Simple water-based tacrolimus enemas for refractory proctitis

Background and Aims: Rectal ulcerative colitis (UC) and Crohn's disease (CD) often do not respond to conventional therapies. Oral and suppository tacrolimus are effective but often poorly tolerated or are complex to formulate. Tacrolimus is topically active, water soluble, and has minimal systemic toxicity when administered rectally; we therefore tested a simple tap water-based enema formulation. Methods: Tacrolimus powder from 1 mg capsules and tap water in a 60 mL syringe were delivered rectally. The primary end-point was endoscopic response (UC: MAYO score reduction by one point; CD: improvement in ulcer number and severity). Secondary end-points included endoscopic remission, clinical response, stool frequency, and rectal bleeding. Results: Seventeen patients [12 UC, five CD, nine female, median age 31 years] with refractory rectal disease were treated. The majority of patients had failed immunosuppressive therapy [88% thiopurine; 71% biologic therapy]. Initial enemas included 1-4 mg tacrolimus daily and 1-3 mg tacrolimus maintenance three times a week for a median of 20 weeks (range 3-204). Concomitant thiopurine or biologic therapy continued. 94% tolerated therapy. Of 12 UC patients, eight (67%) achieved endoscopic remission, one further patient achieved endoscopic response, and median partial MAYO scores decreased (pre:4 vs. post:2; P = 0.010). Of five CD patients, three (60%) achieved endoscopic response, two (40%) endoscopic remission, and three (60%) clinical response. Stool frequency, rectal bleeding, and C-reactive protein levels improved. Strictures became endoscopically passable in all four affected patients. No major adverse events were reported, and four patients had disease flare. Conclusions: Tacrolimus enemas are easy to prepare, well tolerated, effective, and safe. They should be included in the treatment armamentarium for inflammatory bowel disease-related refractory proctitis

Plasma Phosphatidylethanolamine and Triacylglycerol Fatty Acid Concentrations are Altered in Major Depressive Disorder Patients with Seasonal Pattern

Disturbances in peripheral and brain lipid metabolism, including the omega-3 fatty acid docosahexaenoic acid (DHA), have been reported in major depressive disorder (MDD). However, these changes have yet to be confirmed in MDD with seasonal pattern (MDD-s), a subtype of recurrent MDD. The present exploratory study quantified plasma plasmalogen and diacyl-phospholipid species, and fatty acids within total phospholipids, cholesteryl esters, triacylglycerols and free fatty acids in non-medicated MDD-s participants (n = 9) during euthymia in summer or fall, and during depression in winter in order to screen for potential high sensitivity lipid biomarkers. Triacylglycerol alpha-linolenic acid concentration was significantly decreased, and myristoleic acid concentration was significantly increased, during winter depression compared to summer-fall euthymia. 1-stearyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine, a diacyl-phospholipid containing stearic acid and DHA, was significantly decreased in winter depression. Concentrations of cholesteryl ester oleic acid and several polyunsaturated fatty acids between summer/fall and winter increased in proportion to the increase in depressive symptoms. The observed changes in lipid metabolic pathways in winter-type MDD-s offer new promise for lipid biomarker development

Nutrient intakes during pregnancy: the influence of smoking status and age

STUDY OBJECTIVE—To examine the relation of antioxidant and other nutrient intakes in pregnancy to smoking and sociodemographic variables.
DESIGN—Cohort study.
SETTING—St Mary's Maternity Hospital, Portsmouth.
PARTICIPANTS—Pregnant nulliparous women, with no existing complications of pregnancy, were recruited from antenatal booking clinics. A total of 774 women completed seven day food diaries, and supplied detailed data on their use of nutrient supplements.
MAIN RESULTS—Smokers had lower intakes of most micronutrients. After adjustment for the confounding effects of maternal age, height, and education, only vitamin C and carotenoid intakes remained significantly depressed. Age was strongly and significantly associated with the intake of most nutrients, including antioxidants, and this association was independent of other maternal factors. Antioxidant intake was therefore lowest in young women who smoked: for example smokers under 24 years had a mean vitamin C intake of 57 mg (SD 35) compared with 106 mg (SD 52) for non-smokers aged 28 and over (difference 49 mg, 95% CI 39, 59). The corresponding intakes of carotenoid equivalents were 1335 µg (SD 982) and 2093 µg (SD 1283) (difference 758 µg, 95% CI 496,( )1020).
CONCLUSIONS—The study has identified, for the first time, young pregnant women as a group at particular risk of low micronutrient intake. The health implications of poor nutrition now need to be evaluated, particularly for those women who smoke.


Keywords: pregnancy; nutrition; ag