Longitudinal changes in dietary patterns during adult life

Despite the growing interest in dietary patterns, there have been few longitudinal investigations. The objective of the present study was to extend an earlier method of dietary pattern assessment to longitudinal binary data and to assess changes in patterns over time and in relation to socio-demographic covariates. A prospective national cohort of 1265 participants completed a 5 d food diary at three time-points during their adult life (at age 36 years in 1982, 43 years in 1989 and 53 years in 1999). Factor analysis identified three dietary patterns for women (fruit, vegetables and dairy; ethnic foods and alcohol; meat, potatoes and sweet foods) and two patterns in men (ethnic foods and alcohol; mixed). Trends in dietary pattern scores were calculated using random effects models. Marked changes were found in scores for all patterns between 1989 and 1999, with only the meat, potatoes and sweet foods pattern in women recording a decline. In a multiple variable model that included the three time-points, socio-demographic variables and BMI time-dependent covariates, both non-manual social class and higher education level were also strongly associated with the consumption of more items from the ethnic foods and alcohol pattern and the mixed pattern for men (P<0[middle dot]0001) and the fruit, vegetables and dairy pattern and the ethnic foods and alcohol pattern for women (P<0[middle dot]01). In conclusion, longitudinal changes in dietary patterns and across socio-economic groups can assist with targeting public health initiatives by identifying stages during adult life when interventions to improve diet would be most beneficial to health.

Dietary patterns throughout adult life are associated with body mass index, waist circumference, blood pressure, and red cell folate

Dietary patterns are important in the prevention of chronic disease; however, there are few studies that include repeat measures of dietary patterns. The objective of this study was to assess the relations between dietary patterns during adult life (at ages 36, 43, and 53 y) and risk factors for chronic disease at age 53 y. Participants of a longitudinal study of health completed a 5-d food diary at 3 occasions during adult life (n = 1265). Factor analysis was used to identify dietary patterns and a pattern score was calculated from the consumption of the food items in each dietary pattern. Means and 95% CI for dietary pattern scores were calculated for each risk factor category using random effects models adjusted for socio-demographic and health-related behaviors. In women, the fruit, vegetables, and dairy pattern was inversely associated with BMI (P < 0.004), waist circumference (P = 0.0007), blood pressure (P = 0.02), and was positively associated with red cell folate (P < 0.03). The ethnic foods and alcohol pattern was also inversely associated with blood pressure (P = 0.008), whereas the meat, potatoes and sweet foods pattern was positively associated with glycated hemoglobin (P = 0.01). In men, a mixed pattern was inversely associated with waist circumference (P = 0.02) and blood pressure (P = 0.01), whereas there were no significant associations with the ethnic foods and alcohol pattern. Specific dietary patterns throughout adult life were associated with chronic disease risk factors.

Expression of the disintegrin metalloprotease ADAM-10 in prostate cancer and its regulation by dihydrotestosterone, insulin like growth factor -1 and epidermal growth factor in the prostate cell model LNCaP

Purpose: The disintegrin metalloprotease ADAM-10 is a multidomain metalloprotease that is potentially significant in tumor progression due to its extracellular matrix-degrading properties. Previously, ADAM-10 mRNA was detected in prostate cancer (PCa) cell lines; however, the presence of ADAM-10 protein and its cellular localization, regulation, and role have yet to be described. We hypothesized that ADAM-10 mRNA and protein may be regulated by growth factors such as 5α-dihydrotestosterone, insulin-like growth factor I, and epidermal growth factor, known modulators of PCa cell growth and invasion.

Experimental Design: ADAM-10 expression was analyzed by in situ hybridization and immunohistochemistry in prostate tissues obtained from 23 patients with prostate disease. ADAM-10 regulation was assessed using quantitative reverse transcription-PCR and Western blot analysis in the PCa cell line LNCaP.

Results: ADAM-10 expression was localized to the secretory cells of prostate glands, with additional basal cell expression in benign glands. ADAM-10 protein was predominantly membrane bound in benign glands but showed marked nuclear localization in cancer glands. By Western blot, the 100-kDa proform and the 60-kDa active form of ADAM-10 were synergistically up-regulated in LNCaP cells treated with insulin-like growth factor I plus 5α-dihydrotestosterone. Epidermal growth factor also up-regulated both ADAM-10 mRNA and protein.

Conclusions: This study describes for the first time the expression, regulation, and cellular localization of ADAM-10 protein in PCa. The regulation and membrane localization of ADAM-10 support our hypothesis that ADAM-10 has a role in extracellular matrix maintenance and cell invasion, although the potential role of nuclear ADAM-10 is not yet known.

