Characterization and quantitation of 3-alkylthymidines from reactions of mutagenic propylene oxides with thymidine

Thymidine was reacted in methanol with four epoxides of varying mutagenicities: propylene oxide, glycidol, epichlorohydrin and trichloropropylene oxide. A single product was detected with each epoxide, and these products had the same retention times on silica high pressure liquid chromatography (HPLC). UV spectra of the products identified them as 3-alkylthymidines, and this was confirmed by infrared (IR) and nuclear magnetic resonance (NMR) spectra. Mass spectra (MS) analysis showed the products to be consistent with attachment at the least substituted carbon of the epoxide. Formation of 3-alkylthymidines correlated to Taft [sigma]* electron withdrawing values for the substituents on the epoxides and mutagenicities in strain TA100 of the Ames Assay.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24612/1/0000022.pd

Da li Pseudomonas aeruginosa perzistira u biljkama?

Persistence of pathogenic bacteria in plants, is a major threat to human health, especially in plants that are used in food with no heat treatment. The aim of this study was to determine whether there is a possibility of persistence of human isolates of Pseudomonas aeruginosa in cucumbers, cabbage, peppers and tomatoes. In cucumber and cabbage P. aeruginosa was isolated from all 12 plants, tomato by 9 and 7 of pepper plants. Based on the results, there is the possibility of persistence P. aeruginosa in the above vegetables.Mogućnost perzistencije patogenih bakterija u biljkama, predstavlja veliku opasnost po zdravlje ljudi, pogotovo kod biljaka koje se koriste u ishrani bez termičke obrade. Cilj istraživanja bio je da se utvrdi da li postoji mogućnost perzistencije humanog izolata Pseudomonas aeruginosa u krastavcu, kupusu, paprici i paradajzu. Pseudomonas aeruginosa izolovan je iz svih 12 biljaka krastavca i kupusa, iz 9 paradajza i 7 paprika. Na osnovu rezultata rada, u navedenom povrću postoji mogućnost perzistencije P. aeruginosa

Effect of prenatal EPA and DHA on maternal and umbilical cord blood cytokines

Abstract Background Investigators have hypothesized that omega-3 fatty acid supplementation may modulate the immune response. However, available evidence is conflicting. We performed this study to investigate the effect of prenatal eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-rich fish oil supplementation on maternal and fetal cytokine production. Methods This study is a secondary analysis of a randomized controlled trial designed to assess whether prenatal EPA- or DHA-rich fish oil supplementation would prevent perinatal depressive symptoms among women at risk. Enrolled participants received EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg EPA) or soy oil placebo. Maternal venous blood was collected at enrollment (12–20 weeks gestation) and after supplementation (34–36 weeks gestation). Umbilical cord blood was collected at delivery. We analyzed stored plasma specimens for 16 human cytokines using multiplex immunoassays. Maternal and cord blood cytokine levels were compared among the treatment groups. Associations of serum DHA and EPA with maternal and cord blood cytokines were explored via regression analysis. Results We enrolled 126 women, of whom 118 completed the trial. Prenatal supplementation with EPA-rich fish oil significantly lowered maternal IL6, IL15, and TNFα concentrations. However, supplementation with DHA-rich fish oil had no significant effect on maternal cytokine profiles. Maternal serum DHA fraction was significantly associated with IL1α, and maternal serum DHA and EPA fractions were significantly associated with IL 10 concentrations after supplementation. Compared with placebo, supplementation with EPA- or DHA-rich fish oils had no significant effect on cord blood cytokine concentrations. Conclusions Prenatal supplementation with EPA-rich fish oil significantly reduced levels of several inflammatory cytokines in maternal plasma, while prenatal DHA-rich fish oil had no significant effect on cytokine concentrations. Supplementation with EPA- and DHA- rich fish oil had no significant effect on umbilical cord blood cytokine concentrations. Trial registration Clinical Trial Registration: registration number NCT00711971 7/7/2008.https://deepblue.lib.umich.edu/bitstream/2027.42/144528/1/12884_2018_Article_1899.pd

Non-steroidal anti-inflammatory drug (NSAID) use and levels of a lipid oxidation marker in plasma and nipple aspirate fluids

Non-steroidal anti-inflammatory drugs (NSAIDs) are thought to reduce cancer risk by inhibiting cyclo-oxygenases, resulting in deceased formation of inflammatory mediators and oxidative stress. We examined whether the level of one oxidative stress marker, 15-F 2t -isoprostane, was affected by NSAID use in plasma and breast nipple aspirate fluids (NAF) of pre-menopausal women who were participating in a dietary intervention trial ( n =121). Baseline levels of 15-F 2t -isoprostane were lower in NSAID users than non-users in both NAF and plasma, although the differences did not persist after intervention. Over the duration of the study, information on NSAID use was collected five times, and average 15-F 2t -isoprostane levels in both NAF and plasma exhibited a statistically significant trend for decreases with increased frequency of NSAID use. These results indicate that NSAID use can result in lower levels of 15-F 2t -isoprostane, which may have implications for the effects of NSAID use on breast cancer risk.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44237/1/10549_2005_Article_9102.pd

