Is Involvement a Good Thing? The Undesirable Consequences of Topical and Conversational Involvement in the Context of Alcohol Consumption

Whereas there is evidence that interpersonal communication, or conversation, influences predictors of alcohol consumption, the role of involvement in conversation effects remains unclear. This study explored how three aspects of involvement (topical relevance, or how relevant the topic of alcohol is; conversational relevance, or how relevant a conversation about alcohol is; and conversational effort, or how much effort people put into such a conversation), influence conversation effects. After assessing topical relevance, 46 same-sex dyads were requested to talk about the negative consequences of heavy drinking. Within each dyad, one participant was asked to take on an active talking role and the other participant a passive listening role. Next, conversational relevance, effort, and predictors of heavy drinking were measured. Results showed that participants who drank more alcohol found the topic of heavy drinking more relevant. This topical relevance increased conversational relevance and conversational effort. Conversational effort further increased when a talking role was assigned. Furthermore, participants who put more effort in the conversation and found it more relevant had more positive norms, identified more strongly with alcohol, and had higher intentions to drink. These findings suggest that more involvement in an alcohol-related conversation does not always lead to desirable outcomes.     

Application of the adverse outcome pathway framework to genotoxic modes of action

In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc.     

异落新妇甙的结构研究

从百合科菝葵属植物土茯苓(Smilaxg labra Roxb.)根茎的乙醇提取物中分得一个新的天然化合物(I),命名为异落新妇甙(isoastilbin)。根据元素分析,UV,IR,¹H-NMR,¹³C-NMR,2DNMR及FAB-MS,确定化合物I的结构为5,7,3',5'-四羟基二氢黄酮醇-3-O-α-L-鼠李糖甙。     

Evidence for a human IgG1 class switch program

In activated murine B lymphocytes, immunoglobulin class switch recombination occurs as a highly regulated process which is targeted to distinct switch regions. Here we present first evidence that in human B lymphocytes, switch recombination is targeted to distinct switch regions as well. In a panel of clonally unrelated IgG1-expressing human B cells, immortalized by Epstein-Barr virus (EBV) transformation, seven out of nine cells show switch recombination between Sμ and Sγ1 on both alleles, the active and inactive one. The remaining cells show no switch recombination on the inactive IgH locus. The very strong correlation of switch recombination on both alleles of IgG1-expressing cells proves that class switch recombination to IgG1 is not random but directed in human B lymphocytes.     

Circulating gelatinases and tissue inhibitor of metalloproteinase-1 in colorectal cancer metastatic liver disease.

AIMS: The degradation of the extracellular matrix is intrinsic to the invasion and progression of cancer. Matrix metalloproteinase (MMP)-2 and -9 and their natural inhibitors are involved in this process. The study aims to investigate if plasma MMP-2, -9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) can be useful markers in the diagnosis and prognosis of colorectal cancer (CRC) metastatic liver disease. METHODS: Fifty-seven patients undergoing liver metastasis operation were followed prospectively. ProMMP-2, -9 and TIMP-1 plasma levels were determined by zymography and ELISA, before and after the resection of liver metastases. Data were compared with those of healthy controls (n=51) and primary CRC patients (n=94). The diagnostic and prognostic potential was investigated with ROC-curves and Kaplan-Meier survival analysis. RESULTS: Plasma proMMP-2 levels were lower (P<0.001), and TIMP-1 levels higher (P<0.001) in CRC metastatic liver disease than in healthy controls. If compared to those in primary CRC patients, no differences were found. In ROC-curves, the area under the curve was 0.48 and 0.61 for proMMP-2 and -9, respectively. Plasma proMMP-2, -9 and TIMP-1 levels were unsuitable to predict survival. In both diagnostic and prognostic examinations, CEA proved to be a better marker. In the postoperative follow-up, protracted low levels of proMMP-2 seemed related to disease recurrence. CONCLUSION: The preoperative plasma proMMP-2, -9 and TIMP-1 levels have no potential value as diagnostic or prognostic markers in CRC liver metastatic disease.     

The anti-tumour effects of the prodrugs N-l-leucyl-doxorubicin and vinblastine-isoleucinate in human ovarian cancer xenografts.

N-l-leucyl-doxorubicin and vinblastine-isoleucinate can be considered as relatively non-toxic prodrugs from doxorubicin and vinblastine, respectively. A comparative analysis was carried out of the anti-tumour activity of the four compounds as well as vintriptol in four human ovarian cancer xenografts different in histology, growth rate and chemosensitivity. Injections were given i.v. weekly twice into mice bearing well-established s.c. tumours. At equitoxic doses, the amount of drug administered for N-l-leucyl-doxorubicin and vinblastine-isoleucinate was respectively 3-fold and 2-fold higher than the doses of the parent compound. N-l-leucyl-doxorubicin induced a growth inhibition > 50% in three out of four human ovarian cancer lines. The anti-tumour effects obtained were significantly better (P < 0.01) than in the case of doxorubicin. Vinblastine-isoleucinate studied in two of these lines could induce a growth inhibition of > 50%. This prodrug appeared slightly less effective than vinblastine. Insignificant growth inhibition (< 50%) was obtained by vintriptol.     

Accuracy of duplex evaluation one year after varicose vein surgery to predict recurrence at the sapheno-femoral junction after five years.

OBJECTIVE: To investigate whether the results of duplex examination 1 year after sapheno-femoral junction (SFJ) ligation might be helpful in predicting long-term results after 5 years. PATIENTS AND METHODS: Follow-up data concerning patients operated on for primary or recurrent varicose veins of the great saphenous vein were studied 1 year and 5 years after surgery, focusing on the thigh and groin region. Clinical examination was undertaken to detect recurrent thigh varicose veins. The site of SFJ ligation was carefully screened for any signs of neovascularisation by duplex ultrasound. Sensitivity, specificity, positive and negative predictive value of the 1-year duplex scan were calculated, based upon the outcome of a further duplex scan 5 years following surgery. RESULTS: A total of 100 limbs were studied: 50 limbs operated on for primary varicose veins and 50 limbs for recurrent varicose veins. The 1-year duplex ultrasound of the SFJ ligation site had a sensitivity of 80%, a specificity of 91%, a positive predictive value of 70% and a negative predictive value of 95% in assessing the 5 year recurrence rate. CONCLUSION: A postoperative duplex scan of the SFJ 1 year after varicose vein surgery to the great saphenous vein predicts which patients are most likely to have a good outcome 5 years after surgery. The 1-year duplex scan is a reliable diagnostic tool for future studies evaluating the effect of new methods of treating sapheno-femoral incompetence.