Genome-wide methylation profile following prenatal and postnatal dietary omega-3 fatty acid supplementation in pigs.

The objective of this study was to determine how prenatal and postnatal dietary omega-3 fatty acids alter white blood cell (leukocyte) DNA methylation of offspring. Fifteen gilts (n = 5 per treatment) were selected from one of three treatments: (i) control diet throughout gestation, lactation and nursery phase (CON); (ii) algal omega-3 fatty acid supplementation enriched in EPA and DHA (Gromega™ ) fed throughout gestation, lactation and nursery phase (Cn3); or (iii) Gromega™ supplementation maternally, during gestation and lactation only, and control diet during the nursery phase (Mn3). At 11 weeks of age and after 8 weeks of post-weaning nursery feeding, buffy coat genomic DNA was subjected to methyl CpG binding protein sequencing. The methylation enriched profile mapped to 26% of the porcine genome. On chromosome 4, a 27.7-kb differentially methylated region downstream of RUNX1T1 was hypomethylated in the Mn3 and Cn3 groups by 91.6% and 85.0% respectively compared to CON pigs. Conversely, hypermethylation was detected in intergenic regions of chromosomes 4 and 12. Regulatory impact factor and differential hubbing methods were used to identify pathways that were coordinately regulated by methylation due to feeding EPA and DHA during pregnancy. Despite limited ability to detect differential methylation, we describe methods that allow the identification of coordinated epigenetic regulation that could not otherwise be detected from subtle single locus changes in methylation. These data provide evidence of novel epigenetic regulation by maternal and early life supplementation of omega-3 fatty acids that may have implications to growth and inflammatory processes.

Effect of vitamin E supplementation on mRNA expression of superoxide dismutase and interleukin-2 in arsenic exposed goat leukocytes.

The aim of this study was to quantify the expression level of genes involved in antioxidant defenses during inorganic arsenic (iAs) exposure in the blood of goats and to evaluate the regulative activity on these genes of antioxidant vitamin E in the diet. Twenty-four crossbred lactating goats (Alpine × Beetal) were distributed randomly into four equal groups (Control, T(1), T(2) and T(3)) of six in each, on the basis of average body weight (36.10 ± 0.11 kg) and milk yield (1.61 ± 0.004 kg/day). The animals in T(1), T(2) and T(3) were given 50 mg/kg dry matter arsenic daily, while in T(2) and T(3), vitamin E @100 IU and 150 IU/kg dry matter, respectively, was also supplemented additionally for the period of 12 months. Blood was sampled at 0 day then at 3 months interval and analyzed for the expression level of superoxide dismutase (Cu/Zn SOD) and interleukin-2 (IL-2) using real-time PCR technique. Initially there was no difference (p > 0.05) in relative expression of the two genes. But, at 3 months, relative expression of Cu/Zn SOD increased (p < 0.05) in T(1) groups then, at 6 and 9 months expression was decreased (p < 0.05) in all the iAs treated groups whereas at 12 months, vitamin E supplementation increased (p < 0.05) the expression which is comparable to control groups. IL-2 mRNA expression was decreased (p < 0.05) at 6 months in all iAs treated groups, at 9 months there was decline trend but not significantly different whereas at 12 months decline trend was less (p < 0.05) in vitamin E supplemented groups. The result suggests that vitamin E may have a controlling effect on oxidative stress through modulation of SOD and IL-2 expression.

Effect of vitamin E supplementation on arsenic induced oxidative stress in goats.

The present study was designed to assess whether supplementation of different levels of vitamin E to long-term arsenic exposed goats affords protection against the oxidative stress caused by the metalloid. Twenty-four crossbred lactating goats were distributed randomly into four groups (control, T(1), T(2) and T(3)) of six in each. The animals in T(1), T(2) and T(3) were given 50 mg/kg DM arsenic daily, while in T(2) and T(3), vitamin E @100 IU and 150 IU/kg DM, respectively, was also supplemented additionally for the period of 12 months. Compared to control, significant (p < 0.05) decline in SOD (45 %), CAT activities of erythrocytes (63 %), plasma total Ig (22 %) and total antioxidant activity (24 %) was observed in only arsenic treated groups and vitamin E supplementation in both doses produced partial mitigation effect against SOD (23 %, 20 %) and CAT (39 %, 48 %) while complete mitigation against total Ig (16 %, 7 %) and antioxidant activity (10 %, 8 %) was found. Average lymphocyte stimulation index at the end of experiment was (p < 0.05) lower in arsenic exposed groups (1.003 ± 0.01) and significant (p < 0.05) recovery was observed in response of vitamin E supplementation at higher doses (1.138 ± 0.03). So, vitamin E is helpful in reducing the burden of arsenic induced oxidative stress and activities of antioxidant enzymes in goats.

