Overexpression of Aldose Reductase Render Mouse Hepatocytes More Sensitive to Acetaminophen Induced Oxidative Stress and Cell Death     

Munzir M. E. Ahmed  J. A. S. Al-Obosi  H. M. Osman  M. E. Shayoub 《Indian journal of clinical biochemistry : IJCB》2016,31(2):162-170

Acetaminophen (APAP) a commonly used drug for decrease the fever and pain but is capable to induced hepatotoxicity at over dose. This study was carried out to investigate the effect of APAP on the expression of anti-apoptotic and antioxidative defense genes, and whether aldose reductase over-expressing plasmid capable to protect against APAP-induced oxidative stress and cell death. APAP treatment induced oxidative stress and hepatotoxicity, and significantly increased aldose reductase mRNA and protein expression in mouse hepatocyte (AML-12). Unexpectedly, AML-12 cells over-expressing aldose reductase augmented APAP-induced reduction in cell viability, reactive oxygen species (ROS) production, glutathione (GSH) depletion and glutathione S-transferase A2 expression. Moreover, over-expression of aldose reductase potentiated APAP induced reduction on proliferating cell nuclear antigen, B cell lymphoma-extra large (bcl-x_L), catalase, glutathione peroxidase-1 (GPx-1) and abolished APAP-induced B-cell lymphoma 2 (bcl-2) inductions. Further, over-expression of aldose reductase significantly abolished AMP activated protein kinase (AMPK) activity in APAP-treated cells and induced p53 expression. This results demonstrate that APAP induced toxicity in AML-12, increased aldose reductase expression, and over-expression of aldose reductase render this cell more susceptible to APAP induced oxidative stress and cell death, this probably due to inhibition AMPK or bcl-2 activity, or may due to competition between aldose reductase and glutathione reductase for NADPH.  相似文献   

Race-mixing and science in the United States     

Farber P 《Endeavour》2003,27(4):166-170

Scientific racism was widely used as a justification to oppose race-mixing in the United States. Historians have justly criticized this abuse of science, but have overlooked some of the important ways in which science was used in the 1930s and 1940s to overturn scientific racism and opposition to race-mixing. Of particular importance was the cultural anthropology of Franz Boas and the evolutionary biology of Theodosius Dobzhansky, which supplied arguments against racism and fundamentally altered the scientific understanding of race.  相似文献   

Effect of <Emphasis Type="SmallCaps">l</Emphasis>-Thyroxine on Micronuclei Frequency in Peripheral Blood Lymphocytes in Clinical and Experimental Conditions     

Yogita S. Raut  Uma S. Bhartiya  Purushottam Kand  Rohini W. Hawaldar  Ramesh V. Asopa  Lebana J. Joseph  MGR Rajan 《Indian journal of clinical biochemistry : IJCB》2016,31(1):99-103

The aim was to study the genotoxic effect of high concentration of thyroxine (T₄) in vivo in peripheral blood lymphocytes (PBL) of the patients suffering from thyroid disorders. The effect was compared by performing in vitro experiments with addition of increasing concentration of T₄ (0.125–1 µM) in whole blood samples from healthy donors. Cytokinesis-blocked micronuclei (CBMN) assay method was used to assess the DNA damage in the PBL. The study included 104 patients which were grouped as control (n = 49), hyperthyroid (n = 31) and hypothyroid (n = 24). A significant increase in micronuclei (MN) frequency was observed in hyperthyroid patients when compared with the hypothyroid and euthyroid group thereby suggesting increased genotoxicity in hyperthyroidism (p < 0.001). A significant increase in MN frequency was observed at T₄ concentration of 0.5 µM and above when compared to lower T₄ concentrations (0.125 and 0.25 µM) and basal in in vitro experiments (p = 0.000). The results indicate that the T₄ in normal concentration does not exhibit the genotoxic effect, as observed in both the in vivo and in vitro experiments. The toxicity of T₄ increases at and above 0.5 μM concentration in vitro. Therefore acute T₄ overdose should be handled promptly and effectively so as to avoid the possible genotoxic effect of high concentration of T₄ in vivo.  相似文献   

Age related changes in lipid peroxidation and antioxidants in elderly people     

Akila V. Prashant  H. Harishchandra  Vivian D'souza  Benedicta D'souza 《Indian journal of clinical biochemistry : IJCB》2007,22(1):131-134

Advanced age is associated with an accumulation of free radical damage, which leads to physiological and clinical modifications. Age related changes resulting from free radical reactions include increasing levels of lipid peroxides, alterations in enzyme activities and greater osmotic fragility. The present study was conducted to estimate the level of lipid peroxidation product-Malondialdehyde and antioxidants Catalase and Glutathione in elderly people. An increase in lipid peroxidation and decrease in antioxidants was observed in normal elderly people. Highly significant increase in MDA and decrease in antioxidants was observed in elderly people when complicated with diabetes and hypertension. Supplementation of antioxidants may prevent further oxidative injury in elderly people.  相似文献   

