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Biomedical subjects

Julie M W Wallace

Publications and source records attributed to Julie M W Wallace.

5 recordsLinked to original sources

Hypothesis about mechanisms through which nicotine might exert its effect on the interdependence of inflammation and gut barrier function in ulcerative colitis.

Ulcerative colitis (UC) is characterized by impairment of the epithelial barrier and the formation of ulcer-type lesions, which result in local leaks and generalized alterations of mucosal tight junctions. Ultimately, this results in increased basal permeability. Although disruption of the epithelial barrier in the gut is a hallmark of inflammatory bowel disease and intestinal infections, it remains unclear whether barrier breakdown is an initiating event of UC or rather a consequence of an underlying inflammation, evidenced by increased production of proinflammatory cytokines. UC is less common in smokers, suggesting that the nicotine in cigarettes may ameliorate disease severity. The mechanism behind this therapeutic effect is still not fully understood, and indeed it remains unclear if nicotine is the true protective agent in cigarettes. Nicotine is metabolized in the body into a variety of metabolites and can also be degraded to form various breakdown products. It is possible these metabolites or degradation products may be the true protective or curative agents. A greater understanding of the pharmacodynamics and kinetics of nicotine in relation to the immune system and enhanced knowledge of gut permeability defects in UC are required to establish the exact protective nature of nicotine and its metabolites in UC. This review suggests possible hypotheses for the protective mechanism of nicotine in UC, highlighting the relationship between gut permeability and inflammation, and indicates where in the pathogenesis of the disease nicotine may mediate its effect.

Colitis, Ulcerative↗

Whole blood analysis of phagocytosis, apoptosis, cytokine production, and leukocyte subsets in healthy older men and women: the ZENITH study.

Few studies to date have examined age-related changes in markers of immune status in healthy older individuals. The immune status of 93 healthy individuals aged 55-70 years was assessed by two- and three-color flow cytometry and biochemical analysis. There were significant age effects (p <or=.05) on monocyte phagocytic activity and cluster of differentiation (CD) 3/human leukocyte antigen-D-related (HLA-DR) late-activated T lymphocytes (% expression). There was a significant (p <or= 0.1) Age x Sex interaction in absolute counts (x 10(9)/L) of CD3/CD8 total cytotoxic T lymphocytes (CTL), the CD4 T- helper to CD8 CTL ratio, the CD3/CD4/CD45RA naïve T helper to CD3/CD4/CD45RO memory T helper lymphocyte ratio, and interleukin (IL)-1beta (% expression) by activated monocytes. The study shows that alterations in markers of immune status occur between 55 and 70 years, and provides reference values for the lymphocyte measures in healthy men and postmenopausal women in this age group. The study further highlights the need for sex-specific reference ranges for such markers.

Aged↗

Docosahexaenoic acid reduces in vitro invasion of renal cell carcinoma by elevated levels of tissue inhibitor of metalloproteinase-1.

We demonstrate in this study that the n-3 polyunsaturated fatty acids derived from fish oil, namely, eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA), can increase levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) in the renal cell carcinoma cell line caki-1 by 26% and 17.42% respectively. The result of this elevation in TIMP-1 levels is a reduction of 48.48% in caki-1 invasion through the basement membrane component matrigel when cells are treated with DHA. By inhibition of 2-series prostaglandin production, a similar increase in TIMP-1 was observed in caki-1 cells. We conclude that the polyunstaurated fatty acid DHA, a component of fish oil, is capable of significantly reducing the invasive profile of renal cell carcinoma, and that this reduction is regulated by levels of 2-series prostaglandin production.

Carcinoma, Renal Cell↗

Homocysteine is lower in the third trimester of pregnancy in women with enhanced folate status from continued folic acid supplementation.

BACKGROUND: In many countries, current recommendations are that women take a daily 400-mug folic acid supplement from before conception until the end of the 12th week of gestation for the prevention of neural tube defects. Low folate status is associated with an increased concentration of plasma total homocysteine (tHcy), a risk factor associated with pregnancy complications such as preeclampsia. METHODS: In a longitudinal study, we determined tHcy and corresponding folate status in 101 pregnant women at 12, 20, and 35 weeks of gestation, in 35 nonpregnant controls sampled concurrently, and in a subgroup (n = 21 pregnant women and 19 nonpregnant controls) at 3 days postpartum. RESULTS: Plasma tHcy was significantly lower throughout pregnancy compared with nonpregnant controls, with values lowest in the second trimester before increasing toward nonpregnant values in the third trimester. Importantly, mean tHcy concentrations were lower in pregnant women taking folic acid supplements than in those not, an effect that reached significance in the third trimester (5.45 vs 7.40 micromol/L; P <0.05). During the third trimester, tHcy concentrations were significantly higher in pregnant women with a history of miscarriage than in women with no previous history (8.15 vs 6.38 micromol/L; P <0.01). CONCLUSIONS: This is the first longitudinal study to show that homocysteine concentrations increase in late pregnancy toward nonpregnant values; an increase that can be limited by enhancing folate status through continued folic acid supplementation. These results indicate a potential role for continued folic acid supplementation in reducing pregnancy complications associated with hyperhomocysteinemia.

Adolescent↗

Tissue factor expression on monocyte subpopulations during normal pregnancy.

Pregnancy is often referred to as a hypercoagulable state due to changes in the haemostatic system. Tissue factor (TF) is the initiator of blood clotting in vivo. The effect of pregnancy on monocyte TF expression was determined in a longitudinal case control study (89 pregnant, 39 non-pregnant). Using whole blood flow cytometry and CD14 as a monocyte marker, TF expression was measured on all CD14 positive, CD14Bright and CD14Dim cells. TF expression was significantly lower in pregnant women than in non-pregnant control subjects, on all CD14 positive cells at 20 and 35 weeks, on CD14Bright cells at 12 and 35 weeks and on CD14Dim cells at 20 weeks. Additionally, we report that a higher percentage of CD14Dim than CD14Bright cells express TF. These results suggest that, in order to maintain homeostasis in haemostasis in an otherwise hypercoagulable state, monocyte TF expression is reduced during normal pregnancy.

Adult↗