Capecitabine and oral cyclophosphamide : a novel oral treatment combination for advanced cancer

Background: This dose escalation study assessed feasibility of a totally oral chemotherapy regimen using cyclophosphamide and capecitabine. The rationale for this combination was based on the observation that preclinical models of cyclophosphamide up-regulated tumor thymidine phosphorylase and increased the activation of capecitabine. Methods: Eligible patients with advanced cancer were treated with oral cyclophosphamide and capecitabine on a 28-day cycle. If no dose limiting toxicities (DLT) were encountered during the first two treatment cycles, the next patient group was assigned to the next highest dose level until the maximum tolerable dose (MTD) was determined. Results: Twenty-seven patients entered treatment. The majority of non-DLT were grades 1 and 2. DLT experienced in the first 8-week observation period were grade 3 diarrhea (one patient, level III) and grade 3 emesis (two patients, level V). MTD was observed at level 5, 1331 mg/m2/day capecitabine days 1–28 with 125 mg/m2/day cyclophosphamide days 1–14 of the 28-day cycle. The recommended phase II dose is therefore 1331 mg/m2/day capecitabine with 100 mg/m2/day cyclophosphamide. The best response evaluation showed four partial responses (breast, colon, ovary and pancreas). Conclusion: Cyclophosphamide and capecitabine can be combined at their full oral single agent dose with promising tolerability and activity.

Scenarios involving future climate and water extraction: ecosystem states in the estuary of Australia's largest river

 

Disassociation of muscle triglyceride content and insulin sensitivity after exercise training in patients with Type 2 diabetes

Aim/hypothesis. We determined the effect of exercise training on insulin sensitivity and muscle lipids (triglyceride [TGm] and long-chain fatty acyl CoA [LCACoA] concentration) in patients with Type 2 diabetes. Methods. Seven patients with Type 2 diabetes and six healthy control subjects who were matched for age, BMI, % body fat and VO2peak participated in a 3 days per week training program for 8 weeks. Insulin sensitivity was determined pre- and post-training during a 120 min euglycaemic- hyperinsulinaemic clamp and muscle biopsies were obtained before and after each clamp. Oxidative enzyme activities [citrate synthase (CS), β-hydroxy-acyl- CoA (β-HAD)] and TGm were determined from basal muscle samples pre- and post training, while total LCACoA content was measured in samples obtained before and after insulin-stimulation, pre- and post training. Results. The training-induced increase in VO2peak (∼20%, p<0.01) was similar in both groups. Compared with control subjects, insulin sensitivity was lower in the diabetic patients before and after training (∼60%; p<0.05), but was increased to the same extent in both groups with training (∼30%; p<0.01). TGm was increased in patients with Type 2 diabetes (170%; p<0.05) before, but was normalized to levels observed in control subjects after training. Basal LCACoA content was similar between groups and was unaltered by training. Insulin-stimulation had no detectable effect on LCACoA content. CS and β-HAD activity were increased to the same extent in both groups in response to training (p<0.001). Conclusion/interpretation. We conclude that the enhanced insulin sensitivity observed after short-term exercise training was associated with a marked decrease in TGm content in patients with Type 2 diabetes. However, despite the normalization of TGm to levels observed in healthy individuals, insulin resistance was not completely reversed in the diabetic patients.

Regulation of the STARS signaling pathway in response to endurance and resistance exercise and training

The striated muscle activator of Rho signaling (STARS) protein and members of its downstream signaling pathway, including myocardin-related transcription factor-A (MRTF-A) and SRF, are increased in response to prolonged resistance exercise training but also following a single bout of endurance cycling. The aim of the present study was to measure and compare the regulation of STARS, MRTF-A and SRF mRNA and protein following 10 weeks of endurance training (ET) versus resistance training (RT), as well as before and following a single bout of endurance (EE) versus resistance exercise (RE). Following prolonged training, STARS, MRTF-A and SRF mRNA levels were all increased by similar magnitude, irrespective of training type. In the training-habituated state, STARS mRNA increased following a single-bout RE when measured 2.5 and 5 h post-exercise and had returned to resting level by 22 h following exercise. MRTF-A and SRF mRNA levels were decreased by 2.5, 5, and 22 h following a single bout of RE and EE exercise when compared to their respective basal levels, with no significant difference seen between the groups at any of the time points. No changes in protein levels were observed following the two modes of exercise training or a single bout of exercise. This study demonstrates that the stress signals elicited by ET and RT result in a comparable regulation of members of the STARS pathway. In contrast, a single bout of EE and RE, performed in the trained state, elicit different responses. These observations suggest that in the trained state, the acute regulation of the STARS pathway following EE or RE may be responsible for exercise-specific muscle adaptations.