Different effect of Toxoplasma gondii infection on adhesion capacity of fibroblasts and monocytes

This study investigated the effect of infection with the apicomplexan parasite Toxoplasma gondii , in combination with the concomitant cytokine environment (IFN-γ/TNF-α), on adhesion of THP-1 monocytic cells to MRC-5 fibroblasts. Surprisingly, infection of THP-1 cells decreased their adhesion to the MRC-5 cell monolayer. This decrease was compensated by IFN-γ/TNF-α stimulation. In contrast, infection of MRC-5 cells significantly increased adhesion, which was synergistically augmented by cytokine stimulation. Levels of ICAM-1 (CD54) on MRC-5 cells, as well as LFA-1 (CD11a) on THP-1 cells, were not changed by infection, neither in resting, nor in cytokine stimulated cells. These results show that T. gondii infection alters adhesion properties and reactivity to cytokine stimulation in a cell-specific way.     

Specificity and regioselectivity of the conjugation of estradiol, estrone, and their catecholestrogen and methoxyestrogen metabolites by human uridine diphospho-glucuronosyltransferases expressed in endometrium

Uridine diphospho-glucuronosyltransferases (UGTs) inactivate and facilitate the excretion of estrogens to glucuronides (-G), the most abundant circulating estrogen conjugates. The identity of the conjugated estrogens formed by all known overexpressed UGTs (n = 16) was analyzed by comparison with retention time and mass fragmentation of authentic standards by HPLC tandem mass spectrometry methods. Six UGTs, namely 1A1, 1A3, 1A8, 1A9, 1A10, and 2B7, were found to glucuronidate estradiol (E(2)) and estrone (E(1)), their hydroxyls (OH), and their methoxy derivatives (MeO). Addition of glucuronic acid was catalyzed by specific UGTs at positions 2, 3, and 4 of the estrogens, whereas only E(2) was conjugated at position 17 by UGT2B7. Kinetic parameters indicate that the conjugation of E(2) at position 3 was predominantly catalyzed by 1A1, 1A3, and 1A8 and by 1A8 for E(1). Conjugation of 2-OHE(1)/E(2) and 2- and 4-MeOE(1)/E(2) was selective at position 3, mostly catalyzed by 1A1 and 1A8. Of all UGTs, UGT2B7 demonstrated the highest catalytic activities for estrogens and at least 10- to 50-fold higher activity for the conjugation of genotoxic 4-hydroxycatecholestrogens at position 4, compared with the conjugation of E(2), E(1), and 2-hydroxycatecholestrogens. Its presence was further shown in the endometrium by RT-PCR and immunohistochemistry, localizing in the same cells expressing CYP1B1, involved locally in the formation of 4-hydroxycatecholestrogens. Data show that several UGT enzymes detected in the endometrium are involved in the glucuronidation of E(2) and its 2-OH, 4-OH, and 2-MeO metabolites that exert various biological effects in the tissue.     

Application of multicriteria decision analysis in health care: a systematic review and bibliometric analysis

BackgroundThe use of Multi‐Criteria Decision Analysis (MCDA) in health care has become common. However, the literature lacks systematic review trend analysis on the application of MCDA in health care.AimTo systematically identify applications of MCDA to the areas of health care, and to report on publication trends.MethodsEnglish language studies published from January 1, 1980 until October 1, 2013 were included. Electronic databases searches were supplemented by searching conference proceedings and relevant journals. Studies considered for inclusion were those using MCDA techniques within the areas of health care, and involving the participation of decision makers. A bibliometric analysis was undertaken to present the publication trends.ResultsA total of 66 citations met the inclusion criteria. An increase in publication trend occurred in the years 1990, 1997, 1999, 2005, 2008, and 2012. For the remaining years, the publication trend was either steady or declining. The trend shows that the number of publications reached its highest peak in 2012 (n = 9). Medical Decision Making was the dominant with the highest number published papers (n = 7). The majority of the studies were conducted in the US (n = 29). Medical Decision Making journal published the highest number of articles (n = 7). Analytic Hierarchy Process (n = 33) was the most used MCDA technique. Cancer was the most researched disease topic (n = 12). The most covered area of application was diagnosis and treatment (n = 26).ConclusionThe review shows that MCDA has been applied to a broad range of areas in the health care, with the use of a variety of methodological approaches. Further research is needed to develop practice guidelines for the appropriate application and reporting of MCDA methods.