In Search of a ‘Good Story’ for the History of Medicine     

Jonathan Simon 《Metascience》2005,14(3):427-429

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Status and Interrelationship of Zinc,Copper, Iron,Calcium and Selenium in Prostate Cancer     

Bhupendra Pal Singh  Shailendra Dwivedi  Urmila Dhakad  Ramesh Chandra Murthy  Vimal Kumar Choubey  Apul Goel  Satya Narayan Sankhwar 《Indian journal of clinical biochemistry : IJCB》2016,31(1):50-56

Deficiency or excess of certain trace elements has been considered as risk factor for prostate cancer. This study was aimed to detect differential changes and mutual correlations of selected trace elements in prostate cancer tissue versus benign prostatic hyperplasia tissue. Zinc, copper, iron, calcium and selenium were analysed in histologically proven 15 prostate cancer tissues and 15 benign prostatic hyperplasia tissues using atomic absorption spectrophotometer. Unpaired two tailed t test/Mann–Whitney U test and Pearson correlation coefficient were used to compare the level of trace elements, elemental ratios and their interrelations. As compared to benign prostatic tissue, malignant prostatic tissue had significantly lower selenium (p = 0.038) and zinc (p = 0.043) concentrations, a lower zinc/iron ratio (p = 0.04) and positive correlation of selenium with zinc (r = 0.71, p = 0.02) and iron (r = 0.76, p = 0.009). Considerably divergent interrelationship of elements and elemental ratios in prostate cancer versus benign prostatic hyperplasia was noted. Understanding of differential elemental changes and their interdependence may be useful in defining the complex metabolic alterations in prostate carcinogenesis with potential for development of element based newer diagnostic, preventive and therapeutic strategies. Further studies may be needed to elucidate this complex relationship between trace elements and prostate carcinogenesis.  相似文献   

Trusting Virtual Trust   总被引：2，自引：0，他引：2  

Paul?B.?de?LaatEmail author 《Ethics and Information Technology》2005,7(3):167-180

Can trust evolve on the Internet between virtual strangers? Recently, Pettit answered this question in the negative. Focusing on trust in the sense of ‘dynamic, interactive, and trusting’ reliance on other people, he distinguishes between two forms of trust: primary trust rests on the belief that the other is trustworthy, while the more subtle secondary kind of trust is premised on the belief that the other cherishes one’s esteem, and will, therefore, reply to an act of trust in kind (‘trust-responsiveness’). Based on this theory Pettit argues that trust between virtual strangers is impossible: they lack all evidence about one another, which prevents the imputation of trustworthiness and renders the reliance on trust-responsiveness ridiculous. I argue that this argument is flawed, both empirically and theoretically. In several virtual communities amazing acts of trust between pure virtuals have been observed. I propose that these can be explained as follows. On the one hand, social cues, reputation, reliance on third parties, and participation in (quasi-) institutions allow imputing trustworthiness to varying degrees. On the other, precisely trust-responsiveness is also relied upon, as a necessary supplement to primary trust. In virtual markets, esteem as a fair trader is coveted while it contributes to building up one’s reputation. In task groups, a hyperactive style of action may be adopted which amounts to assuming (not: inferring) trust. Trustors expect that their virtual co-workers will reply in kind while such an approach is to be considered the most appropriate in cyberspace. In non-task groups, finally, members often display intimacies while they are confident someone else ‘out there’ will return them. This is facilitated by the one-to-many, asynchronous mode of communication within mailing lists.  相似文献   

Property and the pursuit of knowledge: IPR issues affecting scientific research     

Paul A. David  Bronwyn H. Hall 《Research Policy》2006,35(6):767-771

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Ethics and technology design     

Anders Albrechtslund 《Ethics and Information Technology》2007,9(1):63-72

This article offers a discussion of the connection between technology and values and, specifically, I take a closer look at ethically sound design. In order to bring the discussion into a concrete context, the theory of Value Sensitive Design (VSD) will be the focus point. To illustrate my argument concerning design ethics, the discussion involves a case study of an augmented window, designed by the VSD Research Lab, which has turned out to be a potentially surveillance-enabling technology. I call attention to a “positivist problem” that has to do with the connection between the design context and the use context, which VSD seems to presuppose, and I argue that it is necessary to clearly distinguish between the two, since the designers’ intentions do not always correspond with the users’ practice; in fact, the relation between design and use is very complex and principally unpredictable. Thus, a design theory must accept that foresight is limited to anticipation rather than prediction. To overcome the positivist problem, I suggest a phenomenological approach to technology inspired by Don Ihde’s concept of multistability. This argument, which is general in nature and thus applies to any theory of design ethics, is intended as a constructive criticism, which can hopefully contribute to the further development of design ethics.  相似文献   

Idolising Identity: On Walter Charleton's Self-construction of his Self as a Selfless Self     

Guido Giglioni 《Metascience》2007,16(2):239-245

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