. Hepatic GSH reservoirs were decreased, and inflammatory cells infiltration was observed in liver histopathology. Methimazole?induced hepatotoxicity was severe in GSH‐depleted mice and accompanied with interstitial hemorrhage and necrosis of the liver. Glyoxal trapping agents effectively diminished methimazole‐induced liver injury both in intact and/or GSH?depleted animals.