A randomised trial comparing mesalazine and prednisolone foam enemas in patients with acute distal ulcerative colitis.

Distal ulcerative colitis can be treated with oral or rectal mesalazine, or both. A foam enema preparation has been developed and its efficacy investigated. The aim of this study was to evaluate the efficacy and safety of mesalazine foam enemas compared with prednisolone foam enemas in the treatment of patients with acute distal ulcerative colitis. Patients aged over 18 years presenting with a relapse of distal ulcerative colitis were randomly allocated treatment with mesalazine foam enema (n = 149 evaluable patients) and prednisolone foam enema (n = 146 evaluable patients) for four weeks. A randomised multicentre investigator blind parallel group trial was conducted. It was found that after four weeks of treatment, clinical remission was achieved by 52% of mesalazine treated patients and 31% of patients treated with prednisolone (p < 0.001). There was a trend in favour of more patients in the mesalazine group achieving sigmoidoscopic remission (40% v 31%, p = 0.10). Histological remission was achieved by 27% and 21% of patients receiving mesalazine and prednisolone respectively. Symptoms improved in both treatment groups. Significantly more mesalazine patients had no blood in their stools after four weeks of treatment (67% v 40%, p < 0.001). Prednisolone treated patients had significantly fewer days with liquid stools than mesalazine patients, with a median of 0 and 1 days respectively by week 4 (p = 0.001). In this study mesalazine foam enema was superior to prednisolone foam enema with regards to clinical remission, this was supported by favourable trends in sigmoidoscopic and histological remission rates. Both treatments were well tolerated.

Comparison of bismuth citrate and 5-aminosalicylic acid enemas in distal ulcerative colitis: a controlled trial.

An enema that contained a complex of bismuth citrate and polyacrylate was compared with 5-aminosalicylic acid (5-ASA) enemas for treatment of distal ulcerative colitis. The multicentre trial involving 63 patients was randomised and double blind with enemas given over four weeks; clinical, sigmoidoscopic, and histological assessments were made. Improvements were seen in both treatment groups. Clinical remission was seen in 18 of 32 patients treated with 5-ASA and 12 of 31 patients treated with bismuth citrate-carbomer (chi 2 1.94; p = 0.16). Sigmoidoscopic remission occurred in 20 of 32 patients in the 5-ASA group and 15 of 31 patients given bismuth (chi 2 1.27; p = 0.26). Improvement of rectal biopsy histology by at least one grade was seen in 16 of 32 patients in the 5-ASA group and 14 of 31 patients with bismuth (chi 2 0.15; p = 0.70). Analysis of covariance gave no significant difference between groups, although there was a trend favouring 5-ASA. There was no evidence of bismuth accumulation during the trial. Bismuth enemas may offer a new therapeutic option in distal ulcerative colitis.

A comparison of sucralfate and prednisolone enemas in the treatment of active distal ulcerative colitis.

Sucralfate is well established in the treatment of upper gastrointestinal inflammation and ulceration, and preliminary evidence suggests it may be of benefit in active colitis. We have therefore undertaken a clinical trial to compare enemas of sucralfate (4 g) and prednisolone metasulphobenzoate (20 mg) in the treatment of active distal ulcerative colitis. Forty-four patients were entered into a 4-week study. Two patients were withdrawn because of non-compliance, and five were unable to complete the study: two developed constipation (both allocated to sucralfate) and three were unable to retain the enemas (two prednisolone and one sucralfate). Intention-to-treat analysis showed significant within-treatment improvement in rectal bleeding, sigmoidoscopic grade, and histologic grade in the prednisolone-treated group, and in stool frequency, rectal bleeding, and sigmoidoscopic grade in the sucralfate-treated group. Between-treatment comparisons, however, showed greater resolution of rectal bleeding and more marked improvements in histologic grade in patients treated with prednisolone metasulphobenzoate enemas. Further studies using higher doses of sucralfate would be useful.