The mothers, Omega-3 and mental health study

<p>Abstract</p> <p>Background</p> <p>Major depressive disorder (MDD) during pregnancy and postpartum depression are associated with significant maternal and neonatal morbidity. While antidepressants are readily used in pregnancy, studies have raised concerns regarding neurobehavioral outcomes in exposed infants. Omega-3 fatty acid supplementation, most frequently from fish oil, has emerged as a possible treatment or prevention strategy for MDD in non-pregnant individuals, and may have beneficial effects in pregnant women. Although published observational studies in the psychiatric literature suggest that maternal docosahexaenoic acid (DHA) deficiency may lead to the development of MDD in pregnancy and postpartum, there are more intervention trials suggesting clinical benefit for supplementation with eicosapentaenoic acid (EPA) in MDD.</p> <p>Methods/Design</p> <p>The Mothers, Omega-3 and Mental Health study is a double blind, placebo-controlled, randomized controlled trial to assess whether omega-3 fatty acid supplementation may prevent antenatal and postpartum depressive symptoms among pregnant women at risk for depression. We plan to recruit 126 pregnant women at less than 20 weeks gestation from prenatal clinics at two health systems in Ann Arbor, Michigan and the surrounding communities. We will follow them prospectively over the course of their pregnancies and up to 6 weeks postpartum. Enrolled participants will be randomized to one of three groups: a) EPA-rich fish oil supplement (1060 mg EPA plus 274 mg DHA) b) DHA-rich fish oil supplement (900 mg DHA plus 180 mg EPA; or c) a placebo. The primary outcome for this study is the Beck Depression Inventory (BDI) score at 6 weeks postpartum. We will need to randomize 126 women to have 80% power to detect a 50% reduction in participants' mean BDI scores with EPA or DHA supplementation compared with placebo. We will also gather information on secondary outcome measures which will include: omega-3 fatty acid concentrations in maternal plasma and cord blood, pro-inflammatory cytokine levels (IL-1β, IL-6, and TNF-α) in maternal and cord blood, need for and dosage of antidepressant medications, and obstetrical outcomes. Analyses will be by intent to treat.</p> <p>Discussion</p> <p>This study compares the relative effectiveness of DHA and EPA at preventing depressive symptoms among pregnant women at risk.</p> <p>Trial registration</p> <p>Clinical trial registration number: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00981877">NCT00711971</a></p

The Mediterranean diet: Effects on proteins that mediate fatty acid metabolism in the colon

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88101/1/j.1753-4887.2011.00439.x.pd

Reactions of Mutagenic Propylene Oxides with Deoxynucleosides and Dna.

Methods were developed to quantitate reactivities of propylene oxide, glycidol, epichlorohydrin and trichloropropylene oxide with deoxycytidine, thymidine, deoxyadenosine and deoxyguanosine. Deoxynucleoside reactivity in DNA was quantitated with the more water soluble epoxides, propylene oxide and glycidol. Total deoxynucleoside reactivity in all reactions reflected the epoxides' relative mutagenicities in Ames Assay strain TA100 and Taft (sigma)* electron withdrawing strengths of the substituents on the epoxides. No one specific product detected from the deoxyguanosine or deoxyadenosine reactions was common to all four epoxides, and UV spectra indicated only N alkylation. Deoxycytidine yielded both O- and N-alkylated products. Formation of N-alkylated thymidine by each of the epoxides correlated to TA100 mutagenicity and Taft (sigma)* values. The thymidine and deoxycytidine reaction products were identified by NMR, MS and IR analyses as well as by UV spectra. The order of deoxynucleoside reactivity in DNA with propylene oxide was deoxyguanosine > deoxyadenosine > thymidine > deoxycytidine.Ph.D.PharmacologyEnvironmental scienceUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/159728/1/8402272.pd

243 CHARACTERIZATION AND QUANTITATION OF 3-ALKYLTHYMIDINES FROM REACTIONS OF MUTAGENIC PROPYLENE OXIDES WITH THYMIDINE

SUMMARY Thymidine was reacted in methanol with four epoxides of varying mutagenicities: propylene oxide, glycidol, epichlorohydrin and trichloropropylene oxide. A single product was detected with each epoxide, and these products had the same retention times on silica high pressure liquid chromatography (HPLC). UV spectra of the products identified them as 3-alkylthymidines, and this was confirmed by infrared (IR) and nuclear magnetic resonance (NMR) spectra. Mass spectra (MS) analysis showed the products to be consistent with attachment at the least substituted carbon of the epoxide. Formation of 3alkylthymidines correlated to Taft u* electron withdrawing values for the substituents on the epoxides and mutagenicities in strain TAlOO of the Ames Assay

Reactivity of propylene oxides towards deoxycytidine and identification of reaction products

Deoxycytidine was reacted with four epoxides of varying alkylating rates: propylene oxide, glycidol, epichlorohydrin and trichloropropylene oxide. Deoxycytidine was chosen to compare the reactivities of these epoxides as all sites of possible alkylation, the oxygen and both nitrogens, are involved in base pairing in DNA. Reaction products were separated on HPLC. Products of the least and most reactive epoxides, propylene oxide and trichloropropylene oxide, were characterized by UV, IR, 360 MHz NMR and MS analysis. For the epichlorohydrin and glycidol reactions and all analytical separations, products were characterized by their HPLC retention times and UV spectra. While differences in reactivity among the epoxides towards specific nitrogen and oxygen sites were found, total reactivity correlated with Taft [sigma]*-values of the substituent groups.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24765/1/0000188.pd